Integrative Cardiology

Integrative Cardiology
Weil Integrative Medicine Library
Published Volumes
series editor
andrew t. weil, md
Donald I. Abrams and Andrew T. Weil: Integrative Oncology

Timothy P. Culbert and Karen Olness: Integrative Pediatrics
Victoria Maizes and Tieraona Low Dog: Integrative Women’s Health
Randy Horwitz and Daniel Muller: Integrative Rheumatology
Daniel A. Monti and Bernard Beitman: Integrative Psychiatry
edited by
Stephen Devries, MD, FACC, FAHA
Associate Professor of Medicine,
Division of Cardiology
Feinberg School of Medicine
Northwestern University
James E. Dalen, MD, MPH, FACC

Executive Director, The Weil Foundation
Dean Emeritus and Professor Emeritus of Medicine and Public Health
University of Arizona College of Medicine
1 2011
1
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Library of Congress Cataloging-in-Publication Data

Integrative cardiology / edited by Stephen Devries and James Dalen.
p.; cm. – (Weil integrative medicine library)
Includes bibliographical references.
ISBN 978-0-19-538346-1
1. Cardiovascular system—Diseases—Alternative treatment. 2. Integrative medicine.
I. Devries, Stephen R. II. Dalen, James E., 1932- III. Series: Weil integrative medicine library.
[DNLM: 1. Cardiovascular Diseases—therapy. 2. Complementary Therapies–methods.
3. Integrative Medicine—methods. WG 166 I607 2010]
RC684.A48I58 2010
616.1–dc22 2010014554
ISBN 978-0-19-538346-1
1 3 5 7 9 8 6 4 2
Printed in the United States of America
on acid-free paper
To my father, Robert Devries, of blessed memory—who taught
by example to care deeply about others and to go beyond.
Stephen Devries
This page intentionally left blank
CONTENTS
Foreword ix
Contributors xi
Preface xiii
SECTION I: The Foundations of Integrative Cardiology

1. Nutrition and Cardiovascular Health 3
Andrew T. Weil
2. Exercise 17
Craig S. Smith
3. Botanical Medicine and Cardiovascular Disease 55
Tieraona Low Dog
4. An Aspirin a Day Is Even Better than an Apple a Day! 70
James E. Dalen
5. Metabolic Cardiology 78
Stephen T. Sinatra
6. Acupuncture in Cardiovascular Medicine 100
John Longhurst
7. Spirituality and Heart Health 117
Mary Jo Kreitzer and Ken Riff
vii
viii CONTENTS
8. Cardiac Behavioral Medicine: Mind–Body

Approaches to Heart Health 135
Kim R. Lebowitz
9. Energy Medicine 169
Rauni Prittinen King
SECTION II: Integrative Approaches to Cardiovascular Disease

10. Integrative Approaches to Preventive Cardiology 183
Stephen Devries
11. The Integrative Approach to Hypertension 224
Stephen T. Sinatra and Mark C. Houston
12. Integrative Approaches to Cardiovascular Disease 247
Mimi Guarneri and Christopher Suhar
13. Integrative Approaches to Heart Failure 265
Elizabeth Kaback, Lee Lipsenthal and Mimi Guarneri
14. A Brief Note About Arrhythmias 289
Thomas B. Graboys
15. Integrative Approach to Patients Undergoing Cardiac Surgery 292
Gulshan K. Sethi
Additional Resources 311

Index 315
FOREWORD
C
ardiovascular disease is the leading cause of death worldwide. It is
multifactorial in origin, with a complex interplay of genetic and life-
style influences. A strong relationship exists between diet and heart
health. Stress and other mental/emotional factors play roles as well. Given this
complexity, integrative medicine is ideally suited to both prevent and treat
diseases of the heart and blood vessels.
When I was a medical student in the late 1960s, I was taught that atheroscle-
rosis was irreversible. We now know that is reversible, by lifestyle change
or drug therapy or a combination of the two. Practitioners of integrative med-
icine understand the innate healing capacity of the organism and are not
surprised that many cardiovascular conditions can be stabilized or reversed
through creative application of conventional and unconventional therapies.
Because they are trained in lifestyle medicine and whole person medicine,
they are able to design broader, more effective, and more cost-effective treat-
ment plans than those relying solely on drugs or the techniques of invasive
cardiology.
I am especially pleased to introduce this volume in the Oxford University
Press Integrative Medicine Library series because the editors are longtime
friends and colleagues. Dr. James E. Dalen, an eminent cardiologist and leader
in American academic medicine, was Dean of the University of Arizona’s
College of Medicine in the early 1990s, when I first proposed creating a fellow-
ship program in integrative medicine. As the first medical school dean to
encourage such a program, he took a risk and withstood much criticism.
Today, the Arizona Center for Integrative Medicine is a Center of Excellence of
ix
x FOREWORD
the College of Medicine and the world leader in training physicians and allied
health professionals in medicine of the future. Jim Dalen continues to be a
staunch proponent of integrative medicine and its application to his own spe-
cialty. His co-editor, Dr. Stephen Devries, was one of the first cardiologists to
graduate from the Arizona Center’s fellowship training and is now a leading
practitioner of integrative cardiology.
Together Drs. Devries and Dalen have assembled an outstanding team of
contributing authors and a wealth of useful information for clinicians inter-
ested in using the philosophy and practices of integrative medicine to main-
tain optimum heart health and to manage cardiovascular disease most
effectively. I am certain you will find this book as useful as I do.
Andrew T. Weil, MD
Series Editor
Tucson, Arizona
May, 2010
CONTRIBUTORS
James E. Dalen, MD, MPH, FACC Mimi Guarneri, MD, FACC

Executive Director, The Weil Medical Director
Foundation Scripps Center for Integrative Medicine
Dean Emeritus and Professor Emeritus Division of Integrative Medicine and
of Medicine and Public Health Cardiovascular Diseases
University of Arizona College of Scripps Clinic
Medicine
Mark C. Houston, MD, MS, FACP, FAHA
Stephen Devries, MD, FACC, FAHA Associate Clinical Professor of
Preventive Cardiologist Medicine
Associate Professor of Medicine Vanderbilt University School of
Division of Cardiology Medicine
Feinberg School of Medicine Director, Hypertension Institute and
Northwestern University Vascular Biology
Saint Thomas Hospital
Tieraona Low Dog, MD
Director of the Fellowship Elizabeth Kaback, MD
Arizona Center for Integrative Medicine Cardiologist
Clinical Associate Professor Scripps Center for Integrative Medicine
Department of Medicine Division of Integrative Medicine and
University of Arizona Cardiovascular Diseases
Scripps Clinic
Thomas B. Graboys, MD, FACC
Clinical Professor of Medicine Rauni Prittinen King, RN, BSN, MIH,
Brigham and Women’s Hospital and HN-BC, CHTP/I
Harvard Medical School Director of Programs and Planning
President Emeritus Scripps Center for Integrative
Lown Cardiovascular Research Medicine
Foundation Scripps Clinic
xi
xii CONTRIBUTORS
Mary Jo Kreitzer, PhD, RN Stephen T. Sinatra, MD, FACC,

Director FACN, CNS
Center for Spirituality & Healing Cardiologist
University of Minnesota Assistant Clinical Professor of
Medicine
Kim R. Lebowitz, PhD University of Connecticut School of
Assistant Professor of Psychiatry and Medicine
Surgery
Feinberg School of Medicine Craig S. Smith, MD
Director of Cardiac Behavioral Medicine Director
Bluhm Cardiovascular Institute Coronary Care Unit
Northwestern University University of Massachusetts Memorial
Medical Center
Lee Lipsenthal, MD Assistant Professor of Medicine
Internist University of Massachusetts Medical
Omega Institute for Holistic Studies School
John Longhurst, MD, PhD Christopher Suhar, MD

Professor of Medicine, Physiology and Cardiologist
Biophysics, Pharmacology and Scripps Center for Integrative
Biomedical Engineering Medicine
Lawrence K Dodge Chair in Division of Integrative Medicine and
Integrative Biology Cardiovascular Diseases
Susan Samueli Dodge Chair in Scripps Clinic
Integrative Medicine
Director, Susan Samueli Center for Andrew T. Weil, MD
Integrative Medicine Lovell-Jones Professor of Integrative
University of California, Irvine Rheumatology
Clinical Professor of Medicine,
Kenneth M. Riff, MD Professor of Public Health, and
Vice President Director of the Arizona Center for
Data Strategy and Clinical Research Integrative Medicine
Center for Spirituality & Healing, University of Arizona
University of Minnesota
Gulshan K. Sethi, MD, FACC

Professor of Surgery and Medicine
Medical Director
Circulatory Sciences Program
Director of Clinical Services
Arizona Center of Integrative
Medicine
University of Arizona
PREFACE
C
ardiovascular disease is the most prevalent chronic condition and
most common cause of death in the United States. Treatment of
cardiovascular disorders now consumes more than 10 percent of our
health care expenditures (Lloyd-Jones et al., 2009). How did we get to where
we are now—and where are we going?
Before World War II, nearly all patients with heart disease were diagnosed
as “cardiacs” and treatment was essentially the same for all: a low salt diet,
digitalis, and restricted activity. Over the ensuing decades, the marriage of
medicine and technology has allowed the cardiologist to accurately diagnose
and treat almost every possible type of heart disease.
As a result of these advances, heart disease mortality decreased by an
incredible 64 percent from 1950 to 2005 (National Center for Health Statistics,
2008). From 1994 until 2004, deaths due to stroke and heart disease decreased
by 25 percent. By comparison, cancer deaths decreased by only 5 percent
during the same time period (Rosamond et al., 2007).
This incredible progress, resulting from the infusion of advanced technol-
ogy into cardiac care, has come at a price. The first is the impact on health care
costs. The high-tech treatment of heart disease is very expensive, and is one
of the major causes of the escalation of health care costs, stranding millions of
Americans with inadequate or no health insurance (Dalen and Alpert, 2008).
Lack of adequate health insurance is a significant barrier to preventive health
care in the U.S., and is one of the main reasons that the American health
outcomes trail other Western nations (OECD).The World Health Association
xiii
xiv PREFACE
ranked U.S. health care 39th among 191 countries in 2000 (Blendon et al.,
2001)
The second significant side effect of high-tech cardiac care is that it has
become very impersonal. Most initial visits to a cardiologist are made by
patients who already have symptoms of heart disease. In fact, many patients
first meet a cardiologist when they are admitted on an emergency basis for
an acute coronary syndrome or for congestive heart failure. The cardiologist
is seen as the person who orders (and performs) a variety of invasive pro-
cedures. The patient may be rushed to a catheterization laboratory for a per-
cutaneous coronary intervention procedure. By necessity, there is usually
minimal time to explain the reason for the procedures or to discuss alternative
therapies.
At discharge, patients frequently leave with prescriptions for multiple
expensive medications. Many fail to take all the prescribed medications
because of the expense, or because they do not fully understand the reasons
why they are necessary. To compound the problem, patients may experience
side effects from medication and are often reluctant to continue them.
Consequently, they may be regarded as “noncompliant.”
Despite the many successes, conventional cardiac care often leaves patients
feeling overwhelmed and confused. Patients may be led to believe that their
fate rests with an endless series of complex diagnostic tests and expensive
medications—leaving them little control of their own health destiny.
And there is evidence that we are losing ground in the fight against cardiac
disease. A recent study compared the prevalence of risk factors in American
adults aged forty to seventy-four in 1988 and in 2006 (King et al., 2009).
Obesity increased from 28 percent to 36 percent. Those eating a healthy diet
decreased 16 percent. Regular exercise decreased 10 percent. Especially sadly,
the percentage of smokers did not decline, remaining at 26 percent in 2006.
Clearly we must do much better.
What Is Integrative Medicine?
Integrative medicine is the intelligent combination of conventional medicine

and other healing modalities not commonly taught in Western medical
schools, with an emphasis on maximizing opportunities to promote health
and healing. In addition to incorporating all of the incredible advances
of medication and technology, integrative medicine emphasizes nutrition, life-
style, and attention to mind–body influences. And most importantly, the focus
of integrative approaches is directed at prevention. The style of integrative
medicine is heavily accented on collaboration—that is, seeking to obtain the
PREFACE xv
best possible outcome taking into account the intangible, but vital, nuances of
each patient’s culture, beliefs, and preferences.
Cardiology is ideally suited for an integrative approach. Heart disease is
largely preventable. The influence of nutrition, physical activity, metabolic
factors, and emotional state on heart health is unmistakable. The wide-angle
lens of integrative medicine is a perfect model to address these multifaceted
needs. One of the major benefits of an integrative approach to cardiovascular
care is that patients take an active role in their treatment.
The meteoric rise of integrative medicine is a clear message that patients
are not satisfied with the status quo (Eisenberg et al., 1998, Nahin et al., 2009).
In growing numbers, patients are pursuing scientifically valid options that
include, but go beyond the usual of prescriptions and procedures. They want
to know about a broader range of options for treatment—but even more, they
are pursuing preventive measures with an intensity that is not matched by
offerings of conventional medicine.
This book provides the interested health care practitioner with the tools
needed to begin the journey toward an integrative approach to cardiology. It is
not intended as a comprehensive cardiology text, but more as a starting point
from which to develop integrative strategies focused on maintaining heart
health.
Authors were selected because they are leaders in their respective areas
and share the common background of academic medicine. Yet all are clini-
cians who have been asked to share their best practices. The charge to each
of the authors was to focus on the approaches they have found most effective
in their own practice, and to support their contributions with the best scien-
tific evidence available.
The first section of the book describes the core elements of integrative
cardiology, beginning front and center with a discussion of nutrition.
Foundational chapters that follow discuss exercise, botanicals, aspirin, meta-
bolic cardiology, acupuncture, spirituality, mind–body approaches, and energy
medicine.
Andrew T. Weil, in his chapter on nutrition, focuses on the primacy of
food as medicine for maintaining heart health. Current nutritional trends
are placed in geographic and chronological perspective. Dr. Weil emphasizes
the value of a Mediterranean style antiinflammatory diet for heart health and
distills complex nutrition science into very practical strategies.
In the chapter on exercise, Craig S. Smith reviews the latest in maintaining
heart health, and reviews tips on how to incorporate exercise into a successful
heart health program.
The role of botanicals in the prevention and treatment of cardiovascular
disease is discussed by Tieraona Low Dog in Chapter 3. Dr. Low Dog reviews
xvi PREFACE
the science showing that botanicals can lower blood pressure, improve lipid
profiles, and reduce symptoms of congestive failure. The potential for both
synergy and adverse reactions involving botanicals and prescription therapy is
emphasized.
Although the value of nonprescription therapy is challenged by some,
over-the-counter aspirin is, without a doubt, one of the most potent therapies
available in all of medicine. James E. Dalen describes how to use this time
honored therapy most effectively in Chapter 4.
Metabolic cardiology, as discussed by Stephen T. Sinatra in Chapter 5,
describes how biochemical interventions with nutritional supplements can
promote energy production in the heart. The role of coenzyme Q10, l-carnitine,
d-ribose, and magnesium for support of cardiac systolic and diastolic function
is highlighted.
John Longhurst, in Chapter 6, reviews the scientific underpinnings of the
2000-year-old therapy of acupuncture. He describes how acupuncture may
be a useful adjunct in the treatment of hypertension, and outlines the promise
of its expanded future role in cardiology.
In Chapter 7, Mary Jo Kreitzer and Ken Riff discuss how spiritual practices
such as prayer, meditation, journaling, and interacting with nature can have
important health benefits for patients with cardiovascular disease. We are
reminded that the potential to incorporate spiritual belief for healing is
immense, yet largely untapped.
Kim R. Lebowitz, in Chapter 8, emphasizes the mind–body connection, and
reviews the evidence that depression, anxiety, and stress are not only risk factors
for the development of cardiovascular disease, but lead to adverse outcomes,
including cardiac death. She describes techniques to deal with depression,
anxiety, and stress using stress management programs, relaxation therapy, and
physical activity—therapies that can be as effective as drugs in some patients.
The role of energy medicine in the care plan of patients with cardiovascular
disease is reviewed by Rauni Prittinen King in Chapter 9. The historical
origins of “hands-on healing” techniques such as therapeutic touch and
Qigong date back to Hippocrates. These approaches can be highly successful
in addressing an aspect of healing that is often neglected, yet powerful and
without side effects.
The second section of this book illustrates how the core elements of integra-
tive cardiology described in the first half can be best utilized for prevention
and treatment. This section leads with an overview of integrative approaches
to prevention, and continues with chapters on hypertension, coronary artery
disease, congestive heart failure, arrhythmias, and cardiac surgery. Emphasis
has been placed on practical, clinically useful approaches backed by the best
available literature.
PREFACE xvii
Prevention is the cornerstone of integrative medicine. In Chapter 10,

Stephen Devries highlights powerful opportunities afforded by nutritional
approaches, lifestyle changes, and supplements—combined with conservative
use of medication. The importance of evaluation for inherited risk factors that
go beyond traditional cholesterol tests is reviewed.
In Chapter 11, Stephen T. Sinatra and Mark C. Houston discuss the role of
integrative approaches for the patients with hypertension, especially in patients
with borderline hypertension, and in those who do not tolerate prescription
medication. Drawing on their extensive experience, they offer a focused view
of the simplest and most successful strategies.
Conventional treatment of coronary artery disease is typically confined to
pills and procedures. An expanded, integrative approach is provided by Mimi
Guarneri, and Christopher Suhar in Chapter 12, with special attention paid to
lifestyle changes and awareness of mind–body interactions.
No patients in cardiology are more complex than those with congestive
heart failure. In Chapter 13, Elizabeth Kaback, Lee Lipsenthal, and Mimi
Guarneri illustrate how the diverse needs of these patients can be optimally
addressed by combining conventional care with nutritional supplements and a
mindful, openhearted approach that acknowledges and strengthens their
physical as well as their spiritual heart.
Arrhythmias are a nuisance for some and life-threatening for others.
Thomas B. Graboys puts the current emphasis on high-technology treatment
for arrhythmias in a broader perspective in Chapter 14. He advocates for an
integrative approach that is simple in delivery, yet steeped in the wisdom of
a seasoned clinician.
Patients who undergo cardiac surgery are often overwhelmed by the pro-
cedure, especially when it is required on an emergent basis. In Chapter 15,
Gulshan K. Sethi, a senior cardiovascular surgeon, describes how integrative
techniques can be implemented in the care of patients facing major surgery.
The results of this integration are an improvement in the overall patient expe-
rience, as well as the surgical outcome.
We hope that you find this book a useful guide for your jouney into the
rapidly expanding, and enormously satisfying, field of integrative cardiology.
REFERENCES
Blendon, R. J., Kim, M., Benson, J. M. 2001. The public versus the World Health
Organization on health system performance. Health Aff (Millwood), 20, 10–20.
Dalen, J. E., Alpert, J. S. 2008. National Health Insurance: could it work in the US? Am
J Med, 121, 553–4.
xviii PREFACE
Eisenberg, D. M., Davis, R. B., Ettner, S. L., Appel, S., Wilkey, S., Van Rompay,
M., Kessler, R. C. 1998. Trends in alternative medicine use in the United States,
1990-1997: results of a follow-up national survey. JAMA, 280, 1569–75.
King, D. E., Mainous, A. G., 3rd, Carnemolla, M., Everett, C. J. 2009. Adherence to
healthy lifestyle habits in US adults, 1988-2006. Am J Med, 122, 528–34.
Lloyd-Jones, D., Adams, R., Carnethon, M., DE Simone, G., Ferguson, T. B., Flegal,K.,
Ford, E., Furie, K., Go, A., Greenlund, K., Haase, N., Hailpern, S., Ho, M.,
Howard, V., Kissela, B., Kittner, S., Lackland, D., Lisabeth, L., Marelli, A.,
McDermott, M., Meigs, J., Mozaffarian, D., Nichol, G., O’Donnell, C., Roger, V.,
Rosamond, W., Sacco, R., Sorlie, P., Stafford, R., Steinberger, J., Thom, T.,
Wasserthiel-Smoller, S., Wong, N., Wylie-Rosett, J., Hong, Y. 2009. Heart disease
and stroke statistics–2009 update: a report from the American Heart Association
Statistics Committee and Stroke Statistics Subcommittee. Circulation, 119, e21–181.
Nahin, R. L., Barnes, P. M., Stussman, B. J., Bloom, B. 2009. Costs of complementary
and alternative medicine (CAM) and frequency of visits to CAM practitioners:
United States, 2007. Natl Health Stat Report, 1–14.
OECD Health at a Glance 2009, OECD Publishing.
Pleis JR, Lucas JW, Ward BW. Summary health statistics for U.S. adults: National Health
Interview Survey, 2008. National Center for Health Statistics. Vital Health Stat
10(242). 2009.
Rosamond, W., Flegal, K., Friday, G., Furie, K., Go, A., Greenlund, K., Haase, N., Ho, M.,
Howard, V., Kissela, B., Kittner, S., Lloyd-Jones, D., McDermott, M., Meigs, J.,
Moy, C., Nichol, G., O’Donnell, C. J., Roger, V., Rumsfeld, J., Sorlie, P., Steinberger, J.,
Thom, T., Wasserthiel-Smoller, S., Hong, Y., Committee, F. T. A. H. A. S., Stroke
Statistics Subcommittee 2007. Heart Disease and Stroke Statistics–2007 Update: A
Report From the American Heart Association Statistics Committee and Stroke
Statistics Subcommittee. Circulation, 115, e69–171.
I
The Foundations of
1
Nutrition and Cardiovascular Health
ANDREW T. WEIL
key concepts
■ The mainstream North American diet promotes the develop-

ment of obesity, insulin resistance, metabolic syndrome, and
cardiovascular disease.
■ Refined, processed, and manufactured foods are the chief cul-
prits; they are full of unhealthy fats and high-glycemic-load car-
bohydrate.
■ An antiinflammatory diet, based on the Mediterranean diet,
offers the best protection against cardiovascular disease and also
promotes optimum health, without sacrificing the pleasures of
good food.
■ It is more important to eat the right kinds of fat and right kinds
of carbohydrate than to limit intake of either fat or carbohydrate
to low percentages of total caloric intake.
■
U
nderstanding of the relationship between dietary habits and cardio-
vascular health has developed slowly and changed greatly in recent
years. Epidemiological data first brought to light significant correla-
tions between diet and incidence of atherosclerosis, coronary heart disease,
and myocardial infarction (MI), all rare conditions in many parts of the world
that became epidemic in Western, industrialized societies in the twentieth
century.
The atherogenic effect of high intake of saturated fat was suggested by a
dramatic decrease in heart attacks in Holland, Belgium, Denmark, and other
European countries suffering the deprivations of the Second World War,
followed by a dramatic increase in heart attacks with the return of peace
3
4 THE FOUNDATIONS OF INTEGRATIVE CARDIOLOGY
and prosperity, along with meat, butter, and other animal-derived foods
(Malmros 1980). The incidence of myocardial infarction, especially in middle-
aged men, was at an all-time high in the U.S. in the middle of the last century,
and treatment for it was often ineffective. More alarming was the finding that
early atherosclerotic changes could be found at autopsy in healthy American
men under twenty who had been killed in accidents or war, changes that were
absent in most men of all ages in Asia, Africa, and many other parts of the
world (Beaglehole and Magnus 2002).
As the evidence for saturated fat as a cause of elevated serum cholesterol
and arterial disease grew, physicians urged patients to substitute margarine for
butter, cook with safflower and other polyunsaturated vegetable oils, and
decrease consumption of whole-milk products and eggs.
Medical focus on elevated serum cholesterol as the main risk factor for MI
and on dietary saturated fat as the main driver of elevated serum cholesterol
led, by the 1970s, to condemnation of dietary fat in general as the most harm-
ful element in the Western diet, the one responsible for epidemic atherosclero-
sis in our population. It followed that a healthy, heart-protective diet was
primarily a low-fat diet. A few prominent physicians advocated ultra-low-fat
diets, even advising patients to avoid olive oil and oily fish because of pre-
sumed adverse effects on serum cholesterol. Ornish (1990) demonstrated
reversal of coronary atherosclerosis in patients who followed a strict program
of group support, moderate exercise, stress management, and an ultra-low-fat,
vegetarian diet. The dietary component of his program has never been evalu-
ated apart from the other interventions.
More recent data on the rising incidence in China and Japan of “Western”
diseases, including type 2 diabetes and cardiovascular disease, as people in
those countries have moved away from traditional diets in favor of Western
ones, strongly suggests the importance of nutritional influences relative to
other risk factors. When I lived in Japan as an exchange student in 1959, most
Japanese ate traditional breakfasts of miso soup, steamed rice, a small portion
of broiled salmon or other fish, seaweed, steamed and pickled vegetables, and
green tea. When I returned in the mid-1970s, I found it hard to get that kind
of breakfast except in hotels. The morning meal I saw most Japanese eating in
those years was bacon or sausage and eggs, white toast with butter, or cereal
and milk, and coffee.
Such radical changes in eating habits can affect the health of populations
very quickly, even over a few years. Between 1999 and 2002, I made three trips
to Okinawa to collect information on healthy aging for a book I was writing.
Okinawa had the highest concentration of centenarians in the world, the great-
est rates of longevity, and unusual numbers of very old people in good health.
I found the traditional Okinawan diet (different from that of the rest of Japan)
Nutrition and Cardiovascular Health 5
most interesting. It included a great variety and abundance of land and sea
vegetables, fruits, unusual herbs and spices, fish, tofu, and pork (long sim-
mered to remove fat). But it seemed risky to me to attribute Okinawan health
and longevity to diet alone. People there are genetically distinct, are more
physically active throughout life than we are, and enjoy clean air and water.
Okinawan culture also values aging; the oldest members of the community are
considered living treasures and included in all community activities.
Nevertheless, within a few years of my last visit, Okinawan longevity plum-
meted, especially among men. Experts attributed the change mostly to changed
eating habits, in particular, the sudden popularity of American-type fast food
(Onishi 2004).
Research on nutrition and health has come a long way since the simplistic
view of high intake of dietary fat as the main risk factor for disease in general
and heart disease in particular. It is now clear that the typical Western diet is
unhealthy both because of what it does not provide as well as because of what
it does. We know that there are good fats and bad fats; some types of fat are
strongly heart protective. We know that carbohydrate foods differ in how
quickly they digest and raise blood sugar; those with the highest glycemic load
can be very unhealthy for the many genetically susceptible people in our pop-
ulation. We have confirmed the protective effects of key micronutrients on
cardiovascular health and have identified many protective phytonutrients in
fruits, vegetables, herbs, spices, and beverages. And the new view of athero-
sclerosis and coronary heart disease as an inflammatory disorder makes it a
priority to evaluate the influence of dietary choices on the inflammatory pro-
cess (Fito et al. 2007; Lichtenstein et al. 2006).
With this broader knowledge, we can easily see why the mainstream North
American diet promotes obesity, insulin resistance, and cardiovascular disease:
• It provides too much of the unhealthy fats: saturated fat (especially

from beef, cheese, and other full-fat dairy products); polyunsaturated
vegetable oils (which are pro-inflammatory); and chemically altered
fats, including trans and partially hydrogenated ones (which are
atherogenic and pro-inflammatory) (Simopoulos and Robinson 1999;
Weil 2001). It also provides excessive amounts of pro-inflammatory
omega-6 fatty acids, mostly from refined soybean oil, a ubiquitous,
cheap ingredient found in many processed foods (Simopoulos 1999).
• It is full of high-glycemic-load carbohydrate foods (made from flour,
other refined starches, sugar, and high-fructose corn syrup) that pro-
mote insulin resistance in many people and, by causing spikes in blood
sugar, promote glycation reactions that result in pro-inflammatory
end products (de Groof 2003).
• It is top-heavy in animal foods, especially beef. Diets high in animal

foods correlate with increased cardiovascular risk and other long-
term health risks (Menotti et al. 1999).
• It is full of refined, processed, and manufactured foods new to human
diets. These foods contain numerous additives, artificial ingredients,
and ingredients altered from their natural forms. Introduction of
refined, processed, and manufactured foods in diverse populations
throughout the world is associated with a rapid increase of diseases
common in our society, including cardiovascular disease.
• It is deficient in health-protective fats, especially the antiinflammatory,
anti-thrombotic omega-3 fatty acids, which are mostly found in oily
fish (Harper and Jacobson 2001; Psota, Gebauer, and Kris-Etherton
2006).
• It is deficient in fruits and vegetables, the main dietary sources of pro-
tective antioxidants and phytonutrients (Heber 2002).
• It is often deficient in protective micronutrients, such as folate and
other B-vitamins that regulate homocysteine metabolism (Bonaa
et al. 2006; Joshipura et al. 2001), vitamin D (Scragg et al. 1990; Wang
et al. 2008), and magnesium (Ohira et al. 2009).
Proposed heart-healthy diets of recent years have not addressed all of these
problems and are overly restrictive, making long-term adherence difficult
except for highly motivated patients. Ultra-low-fat diets may worsen omega-3
fatty acid deficiency and fail to lower glycemic load. Ultra-low-carbohydrate
diets may be high in animal foods and unhealthy fats and low in protective
phytonutrients and micronutrients. Calorie-restricted diets may include pro-
cessed foods and worsen deficiencies of essential fatty acids. All of these diets
can reduce risk of cardiovascular disease; recent research shows no significant
advantage to any one of them (Dansiger et al. 2005). But all may fail to pro-
mote optimum long-term health, and their restrictive nature makes it likely
that people will not stick to them.
A more realistic strategy is to design a nutritional program that addresses
all the problems of the mainstream diet without denying people the pleasures
of eating. Very low-fat foods tend to be tasteless and uninteresting. Carbohydrate
foods are comfort foods for many. Vegetables need to be prepared in ways that
make them appetizing.
Using the Mediterranean diet as a template for such a nutritional program
is a sensible starting point. A composite of the traditional diets of Italy, Greece,
Crete, parts of Spain, the Middle East, and North Africa, the Mediterranean
diet is high in fish but low in red meat, high in low-to-moderate glycemic load
carbohydrates, low in sugar, rich in vegetables and fruit, and liberal in the use
of olive oil. Absent are the refined, processed, and manufactured foods that
North Americans consume in such high quantities. Heart health (and general
health) of Mediterranean peoples who eat this way is superior to that of North
Americans (de Lorgeril 1999; de Lorgeril et al. 1994).
It is important to note, however, that the traditional Mediterranean diet,
like the traditional Japanese diet, is rapidly going out of fashion, as fast food
and processed food become increasingly available and popular throughout the
region. In fact, it may only be in remote areas today that people eat the way
their grandparents did.
However, a great advantage of the Mediterranean diet is that it appeals to
people all over the world and can be adapted to local circumstances. Some
descriptions of it in words or pictures fail to distinguish between truly whole-
grain foods and those made with pulverized grains (flour), which have a much
higher glycemic impact. (This is an important point. Many people think that
whole wheat bread is a whole-grain product, and the Food and Drug
Administration allows it to be so labeled. In fact, when grains are milled into
flour, whether or not they retain the germ and some bran, the starch in them
is reduced to tiny particles with a very large collective surface area available for
enzymatic conversion to glucose. All food products made from pulverized
grains have much higher glycemic loads than whole or cracked grains that are
parched, boiled, or steamed.) Also, I think the antiinflammatory power of the
Mediterranean diet can be improved with a few tweaks and additions.
The antiinflammatory diet I recommend is a key strategy for healthy aging,
intended to increase the likelihood of compression of morbidity in the later
years of life. My specific recommendations follow.
The Antiinflammatory Diet
GENERAL
• Aim for variety.

• Include as much fresh food as possible.
• Minimize consumption of processed foods and fast food.
• Eat an abundance of fruits and vegetables.
CALORIC INTAKE
• Most adults need to consume between 2,000 and 3,000 calories a day.
• Women and smaller and less active people need fewer calories.
• Men and bigger and more active people need more calories.
• If you are eating the appropriate number of calories for your level of
activity your weight should not fluctuate greatly.
• The distribution of calories you take in should be as follows: 40 to
50 percent from carbohydrates, 30 percent from fat, and 20 to 30 per-
cent from protein.
• Try to include carbohydrates, fat, and protein at each meal.
CARBOHYDRATES
• On a 2,000-calorie-a-day diet, adult women should eat about 160 to

200 grams of carbohydrates a day.
• Adult men should eat about 240 to 300 grams of carbohydrates a day.
• The majority of carbohydrates eaten should be in the form of less-
refined, less-processed foods with low glycemic loads.
• Reduce consumption of foods made with flour and sugar, especially
bread and most packaged snack foods (including chips and pretzels).
• Eat more whole grains (not whole-wheat-flour products), beans,
winter squashes, and sweet potatoes.
• Cook pasta al dente and eat it in moderation.
• Avoid products made with high-fructose corn syrup.
FAT
• On a 2,000-calorie-a-day diet, 600 of those calories can come from

fat–that is, about 67 grams. This should be in a ratio of 1:2:1 of satu-
rated to monounsaturated to polyunsaturated fat.
• Reduce intake of saturated fat by eating less butter, cream, cheese, and
other full-fat dairy products, as well as chicken with the skin on, fatty
meats, and products made with palm kernel oils.
• Use extra-virgin olive oil as a primary cooking oil. If you want a neu-
tral-tasting oil, use expeller-pressed organic canola oil. High-oleic
versions of sunflower and safflower oil are acceptable also, preferably
non-GMO (genetically modified organism) versions.
• Avoid regular safflower and sunflower oils, corn oil, cottonseed oil,
and mixed vegetable oils.
• Strictly avoid margarine, vegetable shortening, and all products listing
them as ingredients. Strictly avoid all products made with partially
hydrogenated oils of any kind. Avoid products made with refined
soybean oil.
• Include in your diet avocados and nuts–especially walnuts, cashews,

and almonds and nut butters made from them.
• To ensure appropriate intake of omega-3 fatty acids, eat salmon (pref-
erably fresh or frozen wild or canned sockeye), sardines packed in
water or olive oil, herring, black cod (sablefish, butterfish), omega-3
fortified eggs, hemp seeds, flaxseeds (preferably freshly ground), and
walnuts, or take a fish oil supplement (2-3 grams a day).
PROTEIN
• On a 2,000-calorie-a-day diet, daily intake of protein should be

between 80 and 120 grams. Eat less protein if you have liver or kidney
problems, allergies, or autoimmune disease.
• Decrease consumption of animal protein, except for fish and dairy
products.
• Eat more vegetable protein, especially from beans in general and soy-
beans in particular. Become familiar with the range of soy foods avail-
able to find ones you like.
FIBER
• Try to eat 40 grams of fiber a day. You can achieve this by increasing
consumption of fruit (especially berries), vegetables (especially beans),
and whole grains.
• Ready-made cereals can be good sources of fiber, but read labels to
make sure they give you at least 4, and preferably 5, grams of bran per
one-ounce serving.
PHYTONUTRIENTS
• To get maximum natural protection against age-related diseases,

including cardiovascular disease, cancer, and neurodegenerative dis-
ease, as well as against environmental toxicity, eat a variety of fruits,
vegetables, and mushrooms.
• Choose fruits and vegetables from all parts of the color spectrum, espe-
cially berries, tomatoes, orange and yellow fruits, and dark leafy greens.
• Choose organic produce whenever possible. Learn which conven-
tionally grown crops are most likely to carry pesticide residues (see
www.foodnews.org) and avoid them.
• Eat cruciferous (cabbage-family) vegetables regularly.

• Include whole soy foods in your diet (such as edamame, soy nuts, soy
milk, tofu, and tempeh).
• Drink tea instead of coffee, especially good-quality white, green, or
oolong tea.
• If you drink alcohol, use red wine preferentially and in moderation.
• Enjoy plain dark chocolate (with a minimum cocoa content of 70 per-
cent) in moderation.
VITAMINS AND MINERALS
• The best way to obtain all of your daily vitamins, minerals, and micro-
nutrients is by eating a diet high in fresh foods with an abundance of
fruits and vegetables.
• In addition, supplement your diet with the following antioxidant
cocktail:

Vitamin C: 200 milligrams a day
Vitamin E: 400 International Units IU of natural mixed tocopherols
(d-alpha-tocopherol with other tocopherols, or, better, a minimum
of 80 milligrams of natural mixed tocopherols and tocotrienols)

Selenium: 200 micrograms of an organic (yeast-bound) form
Mixed carotenoids: 10,000 to 15,000 IU daily.
• In addition, take daily multivitamin–multimineral supplements that
provide at least 400 micrograms of folic acid. They should contain no
iron (unless you are female and having regular menstrual periods)
and no preformed vitamin A (retinol).
• Take 2,000 IU a day of vitamin D with your largest meal.
• Women may take supplemental calcium, preferably as calcium
citrate, 500 to 700 milligrams a day, depending on their dietary intake
of this mineral; men should avoid supplemental calcium.
WATER
• Try to drink six to eight glasses of pure water a day or drinks that
are mostly water (tea, very diluted fruit juice, sparkling water with
lemon).
• Use bottled water or get a home water purifier if you tap water tastes
of chlorine or other contaminants, or if you live in an area where the
water is known or suspected to be contaminated.
The following chart offers practical suggestions for how to incorporate

appropriate amounts of heart-healthy foods into your diet.
Because chronic, inappropriate inflammation appears to be the common
root of much age-related disease, this kind of diet promotes optimum health at
any age and broadly reduces risk of disease, including cardiovascular disease.
It avoids the problems of restrictive diets, allowing for much variety and plea-
sure in eating. It takes account of the most current findings of research on
nutrition and health. It is the best corrective remedy for the dietary habits that
now prevail in North America and are rapidly spreading to other parts of the
world, habits that undermine health in general and heart health in particular.
Healthy Sweets
How much: Sparingly
Healthy choices: Unsweetened dried fruit, dark chocolate, fruit sorbet
Why: Dark chocolate provides polyphenols with antioxidant activity. Choose
dark chocolate with at least 70 percent pure cocoa and have an ounce a few
times a week. Fruit sorbet is a better option than other frozen desserts.
Red Wine
How much: Optional, no more than 1–2 glasses per day
Healthy choices: Organic red wine
Why: Red wine has beneficial antioxidant activity. Limit intake to no more
than 1–2 servings per day. If you do not drink alcohol, do not start.
Tea
How much: 2–4 cups per day
Healthy choices: White, green, oolong teas
Why: Tea is rich in catechins, which are antioxidant compounds that reduce
inflammation. Purchase high-quality tea and learn how to correctly brew it
for maximum taste and health benefits.
Healthy Herbs & Spices

How much: Unlimited amounts
Healthy choices: Turmeric, curry powder (which contains turmeric), ginger
and garlic (dried and fresh), chili peppers, basil, cinnamon, rosemary, thyme
Why:Use these herbs and spices generously to season foods. Turmeric and
ginger are powerful, natural, antiinflammatory agents.
Other Sources of Protein

How much: 1–2 servings a week (one portion is equal to 1 ounce of cheese, 1
eight-ounce serving of dairy, 1 egg, or 3 ounces cooked poultry or skinless meat)
Healthy choices: Natural cheeses, natural yogurt, omega-3 enriched eggs,

skinless poultry, grass-fed lean meats
Why: In general, try to reduce consumption of animal foods. If you eat
chicken, choose organic, cage-free chicken and remove the skin and
associated fat. Use organic dairy products moderately, especially yogurt
and natural cheeses such as Emmental (Swiss), Jarlsberg, and
true Parmesan. If you eat eggs, choose omega-3 enriched eggs (made by
feeding hens a flax-meal-enriched diet), or organic eggs from free-range
chickens.
Cooked Asian Mushrooms

How much: Unlimited amounts
Healthy choices: Shiitake, enokidake, maitake, and oyster mushrooms (and
wild mushrooms if available)
Why: These mushrooms contain compounds that enhance immune func-
tion. Never eat mushrooms raw, and minimize consumption of common
commercial button mushrooms (including crimini and portobello).
Whole Soy Foods

How much: 1–2 servings per day (one serving is equal to one-half cup tofu or
tempeh, 1 cup soymilk, one-half cup cooked edamame, 1 ounce of soynuts)
Healthy choices: Tofu, tempeh, edamame, soy nuts, soymilk
Why: Soy foods contain isoflavones that have antioxidant activity and
are protective against cancer. Choose whole soy foods over fractionated
foods, such as isolated soy protein powders and imitation meats made with
soy isolate.
Fish & Seafood

How much: 2–6 servings per week (one serving is equal to 4 ounces of fish or
seafood)
Healthy choices: Wild Alaskan salmon (especially sockeye), herring, sardines,
and black cod (sablefish)
Why: These fish are rich in omega-3 fats, which are strongly antiinflammatory.
If you choose not to eat fish, take a molecularly distilled fish oil supplement,
2–3 grams per day.
Healthy Fats
How much: 5–7 servings per day (one serving is equal to 1 teaspoon of oil,
2 walnuts, 1 tablespoon of flaxseed, or 1 ounce of avocado)
Healthy choices: For cooking, use extra-virgin olive oil and expeller-pressed
organic canola oil. Other sources of healthy fats include nuts (especially
walnuts), avocados, and seeds (including hemp seeds and freshly ground
flaxseed). Omega-3 fats are also found in cold-water fish, omega-3 enriched
eggs, and whole soy foods. High-oleic sunflower or safflower oils may also be
used, as well as walnut and hazelnut oils in salads and dark roasted sesame
oil as a flavoring for soups and stir-fries.
Why: Healthy fats are those rich in either monounsaturated or omega-3 fats.
Extra-virgin olive oil is rich in polyphenols with antioxidant activity, and
canola oil contains a small fraction of omega-3 fatty acids.
Whole & Cracked Grains

How much: 3–5 servings a day (one serving is equal to about one-half cup
cooked grains)
Healthy choices: Brown rice, basmati rice, wild rice, buckwheat, groats,
barley, quinoa, steel-cut oats
Why: Whole grains digest slowly, reducing frequency of spikes in blood sugar
that promote inflammation. “Whole grains” means grains that are intact or
in a few large pieces, not whole wheat bread or other products made from
flour.
Pasta (al dente)

How much: 2–3 servings per week (one serving is equal to about one-half cup
cooked pasta)
Healthy choices: Organic pasta, rice noodles, bean thread noodles, and part
whole wheat and buckwheat noodles, such as Japanese udon and soba
Why: Pasta cooked al dente (when it is slightly firm rather than soft, and
has “tooth” to it) has a lower glycemic index than fully cooked pasta. Low-
glycemic-load carbohydrates should be the bulk of your carbohydrate intake,
to help minimize spikes in blood glucose levels.
Beans & Legumes

How much: 1–2 servings per day (one serving is equal to one-half cup cooked
beans or legumes)
Healthy choices: Beans like Anasazi, adzuki, and black, as well as chickpeas,
black-eyed peas and lentils
Why: Beans are rich in folic acid, magnesium, potassium, and soluble fiber.
They are a low-glycemic-load food. Eat them well cooked, either whole or
pureed into spreads like hummus.
Vegetables
How much: 4–5 servings per day minimum (one serving is equal to 2 cups
salad greens, or one-half cup vegetables cooked, raw, or juiced)
Healthy choices: Lightly cooked dark leafy greens (spinach, collard greens,
kale, Swiss chard), cruciferous vegetables (broccoli, cabbage, Brussels sprouts,
kale, bok choy, and cauliflower), carrots, beets, onions, peas, squashes, sea
vegetables, and washed raw salad greens
Why: Vegetables are rich in flavonoids and carotenoids, with both antioxi-
dant and antiinflammatory activity. Go for a wide range of colors, eat them
both raw and cooked, and chooseorganic when possible.
Fruits
How much: 3–4 servings per day (one serving is equal to 1 medium-sized
piece of fruit, one-half cup chopped fruit, or one-quarter cup of dried fruit)
Healthy choices: Raspberries, blueberries, strawberries, peaches, nectarines,
oranges, pink grapefruit, red grapes, plums, pomegranates, blackberries,
cherries, apples, and pears––all are lower in glycemic load than most tropical
fruits
Why: Fruits are rich in flavonoids and carotenoids, with both antioxidant
and antiinflammatory activity. Go for a wide range of colors, choose fruit
that is fresh and in-season or frozen, and buy organic when possible.
Supplements
Recent research has questioned the value of “vitamin therapy” with supple-
mental antioxidants (vitamin E, vitamin C, beta-carotene, and selenium) for
improving serum cholesterol levels or existing coronary artery disease
(Brown et al. 2001). Most studies have used d-alpha-tocopherol, not the full
complex of tocopherols and tocotrienols that occur in natural vitamin E, and
they have used isolated beta-carotene, not a complex of carotenoids more
representative of the family of pigments found in many fruits and vegeta-
bles. I recommend the above forms and doses of vitamins C and E, mixed
carotenoids, and selenium for general health-protective effects, especially
because daily consumption of fruits and vegetables is generally low in much
of the North American population.
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2
Exercise
CRAIG S. SMITH
key concepts
■ Physical inactivity is one of the most prevalent modifiable risk

factors for coronary artery disease.
■ Regular exercise induces physiologic changes in multiple organ
systems that allow for greater exertional capacity across all age
groups.
■ Aerobic training has favorable effects upon cardiovascular risk
factors including hypertension, diabetes mellitus, cholesterol
levels, and blood clotting factors. Resistance training appears to
have beneficial effects as well.
■ An exercise prescription should be tailored to maximize com-
pliance and modified, as needed, based on cardiac status and
other medical conditions.
■
Introduction
I
t has long been recognized, and promoted, that regular physical activity is
associated with improved personal longevity and health. In recent decades,
this belief has been reinforced by an increasing body of evidence in the
scientific literature demonstrating a wide range of health benefits linked to
physical fitness, regardless of age, place of origin, or gender. The cumulative
effect of this evidence has led to a heightened awareness in both the medical
profession and the general public of the importance of regular physical activity
as both a preventive and therapeutic tool. While there have been formal
recommendations and calls to action for increased physical activity by the
17
surgeon general and various medical organizations, many individuals have

embarked on exercise regimens on their own, as evidenced by the increasing
number of individuals who report regular physical activity in their lives
(Caspersen 2000; Morbidity and Mortality Weekly Report 2008). Despite the
apparent acceptance by the public and the medical profession of the impor-
tance of physical activity, more than 60 percent of Americans do not achieve
recommended activity levels, and one-quarter of the population remains sed-
entary, reporting little to no activity (Jones et al. 1998).
In the United States, over 250,000 deaths per year are attributed solely to a
sedentary lifestyle, most of which are due to complications of cardiovascular
disease and type 2 diabetes mellitus (Pate et al. 1995). This represents appro-
ximately 12 percent of all deaths per year. The lack of physical activity is asso-
ciated with a doubling of the risk for coronary events, the largest cause
of mortality in the population (Powell and Blair 1994). As such, a sedentary
lifestyle represents the most prevalent modifiable risk factor for mortality
in the population at large, and its elimination accrues health benefits for the
individual on par with smoking cessation, treatment of high blood pressure,
and reduction of obesity (Miller, Balady, and Fletcher 1997).
The wide range of health benefits derived from physical activity and exercise is
likely reflective of the multitude of body systems involved, and the scope of body
traits and functions encompassing the concept of physical fitness. These include
cardiopulmonary endurance, skeletal muscle power and endurance, speed,
flexibility, body composition, and balance. Ironically, while the multifaceted
nature of exercise is likely responsible for its varied benefits, it also makes its study
more difficult. Randomized trials to evaluate the effects of exercise are often
plagued with noncompliance to exercise regimens, “drop-in” of controls who
perform exercise (and the unethical stance of asking them not to), and inadequate
subject numbers to account for the multitude of patient factors and the varied
types of exercise performed to allow statistically significant conclusions. As a
result, most of the scientific literature is based on observational studies, which are
subject to bias due to confounding variables such as adoption of a heart-healthy
diet, increased medical care, and alterations in other behaviors that may have
health benefits above and beyond the performance of exercise alone. Nevertheless,
the preponderance of evidence strongly favors the adoption of regular exercise in
improving overall health–and particularly cardiovascular health.
Physiology
Exercise places a considerable demand upon the heart which, in turn, undergoes
dramatic physiologic changes to accommodate the body’s needs. Despite massive
Exercise 19
increases (up to 50x) in skeletal muscle metabolism and work performed

with even moderate physical activity, oxygen delivery to peripheral tissue
and acid-base balance remain remarkably stable during exercise. This is made
possible by a complex and tight coupling of the neuromuscular, peripheral
muscles/vasculature, respiratory, and cardiac systems to ensure that the
metabolic needs of exercising muscle are met. As a result of such multisystem
interaction, a large increase in cardiac output occurs that is proportional to
the increased metabolic demands on the body. Due to the fact that so many
systems are involved in the exercise response, evaluation of exercise tolerance
via multiparameter exercise testing is an invaluable tool in both diagnosis and
prognosis for a number of health conditions. An adequate response to exercise
testing will, in most cases, rule out any serious pathology within the cardiopul-
monary and neuromuscular systems, although compensatory responses can
occur for more mild disease.
The amount of physical exercise performed can be estimated by a number of
parameters. The most common include directly measuring the amount of work
performed (in watts), or by assessing how much metabolic fuel (O2) is con-
sumed in the process. Directly measuring work performed (watts) to assess
exercise capacity/tolerance can be misleading due to the fact that a number of
factors (most commonly obesity) may increase the work of exercise, but not
reflect the condition of the cardiopulmonary systems. As a result, exercise
capacity is most often assessed by oxygen consumption. This is done either by
directly measuring consumption, generating a maximum amount of oxygen
uptake (or VO2 max), or is estimated by clinical history. The units used to esti-
mate the metabolic cost of physical activity are referred to as metabolic equiva-
lents (or METs). A single MET is defined as the amount of oxygen consumed
(approximately 3.5ml O2/kg/min) by an average adult at rest. This clinical esti-
mation correlates well with measured VO2 across a broad array of activities and
is highly predictive of exercise capacity. The metabolic equivalents of various
common activities are listed in Table 2.1 (Pate, 1995). METs perform by an
individual in his or her daily life is an important tool in formulating an effective
exercise program as well as screening for general cardiovascular health.
PERIPHERAL MUSCLE AND VASCULATURE
The peripheral, or skeletal, muscles performing the work of exercise are

specialized and excel in various types of work. Their efficiency and metabolism
greatly influence the demand placed on the heart to supply the oxygen and
other nutrients required for exertion. Muscle fibers are clustered into groups
of homogenous muscle units, all of which are innervated by a single motor
Table 2.1. Examples of Common Physical Activities for Healthy US Adults by

Intensity of Effort Required in MET Scores and Kilocalories per Minute
LIGHT MODERATE HARD/VIGOROUS
< 3 METs or <4 kcal/min 3–6 METs or 4–7 kcal/min 6 METs or > 7 kcal/min
Walking slowly/strolling Walking briskly (3–4 mph) Walking briskly uphill or

(1–2 mph) with a load
Cycling, stationary (<50 W) Cycling for pleasure or Cycling, fast or racing

transportation (< 10 mph) (>10 mph)
Swimming, slow treading Swimming, moderate effort Swimming, fast treading

or crawl
Stretching exercises/yoga General calisthenics Cross-country skiing/

cardio machine
∗∗∗ Racket sports/table tennis Singles tennis/

racquetball
Golf, power cart Golf, pulling cart/carrying clubs ∗∗∗
Bowling ∗∗∗ ∗∗∗
Fishing, sitting Fishing, standing/casting Fishing in stream
Boating, power Canoeing, leisurely (up to 4 mph) Canoeing, rapid (>4 mph)
Home care, carpet Home care, general cleaning Moving furniture

sweeping
Mowing lawn, riding Mowing lawn, power mower Mowing lawn, hand push
mower mower
Home repair, carpentry Home repair, painting ∗∗∗
Pate et al. 1995. Physical activity and public health—a recommendation from the Centers
for Disease Control and prevention and the American College of Sports Medicine. JAMA 273:
402–407.
neuron and can be one of two types: red or “slow” fibers (twitch type 1) and
white or “fast” fibers (twitch type 2). Metabolically, the muscle types are dis-
tinct, allowing for specialization. Fatigue-resistant type 1 fibers have a high
oxidative (oxygen-using) capacity, which is best suited for endurance exercise.
Type 2 fibers have a high glycolytic (glucose-using) capacity and best suited for
burst activity with heavy loads, but are prone to fatigue. The relative amount of
each muscle type in the body is genetically predetermined and cannot be
altered with exercise training. However, regular exercise can increase blood
supply to muscle via recruitment of capillary networks, as well as increase the
Exercise 21
mitochondria in muscle fibers, leading to greater capacity of substrate utilization

and efficiency (Terjung, 1995).
The energy “currency” of muscle contraction are high-energy phosphates,
generated from the hydrolysis of adenosine triphosphate (ATP). ATP is pro-
duced primarily through pathways that require either glucose (anaerobic) or
oxygen (aerobic). Despite massive turnover and relatively small ATP stores in
the cell, the concentration of ATP remains remarkably constant during exer-
cise. This is due to a redundancy and overlap in the three primary energy
sources of muscle tissue: the phosphocreatine shuttle, anaerobic glycolysis,
and oxidative phosphorylation.
Phosphocreatine (PCr) is a small particle that serves as a high-energy phos-
phate reservoir near actin-myosin complexes (responsible for muscle contrac-
tion) and quickly replenishes supplies of ATP and reduces concentration of
ADP locally, to allow for continued muscle contraction. This is accomplished
by creatine kinase:
PCr + ADP ÆCr + ATP ´ ADP + Pi
When ATP is used for muscle contraction, PCr “donates” a high-energy phos-
phate to keep ATP concentration high near the muscle. This rapid availability
of phosphate near the actin-myosin complex serves as the first energy “buffer”
for muscle and is particularly useful for bursts of activity. The use of creatine
as an oral supplement has been shown to improve muscle performance for
short intense activities, but not for endurance work. Whether the use of cre-
atine supplementation helps patients with heart failure—who are unable to
provide enough blood flow to meet the energy demands of peripheral muscle—
remains uncertain.
Anaerobic glycolysis is the process in which glucose is utilized to produce
ATP, ultimately yielding lactate. This occurs when the energy requirement of
muscle outstrips its oxygen supply. It is a particularly useful pathway during
short intense exercise, as the speed at which ATP is produced is 100 times that
of oxidative phosphorylation (but yields less ATP per molecule).
Oxygen-dependent oxidative phosphorylation of glycogen and free fatty
acids is the most efficient, and largest, source of intracellular ATP. With exer-
cise training, skeletal muscle is able to increasingly utilize fat as a substrate for
oxidation, prolonging the duration and amount of work performed until gly-
cogen stores are utilized. Peripheral muscle fatigue during endurance activity
is not limited by the availability of high energy phosphates, but is instead trig-
gered by the depletion of glycogen stores and the rise of blood lactate concen-
tration. The threshold of exertion at which this occurs is called the lactate
threshold, and is not due to lack of oxygen delivery to muscles, but rather to
accumulation of lactate (via pyruvate) which exceeds the muscle capacity to

process this byproduct through the Krebs cycle (Graham and Saltin 1989;
Putman et al. 1995; Stainsby et al. 1989). Lactate threshold is a powerful pre-
dictor of cardiovascular health, and a clinically useful tool in evaluation and
prognosis of patients with cardiovascular disease, particularly in cases of heart
failure, where it is often used to determine cardiac transplant status (Sue and
Hansen 1984; Wasserman and McIlroy 1964). While habitual exercise cannot
increase the type of muscle cells present, it can substantially increase both the
maximum work and the lactate threshold in normal individuals and those
with cardiopulmonary disease. For optimal improvement in cardiovascular
fitness to occur, exercise intensity should approach the lactate threshold.
Peripheral circulation plays a central role in directing the increased cardiac
output to nutrient-starved exercising skeletal muscle, and thus in maintaining
the physiological homeostasis required for continued activity. While cardiac
output may increase 5-fold with vigorous exercise, the rise in mean systemic
blood pressure is far less, due to the reduction of systemic vascular resistance
(SVR). This drop in vascular resistance is mediated through selective constric-
tion and dilation of vascular beds, which in turn are mediated by the nervous
system. With exercise, parasympathetic activity is withdrawn and plasma cat-
echolamines rise, as a result of sympathetic activity. Vasoconstriction occurs
in the majority of the body’s vascular beds, with the exception of skeletal
muscle that undergoes nitric-oxide mediated vasodilation. At maximal exer-
cise, skeletal muscle can receive upwards of 90 percent of systemic blood flow,
compared with one-fifth of cardiac output at rest (Wade and Bishop 1962).
Similarly, metabolically inactive organs, such as the GI tract, can see reduc-
tions of cardiac output of up to 90 percent of their resting levels (less than 1
percent of total blood flow at peak exercise). This preferential shunting of car-
diac output can be augmented by repeated training (Koller et al. 1995). Unlike
skeletal muscle, the pulmonary circulatory system receives virtually all of the
cardiac output and shunting is decreased during exercise. However, a similar
NO-mediated vasodilatory mechanism occurs within the pulmonary vascula-
ture. This allows for accommodation of the increase in cardiac output without
a subsequent rise in pulmonic pressures, aiding the return of peripheral deox-
ygenated blood to the heart.
PULMONARY CONTRIBUTION TO EXERCISE TOLERANCE
Despite a nearly 15-fold increase in whole body oxygen uptake and a 10-fold
increase in minute ventilation with intense exercise, systemic arterial oxygen
content remains remarkably stable even with extreme exertion. The partial
Exercise 23
pressure of oxygen (and its diffusion across the alveolar-capillary membrane)

is maintained in spite of the increased extraction by a number of compensatory
mechanisms. These include an increase in breathing rate (minute ventilation),
more efficient elimination of CO2 during exercise, a reduction in low ventila-
tion/low perfusion areas of the lung due to larger volume breaths, and greater
cardiac output into the lung vasculature (Jones, 1984). These respiratory mech-
anisms are typically more than sufficient to maintain physiologic homeostasis
at prolonged peak exercise. It is exceedingly rare that either oxygen diffusion
or pulmonary mechanics are the limiting factors to maximum exert ional tol-
erance. For the vast majority, maximal exercise capacity and cardiovascular
fitness are limited by factors affecting cardiac output and function.
CARDIAC PHYSIOLOGY
Cardiac output, the major determinant of exercise capacity, is increased by

alterations in both heart rate and the stroke volume of the heart, and increases
by 5ml/min for every 1ml/min increase in oxygen consumption. Habitual
exercise may increase the maximum cardiac output attained (approximately 5
times the resting output), but it does not alter the slope of the relationship of
CO to VO2. The relationship between VO2 and heart rate is linear, however,
with the near instantaneous increase in heart rate at the beginning of exercise
due to vagal tone withdrawal. Later increases in heart rate are mediated
through sympathetic responses triggered by pulmonary stretch receptors and
increased circulating catecholamines. At extremely high levels of exertion,
heart rate contributes proportionally more to changes in CO than stroke
volume of the heart; however, both age and nutritional factors determine the
maximum heart rate that is obtainable. An accurate predictor of maximal
heart rate in adults is:
Max HR= 208 – 0.7(age) (Tanaka, Monahan, and Deals 2001)
Stroke volume, on the other hand, increases in a hyperbolic fashion with exer-
cise (Blomqvist and Saltin 1983) by two mechanisms: changes in the contrac-
tility of heart muscle and increases in left ventricular end-diastolic volume
(LVEDP). Diastolic volume can increase up to 40 percent during exercise,
increasing cardiac output via the Frank-Starling principle. The augmentation
of venous return to the heart during exertion is accomplished through greater
negative intrathoracic pressures generated by increased respiratory effort,
and increased venous flow via the pumping of limbs and venoconstriction.
Changes to cardiac contractility are not related to venous return and filling
characteristics per se, but are reflective of a more intrinsic forceful contraction
due to neurohormonal effects, which results in greater emptying of the left
ventricle (ionotropy).
The body’s response to intensive exercise requires a highly coordinated and
tightly coupled biofeedback across many organ systems. While maximal car-
diac output usually limits aerobic capacity, habitual exercise and physical
activity increases the capacity and efficiency of almost all systems involved in
this integrated response.
Exercise Benefits and Prevention of CV Disease
Coronary heart disease (CHD) remains the leading killer of both men and
women in most developed areas of the world, and in the United States it
exceeds the number of deaths of the next seven causes combined (American
Heart Association 2002; Yusuf et al. 2001). Because CHD is often fatal, and
over one-half of individuals who die suddenly from CHD have no prior symp-
toms, it is imperative to identify strategies to reduce the risk of CHD in the
general population. A sedentary lifestyle carries a risk for development of
CHD on par with the more traditionally recognized factors of cigarette smok-
ing, hypertension, and hypercholesterolemia (Fletcher et al. 1996). Physical
inactivity has now been recognized by the American Heart Association as one
of the four modifiable risk factors for CHD (Fletcher et al. 1996). While the
benefits of habitual exercise appear to apply to both the general population
and individuals with established coronary heart disease, it has been more dif-
ficult to demonstrate the cardioprotective effects of exercise in the general
population due to lower event rates when compared to individuals with estab-
lished cardiovascular disease.
Despite these limitations, there exists an abundance of evidence to recom-
mend exercise training to the general population on its own merits. Short- and
long-term aerobic exercise is associated with increased quality of life for both
physical and psychological attributes. In addition to reductions in body weight
and fat content, exercise is beneficial in prevention and management of mus-
culoskeletal injuries and disorders (Braith and Stewart 2006). Regular exercise
is also associated with reduced prevalence and severity of stress, anxiety and
depression (Martin et al. 2009; Martinsen, Medhus, and Sandvik 1985;
Warburton, Gledhill, and Quinney 2001).
The physiological changes in the heart induced with exercise may be intrin-
sically cardioprotective, but may also favorably modify other risk factors for
disease. When combined with a smoking cessation program, exercise facili-
tates short- and long-term smoking cessation and attenuates the weight gain
Exercise 25
often seen after cessation (Marcus et al. 1999; Shepard and Shek 1999). These
diverse benefits of exercise translate into more cost-effective health care, with
reductions of over $300 per year in direct medical costs for individuals with
regular physical activity and, approximately $5000 per year of life saved in
individuals with known coronary heart disease (Ades, Pashkow, and Nestor
1997; Pratt, Macera, and Wang 2000).
Improvement in exercise capacity is the most consistent benefit seen with
regular exercise (Wenger et al. 1995). As cardiac output is the major determi-
nant of exercise capacity, it is not surprising that many of the structural and
functional changes that occur with endurance training augment stroke volume
in particular. These changes include alterations that directly affect cardiac
functioning (central adaptations) or improve peripheral oxygenation extrac-
tion for any given CO (peripheral adaption). The latter is likely due to the
increase in skeletal muscle capillary networks seen with exercise. A 1–5 month
regimen of aerobic exercise performed at 50–80 percent of maximal heart rate
for 30 minutes 3–5 times weekly is frequently used in the literature to elicit
exercise-induced physiological changes, and will often result in an increase in
exercise capacity upwards of 30 percent.
PHYSIOLOGIC CHANGES WITH EXERCISE
Increase in stroke volume is the predominant change in cardiac output with

exercise, and occurs across all levels of physical activity. A large part of the
increased volume occurs primarily due to increased preload as a result of
increases in diastolic and plasma volume (Green, Jones, and Painter 1990;
Rerych et al. 1980; Seals et al. 1994). Considerable enlargement of the ventricle
can occur in elite athletes to accommodate a larger stroke volume, but is not
associated with the abnormalities in ventricular function seen with dilated car-
diomyopathies (Pelliccia et al. 1999; Pluim et al. 2000). Cardiac muscle hyper-
trophies resulting in greater cardiac mass and, likely, greater contractility.
The other determinant of cardiac output—heart rate—is lowered at rest
and with mild exertion due to increased vagal tone, but is augmented at peak
exercise levels. As a consequence, there is greater baroreflex sensitivity and
heart rate variability in physically fit individuals. Endothelial function is also
improved with training, increasing vasodilatory responses at higher cardiac
outputs and improving blood flow to areas of greater metabolic demand.
Coronary arteries in endurance athletes are similar in size to age-matched sed-
entary controls, but exhibit 200 percent greater vasodilatory response to nitro-
glycerin (Currens and White 1961; Haskell et al. 1993). It is believed the short,
repetitive increases in pressure and shear stress seen with exertion create a
favorable milieu for the release of the vasodilators nitric oxide and prostacy-
clin from vascular endothelium, as opposed to prolonged periods of exposure,
as seen with chronic hypertension (Niebauer and Cooke 1996).
EXERCISE BENEFITS
Early studies demonstrating the benefits of physical activity were observational

in nature and found lowered rates of total mortality and cardiovascular events
in active individuals (Morris et al. 1953; Taylor et al. 1962). Many of these early
studies compared individuals with physically demanding jobs with their more
sedentary peers. As rates of leisure-time physical activity in the general popu-
lation grew, more recent studies have relied on estimates of energy expenditure
from activity questionnaires. Almost all have shown a strong inverse relation-
ship between habitual physical activity and rates of cardiovascular disease and
death, regardless of gender, age or origin. The best known of these studies is
the Harvard Alumni Study, which was a retrospective analysis of self-reported
physical activity over 12 years in 10,269 men. Men who were physically active
at baseline (defined as total physical activity of >2000 kcal a week and includ-
ing home repair, yard work, or exercise for 30 minutes/day on most days of the
week) had a 25 percent lower risk of death from any cause and a 36 percent
reduction in cardiovascular death when compared to their sedentary controls
(Paffenbarger et al. 1986; Paffenbarger et al. 1993; Sesso, Paffenbarger, and
Lee 2000). Data from the MR FIT Trial (Multiple Risk Factor Intervention
Trial) yielded similar results where moderately active men (leisure time activi-
ties of 224kcal/day) had 70 percent of the overall deaths and 63 percent of
the deaths from cardiovascular causes when compared to inactive men (Leon
et al. 1987). In a metanalysis of over 40 studies, the relative risk of developing
coronary artery disease was 1.9 in sedentary individuals, on par with the risk
seen with other coronary risk factors, such as smoking and high cholesterol
(Powell et al. 1987). Instead of subjective questionnaires, the use of objective
and quantitative measures to evaluate energy expenditure may correlate more
strongly with cardiovascular risk. Energy expenditure as measured by radio-
isotope-labeled water was more predictive of reductions in overall mortality
in an elderly population (70–82 years of age) over 6 years than self-reported
exercise levels (Manini et al. 2006). Individuals in the highest measured activ-
ity level had a hazard ratio of 0.3 for all causes of mortality when compared
to the lowest activity group. Similar findings were found when comparing
activity levels based on metabolic equivalents (METs) in a large analysis com-
prising over 100,000 participants (Kodama et al. 2009).
Exercise 27
The cardioprotection conferred by physical activity (self-reported or

objective) appears to be a graded response to the duration of activity and
occurs regardless of the presence of cardiovascular disease. The Framingham
Heart Study demonstrated an increase of life expectancy at all levels of activity
in those with and without cardiovascular disease, with the greatest gains seen
in those individuals (men or women) in the highest tertile of activity (see
Figure 2.1). (Franco et al. 2005). In the Nurses’s Health Study (women between
40 and 65 years of age), age-adjusted relative risk of coronary events decreased
across increasing quintile groups of energy expenditure (0.88–0.66) (Manson
et al. 1999). In men and women, distance of daily walking was strongly corre-
lated with lower mortality rates (Hakim et al. 1998; Lee et al. 2001). This graded
cardioprotective effect of exercise is also well demonstrated in the Finnish
Twin Cohort study. In almost 8000 same-sex pairs of twins, the odds ratio for
death was 0.44 in regular vigorous exercisers as compared to 0.66 in those who
only occasionally exercised (Kujala et al. 1998).
Intensity of exercise, in addition to duration, appears to play an important
role in both identifying cardiovascular risk and accruing the cardiovascular
LE With CVD LE Free of CVD

40 36.0
32.5 34.0
35
29.9 6.6
30 27.6 6.6
Life Expectancy, y
26.2 6.4
25 7.1
6.6 6.8
20
15 26.1 27.4 29.4
22.8
10 19.7 20.8
5
0
Low Moderate High Low Moderate High
Men Women
Level of Physical Activity
Figure 2.1. Effect of physical activity level on life expectancy (LE) at age 50 years.
All LEs have been calculated with hazard ratios adjusted for age, sex, smoking, exami-
nation at start of follow-up period, and any comorbidity (cancer, left ventricular
hypertrophy, arthritis, diabetes, ankle edema, or pulmonary disease). CVD indicates
Franco et al. 2005. Effects of physical activity on life expectancy with cardiovascular disease.
Archives of Internal Medicine 165: 2355.
benefit of exercise. Separately, both regular and high-intensity activity are

cardioprotective, but the addition of vigorous exercise to moderate activity
(defined as 30 minutes of activity most days a week) confers an additional
reduction in cardiovascular risk across gender, ethnicity, and body mass index
of upwards of 50 percent. (Leitzman et al. 2007; Manson 1999). Even the per-
ception of intense exercise appears to have cardioprotective benefits. Over a
5-year follow-up period in 7337 men (mean age 66 years), participants who
perceived their exercise to be of moderate to high intensity had a substantially
lower (RR of 0.66-0.72) risk of coronary heart disease when compared to their
peers who felt their exercise intensity was weak. This protection was observed
even in individuals whose actual exercise did not meet current recommenda-
tions for either intensity or duration (Lee et al. 2003).
The degree of cardiovascular fitness, as defined by both the duration and
maximal oxygen uptake during exercise performance, is associated with
reduced rates of overall and cardiac mortality and morbidity (Blair et al. 1989;
Ekelund et al. 1988; Powell et al. 1987). In 3043 participants in the Framingham
Heart Study, greater exercise capacity on a treadmill was predictive of a lower
coronary risk over an 18-year follow-up, with an incremental decrease in risk
seen with each MET achieved (Balady et al. 2004). In middle-aged men, meta-
bolic equivalents were the strongest predictor of mortality regardless of the
presence or absence of cardiovascular disease, with each MET conferring a
12 percent reduction in mortality (Myers et al. 2002).
Exercise-induced ST segment deviation was not predictive of cardiovascular
death in women, whereas total exercise capacity and heart rate recovery were
strongly correlated and those below the median for both measures had a hazard
ratio for death of 3.5 (Mora, et al. 2003). In trials involving both genders, the
least exercise-conditioned participants (as measured by treadmill exercise per-
formance) had 8-fold higher rates of cardiovascular death compared to the best
conditioned participants (Blair et al. 1995; Ekelund et al. 1988).
The observational nature of these studies does subject the conclusions to
selection bias. Higher activity and exercise levels may be achieved only by
healthier individuals, and the observed reductions in mortality rates may be
attributable not to cardioprotective effects of exercise, but rather reflect the
fact that healthier individuals live longer. Arguing against this criticism are
several randomized animal models which demonstrate reductions in coronary
atherosclerosis with exercise (Kramsch et al. 1981), in addition to several
“crossover” observational studies in humans. In one such study, exercise capac-
ity was assessed in nearly 10,000 men (mean age 43) across 5 years. Those
subjects who remained unfit throughout the observational period had a three-
fold higher rate of death than their fit colleagues. Initially unfit subjects who
Exercise 29
A Normal Subjects C Subjects with Cardiovascular Disease

100 100
Percentage Surviving
>8 MET
75 75
>8 MET
5–8 MET
50
<5 MET 50 5–8 MET
<5 MET
25
25
0
0 3.5 7.0 10.5 14.0 0
0 3.5 7.0 10.5 14.0
B Normal Subjects
Subjects with Cardiovascular Disease
100
D
100
>100%
75 75–100% 75
50–74% >100%
75–100%
50 50 <50%
<50% 50–74%
25 25
0 0
0 3.5 7.0 10.5 14.0 0 3.5 7.0 10.5 14.0
Years of Follow-up Years of Follow-up
Figure 2.2. Survival Curves for Normal Subjects Stratified According to Peak Exercise
Capacity (Panel A) and According to the Percentage of Age-Predicted Exercise
Capacity Achieved (Panel B) and Survival Curves for Subjects with Cardiovascular
Disease Stratified According to Peak Exercise Capacity (Panel C) and According to the
Percentage of Age-Predicted Exercise Capacity Achieved (Panel D).
Myers et al. 2002. Exercise capacity and mortality among men referred for exercise testing. NEJM
346: 793. Reprinted with permission.
became exercise-trained by the end of the study, however had reductions of

44 percent and 52 percent in all causes and cardiac mortality (Blair et al. 1995).
Another study found similar reductions in previously inactive men who
underwent exercise training (Paffenbarger, 1993). While there is not conclu-
sive evidence that withdrawal of activity increases cardiac risk, the Harvard
Alumni Study found physically fit individuals who became inactive over time
had the same risk of death as those who remained inactive throughout their
lives (Paffenbarger et al. 1986). Although a large randomized, controlled trial
to demonstrate the cardioprotective effects of exercise will not likely be per-
formed due to the necessary size, cost, and compliance issues, the multitude of
epidemiological studies (in addition to the plausible biological mechanisms)
have led the American Heart Association to conclude that physical activity
reduces the risk of coronary artery disease (Thompson et al. 2003)
Exercise and Cardiovascular Risk Factors
Given the complex interactions of established risk factors on cardiovascular

morbidity and mortality, measuring the direct impact of exercise on cardiac
risk predictors is difficult. Weight loss associated with regular exercise can
directly affect other risk factors such as hypertension and insulin resistance
independent of the potential benefit of exercise. Nevertheless, similar to over-
all cardiac risk, enough evidence exists to support the claim that regular phys-
ical activity has a favorable effect on a number of cardiac risk factors, including
hypertension, diabetes/insulin resistance, and obesity. In general, the reduc-
tion of cardiac risk factors achieved with exercise is less than that of pharma-
cologic intervention. However, the magnitude of reduction with exercise
may be enough to obviate the need for further intervention in patients at risk.
Type of exercise regimen, concomitant weight loss, and dietary modifications
all add to the variable effect that exercise confers on an individual’s cardiovas-
cular risk profile.
HYPERTENSION
Distinct from other risk factors, beneficial effects on hypertension are seen
in both acute and long-term exposure to exercise. Immediately at the end of
exercise, reductions in cardiac output and heart rate are seen from a simulta-
neous increase in vagal tone and removal of sympathetic stimulation. Due to
persistent vasodilatory responses in the muscle vascular bed, systemic vascu-
lar resistance remains low for up to 12 hours after intense activity, with even-
tual normalization of blood pressure by baroreceptor reflexes (Pescatello et al.
1991). Over 40 randomized trials have demonstrated a reduction in resting
blood pressure and some have shown a decreased incidence of hypertension
with long-term aerobic exercise (Arroll and Beaglehole 1992; Seals and
Hagberg 1984). The baseline resting blood pressure appears to be an important
mediator of the magnitude of the exercise effect. Normotensive subjects, on
average, will decrease systolic and diastolic blood pressure by 2.6 and 1.8mmHg,
respectively. Hypertensive subjects demonstrate greater reduction, with mean
systolic and diastolic reductions of 7.4mmHg and 5.8mmHg (Fagard, 2001).
The magnitude of exercise effect on blood pressure (up to 15mmHg in some
studies) suggests the initiation of regular aerobic regimen may be the sole
intervention required for mildly hypertensive patients. Conversely, lack of
exercise is a risk factor for the development of hypertension (Blair et al. 1984).
Exercise 31
Maintenance of blood pressure reduction is also dependent on the continua-

tion of exercise, with regression to pre-exercise BP seen with discontinuation
of regular exercise (Somers et al. 1991).
Unlike other cardiovascular benefits derived from exercise, reductions in
blood pressure are not dependent upon the frequency of exercise, but rather
the intensity. Blood pressure was as reduced in hypertensive subjects in
one study with 60 minutes/week of moderately intense exercise (50 percent
max VO2) as it was with subjects who performed double the frequency and
duration of exercise (Ishikawa-Takata, Ohta, and Tanaka 2003). The lack of
correlation between time spent exercising and reduction in blood pressure
suggests a threshold effect on blood pressure and a flat dose-response curve
with regards to exercise frequency. One proposed mechanism for reduction
of blood pressure by aerobic exercise is the augmentation of endothelium-
dependent vasodilation by nitric oxide, which occurs when moderate intensity
exercise is undertaken. Due to the effects of nitric oxide, systemic vascular
resistance is reduced with aerobic exercise, resulting in isolated elevation of
systolic blood pressure during exercise. An exaggerated blood pressure
response to aerobic exercise (defined as BP> 210mmHg in men and >190mmHg
in women) may reflect abnormalities in cardiovascular regulatory mech-
anisms and can predict increases risks of left ventricular hypertrophy, coro-
nary artery disease and cardiovascular morbidity (Mundal et al. 1996; McHam
et al. 1999).
In contrast to aerobic exercise, resistance training (or pure isometric
exercise) has historically not been considered beneficial in controlling hyper-
tension. This has been in part due to the acute rise in systolic and diastolic
blood pressure seen in strength training (as high as 230–330/170–250 mmHg)
(Morales et al. 1991). Unlike aerobic training, vascular resistance increases in
strength training due in part to mechanical compression of the skeletal muscle
vascular beds. While some long-term strength training protocols have resulted
in reductions of systolic and diastolic BP, these have been modest at best. The
recent adoption of circuit training, which involves moving quickly between
higher repetition and lower resistance exercises, adds a component of aerobic
training to the workout and may result in improved blood pressure effects.
Several programs including resistance training to aerobic exercise regimens
have shown favorable reductions in both resting systolic and diastolic BP
(Cornelissen and Fagard 2005; Kelly and Kelly 2000). This, and the fact that
resistance training is correlated with improved glycemic control (as evidenced
by reduced HbA1c) and a reduction in total body fat mass, has led the American
Heart Association and the American College of Sports Medicine to endorse
resistance training as a complement to aerobic exercise in the treatment of
hypertension.
LIPIDS
Regular aerobic exercise has favorable effects on lipid profiles, but the effect is
modest as assessed by standard serological assays. While early observational
studies showed significant lipid differences in runners as compared to their
sedentary peers, confounding variables of a heart-healthy diet and lifestyle,
body weight, and comorbidities made any causal relationship difficult to con-
firm (Wood et al. 1976; Wood et al. 1988; Williams et al. 1986). Subsequently,
randomized trials have found a definite beneficial effect of exercise, albeit
more it is modest than original cross-sectional studies had suggested.
A metaanalysis of 52 trials of at least 12 weeks of exercise training showed
reductions in triglyceride and LDL-C concentrations of 3.7 percent and 5 per-
cent, with an increase in HDL-C of 4.6 percent (Leon and Sanchez 2001a; Leon
and Sanchez 2001b). In comparison to the effects of exercise on hypertension,
exercise intensity and duration mediate the effect on lipoproteins, with dura-
tion of exercise contributing more (King 1995 et al.; Kokkinos et al. 1995). In
addition, there is a graded dose–response in modifying lipoproteins with
regards to exercise duration. In a randomized trial involving men and women,
frequent low-intensity exercise was associated with significantly higher HDL
levels than higher intensity, less frequent exercise (King et al. 1995). Another
randomized study comparing frequency of high intensity regimens found only
a significant decrease in very-low-density lipoprotein and increase in HDL
with more frequent exercise (Kraus et al. 2002). This effect was independent of
change in body weight.
Several studies have also suggested gender plays a role in exercise effects
on lipoproteins (Stefanick et al. 1998; Wood et al. 1991). Gender-specific
changes in lipid profiles were seen in several studies where men and women
were randomized to diet alone, diet with exercise (moderate intensity), or
controls. While weight loss occurs in both genders and both intervention
groups, diet alone did not change HDL levels compared with controls, and
actually caused a decrease in HDL concentrations in women (Wood et al.
1991). An AHA, step-2 diet alone was not found to reduce total cholesterol
or LDL, but when added to exercise produced significant decreases in both
(Stefanick et al. 1998). Diet with exercise does appear to significantly raise
HDL in men, but not in women (Wood et al. 1991). These results highlight
the importance of including regular exercise into any dietary intervention,
and in the difficulty in isolating the effects of both due to differences in base-
line lipid profiles, body mass, and the broad variability of diet and exercise
programs.
Exercise 33
10
8
6
4
2
0
Change (%)
−2
−4
−6
−8
−10 Control group
Exercise group
−12 Diet group
Diet-plus-exercise group
−14 ∗ † ‡
−16
Women Men Women Men
HDL Cholesterol LDL Cholesterol
Figure 2.3. Mean Changes in Plasma HDL Cholesterol and LDL Cholesterol Levels
in the Study Groups at 1Year. The vertical lines represent 95 percent confidence
intervals. Significance levels, after Bonferroni’s adjustment for the six pairwise com-
parisons, are indicated as follows: the asterisk denotes P<0.05 for the comparison with
the control group, the dagger P<0.001 for the comparison with the control group, and
the double dagger P<0.001 for the comparison with the exercise group.
Stefanick et al. 1998. Effects of diet and exercise in men and postmenopausal women with
low levels of HDL cholesterol and high levels of LDL cholesterol. NEJM 339: 12. Reprinted with
permission.
Alterations in the activity of enzymes involved in lipid metabolism likely

mediate the effect of exercise on lipid profiles. Accompanying the absolute
increase in HDL levels with exercise is a shift to the larger, more cardioprotec-
tive HDL2 particle from the smaller HDL3. Exercise increases lipoprotein lipase
(LPL) activity, resulting in greater breakdown of triglyceride-rich particles gen-
erating greater HDL2,while decreases in hepatic triglyceride lipase (HTGL)
reduce catabolism of the HDL2 particle leading to higher concentrations (Seip
et al. 1993). Exercise also alters the chemical composition of LDL particles,
causing a shift toward the larger LDL subtypes which are less atherogenic
(Houmard et al. 1994). The shift toward more cardioprotective subtypes of both
LDL and HDL would not be seen on most lipid assays obtained in clinical prac-
tice, and thus, the modest absolute concentrations of lipid changes observed
with exercise may underestimate the true benefit derived from exercise.
DIABETES MELLITUS
Insulin resistance, glucose intolerance, and diabetes mellitus are powerful

mediators of cardiovascular risk and often precede the clinical onset of clini-
cally apparent disease. Habitual physical activity has been shown to favorably
affect insulin resistance, glucose intolerance, postprandial hyperglycemia, and
hepatic glucose output resulting in HbA1C reductions of up to 1 percent and
reduced use of diabetic medications (Thompson et al. 2001). Perhaps due to
the diverse nature of the benefits associated with exercise, large cohort studies
have demonstrated that the substantial lowering of cardiovascular morbidity
in diabetics is greater than would be expected from glucose lowering alone
(Sigal et al. 2007). In type 2 diabetic patients, there is an incremental benefit to
both duration and pace of aerobic exercise independent of age, gender, body
mass, and severity of diabetes (Tanasescu et al. 2003). One analysis concluded
that two hours of walking per week could prevent one death for every 61
diabetic adults (Gregg et al. 2003). As with cardiovascular risk in the general
population, cardiovascular fitness, as defined by exercise capacity, is highly
predictive of all-cause and cardiac mortality rates in type 2 diabetic patients
(Wei et al. 2003).
Regular compliance with an exercise regimen leads to more efficient energy
utilization by skeletal muscles. In addition to the aforementioned increase in
skeletal muscle blood flow and mitochrondria found in exercise-trained indi-
viduals, there is an upregulation of the insulin-responsive glucose transporter,
GLUT 4, on skeletal muscle cells (Rodnick et al. 1990). GLUT 4 promotes glu-
cose uptake from the blood into muscles, and is likely the mediator of increased
insulin sensitivity seen with exercise. The ability of resistance training to
increase skeletal muscle mass allows it to play an important role in regulating
glucose metabolism. A comprehensive resistance training program has the
capacity to recruit equal, if not greater, muscle mass over extended periods of
time when compared with aerobic training. Resistance training has been dem-
onstrated to favorably influence insulin responses to glucose loads in both dia-
betic and normal subjects in men and women across the full age spectrum
(Miller et al. 1994; Smutok et al. 1993). Several studies have randomized dia-
betic patients to aerobic, resistance, or combined exercise programs. Improved
HgA1c or insulin sensitivity were observed in all groups that performed exer-
cise, with the most favorable results associated with combined aerobic and
resistance regimens (Cuff, 2003; Sigal, 2007; Snowling and Hopkins 2006).
In the acute response to exercise, diabetes may exhibit more volatility in
blood glucose, particularly in insulin-dependent diabetics. In the presence of
Exercise 35
an exogenous source of insulin (i.e., insulin injections), exercise-induced cat-

echolamine responses may paradoxically elevate serum glucose (in poorly
controlled diabetics) or precipitously drop serum glucose if exercise is unusu-
ally vigorous (tightly controlled diabetics). Oral and diet-controlled type 2
diabetics experience less variability in serum glucose with exercise, but serum
glucose can be lowered if medications and meals are taken prior to vigorous
exercise (Poirier et al. 2000). There is conclusive evidence, however, that the
long-term physiologic changes induced with exercise training are beneficial in
glycemic control and are present even in the absence of weight loss (Duncan
et al. 2003).
Several studies are suggestive that regular exercise may prevent the devel-
opment of type 2 diabetes mellitus, likely through increased insulin sensitivity
(Helmrich et al. 1991; Lynch et al. 1996). Physical activity at the level of brisk
walking (5.5 METs) for at least 40 minutes per week appears to be protective
(Lynch et al. 1996).
Due to the high incidence of occult vascular disease in long-standing dia-
betics, it is recommended that anyone over the age of 35 with diabetes of
10 years duration undergo a complete physical examination prior to starting
an exercise regimen. In sedentary subjects, the risk of myocardial infarction is
increased with the adoption of vigorous exercise (Willich et al. 1993). As dia-
betes is often associated with a sedentary lifestyle (upwards of 60 percent prev-
alence in one survey) and obesity, strong consideration should be given to
performing an exercise stress test prior to the initiation of an exercise pro-
gram. Unfortunately, there are presently no randomized trials or large cohort
studies that have looked at the utility of exercise stress testing in diabetics prior
to starting regular physical activity (Nelson, Reiber, and Boyko 2002). In a
recent statement, the American Diabetic Association (ADA) recommended
an exercise stress test be performed in individuals who meet the any of the fol-
lowing criteria (Sigal et al. 2004):
• Age >40 years, with or without CVD risk factors other than diabetes
• Age >30 years and

Diabetes of >10 years duration

Hypertension

Cigarette Smoking
Dyslipidemia
Secondary complications of diabetes (retinopathy, nephropathy-
including microalbuminuria)
• Known coronary artery disease, peripheral vascular disease
• Autonomic neuropathy
• Advanced nephropathy with renal failure.
The presence of diabetic complications should be considered before an

exercise regimen is prescribed. Patients with peripheral neuropathy should
avoid long durations of weight-bearing exercise (running) that may precipitate
or exacerbate foot ulcers. Similarly, high-intensity resistance training should
be discouraged in individuals with retinopathy, given the elevation of both
systolic and diastolic blood pressure that occurs (as above). Diabetics should
be instructed to carefully monitor their blood glucose before, during, and after
exercise so that any changes can be anticipated in subsequent sessions. With
exercise, insulin requirements will be expected to be reduced by 30 percent.
The depletion of muscle glycogen with prolonged exercise may result in hypo-
glycemia. Carbohydrate-rich foods or energy supplements should be available
and taken with aerobic exercise of long-duration (1 hour), both during the
exercise and for several hours afterwards.
Currently, the American Diabetic Association recommends implementing
a goal-based exercise protocol for diabetic patients (Sigal et al. 2004):
• For reduction of CVD, improved glycemic control and weight

maintenance: 150min/wk of moderate-intensity aerobic exercise
(50–70 percent max HR) or 90min/wk of vigorous exercise (>70 per-
cent max HR). This should be done at least 3 days/wk with never more
than 2 consecutive days off.
• For greater CVD reduction: ≥4hrs/wk of moderate to vigorous
aerobic and/or resistance exercise
• For long-term weight loss and maintenance: 7hrs/wk of aerobic
exercise.
When resistance training is added, the ADA recommends three sessions

per week, performing large muscle group exercises. Resistance training should
include 3 sets with 8–10 repetitions of a weight that produces near failure at
the last repetition (Sigal et al. 2004).
HEMOSTATIC EFFECTS
The intrinsic clotting mechanism plays a substantial role in the pathogenesis of

cardiovascular disease. There is significant evidence that exercise conditioning
has a favorable effect on the body’s fibrinolytic system. In one study, platelets
exhibited less adhesion and aggregation after eight weeks of performing
moderate-intensity exercise when compared to sedentary peers, and return to
baseline levels with cessation of regular exercise (Wang, Jen, and Chen, 1995).
It remains controversial whether or not exercise reduces whole blood viscosity,
Exercise 37
with disparate results seen in the medical literature. Nevertheless, regular

physical activity does appear to influence hemostatic factors that mediate vas-
cular thrombosis, and is a recommended therapy for patients with both car-
diac and peripheral vascular disease.
EXERCISE IN SELECTED POPULATIONS
Women
In the United States, one woman dies every minute from cardiovascular dis-
ease (Mosca et al. 2004). Despite this, only 7 of the 43 studies of exercise and
primary prevention of cardiovascular events have included women (Manson
et al. 2002). Thankfully, several of these studies, most notably the Nurse’s
Health Study and the Women’s Health Initiative Observational Study, were
of considerable size (over 70,000 subjects each) to allow for definite conclu-
sions regarding the protective effect of physical activity and cardiovascular
risk. The available evidence suggests that women derive similar cardioprotec-
tive effects from exercise as men. In women with or without cardiovascular
disease, physiologic changes with exercise occur on par with men, resulting
in increases up to 20–30 percent of VO2 max with training (Cannistra
et al. 1992; Spina et al. 1993). In addition to physiologic changes, clinical
outcomes are also similarly improved in women, despite the lack of improve-
ment in lipid profiles as seen with men (as above). All cause mortality is
increased 5-fold in the least conditioned women, and cardiovascular risk is
reduced by 30–50 percent with exercise in both genders. Cardiovascular ben-
efit appears to be independent of age and ethnicity in postmenopausal women,
and can be obtained with both moderate and vigorous exertion (Manson
et al. 2002).
The Young
While physical activity in children is difficult to quantify, over the last several
decades children have been spending more time in sedentary activities, and
the prevalence of childhood obesity is increasing (Ross and Gilbert 1985;
Ross and Pate 1987; Dietz and Gortmaker 1985). Cardiovascular events in
children remain rare, but exercise habits in childhood have been shown to
mirror activity levels as an adult (Kuh and Cooper 1992). A majority of
12-year-old children will have developed one modifiable cardiovascular risk
factor (Riddoch and Boreham 1995). The efficacy of direct intervention on
childhood risk factors remains controversial, but there is evidence that school-
based programs can reduce the sedentary behavior patterns observed with
advancing age (Kelder, Perry, and Klepp 1993).
Participation in organized team sports is highest in adolescence and young
adulthood. While cardiac events remain low in this age group, the sudden
deaths of young competitive athletes are tragic and often due to unsuspected
cardiovascular disease. Both in the United States and Europe, the incidence of
sudden death in young athletes appears to be increasing (Maron, 2003). The
majority of deaths that occur in U.S. athletes under the age of 35 are due to
congenital or acquired cardiac malformation, as opposed to coronary artery
disease in older individuals. Most of these deaths are due to hypertrophic car-
diomyopathy or coronary anomalies, and occur in sports with intense bursts
of activity, such as football or basketball. The combined prevalence of all of
these disease states in young athletes is approximately 0.3 percent, with the
Other (3%) Normal heart (3%)

Other congenital HD (2%)
Ion channelopathies (3%)
Aortic rupture (2%)
Sarcoidosis (1%)
Dilated C-M (2%)
AS (3%)
CAD (3%)
HCM (36%)
Tunneled LAD (3%)
%)
MVP (4
) )
(4% %
VC (6
AR
itis
rd
ca
yo Coronary artery
M
anomalies (17%)
Indeterminate LVH -
possible HCM (8%)
Figure 2.4. Distribution of cardiovascular causes of sudden death in 1435 young com-
petitive athletes. From the Minneapolis Heart Institute Foundation Registry, 1980 to
2005. ARVC indicates arrhythmogenic right ventricular cardiomyopathy; AS, aortic
stenosis; CAD, coronary artery disease; C-M, cardiomyopathy; HD, heart disease;
LAD, left anterior descending; LVH, left ventricular hypertrophy; and MVP, mitral
valve prolapse.
Maron, B. J. et al. 2007 (Update). Recommendations and considerations related to preparticipa-
tion screening for cardiovascular abnormalities in competitive athletes. Reprinted by permission
from Circulation 2007; 115:1643–1655. Copyright 2007 American Heart Association.
Exercise 39
most common condition, hypertrophic cardiomyopathy, present in 1:500

people in the general population (Maron 2003; Maron et al. 2007). The overall
occurrence of sudden death in high school athletes is estimated at 1:200,000
per year (Maron 2003; Maron et al. 2007).
The sheer numbers of young competitive athletes (approximately 10 million),
combined with the low prevalence of disease, makes the adoption of a univer-
sal screening strategy for elevated cardiovascular risk difficult in this popula-
tion. At present, the American Heart Association recommends a personal and
family history in addition to a physical examination before participation in
competitive sports as an effective screen for cardiovascular disease (Maron
et al. 2007). The recommendations highlight 12 items in the pre-participation
screening. A positive value of 1 of the 12 items may be judged sufficient to
Table 2.2. The 12-Element AHA Recommendations for Pre-Participation

Cardiovascular Screening of Competitive Athletes
Medical history∗
Personal history
1. Exertional chest pain/discomfort
2. Unexplained syncope/near-syncope†
3. Excessive exertional and unexplained dyspnea/fatigue, associated with exercise
4. Prior recognition of a heart murmur
5. Elevated systemic blood pressure
Family history
6. Premature death (sudden and unexpected, or otherwise) before age 50 years due to
heart disease, in ≥1 relative
7. Disability from heart disease in a close relative <50 years of age
8. Specific knowledge of certain cardiac conditions in family members: hypertrophic
or dilated cardiomyopathy, long-QT syndrome or other ion channelopathies,
Marfan syndrome, or clinically important arrhythmias
Physical examination
9. Heart murmur‡
10. Femoral pulses to exclude aortic coarctation
11. Physical stigmata of Marfan syndrome
12. Brachial artery blood pressure (sitting position)§
∗ Parental verification is recommended for high school and middle school athletes.
†
Judged not to be neurocardiogenic (vasovagal); of particular concern when related to exertion.
‡
Auscultation should be performed in both supine and standing positions (or with Valsalva
maneuver), specifically to identify murmurs of dynamic left ventricular outflow tract obstruction.
§
Preferably taken in both arms.
Maron, B. J., et al. 2007. Recommendations and considerations related to preparticipation screen-
ing for cardiovascular abnormalities in competitive athletes: 2007 Update. Reprinted by permis-
sion from Circulation 2007; 115: 1643–1655. Copyright 2007 American Heart Association.
warrant further cardiac evaluation. The use of a routine screening ECG, while
recommended by the European Society of Cardiology and the International
Olympic Committee, has not been universally accepted, and at present, is left
up to the discretion of the practitioner. Possibly due to physiologic changes
of exercise on the heart, ECG abnormalities can occur in up to 40 percent of
well-conditioned athletes (Maron et al. 2007). Furthermore, exercise-induced
cardiac enlargement can often mimic hypertrophic cardiomyopathy on echo-
cardiograms, making it difficult to distinguish between an adaptive physiologic
response and a life-threatening cardiac condition. At present, a targeted and
complete personal and family history, combined with a thorough physical
examination, appear to be the most practical screening strategy for young
adults prior to initiation of competitive sports.
The Elderly
Age-related changes in cardiovascular physiology likely contribute to the greater

incidence of and worse prognosis for cardiovascular disease in individuals over
the age of 70. Reductions in maximum heart rate, stroke volume reserve, and
VO2 max are accompanied by increases in central artery stiffness, left ventricu-
lar mass, and impaired diastolic filling (Gerstenblith, Lakatta, and Weisfeldt
1976). Exercise training attenuates some of these changes, with less aortic stiff-
ness, improved ventricular filling, increased nitric-oxide mediated vasodilation,
and a slower rate of decline in exercise capacity seen with regular activity
(Ehsani et al. 1991; Forman et al. 1992; Vaitkevicius et al. 1993). It is important
to note that no adverse outcomes have been reported in older subjects enrolled
in exercise programs. Both older men and women demonstrate improvement
in exercise capacity with training even in the presence of CVD, and have 25 to
50 percent lower risk of death with regular exercise (Blair et al. 1995; Miller,
Balady, and Fletcher 1997; Paffenbarger, 1993). In addition to cardiovascular
protection, aerobic and/or resistance exercise has been associated with reduced
cognitive decline, physical disability, and prolonged autonomy (Miller, Balady,
and Fletcher 1997). For these reasons, older individuals of both genders should
be strongly encouraged to incorporate exercise into their daily regimen.
The Prescription of Exercise
For the beneficial effects of exercise to be maintained, physical activity needs

to be a permanent lifestyle behavior. The recommendation of a health care
provider and an exercise prescription can be powerful motivating factors for
change, but lasting change is difficult to achieve for most patients. Long-term
Exercise 41
compliance with exercise programs in patients enrolled in studies is often a

discouragingly low 20 to 50 percent, even at one year of follow up (Schneider
et al.1992; Simons-Morton et al.1998). Poor long-term compliance, in addi-
tion to financial and time constraints, makes physical activity counseling dif-
ficult to incorporate into an active medical practice. In addition, many health
care providers feel they lack training to provide specific recommendations and
to implement counseling in a cost-effective manner. The Centers for Disease
Control developed Project PACE: Physician-Based Assessment and Counseling
for Exercise in an attempt to address some of these issues (Patrick et al. 1996).
This system is a tool designed to help providers utilize paramedical personnel
to efficiently introduce physical activity counseling into practice.
Factors that have been identified to positively influence adherence to an
exercise recommendation are continued intervention/counseling, multiple
contacts, supervised activity, and utilization of behavioral approaches (Fletcher
et al. 2001). The latter includes a selection of exercises that are enjoyable to the
patient. These should incorporate activities in which the person feels both com-
fortable and safe. Realistic goals, a social support network, and feedback are
essential components. Health care providers themselves should personally
engage in regular exercise—not just to set an example, but to offer insight into
identifying barriers that arise when attempting to maintain an exercise pro-
gram. One approach that appears to aid adherence to exercise is the recom-
mendation that exercise start slowly and gradually increase to meet the target
level. Shorter duration, less intense, and less frequent exercise is safer and more
realistic for previously sedentary individuals to achieve. Exercise programs that
begin immediately with high intensity activity are associated with higher drop-
out rates (Schneider et al. 1992). Successful implementation of effective exer-
cise programs in the health care setting will not only require improved education
of providers, but changes in health care policy and reimbursement as well.
RISKS
The benefits of exercise far outweigh the potential risks, but consideration
should be given to individualize recommendations in an effort to avoid poten-
tial harm. The most common risk of exercise is musculoskeletal injury, typi-
cally from overuse. As up to one-third of injured adults fail to return to exercise
within a year (Hootman et al. 2002), proven prophylactic strategies such as
gradual initiation of exercise, supervised activity, and stretching are of tanta-
mount importance. Intensity and nature of impact correlate more closely with
musculoskeletal injury than duration and should be adjusted accordingly.
Rare, but potentially catastrophic, risks of exercise include cardiac arrhythmia,
myocardial infarction and sudden cardiac death.
Unlike younger athletes, occult coronary artery disease is the overwhelm-

ing cause of exercise-related deaths in individuals over 40. Performance
of high-intensity exercise appears to increase the incidence of sudden death.
In the Physician’s Health Study, the relative risk of sudden death in men was
16.9 up to 30 minutes after exercise when compared with other time periods
(Albert et al. 2000). This increase is also observed in women. However, the
absolute risk remains exceedingly low during any given episode of vigorous
exertion and has been estimated at 1 per 1.5 million episodes of exercise
(Albert et al. 2000). Fatality rates observed in health clubs have been estimated
at 1 case per approximately 900,000 person-hours (Vander, Franklin, and
Rubenfire 1982). Furthermore, while the chance of sudden death is increased
with intensive exercise, this risk is attenuated with the performance of habitual
exercise. In sum, the absolute risk of death for intensive-trained individuals is
lower than their sedentary peers (Whang et al. 2006). Unaccustomed rigorous
activity in sedentary adults confers the greatest risk of sudden cardiac death.
The likely mechanisms of cardiac arrest with exercise include myocardial
infarction from a ruptured cholesterol plaque, or cardiac arrhythmia.
Similar to sudden death, myocardial infarctions are more likely to occur
with exercise, but are less likely to occur in individuals who exercise regularly.
Intense exercise in conditioned individuals confers a risk of myocardial infarc-
tion 2.4 times the baseline level, compared to over 100 times the risk in seden-
tary persons (Mittleman et al. 1993). While still rare, heart attacks occur up to
seven times more frequently than sudden death during exercise. Physical
activity of ≥6 METs within one hour is reported in up to 7 percent of patients
with myocardial infarction (Willich et al. 1993). Nevertheless, the ability of
exercise to reduce cardiovascular events has been demonstrated in symptom-
atic and asymptomatic coronary patients as well as healthy individuals, and
should be encouraged in all individuals.
Both ventricular and atrial arrhythmias are also more likely to occur during
exercise, and are much more common in individuals with prior arrhythmia or
structural heart disease. Regular exercise reduces the incidence of arrhythmia,
likely due to increased vagal tone and reduction of sympathetic nerve stimula-
tion. Of note, this is distinct from arrhythmias observed during diagnostic
cardiac exercise testing, whose significance for predicting flow-limiting coro-
nary disease is well documented.
PRE-EXERCISE EVALUATION
Medical screening prior to the initiation of an exercise program ensures the

lowest possible risk of injury or death during exercise. The presence of signifi-
Exercise 43
cant medical comorbidities would likely necessitate further testing and possi-
bly specialist consultation prior to starting exercise under close supervision.
For individuals with known or suspected cardiovascular disease, the American
Heart Association has published recommendations for secondary prevention,
which include enrollment in cardiovascular rehabilitation programs (Fletcher
et al. 2001). While all individuals derive benefit from exercise training, the
purpose of the medical evaluation is to help guide the level of supervision and
monitoring required during exercise and the individualization needed in the
exercise prescription.
A fitness facility, not a health care provider’s office, may be the site of initial
contact where an evaluation should be performed. The American College of
Sports Medicine/AHA (among others) has published pre-participation screen-
ing questionnaires which will prompt for referral to a healthcare professional
if indicated (Balady et al. 1998).
In the medical evaluation of an apparently healthy individual, the medical
history should focus on risk of cardiovascular disease and the chance of injury if
unsupervised. The latter may include severe obesity or neuromuscular disorders.
Prior MI, bypass surgery, angioplasty, valvular heart disease, congestive heart
failure, or congenital heart disease should be referred for further evaluation and
possible testing prior to initiation of exercise. Symptoms of chest discomfort,
shortness of breath with daily activities, and leg pain consistent with peripheral
arterial disease should be considered cardiovascular disease equivalents and
require referral for subsequent evaluation. All murmurs on exam should be
regarded as indicating cardiovascular disease and triaged accordingly.
Absent any concerns generated in the history and physical examination, age
is the predominant factor determining further evaluation (Fletcher et al. 2001):
• For men <45 years and women <55 years of age with no signs or
symptoms of cardiovascular disease no further workup is required.
• Men ≥ 45 years and women ≥ 55 years with diabetes or 2 other risk
factors for coronary artery disease should perform an exercise stress
test if vigorous exercise is planned. An abnormal test should be fol-
lowed up accordingly and the patient medically managed as if cardio-
vascular disease is present (Gibbons et al. 1997).
If a higher-risk individual chooses not to perform stress testing, modified

exercise targets should be employed, and the patient referred for medical
supervision by trained professionals (to include ACLS certification) during the
initial phases of exercise. Supervised training for 6–12 sessions is recom-
mended, and the individual should be trained in how to monitor his or her
own activity.
Individuals with active/uncontrolled disease should be discouraged from

participation in exercise. The AHA statement on exercise lists conditions
that are contraindications to exercise (Fletcher et al. 2001), as well as specific
recommendations for the amount of exercise that can be tolerated in patients
with active cardiovascular disease.
EXERCISE PRESCRIPTION FOR CARDIOVASCULAR PREVENTION
A threshold of exercise intensity and frequency is likely required to achieve

cardiovascular protection, and appears to be subject to individual variability.
When assessing exercise intensity it is sometimes useful to differentiate
between absolute intensity and relative intensity. Absolute intensity refers to
the metabolic cost of each exercise, and is typically defined by METs (see
above). Relative intensity refers to the percentage of maximum heart rate (or
VO2 max) achieved. For practical purposes, defining activity based on METs
is often the most useful when counseling middle-aged individuals for activity
that confers cardiovascular protection. However, age must be taken into con-
sideration. Due to the age-associated decline in heart rate and max VO2, an
activity of moderate intensity for a middle-aged individual may represent
exercise that is too light for an at-risk patient in his or her 30s, or too vigorous
for an 80-year-old. At the extremes of age, relative intensity defined by heart
rate may be a more appropriate metric to follow.
Higher intensity exercise is required to attain gains cardiovascular fitness,
but not to provide cardiovascular protection (Hagberg et al. 1989; King et al.
1995). It is true, however, that increasing energy expenditure is related to
incremental decrease in cardiovascular risk (Paffenberger, 1986). There is sig-
nificant evidence to suggest that the threshold at which cardiovascular benefit
occurs is at moderately intense exercise between 4 and 6 METs in trials involv-
ing middle-aged subjects (Fletcher et al. 2001). This would equate to exercise
that burns 4–7kcal/min, and lies between 50–70 percent of maximum pre-
dicted heart rate. Examples of activities in this range can include brisk walking
(3–4 miles per hour), yard work, leisurely cycling, and golf. This level of exer-
tion should be achieved after a warm-up period lasting several minutes.
Exercise can be increased to upwards of 85 percent (high intensity) of maximal
heart rate if well tolerated. Older individuals will accrue cardiovascular benefit
from activity as low as 2.0 METs (age 80–89). From a logistical standpoint, a
moderate level of activity has the advantage of greater compliance the exercise
program, while reducing the risk of complications or injury. If exercise is well
tolerated, however, a more rigorous program has the advantages of achieving
Exercise 45
the same (if not more) cardiovascular protection in less time, as well as the
opportunity to improve cardiovascular fitness.
To confer benefit, exercise does not need to be continuous but can be per-
formed throughout the day in short intervals, allowing for integration into
one’s daily life. Emphasis should be placed on aerobic activity, with resistance
training as a supplement. The American Heart Association and the American
College of Sports Medicine recommend 30–60 minutes of moderate intensity
five days a week, or 20 minutes of high intensity exercise three times per week
(Haskell et al. 2007). This equates to a minimum of 150 minutes spent per week
in moderate aerobic activity. Other societies have recommended similar tar-
gets, with slightly longer duration of intensive exercise at 75 minutes per week
(U.S. Department of Health & Human Services 2008). Not surprisingly, the
total amount of exercise performed does highly correlate with weight loss in
addition to cardioprotection.
Significant health benefits can be derived from occupational and leisure-
time activities. Leisure activity should target between 700–1000 kcal/week
to confer benefit. As previously mentioned, prior studies have demonstrated
reduced cardiac event rates in individuals with physically active jobs. However,
unless one hour of brisk walking per day is reliably performed (i.e. postal
route), supplemental activity off-hours should be incorporated into daily
life. Heavy-lifting occupations that meet requirements are increasingly rare
in today’s society. To meet criteria, greater than 20lbs of lifting at least once
an hour, or constant moving of loads without mechanical help, would be
necessary to achieve cardiovascular benefit.
Flexibility and stretching exercises should be encouraged, but not take the
place of, aerobic exercise. Emphasis should be given to the hamstring and
lower back areas in an effort to reduce chronic lower back injury. In addition,
individuals over 40 years of age should avoid repetitive high-impact aerobic
activity, and vary the exercises performed accordingly.
Although resistance training affects cardiovascular risk factors less than
aerobic exercise, it is an accepted and encouraged part of a comprehensive
exercise regimen. In addition to its previously described benefits, increased
muscle mass can reduce the chance of subsequent injury and increase the basal
metabolic rate. Performance of 8–10 exercises targeting the large muscle groups
(chest, arms, back, abdominals, and legs) is recommended. The exercises need
only consist of a single set of 8–12 repetitions (10–15 repetitions at less weight
for older persons to prevent injury) and be performed 2–3 times per week.
This appears to be the minimum required for muscle group adaptation and
maintenance. Any cardiovascular benefit from additional sets and frequency
appears to be small (Feignenbaum and Pollock 1997).
Physical inactivity is the cardiac risk factor that affects the largest number of
individuals in the population, and its reduction through exercise confers ben-
efits on par with other well-established cardiovascular therapies. In addition to
improving cardiovascular health, adherence to an exercise program has a broad
range of benefits for the individual and the society. Greater emphasis on adher-
ence to formal exercise programs involving research, health care policy, and
pubic service announcements would reap considerable benefits for the popula-
tion as a whole. In addition, a health care provider’s act of encouraging, educat-
ing, and supporting regular daily exercise may provide the greatest opportunity
to improve the long term health and quality of life of the individual.
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3
Botanical Medicine and
Cardiovascular Disease
TIERAONA LOW DOG
key concepts
■ A number of botanicals show promise in the field of cardiology,

particularly when used within the context of an integrative
approach.
■ Hawthorn improves symptoms of congestive heart failure;
hibiscus and garlic can lower blood pressure; red yeast rice and
plant sterols effectively improve lipids; parsley seed has diuretic
and naturietic activity; and pycnogenol and horse chestnut
extract may be used to manage chronic venous insufficiency.
■ Clinicians should inquire about patient use of all dietary sup-
plements, including botanicals, and document that usage in the
medical chart.
■ Report adverse events from dietary supplements to FDA
Medwatch and/or your local poison control center.
■
Introduction
H
erbal medicine, also referred to as phytotherapy or botanical medi-
cine, utilizes plants, plant parts, and preparations made from plants
for therapeutic and/or preventive purposes. Herbal medicine gave
rise to the modern sciences of botany, pharmacy, perfumery, and chemistry.
The role of herbal medicine in the management of cardiovascular disease has
been a long and distinguished one. Ancient physicians and healers noted that
remedies such as squill and foxglove could ease the suffering from dropsy, an
55
outdated term for congestive heart failure (CHF). Hawthorn was noted to ben-
efit the aging heart centuries ago. As the science of pharmacy evolved, the first
effective treatment for hypertension, reserpine, and for CHF, digoxin, were
derived from plants (Rauwolfia serpentina and foxglove, respectively). Through
isolating the potent actives in these plants, pharmaceutical products can be
produced with a consistent and uniform composition. Indeed, one primary
drug discovery model has been the identification, isolation, and production of
single active compounds. These active compounds can then be researched,
patented, and sold as drugs.
While some drugs are made directly from plant material, these isolated
compounds are not considered herbal medicines in the classic sense, because
in traditional practice, the plants themselves are considered medicinally func-
tioning wholes. They are chemically complex mixtures and thus the entire
plant, or the part being used (the root, leaf, or seed, for example), is considered
the “active.” Unfortunately, there has been little financial incentive to study
herbal medicines that can be easily grown in the garden or harvested in the
wild. And for herbal manufacturers that do spend the money to do clinical
trials on their herbal product, there is no “patent protection” as there is for
drugs. Furthermore, there is no way for consumers or clinicians to readily dis-
tinguish the clinically tested product from the myriad of “me-too” products in
the marketplace which piggyback off the research of others.
All too often the research that is undertaken is focused on the use of one
particular herb for one specific condition, though most experienced herbal
practitioners individualize their prescriptions based upon the unique charac-
teristics of the patient. Herbal mixtures are often preferred over single herbs
as they are thought to offer greater efficacy, and to some degree, greater safety.
Multi-herb formulations may have additive, or synergistic, effects, and second-
ary herbs can be included to modify potential side effects from the primary
herb. For example, hawthorn may be combined with hibiscus or dandelion for
a patient who has some early CHF. Hawthorn is a positive inotrope and has
been shown to improve CHF symptoms, while hibiscus and dandelion have
noted diuretic activity. Given the number of traditional medical systems that
utilize herbal formulations, the focus on single-herb preparations may be a
critical shortcoming in botanical research. Nevertheless, monotherapy is prob-
ably the best approach for the clinician who is just starting to use herbs in his
or her practice. Getting to know each herb in this way allows the practitioner
to gain greater familiarity and expertise with its use.
Knowledge and tradition are not stagnant, and the field continues to evolve
alongside modern scientific research. Today, we know that plant sterols can
effectively reduce cholesterol and are added to food products as part of a
Botanical Medicine and Cardiovascular Disease 57
“heart-healthy” dietary approach. Flavonoids, responsible for the colors of

flowers, fruit, and sometimes the leaves of plants, are thought to reduce the
risk of coronary artery disease through the inhibition of platelet aggregation,
reducing injury from ischemia and reperfusion (Aviram 1998). The monoun-
saturated fat in olive oil and multiple constituents within garlic have proven to
be beneficial to the cardiovascular system when consumed as part of a healthy
diet. Red yeast rice, which contains naturally occurring statins, has been shown
to lower cholesterol. Parsley seed has significant diuretic and naturietic activ-
ity. Hibiscus lowers blood pressure. From the broadly useful to the very spe-
cific, from crude plant to highly refined extract, the field of herbal medicine
continues to grow and flourish.
Quality of Botanical Products
Given the dizzying array of herbal medicines, it is understandable that both

consumers and health care professionals have difficulty navigating the aisles
of natural food stores and pharmacies. In addition to questions of efficacy and
safety inherent to the individual plant, there are also concerns about the qual-
ity of dietary supplements in general, and botanical products in particular.
Some long-established medical systems, such as Ayurveda and Traditional
Chinese Medicine, occasionally include heavy metals and toxic herbs as part
of their therapeutic approach. Indeed, a number of herbal products from India
and China have been found to contain significant levels of heavy metals, toxic
herbs, and undeclared pharmaceutical medications (Gardiner et al. 2008). In
many cases where herbal products have been found to have had significant
adverse effects, these effects were not due to the herbs listed on the label, but
rather were the result of substitution or contamination of the declared ingredi-
ent, intentionally or accidentally, with a more toxic botanical, a poisonous
metal, or a potent non-herbal drug substance (De Smet 1996).
With the passage of the new good manufacturing guidelines (GMP) by
the Food and Drug Administration (FDA), the problems of contamination,
adulteration, and poor quality will hopefully become less of an issue in the
future (Food and Drug Administration 2007). The inspection of dietary
supplement manufacturers by the FDA increased in 2009, when companies
were required to come into compliance with the new guidelines. This burden
on manufacturers, however, should actually help the industry in the long
run, as consumers will become more confident in the products they purchase,
and health care providers will be more comfortable making supplement
recommendations.
Safety
With widespread consumer use, but a general lack of knowledge about the
safe and effective use of dietary supplements, particularly herbal medicines,
among the majority of health care providers, it is important to address
concerns of safety. Overall, the majority of the herbs and herbal supplements
generally available in the United States and Europe have a relatively good
safety profile when used appropriately, if they are manufactured to high qual-
ity standards. As more concentrated herbal products are introduced into
the marketplace, many of which will be taken for extended periods of time,
new questions of safety will undoubtedly arise. The chronic use of certain
herbs (e.g., comfrey, licorice) can cause hepatic, renal, or electrolyte abnor-
malities. Like any chemically active substance, whether an herb is safe or toxic
depends upon the dose, type of product, and underlying constitution and
health of the patient.
Perhaps more worrying to clinicians is the concern that concomitant use of
botanical remedies with prescription or over-the-counter medications may
lead to adverse interactions, especially in the elderly and those with dimin-
ished renal or hepatic function. A national survey noted that 16 percent of
prescription drug users also reported taking one or more herbal supplements
within the prior week (Kaufman, 2002). It is imperative that clinicians talk
with patients about their use of botanical medicines and other dietary supple-
ments, to help prevent potentially dangerous herb–drug interactions. There
are wide variety of herbal practices and products available, which makes
generalizations difficult; however, by asking a few open-ended questions, clini-
cians should be able to assess the patient’s beliefs, cultural practices, and use of
botanical remedies. Some questions clinicians might find useful follow.
• When you were growing up did you, or your family, ever use any
medicinal plants or herbal remedies to improve your health or treat
an illness?
• How do you use herbs or herbal remedies in your home?
• Are you taking any herbs or herbal medicines now? If so, what are you
trying to treat and do you think the herbs are working?
Document all patient responses in their medical chart and be alert for
potential adverse effects and herb–drug interactions, as well as any therapeutic
benefit.
If you suspect a possible adverse effect, report it to FDA Medwatch at

www.fda.gov/medwAtch. Another excellent resource is to contact your local
poison control center. The new nationwide toll-free number for poison control
is 800-222-1222.
Herbal Medicine in Cardiology
Since specific cardiovascular disorders are covered in depth throughout this

text, this section will explore in broad terms the physiological action of plants
that are utilized in the treatment of cardiovascular disease. When examining
botanicals, it is useful to start with a basic understanding of how they work.
In some cases, scientific research has identified key compounds within the
plant that account for its physiological effects; in other cases, there are multiple
compounds working in harmony that account for the overall therapeutic
effect, making the hunt for an “active compound” futile at best. More than
2000 years ago, practitioners observed the physiologic action of plants and
were able to use them effectively even in the absence of isolating specific com-
pounds or having a detailed understanding of cellular physiology. Plants were
effectively used to treat congestive heart failure, or dropsy as it was once
known, though it would be centuries before the cardioactive glycosides were
identified and isolated.
Thus, this chapter is a blending of traditional wisdom and modern science,
observation and reductionism. It is beyond the scope of this chapter to address
all herbal actions, thus, it will focus only on those commonly considered when
addressing cardiovascular disease.
While this chapter focuses on the use of botanical medicines, it should be

implicitly understood that the use of these remedies must exist within a
framework that includes appropriate diagnosis and other integrative treat-
ment approaches dietary recommendations, mind–body therapies, manual
medicine, or other methods that may promote wellness and healing in the
patient. For the specific integrative management of hypertension, dyslipi-
demia, congestive heart failure, or another specific condition, please see the
appropriate chapters in this book.
ANTI-HYPERTENSIVE HERBS
There are a number of herbs that may be used to address mild cases of
hypertension. Without question, Rauwolfia serpentina is the best known and
understood. The roots of Rauwolfia have been used in India for centuries to
relieve anxiety and treat psychiatric disorders. The isolated alkaloid, reserpine,
revolutionized the management of hypertension in the 1950s. Reserpine
depletes adrenergic neurons of norepinephrine, resulting in decreased sympa-
thetic tone and vasodilation and also likely explaining its traditional use for
certain psychiatric illnesses. Studies show that reserpine plus a thiazide diuretic
has similar efficacy to nifedipine or enalapril (Griebenow et al. 1997; Manyemba
1997). There are concerns for side effects from reserpine (e.g., sedation,
depression) one study noted adverse effects in eleven patients (17.2%) in the
reserpine/diuretic group and nine patients (14.3%) in the enalapril group
(Griebenow et al. 1997). Low dose reserpine is used in a number of poorer
countries when diuretics are not sufficient to control blood pressure. Rauwolfia
is still used by some naturopathic practitioners in non-standardized prepara-
tions. Given the variability of alkaloid levels in the root, this practice should
not be encouraged.
More commonly, herbalists will use diuretics to lower blood pressure
(discussed later in this chapter). A recent metaanalysis concluded that garlic
(Allium sativum) preparations modestly reduce blood pressure in patients with
hypertension. One study showed that grape seed extract reduces systolic and
diastolic blood pressure by twelve and eight points, respectively (Sivaprakasapillai
et al. 2009). Other plants such as linden flower (Tilia platyphllos) and mistletoe
(Viscum album) are also used. But it is hibiscus (Hibiscus sabdariffa) that is
gaining the most attention. The calyces (the outer parts of the flower) are used
in the traditional medicines of India, Africa, Mexico, and South America.
Commonly sold in the American southwest and Mexico as Flor de Jamaica,
studies show that hibiscus is an effective hypotensive agent. It is a reliable
diuretic and inhibits calcium influx into vascular smooth muscle cells (Ajay
et al. 2007; Wright et al. 2007, Ajay 2007). Two studies have shown the
standardized extract (9.6 mg anthocyanins) to be as effective as captopril
and lisinopril in lowering blood pressure (Herrera-Arellano et al. 2004;
Herrera-Arellano et al. 2007). A study of type 2 diabetics found significant
reduction in systolic blood pressure after one month (Mozaffari-Khosravi et al.
2009).
CARDIOACTIVE HERBS
A number of plants contain potent cardioactive glycosides, or substances that

increase the contractility and efficiency of the heart without increasing the
need for oxygen. Cardioactive herbs traditionally found prominence in the
treatment of heart failure. The most widely known in this class include fox-
glove (Digitalis purpurea), white squill (Urginea maritima) and lily-of-the-
valley (Convallaria majalis). Of these, foxglove has been most broadly used
and its glycosides the most researched. In 1785 William Withering, an English
physician, published a treatise on his treatment of heart patients with foxglove
extract, also known as digitalis, though the medicinal use of the plant stretches
originated centuries earlier. A Cochrane review of 13 studies (7896 partici-
pants) of the use of digitalis in the treatment of CHF concluded that “The lit-
erature indicates that digitalis may have a useful role in the treatment of
patients with CHF who are in normal sinus rhythm. New trials are needed to
elucidate the importance of digitalis dosage, and its usefulness in the era of
beta-blockers” (Hood et al. 2004).
While less known than foxglove, the dried sliced bulbs from white squill
have been used to treat heart failure for more than 3,500 years. The remedy
appears in the Egyptian Ebers papyrus (1500 BCE) and Hippocrates described
its use in 5 BCE. The cardioactive glycosides in squill are poorly absorbed
across the GI tract, thus it carries less risk of cumulative toxicity.
Lily-of-the-valley has a long and proven reputation in herbal medicine for
the treatment of cardiac complaints. It is similar to digitalis but less cumula-
tive, associated with fewer adverse effects, and as it has less effect on the con-
duction system, it is preferred for CHF with bradycardia. The German
Commission E monograph approves the use of the herb for “mild cardiac
insufficiency, heart insufficiency due to old age, and chronic cor pulmonale
(Blumenthal 1998).”
Cardiac glycosides have a low therapeutic index and care must be taken when
prescribing them. Given the variability of glycoside levels in the herbs, stan-
dardized products are highly recommended. Only qualified health care pro-
fessionals who are well-versed in the management of cardiac patients should
administer these cardioactive botanicals.
CARDIAC TONICS
In general, herbalists focus on cardiac tonics when addressing the aging heart
and treating mild hypertension and early heart failure. While there are a
number of cardiac tonics, those that dominate the field come from great herbal
traditions. From Euro-American tradition we have hawthorn ( Crataegus spp),
from Ayurveda there is arjuna (Terminalia arjuna), and from the Mediterranean
and Middle East comes Bishop’s weed (Ammi visnaga). Papyrus writings from
ancient Egypt describe the use of Ammi visnaga for the treatment of asthma,
painful kidney stones, and angina. Arjuna tree bark has been used to treat
angina for more than 3,000 years (Narayana and Kumaraswamy 1996).
Experimental studies show that it exerts significant positive inotropic and
hypotensive effects, increasing coronary artery flow and protecting the myo-
cardium against ischemic damage. It also has mild diuretic, antithrombotic,
prostaglandin- enhancing, and hypolipidaemic activity (Dwivedi 2007).
Hawthorn, a flowering shrub in the rose family, has been used by physicians
and herbalists for roughly 2,000 years, and its efficacy and uses have been par-
ticularly widely researched. Hawthorn is widely accepted in Europe as a treat-
ment for mild cases of CHF and minor arrhythmias. While there have been
many clinical studies, the largest was the Survival and Prognosis: Investigation
of Crataegus Extract WS 1442 in Congestive Heart Failure (SPICE) trial.
Conducted in 13 European countries, researchers randomized 2681 patients
with NYHA class II-III heart failure and a left-ventricular ejection fraction
(LVEF) <35% to receive either WS-1442 or placebo for two years, in addition
to their standardized CHF therapy (Holubarsch et al. 2007). Overall, no
beneficial effect was noted. However, in a prospectively planned subgroup
analysis, patients who received hawthorn and had an LVEF of 25 to 35 percent
showed a significantly reduced risk of sudden cardiac death from month 12
to month 24; no such signal emerged for patients with the poorest ventricular
function. This is consistent with the notion that hawthorn is a tonic and that
it is most beneficial in cases of modest dysfunction. It also speaks to its
anti-arrhythmic action. Herbalists generally combine hawthorn with omega-3
Tea is good for the heart. A metaanalysis (Peters, Poole, and Arab 2001) of tea
consumption in relation to stroke, myocardial infarction, and all coronary
heart disease concluded that the incidence rate of myocardial infarction was
estimated to decrease by 11% with an increase in tea consumption of 3 cups
per day (95% CI: 0.79, 1.01) (1 cup = 237 ml)
fatty acids, likely resulting in an additive effect. Importantly, the SPICE trial
found no evidence of herb–drug interactions with any of the drugs taken by
the participants. Cochrane reviewers concluded that when taken in totality,
the evidence “suggests that there is a significant benefit in symptom control
and physiologic outcomes from hawthorn extract as an adjunctive treatment
for chronic heart failure” (Pittler, Guo, and Ernst 2008).
DIURETICS
Diuretics, both in conventional and herbal medicine, are used in the manage-
ment of hypertension and heart failure. Many plants have diuretic effects,
but those that have shown the most promise using modern scientific methods
include parsley (Petroselinum sativum), horsetail (Equisetium spp), fennel
(Foeniculum vulgare), hibiscus (Hibiscus sabdariffa), and the African tradi-
tional medicine Spergularia purpurea, with all showing diuretic and naturietic
effects (Wright et al. 2007).
Parsley is both a culinary herb and an herbal medicine. While the herb can
be used as a diuretic, the seeds are stronger. Parsley seed reduces the activity
of Na+–K+ ATPase in both the renal cortex and medulla, leading to a reduc-
tion in sodium and potassium and resulting in osmotic water flow into the
lumen and diuresis (Kreydiyyeh and Usta 2002). The German Commission E
recognizes both the root and leaf of dandelion for the stimulation of diuresis
(Blumenthal 1998), though studies indicate that the leaf is superior (Wright
et al. 2007).
Diuretics are often used in conjunction with hawthorn for those with mild
hypertension. Serum electrolytes should be periodically monitored.
HYPOLIPIDEMIC PLANT PRODUCTS
Several plant and natural products that are well known for lipid management
include plant sterols, psyllium (Plantago ovata), red yeast rice (Monascus pur-
pureus), garlic (Allium sativum), guggul (Commiphora mukul), artichoke
(Cynara scolymus), and policosanol. The most beneficial in clinical trials are
phytosterols, psyllium, and red yeast rice. Phytosterols impair intestinal
absorption of cholesterol, resulting in a 10–15 percent reduction in LDL-C
with daily intakes of 2 to 3 grams (Plat and Mensink 2001). Plant sterols can be
safely combined with statins, niacin, or red yeast rice, and both the American
Heart Association and the National Cholesterol Education Program Expert
Panel endorse their use. Psyllium and other soluble fibers should be encour-
aged for cardiovascular and overall health.
Red yeast rice products are prepared from cooked, non-glutinous white rice
fermented by the yeast Monascus purpureus. Red yeast rice contains naturally
occurring statins referred to as monocolins, as well as isoflavones and plant
sterols (McCarthy 1998), all of which contribute to its lipid-lowering effects. A
metaanalysis of randomized controlled trials reported that LDL-C is lowered
by 27–32 percent, triglycerides are lowered by 27–38 percent, and HDL-C is
raised by 15–22 percent (Liu et al. 2006). Quality control is a concern, how-
ever, as laboratory testing has found that red yeast products vary widely in
their monocolin content and some contain the mycotoxin citrinin, which is
nephrotoxic in animals (Consumerlabs 2009; Heber et al. 2001). Strict regula-
tions and guidelines are needed to limit the total daily amount of monocolin
and guarantee the absence of mycotoxins.
Red yeast rice can be a suitable choice in patients who do not tolerate statins.
Given the variability in monocolin content, it is advisable to draw labs 8 to
10 weeks after initiation of therapy to determine effectiveness and possible
impact on liver function. Coenzyme Q-10 is often recommended in conjunc-
tion with red yeast rice, as it is with prescription statin drugs.
NERVINE RELAXANTS
Nervine relaxants are those herbs that have a mild tranquilizing or calmative
effect. As chronic stress and depression have both been associated with
increased risk of cardiovascular disease, herbalists generally consider the addi-
tion of a nervine relaxant in their treatment protocol. Those that are typically
used specifically for the cardiovascular system include motherwort (Leonurus
cardiaca) and valerian (Valeriana officinalis). Motherwort is often included
in formulae for hypertensive individuals with a nervous/stress component.
The alkaloids in motherwort, stachydrine, and leonurine are mildly sedating
and hypotensive. Research suggests that leonurine is an inhibitor of vascular
smooth muscle tone, probably acting by inhibiting Ca2+ influx and the release
of intracellular Ca2+ (Chen and Kwan 2001). Lavandulifolioside, another con-
stituent, is responsible for the negative chronotropic and hypotensive effects
reported with motherwort administration (Milkowska-Leyck, Filipek, and
Strzelecka 2002). Those with a “nervous heart” often find relief from palpita-
tions and anxiety-provoked simple tachycardia.
Valerian is often considered in cases where hypertension is accompanied by
stress and insomnia. It is unclear if the hypotensive activity reported by clini-
cians is due to the general calming effect of the herb or a direct vasodilatory
effect. One study found that when valerian was given for seven days to indi-
viduals performing psychological stress tests, there was a significant decrease
in systolic blood pressure and heart rate compared to controls (Cropley et al.
2002). Valerian has been used for at least 1000 years as a calming agent and
sedative. It was officially categorized as a tranquilizer in the United States
Pharmacopoeia from 1820 to 1942. Unlike conventional benzodiazepines, val-
erian is not addictive and has been shown to reduce anxiety (Andreatini et al.
2002) and total stress severity and to induce sleep (Wheatley 2001).
VASCULAR TONICS
Relieving the discomfort of varicose veins or chronic venous insufficiency

(CVI) has long been under the herbalist’s purview. The seeds and bark of
the horse chestnut tree have been used as vascular tonics in Europe for at least
400 years. The seed was primarily used for the treatment of varicose veins,
hemorrhoids, phlebitis, neuralgia, and rheumatic complaints. A metaanalysis
of six trials found that horse chestnut extract was superior to placebo for CVI,
and one trial indicated it is as effective as treatment with compression stock-
ings (Pittler and Ernst 2006). Pycnogenol (patented trade name for a water
extracted French maritime pine bark [Pinus pinaster ssp. Atlantica]) has been
shown in clinical trials to rapidly improve CVI, and when taken both inter-
nally and applied topically, it heals venous ulcerations (Belcaro et al. 2005;
Cesarone et al. 2006). Other vascular tonics include bilberry (Vaccinium myr-
tillis) and ginkgo (Ginkgo biloba).
Summary
When reviewing the history and contemporary research, it is clear that

herbal medicines have played, and continue to play, a significant role in treat-
ing disease and improving health. Given the vast number of botanicals that
have yet to be explored for their medicinal effects, it is likely that plants will
continue to contribute to our understanding and management of cardiovascu-
lar disease. However, there remains much work to be done from “bench to
bedside” to determine which botanicals are most efficacious and how they are
best used in clinical practice. Unlike many pharmaceutical drugs, there are few
long-term outcome studies using medicinal plants. While this chapter cites the
clinical trials that are being conducted on herbal medicines for cardiovascular
health, the research literature reflects only a very small percentage of plants
that have potential benefit. There is a definite need for more rigorous and
creative research in this area.
The following is a list of resources that clinicians may use to obtain current,
authoritative information regarding the safe and effective use of herbal therapies.
GOVERNMENT WEB SITES
The National Center for Complementary

and Alternative Medicine (NCCAM)
www.nccam.nih.gov
NCCAM provides information on complementary and alternative medicine for
consumers, health care providers, and researchers. The site include fact sheets, an
online newsletter, clinical trial information, and general health information in both
English and Spanish.
Office of Dietary Supplements (ODS)

www.ods.od.nih.gov/index.aspx
This is a very helpful site with a wealth of free material available. In the “Quick Links”
section you can access dietary supplement fact sheets and a link to the International
Bibliographic Information on Dietary Supplements (IBIDS).
Health Canada
www.hc-sc.gc.ca
The Canadian government regulates natural health products by licensing those
with proof of safety and efficacy. This is a helpful Web site that provides a list of prod-
ucts licensed in Canada and also contains a number of monographs.
OTHER WEB SITES
American Botanical Council

www.herbalgram.org
The American Botanical Council is a nonprofit and international member-based
organization providing education using science-based and traditional information on
herbal medicine. The Web site offers an excellent online bookstore and an “Herb Clip”
service summarizing current research articles, as well as an educational resource

section offering continuing education credits for health care professionals.
Natural Medicines Comprehensive Database

www.naturaldatabase.com
Th herbal monographs available on this site include extensive information about
common uses, evidence of efficacy, safety, mechanisms, interactions, and dosage. This
site also provides continuing medical education courses, information organized by
medical condition, a listserv, and a section on supplement–drug interactions. This Web
site is available by subscription only.
Natural Standard
www.naturalstandard.com
This subscription-only site is an independent collaboration of international clini-
cians and researchers who have created a database that can be searched by CAM subject
or by medical condition. The quality of evidence is ranked for each supplement.
Consumer Labs
www.consumerlabs.com
This site, available by subscription, evaluates commercially available dietary supple-
ments for composition, purity, bioavailability, and consistency of products.
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4
An Aspirin a Day Is Even Better
than an Apple a Day!
JAMES E. DALEN
key concepts
■ Aspirin is effective in the primary and secondary prevention of

myocardial infarction and ischemic stroke.
■ The primary side effect of aspirin is bleeding. As compared to
placebo, aspirin, at doses from 81 to 325 mg/day, is associated
with an excess of one to three cases of major bleeding per 1,000
patients per year.
■ The incidence of major bleeding is not dose related at doses
from 81 to 325 mg/day.
■ Doses less than 162 mg/day have been ineffective in preventing
stroke and myocardial infarction in 6 primary prevention trials.
■ The author recommends a dose of 162 mg (two baby aspirin per
day) for the primary and secondary prevention of stroke and
myocardial infarction.
■
D
aily aspirin consumption for the prevention of myocardial infarction
and stroke is a classic example of an unconventional therapy that has
become conventional therapy.
Aspirin was first synthesized in 1853 by Bayer. It began to be used for the
treatment of rheumatism in 1899 (Dalen 1991). The first report suggesting that
aspirin may have a cardiovascular indication was a paper by Craven published
in 1950. He reported that aspirin prevented heart attacks. Six years later,
Craven reported that aspirin also prevented strokes (1956). Craven based his
reports on clinical observations and a clinical trial without controls. As a busy
general practitioner, he noted an increased incidence of bleeding in patients in
70
An Aspirin a Day Is Even Better than an Apple a Day! 71
whom he had performed a tonsillectomy. He noted that the increase in bleed-

ing occurred about the same time that he began to use aspergum (aspirin) as a
post-operation pain reliever. He concluded that aspirin was a mild anticoagu-
lant. At that time, patients with myocardial infarction were treated with
dicumarol, an oral anticoagulant. He reasoned that dicumarol might prevent
heart attacks in those at increased risk. He worried that dicumarol would cause
excess bleeding; but his newly discovered mild anticoagulant, aspirin, might
just do the trick. In 1948 he advised all his male patients aged 45 to 65 to take
10 to 30 grains (650 mg to 2 grams) of aspirin a day. After 2 years, he noted that
none of his 400 patients had suffered a myocardial infarction (Craven, 1950).
He continued his trial, and in 1953 he reported that not a single member of his
study group of 1465 healthy overweight and sedentary men had suffered a
myocardial infarction (Craven, 1953). He did not have a control group, and
there was limited statistical analysis. He stated that “in such a large group of
subjects of this type most likely to experience coronary episodes it is—to say
the least—remarkable that all remained healthy and active” (Craven, 1953).
In 1953, Craven decreased the aspirin dose to 325 mg per day. In 1956
he reported that none of his now 8000 patients taking aspirin had suffered
a myocardial infarction and that none had suffered a stroke or transient
ischemic attack (TIA)—so he reported that aspirin also prevents strokes
(Craven, 1956).
After I published an article in 1991 (Dalen 1991) about Craven’s reports I
received a call from a New York Times reporter asking for me for more infor-
mation about Dr. Craven. I suggested that he call the local medical society
in Glendale, California to determine if any physicians remembered Craven.
He located two physicians who knew Craven. One said that Craven was a
genius, the other said that he was crazy! I do not know if he was a genius, but
he certainly was right about aspirin.
After hundreds of randomized clinical trials it has become clear that aspirin
is effective in the primary and secondary prevention of stroke and myocardial
infarction. (Dalen, 1991) A metaanalysis of more than 100 randomized trials
found that aspirin prevents vascular death by 15 percent, and non-fatal vascu-
lar events (myocardial infarction and stroke) by 30 percent (Antithrombotic
Trialists Collaboration 2002). Not bad for an over-the-counter drug costing
pennies!
Aspirin inhibits platelet activation by inactivating platelet COX-I activity.
The inhibition of platelet activation decreases the incidence of thrombosis in
atherosclerotic coronary and cerebral arteries. Aspirin does not decrease the
incidence of atherosclerosis; it decreases the incidence of myocardial infarc-
tion and stroke in patients who have atherosclerosis involving the coronary or
cerebral arteries. Aspirin is not effective in preventing venous thrombosis.
At present more than 30 million Americans, including 49 percent of all

Americans ages 65 and older, take aspirin for prevention of stroke and myo-
cardial infarction. Aspirin therapy for prevention has evolved into conven-
tional, mainstream therapy.
Complications of Aspirin
The primary complication of aspirin therapy is bleeding, especially gastroin-

testinal bleeding. The incidence of minor bleeding increases with the dose of
aspirin. However, in doses ranging from 50 mg/day to 325 mg/day, the inci-
dence of major bleeding is not related to the dose of aspirin. The excess of
major bleeding compared to placebo is one to three cases per 1000 patients per
year (Berger et al. 2009; Patrono et al. 2008). In five placebo-controlled trials
involving 368,000 patient years of aspirin therapy, there was no difference in
the risk of fatal bleeding between aspirin (50–500 mg/day) and placebo, as
shown in Table 4.1 (Collaborative Group of the Primary Prevention Project
2001; Hansson et al. 1998; Peto et al. 1988; Ridker et al. 2005; Steering
Committee of the Physicians’ Health Study Group 1989).
Contraindications to Aspirin
The only absolute contraindications to aspirin are a documented allergy to

aspirin or non-steroidal antiinflammatory drugs, or the presence of active
Table 4.1. Fatal Bleeding During Aspirin Therapy

Fatal Bleeds
Study Dose/Day Pt/years ASA Placebo
WHS, 2005 50 mg 199,380 2 3
HOT, 1998 75 mg 17,850 7 8
PPP, 2001 100 mg 80,928 1 3
PHS, 1989 160 mg 55,175 1 0
UK, 1988 500 mg 15,41 3 3
TOTAL 14 17
WHS = Women’s Health Study HOT = Hypertension Optimal Treatment Study PPP = Primary
Prevention Project PHS = Physician’s Health Study UK = British Physician Study
bleeding. The relative contraindications are a history of peptic ulcer or GI

bleeding.
What is the Right Dose?
The appropriate dose for primary and secondary prevention of stroke remains
controversial. All agree that it is 325 mg/day or less. However, some suggest
81mg (one baby aspirin), some say 162 mg (two baby aspirin), and some sug-
gest 325 mg (one adult aspirin). Others suggest any dose from 81 to 325 mg.
Determining the recommended dose should not be so difficult. The price of
aspirin is minimal and there is no difference in the incidence of major bleed-
ing in doses ranging from 81 to 325 mg.
There is some evidence that the dose for secondary prevention in patients
with a history of coronary artery disease or stroke is less than the dose required
for primary prevention The European Stroke Prevention Study found that
50 mg of aspirin per day decreased the risk of recurrent stroke by 18% in
patients with a history of stroke or TIA. (Diener, 1996).
In patients with stable angina pectoris Juul-Moller reported a 34% reduc-
tion in myocardial infarction (MI) or death as compared to placebo in patients
treated with 75 mg of aspirin daily. (Juul-Moller, 1992.) In a study of 796 men
with unstable angina there was a 31% reduction in myocardial infarction or
sudden death with 75 mg of aspirin per day. (RISC Group,1990). Other studies
of secondary prevention in patients with a history of stroke or myocardial,
infarction have found doses of 160 mg or 300 mg per day to be effective.(Lewis,
1983; ISIS-2, 1988; CAST,1997).
The most commonly recommended dose for primary prevention of myo-
cardial infarction and stroke is 81 mg/day (Bhatt et al. 2008). I believe that this
dose is too low. Doses less than 162 mg/day failed to prevent stroke and myo-
cardial infarction in six primary prevention trials (Collaborative Group of the
Primary Prevention Project 2001; Hansson et al. 1998; Ogawa et al. 2008;
Ridker et al. 2005; Belch et al. 2008; Fowkes. 2009.
Strong evidence that an aspirin dose of 162 mg/day is effective in the pri-
mary prevention of myocardial infarction was reported by the US Physicians’
Health study. (Physicians’ Health Study Group, 1989). More than 20,000 US
physicians were randomized to 325 mg of aspirin every other day or placebo.
After five years of follow-up there was a 44% reduction in MIs in those taking
aspirin.
I am convinced that the optimal dose for primary and secondary preven-
tion of myocardial infarction and stroke in men and women is 162 mg/day
(Dalen 2010) . This can be given as 2 baby aspirin a day, one-half adult aspirin
a day, or one adult aspirin every other day; whichever is most convenient for
the patient. There is no clear evidence that buffered aspirin or enteric-coated
aspirin are less effective or have fewer side effects than regular aspirin.
What about Aspirin Resistance?
Some patients who have been prescribed long-term aspirin therapy develop
myocardial infarction or stroke. When this occurs does it mean treatment fail-
ure, or does it indicate that the patient is resistant to aspirin? Or, is there
another explanation?
Treatment failure is certainly a reasonable explanation. No therapy, conven-
tional or unconventional, is 100 percent effective. Patients have myocardial
infarction and/or stroke despite effective therapy of hypertension or hyperlipi-
demia, so why should aspirin therapy be any different?
Some suggest that the explanation for the occurrence of vascular event in
patients prescribed aspirin is aspirin resistance, that is, the failure of aspirin to
suppress thromboxane generation and thus not prevent platelet aggregation.
Some have suggested that all 30 million patients taking aspirin therapy should
be tested for aspirin resistance.
The gold standard for determining aspirin’s effect on platelets is optical
aggregometry, also called light transmission aggregometry. Several other
platelet function tests that can be performed at the bedside are also available
(Dalen 2007).
Unfortunately, these tests are not concordant. The incidence of aspirin
resistance utilizing optical aggregometry is less than 1 percent in most reports.
The incidence with the two bedside tests is much higher; in the range of 20 to
30 percent (Dalen 2007).
Reports that patients with laboratory evidence of aspirin resistance are at
increased risk of myocardial infarction or stroke are inconclusive. The clinical
relevance of aspirin resistance is uncertain. I agree with the recent recommen-
dation from the American College of Chest Physicians that routine testing for
aspirin resistance is not indicated (Patrono et al. 2008).
There is a third explanation for the occurrence of stroke or myocardial
infarction in patients prescribed aspirin: noncompliance (Dalen 2007). A very
significant study reported on 190 patients with myocardial infarction who had
been prescribed 81 to 325 mg aspirin/day. Seventeen (9 percent) were aspirin
resistant by light aggregometry. When the 17 were questioned, 10 admitted
that they were not taking the aspirin. When the test was repeated after the 17
were observed ingesting 325 mg aspirin, only one patient was found to be aspi-
rin resistant (Schwartz, 2005).
Several other studies have confirmed the findings of Schwartz: aspirin resis-
tance is very rare in patients who actually take aspirin. Noncompliance is the
most common explanation for aspirin resistance as measured by laboratory
tests. The most common cause of stroke or myocardial infarction in patients
who are compliant with aspirin therapy is treatment failure. There is no evi-
dence that myocardial infarction or stroke occurring in patients prescribed
aspirin is due to aspirin resistance.
Who should take Aspirin?
In the absence of contraindications, all patients with evidence of coronary

artery disease— including patients with a history of myocardial infarction,
coronary artery bypass surgery, angioplasty, or angina, and patients in whom
coronary disease has been diagnosed by angiography—should take 162 mg
aspirin/day for their entire lives. Lifelong aspirin therapy is also indicated
in patients with a history of ischemic stroke, and patients with peripheral
arterial disease. Aspirin is also recommended in patients who are at increased
risk of having asymptomatic coronary artery disease. Patients with multiple
risk factors—including diabetes, hypertension, hypercholesterolemia, and
smoking—should take aspirin unless there are contraindications.
In addition, age is a risk factor for coronary artery disease in the United
States. One should consider aspirin therapy in men age 50 and older, and post-
menopausal women.
In patients with atrial fibrillation, aspirin (325 mg/day) is indicated when
there are contraindications to long-term warfarin therapy. Aspirin decreases
the incidence of stroke and arterial embolism in patients with atrial fibrillation
by 21 percent, compared to 68 percent with warfarin therapy (Singer et al.
2008).
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5
Metabolic Cardiology
STEPHEN T. SINATRA
key concepts
■ Attention to the energy demands of diseased hearts is often

missing in conventional cardiology practice.
■ Disease states and the use of certain medications are asso-
ciated with depletion of key factors needed for cardiac energy
production.
■ Metabolic support with D-ribose, Coenzyme Q10, L-carnitine,
and magnesium can be important for the maintenance of myo-
cardial energy reserves.
■
O
ptimal cardiovascular function is dependent on maintaining adequate
energy reserves. Metabolic cardiology highlights the importance of
sustaining key enzymatic and biochemical reactions that revitalize the
energy charge in oxidative ischemic or hypoxic hearts (Sinatra 2005; 2009).
Efforts to support the metabolic needs of the heart have well documented
benefits, yet are not known to most cardiologists. The therapies to be outlined
carry the added advantage of an excellent safety profile a key factor in light of
the finding that the fourth leading cause of death in the United States is prop-
erly prescribed medications (Lazaron, Pomeranz, and Corey 1989). The impor-
tance of supporting energy production in myocytes and the preservation of
the mitochondria in these cells will be the focus of this discussion.
Cardiac Energy Metabolism: Bench to Bedside
Bioenergetics is the study of energy transformation in living organisms.

Understanding the distinction between the concentration of ATP in the cell
78
Metabolic Cardiology 79
and the efficiency of ATP turnover and recycling is central to our appreciation
of cellular bioenergetics. It is now widely accepted that one characteristic of
the failing heart is the persistent and progressive loss of energy. The require-
ment for energy to support the systolic and diastolic work of the heart is abso-
lute. Therefore, a disruption in cardiac energy metabolism, and the energy
supply/demand mismatch that results, can be identified as the pivotal factor
contributing to the inability of failing hearts to meet the hemodynamic require-
ments of the body. In her landmark book, ATP and the Heart, Joanne Ingwall,
PhD, describes the metabolic process associated with the progression of CHF,
and identifies the mechanisms that lead to a persistent loss of cardiac energy
reserves as the disease process unfolds (2002).
The heart consumes more energy per gram than any other organ, and the
chemical energy that fuels the heart comes primarily from adenosine triphos-
phate, or ATP (Figure 5.1). The chemical energy held in ATP is resident in the
phosphoryl bonds, with the greatest amount of energy residing in the outer-
most bond holding the ultimate phosphoryl group to the penultimate group.
When energy is required to provide the chemical driving force to a cell, this
ultimate phosphoryl bond is broken and chemical energy is released. The cell
then converts this chemical energy to mechanical energy to do work.
The consumption of ATP in the enzymatic reactions that release cellular
energy yields the metabolic byproducts adenosine diphosphate (ADP) and
inorganic phosphate (Pi) (Figure 5.2). A variety of metabolic mechanisms have
evolved within the cell to provide rapid re-phosphorylation of ADP to restore
ATP levels and maintain the cellular energy pool. But, these metabolic mecha-
nisms can easily become disrupted, tipping the balance in a manner that creates
a chronic energy supply/demand mismatch that results in an energy deficit.
NH2
N C N
HC
CH
N C N
O O O Adenine
O
O− P O P O P O
H H
O− O− O−
H H
3 - Phosphates OH OH
D-Ribose
Figure 5.1. ATP is composed of D-ribose, adenine, and three phosphate groups.
Breaking the chemical bond attaching the last phosphate group to ATP releases chem-
ical energy that is converted to mechanical energy to perform cellular work.
ATP
+Pi −Pi
ADP
Figure 5.2. When ATP is used the remaining byproducts are adenosine diphosphate
(ADP) and inorganic phosphate (Pi). ADP and Pi can then recombine to form ATP in
the cellular processes of energy recycling. When oxygen and food (fuel) is available,
energy recycling occurs unimpeded millions of times per second in every cell in the
body. Lack of oxygen or mitochondrial dysfunction severely limits the cell’s ability to
recycle its energy supply.
The normal non-ischemic heart is capable of maintaining a stable ATP con-

centration despite large fluctuations in workload and energy demand. In a
normal heart, the rate of cellular ATP synthesis via re-phosphorylation of ADP
closely matches ATP utilization. The primary site of cellular ATP re-phospho-
rylation is the mitochondria, where fatty acid and carbohydrate metabolic
products flux down the oxidative phosphorylation pathways. ATP recycling
can also occur in the cytosol via the glycolytic pathway of glucose metabolism,
but in normal hearts this pathway accounts for only about 10 percent of ATP
turnover.
ATP levels are also maintained through the action of creatine kinase in a
reaction that transfers a high-energy phosphate creatine phosphate (PCr) to
ADP to yield ATP and free creatine. Because the creatine kinase reaction is
approximately 10 times faster than ATP synthesis via oxidative phosphoryla-
tion, creatine phosphate acts as a buffer to assure a consistent availability of
ATP in times of acute high metabolic demand. Although there is approxi-
mately twice as much creatine phosphate in the cell as ATP, there is still only
enough to supply energy to drive about 10 heartbeats, making the mainte-
nance of high levels of ATP availability critical to cardiac function.The content
of ATP in heart cells progressively falls in CHF, frequently reaching and then
stabilizing at levels that are 25 percent to 30 percent lower than normal (Ingwall
2004; 2006). The fact that ATP falls in the failing heart means that the meta-
bolic network responsible for maintaining the balance between energy supply
and demand is no longer functioning normally. It is well established that
oxygen deprivation in ischemic hearts contributes to the depletion of myocar-
dial energy pools, but the loss of energy substrates in the failing heart is a
unique example of chronic metabolic failure in the myocardium.
One of the mechanisms responsible for energy depletion in heart failure is

the loss of energy substrates and the delay in their resynthesis. In conditions
where energy demand outstrips supply, ATP is consumed at a rate that is faster
than it can be restored via oxidative phosphorylation or the alternative path-
ways of ADP re-phosphorylation. The cell has a continuing need for energy, so
it will use all its ATP stores and then break down the by-product, adenosine
diphosphate (ADP), to pull the remaining energy out of this compound as
well, resulting in the production of adenosine monophosphate (AMP).
Since a growing concentration of AMP is incompatible with sustained
cellular function, it is quickly broken apart and the by-products are washed
out of the cell. The net result of this process is a depletion of the cellular pool
of energy substrates. When the by-products of AMP catabolism are washed
out of the cell, they are lost forever (Figure 5.3). It takes a long time to replace
these lost energy substrates, even if the cell is fully perfused with oxygen again.
This reduction in energy is like a depleted car battery struggling to start the
engine. In diseased hearts the energy pool depletion via this mechanism can
Heart or Muscle Cell Plasma
Adenosine
5’ nucleotidase
ADP ADP
Net Loss
Adenylate kinase of
Purines
ATP AMP
AMP deaminase
IMP
Inosine
Hypoxanthine
Figure 5.3. When the cellular concentration of ATP falls and ADP levels increase, two
molecules of ADP can combine. This reaction provides one ATP, giving the cell addi-
tional energy, and one AMP. The enzyme adenylate kinase (also called myokinase)
catalyzes this reaction. The AMP formed in this reaction is then degraded and the
byproducts are washed out of the cell. The loss of these purines decreases the cellular
energy pool and is a metabolic disaster to the cell.
be significant, reaching levels that exceed 40 percent in ischemic heart disease

and 30 percent in heart failure.
Under high workload conditions, even normal hearts display a minimal
loss of energy substrates. These substrates must be restored via the de novo
pathway of ATP synthesis. This pathway is slow and costly in terms of energy,
requiring consumption of six high-energy phosphates to yield one newly syn-
thesized ATP molecule. The slow speed and high energy cost of de novo syn-
thesis highlights the importance of cellular mechanisms designed to preserve
energy pools. In normal hearts the salvage pathways are the predominant
means by which the ATP pool is maintained.
While de novo synthesis of ATP proceeds at a rate of approximately 0.02
nM/min/g in the heart, the salvage pathways operate at a rate that is 10 times
higher (Manfredi and Holmes 1985). The function of both the de novo and
salvage pathways of ATP synthesis is limited by the cellular availability of
5-phosphoribosyl-1-pyrophosphate, or PRPP (Figure 5.4). PRPP initiates
these synthetic reactions, and is the sole compound capable of donating the
D-ribose-5-phosphate moiety required to re-form ATP and preserve the
energy pool. In muscle tissue, including that of the heart, formation of PRPP
is slow and rate limited, impacting the rate of ATP restoration via the de novo
and salvage pathways.
Adenine
D-Ribose PRPP
ATP AMP Adenosine
De Novo Synthetic Catabolic & Salvage

Pathway Pathways
IMP Hypoxanthine
PRPP
D-Ribose PRPP D-Ribose Uric Acid
Denotes intermediate steps
Figure 5.4. Replacing lost energy substrates through the de novo pathway of energy
synthesis begins with D-ribose. D-ribose can also “salvage” AMP degradation prod-
ucts capturing them before they can be washed out of the cell. Both the de novo and
salvage pathways of energy synthesis are rate limited by the availability of D-ribose in
the cell.
Energy Starvation in the Failing Heart
The chronic mechanism explaining the loss of ATP in CHF is decreased ATP
synthesis relative to ATP demand. In part, the disparity between energy supply
and demand in hypertrophied and failing hearts is associated with a shift in
relative contribution of fatty acid versus glucose oxidation to ATP synthesis.
The major consequence of the complex readjustment toward carbohydrate
metabolism is that the total capacity for ATP synthesis decreases. At the same
time, the demand for ATP continually increases as hearts work harder to cir-
culate blood in the face of the increased filling pressures that are associated
with congestive heart failure and cardiac dilation.
The net result of this energy supply/demand mismatch is a decrease in the
absolute concentration of ATP in the failing heart, and this decrease in abso-
lute ATP level is reflected in a lower energy reserve in the failing and/or hyper-
trophied heart. A declining energy reserve is directly related to heart function,
with diastolic function being the first to be affected, followed by systolic func-
tion, and finally global performance (Figure 5.5). In ischemic or hypoxic
hearts, the cell’s ability to match ATP supply and demand is disrupted leading
Sodium/Potassium Pump
Calcium Pump Contraction

Normal
kJ/mole
(absolute value)
70 56 52 48 46 40
Contractile
Reserve
Figure 5.5. Cellular energy levels can be measured as the free energy of hydrolysis of
ATP, or the amount of chemical energy available to fuel cellular function. Healthy,
normal hearts contain enough energy to fuel all the cellular functions, with a contractile
reserve for use in emergency. Cellular mechanisms used in calcium management
and cardiac relaxation (Diastole) require the highest level of available energy. Sodium/
potassium pumps needed to maintain ion balance are also significant energy consum-
ers. The cellular mechanisms associated with contraction require the least amount of
cellular energy. Thus, when ATP levels drop, and since more energy is required to
break calcium bonds, diastolic dysfunction deteriorates. Therefore, filling the heart
with blood requires more ATP than emptying the heart.
to both depletion of the cardiac energy pool and dysfunction in mitochondrial

ATP turnover mechanisms. When ATP levels drop, diastolic heart function
deteriorates.
Diastolic dysfunction is an early sign of myocardial failure, despite the
presence of normal systolic function and preserved ejection fraction. High
concentrations of ATP are required to activate calcium pumps necessary
to facilitate cardiac relaxation and promote diastolic filling. This observation
leads to the conclusion that, in absolute terms, more ATP is needed to fill
the heart than to empty it, consistent with Starling’s Law, which requires
more energy in diastole than in systole. This absolute requirement for ATP in
the context of cardiac conditions in which energy is depleted makes a meta-
bolic therapeutic approach such a reasonable intervention.LaPlace’s law
confirms that pressure overload increases energy consumption in the face of
abnormalities in energy supply. In failing hearts these energetic changes
become more profound as left ventricle remodeling proceeds (Gourine et al.
2004; Hu et al. 2006; Ye et al. 2001),8 but they are also evident in the early
development of the disease (Maslov et al. 2007). It has additionally been found
that similar adaptations occur in the atrium, with energetic abnormalities
constituting a component of the substrate for atrial fibrillation in CHF (Cha
et al. 2003).
Left ventricular hypertrophy is initially an adaptive response to chronic
pressure overload, but it is ultimately associated with a 10-fold greater likeli-
hood of subsequent chronic CHF. While metabolic abnormalities are persis-
tent in CHF and left ventricular hypertrophy, at least half of all patients with
left ventricular hypertrophy-associated heart failure have preserved systolic
function, a condition referred to as a diastolic heart failure.
Oxidative phosphorylation is directly related to oxygen consumption,
which is not decreased in patients with pressure-overload left ventricular
hypertrophy (Bache et al. 1999). Metabolic energy defects, instead, relate to
the absolute size of the energy pool and the kinetics of ATP turnover through
oxidative phosphorylation and creatine kinase. Dysfunctional ATP kinetics
is similar in both systolic and diastolic heart failure, and may be both an initi-
ating event and a consequence.Inadequate ATP availability would be expected
to initiate and accentuate the adverse consequences of abnormalities in
energy-dependent pathways. Factors that increase energy demand, such as
adrenergic stimulation and systolic overload, exaggerate the energetic deficit.
Consequently, the hypertrophied heart is more metabolically susceptible to
stressors such as increased chronotropic and inotropic demand, and ischemia.
In humans, this metabolic deficit is shown to be greater in compensated left
ventricular hypertrophy (with or without concomitant CHF) than in dilated
cardiomyopathy (Smith et al. 2006; Weiss, Gerstenblith, and Bottomley 2005).
Hypertensive heart disease alone was not shown to contribute to alterations

in high energy phosphate metabolism, but it can contribute to left ventricular
hypertrophy and diastolic dysfunction, which can later alter cardiac energetics
(Beer et al. 2002; Lamb et al. 1999). Further, for a similar clinical degree
of heart failure, volume overload hypertrophy does not, but pressure overload
does, induce significant high-energy phosphate impairment (Neubauer et al.
1997).
Type 2 diabetes has also been shown to contribute to altering myocardial
energy metabolism early in the onset of diabetes, and these alterations in car-
diac energetics may contribute to left ventricular functional changes (Diamant
et al. 2003). The effect of age on progression of energetic altering has also been
reviewed, with results of both human (Schocke et al. 2003) and animal (Perings
et al. 2000) studies, suggesting that increasing age plays a moderate role in the
progressive changes in cardiac energy metabolism that correlates to diastolic
dysfunction, left ventricular mass, and ejection fraction.
Cardiac energetics also provide important prognostic information in
patients with heart failure, and determining the myocardial contractile reserve
has been suggested as a method of differentiating which patients would most
likely respond to cardiac resynchronization therapy (CRT) seeking to reverse
LV remodeling (Ypenburg et al. 2007). Patients with a positive contractile
reserve are more likely to respond to CRT and reverse remodeling of the left
ventricle. Non-responders show a negative contractile reserve, suggesting
increased abnormality in cardiac energetics.
Taken together, results of clinical and laboratory studies confirm that energy
metabolism in CHF and left ventricular hypertrophy is of vital clinical impor-
tance. Impaired diastolic filling and stroke volume limit the delivery of
oxygen-rich blood to the periphery. This chronic oxygen deprivation forces
peripheral muscles to adjust and down-regulate energy turnover mechanisms,
a contributing cause of symptoms of fatigue, dyspnea and muscle discomfort
associated with CHF.
The following discussion will review metabolic interventions intended to
preserve myocardial energy substrates. Therapies to be discussed include:
D-ribose, Coenzyme Q10, L-carnitine, and magnesium.
ENERGY NUTRIENTS FOR CONGESTIVE HEART FAILURE
D-ribose (Ribose)
The effect of the pentose monosaccharide, D-ribose, in cardiac energy metab-

olism has been studied since the 1970s, with clinical studies describing its
value as an adjunctive therapy in ischemic heart disease first appearing in

1991. Ribose is a naturally occurring simple carbohydrate that is found in
every living tissue, and natural synthesis occurs via the oxidative pentose
phosphate pathway of glucose metabolism. But the poor expression of gate-
keeper enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate
dehydrogenase limit its natural production in heart and muscle tissue. The
primary metabolic fate of ribose is the formation of 5-phosphoribosyl-1-pyro-
phosphate (PRPP) required for purine synthesis and salvage via the purine
nucleotide pathway. PRPP is rate limiting in purine synthesis and salvage,
and concentration in tissue defines the rate of flux down this pathway. In this
way, ribose is rate limiting for preservation of the cellular adenine nucleotide
pool.
As a pentose, ribose is not used by cells as a primary energy fuel. Instead,
ribose is preserved for the important metabolic task of stimulating purine
nucleotide synthesis and salvage. Approximately 98 percent of consumed
ribose is quickly absorbed into the bloodstream and is circulated to remote
tissue with no first pass effect by the liver. As ribose passes through the cell
membrane it is phosphorylated by membrane bound ribokinase before enter-
ing the pentose phosphate pathway downstream of the gatekeeper enzymes.
In this way, administered ribose is able to increase intracellular PRPP concen-
tration and initiate purine nucleotide synthesis and salvage.
The use of ribose in congestive heart failure was first reported in the
European Journal of Heart Failure in 2003 in a double-blind, placebo con-
trolled, crossover study which included patients with chronic coronary artery
disease and NYHA Class II/III CHF (Omran et al. 2003). Patients underwent
two treatment periods of three weeks each, during which either oral ribose
(5 g t.i.d.) or placebo (glucose; 5 g t.i.d.) was administered. Following a one-
week washout period, the alternate test supplement was administered for three
weeks. Before and after each three-week trial period, assessment of myocardial
function was made by echocardiography, and the patient’s exercise capacity
was determined using a stationary exercise cycle. Participants also completed
a quality of life questionnaire. Ribose administration resulted in significantly
enhanced indices of diastolic heart function and exercise tolerance, and was
also associated with improved quality of life score. By comparison, none of
these parameters were changed with glucose (placebo) treatment.
In addition to impaired pump function, CHF patients exhibit compromised
ventilation and oxygen uptake efficiency that presents as dyspnea. Ventilation
efficiency slope and oxygen uptake efficiency slope are highly sensitive predic-
tors of CHF patient survival that can be measured using sub-maximal exercise
protocols that included pulmonary assessment of oxygen and carbon dioxide
levels. In one study, ribose administration (5 g, t.i.d.) to NYHA Class III/IV
CHF patients significantly improved ventilation efficiency, oxygen uptake

efficiency, and stroke volume (Vijay et al. 2005).
A second study (Carter et al. 2005) showed that in NYHA Class II/III CHF
patients ribose administration significantly maintained VO2max when
compared to placebo and improved ventilatory efficiency to the respiratory
compensation point. A third (Sharma et al. 2005), similar, study involving
patients with NYHA Class III CHF patients investigated the effect of ribose on
Doppler derived Myocardial Performance Index (MPI), VO2max, and ventila-
tory efficiency—all powerful predictors of heart failure survival in a Class III
heart failure population. Results showed that ribose improved MPI and venti-
latory efficiency while preserving VO2max. Results of these studies show that
ribose stimulates energy metabolism along the cardiopulmonary axis, thereby
improving gas exchange.
Increased cardiac load produces unfavorable energetics that deplete
myocardial energy reserves. Because ribose is the rate limiting precursor for
adenine nucleotide metabolism, its role in preserving energy substrates in
remote myocardium following infarction was studied in a rat model (Befera
et al. 2007). In this study, male Lewis rats received continuous venous infusion
of ribose or placebo via an osmotic mini-pump for 14 days. One to two days
after pump placement, animals underwent ligation of the left anterior descend-
ing coronary artery to produce an anterior wall myocardial infarction.
Echocardiographic analysis performed preoperatively and at two and four
weeks following infarction was used to assess functional changes as evidenced
by ejection indices, chamber dimensions, and wall thickness.
By all three measured indices, ribose administration better maintained
the myocardium. Contractility and wall thickness were increased, while less
ventricular dilation occurred. This study showed that the remote myocardium
exhibits a significant decrease in function within four weeks following myo-
cardial infarction, and that, to a significant degree, ribose administration
attenuates this dysfunction.
A note about D-Ribose dosage: the data presented suggests that D-Ribose
may have significant value as an adjunct to traditional therapy for congestive
heart failure. A dose range of 10 to 15 g/day is recommended. If patients
respond favorably after two to three weeks, a lower dose of 5 g/dose two times
per day could be tried. Individual doses of greater than 10 grams are not rec-
ommended, because high single doses of hygroscopic carbohydrate may cause
mild gastrointestinal discomfort or transient lightheadedness. It is suggested
that ribose be administered with meals or mixed in beverages containing a
secondary carbohydrate source. D-Ribose may actually lower glucose levels
so, in diabetic patients prone to hypoglycemia, ribose should be administered
in fruit juices.
Coenzyme Q10
Coenzyme Q10 or ubiquinone, so named for its ubiquitous nature in cells, is a

fat-soluble compound that functions as an antioxidant and coenzyme in the
energy-producing pathways. As an antioxidant, the reduced form of CoQ10
inhibits lipid peroxidation in both cell membranes and serum-low density
lipoprotein, and also protects proteins and DNA from oxidative damage.
Coenzyme Q10 also has membrane stabilizing activity. However, its bioener-
getic activity and electron transport function for its role in oxidative phospho-
rylation is probably its most important function.
In CHF, oxidative phosphorylation slows due to a loss of mitochondrial
protein and lack of expression of key enzymes involved in the cycle. Disruption
of mitochondrial activity may lead to a loss of Coenzyme Q10 that can further
depress oxidative phosphorylation. In patients taking statin drugs, the mito-
chondrial loss of Coenzyme Q10 may be exacerbated by restricted Coenzyme
Q10 synthesis resulting from HMG-CoA reductase inhibition (Figure 5.6).
It has been reported that long term treatment with atorvastatin may increase
plasma levels of brain natriuretic peptide (BNP) in coronary artery disease
when associated with a greater reduction in plasma Coenzyme Q10 (Suzuki
et al. 2008).
Although Coenzyme Q10 is found in relatively high concentrations in the
liver, kidney, and lungs, the heart requires the highest levels of ATP activity
Acetyl CoA
HMG-CoA
HMG-CoA reductase
Mevalonic prophosphate
CoEnzyme Q10 Dolichols
Squalene
Cholesterol
Figure 5.6. Statin drugs (HMG-CoA reductase inhibitors) can reduce natural coen-
zyme Q10-synthesis in the body.
because it is continually aerobic and contains more mitochondria per gram

than any other tissue in the body. Cardiomyocytes, for example, contain more
than 3,500 mitochondria per cell, compared to a bicep muscle cell that houses
approximately 200 mitochondria per cell. Tissue deficiencies and low serum
blood levels of Coenzyme Q10 have been reported across a wide range of car-
diovascular diseases, including diastolic dysfunction, CHF, hypertension,
aortic valvular disease and coronary artery disease and research suggests that
Coenzyme Q10 support may be indicated in these disease conditions
(Langsjoen and Langsjoen 1999; Langsjoen, Littarru, and Silver 2005).
While the medical literature generally supports the use of Coenzyme
Q10 in CHF, the evaluated dose-response relationships for this nutrient have
been confined to a narrow dose range, with the majority of clinical studies
having been conducted on subjects who were taking only 90 to 200 mg daily.
At such doses, some patients have responded, while others have not. In
22 controlled trials of supplemental CoQ10 in congestive heart failure, 19 have
shown benefit while 3 failed to demonstrate improvement in any significant
cardiovascular function (Langsjoen and Langsjoen 1999; Langsjoen, Littarru,
and Silver 2005). The three that concluded no benefit had limitations that will
be discussed.
In the study conducted by Permanetter et al, (1992), a 100-mg dose of
Coenzyme Q10 failed to show benefit. However, actual blood levels of CoQ10
were not obtained in this investigation; thus it is impossible to know if a thera-
peutic blood level was ever achieved. In the second trial by Watson et al. (2001),
a mean treatment plasma CoQ10 level of only 1.7 g/ml was obtained with only
two of the 30 patients having a plasma level greater than 2.0g/ml. The third
study, performed by Khatta and colleagues (2000), demonstrated a mean treat-
ment plasma CoQ10 level of 2.2 +/− 1.l g/ml, and indicated that approximately
50 percent of the patients had plasma levels as low as 1.0 g/ml. Unfortunately,
these last two clinical trials are frequently quoted as CoQ10 failures, despite
the fact that adequate blood levels were not achieved.
In patients with CHF or dilated cardiomyopathy, higher doses of Coenzyme
Q10 in ranges of at least 300 mg or more daily is required to obtain therapeutic
blood levels, defined as greater than 2.5 g/ml and preferably 3.5 g/ml (Sinatra
2000). In a previous analysis in three patients with refractory congestive heart
failure, such higher doses of CoQ10 were required in order to get such a thera-
peutic result (Sinatra 1997).
In a later investigation at the Lancisi Heart Institute in Italy, researchers stud-
ied 23 patients with a mean age of 59, using a double-blind, placebo-controlled,
cross-over design. Patients were assigned to receive 100 mg of oral CoQ10
three times per day plus supervised exercise training. The study concluded that
CoQ10 supplementation improved functional capacity, endothelial function
and left ventricular contractility in CHF without any side effects (Belardinelli
et al. 2006).
In a long-term study of 424 patients with systolic and/or diastolic dysfunc-
tion in the presence of CHF, dilated cardiomyopathy, or hypertensive heart
disease, a dose of 240 mg/day maintained blood levels of Coenzyme Q10 above
2.0 g/ml, and allowed 43 percent of the participants to discontinue one to three
conventional drugs over the course of the study (Langsjoen et al. 1994).
Patients were followed for an average of 17.8 months, and during that time, a
mild case of nausea was the only reported side effect. This long-term study
clearly shows Coenzyme Q10 to be a safe and effective adjunctive treatment
for patients with systolic and/or diastolic left ventricular dysfunction with or
without CHF, dilated cardiomyopathy, or hypertensive heart disease.
These results are further confirmed by an investigation involving 109
patients with hypertensive heart disease and isolated diastolic dysfunction
showing that Coenzyme Q10 supplementation resulted in clinical improve-
ment, lowered elevated blood pressure, enhanced diastolic cardiac function
and decreased myocardial thickness in 53%of study patients (Langsjoen,
Willis, and Folkers 1994).
Plasma CoQ(10) concentration has been shown to be an independent pre-
dictor of mortality in patients with congestive heart failure (Molyneux et al.
2008). New Zealand researchers studied the relationship of plasma CoQ10
levels and survival in patients with chronic heart failure. In their cohort of 236
patients (mean age 77 years), they concluded that plasma CoQ10 concentra-
tion was an independent predictor of mortality. A blood level of 0.73 Mol/l∗ or
more was the best predictor for survival. Researchers suggested that lower con-
centrations of plasma CoQ10 might be detrimental in the long-term prognosis
of CHF.
The effect of Coenzyme Q10 administration on 32 heart transplant candi-
dates with end-stage CHF and cardiomyopathy was reported in 2004 (Berman
et al. 2004). The study was designed to determine if Coenzyme Q10 could
improve the pharmacological bridge to transplantation and the results showed
three significant findings. Following six weeks of Coenzyme Q10 therapy, the
study group showed elevated blood levels from an average of 0.22 mg/l to
0.83 mg/l∗, an increase of 277 percent (note that different labs in other coun-
tries have different standardizations of CoQ10). By contrast, the placebo group
measured 0.18 mg/l at the onset of the study and 0.178 mg/l at six weeks. Second,
the study group showed significant improvement in 6-minute walk test dis-
tance, shortness of breath, NYHA functional classification, fatigue, and episodes
of waking for nocturnal urination. No such changes were found in the placebo
group. These results strongly show that Coenzyme Q10 therapy may augment
pharmaceutical treatment of patients with end-stage CHF and cardiomyopathy.
I have suggested that a new emerging field in “Metabolic Cardiology” will most
likely be realized by those who treat the energy-starved heart at the mitochon-
drial level (Sinatra 2004).
Levocarnitine (L-Carnitine or Carnitine)
Carnitine is derived naturally in the body from the amino acids lysine and
methionine. Biosynthesis occurs in a series of metabolic reactions involving
these amino acids, complemented with niacin, vitamin B6, vitamin C, and iron.
Although carnitine deficiency is rare in a healthy, well-nourished population
consuming adequate protein, CHF, left ventricular hypertrophy, and other car-
diac conditions causing renal insufficiency can lead to cellular depletion and
conditions of carnitine deficiency.
The principal role of carnitine is to facilitate the transport of fatty acids
across the inner mitochondrial membrane to initiate beta-oxidation. The inner
mitochondrial membrane is normally impermeable to activated coenzyme
A (Co A) esters. To affect transfer of the extracellular metabolic byproduct
acyl-Co A across the cellular membrane, the mitochondria delivers its acyl
unit to the carnitine residing in the inner mitochondrial membrane. Carnitine
(as acetyl-carnitine) then transports the metabolic fragment across the mem-
brane and delivers it to coenzyme A residing inside the mitochondria. This
process of acetyl transfer is known as the carnitine shuttle, and the shuttle also
works in reverse to remove excess acetyl units from the inner mitochondria for
disposal. Excess acetyl units that accumulate inside the mitochondria disturb
the metabolic burning of fatty acids. Other crucial functions of intracellular
carnitine include the metabolism of branched-chain amino acids, ammonia
detoxification, and lactic acid clearance from tissue. Carnitine also exhibits
antioxidant and free radical scavenger properties.
Although the role of carnitine in the utilization of fatty acids and glucose in
cardiac metabolism has been known for decades, the relationship between
carnitine availability in heart tissue, carnitine metabolism in the heart, and
carnitine’s impact on left ventricular function has been elucidated only recently.
Two independent studies have investigated the relationship between tissue
carnitine levels and heart function and have evaluated the possibility that
plasma or urinary carnitine levels might actually serve as markers for impaired
left ventricular function in patients with CHF.
In the first study of carnitine tissue levels and CHF, the myocardial tissue
from 25 cardiac transplant recipients with end-stage CHF and 21 control donor
hearts was analyzed for concentrations of total carnitine, free carnitine, and
carnitine derivatives. Compared to controls, the concentration of carnitines in
the heart muscle of heart transplant recipients was significantly lower in patients,
and the level of carnitine in the tissue was directly related to ejection fraction.
This study concluded that carnitine deficiency in the heart tissue might be
directly related to heart function (El-Aroussy 2000).The second study measured
plasma and urinary levels of L-carnitine in 30 patients with CHF and cardio-
myopathy and compared them to 10 control subjects with no heart disease
(Narin 1997). Results showed that patients with CHF had higher plasma and
urinary levels of carnitine, suggesting that carnitine was being released from
the challenged heart muscle cells. Similarly, the study demonstrated that the
level of plasma and urinary carnitine was related to the degree of left ventricular
systolic dysfunction and ejection fraction. This finding suggests that elevated
plasma and urinary carnitine levels, reflecting loss of carnitine from compro-
mised cardiomyocytes, might represent measurable physiological markers for
myocardial damage and impaired left ventricular function.
A previous investigation examined the effect of long-term carnitine admin-
istration on mortality in patients with CHF and dilated cardiomyopathy. This
study followed 80 patients with moderate to severe heart failure (NYHA class
III/IV) for three years. After a three-month period of stable cardiac function
on standard medical therapy, patients were randomly assigned to receive either
two grams of carnitine per day or a matched placebo. After an average of 33.7
months of follow up, 70 patients remained in the study (33 taking placebo and
37 supplementing with carnitine) and at the end of the study period 63 had
survived (27 placebo and 36 carnitine). This study determined that carnitine
provided a benefit to longer-term survival in late-stage heart failure in dilated
cardiomyopathy (Rizos 2000).
A similar placebo-controlled study evaluated 160 myocardial infarction
survivors for twelve months (Davini et al. 1992). Eighty subjects were included
in each group; the study group received a daily dose of 4 grams of L-carnitine;
the controls received a placebo. Both the carnitine and control groups contin-
ued their conventional therapeutic regimen while on the test substance.
Subjects in both groups showed improvement in arterial blood pressure, cho-
lesterol levels, rhythm disorders, and signs and symptoms of CHF over the
study period, but all-cause mortality was significantly lower in the carnitine
compared to the placebo group (1.2 percent and 12.5 percent, respectively).
A further double-blind, placebo-controlled trial by Singh and coworkers
studied 100 patients with suspected myocardial infarction. Patients taking
carnitine (2 g/day for 28 days) showed improvement in arrhythmia, angina,
onset of heart failure, and mean infarct size, as well as a reduction in total car-
diac events. There was a significant reduction in cardiac death and non-fatal
infarction in the carnitine group versus the placebo group (15.6 percent vs.
26 percent respectively) (Singh et al. 1996).
In a European study of 472 patients published in the Journal of the American

College of Cardiology, nine grams per day of carnitine was administered
intravenously for five days followed by six grams per day orally for the next
twelve months (Iliceto et al. 1995). The study validated previous findings,
demonstrating an improvement in ejection fraction and a reduction in left
ventricular size in carnitine-treated patients. Although the European study
was not designed to demonstrate outcome differences, the combined incidence
of CHF death after discharge was lower in the carnitine group than placebo
group (6.0 percent vs. 9.6 percent, respectively)—a reduction of more than
30 percent.
A newer form of carnitine, glycine propionyl L-carnitine (GPLC), demon-
strated significant advantages in the production of nitric oxide and lower
malondialdehyde (MDA)—a marker of lipid peroxidation and oxidative
damage. This form of carnitine resulted in vasodilation via a nitric oxide
mechanism inhibition. GPLC also blocked key steps in the process of platelet
aggregation and adhesion, as well as reducing levels of lipid peroxidation and
oxidative damage (Bloomer, Smith, and Fisher-Wellman 2007).
Magnesium: Switching on the Energy Enzymes
Magnesium is an essential mineral critical for a wide range of energy requiring

processes including: protein synthesis, membrane integrity, nervous tissue con-
duction, neuromuscular excitation, muscle contraction, hormone secretion,
maintenance of vascular tone, and intermediary metabolism. Deficiency may
lead to changes in neuromuscular, cardiovascular, immune, and hormonal
function. Magnesium deficiency is now considered to contribute to many dis-
eases, and the role of magnesium as a therapeutic agent is expanding.
A German study of 16, 000 patients were assigned to subgroups based
on gender, age, and state of health (Schimatschek and Rempis 2001).
Hypomagnesemia was identified in 14.5 percent of all persons examined, and
suboptimal levels were found in yet another 33.7 percent, for a total of 58.2
percent—more than half of those evaluated.
Magnesium deficiency reduces the activity of important enzymes used in
energy metabolism. Hypomagnesemia can result in progressive vasoconstric-
tion, coronary spasm, and even sudden death (Turlapaty and Altura 1980).
In anginal episodes due to coronary artery spasm, treatment with magnesium
has been shown to be efficacious (McLean 1994). Magnesium deficiency, which
is better detected by mononuclear blood cell magnesium than the standard
serum level performed at most hospitals, predisposes to excessive mortality
and morbidity in patients with acute MI (Elin 1998).
While magnesium is found in most foods—particularly beans, figs, and

vegetables—deficiencies are common. Softened water, depleted soils, and a
trend toward lower vegetable consumption are the culprits contributing to
these rising deficiencies. Major magnesium deficiencies exist especially in the
insulin resistance/metabolic syndrome as well as in prolapse mitral valve.
Magnesium has shown considerable efficacy in relieving symptoms of
mitral valve prolapse (MVP). In a double-blind study of 181 participants,
serum magnesium levels were assessed in 141 patients with symptomatic MVP
and compared to those of 40 healthy control subjects (Lichodziejewska et al.
1997). While decreased serum magnesium levels were found in 60 percent
of patients with MVP, only 5 percent of the control subjects showed similar
decreases. The second phase of the study investigated response to treatment.
Participants with magnesium deficits were randomly assigned to receive
magnesium supplement or placebo. The frequency of symptoms was sig-
nificantly reduced with magnesium supplementation; significant reductions
were noted in weakness, chest pain, shortness of breath, palpitations, and even
anxiety.
The combination of magnesium and coenzyme Q10 has been extremely
promising. I have seen this combination alleviate 80 to 90 percent of symptoms,
including chest pain, shortness of breath, easy fatigability, and palpitations. The
combination of magnesium and CoQ10 is more efficacious than beta blockers.
The enhanced quality of life is probably due to some improvement in diastolic
dysfunction, which often is present in women with MVP.
Summary
Attention to the energy demands of diseased hearts is often missing in conven-

tional cardiology practice. Metabolic support with D-ribose, Coenzyme Q10,
L-carnitine, and magnesium can be important for the maintenance of contrac-
tile reserve and energy charge in minimally oxidative ischemic or hypoxic
hearts. Preservation of cellular energy charge provides the chemical driving
force needed to maintain cell and tissue viability and function.
Summarized below is a metabolic cardiology approach to mild to moderate
congestive heart failure, severe congestive heart failure, dilated cardiomyo-
pathy, and mitral valve prolapse. The program that I have found to be most
effective for the patients I treat in my practice includes the following:
Congestive heart failure
1. Multivitamin/mineral foundation program with 1 gram of fish oil

2. Coenzyme Q10: 300–360 mg
3. L-carnitine: 2,000–2,500 mg
4. D-ribose: 10–15 grams
5. Magnesium: 400–800 mg
Severe congestive heart failure, dilated cardiomyopathy, patients awaiting

heart transplantation

2. Coenzyme Q10: 360–600 mg
3. L-carnitine: 2,500–3,500 mg
4. D-ribose: 15 grams
Note: If quality of life is still not satisfactory, add 1500 mg of hawthorn

berry and 2–3 grams of taurine, as the addition of these two nutraceuticals has
helped many of my patients with severe refractory congestive heart failure.
Mitral valve prolapse

2. Coenzyme Q10: 90–180 mg daily
3. L-carnitine: 500–1000 mg
4. D-ribose: 5 grams
Conclusion
Cardiovascular function depends on the operational capacity of myocardial

cells to generate the energy to expand and contract. Insufficient myocardial
energy contributes significantly to CHF. Literally, heart failure is an “energy-
starved heart.”
Although there may be several causes of myocardial dysfunction, the energy
deficiency in cardiac myocytes plays a significant role. It is no longer enough
that physicians focus on the fluid retention aspects of “pump failure.” For
instance, diuretic therapies target the kidneys indirectly to relieve the sequelae
of CHF without addressing the root cause. Inotropic agents attempt to increase
contractility directly, yet fail to offer the extra energy necessary to assist the
weakened heart muscle. Metabolic solutions, on the other hand, treat the heart
muscle cells directly. “Metabolic cardiology” supports the biochemical inter-
ventions that can be employed to directly improve energy substrates and there-
fore energy metabolism in heart cells.
D-Ribose, Coenzyme Q10, L-carnitine and magnesium all promote cardiac

energy metabolism and help normalize myocardial adenine nucleotide con-
centrations. These naturally occurring compounds exert a physiological benefit
that, by providing energy substrates, support the production of ATP. All of
these interventions positively impact on cardiac systolic and diastolic function.
Acknowledging this metabolic support for the heart provides a missing link
that offers great potential for the future treatment of cardiovascular disease.
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6
Acupuncture in Cardiovascular Medicine
JOHN LONGHURST
key concepts
■ Meridians and acupoints along the meridians in Traditional

Chinese Medicine serve as a guide for therapists, directing them
where to achieve the best clinical responses. Neither meridians
nor acupoints are represented by an anatomical structure, but
many are located over major neural pathways.
■ Acupuncture works by stimulating somatic sensory neural
pathways to activate regions of the brain that regulate auto-
nomic neural outflow, and hence cardiovascular function.
■ A number of excitatory and inhibitory neurotransmitters/
neuromodulators in both long- and short-loop pathways in the
hypothalamus, midbrain, and medulla underlie acupuncture’s
ability to lower elevated blood pressure.
■ Manual and low frequency electroacupuncture are the most
effective forms of stimulation used to lower elevated blood
pressure.
■ Key features of acupuncture differentiating it from simple
somatosensory stimulation are its point-specific effects, slow
onset (requiring minutes to days before a response is observed),
and prolonged action (which can last for hours to weeks after
therapy).
■ Acupuncture’s principal cardiovascular effect is to normalize
blood pressure.
■ Small trials suggest that acupuncture may be able to reduce
angina in patients with demand-induced myocardial ischemia.
100
■ Although theoretically acupuncture should be able to modify
many cardiovascular risk factors, such as obesity, smoking,
hypercholesterolemia and hypertension, only hypertension has
been shown to be modified in well-constructed clinical trials.
Better prospective randomized clinical trials are necessary to
determine acupuncture’s influence on other risk factors.
■
Traditional Chinese Medicine
A
cupuncture originated over 2,000 years ago as a therapy in Traditional
Chinese Medicine (TCM). The technique and practice of acupuncture
was shaped empirically through trial, error, and success and, in fact,
even today much teaching of this ancient technique is based on observations
of masters and practitioners that were recorded in texts and passed down
to students as dogma. Only in the last few decades has modern science begun
to provide insight into the mechanisms and actions of acupuncture. Since
the early 1970s there have been over 500 randomized controlled clinical trials
investigating the clinical influence of acupuncture (Klein and Trachtenberg
1997; Vickers 1998), yet its influence has been proven rigorously for only a few
diseases, most notably pain and nausea and vomiting.
Acupuncture is a form of energy-based medicine, and the energy is referred
to as Qi. This energy flows through a system of twelve principal channels, or
meridians, that lie along the skin’s surface and are named after and connect to
twelve Chinese organs. Although somewhat controversial, there is no proven
anatomical basis for the meridians and they cannot be reliably detected with
instruments that measure skin resistance. Furthermore, the Chinese organs,
while sometimes named similarly to Western visceral organs, are not exactly
equivalent. For example, the heart meridian connects to the Chinese heart,
which actually represents the Western equivalent of the heart and the brain.
Along these meridians are small nodes or acupuncture points (acupoints)
through which therapists place sterile stainless steel needles during treatment.
Although neither the meridians nor acupoints have a physical basis, they are
useful because they direct the therapist where stimulation should occur to
obtain the best clinical result. Thus, meridians and acupoints act as road maps
for acupuncture therapy. A number of acupoints have been shown experimen-
tally to exert strong cardiovascular responses (Figure 6.1).
P
LI
L7
P5
L14
P6
GB
ST
control
ST36
active GB37 ST37
GB39
Figure 6.1. Diagram of acupoints along meridians that cause strong (active points,
filled circles) or weak (control points, open circles) cardiovascular responses. See text
for discussion of individual points. Meridians are identified according to Traditional
Chinese Medicine theory as belonging to the principal Chinese organs to which they
connect and influence, including the gallbladder (GB), large intestine (LI), lung (L),
pericardial (P) and stomach (ST) meridians. The numbers for acupoints refer to stan-
dardized reference system to distinguish points along each meridian. Modified from
Li, Ayannusi, Reed, & Longhurst 2004.
Acupuncture is an empirically developed ancient therapy. Modern science

has found substantial truth in many of its concepts, particularly Qi, the
energy that circulates through meridians. Western science translates Qi to
acupuncture-triggered neural impulses in somatic sensory nerves that trans-
mit information to the brain to alter cardiovascular function.
Acupuncture in Cardiovascular Medicine 103
MECHANISM OF ACTION
Acupuncture is one of the few areas of integrative medicine for which the
mechanism of cardiovascular action has been explored (Lin et al. 2001;
Longhurst, J. 1998; Longhurst, J. C. 2002).
Over the last two decades, studies in both China and the United States have
used a number of experimental preparations that lend themselves to acupunc-
ture and careful measurement of its action to modify cardiovascular function.
We now recognize that many meridians overlie neural pathways containing
both motor and sensory nerves, which can be activated by needle stimulation.
Motor nerve activation during electroacupuncture is useful because it pro-
vides a gauge to adjust the stimulation intensity, which generally is set at motor
threshold. Sensory nerves, on the other hand, carry information resulting
from acupuncture stimulation to the brain, which biologically transduces the
input from different sources of acupoint stimulation to modify autonomic and
humoral output to the heart and vascular system. Thus, from a physiological
perspective, acupuncture needle stimulation activates sensory neural path-
ways, which provide input to regions of the central nervous system that regu-
late cardiovascular function (Longhurst J.C. 2007b). Acupuncture-related
activation of thin fiber somatic sensory pathways (including both finely myeli-
nated group III and unmyelinated group IV nerve fibers) provides input to
the spinal cord dorsal horn and ultimately the intermediolateral columns
(containing sympathetic motor nerves), arcuate nucleus in the ventral hypo-
thalamus, midbrain ventrolateral periaqueductal gray (vlPAG), especially the
caudal vlPAG and the rostral ventrolateral, and raphe pallidus nuclei in the
medulla (rVLM and NRP)—regions that regulate sympathetic (and probably
parasympathetic) outflow. Input derived from manual acupuncture and
low frequency, low intensity electroacupuncture to these lower brain regions
leads to the release of a number of modulatory (inhibitory) neuropeptide
systems, including opioids (endorphins and enkephalins), γ-aminobutyric
acid (GABA), nociceptin, serotonin, and endocannabinoids, as well as excit-
atory amino acids like glutamate and acetylcholine, which ultimately inhibit
sympathetic (and likely parasympathetic) outflow to the heart and vascular
system (Longhurst, J. C. 2002; 2007b). In the spinal cord, acupuncture appears
to inhibit sensory inflow and sympathetic outflow through both opioid and
nociceptin mechanisms of blockade (Zhou et al. 2006, Zhou et al. 2009).
When blood pressure is within the normal range, acupuncture causes only
minimal changes (Li et al. 2004). Conversely, acupuncture inhibits sympa-
thetic outflow and reduces blood pressure when it is elevated during excitatory
reflex activation—for example, during stimulation of sensory nerves associ-

ated with visceral organs like the gallbladder with bradykinin (related to
inflammatory pain), or gastric distension, or in spontaneously hypertensive
rats or in humans during exercise (Li et al. 2002; Li et al. 2004; Longhurst, J. C.
1998; Tjen-A-Looi, Pan, and Longhurst 1998; Vickers 1998).
Acupuncture can be differentiated with respect to its cardiovascular actions
from non-specific somatosensory stimulation with regard to both point speci-
ficity and the prolonged nature of its action. Relatively brief somatosensory
reflex cardiovascular responses lasting for a few seconds or minutes that adapt
quickly to maintained stimulation, and which return to baseline values shortly
after termination of stimulation, can be elicited from stimulating almost
any somatic or sensory nerve. Strong somatosensory stimulation generally
increases blood pressure, while low-intensity stimulation typically does not
alter or only briefly lowers blood pressure. The concept of point specificity
refers to the differential physiological cardiovascular and clinical response to
stimulation of individual acupoints (Longhurst, J.C. 2007b). In this respect,
some acupoints (such as P5 and P6, which lie along the pericardial meridian
overlying the median nerve in the wrist) exert a stronger influence on the
cardiovascular system than other nearby acupoints (such as LI6 and LI7,
located along the large intestine meridian on the forearm over the superficial
radial nerve) (Tjen-A-Looi, Li, and Longhurst 2004). Studies also have shown
that the extent of influence on sympathetic outflow from stimulation of each
individual acupoint is highly correlated with the extent of input that they
provide to regions of the brainstem that control autonomic and ultimately
cardiovascular function. The existence of point specificity is controversial, but
clearly evidence for its presence, shown in multiple studies, is valuable, because
the ability to stimulate some acupoints that cause a strong physiological
response (e.g., to reduce blood pressure) may be important clinically (Fu, Guo,
and Longhurst 2008; Li et al. 2002; Li et al. 2004; Li, Tjen-A-Looi, and Longhurst
2006; Tjen-A-Looi, Li, and Longhurst 2004; Zhou et al. 2005; Zhou et al.
2006).
Acupuncture’s prolonged action is determined by the mode of sensory
nerve stimulation, duration of stimulation, and network processing in
cardiovascular centers in the hypothalamus, midbrain, and brainstem that
are activated by acupuncture-induced somatic sensory nerve stimulation.
In addition, the extent of release of neurotransmitters in the CNS over time
with repeated stimulation, which increases genetic expression of neuromodu-
latory neurotransmitter precursors, likely accounts for the long-term action
of electroacupuncture on blood pressure (Li and Longhurst 2007; Li, Tjen-
A-Looi, and Longhurst 2009). Low frequency (2–6 Hz) or manual acupunc-
ture provided at acupoints known to have a strong cardiovascular effect for
30 to 45 minutes seems to be most effective, reducing sympathetic outflow

after 10 to 15 minutes of stimulation, and lasting for many minutes to hours or
even days after acupuncture, depending on the model of investigation and the
extent of repeated stimulation (Li and Longhurst 2007; Lin et al. 2001; Zhou
et al. 2005). The cardiovascular influence of electroacupuncture in anesthe-
tized experimental studies can last for 1 to 2 hours, and for 10 to 12 hours in
studies conducted in awake subjects (Lin et al. 2001), whereas repetitive acu-
puncture administered once weekly over a course of eight weeks in patients
with mild to moderate hypertension can exert a cardiovascular influence for
several weeks (Li and Longhurst 2007; Longhurst, J. C. 2007a). Studies are
needed to determine how frequently these blood- pressure-lowering effects of
acupuncture must be reinforced.
Acupuncture seems to have the ability to reduce activity of neurons in regions

controlling cardiovascular function that have been stimulated. Without an
increase in neuronal discharge, there is nothing for acupuncture to influence,
and thus, in normotensive conditions, acupuncture does not alter blood pres-
sure. But if sympathetic activity is elevated, it can be reduced by acupuncture
to lower blood pressure. Conversely, preliminary studies suggest that if the
parasympathetic system is activated, to lower heart rate and blood pressure,
acupuncture may be able to reduce vagal outflow and hence restore low blood
pressure. Hence, acupuncture appears to be able to normalize elevated or
depressed blood pressure.
Clinical Actions of Acupuncture
A number of cardiovascular risk factors, including hypertension, obesity, and

hypercholesterolemia potentially can be influenced by acupuncture. In addi-
tion it may be efficacious in stroke, coronary and peripheral vascular disease
(Longhurst, J. C. 2007a), although clearly more studies are warranted.
HYPERTENSION
Because acupuncture can decrease elevated sympathetic outflow and sym-

pathoexcitatory reflex responses associated with elevated blood pressure, there
is a rationale for using it to treat hypertension particularly in patients who
do not want to take antihypertensive medications or who want the possibility
of reducing the dosage of these drugs (Longhurst, J.C. 2007a). However, the
results of clinical trials are mixed. Experimental studies in quadriplegic rats
suggest that transcutaneous electrical stimulation (TENS), which shares some

features with electroacupuncture, decreases the exaggerated blood pressure
responses associated with colon distension (Collins and DiCarlo 2002).
Although acupuncture appears to be safe (Averill et al. 2000), no clinical trials
are available on its effect in spinal patients experiencing autonomic dysreflexia.
Blood pressure in spontaneously hypertensive rats is reduced by acupuncture
of acupoints located over the deep peroneal nerve for periods lasting up to
12 hours (Yao, Andersson, and Thoren 1982). A small study of fifty patients
suggested that thirty minutes of acupuncture lowers both systolic and diastolic
pressure (Chiu, Chi, and Reid 1997). However, the SHARP trial (Stop
Hypertension with Acupuncture Research Trial), which treated patients with
moderate hypertension over a twelve-week period, demonstrated no influence
on blood pressure over and above the response to an invasive sham control,
when blood pressure was measured intermittently with mercury sphygmoma-
nometers (Macklin et al. 2006). However, large and small trials incorporating
ambulatory monitoring have demonstrated small, but consistent, decreases
in blood pressure in patients with mild to moderate hypertension, especially
if acupoints are used that have been shown to have a strong cardiovascular
influence (P5, P6, St36, and St37, referring to points along the pericardial
and stomach meridians overlying the median and deep peroneal nerves—see
Fig. 6.1) (Flachskampf, Gallasch, and Gefeller 2007; Li and Longhurst 2007a).
Acupuncture may influence systolic and mean arterial pressure more than dia-
stolic blood pressure. The onset action is slow, frequently requiring several
acupuncture treatments over a course of several weeks before a sustained
decrease in blood pressure is observed. Blood pressure decreases by five to
twenty mmHg and tends to remain low for up to four weeks following cessa-
tion of a two-month period of treatment.
CHOLESTEROL
In addition to hypertension, experimental studies demonstrate that acupunc-

ture can lower cholesterol. Daily acupuncture for a two-week period reduces
the increase in cholesterol in experimental models fed high cholesterol diets
(Li and Zhang 2007; Wu and Hsu 1979). There are no good randomized
control clinical trials, but a small non-randomized, unblinded trial of electroa-
cupuncture that did not incorporate a control acupoint group demonstrated
similar or greater weight loss, LDL cholesterol and triglyceride reduction,
and greater HDL reduction, compared to a control group that were fed a low
caloric diet (Cabioglu and Ergene 2005). More adequately powered, prospec-
tive clinical trials incorporating adequate controls need to be conducted to
determine if acupuncture effectively lowers cholesterol in patients with coro-

nary disease.
OBESITY
Stimulation of auricular acupoints used to treat overweight patients provides

input to regions of the brain that regulate food ingestion, including the ventro-
medial and ventrolateral hypothalamus (Shiraishi et al. 2009). However, the
efficacy of acupuncture to consistently assist with weight loss in obesity is less
certain. Experimental studies (Asamoto and Takeshige 1992) in rats have
shown that auricular acupuncture leads to a 5 percent loss in weight over a
period of two to three weeks. The results of clinical trials are mixed, with
uncontrolled studies showing small decreases (Dung 1986; Huang, Yang, and
Hu 1996; Mazzoni et al. 1999; Mok et al. 1976; Sacks 1975; Shafshak 1995;
Soong 1975; Sun and Xu 1993) and many showing either very modest or no
weight loss that could be ascribed to acupuncture. Most trials lack suitable
controls. Thus, weight loss trials using acupuncture represent another area of
needed research.
SMOKING CESSATION
Because acupuncture leads to the release of endogenous opioids, it has been

thought that it may be useful in treating addictive habits like smoking. With
respect to addiction, acupuncture reduces symptoms in subjects addicted to
opiates like morphine (Han and Zhang 1993; Wen and Cheung 1973). However,
metanalyses of relevant clinical trial with respect to smoking cessation reveals
that many are low quality and short term, lack suitable controls, and do not
provide sufficient information to assess their quality (White, Resch, and Ernst
1999). Thus, at present, insufficient data are available to determine the efficacy
of acupuncture in smoking cessation. More research needs to be conducted
in this area.
Acupuncture appears to lower blood pressure or reduce ischemia in only 70

percent of patients. Although more research is required, experimental studies
suggest that antagonistic neuropeptides, such as cholecystokinin, may pre-
vent acupuncture’s normal action to release opioid neurotransmitters that
limit sympathetic outflow.
MYOCARDIAL ISCHEMIA
Through an opioid mechanism, acupuncture lowers myocardial oxygen

demand, and hence reduces demand-supply imbalances and regional ventric-
ular dysfunction in experimental myocardial ischemia (Chao et al. 1999;
Li et al. 1998). Similarly, small studies demonstrate that both TENS and acu-
puncture reduce myocardial ischemia that occurs during exercise in patients
with angina and ECG evidence of ischemia (Ballegaard et al. 1990; 1995; 1999;
Ballegaard, Meyer, and Trojaborg 1991; Ballegaard, Norrelund, and Smith
1996; Emanuelsson et al. 1987; Mannheimer et al. 1982; 1985; 1989; Richter,
Herlitz, and Hjalmarson 1991). TENS is not exactly equivalent to acupunc-
ture, since much stronger intensities of stimulation and higher frequencies
are used during the transcutaneous stimulation, which also is not directed at
specific locations (acupoints) over neural pathways. Although there is some
debate about whether acupuncture increases coronary blood flow, it does
lower the increase in blood pressure and the double product (but not the ele-
vated heart rate) associated with exercise, hence reducing myocardial oxygen
demand (Li et al. 2004).
A few studies have examined the influence of acupuncture in situations
that can provoke angina. For example, acupuncture also decreases the reflex
excitatory responses to mental stress (Middlekauff, Yu, and Hui 2001). It is
important to note that the influence of acupuncture is not universal, since
it occurs in only 70 percent of individuals (Li et al. 2004; Middlekauff, Yu,
and Hui 2001). This raises the question of which individuals are most likely to
respond. In this regard, individuals demonstrating changes in pain threshold
and finger skin temperature in response acupuncture appear to be most
responsive to acupuncture (Ballegaard et al. 1990; Ballegaard, Meyer, and
Trojaborg 1991).
Several small studies have evaluated the influence of acupuncture in patients
with symptomatic coronary artery disease. A course of acupuncture therapy
employed over a period of several weeks decreases nitroglycerin consumption
and the rate of anginal attacks in patients with stable angina (Ballegaard et al.
1990; Ballegaard, Meyer, and Trojaborg 1991; Liu et al. 1986; Richter, Herlitz,
and Hjalmarson 1991). A prospective non-randomized study of patients in
which acupuncture was administered as part of a lifestyle program incorporat-
ing stress reduction and healthy eating documented decreases in medication
usage, in-patient days and the accumulated mortality rate (Ballegaard et al.
1999; 2004; Ballegaard, Norrelund, & Smith 1996). The specific contribution
of acupuncture to these beneficial effects has not been determined.
PERIPHERAL VASCULAR DISEASE
TENS increases the survival of skin flaps in experimental models as well as in

patients undergoing reconstructive surgery (Cramp et al. 2002; Lundeberg,
Kjartansson, and Samuelson 1998). Spinal cord stimulation, which may involve
activation of many of the same central neural regions as acupuncture
(Longhurst, J. 2001), increases skin temperature, reduces pain and ulcer for-
mation, and leads to tissue salvage in patients with peripheral vascular insuf-
ficiency (Augustinsson et al. 1985; Jivegard et al. 1987; 1995). No trials of
acupuncture’s influence in patients with peripheral vascular disease have been
published. Thus, symptomatic peripheral arterial disease represents yet another
area of needed future study.
Summary and Conclusions
Acupuncture through stimulation of sensory nerve pathways that project to

cardiovascular regulatory regions in the brain and spinal cord has the ability to
markedly reduce sympathetic outflow, and hence lower elevated blood pres-
sure and myocardial oxygen demand. Interestingly, acupuncture does not alter
blood pressure when it is in the normal range. In addition to lowering blood
pressure, acupuncture may be able to reduce demand-induced myocardial
ischemia mainly by lessening demand, rather than increasing the blood supply.
The efficacy of acupuncture in reducing cardiovascular risk is much less
apparent. It may assist in weight loss, although the changes typically are quite
small. It also may reduce elevated cholesterol, but does not appear to consis-
tently help smokers quit. Studies showing the cardiovascular effects are rea-
sonably strong in experimental animals. Clinical trials of acupuncture,
however, are not as numerous and tend to be small and frequently are not
prospective or adequately controlled. It is clear that much more research on
the role of acupuncture in cardiovascular disease is needed. Both mechanistic
studies defining acupuncture’s action and prospective, and adequately pow-
ered and carefully controlled randomized clinical trials should be conducted.
Mechanistic studies can help guide the clinical studies by identifying points
that can exert the strongest cardiovascular influence, the best modalities of
stimulation, and the best combinations of acupoints stimulated to achieve
optimal responses.
However, in designing trials for acupuncture, a number of issues that often
have not been addressed in past studies need to be taken into account. One of
the most important considerations in constructing clinical trials of acupunc-

ture is the sham control. The literature suggests that simply placing (but not
manipulating or electrically stimulating) a needle in an active acupoint or
stimulation of an “inactive” acupoint may serve as an adequate strong control
(Mayer 2000; Zhou et al. 2005), since in the absence of neural stimulation (i.e.,
stimulation outside a classical meridian) deqi, the neurological sensation asso-
ciated with good responses during acupuncture, may not occur. It is clear that
acupuncture trials cannot be reliably double-blinded, since it is not possible to
prevent the acupuncturist from knowing exactly where to place the needle.
Another issue to consider in constructing acupuncture trials is the method
for choosing acupoints. On one hand, TCM theory dictates that acupoints
should be selected after obtaining a history followed by tongue and pulse phys-
ical diagnosis. This method leads to selection of variable combinations of
points that are stimulated, depending on the individual acupuncturist’s assess-
ment. The different locations of stimulation increase the number of patients
that have to be studied to adequately power studies, and thus determine statis-
tically significant responses to acupuncture. This approach has led to more
failures than successes in studies addressing clinically significant cardio-
vascular responses to acupuncture. A more standardized approach, commonly
adapted in Western medical trails, is to select a fixed number of points that
are always stimulated. Although the desire to simulate the actual practice of
TCM is understandable, we have been able to use observations in experimen-
tal studies to help guide in the selection of the best points to stimulate to evoke
reproducible acupuncture responses in approximately 70 percent of our prep-
arations and in a preliminary clinical trial for hypertension (Li and Longhurst
2007). This more standardized approach, guided by modern biology, clearly is
repugnant to many TCM practitioners, but it does allow critical testing of acu-
puncture’s clinical responses—a necessary condition if this therapy is ever to
be fully accepted by Western medicine. Without such critical testing, acupunc-
ture will likely remain relegated largely to street corner clinics unassociated
with mainstream medicine.
Clinical Application of Acupuncture

in Cardiovascular Disease
At present, acupuncture probably can be used safely to treat patients with

mild to moderate hypertension, i.e., blood pressures below 170/105 mmHg.
Approximately 70 percent of patients likely will respond to the intervention,
but unfortunately at the present time, we cannot determine which patients
are more likely to be responsive. It should be kept in mind that acupuncture,
especially electroacupuncture, is most effective in reducing systolic and mean

blood pressure and is less effective in reducing diastolic pressure. Hence, it
may be useful in subjects with reduced vascular compliance, including older
patients. It can be used in patients off pharmacological therapy or in combina-
tion with antihypertensive drugs. Practitioners should be aware that the onset
of action of the blood-pressure-lowering effects of acupuncture may take sev-
eral weeks to develop, if it is employed once weekly for 30 minutes, using low
frequency (2 Hz), low intensity (2–6 mA) electroacupuncture at acupoints that
display cardiovascular activity, e.g., P5-P6 and St36-St37. Initial trials have
determined that short courses (2 months) of electroacupuncture are effective,
but few data are available to guide its use more chronically. Reinforcement of
the initial therapy most likely will be required, either once each week or once
every other week. If a patient is on drugs when the acupuncture is begun, there
is a possibility that the drug therapy over time can be reduced, or possibly even
stopped. However, drug therapy manipulation should be done in active collab-
oration with a physician. Thus, interaction between acupuncturists and Western
physicians is recommended as the safest course for therapy at this time.
Future Research
A number of important clinical issues still need to be addressed in studies of

acupuncture’s role in cardiovascular medicine.
First, we need properly constructed trials on smoking, weight loss, and cho-
lesterol reduction.
Second, the potential for acupuncture to raise blood pressure in subjects
who have symptomatic hypotension needs to be evaluated, since early experi-
mental results suggest that acupuncture can increase blood pressure when it
has been lowered. The concept in these studies is that acupuncture does not
just lower blood pressure if it is elevated, but rather it normalizes pressure, by
raising it if it is too low, lowering it when it is high, and not altering it within
the normal range. The idea of achieving homeostasis with acupuncture is
entirely consistent with TCM theory, which states that stimulation of acu-
points along meridians normalizes the imbalance of energy flow (Qi, see
above), which occurs in disease states.
Third, although we are beginning to accept the possibility that acupuncture
may be able to lower blood pressure in patients with hypertension, perhaps for
prolonged periods of time, we do not know how often we need to reinforce this
beneficial effect after the initial course of therapy.
Fourth, the importance of stimulating multiple points, although com-
monly used by most acupuncturists, has not been evaluated prospectively in
sufficiently large sample sizes to provide a definitive answer. In fact, current

experimental data suggest that stronger effects may not always be achieved by
simultaneously stimulating two strong sets of cardiovascular acupoints
(Zhou et al. 2005). However, there is evidence that acupuncture can have an
influence at multiple levels in the brain and spinal cord (Longhurst, J.C. 2007b).
Thus, the regional cardiovascular influence of acupuncture in the spinal cord
(Zhou et al. 2006) likely can be supplemented by its more global actions in
higher centers in the hypothalamus, midbrain, and medulla (Longhurst, J.C.
2007b).
Fifth, another concern that must be addressed in future acupuncture
research is why only 70 percent of individuals respond to acupuncture, even
when needles are carefully placed in acupoints known to have strong cardio-
vascular effects (Li et al. 2004). It is likely that counter-regulatory neurotrans-
mitter systems like cholecystokinin can antagonize the action of opioid
neuromodulators that are released by acupuncture during its action on cardio-
vascular centers in the brain (Huang 2007; Tang 1997). A reasonable, testable
hypothesis, therefore, is that administration of an inhibitor of the CCKA or
CCKB receptor system may convert some non-responders into responders or
may enhance the effect of acupuncture in responsive individuals.
Sixth, the method of acupuncture application needs further consideration.
As noted above, TENS causes many of the same cardiovascular responses that
occur with acupuncture. In addition, it is well known that TENS can help con-
trol pain much like acupuncture (Longhurst, J. 1998). Although there are fun-
damental differences between acupuncture and TENS (see above), it may be
possible to construct a noninvasive skin electrode system that could be used
with stimulation parameters that are more like electroacupuncture (i.e., low
intensity and low frequency) and that can be directed to stimulate specific acu-
points known to have a strong cardiovascular influence. Such an electrode
system then could be used in patients who cannot regularly visit an acupunc-
turist or in military personnel who need a means to help them deal with the
emotional and cardiovascular stress that they regularly encounter. A noninva-
sive system would make acupuncture much more available for individuals
who want to take responsibility for their own health care.
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7
Spirituality and Heart Health
MARY JO KREITZER AND KEN RIFF
key concepts
■ Spirituality has been defined in a multitude of ways and is gen-

erally understood to be related to, but distinct from, religiosity.
In the broadest sense, spirituality is focused on purpose, mean-
ing, and connectedness with self, others, and a higher power.
Spirituality is recognized as an integral part of being human
that is very interconnected with health and well-being.
■ A spiritual assessment or screening can be conducted by a physi-
cian, nurse, spiritual care provider, or other health professional
as a routine part of providing care. It is common for screening
questions to be incorporated into standard health history inter-
views and forms.
■ Emotional and spiritual pain, loneliness, despair, and isolation
are examples of spiritual issues that are known to be related to
heart disease.
■ Commonly used spiritual practices include prayer, meditation,
journaling, labyrinth walking, and interacting with nature.
■
I
n a compelling book titled Love and Survival: The Scientific Basis for the
Healing Power of Intimacy, Dean Ornish, most well-known for demon-
strating that comprehensive lifestyle changes can reverse even severe
coronary heart disease, writes about the emotional, psychological, and spiri-
tual dimensions of “opening your heart.” He notes that in his experience, when
the emotional heart and the spiritual heart begin to open, the physical heart
often follows. The core message conveyed is that “anything that promotes a
sense of isolation often leads to illness and suffering. Anything that promotes
117
a sense of love and intimacy, connection and community, is healing” (Ornish

1998, 14).
The approach to care that Ornish is describing reflects the growing sense
that we need to move beyond the biopsychosocial model of care proposed by
Engel (1977) to one that encompasses what is often called whole-person care,
a biopsychosocial-spiritual model. A growing number of medical schools
teach content or even entire courses in spirituality (Puchalski and Larson
1998), and the Joint Commissions on Healthcare Organization (2008) requires
that spiritual care be available to patients in hospital settings. This chapter will
explore the implications of spirituality for heart health by examining defini-
tions of spirituality, the relationship between spirituality and clinical outcomes,
the role of the health professional in meeting the spiritual needs of patients
and families, and ways to support and nurture the spirituality of professional
caregivers.
Throughout history, and across all cultures, spiritual beliefs and practices
have been expressed in a myriad of ways. The word “spirit” comes from the
Hebrew work ruah, which means wind, breath, or air that which gives life
(Golberg,1998). Greeks viewed the spirit in opposition to the body and any
material reality. In Chinese, spirit means chi or vital energy (Chiu, 2000). The
Latin word, spiritus, means breath. Spirituality, in its broadest sense, is recog-
nized as an integral part of being human that is deeply interconnected with
health and well-being.
The healing professions of nursing and medicine, were grounded in spiritu-
ality from their earliest beginnings. In ancient societies, the connection
between spirituality and healing was so close that the roles of priest, shaman,
and healer were one and the same. Hildegard of Bingen, a twelfth-century
Christian mystic was well known for her use of herbs, art, music and prayer.
The first hospitals were founded by religious orders and missionary move-
ments across centuries and continents; from the beginning, they have recog-
nized the need for spiritual healing along side physical healing.
It has only been since the time of the scientific revolution and the advent
of dualism, in the seventeeth century, that a wall of separation has divided
the physical and spiritual care of people into mutually exclusive, and often
antagonistic, camps. Medicine was charged with caring for the body, and later
the mind, while religion was left with the care and feeding of the soul. As a
result, contemporary Western science, including the disciplines of medicine
and nursing, has often dealt with the spiritual side of human nature by ignor-
ing it and viewing it as beyond the scope of their professional practice.
Over the past 20 years, there has been a growing interest in both the lay
press and the professional literature on the topic of spirituality and its impact
Spirituality and Heart Health 119
on health and well-being. Increasingly, consumers are demanding care that is

holistic and attentive to the whole person—mind, body, and spirit. Clinicians
are beginning to recognize the importance of both assessing and addressing
spiritual needs of patients, and researchers are establishing a link between
spirituality and spiritual interventions and health outcomes.
The role of the health professional in addressing the spiritual issues of
patients is not without some controversy. As noted by Post, Puchalski, and
Larson (2000), there are physicians who may still think that it is inappropriate
to discuss spiritual matters with patients, either because they see themselves as
lacking the expertise to do so, or feel that it may be an intrusion. Post, Puchalski,
and Larson note, however, that there is a preponderance of evidence that con-
firms that many patients welcome such discussion. Davidson (2008) asserts
that good medicine should include sensitivity to the spiritual dimension of
patients’ lives, and Magyar-Russell et al. (2008) argue that the physician who
knows little about a patient’s family status, occupation, and spiritual and reli-
gious beliefs may provide inadequate therapeutic guidance despite being tech-
nically competent. The goal of the clinician, suggests Hart (2008), should be
“to figure out what the patient finds supportive or important and then to
encourage such healthy practices in each patient’s life rather than injecting
practitioners’ own thoughts or belief systems into the patient’s life”. Hart goes
on to emphasize that a clear, ethical plan for how to address the issue of spiri-
tuality with patients is important.
Defining Spirituality
Spirituality is a multidimensional construct that has been defined in a multi-

tude of ways, and is generally understood to be related to but distinct from
religiosity (Albaugh 2003; Ameling and Povilonis 2001; Chiu et al. 2004; Fry
1998; Narayanasamy 1999; Tanyi 2002). Religious beliefs are associated with
a particular faith tradition. Participation in or commitment to a religion may
involve adherence to certain beliefs (ideology), religious practices (prayer,
sacraments, and rituals), religious proscriptions (dietary modifications or
avoidance of tobacco, alcohol, or drugs), and participation in a religious com-
munity. Spirituality is understood to be a broader concept that includes many
dimensions. Murray and Zentner (1989) define spirituality as a quality that
goes beyond religious affiliation and that strives for inspiration, reverence,
awe, meaning, and purpose, even in those who do not believe in God. The
spiritual dimension, they suggest, is in harmony with the universe, strives
for answers about the infinite, and comes into focus when the person faces
Table 7.1. Characteristics of Spirituality
Connectedness/relationships with self, others, Higher Power, nature

Meaning and purpose in life
Transcendence
Love/compassion
Wholeness
Energy
emotional stress, physical illness, or death. Spirituality has also been described
as a process and sacred journey (Mische 1982), the essence or life principle
of a person (Colliton 1981), an experience of the radical truth of things
(Legere,1984), and the propensity to make meaning (Reed 1992). Waldfogel
(1997) notes that the experiences of joy, love, forgiveness, and acceptance all
depend on, and are manifestations of, optimal spiritual well-being. Cohen
(1993) adds that spirituality involves finding deep meaning in everything,
including illness and death, and living life according to a set of values. Chiu
et al. describe spirituality as a power, force, or energy that stimulates creativity,
motivation, or a striving for inspiration (2004). The simplest and most straight-
forward definition is from Pargament (1997), who defined spirituality as the
“search for the sacred.” Table 7.1 lists characteristics commonly associated
with spirituality.
RELATIONSHIP BETWEEN SPIRITUALITY AND HEALTH OUTCOMES
A number of studies report findings suggesting that spiritual and religious

beliefs overall contribute to positive health benefits, including stress reduction
and an increased sense of well-being (Larson et al. 1992). A metaanalysis of
42 studies revealed that attendance at church, synagogue, mosque, or Buddhist
monastery is related to longer life (McCullough et al. 2000). The odds of sur-
vival were significantly greater for people who scored higher on measures of
religious involvement than for people who scored lower, even after controlling
for a variety of social and health-related variables.
These findings mirror a number of earlier studies that focused on the
relationship between social support, isolation, and heart disease. Ruberman
et al. (1984) studied over 2,300 men who had survived a heart attack. Men
who identified themselves as being socially isolated and having a high degree
of life stress had more than four times the risk of death as men who reported
low levels of isolation and stress, even when controlling for factors such as
smoking, diet, weight, and exercise. Interestingly, these psychosocial effects
had a much more powerful effect on premature deaths than did the beta-
blocker drugs that were the primary focus of the study. Williams et al. (1992)
studied over 1,300 men and women who had undergone coronary angioplasty
and were found to have at least one severely occluded coronary artery. In
following these patients five years post-procedure, it was found that men
and women who were not married and who did not have a close confidant
were three times more likely to have died than those who were married, had a
confidant, or both.
In addition to the extensive body of literature on the health-related benefits
of social support and community, many studies have been conducted that have
focused more specifically on the relationship between spiritual health and heart
health. Haskell (2003) reported that patients who score higher on spirituality
or religious scales have lower mortality due to coronary artery disease or car-
diac surgery-related complications. Similarly, Morris (2001), in reporting on
Ornish’s Lifestyle Heart Trial, reported that the degree of spiritual well-being
may be an important factor in the progression or regression of coronary artery
disease. Patients with the lowest scores on spiritual well-being had the most
progression of coronary obstruction, while those with the highest scores had
the most regression. Spirituality has also been found to be correlated to depres-
sion in patients with chronic heart failure. Depression is known to be associ-
ated with a variety of adverse health outcomes in cardiac patients, including
poor quality of life, more frequent hospitalizations and higher mortality. In a
study of outpatients with heart failure, Bekelman et al. (2007) found that greater
spiritual well-being was strongly associated with less depression, thereby sug-
gesting that spirituality may be a modifiable coping resource that potentially
could reduce or prevent depression, and thus improve quality of life, among
other outcomes. Not all studies, however, have reported consistent results in
relating spirituality with positive health outcomes. In a study of 503 patients
surviving an acute myocardial infarction, Blumenthal et al. (2007) found little
evidence that self-reported spirituality, frequency of church attendance, or fre-
quency of prayer was associated with cardiac morbidity or all-cause mortality
in patients with depression and/or low perceived support.
There is a growing body of literature focused on the effects of intercessory
prayer on health outcomes in patients with heart disease. The studies (Aviles
et al. 2001; Benson et al. 2006; Byrd 1988; Harris et al. 1999; Krucoff, Crater,
and Lee 2006) have varied considerably in methodological rigor, the popula-
tions studies, and the endpoints measured. While trends have been reported in
the various studies, as a whole, the results have been inconclusive.
Assessing Spirituality
A spiritual assessment or screening can be conducted by a physician, nurse,

spiritual care provider. or other health professional as a routine part of provid-
ing care. It is common for screening questions to be incorporated into stan-
dard health history interviews and forms. Table 7.2 provides an example of
questions that may help to detect a spiritual need or issue.
The FICA interview guide (Puchalski and Romer 2000) is frequently used
to obtain a spiritual history in clinical settings. FICA is an acronym that stands
for faith, importance/ influence, community, and address. Within each of these
four areas, there is a set of questions such as: What is your faith? How impor-
tant is your faith? Are you part of a religious community? How would you like
spiritual issues addressed in your care? A tool called Hope, developed by
Anadarajah, Long, and Smith (2001), taps into four similar domains. Examples
of questions in the interview guide include:
• H stands for sources of hope, meaning, comfort, strength, peace, love

and connection

What do you hold onto in difficult times?
What sustains you and keeps you going?
• O stands for organized religion

Are you part of a spiritual or religious community?
What aspects of your religion are helpful or not so helpful to you?
• P stands for personal spirituality and practices

Do you have personal spiritual beliefs that are independent of your
religion?

What spiritual practices do you find most helpful to you personally?
Table 7.2. Spiritual Screening Questions
What are your sources of hope, strength, comfort and peace?
Are you part of a religious or spiritual community?
What spiritual practices do you find most helpful to you personally?
Are there any specific practices or restrictions I should know about in providing your
health care?
Leonard, B., and D. Carlson. 2003. Spirituality in Healthcare. www.csh.umn.edu/modules/

index.html
• E stands for effects on medical care and end-of-life issues.

Has being sick affected your ability to do things that usually help
you spiritually?
Beyond these tools, there are a growing number of standardized measures

that have been developed to assess spiritual and religious beliefs and pra-
ctices for the purpose of research and evaluation. The Spiritual Well-Being
Scale (SWBS), developed by Paloutzian and Ellison (1983), measures both
religious and existential well-being. Religious well-being refers to one’s rela-
tionship with God or some higher power, and existential well-being refers to
a sense of purpose in life and satisfaction with life. The Serenity Scale, devel-
oped by Roberts and Aspy (1993) and abbreviated by Kreitzer et al. (2009),
focuses on a dimension of spirituality called serenity. Serenity is defined as
being a spiritual experience of inner peace that is independent of external
events.
Addressing Spiritual Issues
When patients develop heart disease, they may experience a number of

physical symptoms including pain, shortness of breath, palpitations, lack of
energy, sweating, nausea, dizziness, weakness, and edema. The predominant
orientation of biomedicine is on curing—that is, diagnosing, treating, and
repairing the broken or damaged part of the body. This requires technical
competence on the part of the health care provider, as well as access to tech-
nology, and an environment in which care can be safely provided. Without a
doubt, patients seek care to be cured, relieved of the burden of their illness or
disease. The human experience, however, encompasses more than the physical
symptoms that are often the stimulus for seeking care. A diagnosis of heart
disease and its ensuing treatment may release a cascade of feelings and
emotions ranging from anxiety and fear to profound sadness, depression, grief,
loss, hopelessness, anger, isolation, or spiritual distress. As noted by Milstein
(2005), the trauma of a diagnosis may shatter the person’s beliefs about the
predictability of the world and create a sense of meaninglessness. A critical
task is to “make sense” of the loss and sort out its significance in the larger
context of one’s life. This is the work of spirituality and healing. Spirituality, as
noted earlier, focuses on finding meaning, purpose, and connections. Healing
is about restoring wholeness and integration and requires attending to the
whole person—body, mind, and spirit. An integrative approach as described
by Milstein includes a focus on curing and healing, on “being with” as well as
“doing to.”
“Being with” patients is a way for health care providers to more deeply con-
nect with patients, and in doing so, provide spiritual support. This requires,
however, cultivation of skills such as deep listening, compassion, and presence.
• Deep listening: Enables the health care provider to be alert for mean-
ings, connections, and yearnings reflected in conversations. It is impor-
tant to listen to both what is said as well as what is not said. Authenticity
is critically important. Patients can sense when the listener is distracted
or not really interested.
• Compassion: Cultivating compassion develops within us a conscious-
ness of other’s distress and suffering and a desire to alleviate it.
• Mindfulness: The skill of mindfulness enables us to be anchored in
the present moment and free ourselves of reactive, habitual patterns
of thinking, feeling, and acting.
• Presence: When we are truly present to another human being, we are
intentionally choosing to be with another in a healing way. This requires
more than just physical presence. In Western culture, there is a strong
bias toward action. Health care providers too often feel that they are
not effective unless they are doing something. Presence requires being,
not doing. This may be especially challenging for providers during
times of expressions of anger or anguish by patients or families. It is
also difficult because in a fee-for-service environment, providers are
paid to “do something” and are not paid for presence.
As noted by Anandarajah (2008), “The therapeutic intervention at this heart

level is at once both simple and extremely difficult. It requires that health care
professionals bring their humanity (?) to the medical encounter”.
Health care providers need to recognize that at times, the person most able
to meet the patient’s needs is a professional trained in spiritual care, such as a
chaplain or a community-based religious leader. This is particularly important
if the patient is seeking support for specialized prayer, or ritual. While the
chaplain or a religious leader may be the primary spiritual care provider, spir-
itual care can be effectively and interchangeably provided by multiple mem-
bers of the care team.
In an exploratory study of spiritual care at the end of life, Daaleman and
his colleagues (2008) identified barriers to and facilitators of spiritual care.
Lack of sufficient time was a major barrier, as were institutional obstacles such
as absence of privacy and lack of continuity of providers. Social, religious,
or cultural discordance between caregivers and patients was another obstacle
to care. Having ample time to foster relationships with a facilitator was impor-
tant, as was effective communication among the caregivers and between the
caregivers and the patient. Health care providers also noted that their personal
experiences with serious illness and death helped them to more effectively
provide spiritual care to patients.
Many patients engage in spiritual self-care practices that health care provid-
ers should be aware of which enhance their health, well-being, and ability to
cope with illness. Commonly used spiritual practices include the following:
• Prayer: There are many forms of prayer. Prayer may be offered in

words, song, sighs, cries, gestures, or silence. Prayer may be individual
or communal, public or private. Prayers may be petitions or requests
for healing, for peace, for safety, for acceptance, for strength to con-
tinue, as well as for courage. Prayer is a means of reaching out and
connecting with a higher power.
• Meditation: Meditation is a self-directed practice for relaxing the body
and calming the mind that has been used by people in many cultures
since ancient times. Kabat-Zinn (2005) emphasizes that meditation is
best thought of as a way of being, rather than a collection of techniques.
Mindfulness expands the capacity for awareness and for self-knowing.
When a mindful state is cultivated, it frees people from routinized
thought patterns, senses, and relationships, and the destructive mind
states and emotions that accompany them. When people are able to
escape from highly conditioned, reactive, and habitual thinking, they
are able to respond in more effective and authentic ways.
• Music, Art, and Nature: The arts are powerful healing tools that can
help people explore feelings, gain new insights and perspectives, and
enhance other spiritual practices. For some, being in nature is a pow-
erful spiritual experience.
• Journaling: Journaling is both a way to record experiences and a way
to get in touch with inner thoughts and feelings. People who journal
on a regular basis often find it to be a way to measure progress in self-
growth and attain a broader perspective on life and relationships.
• Walking a Labyrinth: A labyrinth is a circuitous path that leads to a
center. It is different from a maze that has twists, turns, and blind
alleys. A labyrinth has only one way in to the center and one way out.
When people walk the labyrinth, they may pray, meditate, listen to
music, or just observe nature. People report that when they walk a
labyrinth, they gain insight or perspective. For some people, walking
a labyrinth is both an actual physical experience as well as a metaphor
for life’s journey.
• Spiritual Direction or Counseling: Spiritual directors or counselors
accompany people on their spiritual journeys. They help people
explore such spiritual issues as grief, loss, anger, and abandonment, as

well as life challenges. They may offer guidance in prayer, journaling,
and reading of sacred texts. Spiritual directors may also help explore
how God or the divine is present and active in one’s life. Spiritual
directors are listeners and companions. Like other forms of counsel-
ing, spiritual directors do not give answers, but rather assist individu-
als in exploring questions, issues, and concerns in their lives. Spiritual
directors are found at retreat centers and in private practice and may
be employed by health care institutions or faith communities.
Spirituality of Physicians
Medicine’s deepest roots spring from a spiritual foundation. Modern medicine

evolved from the tradition and role of the spiritual healer. Whether in ancient
Babylonia and Egypt (Jayne 2003) or in more contemporaneous tribal cultures
(Aldridge 1991), the community healer utilized spiritual power to address the
underlying spiritual issues thought to be at the basis of the patient’s disease.
Even today, many religious orders are deeply engaged in health care and offer
a combination of biomedicine and spirituality (or religion) to address both the
physical and spiritual needs of their patients.
The previous section documented the growing interest in, and extensive
literature on, patient and family spiritual issues. The literature on nurse spiri-
tuality is also rich, in part due to the importance of spirituality in the practice
of holistic nursing (3). In contrast to these voluminous literatures, the study of
physician spirituality is conspicuous in its absence.
The perceived importance of physician spirituality has faded as medicine
has become scientifically-based. The Western conception of the duality of body
and spirit, combined with the spectacular successes that have accrued from
considering disease as a biological disorder that can be understood through
rational scientific inquiry, has led many to dismiss physician spirituality as a
relic of a superstitious past.
However, relationships have symmetry, and it is fundamentally flawed to
consider the impact of patient spirituality on the physician–patient relation-
ship without also considering the impact of physician spirituality. Disregarding
physician spirituality opens physicians up to the risk of misunderstanding
a critical dimension of the physician–patient relationship, or missing chances
to help patients cope with their fears and their pain; the physician may also
miss opportunities to derive deep fulfillment from their professional work—
perhaps the only source of true long-term satisfaction left in the modern prac-
tice of medicine. We consider each in order.
Physician Spirituality and the Physician–Patient

Relationship
There appears to be general agreement that patient spirituality and religious

issues are important determinants of decision-making and coping skills when
dealing with illness, and thus deserve study and attention (Astro, Puchalski,
and Sulmasy 2001; Mueller, Plevak, and Rummans 2001). These religious
influences on the healthcare process are not confined to patients. Curlin and
colleagues found that 55 percent of physicians agree with the statement, “My
religious beliefs influence my practice of medicine” (2005).
However, as a group, physicians’ religious characteristics are significantly
different from the U.S. population as a whole. These differences include increased
physician affiliation with religions that are underrepresented in the general
population, an increased likelihood to consider themselves spiritual but not
religious, and twice the likelihood of coping with major problems without rely-
ing on God (Curlin et al. 2005). These differences might be expected to have an
impact on important components of the physician–patient relationship.
Sulmasy (1997)) has developed a four-quadrant model that explores
physician–patient interactions categorized by the status of physician and
patient religious beliefs. In one quadrant, both the patient and the physician
believe in God. In this situation, there is the foundation for meaningful
dialogue, tempered by the potential problem of different religious traditions.
In the converse situation, neither the patient nor the physician believe in God.
Here, religious or spiritual matters may not be important components of the
relationship.
When the patient believes in God and the physician does not (statistically
the most likely probability), the physician needs to know how best to respect
the patient’s beliefs within the context of his own belief system. In this statisti-
cally probable situation, it is important for physicians to be very clear on their
own spiritual beliefs (or lack thereof) in order to feel comfortable and support-
ive interacting with a patient who just as firmly may feel very differently.
The last combination, and statistically the least probable, is for the physician
to believe in God while the patient does not. Here the potential danger is for a
physician, motivated by a desire to help a human being in distress, to inject
religion or spirituality into the relationship when it is not desired. However,
the normal process of obtaining a spiritual assessment serves to identify this
potentially awkward situation and will guide the perceptive clinician appropri-
ately. It is considered inappropriate for a physician to proselytize on behalf of
his or her religious or spiritual beliefs.
Koenig (2008) has described seven reasons physicians may want to assess
and address their patients’ spiritual needs.
1. Many patients are religious, and many would like their faith to be a
factor in their health care.
2. Religion influences patients’ abilities to cope with their illnesses.
3. Religious beliefs and practices may influence health outcomes.
4. Patients may be isolated from their traditional sources of religious
support.
5. Religious beliefs may impact medical decisions and choices of therapies.
6. Religious commitments may influence the type of follow-up care and
support a patient receives after leaving the hospital.
7. The Joint Commission requires a spiritual history be taken and docu-
mented on every patient admitted to an acute care hospital.
Physician Spirituality and Compassion
Few, if any, physicians would challenge the proposition that compassion is

a desirable trait in a physician. Yet few, if any, would disagree that compassion
is in increasingly short supply in modern healthcare. Yet of the six “C”
characteristics Emmanuel and Dubler (1995) defined as necessary in an ideal
physician–patient relationship (choice, competence, communication, com-
passion, continuity, and [no] conflict of interest), compassion may be the only
one not threatened by the effects of the changes sweeping across American
healthcare.
In contrast to sympathy (sharing the feelings of another) or empathy (iden-
tifying with the feelings of another), compassion includes the desire to be of
help and to alleviate the suffering of another. Sympathy and empathy may
result from individual personality characteristics, or may be skills that can be
taught in professional training (Burack et al. 1999; Carmer and Glick 1996;
Pence 1983). Compassion, on the other hand, has traditionally been more
closely associated with spirituality, particularly Buddhism and Christianity.
As described by Rinpoche and Shlim (2006), compassion is defined in
Buddhism as the sincere desire to alleviate the suffering of another. Buddhists
believe that people are fundamentally and inherently compassionate, but our
compassion is masked by the distractions and fears created by our mind, par-
ticularly anger and attachment. Thus, in the Buddhist tradition, the way to
cultivate compassion is to learn how to move beyond the mind-generated
traps of anger and attachment. The tools used to do so include meditation,
yoga, service to others, and the cultivation of a calm and detached mind.
The Christian canon has many references to the compassion of Jesus. In

Matthew 20:34, Jesus is described as a compassionate healer: “So Jesus had
compassion on them, and touched their eyes: and immediately their eyes
received sight, and they followed him.” Matthew 9:36 describes Jesus as a com-
passionate leader: “When he saw the crowds, he was deeply moved with com-
passion for them, because they were troubled and helpless, like sheep without
a shepherd.” Jesus as a compassionate healer is again referenced in Matthew
14:14: “When He went ashore, He saw a large crowd, and felt compassion for
them and healed their sick.”
Thus the pursuit and engagement of physician spirituality may be a power-
ful aid in fostering the development of physician compassion.
Physician Spirituality and Professional Satisfaction
There has been a profound increase in physician professional dissatisfaction

over the past twenty years. In 1973, 15 percent of several thousand practicing
physicians expressed any doubt that they had made the correct career choice.
Surveys over the past 10 years have found that 30–40 percent of physicians now
state they would not choose medicine as a career if starting out today. Many
causes have been postulated, including managed care, the malpractice crisis,
disparate expectations between what patients demand and what physicians can
deliver, and lack of time (Zugler 2004). While improving physician satisfaction
has obvious benefit to the physician and the profession, it also appears that
patients of satisfied physicians are also more satisfied (Haas et al. 2000).
Physician stress and dissatisfaction are not limited to practicing physicians.
Shanafelt et al. (2002) found that 76 percent of internal medicine residents met
criteria for burnout, including high scores on depersonalization or emotional
exhaustion subscales, leading one writer to ponder, “Who is sicker: patients—
or residents?” (Clever 2002).
Sulmasy points out that illness, especially serious illness, is a spiritual event
(1999). Patients must grapple with questions of a transcendent nature, includ-
ing meaning, relationships, and ultimately life’s value. It is these critical issues
that constitute the spiritual aspects of health care, yet they are ignored and
even disincentivized in our scientifically reductionist, industrialized medical
culture.
Perhaps, then, the cause of this growing professional dissatisfaction is more
fundamental than the environmental issues that have been proposed. Perhaps
it falls more in line with Moore’s plea: “I have plenty of machinery around
me; what I really need is a more enchanting world in which to live and work”
(1996).
As experienced physicians reflect back on their careers, they frequently

recollect experiences that are more spiritual than technical. Lown muses, “No
pleasure is quite akin to the joy of helping other human beings secure and
lengthen their hold on life” (1999) Siegel states, “The healing I have done as a
doctor has always come back to me tenfold. So who is the healer, who is the
healed?” (1989). The compelling stories of medicine are filled with spiritual
values and experiences that are outside of the narrow scope of technical bio-
medicine (Lacombe 1995).
Grubb (2003) pleads for a medicine “with a little more soul.” He suggests
that making a spiritual connection with patients will help physicians at least as
much as patients. In a series of essays, Grubb has given us profound examples
of experiencing the transcendent in the midst of normal medical practice, and
the profoundly rewarding effect it has had on him as a physician and as an
individual (Grubb 1998; 1999a; 1999b; 2000; 2002; 2003; 2005; 2006a; 2006b).
He proposes that if physicians can reconceptualize themselves as healers who
dedicate their lives to reducing human suffering, as opposed to being solely
technicians, they will reconnect with the passion and dedication that initially
directed them to medicine.
Conclusion
Spirituality and scientific biomedicine are not mutually exclusive. They deal
with different components of the human being and the relationships between
human beings. As Sulmasy (1999) observes, there is no reason that physic-
ians can not practice excellent biomedicine and still be aware of the spiritual
dimension of their work, and be responsive to the spiritual needs of their
patients.
Yet these different components are interconnected and interwoven in both
the physician and the patient in subtle but powerful ways. Many patients seem
to do better physically when their spiritual needs are addressed (Siegel 1986).
Similarly, physicians seem to be far more satisfied in their practice when they
allow themselves to include both their patients’ and their own spirituality in
their work (Sulmasy 1997). The physician–patient relationship is strength-
ened. Physicians will find it easier to maintain a compassionate demeanor with
their patients as they nurture their own spiritual dimension. Physicians may
be able to rise above their profound dissatisfaction with the circumstances sur-
rounding health care as they rediscover the deeper meaning of their work and
its implications.
At the dawn of the twenty-first century, it may be that the most profound
revolution awaiting Western biomedicine is not genomics, nanotechnology, or
artificial organs, but rather the reintroduction of spirituality into the practice
of medicine, resulting in extraordinary improvements in the satisfaction of
patient and healer alike.
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8
Cardiac Behavioral Medicine: Mind–Body
Approaches to Heart Health
KIM R. LEBOWITZ
key concepts
■ Psychological distress, including depression, anxiety, and stress,

is common among cardiac patients.
■ The presence of psychological distress can interfere with a
patient’s ability to engage in healthy lifestyles and follow medi-
cal recommendations.
■ Depression, anxiety, and stress have emerged as independent
risk factors for the development of cardiac disease and are asso-
ciated with an increased risk in cardiac morbidity and mortality.
■ The causal mechanisms linking emotional health and cardiac
outcomes remain unknown, but likely involve physiological and
behavioral pathways.
■ Cardiac patients should be routinely screened for emotional
distress and referred for treatment when applicable.
■ Treatment for psychological distress among cardiac patients is
efficacious, safe, and has a positive impact on emotional func-
tioning, quality of life, and lifestyle behaviors, although there
is no research to indicate at present that treatment improves
cardiac outcomes.
■
I
t was Hippocrates who commented, “You ought not to attempt to cure the
body without the soul. The cure of many diseases is unknown to physi-
cians because they disregard the whole.” In the seventeenth century,
William Harvey, one of the pioneers of cardiovascular physiology, observed a
more specific connection between emotions and cardiovascular functioning,
135
remarking that “a mental disturbance provoking pain, excessive joy, hope or

anxiety extends to the heart where it affects temper and rate.” (Harvey 1628,
109). The mind–body connection, as it relates specifically to cardiac health,
has been the epicenter of empirical investigation for the past several decades in
the emerging field of behavioral medicine. Cardiac behavioral medicine refers
to a multidisciplinary approach to cardiac health that examines behavioral,
social, and psychological factors that contribute to, maintain, or follow a car-
diac diagnosis or event.
The origins of cardiac behavioral medicine lie within the traditional risk
factors for cardiovascular disease. The field of cardiology provides a strong,
direct link between individuals’ behaviors and physical health. With the excep-
tion of age, sex, and family history, the traditional risk factors for cardiovascu-
lar disease are predominantly modifiable and reflect an individual’s lifestyle
behaviors, including smoking, diet, and activity. Cardiac behavioral medicine
specialists—including psychologists, psychiatrists, social workers, physicians,
dieticians, and exercise therapists—can work together to help individuals ini-
tiate and maintain behavior changes that can contribute to cardiac risk reduc-
tion and overall improvement in health.
Cardiac behavioral medicine also addresses the psychological component
of cardiac health, which will be the focus of this chapter. Cardiac patients are
at increased risk of experiencing emotional distress and impaired quality of
life compared with the general population (Rozanski, Blumenthal, and Kaplan
1999; Skala, Freedland, and Carney 2005). For example, more than 30 percent
of individuals with a recent myocardial infarction (MI) report significant
depression (Lichtman et al. 2008; Skala, Freedland, and Carney 2005). This
mind–body relationship is bidirectional; psychological disorders and person-
ality characteristics also have been shown to have a negative impact on cardiac
health, facilitating the development of cardiac disease and predicting increased
morbidity and mortality following a cardiac event (Kubzansky and Kawachi
2000; Lichtman et al. 2008). A large multinational study (INTERHEART)
demonstrated that psychosocial factors (including depression, stress, anxiety,
anger, and social isolation) accounted for 32 percent of the risk for coronary
artery disease (CAD). The magnitude of the risk conferred by psychosocial
factors was equivalent to smoking and almost double the risk associated with
hypertension (Rosengren et al. 2004; Yusuf et al. 2004). Psychological distress
also can impede patients’ ability to follow medical recommendations and
reduce their cardiovascular risk through lifestyle modification (Carney et al.
2002). Assessment and treatment of mood and emotional distress should
be integrated into cardiac care to optimize health, reduce cardiovascular risk,
aid with adjustment to an illness, and enhance quality of life (Grissom and
Cardiac Behavioral Medicine: Mind–Body Approaches to Heart Health 137
Phillips 2005). This chapter will review depression, anxiety, and stress within
the cardiac population, as these are the most common psychological anteced-
ents and consequences of cardiac illness.
Depression
Clinical depression is a common sequelae of cardiac disease and cardiac sur-

gery, impacting approximately 15 to 25 percent of cardiac patients, and up to
double that in studies that include subclinical levels of depression. (Grissom
and Philllips, 2005; Lichtman et al. 2008; Rudisch and Nemeroff, 2003).
Depression has drawn attention not only because of its prevalence in this pop-
ulation, but because depression has emerged as an independent risk factor for
the development of CAD as well as a predictor of morbidity and mortality,
especially among post-MI patients (Lichtman et al. 2008).
The prevalence of depression is 3 times higher among cardiac patients than it

is in the general population.
Emotions represent a healthy form of expression and are a typical part of

any significant event, including a medical diagnosis. Sadness, frustration, fear
and even relief are commonly exhibited at various stages of medical treatment
and are completely healthy. Emotions become problematic when they co-oc-
cur with a variety of other symptoms, last for a specific period of time, and
either cause the individual distress or interfere with an individual’s ability to
function, at which point they constitute a syndrome or psychological disorder.
Isolated symptoms or transient emotions are not to be confused with mental
disorders. Tearfulness or sadness alone does not constitute depression.
Clinical depression (Major Depressive Disorder or MDD) is characterized
by the presence of one or more major depressive episodes, each which requires
the presence of depressed mood or markedly reduced interest in most activi-
ties for at least two weeks, plus the addition of at least four other depressive
symptoms (American Psychiatric Association 2000; see Table 8.1). Symptoms
of depression can be emotional, somatic, or cognitive in nature. Emotional
symptoms include sadness, hopelessness, and anhedonia. Somatic symptoms
involve change in body systems or routines and include change in appetite,
weight change, sleep disturbances, psychomotor retardation or agitation,
fatigue and loss of energy. Cognitive symptoms of depression include dimin-
ished memory or concentration, feelings of worthlessness, excessive guilt, and
Table 8.1. DSM-IV-TR Symptoms Of A Depressive Episode*
Emotional
• Depressed mood∗∗
• Loss of interest in most activities∗∗
• Increased tearfulness
Somatic
• Appetite or weight change
• Insomnia or hypersomnia
• Psychomotor agitation or retardation
• Fatigue or low energy
Cognitive
• Feelings of worthlessness or guilt
• Diminished concentration or decision-making
• Suicidal thoughts or behaviors
∗
Symptoms appear for at least two weeks and are associated with distress or impairment in
functioning
∗∗
At least one of these symptoms must be present, plus at least four others
suicidal thoughts. The symptoms of depression must represent a change from

the individual’s baseline level of functioning and be severe enough to cause
disability or interference in daily functioning. Many research studies in the
cardiac arena examine the presence of depression several days after a cardiac
event. As a result, the symptom duration criterion (2 weeks) is often disre-
garded. When symptoms of depression are present but the criteria for a major
depressive episode are not met, other potential mood disorder diagnoses can
include dysthymia (mild chronic depression), adjustment disorder, or minor
depression (same criteria as major depression but only one to three additional
symptoms are experienced per episode). Table 8.2 summarizes characteristics
Table 8.2. Factors Associated With An Increased Risk Of Developing Depression

• Female gender
• Younger age (diagnosis or symptom onset <60 years)
• Previous episodes of clinical depression
• Minimal social support
• Recent stressful life events
• Functional limitations in patients with heart failure∗
• Family history of clinical depression
∗
With the exception of heart failure, disease status or severity does not predict depression.
in cardiac patients that are associated with an increased risk of developing

depression.
DEPRESSION, COMPLIANCE, AND TRADITIONAL

RISK FACTORS FOR CAD
Depression clusters with a majority of the established risk factors for heart
disease and is associated with unhealthy lifestyle behaviors.
Smoking
A history of depression confers a three-fold increase in the likelihood of

becoming a smoker (Breslau et al. 1998; Joynt, Whellan, and O’Connor 2003).
The prevalence of smoking in the depressed population hovers around 49 per-
cent. There is a dose-dependent relationship between depression and smok-
ing, where more severe depression predicts a greater likelihood of smoking
(Anda et al. 1990; Rudisch and Nemeroff 2003). Depression also impedes
successful smoking cessation (Glassman et al. 1990). Depressed individuals
are 40 percent less successful at quitting smoking, at least in part because they
experience more physiological symptoms of withdrawal. The relationship
between depression and smoking is bidirectional: smokers are at increased
risk of developing clinical depression (Breslau et al. 1998).
Non-Adherence to Medical Recommendations
Depressed cardiac patients are less likely to adhere to medical recommenda-

tions and are more likely to drop out of cardiac rehabilitation (Blumenthal
et al. 1982; Joynt et al. 2003; Rudisch and Nemeroff, 2003). Carney et al. (1995)
tracked compliance to daily aspirin for 3 weeks in patients with CAD.
Non-depressed patients were compliant with aspirin 69 percent of the time;
clinically depressed patients exhibited a mere 45 percent compliance rate.
Some studies suggest that noncompliance in and of itself (rather than to a
specific treatment) is a prognostic indicator of poorer outcomes, as indicated
by increased morbidity and mortality associated with noncompliance to a
placebo (Granger et al. 2005;l McDermott, Schmitt, and Wallner 1997). The
extent to which noncompliance is a marker of depression in these studies has
not been examined.
Obesity
Several studies have found that obesity is associated with an increased risk
of depression, with 25 percent of obese individuals meeting criteria for depres-
sion (Joynt et al. 2003; Simon et al. 2006). Depressed individuals have a greater
BMI and present with increased central and whole-body adiposity compared
with matched controls (Miller et al. 2002).
Diabetes
Depressed individuals are more than twice as likely to develop diabetes over a
13-year period, and diabetics are twice as likely to be depressed compared with
the general population. Depression negatively influences glycemic control and
increases risk of diabetic complications (Joynt et al. 2003).
Other Traditional Risk Factors
Depression is associated with an increase in homocysteine levels, with up to

50 percent of depressed individuals exhibiting levels that would confer an
increased cardiac risk. Further, the use of folate to lower homocysteine levels
has been found to have antidepressant properties (Joynt et al. 2003). Hypertension
is more prevalent among depressed populations than healthy controls (Carney
et al. 2002). Hypercholesterolemia is one of the only established risk factors for
cardiovascular disease that is inversely correlated with depression. Depression is
associated with low levels of serum cholesterol, and recovery from depression
may be associated with an increase in cholesterol (Joynt et al. 2003). Physical
activity and exercise tolerance are inversely related to symptoms of depression
(Carney et al. 2002).
Cardiac risk reduction via behavior change can be challenging for most
patients, but may be particularly daunting to an individual with clinical depres-
sion. Remember, depressed individuals are likely experiencing diminished
motivation, apathy, and deficits in concentration and memory, not to mention
possibly suicidal thoughts—each of which alone can be a major barrier to
successfully executing lifestyle changes and appropriately following medical
recommendations. Recognizing and addressing depression is an important
first line of treatment for patients who require behavioral risk reduction.
Following the resolution of depression, patients are more likely to be involved

and motivated members of the medical team, with more sufficient emotional
and cognitive resources to successfully initiate and maintain lifestyle changes.
DEPRESSION AS A PREDICTOR OF MORBIDITY AND MORTALITY
The seminal studies of Frasure-Smith et al. (1993; 1995) evaluated the impact
of MDD on survival among 222 post-MI patients. Depression emerged as an
independent risk factor for mortality, conferring a risk equivalent to that of
established risk factors, including left ventricular ejection fraction and previous
MI. Those who were depressed in the hospital were four times more likely to
die within 6 months, compared to those who were not depressed, regardless
of disease severity and risks factors (Frasure-Smith et al. 1993). Mortality rates
at an eighteen-month follow-up were 40 percent among those who experienced
recurrent depression in the hospital (e.g., they were depressed in the hospital
plus had a prior history of depression) compared with 7 percent for those
who were non-depressed (Frasure-Smith et al. 1995). Investigations that did
not formally assess for clinical depression have found associations between
depressive symptoms and cardiac outcomes among post-MI patients, including
increased mortality and repeat cardiac events (Rudish and Nemeroff 2003).
The relationship between depression and mortality has been most thor-
oughly investigated in the post-MI population, but depression also appears to
predict cardiac and all-cause mortality among patients with unstable angina,
CAD, congestive heart failure, individuals without coronary disease at the
time of study enrollment, and among patients undergoing coronary artery
bypass graft (CABG) and valve surgery (Blumenthal et al. 2003; Burg et al.
2003b; Carney and Freedland 2003; Ho et al. 2005; Jiang et al. 2001; van Melle
et al. 2004).
The presence of MDD or subclinical depressive symptoms, particularly
among patients with CAD and those undergoing CABG, has also been associ-
ated with morbidity and less favorable cardiac outcomes, including repeat
hospitalizations, subsequent cardiac surgery, myocardial ischemia, MI, angio-
plasty, increased health care costs and utilization, failure to return to previous
There is a dose-dependent relationship between depression and mortality,

where more severe depressive symptoms are associated with a greater risk of
mortality. This relationship provides further support of a causal link between
depression and cardiac outcomes.
activities, continued surgical pain, and diminished quality of life (Burg et al.
2003a; Carney et al. 1988; Carney and Freedland 2003; Frasure-Smith et al.
2000; Jiang et al. 2003; Mallik et al. 2005; van Melle et al. 2004).
DEPRESSION AND THE DEVELOPMENT OF

CORONARY ARTERY DISEASE
Depression in otherwise healthy individuals predicts incident CAD and car-

diac mortality even decades later. One study found a relative risk of 4.16 for
incident CAD among community residents with MDD (Pratt et al. 1996). The
consistent findings are impressive given the heterogeneity of the studies, which
have varied with respect to depression severity (e.g., a clinical diagnosis of
MDD versus current or previous depressive symptoms), symptom assessment
(questionnaires versus clinical interview), age (ranging from individuals in
their twenties to older adults at study onset), and length of follow-up (months
to decades). A clinical diagnosis of depression appears to carry a greater risk
than subclinical depressive symptoms (Carney and Freedland 2003).
MECHANISMS OF ACTION LINKING DEPRESSION

AND CARDIAC OUTCOMES
Although the link between depression and poor cardiac outcomes is well
established, the mechanisms of action are minimally understood. The most
obvious explanation is behavioral. Given that depressed individuals are less
physically active, more likely to smoke, less compliant with medical recom-
mendations, and less likely to eat a heart- healthy diet, lifestyle behaviors seem
to be the most plausible explanation for why depression can lead to the devel-
opment of CAD or a poorer prognosis after a cardiac event. However, lifestyle
behaviors account for no more than 50 percent of the variance in this relation-
ship, and in most studies, depression remains a predictor of morbidity and
mortality independent of these risk factors (Carney et al. 2002; Rudisch and
Nemeroff 2003).
Physiological mechanisms must be involved as well, although there is min-
imal concrete empirical support for any particular pathophysiological mecha-
nism at present. Despite depressed individuals appearing sluggish on the
outside, there is evidence that depression is associated with physiological
hyperarousal, either heightened sympathetic activity, diminished parasympa-
thetic regulation, or both. Depression is associated with a high resting heart
rate and decreased heart rate variability (Joynt et al. 2003; Rozanski, Blumenthal,
and Kaplan 1999). Other hypothesized physiological pathways include inflam-
mation that leads to endothelial damage, hypercoagulability as reflected by
increased platelet activation in depressed individuals that may lead to throm-
bus formation, and rhythm disturbances that predispose depressed individu-
als to sudden cardiac death (Joynt et al. 2003; Rozanski, Blumenthal, and
Kaplan 1999; Rudisch and Nemeroff 2003).
Anxiety
Anxiety disorders are the most common group of psychological disorders in

the United States, affecting 25 percent of Americans across the lifespan (Kessler
et al. 1994). Each of the different anxiety disorders share various symptoms
of severe anxiety and carry a significant level of impairment. The specific
symptoms, time frames, behaviors, and level of severity help to differentiate
the various anxiety disorders (see Table 8.3). The prevalence of anxiety disor-
ders and subclinical anxiety is greater among cardiac patients than in the
general population. For example, 15 percent of patients presenting to the ED
with noncardiac chest pain and up to 25 percent of patients seen in cardiology
practices have panic disorder, which has a 0.9% prevalence rate in the general
population (American Psychiatric Association 2000; Fleet et al. 1996; Janeway
2009). Cardiac patients often report anxiety following a cardiac diagnosis,
after discharge of an implantable cardiac defibrillator (ICD), with symptom
onset, or precipitating a cardiac procedure, including surgery. Among cardiac
Table 8.3. Psychological Disorders That Incorporate

Anxiety as a Predominant Symptom
Generalized anxiety disorder

Panic disorder with or without agoraphobia
Agoraphobia without a history of panic
Specific phobia
Social phobia
Obsessive-compulsive disorder
Posttraumatic stress disorder
Acute stress disorder
Adjustment disorder with anxious mood
patients, anxiety can manifest itself as excessive worry, fear, phobias, panic
attacks, agoraphobia, or increased health-checking behaviors.
Epidemiological data demonstrate an association between anxiety symp-
toms and CAD outcomes (Kubzansky et al. 1998; Kubzansky and Kawachi
2000). Several large-scale community-based longitudinal studies have demon-
strated that anxiety disorders are associated with increased risk for the devel-
opment of CAD, ventricular arrhythmias, coronary death, and sudden cardiac
death. Specifically, the multivariate relative risk of fatal CAD among the most
anxious in these studies ranged from 2.41 to 7.8, compared with those not
presenting with anxiety (Kubzansky and Kawachi, 2000; Watkins et al. 2006).
Furthermore, a dose-dependent relationship has been observed between anxi-
ety symptoms and cardiac death (Rozanski, Blumenthal, and Kaplan 1999).
Most of the longitudinal studies have examined men only, despite an increased
prevalence of anxiety among women. One study that included women, the
Framingham Heart Study, found anxious symptoms associated with increased
MI and coronary death at a 20-year follow-up among homemakers, but not
among women employed outside the home (Eaker, Pinsky, and Castelli 1992).
Much less is known about the prevalence of anxiety in specific sub-cardiac
populations, or the relationship between anxiety symptoms and disorders with
the development or progression of non-CAD cardiac disorders.
Anxiety among cardiac patients can stem from patients’ perceived inability
to predict or control cardiac events, symptoms, or disease course. As human
beings, we constantly search our surroundings for a sense of order and control.
With any perceived loss of control or predictability, anxiety can result. In an
effort to increase a sense of predictability, patients can become hypervigilant
toward their surroundings and their bodies; they may start to avoid circum-
stances that they perceive as dangerous, and they may engage in health-checking
behaviors or other safety behaviors to inflate their sense of safety.
PANIC
Panic disorder is characterized by recurrent panic attacks combined with

concern about future attacks or the consequences of future attacks. A panic
attack is a sudden episode of intense fear or discomfort that is associated with
several cognitive and physical symptoms, several of which also are cardinal
features of cardiac disease, including chest pain, palpitations, sweating, short-
ness of breath, sensations of choking, and hot flashes (American Psychiatric
Association 2000; see Table 8.4 for diagnostic criteria). Panic attacks are often
terrifying for the individual due to the intensity and sudden onset of symp-
toms, combined with a sense of danger. Because of the overlap of symptoms,
Table 8.4. DSM-IV-TR Symptoms of a Panic Attack∗
Physical
• Palpitations or increased heart rate
• Sweating
• Trembling
• Shortness of breath
• Sensation of choking
• Chest pain or tightness
• Nausea or abdominal distress
• Dizziness, lightheadedness, or feeling faint
• Numbness or tingling sensations
• Chills or hut flashes
Emotional
• Fear of dying
• Fear of losing control or going crazy
• Feelings of detachment from oneself or feelings of unreality
∗A panic attack requires at least 4 symptoms present during a discrete period of intense fear
or discomfort. The onset of symptoms is abrupt and symptoms reach peak intensity within
10 minutes.
many patients with panic disorder present to the ED and often undergo costly
and invasive cardiac testing, with normal results. In fact, panic disorder is 30
to 50 times more common among patients with noncardiac chest pain com-
pared with the general population (Fleet, Lavoie, and Beitman 2000).
Among cardiac patients, anxiety often is related to physical health, resulting
in increased awareness and perception of physical sensations, as if looking at
one’s body through a microscope. A cognitive model of panic asserts that mis-
interpreting a physical symptom as threatening will trigger fear and physiolog-
ical arousal (hence, more physical symptoms), creating a self-sustaining
downward spiral of anxiety and physical symptoms, resulting in a panic attack
(Craske and Barlow 1993). See Figure 8.1 for an example of how catastrophic
thoughts can trigger and sustain panic.
Following a new diagnosis, cardiac patients may have difficulty interpreting
physical symptoms accurately due to limited experience with their new health
condition, often leading to anxiety. For example, Michael was a 59-year-old
professional Caucasian married male, newly diagnosed with atrial fibrillation.
He became astutely aware of all symptoms in his body following this diagnosis,
and he was uncertain how to determine which symptoms were benign and
which warranted medical attention. As a result, he called his cardiologist every
time he noticed a new symptom, which initially resulted in several urgent
Physical symptom
e.g., palpitations
Heightened panic Catastrophic thought

e.g., “I’m going to have a
heart attack and die”
Increased arousal and

physical symptoms
Fear or panic
Figure 8.1. A model of the interactive cycle of physical symptoms, cognitive distor-
tions, and emotions that can lead to panic.
phone calls per week. With education and more experience with his body,
Michael became more adept at interpreting his symptoms more accurately.
Additional information, often acquired through a combination of personal
experience and medical feedback, will be sufficient for many patients to decrease
their anxiety about their physical symptoms. This is comparable to having a
new baby. At first, a new parent is unsure of which patterns or symptoms exhib-
ited by the baby are benign versus problematic. First-time parents are more
cautious and call their pediatrician’s office more often than repeat parents, who
have learned from firsthand experiences with their previous children. For many
patients, a new diagnosis brings about a healthy increase in anxiety that will
resolve with experience and increased comfort. For others, however, the panic
becomes more frequent and disabling, leading to panic attacks.
AVOIDANCE
In an effort to predict cardiac events and control their health, anxious cardiac
patients may start to avoid certain places or activities that they perceive as
dangerous or embarrassing should they fall ill. Just as Pavlov’s dogs learned to
salivate by the sound of a bell, cardiac patients can develop learned responses
based on their cardiac experiences. If Laura’s ICD fired at the movie theater,
she may start to avoid the movie theater in hopes of avoiding another dis-
charge. After Ron experiences chest pain on the treadmill, he may choose to
ignore exercising in an attempt to avoid similar symptoms. This logic works
well when situational factors are responsible for cardiac events. In a majority
of circumstances, however, the physiology has little to do with the logistics of

the situation. Unfortunately, many individuals process the situational factors
in an attempt to maintain some control and predictability over their health.
Avoidance is a key characteristic of anxiety disorders and is typically uti-
lized to provide instant reduction or avoidance of anxiety. A child who is afraid
of dogs may cross the street to avoid interacting with a dog. This behavior
eliminates anxiety in the short term. However, in the long run, avoidance ends
up maintaining and even strengthening a specific fear. Ultimately, exposing an
individual to the feared stimuli (e.g., dogs, needles, exercising) can help the
patient develop confidence and more accurate perceptions, leading to reduced
anxiety in the long term (Craske and Barlow 1993).
Agoraphobia in cardiac patients refers to a marked anxiety in situations or

places where escape would be difficult (or embarrassing) or help would be
unavailable should panic symptoms or cardiac symptoms occur. This anxiety
generally leads to pervasive avoidance of a variety of situations such as being
alone, traveling in a bus or airplane, or being in an elevator.
WORRY
Worry is the cognitive component of anxiety and refers to future-oriented

thinking about possible negative outcomes to a situation—that is, the “what
if ’s.” Worry is healthy and is the driving force behind problem-solving and
planning. For individuals with Generalized Anxiety Disorder, the worry
becomes excessive and uncontrollable, causing distress and disability. Subclinical
worry has been associated with an increased risk in developing CAD and expe-
riencing cardiac mortality (Rozanski, Blumenthal, and Kaplan 1999). Cardiac
patients, like many medical patients, experience worry about their health, mor-
tality, finances, prognosis, test results, family relations, and coping resources.
Table 8.5 lists some common worries among cardiac patients.
MECHANISMS OF ACTION LINKING ANXIETY

AND CARDIAC OUTCOMES
There remains much to learn about the association between anxiety and car-
diac health, including gaining a better understanding of the potential pathways.
Current theories suggest physiological and behavioral pathways. The increased
Table 8.5. Common Areas of Worry and Stress Among Cardiac Patients
• Fear of physical symptoms, such as fatigue, breathlessness, palpitations, or
lightheadedness
• Body image concerns including surgical scars, implanted devices, or weight changes
• Lack of independence
• Fear of intubation with surgery
• Fear of ICD discharge or syncope
• Fear of death
• Fear that heart will stop (or will not restart after surgery)
• Fear of being a burden to others
• Worry about meeting financial obligations
• Fears about inability to caregive or parent effectively
• Worry about life expectancy and inability to meet goals
• Concern about treatment side effects
• Worry about test results and prognosis
• Fear of pain and inadequate pain management
• Concern of contributing to stress in the marriage or family
risk of cardiac death associated with anxiety is related to sudden cardiac death
and not MI (Kubzansky et al. 1998; Rozanski, Blumenthal, and Kaplan 1999),
suggesting that ventricular arrhythmias may be a possible mechanism (Watkins
et al. 2006). Reduced heart rate variability further suggests abnormal auto-
nomic control among anxious individuals. Alternate possibilities include the
promotion of atherogenesis, perhaps through hypertension, and the triggering
of coronary events, possibly through plaque rupture or coronary vasospasm.
From a behavioral perspective, anxiety is associated with poor sleep, decreased
activity, an unhealthy diet, increased smoking, and increased alcohol and
drug use (Kubzansky et al. 1998; Kubzansky and Kawachi 2000). The extent
to which these behaviors mediate the relationship between anxiety and CAD
is unclear.
Stress
Stress is a common experience among cardiac patients and has been correlated
with the development of CAD and the onset of acute cardiac events. Stress,
unlike depression and anxiety, is not a diagnostic clinical syndrome, but
rather a reaction to a real or perceived danger or challenge. Stress incorporates
physical, emotional, cognitive, and behavioral symptoms, and can often lead
to psychological disorders such as depression or anxiety (Baum, Gatchel,
and Krantz 1997). One of the most predictable and prominent physiological
Hormones secreted
Cardiovascular system activated Platelet activity

( HR, BP, vasoconstriction)
Stored fat converts

Digestion inhibited to energy
Sexual functioning
Immune functioning inhibited
inhibited
Blood flow diverts from
extremities to larger muscles
Figure 8.2. The sympathetic nervous system: An overview of some physiological

changes that occur when the “fight or flight” response is activated.
components of stress is the activation of the sympathetic nervous system, the

body’s “flight or flight” response, which mobilizes the body’s resources to pro-
mote safety in the wake of an emergency. Figure 8.2 summarizes a few of the
physiological changes that occur during the stress response. Although the
body’s stress response is a way to safe guard the body against danger, repeated
or sustained activation of the fight or flight response (i.e., chronic stress) can
cause wear and tear on various organ systems, leading to hypertension, athero-
sclerosis, immune dysfunction, digestive disorders, fertility problems, and
depression (Baum, Gatchel, and Krantz 1997).
ACUTE STRESS AND CARDIAC EVENTS
Anecdotal reports and case studies have long speculated about an association
between acute stress and cardiac events. Retrospective studies have found that
up to one-quarter of heart attack patients report experiencing anger or upset
in the hours prior to symptom onset (Krantz et al. 1996). Epidemiological
studies have found increased cardiac events following large-scale acute stres-
sors such as earthquakes and terrorist activity. On the day of the 1994 Los
Angeles earthquake, the occurrence of sudden cardiac death rose from a daily
average of 4.6 to 24 on the day of the earthquake (Leor, Poole, and Kloner
1996). Meisel et al. (1991) reported a sharp increase in myocardial infarction
and a 2-fold increase in sudden cardiac death among residents near Tel Aviv
during the initial days of the missile attacks during the 1991 Gulf War.
Ventricular arrhythmias more than doubled among New York City residents
with defibrillators in the month following September 11, 2001 (Steinberg
et al. 2004).
Laboratory and observational studies have found that mental stress can
trigger myocardial ischemia among patients with CAD, including those who
do not have exercise-induced ischemia (Holmes et al. 2006; Ramachandruni
et al. 2006). Mental-stress induced ischemia is predominantly silent and may
occur in 40 to 70 percent of patients with CAD (Krantz et al. 1996). Laboratory
studies have documented myocardial ischemia during mental stressors, includ-
ing arithmetic tests, speech tasks, and when recalling a situation that previ-
ously made the patient angry (Holmes et al. 2006; Rozanski, Blumenthal,
and Kaplan 1999). In addition to ischemic events, laboratory mental stressors
have been found to trigger the onset of blood pressure increases (with rela-
tively low heart rate increases), wall motion abnormalities, and acute drops
in ejection fraction among individuals with CAD (Krantz et al. 1996). It is
worth noting that the contrived laboratory stressors may underrepresent the
potency of mental stress in real-life situations. Ambulatory monitoring found
that emotional distress experienced during daily life among individuals with
CAD more than doubled the likelihood of transient ischemia in the subse-
quent hour (Gullette et al. 1997).
CHRONIC STRESS AND THE DEVELOPMENT OF CAD
Chronic psychosocial stress has been implicated in the development of coro-

nary atherosclerosis. Job strain is a well-studied chronic life stress often associ-
ated with CAD. Jobs with high demands and low decision latitude have been
associated with a 4-fold increase in cardiac-related deaths across time (Karasek
et al. 1981). Jobs with minimal control or insufficient rewards also have been
related to cardiac events and progression of atherosclerosis (Rozanski,
Blumenthal, and Kaplan 1999). Although some negative studies have been
reported, a majority of the evidence points to a positive association between job
stress and CAD risk. Chronic stress also has been examined in terms of recent
life changes or culmination of life stressors. Although most of these studies are
retrospective or rely on report bias, the majority of findings suggest an associa-
tion between increased life stressors and cardiac morbidity and mortality
(Baum, Gatchel, and Krantz 1997; Holmes et al. 2006; Krantz et al. 1996).
An extensive body of evidence from animal models nicely illustrates the
impact of chronic social stress on atherosclerosis. Studies with cynomolgus
monkeys, whose social organization is characterized by hierarchies of social
dominance, generated chronic social stress by reorganizing groupings of mon-

keys and therefore causing unstable social groups. Compared with controls
(who remained in a stable social group), the stressed monkeys experienced
extensive coronary artery atherosclerosis, particularly the high ranking or
dominant male monkeys (Manuck, Kaplan, and Matthews 1986). Studies of
non-primates also have demonstrated effects of social stress on atherosclerotic
changes of the coronary arteries and aorta (Manuck, Kaplan, and Matthews
1986). Cardiovascular hyperresponsivity during stress, as evidenced by stress-
induced heart rate changes in monkeys, may account for some of the disease
progression (Manuck, Kaplan, and Clarkson 1983).
MECHANISMS OF ACTION LINKING STRESS AND CARDIAC OUTCOMES
There is currently minimal direct evidence elucidating the pathophysiological

processes that may promote stress-induced cardiac events. Hypothesized mech-
anisms include coronary vasoconstriction, autonomic dysfunction including
cardiovascular reactivity, the promotion of plaque rupture and thrombus for-
mation from endothelial dysfunction and prothrombotic responses, platelet
aggregation, and electrical instability leading to ventricular arrhythmias
(Bhattacharyya and Steptoe, 2007; Holmes et al. 2006; Rozanski, Blumenthal,
and Kaplan 1999). Neuroendocrine changes also may be involved, as illus-
trated by changes in reproductive hormones among female monkeys at
greater risk of atherosclerotic change (Manuck, Kaplan, and Matthews 1986).
Psychosocial and behavioral pathways may be partly involved as well. Stress
increases unhealthy behaviors such as smoking, alcohol consumption, inactiv-
ity, and a poor diet (Baum, Gatchel, and Krantz, 1997). Social support has a
protective value and appears to diffuse the deleterious effects of stress, possibly
by both behavioral and physiological pathways (Rozanski, Blumenthal, and
Kaplan 1999; Skala, Freedland, and Carney 2005).
Treatment Modalities
Treatment goals for emotional distress in cardiac patients are multiple and
include: 1) reducing emotional distress; 2) improving quality of life and patient
functioning; and 3) enhancing the patient’s ability to follow medical recom-
mendations and engage in healthy behaviors. Ideally, a reduction in depres-
sion, anxiety, and stress also would translate into reduced cardiovascular risk,
but large clinical trials to date have yet to show a significant treatment effect on
cardiac outcomes (Lichtman et al. 2008; Writing Committee for the ENRICHD
Investigators 2003). Research examining specific mechanisms of action

will hopefully lead to refined treatments targeted at physiological pathways
implicated in the mind–body relationship. Current treatment options for
depression, anxiety, stress, and poor adjustment to a cardiac event are varied
and include pharmacotherapy, psychotherapy, stress management, relaxation
therapy, physical activity, and less traditional options such as laughter, yoga,
acupuncture, and massage. A majority of treatment outcome trials focus
specifically on depression and primarily utilize the post-MI population.
PHARMACOTHERAPY
Safety considerations are a salient concern that may prevent some care pro-
viders from prescribing antidepressants or anxiolytics to cardiac patients.
There are minimal clinical trials exploring the safety and efficacy of antide-
pressants in cardiac patients, but those limited trials have focused on post-MI
patients. Results from these trials indicate that two selective serotonin reuptake
inhibitor (SSRI) antidepressants are relatively safe for patients with CAD and
are effective in treating moderate, severe, and recurrent depression: sertraline
and citalopram (Glassman et al. 2002; Lespérance et al. 2007; Roose and
Miyazaki 2005). These two SSRIs are considered the first-line antidepressant
drugs for patients with CAD (Lichtman et al. 2008). The Sertraline
Antidepressant Heart Attack Randomized Trial (SADHART) found sertraline
to be more effective than placebo in reducing moderate and severe depression
in 369 depressed post-MI patients who were randomized to treatment or
placebo for 6 months. A non-significant trend favored sertraline over placebo
in reducing severe adverse cardiovascular outcomes (Glassman et al. 2002).
A post hoc analysis of the Enhancing Recovery in Coronary Heart Disease
Patients (ENRICHD) study found that patients treated with an SSRI (non-
randomized, but added in addition to cognitive behavioral therapy or usual
care) had a 42 percent reduction in adverse cardiac outcomes, including recur-
rent MI and death, compared with depressed participants who did not receive
antidepressants (Writing Committee for the ENRICHD Investigators 2003).
SSRIs have no significant impact on blood pressure, heart rate, or cardiac con-
duction, making them a much safer and more favorable option over tricyclic
antidepressants, which have been associated with antiarrhythmic properties,
adverse side effects such as postural hypotension, and a less tolerable side effect
profile (Glassman et al. 2002; Roose and Miyazaki, 2005). Less is known about
antidepressants in non-CAD cardiac patients or about the safety and efficacy
of anxiolytics in cardiac populations. The most common pharmacological
treatment of anxiety includes benzodiazepines and SSRIs (Janeway 2009).
Many antidepressants have anxiolytic properties that can reduce the irrit-
ability and worry that often accompany anxiety.
Cardiotoxic side effects, adverse side effects, dependency (with benzodiaz-

epines), and drug–drug interactions require careful consideration prior to
beginning pharmacotherapy in cardiac patients. Education should always
accompany prescriptions. Patients often are unaware of the side-effect profile
of medications, or that these side effects usually diminish with time. They often
misunderstand the delayed response associated with antidepressants and the
importance of continuing the use of medication. Once started, cardiac patients
should be monitored closely for the first two months and routinely thereafter
to monitor suicidal risk, side effects, dosing titrations, and compliance with
medication (Lichtman et al. 2008). Approximately 15 percent of patients dis-
continue antidepressant use within the first six months due to adverse side
effects or lack of efficacy (Lespérance and Frasure-Smith 2000).
COGNITIVE BEHAVIORAL THERAPY
Although psychotherapy is effective in reducing emotional distress, minimiz-

ing relapse, improving quality of life, and enhancing motivation in depressive
and anxious patients, only a few trials have examined the efficacy and safety of
psychotherapy among cardiac patients. The most efficacious non-pharmaco-
logic treatment for depression or anxiety among cardiac patients is cognitive
behavioral therapy (CBT). (Lett, Davidson, and Blumenthal 2005; Skala,
Freedland, and Carney 2005).
CBT operates on the premise that feelings and behaviors are dictated by
thoughts, and that maladaptive thought patterns can be identified and changed
to reduce psychological distress (Beck 1995). For example, an individual with
depression may have the thought “I am worthless;” an individual with anxiety
may have the thought “I am in danger;” and a stressed individual may have the
thought “I have to be perfect.” Therapy takes a direct approach to help the patient
identify, test, and replace irrational beliefs, often by engaging in behavioral or
cognitive exercises. The behavioral component of treatment may incorporate:
increasing pleasurable activities, establishing daily routines, improving sleep
patterns, facing feared situations, mobilizing social support, journaling daily
thought patterns, increasing physical activity, or developing healthy responses
to fears or emotions. CBT is an efficacious and empirically validated treatment
for depression, anxiety, and numerous other psychological disorders.
A key component of the treatment of many anxiety disorders incorporates

some form of exposure to the feared object, whether physical symptoms, situ-
ations, or places (Craske and Barlow 1993). CBT asserts that fear is maintained
(and may increase) with avoidance, because avoidance avoids any opportunity
to learn that the feared object may not be dangerous. Exposure provides learn-
ing opportunities to increase patients’ sense of mastery and comfort in the face
of a feared situation, and to help patients test and replace irrational beliefs
related to their fears. Exposure can be imaginal or “in vivo” (real life). Regardless
of which form exposure takes, exposure can be done gradually, whereby
the therapist begins with a low-feared situation and slowly progresses to more-
feared situations as the patient habituates. Exposure also can be done
more abruptly, called flooding, where the therapist exposes the patient to the
most-feared situation immediately. Although gradual (or graded) exposure
is most common, both are effective. Table 8.6 outlines a graded exposure
hierarchy for a cardiac patient who developed panic and agoraphobia after
multiple syncopal episodes. The use of relaxation training often is utilized in
Table 8.6. Example of a Graded Fear Hierarchy for Exposure Treatment

with a Cardiac Patient Exhibiting Panic and Agoraphobia After
Multiple Syncope Episodes∗
1. Sit in the therapist’s office with only the therapist present (note: he initially required a
friend to be present).
2. Sit in the waiting room for 10 minutes without my friend present.
3. Walk in place to get my heart rate up, with therapist present.
4. Close the bathroom door when showering or using the restroom (note: he initially
required a friend to be present for fear of syncope).
5. Ride an elevator by myself.
6. Stand outside my house by myself for 10 minutes.
7. Walk down the street by myself for 15 minutes.
8. Eat a meal at home by myself.
9. Sit in my car by myself for 10 minutes.
10. Drive around the block by myself.
11. Stay at home alone for 1 hour.
12. Drive on the highway with a passenger present.
13. Drive on the highway for 2 exits (and back) by myself.
14. Stay at home alone all day by myself.
15. Drive myself to visit with friends at my old job.
16. Leave my house and walk to a restaurant or store by myself (gone 2 hours).
17. Drive on the highway at night and/or when raining.
∗
This graded hierarchy was created with direct input from the patient, based on his presenting
fears and his degree of distress in certain circumstances, particularly those circumstances in
which he was alone.
treatment for anxiety. Because anxiety and relaxation contradict each other,
the body cannot be both relaxed and anxious at the same time.
To date, the ENRICHD trial is the only published randomized clinical trial
that examined psychotherapy (CBT) for treatment of depression in patients
with CAD. A total of 2,481 post-MI patients with either depression or low
perceived support were randomized to six to twelve weeks of CBT or usual
care, with patients receiving an SSRI when indicated for severe or persistent
depression. At 6 months, CBT was favored over usual care in reducing depres-
sion, despite improvements in both groups. Although CBT was effective at
reducing depressive symptoms, treatment had no impact on cardiac outcomes
or survival (Writing Committee for the ENRICHD Investigator, 2003).
Lespérance et al. (2007) recently evaluated the impact of short-term interper-
sonal psychotherapy (IP) plus simultaneous use of citalopram among clini-
cally depressed individuals with CAD (the CREATE trial). Following twelve
weeks of treatment, citalopram was superior to placebo in reducing depression.
However, there was no additional benefit to IP above clinical management.
Of note, the clinical management control consisted of weekly 25-minute
sessions with a trained therapist who focused on education, support, encour-
agement of adherence to medication use, and problem-solving for side effects.
These findings could suggest that the active problem-solving approach of
clinical management (in some ways similar to CBT) may not be inert.
STRESS MANAGEMENT
Stress management is a nonspecific heterogeneous term that can encompass

many treatment modalities, including cognitive behavioral strategies, educa-
tion, and relaxation training. Stress management has been found to be effective
in reducing headaches, cardiovascular reactivity, immune dysfunction, hyper-
tension, and pain (Bernstein and Carlson 1993). Some studies have reported
improved cardiac outcomes following stress management in patients with CAD
(Blumenthal et al. 1997; Blumenthal et al. 2005). Blumenthal and colleagues
(1997) found that a four-month stress management program for patients with
CAD was successful in reducing mental stress-induced ischemia, ambulatory
ischemia, and cardiac events at a three-year follow-up. The following compo-
nents are often utilized in stress management.
Education
Patients typically benefit from information about stress, particularly about the
physiological effects of stress on the body. Understanding the physiology
behind their symptoms can offer relief and empowerment. Furthermore,

awareness of the deleterious effects of stress on the body can improve patients’
motivation to reduce stress and adopt healthier coping strategies.
The educational component also can address why stress is experienced.
Lazarus (1966) describes the role of cognitive appraisals in stress. Specifically,
stress occurs when a situation is perceived as dangerous, or when the resources
to deal with the situation are perceived as insufficient. The balance of these
appraisals can shift across time as information, coping skills, and personal
abilities change. The essential component to this theory is that appraisals of a
situation and internal resources dictate whether the stress response is acti-
vated. Altering those perceptions can be critical to reducing stress. Cognitive
therapy can be used to address inaccuracies in someone’s threat perceptions.
A variety of tools can be used to increase someone’s resources so they feel more
adept at handling the situation at hand.
Protecting Healthy Behaviors
During stressful situations, many individuals are apt to forego healthy life-
styles and behaviors, which can be detrimental to healthy coping. Protecting
sleep, exercising regularly, eating a well-balanced diet, and minimizing alcohol
consumption are simple ways to reduce the effects of stress on the body and to
increase the body’s resources to cope with stressful events. Something as simple
as poor sleep in the hospital can diminish someone’s coping resources, so that
events seem more overwhelming or challenging. Patients should be encour-
aged to protect their health by engaging in positive behaviors, particularly
during stressful times.
Improving Coping Strategies
Coping refers to the behavioral or psychological strategies that are employed

to tolerate or reduce a stressful situation. When coping skills and resources
are healthy and intact, individuals are less likely to experience stress (Lazarus
and Folkman 1984). Coping styles can generally be categorized as either
problem-focused or emotion-focused. The former employs efforts to actively
reduce the stressful situation, whereas the latter entails efforts to regulate or
reduce the emotional consequences of the stressful event. Both types of coping
are helpful, but coping may be most beneficial when the style of coping matches
the level of control of a situation. When a stressful situation is perceived as less
controllable (which is often the case with physical illness), emotion-focused

coping may be preferable. Simply put, if the situation cannot be changed, an
individual’s reaction to that situation can always be controlled.
Even when the style of coping is well-matched to the situation’s level of
control, favored coping strategies can be inaccessible during illness, particu-
larly when activity or independence are limited. For example, Veronica was
a 35-year-old married female, employed full time, the mother of a toddler,
who was hospitalized for valve replacement surgery. Veronica was emotionally
healthy with no history of psychiatric distress. Her coping strategies were
healthy and she typically coped with stress by running daily, practicing yoga
weekly, remaining active, playing with her daughter, cooking, and maintaining
control over her environment. During her hospitalization and recovery peri-
ods, Veronica’s typical coping strategies were inaccessible to her, triggering
emotional distress. Intervention with Veronica helped her develop coping
strategies that were more accessible in the hospital and equally effective for
her, such as imagery, listening to music, creating a recipe book, and updating
her daughter’s baby album. Veronica was able to sustain her emotional stability
despite losing access to her typical coping strategies.
Relaxation
An important component of stress management (as well as a popular adjunct

to other treatment modalities) is relaxation training, which aims to reduce or
reverse the physiological effects of stress on the body and associated emotional
distress. The relaxation response triggers activation of the parasympathetic
nervous system, which works to restore physiological homeostasis following
activation of the fight or flight response. Relaxation can come in many forms,
including diaphragmatic breathing, progressive muscle relaxation (which
involves the systematic tensing then releasing of muscle groups in the body),
imagery, hypnosis, biofeedback, or a combination of the above. Among car-
diac rehabilitation patients, progressive muscle relaxation has been associated
with reductions in symptoms of depression, resting heart rate, and medication
dosages (Collins and Rice 1997).
Another way to increase the relaxation response is to encourage patients to
take a daily “time out” from stress. Protecting daily time for relaxation or a
pleasurable activity can help reduce the emotional and physiological toll of
stress. Pleasurable activities will vary by individual, but a time out may incor-
porate exercise, a bubble bath, reading a book, completing a crossword puzzle,
having coffee with a friend, cooking a new recipe, gardening, listening to
music, visiting a park, or getting a massage. As long as the activity is perceived

as pleasurable, regardless of whether it is physically active or passive in nature,
it can help protect the mind and body from the effects of daily stress.
Exercise
Increasing evidence points to exercise as an effective adjunct treatment for

depression, anxiety, and stress (Barbour, Edenfield, and Blumenthal 2007).
One longitudinal study found that a 4-month aerobic exercise program was as
effective in treating MDD as sertraline. Furthermore, a 10-month follow-up
revealed that patients in the exercise group had lower relapse rates than those
in the medication group (Babyak et al. 2000; Blumenthal et al. 1999; Blumenthal
et al. 2007). Controlled trials with cardiac patients are limited and many stud-
ies have methodological imitations, relying on self-report or lacking a control
group. However, the few randomized controlled exercise trials among post-MI
patients suggest that exercise is effective at reducing depressive symptoms
across time compared with usual care, particularly when the exercise program
is not home-based (Lett, Davidson, and Blumenthal 2005; Lichtman et al.
2008). Controlled trials are still needed to determine the impact of exercise on
cardiac patients presenting with psychological disorders.
Other Therapeutic Modalities
The therapeutic modalities summarized in this chapter represent the most

common and efficacious treatments for emotional distress and stress, but the
most effective strategies for any given patient will be ones that take into account
that particular patient’s needs, resources, and preferences. For example, while
efficacious, pharmacotherapy should not be the first line of treatment for a
patient who is resistant to taking psychotropic medications. Similarly, exercise
may not be an appropriate antidepressant for an angina patient with a positive
stress test. Therefore, flexibility in treatment planning is imperative for cardiac
patients, many of whom have barriers to engaging in traditional treatment,
whether those barriers be physical, social, financial, geographical or time-
based. Alternative approaches, such as online or telephone-based therapies,
may help overcome some of these barriers; however, a lack of empirical inves-
tigations has made it difficult to determine the efficacy and safety of such
approaches with cardiac patients.
The use of complimentary or alternative therapies also may be helpful
adjuncts to treatment for cardiac patients. Although these approaches are
less conventional treatments for psychological distress, they may be effective

in helping to reduce physiological tension and emotional distress. An indi-
vidual’s emotional resources typically can be enhanced by engaging in any
enjoyable activity, which can often take the form of a complementary modal-
ity, such as Qigong, yoga, Reiki, Healing Touch, massage, laughter, prayer, or
acupuncture.
Role of the Medical Team: SERF
Given the prevalence of emotional distress in cardiac patients and its impact
on morbidity and mortality, comprehensive cardiac care should incorporate
assessment of emotional functioning (see Table 8.7). Emotional distress hin-
ders patients’ compliance, impedes their success at making lifestyle changes,
contributes to a diminished quality of life, and predicts poorer cardiac outcomes.
The accumulation of research findings within cardiac behavioral medicine
emphasizes the importance of addressing emotional health routinely with
cardiac patients, which was recognized by the American Heart Association
in 2008 with their endorsement for the screening of depression in patients
with coronary heart disease (Lichtman et al. 2008). A positive screen should
result in a referral to a mental health professional and closer follow-up moni-
toring of patients’ cardiac health (Lichtman et al. 2008). As a cardiac psycholo-
gist, I strongly encourage the medical team to SERF with their patients. This
is a simple acronym I created based on a compilation of the existing research
and suggested best practices to date, to provide professionals with an easy
guide of how to incorporate emotional functioning into conventional clinical
practice.
Table 8.7. The Role of the Medical Team in Addressing

Psychological Distress: SERF
SCREEN for depression and emotional distress
EDUCATE patients about the symptoms, prevalence, and cardiac risk

related to depression, anxiety, and stress (and ENCOURAGE them to
report symptoms)
REFER patients who screen positively to a mental health provider for

comprehensive evaluation and/or treatment
FOLLOW depressed and distressed patients more closely to monitor

their compliance and cardiac health
SERF STEP 1: SCREENING
There are no diagnostic tests for depression or anxiety. The only way to for-
mally diagnosis a patient with a psychological disorder is through clinical
evaluation by a mental health professional. In lieu of comprehensive assess-
ment, screening for emotional distress is gaining popularity in cardiac settings.
In 2008, the American Heart Association formally recognized depression as a
risk factor for morbidity and mortality among patients with coronary heart
disease and called for routine screening of depression (Lichtman et al. 2008).
Screening questions require minimal time or expense and can be completed in
multiple settings and by a variety of team members. A positive screening will
alert the medical team that a patient requires a referral to a mental health
professional for a complete evaluation and possible treatment. Additionally, a
positive screening will alert the medical team that a patient may be at increased
risk of noncompliance, unhealthy lifestyle behaviors, morbidity, mortality, or
the development of heart disease.
To determine whether an individual is at increased cardiac risk due to
depression, a depression screening should incorporate the following three
questions, at a minimum:
1. Have you ever been diagnosed with or treated for depression?

2. Have you been feeling sad, down, or hopeless for the past week or more?
3. Have you recently lost interest in activities that used to be pleasurable?
The following screening questions should be added to screen for nonspecific

emotional distress:
1. Have you (or has anyone close to you) recently noticed a change in
your mood or personality for the worse?
2. Have you been feeling anxious or stressed lately, to the point where
your mood or routines have been affected?
3. Does everyday life seem harder to cope with lately?
SERF STEP II: EDUCATE
Patients often are upset to learn afterwards that their experience of depres-
sion following a cardiac event was not an isolated incident. Patients should
be educated up front about the potential emotional consequences of a cardiac
procedure or surgery in the same manner that they are educated about poten-
tial physical complications. At minimum, patients should be educated about
the symptoms and prevalence of depression, especially after a heart attack and
after cardiac surgery. Educating patients about depression, anxiety, and stress
does not facilitate the development of these conditions, yet the information
can provide relief and comfort if those symptoms arise. Furthermore, patients
should be informed that depression and stress have a negative impact on their
cardiac health so that patients respond appropriately to symptoms when they
emerge. The negative stigma that often surrounds mental illness (and which
can be a barrier to seeking treatment) can be reduced if the topic is addressed
directly and proactively by the medical team.
SERF STEP III: REFER
Patients who screen positively for depression, or who acknowledge emotional

distress, should be referred to a mental health provider for comprehensive eval-
uation, diagnosis, and treatment when applicable. In their editorial, Grissom
and Phillips (2005) highlight the importance of education and referral, stating,
When treatment [for depression] seems indicated, the physician’s task

is not necessarily to treat the patient, but instead, to motivate the patient
to accept referral. Helping the patient to understand that depression
commonly accompanies chronic illness, that it complicates treatment,
and that, in most cases, it can successfully be treated can reduce the
stigma and improve motivation. (pg. 1214)
Appropriate mental health referrals may include psychologists, psychiatrists,

psychiatric nurses, social workers, or clinical counselors. Most academic med-
ical centers or university settings have a department of psychiatry that will
house resources for clinical evaluation or treatment, often with specialization
in the growing field of behavioral medicine.
SERF STEP IV: FOLLOW
The presence of depression, anxiety, or stress should place a patient in an

increased risk stratification. At this time, it is unclear whether treatment for
psychological disorders translates into a reduction in cardiovascular risk.
However, patients with depression, anxiety, or stress should be followed more
closely than if they were not at increased cardiac risk. The frequency or form
of follow-up best suited for distressed cardiac patients is unknown, but may
include more frequent office visits, EKGs, or assessment of blood levels of
medications.
Conclusions
Depression, stress, and anxiety are common experiences among cardiac

patients. Unfortunately, their high prevalence often leads to a false conjecture
on the part of the medical team that emotional distress is a “normal” or
“healthy” reaction following a cardiac event. Psychological factors are far from
benign healthy reactions, but play a significant role in the onset, course, and
prognosis of cardiac disorders—perhaps almost as significant a role as tradi-
tional risk factors. Table 8.8 summarizes symptoms of emotional distress that
may present in cardiac settings and have an impact on patients’ emotional and
Table 8.8. Signs and Symptoms that a Patient may be

Depressed, Anxious, or Stressed
Symptom Presentation:
• Change in sleep (insomnia or hypersomnia)
• Change in weight without effort
• Increased irritability
• Sadness or tearfulness
• Minimal motivation
• Excessive fatigue or lack of energy
• Excessive worry about physical symptoms
Functional Impairment:
• Has not returned to previous levels of activity as expected
• Requests an extension of medical leave from work
• Unnecessary avoidance of certain activities or situations because of health concerns
• Poor hygiene
• Difficulty coping with medical status or life changes
• Reduced interest in previously pleasurable activities
Medical Management Challenges:

• Multiple visits to the ER or doctor’s office for unexplained symptoms
• Difficulty complying with medication or treatment regimen
• Frequent phone calls to the medical team to seek reassurance or to report the same
symptom without being asked
• Concern about symptoms or test results despite significant reassurance and
information
• Multiple missed appointments
cardiovascular health. Although there are no consistent data to confirm

whether psychological treatment can reduce cardiovascular risk, the treat-
ments available for psychological disorders are efficacious, safe, and result in
improved quality of life for cardiac patients. The incorporation of psychologi-
cal health is a necessary component of comprehensive cardiac care.
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9
Energy Medicine
RAUNI PRITTINEN KING
key concepts
■ Energy medicine is predicated on the concept that energy

emanates from the body, and it can be influenced by skilled
practitioners to promote health and healing.
■ The human energy system has three components: meridians
or energy tracts, chakras or energy centers, and auras or energy
fields.
■ Ancient cultures have been using energy healing modalities
throughout history, including the Egyptians, Greeks, Chinese,
the Indians, and Native Americans.
■
Energy Medicine
E
nergy medicine, also referred to as vibrational medicine, is the art and
science of bringing balance and well-being into our lives. Our bodies
are always looking to return to their natural state of health. The energy
healing modalities are techniques to assist or enhance the process of healing.
For the body to function at its absolute peak of performance, all parts
and processes must be interconnected by a system that delivers energy and
information at the fastest possible speed available in nature. In the living body,
each electron, atom, chemical bond, molecule, cell, tissue, and organ has its
own vibratory character (Oschman 2000), as does the body as a whole. Energy
medicine seeks to understand this vibratory energy, and to interact with it to
facilitate healing (Gerber 1988).
When we are around other people, we are continuously interacting energeti-
cally, with words, sound vibrations, and our very acts of thinking. With healing
169
intent we can enhance this interaction, and with a trained compassionate

energy transfer from our hands, we have a very powerful yet subtle tool to
alleviate suffering.
There are various hands-on healing studies that have looked at Therapeutic
Touch, Qigong, and Healing Touch (Wind Wardell 2008,) but their exact
mechanisms are still under investigation. It has been suggested that hands-on
healers, through repeated practice of various techniques, might increase the
size of their brain areas devoted to movement and finger sensitivity. This, in
turn, could enhance the biomagnetic output from those areas of the brain, as
it does in those who play stringed instruments. An increase in the strength of
the brain waves would lead to a corresponding increase in the output from the
fingers, as the brain waves are conducted to the fingers via the perineural and
circulatory systems output from those areas (Oschman 2000).
Robert C. Beck’s research on the brain wave activity of healers from a
wide variety of subcultures around the world showed that all the healers
produced similar brain wave patterns when they were in their “altered state”
while performing a healing. Whatever their beliefs and customs, all healers
registered brain wave activity averaging 7.8–8.0 cycles/second while in their
healing state (Oschman 2000). This frequency is synchronized with the
earth’s geoelectric micropulsation, known as Schumann resonance. A Healing
Touch practitioner is instructed to “find a quiet place within and center” before
starting their hands-on healing. They are also instructed to connect to the
earth’s energy by grounding. This is combined with a healing intent for the
client’s or patient’s highest good. Barbara Brennan, healer, author, and scientist
writes,
There is a vertical flow of energy that pulsates up and down the field
in the spinal cord. It extends out beyond the physical body above the
Properties of Chakras
• We are energy or light beings as well as physical beings.

• Chakras are energy vortexes or wheels of spinning light that generate color.
• Chakras store information energetically, throughout our life.
• Chakras functions as our defense mechanism.
• The frequency of the spin generates the color.
• There are seven major chakras at the midline of the body.
• There are minor chakras in each joint, the palms of the hands, and the
soles of the feet.
Energy Medicine 171
head and below the coccyx. I call this the main vertical power current.
There are swirling cone-shaped vortexes called chakras in the field. Their
tips point into the main vertical power current, and their open ends
extend to the edge of each layer of the field they are located in. (Brennan
1987).
The healing power of touch dates back to Hippocrates, the Greek physician
and father of modern medicine who noted that, “a force flowed from people’s
hands.” Hippocrates used various words for this energy. Pythagoras, in Greece,
referred to a “vital energy perceived as a luminous body that could produce
cures.” Paracelsus referred to a vital force and matter, calling it “illiaster.” Today
we call this “energy” flow. This energy has various names depending on the
culture; Chi in China, Prana in India, Ki in Japan, or Mana in Polynesia, for
example (Brennan 1993). Multicultural “bioenergy” healings have been
reported throughout the history of humankind. Native Americans and aborig-
inal Australians, for example, have learned these techniques from their ances-
tors, as did the ancient Egyptians and Greeks (Bruyere 1989).
Dr. Valerie Hunt is internationally recognized for her pioneering research
on human energy fields. She has discovered vibration patterns during pain,
disease, and illness, and in various emotional and spiritual states. She has
found scientific evidence of individualized field signatures and subtle ener-
getic happenings between people and within groups (Hunt, 1995).
There are many paths to healing the body, mind and soul. Healing Touch
and other energy-based therapies, including acupuncture, acupressure, Reiki,
reflexology, Therapeutic Touch, and others, use the concept of the human
energy system as the basis of their approaches.
Acupuncture
A tradition that is well over 2,500 years old, acupuncture represents one of the
longest continuous forms of healing in existence. Acupuncture is based on
important energy concepts, most notably Qi and Yin/Yang. Yin/Yang explores
the important coexistence and necessary balance of opposites in the universe
and within each individual (Stux 1998). Qi describes the vital force, or energy,
that flows through each person. In a state of health, one’s Qi circulate through-
out the body in energy tracts known as meridians (Beinfield and Korngold
1992). Illness manifests as blockage or deficiency in one or more aspects of
a meridian. Acupuncture techniques attempt to maintain balance and reduce
illness by restoring the flow of Qi through the manipulation of acupuncture
points and meridians (Kaptchuk, 2000).
Since the 1970s, when acupuncture first became popularized in the West,
more than 1400 randomized controlled trials have been completed to examine
its efficacy. A 1998 consensus statement by the National Institute of Health
(NIH), as well as follow-up studies, endorsed the use of acupuncture for the
adjunctive treatment of pain conditions (low back pain, fibromyalgia, tennis
elbow, headache, osteoarthritis, carpal tunnel syndrome, etc.) as well as other
conditions (including nausea from pregnancy, surgery or chemotherapy;
hypertension, infertility, asthma, stomach disorders, and addiction). The NIH
study concluded “further research is likely to uncover additional areas where
acupuncture will be helpful” (1998) leading to more than 10 million treat-
ments each year in the hope of maximizing the benefits of this positive,
energy-based treatment (National Institutes of Health Consensus Conference
1998; White 1999).
Tai Chi and Qi Gong
Tai Chi and Qigong, the preeminent health practices developed in ancient
China, are the major branches of modern Traditional Chinese Medicine. They
consist of deep relaxation techniques for stress reduction, breathing exercises,
visualizations to enhance mental acuity, self-massage, acupoint stimulation,
and gentle fluid movements coordinated with the breath to release physical
and emotional stress. All of these exercises promote the flow of bio-photon
energy throughout the body known as “Qi” or “Chi.” Qi Gong creates rather
than exerts energy, so practitioners simultaneously feel completely relaxed and
vitalized.
The unique contribution of Qi Gong to mind–body practice is the primary
focus on the mind to guide the physical and emotional body. Techniques
may be performed standing or in a seated position, so physically challenged
individuals may experience the full benefit of the exercises. There are thou-
sands of Qi Gong systems; the most popular in the West is the more physically
oriented Tai Chi.
Taylor-Piliae and colleagues conducted a study to determine whether Tai
Chi improves balance, muscular strength, endurance, and flexibility in patients
with cardiac risk factors. Thirty-nine adults participated in a 60-minute Tai
Chi exercise class three times per week. Statistically significant improvements
were observed in all balance, muscular strength, and endurance and flexibility
measures after six weeks with further improvement by week 12 (Taylor-Piliae
et al. 2006). In 2004, Yeh and colleagues randomized 30 patients with conges-
tive heart failure to 12 weeks of either Tai Chi or the standard care. Patients in
Energy Medicine 173
the Tai Chi group demonstrated decreased levels of B-type natriuretic peptide,
and improved 6-minute walk tests (Yeh et al. 2004). Multiple studies have
demonstrated a reduction in blood pressure (Schaller 1996; Thornton, Sykes,
and Tang 2004) and improvement in heart rate variability in patients taught
Tai Chi and Qi Gong (Lee et al. 2002; Lu and Kuo 2003).
Since the 1950s, the Chinese government has conducted hundreds of
scientific studies on the medical effectiveness of Qi Gong using Western
medicine-approved measurements. The NIH has funded over 11 studies to
date regarding Qi Gong’s effectiveness in treating coronary disease, hyperten-
sion, fibromyalgia, chronic pain, basal cell carcinoma, geriatric health, and
depression.
Reiki
Reiki is an ancient hands-on healing practice that originated in Japan with

the spiritual teacher, Mikao Usui, a monk and educator who lived during the
early twentieth century. The term “reiki,” is derived from two Japanese words:
rei, or universal, and ki, or life energy. Reiki is based on the belief that there is
a universal energy source, and a person can be trained to access it to facilitate
healing. The healing involves the transference of energy between practitioner
and client. The practitioner places their hands lightly on or just above the
person receiving treatment. The goal is to enhance the person’s own healing
response by restoring and realigning their biofield. Reiki is used to alleviate
chronic pain, decrease anxiety, and promote deep relaxation. Reiki can be
used as a self-care healing practice, or as a complementary therapy in a health
care setting.
In 2002, a survey by the National Center for Health Statistics and the
National Center for Complementary and Alternative Medicine (NCCAM)
found that more than 2.2 million adults in the United States have used Reiki.
Training in Reiki has three levels, each focusing on a different aspect of prac-
tice. Each level or degree includes one or more initiations or attunements.
Mackay and colleagues evaluated autonomic changes during and after Reiki
treatments. Although small in size, the researchers noted a significant reduc-
tion in heart rate and blood pressure compared to placebo and control groups
(Mackay, Hansen, and McFarlane 2004). This study implies that Reiki impacts
the autonomic nervous system and may offer a potential healing modality to
alleviate stress and anxiety. NCCAM is currently conducting research to
evaluate the effectiveness and safety of Reiki in patients with prostate cancer,
fibromyalgia, and neuropathy.
Healing Touch
Healing Touch is an energy-based approach to health and healing. It is a col-

lection of energy- based healing modalities from various cultures and healers,
founded in the late 1980s by Janet Metgen, RN, for use by registered nurses
and other health care professionals.
Healing Touch uses touch to influence the human energy system, specifi-
cally the energy field that surrounds the body, and the energy centers that
control the energy flow from the energy field to the physical body. Disruption
in the human energy system is viewed as a blockage of energy flow. The block-
ages can lead to illness or be the result of illness.
Healing Touch utilizes the hands to clear, energize, and balance the human
and environmental energy fields, thus affecting physical, emotional, mental
and spiritual health. Therapy is based on a heart-centered, caring relationship,
in which the practitioner and client come together energetically to facilitate the
client’s health and healing. The goal in Healing Touch is to restore harmony
and balance in the energy system, placing the client in the best state possible
to self-heal. Healing Touch complements conventional health care and is used
in collaboration with other approaches to health and healing (Healing Touch
Certification Program, Healing Touch International, Inc. 1996).
The human energy system includes energy tracts (meridians), energy cen-
ters (chakras), and energy fields (auras). “Chakra” is a Sanskrit word meaning
wheels of spinning light (Bruyere 1989). The frequency of the chakra spin gen-
erates its color. Chakras store information energetically, throughout a person’s
life. Chakras also function as defense mechanisms. The human energy body
has seven major chakras in the midline of the body. Energy centers are also
Table 9.1. The Seven Major Chakras

Chakra Function Gland Color Sound Musical Key of
One Physical Adrenal Red Lam C
Two Emotional Gonads Orange Vam D
Three Mental/Self Pancreas Yellow Ram E
Four Love/Forgiveness Thymus Green Yam F
Five Expression Thyroid Blue Ham G
Six Intuition Pituitary Indigo Am A
Seven Spiritual Pineal Lilac/White Om B

Energy Medicine 175
located in each joint. The largest are in the shoulders, hips, and knees. Smaller
energy centers are located in the palms of our hands and soles of our feet.
(Hover-Kramer 2002). The first major chakra is located at the base of the spine
(root), second below the naval (sacral), third above the naval (solar plexus),
fourth at the mid chest (heart), fifth at the lower part of the throat (throat),
sixth in the forehead just above the eyebrow (third eye) and seventh on top of
the head (crown). These chakras work with the endocrine glands to provide
continuous communication with the physical body. Each of the major chakras
has a color and sound vibration.
The first chakra, or root, is at a lower vibration, creating a red color.
The sacral or second is orange, the solar plexus chakra is yellow, the fourth or
heart chakra is green, the fifth or throat chakra is sky blue, and the sixth chakra
is indigo. The seventh chakra has the highest vibration and gives the color of
white with a hue of lilac. This is the same prism of color seen in the rainbow.
Therefore, we are light beings as well as physical beings.
Healing Touch training is organized in five levels of workshops. Certification
as a practitioner is available to those who meet eligibility requirements and
have successfully completed Levels 1–5 as taught by a certified Healing Touch
Table 9.2. Journey to Self-Healing with Chakras
First or Root Chakra (Physical): Color Red, Gland Adrenal, Sound Lam, Note C
In Balance: Profound connection to nature and understanding of its flow. Grounded.
Imbalance: Inability to trust nature. Focus on material possessions. Fear and need to
satisfy own desires and wishes. Ungrounded.
Second or Sacral Chakra (Emotional): Color Orange, Gland Gonads, Sound Vam, Note D
In Balance: A considerate, friendly, kind, and open person.
Imbalance: Unstable, unsure in sexual and emotional matters. Guilt and cannot express
feelings. Suppresses natural needs.
Third or Solar Plexus (Mental/Self): Color Yellow, Gland Pancreas, Sound Ram, Note E
In Balance: Feeling of inner calm, peace, and wholeness. Logical thinking. Inner
acceptance and tolerance of others. A balance of the spiritual and material worlds. Healthy
self esteem.
Imbalance: No trust in natural flow. Shame and need to dominate. Great need for material
security. Poor self esteem.
Fourth or Heart Chakra (Love and Forgiveness): Color Green, Gland Thymus, Sound
Yam, Note F
In Balance: Feeling of wholeness. Acceptance of the flow of life and relationships. Able to love.
Imbalance: Love given is not sincere. Cannot accept love given by others. Looks for
rewards. Grief.
(continued)
Table 9.2. (Continued)
Fifth or Throat Chakra (Self Expression): Color Blue, Gland Thyroid/Parathyroid,

Sound Ham, Note G
In Balance: Speaking one’s own truth. Knows balance of silence and speech. Self-
expression and creativity. Trusts intuition, knows how to listen to the “inner voice.”
Imbalance: Cannot find expression despite much talking. Unable to express ones truth,
lies. Fearful of being judged and rejected. Afraid of silence.
Sixth or Third Eye Chakra (Intuition): Color Indigo, Gland Pituitary, Sound Am, Note A
In Balance: Awareness of spiritual side of being. Inner awareness and knowing in everyday
life. Dreams and Wisdom. Connects to the universe.
Imbalance: Rejects spiritual aspects of self and others. Illusions. Focus on science and
intellect. Only sees obvious, surface moving. Afraid of intuition.
Seventh or Crown Chakra (Spiritual): Color White/Lilac, Gland Pineal, Sound Om,
Note B
In Balance: Living with the knowledge of unity. Knowing that the self reflects in the
divine. Abandon individual ego for universal ego.
Imbalance: Unable to let go of anxiety, fear, and attachment. Unable to imagine cosmic
unity. Unsatisfied and depressed.
instructor. This organized infrastructure and credentialing makes this energy

healing modality easy to implement in any healthcare setting.
Healing Touch in Clinical Practice
PREOPERATIVE AND POSTOPERATIVE
The goal of preoperative Healing Touch is to decrease anxiety and pain by

opening the energy centers, or chakras, and balancing the energy fields. The
patient is prepared to enter surgery with the best possible outcome. The treat-
ment goal for postoperative Healing Touch is also to affect the energy system
and open closed chakras. Cardiac patient undergoing coronary stenting or
open-heart surgery at the Scripps Clinic and the Scripps Green Hospital receive
pre- and postoperative Healing Touch and guided imagery treatments. A pro-
tocol is in place for open-heart surgery patients to have an integrative service
coordinator, who is a nurse, provide Healing Touch. Patients are provided with
guided imagery CDs and a portable CD player to prepare them psychologically
and emotionally for their upcoming surgery. When the patient returns to the
intensive care unit after surgery, they receive another Healing Touch treatment
and guided imagery CD, which focuses on pain management.
Energy Medicine 177
Additionally, it is my experience that Healing Touch, guided imagery, and

hypnosis are wonderful ways to prepare patients for cardiac transplantation.
VASCULAR DISEASE
The sympathetic nervous system, when unchecked, leads to the outpouring of

stress hormones—most notably adrenaline, aldosterone, noradrenaline, and
cortisol. These hormones lead to platelet aggregation, hypertension, hyper-
lipidemia, arrhythmia, central obesity, and immune system suppression. The
cardiovascular literature reports an increased risk of acute coronary syndrome
and myocardial infarction during times of stress.
Various energy healing techniques can be employed to decrease stress hor-
mones, such as adrenalin and noradrenalin, thereby decreasing sympathetic
tone. While working in the coronary care unit (CCU) or in the cardiac cathe-
terization laboratory, these techniques can often calm and relax a patient while
waiting for medication to take effect. These techniques are not a substitute for
conventional care but a perfect complement to it as they place the patient in a
relaxed parasympathetic state.
Simple energy healing techniques can be used with and taught to patients
and caregivers to help with peripheral vascular disease. It is important to keep
in mind that your intent to heal is as important as the techniques you use.
Spiritual Crises, Death, and Dying
When a person is admitted to a critical care unit, they are not only in physical
crisis, but in emotional and spiritual crisis as well. They are afraid of pain,
potential disability, and dying. A holistic approach requires listening to those
concerns and finding an opening to discuss difficult topics. I instruct my stu-
dents of Healing Touch (many of them nurses and doctors) to introduce
Healing Touch as a stress reduction technique. For the anxious and worried
patient, less information is often more. If the patient wants to have more details
frequently they will ask for them.
Since Healing Touch works on all levels—body, mind, emotions, and spirit—
the patient will usually easily express their fears and concerns. Energy healing
is also a wonderful way to ease the dying process, whether it is in the hospital,
hospice, or a home setting. Healing Touch has techniques that relax the body,
allowing pain, anxiety and even struggled breathing to ease. When curing is
not possible, healing can still take place. Very frequently a dying person will
want to heal life issues such as troubled relationships. During a treatment they
may “experience” their deceased loved ones’ presence. The Healing Touch pro-
vider may be totally unaware of this communion.
Frequently, family members present during the Healing Touch treatment
find the environment to be very healing for them. This is due to the calm
energy that is created by the grounded provider of Healing Touch. After all the
emotional turmoil loved ones have gone through, whether this is a sudden
death or the result of a prolonged illness, the emotional exhaustion and letting
go is often appreciated.
What a Clinician should know before

making Energy Medicine Referrals
If you work in a health care setting, find an individual certified to provide

energy healing for your patients. Your healer must be familiar with conven-
tional medicine and how it functions. For example, an ICU can be an intimi-
dating place to a non-medical Healing Touch provider. The energy healer
must “speak the language” of a health care provider to ensure accurate com-
munication. The allopathically trained healer may pick up problems during
the healing sessions, such as low oxygenation, hemodynamic changes (if the
patient is monitored), and sleep apnea. There are so many issues and events
that happen in the health care setting that you can “bypass” potential problems
by choosing a healer that is familiar with health care practice regulations. Make
sure that your healer is certified in their field, ideally by an accredited organi-
zation, such as a Certified Healing Touch Practitioner (CHTP) by Healing
Touch International or the Healing Touch Program, which are sponsored by
the American Holistic Nurses Association (AHNA). Be aware of the fact that
there may be certification programs that are less well known. Become familiar
with a program and its certification policies before referring patients. It is also
a good idea to obtain several professional and personal recommendations.
When making a referral for an energy medicine consultation, it is impor-
tant to clearly express to the referring practitioner your reason for referral and
desired outcome. For example, the CAM practitioner may be a Doctor of
Oriental Medicine (OMD) or a doctor of Naturopathy (ND). The patient may
not know the difference between these doctors and allopathic physicians. It is
also good to keep in mind (and address any related issues immediately if
needed) that the CAM practitioner in a health care setting always aligns him-
self or herself with the health care model. It is important that the CAM practi-
tioner does not advise the patient to replace traditional medicine with
complementary therapies, but rather understands the supportive and comple-
mentary role that integrative medicine plays.
Energy Medicine 179
REFERENCES
Beinfield, H., and Korngold, E. 1992. Between heaven and earth: A guide to Chinese
medicine. New York: Ballantine Books.
Brennan, B. 1987. Hands of light. New York: Pleiades Books.
Brennan, B. 1993. Light emerging: The journey of personal healing. New York: Bantam
Books.
Bruyere, R. 1989. Wheels of light: A a study of the chakras, vol. 1. Sierra Madre, CA: Bon
Productions.
Gerber, R. 1988. Vibrational medicine: New choices for healing ourselves. Santa Fe: Bear.
Healing Touch International, Inc. 1996.
Hover-Kramer, D. 2002. A healing touch: A guidebook for practitioners, 2nd ed. Albany,
NY: Delmar.
Hunt, V. 1995. Infinite mind: The science of human vibrations. Malibu, CA: Malibu
Publishing Co.
Kaptchuk, T. J. 2000. The web that has no weaver: Understanding Chinese medicine.
Chicago, IL: Contemporary (McGraw-Hill).
Lee, M. S., H. J. Huh, B. G. Kim, et al. 2002. Effects of Qi-training on heart rate vari-
ability. American Journal of Chinese Medicine 30(4): 363–70.
Lu, W. A., and C. D. Kuo. 2003. The effect of Tai Chi Chuan on the autonomic nervous
modulation in older persons. Medicine and Science in Sports and Exercise 35(12):
1972–76.
Mackay, N., S. Hansen, and O. McFarlane. 2004. Autonomic nervous system changes
during Reiki treatment: A preliminary study. Journal of Alternative and
Complementary Medicine 10(6): 1077–81.
National Institutes of Health Consensus Conference. 1998. Acupuncture. Journal of the
American Medical Association. 280(17): 1518–24.
Oschman, J. L. 2000. Energy medicine: The scientific basis. London: Churchill-
Livingstone.
Schaller, K. J. 1996. Tai Chi Chih: An exercise option for older adults. Journal of
Gerontological Nursing 1996 22(10): 12–17.
Stux, G., and B. Pomerantz. 1998. Basics of acupuncture. New York: Springer Publishing,
(1998).
Taylor-Piliae, R. E., W. L. Haskell, N. A. Stotts, and E. S. Froelicher. 2006. Improvement
in balance, strength, and flexibility after 12 weeks of Tai chi exercise in ethnic
Chinese adults with cardiovascular disease risk factors. Alternative Therapies in
Health and Medicine 12(2): 50–58.
Thornton, E. W., K. S. Sykes, and W. K. Tang. 2004. Health benefits of Tai Chi exercise:
improved balance and blood pressure in middle-aged women. Health Promotion
International 19(1): 33–38.
White, A., and E. Ernst. 1999. Medical acupuncture: A western scientific approach.
Edinburgh: Churchill Livingstone.
Wind Wardell, D. 2008. Healing touch research survey, 9th ed. Denver: Healing Touch
International, Inc.
Yeh, G. Y., M. J. Wood, B. H. Lorell, et al. 2004. Effects of tai chi mind-body movement
therapy on functional status and exercise capacity in patients with chronic heart
failure: A randomized controlled trial. American Journal of Medicine 117(8):
541–48.
II
Integrative Approaches to
10
Preventive Cardiology
STEPHEN DEVRIES
key concepts
■ Nutritional strategies emphasizing a Mediterranean-style diet can

have therapeutic benefit at least as potent as lipid management,
yet are not typically emphasized in conventional cardiology.
■ Exercise improves heart health in a dose-response relationship:
as little as 30 minutes of walking per day is helpful. Longer/
more intensive workouts can result in up to a 40 percent reduced
risk of heart disease.
■ Conventional measurement with a standard cholesterol panel is
an incomplete assessment; serious heart risks, often inherited,
can be uncovered by evaluation of LDL particle size and number,
HDL, Lp(a), and high sensitivity CRP.
■ Intolerance to prescription statin therapy is common and can
be overcome with many effective strategies.
■ Several supplements have potent lipid altering properties and
should be considered as therapeutic options, including red yeast
rice, fish oil, niacin, soy, fiber, and stanols/sterols.
■ Emotional health, especially stress level, is a major determinant
of heart health.
■
C
ardiologists are typically regarded as disaster relief specialists. It all
begins with their training. Most young physicians enter the field of
cardiology with the anticipation of caring for patients in the throes of a
life-threatening emergency. The molding of cardiologists as high-tech emer-
gency specialists is further reinforced in their hospital-based training programs.
183
184 INTEGRATIVE APPROACHES TO CARDIOVASCULAR DISEASE
Training rotations are typically divided into segments defined either by pro-
cedures (cardiac catheterization, electrophysiology, or echocardiography,
for example) or by inpatient clinical service (coronary care unit or telemetry
unit, for example). It is no wonder when, at the completion of training, most
newly minted cardiologists gravitate toward managing patients with advanced
The focus of most cardiologists, based both on interest and expertise, is to
work with patients with advanced disease. Patients, on the other hand, are
increasingly focused in a different direction—one emphasizing prevention
and self-care. Based on the nature of their training, it is not surprising that
most cardiologists feel ill prepared when it comes to prevention.
A growing segment of the public seeks to become more proactive in their
health care. Patients are asking questions about how they can best protect their
health. They want to know about diets, exercise and, in many cases, they want
to explore all options available to them—including the use of nonprescription
therapy. Unfortunately, cardiologists are typically poorly prepared to address
these therapies. Patients tell me that they have rarely received helpful dietary
information from physicians. Occasionally, referrals are made to a dietitian
or exercise specialist, but patients often perceive that these referrals are made
without the gravitas associated with other “high-tech” prescriptions. When
patients inquire about supplements, they are often met with ridicule or, at best,
a lack of information. Because training in medical school and beyond typically
does not include discussion of nonprescription therapeutics, physicians often
cannot help their patients in sorting through the potential role of therapies
other than pills and procedures.
Moreover, when pills are used—whether they are prescription or over-the-
counter—they are an incomplete solution at best. For example, prescription
statins have been shown to provide no more than a one-third reduction in
the risk of future cardiac events. Although this is a powerful and important
treatment, it still leaves two-thirds of the risk on the table—a risk that a more
comprehensive approach to prevention can address. It is in this gap that an
integrative approach to preventive cardiology is born.
An integrative approach to preventive cardiology is the intelligent combi-
nation of a wide variety of therapies combining conventional and alternative
strategies. The foundation of an integrative approach rests on lifestyle changes
incorporating nutrition, exercise, and mind/–body connections. These inter-
ventions are highly effective, cheap, and offer myriad benefits extending far
beyond the promotion of cardiovascular health. For those with several risk
factors or with established heart disease, the “foundations” of lifestyle changes
are conjoined with the best that science has to offer, including conven-
tional medication and procedures. In this chapter, the palette that makes
up this integrative approach to preventive cardiology will be explored, with
Integrative Approaches to Preventive Cardiology 185
an emphasis on practical strategies that can be readily incorporated into

practice.
Nutrition for Heart Health
Most health professionals intuitively understand the value of diet in maintain-

ing good health. However, while the importance of diet is generally under-
stood, the power of dietary interventions is not adequately recognized. The
following discussion will focus on a “Mediterranean-style” diet. Although a
wide range of diet strategies have been proposed for promotion of cardiovas-
cular health, including ultra-low-fat and ultra-low carbohydrate diets, the
Mediterranean-style approach has the advantage of the best supporting evi-
dence focused primarily on cardiovascular benefits, but extending far beyond.
The Mediterranean diet emphasizes three key nutritional strategies proven
to be beneficial: 1) substitution of polyunsaturated fat for saturated and trans
fats, 2) consumption of omega-3 fatty acids from fish or plant sources and
3) focus on a diet rich in vegetables and fruit that emphasizes whole grains and
is low in refined carbohydrates (Hu and Willett 2002).
The Lyon Diet Heart study (de Lorgeril et al. 1994) was a landmark trial that
was the first to demonstrate the potency of a Mediterranean-style diet for pre-
vention of heart disease. This study of myocardial infarction survivors evalu-
ated the impact of dietary changes on cardiovascular events and death. Patients
in the experimental group were advised to adopt a Mediterranean-style diet
including more vegetables, more fish, and less red meat. Butter and cream
were replaced with a canola-based margarine. Patients were advised to use this
spread or olive oil as their sole cooking and food preparation oil. They were
also advised to reduce their consumption of refined grains and to choose whole
grain products. The control group followed a “prudent” diet and received
advice from a hospital dietitian or attending physician advising the American
Heart Association Step I diet, emphasizing reduction of total fat, saturated fat,
and cholesterol.
This test of the Mediterranean diet was intended to run for five years.
However, an intermediate analysis by the oversight committee halted the study
after a mean follow-up of 27 months due to the finding of significant early
benefit in the Mediterranean diet group. A striking 73 percent risk reduction
was observed for the combined end points of cardiac death and non-fatal
myocardial infarction.
Five years after the publication of the initial study, findings from an extended
follow-up of the Lyon Diet Heart Study were reported (de Lorgeril 1999).
This follow-up study demonstrated that the considerable early benefit of the
Mediterranean diet group was maintained: the composite end point of cardiac
deaths and nonfatal myocardial infarction was reduced by 72 percent

(p<0.0001).
Diet is a form of “interventional cardiology:” The Mediterranean Diet has

been shown to reduce the risk of a cardiac event by 73 percent, a therapy
more potent than any other treatment in cardiology.
Although the study design of the Lyon trial did not specify the quantity
of any particular food item to be eaten, a diet history was recorded at the com-
pletion of the trial to better understand what was actually consumed
(Simopoulos and Visioli 2000). For example, the intake of fresh vegetables in
the Mediterranean diet group was 427 ± 222 [SD] g vs 340 ± 203 g in the
controls, p<0.005; fresh fruit in the Mediterranean diet group was 271 ± 218 g
vs 214 ± 201 g in the controls, p = 0.05.
The dramatic decrease in cardiovascular events associated with the
Mediterranean-style diet is not surprising in light of subsequent studies dem-
onstrating benefit from its constituent parts. In a combined analysis from the
Nurses’ Health Study and the Health Professionals’ follow-up study, each serv-
ing of fruit or vegetables was associated with a 4 percent reduction in the risk
of coronary disease (Joshipura et al. 2001). Of particular note, each daily serv-
ing of green leafy vegetables was associated with a 23 percent reduction in the
risk of coronary disease. Similarly, in a trial examining the use of fish oil in
survivors of myocardial infarction, a 53 percent reduction in the risk of sudden
death was noted as early as four months after one gram per day of fish oil was
started (Marchioli et al. 2002).
The Lyon diet study was performed in Europe, raising questions about the
reproducibility of the findings to other regions and cultures. An Indian study
performed in 2002 examined 1000 participants either with coronary artery
disease or at high risk for heart disease. Individuals were encouraged to eat
large amounts of fruit, vegetables, nuts, and whole grains. Mustard seed oil or
soybean oil were used in place of olive oil due to accessibility and local prefer-
ence. High intake of foods rich in omega-3 was encouraged and sources were
largely from mustard or soybean oil, walnuts, grains, and vegetables rather
than from fish. After two years of follow-up, there was a 52 percent reduction
in total cardiovascular end points in the Mediterranean-style diet group
compared to controls (Singh et al. 2002).
Since the Lyon Diet Heart Study and the Indo–Mediterranean diet study were
published, several retrospective analyses have been performed demonstrating
benefits of the Mediterranean style diet extending beyond the cardiovascular
system.
One of the most intriguing benefits of the Mediterranean-style diet is the

associated reduced risk of cancer—a finding identified in the original Lyon
study and reproduced in subsequent trials. Although the Lyon study was not
intended to evaluate the impact on cancer, the adjusted cancer risk in the
Mediterranean diet group compared to controls was 61 percent (p =0.05).
A subsequent metaanalysis of a Mediterranean-style diet compared 12,000
individuals with cancer to 10,000 healthy controls and identified a 70 percent
reduction in the risk of cancer for those individuals consuming the highest
versus lowest percentile of vegetable (Gallus, Bosetti, and La Vecchia 2004).
The NIH–AARP Diet and Health study performed in the United States
followed over 380,000 individuals with no known history of cancer or heart
disease (Mitrou et al. 2007). In this investigation, the reduction in cancer mor-
tality in those with high versus low conformity to a Mediterranean diet was
17 percent in men (p<0.001) and 12 percent (p<0.05) for women. Similarly,
cardiovascular mortality was reduced in the high versus low Mediterranean
diet adherence groups by 22 percent in men (p<0.001) and 19 percent in
women (p<0.02). Most importantly, high adherence to a Mediterranean-style
diet was associated with a reduction in all cause mortality of 21 percent in
men and 20 percent in women (p<0.001 for both). A larger analysis of over
514,000 patients demonstrated an inverse association between adherence to
a Mediterranean diet and death (Sofi et al. 2008). Increasing adherence to a
Mediterranean-style diet showed incremental reduction of total mortality, as
well as cardiovascular and cancer death, as previously demonstrated.
In addition to reducing the risk of death from heart disease and cancer, the
Mediterranean diet appears to reduce the risk of developing other conditions
that impact on quality of life, including Parkinson’s disease and Alzheimer’s
disease (Scarmeas et al. 2009; Sofi et al. 2008).
The mechanism of benefit of the Mediterranean-style diet is not completely
understood. Surprisingly, the potent benefits of the Mediterranean diet are
not associated with a significant improvement in standard lipid values
(de Lorgeril 1999). There was no significant change in total cholesterol, LDL
cholesterol, HDL cholesterol, or triglycerides between the Mediterranean-style
diet group and controls.
What factors could account for the observed benefits? Most evidence sug-
gests that the Mediterranean-style diet is antiinflammatory (Esposito et al.
2004; Giugliano, Ceriello, and Esposito 2006), although there is some evidence
to the contrary (Michalsen et al. 2006). The Mediterranean diet improves
endothelial function (Esposito et al. 2004), and decreases the likelihood of
developing the metabolic syndrome (Esposito et al. 2004). The impact of a
Mediterranean-style diet on the metabolic syndrome is appreciable. In a study
of 180 patients with metabolic syndrome randomized to either a “prudent” or
a Mediterranean diet, 56 percent of those in the Mediterranean diet group lost
their diagnosis of metabolic syndrome, while only 13 percent in the prudent

diet group did so (p<0.001).
With regards to weight loss, the Mediterranean-style diet appears to be
more effective than a low-fat diet, and especially helpful for glucose control.
A two-year trial of 322 moderately obese individuals compared three diets:
low carbohydrate, low-fat, and Mediterranean. Among the 36 patients with
diabetes, only the Mediterranean-style diet group was shown to lower fasting
plasma glucose level (Shai et al. 2008). The Mediterranean-style diet group
had a 33 mg/dL decrease in glucose. Surprisingly, this improvement in glucose
level was far greater than that seen in the low carbohydrate diet group.
The benefits of a Mediterranean-style diet are unequivocal. The challenge

for health providers is to learn how to counsel patients to adopt the diet and
reap the multifold benefits. Based on the diet consumed in the Lyon study, a
simple daily diet prescription can be advised:
• vegetables: 1 colorful side salad with both lunch and dinner every day and
a side of vegetables with dinner
• fruit: berries with breakfast and an apple or orange later in the day
• fish: 2 fish dinners per week
• grains: minimize refined carbohydrates and emphasize “whole” grains
• oil: exclusive use of olive or canola
• red meat: minimize
The gulf between the typical Western diet and the Mediterranean-style
“ideal” diet is wide, and many patients will not be able to consistently adhere
to the optimal levels of intake. Fortunately, benefits can still be accrued by
incremental adherence, as there exists a “dose-response” relationship between
adherence and benefit. Both the NIH–AARP (Mitrou et al. 2007) and the
514,000 patient metaanalysis (Sofi et al. 2008) demonstrated clear incremental
benefit with increasing degrees of adherence to a Mediterranean-style diet.
Therefore, if a patient currently is consuming one serving of vegetable or fruit
per day, clear benefit would be expected from an incremental change, by even
as little as one additional daily serving of vegetable, fruit, and fish.
Exercise
In addition to diet, exercise is among the most potent interventions avail-

able for prevention of heart disease. The benefits of exercise extend far beyond
cardiovascular health and include longevity. For example, performance of
moderate intensity physical activity, including brisk walking at 3–4 mph for
five days per week, results in up to a 30 percent reduction in all cause mortality
(Lee and Skerrett 2001). Unfortunately, the potential benefits of exercise are
rarely realized. Health care professionals are often pessimistic regarding the
capacity of their patients to adopt an exercise program. This attitude can
become a self-fulfilling prophecy, as the likelihood of patient success is related,
in part, to the patient’s perception of how important exercise is to the health
care professional.
How much exercise is required in order to obtain benefit? Although there
appears to be a dose-response relationship between exercise and all cause
mortality, even modest levels of exercise are beneficial. In a group of over
44,000 men enrolled in the Health Professionals Follow-Up Study, as little as
thirty minutes per day of brisk walking was associated with an 18 percent
reduction in the risk of coronary heart disease (Tanasescu et al. 2002). More
intensive exercise, including running one hour or more per week, resulted in
greater benefit, with a 42 percent risk reduction. In a study of over 73,000 post-
menopausal women enrolled in the Women’s Health Initiative Observational
Study, even women with a relatively low level of exercise (median of 4.2
MET-hr/week) experienced a 27 percent reduction in risk of coronary heart
disease (Manson et al. 2002). Again, more active women, who exercised 10.0
MET-hr/week or 32.8 MET-hr/week, had successively greater risk reductions
of 31 percent and 53 percent, respectively.
The mechanism of benefit from exercise for the prevention of heart disease
is multifaceted. Exercise is clearly beneficial in reducing hypertension, improv-
ing dyslipidemia (reducing LDL cholesterol, reducing triglycerides, and
increasing HDL cholesterol), improving glycemic control, and reducing stress.
Exercise has also been shown to be a powerful mediator of endothelial func-
tion (Hambrecht et al. 2000).
Although aerobic exercise is typically recommended for cardiovascular
health, resistance training confers additional benefit, including a favorable
influence on blood pressure and glycemic control (Braith and Stewart 2006).
In men, resistance training is associated with a reduction in the risk of coro-
nary heart disease. Men who trained with weights for 30 minutes or more per
week had a 23 percent reduced risk of heart disease compared to no resistance
training (Tanasescu et al. 2002).
A common dilemma for the practitioner is whether or not to proceed with
stress testing in a sedentary, but asymptomatic, individual prior to beginning
an exercise program. The rationale to do so is supported by a study demon-
strating that the relative risk of cardiac arrest during exercise in a previously
sedentary individual is as high as 56-fold compared to the risk at rest (Siscovick
et al. 1984). The ACC/AHA Exercise Guidelines do not recommend routine
Practical tips: the goal of exercise for primary prevention of heart disease
should include, as a minimum, 30 minutes of moderate intensity exercise on
most days. A simple strategy of brisk walking for 30 minutes per day, broken
into 10–15 minute blocks if necessary, is an excellent start. More intensive exer-
cise sessions for longer duration appeared to be of additional benefit and
should be encouraged as a goal. The addition of resistance training to an aer-
obic program has added benefit, not only for general fitness, but also for car-
diovascular health. These recommendations are in accordance with American
Heart Association Guidelines for primary prevention of cardiovascular disease
(Pearson et al. 2002).
screening of asymptomatic individuals, but do acknowledge potential benefit

of stress testing sedentary individuals with multiple cardiovascular risk factors
prior to beginning an exercise program as a Class IIb indication, where “con-
flicting evidence” in which the “usefulness/efficacy is less well established by
evidence/opinion” (Gibbons et al. 2002). The practitioner should take into
account the number and extent of cardiovascular risk factors, especially diabe-
tes, in making a decision about proceeding with stress testing individuals prior
to beginning an exercise program.
Cholesterol
Cholesterol management is often the focal point of efforts to prevent heart

disease. On closer inspection, a more balanced emphasis may be appropriate.
As many as one-third of individuals with myocardial infarction have a total
cholesterol level in the “normal range” of under 200 mg/dl. Similarly, many
individuals with elevated cholesterol levels never develop cardiac events.
A balanced view, supported by the literature, clearly demonstrates that
cholesterol is only one of many important factors in the development of heart
disease. A wealth of information exists in both primary and secondary preven-
tion trials demonstrating the value of cholesterol reduction with statin therapy.
The risk reduction most commonly observed in these trials is approximately
one-third. In this chapter, strategies will be discussed to maximize opportuni-
ties for treatment of cholesterol disorders, with an emphasis on integrative
approaches.
Traditionally, the primary target of lipid therapy is the cholesterol content
of low-density lipoprotein (LDL). The emphasis on LDL is well-placed, based
on outcomes data from LDL lowering clinical trials. Conventional guidelines
for treatment of LDL, along with the rationale for therapy, are carefully sum-
marized in the Adult Treatment Panel guidelines (Grundy et al. 2004).
Despite the clear importance of LDL, there is considerable controversy that
this marker may not be the best indicator of LDL-related risk. Conventional
lipid tests measure the cholesterol content in LDL. Interestingly, the choles-
terol content of LDL particles can vary substantially from person to person.
The explanation for this is that some individuals have a predominance of small,
dense LDL particles. For others, the LDL cholesterol exists as larger, more
buoyant particles. Smaller particles are associated with greater risk, as they are
more easily oxidized and are mechanically better able to intercalate within the
plaque (Tribble et al. 1992).
If the LDL particles are small and, therefore, carry less cholesterol per par-
ticle, any given LDL cholesterol concentration will be associated with a greater
number of LDL particles. Therefore, two individuals can have the same LDL
cholesterol level, yet have a very different number of atherogenic LDL particles
and, consequently, very different risks.
Interestingly, the risk of cardiovascular events is more closely linked to the
number of LDL particles than to their cholesterol content, with higher risk
closely linked to a higher number of atherogenic particles (Barter et al. 2006).
For that reason, many lipidologists argue that a test of the number of athero-
genic particles is a more useful gauge of risk, and a superior end point to ther-
apy, than the LDL cholesterol.
A useful, and simple, indicator of the number of atherogenic particles is the
calculation of non-HDL cholesterol. This term is obtained from the standard
lipid panel, and can by calculated by subtracting HDL cholesterol from the
total cholesterol. Non-HDL cholesterol has been found to more closely corre-
late with cardiac risk than LDL-C, especially in situations where triglycerides
are > 200 mg/dl (Packard and Saito 2004).
An alternative measurement of the number of LDL particles (LDL-P) is a
nuclear magnetic resonance test. This is a proprietary test that typically is
reported bundled with an assessment of LDL size, and is a better predictor of
cardiovascular risk better than LDL cholesterol (Hsia et al. 2008).
Arguably the most robust measurement of atherogenic particle burden is
Apolipoprotein B (ApoB). The value of ApoB as a marker of risk is the conve-
nient fact that each atherogenic particle, including low density lipoprotein,
very low density lipoprotein, intermediate density lipoprotein, and lipoprotein
(a), contain one and only one molecule of ApoB. Therefore, ApoB can be
considered an aggregate marker of the overall risk of atherogenic particles.
This is a relatively cheap and reproducible test demonstrated to correlate with
cardiovascular risk to a degree similar to LDL-P and superior to non-HDL
cholesterol (Sniderman 2005).
Table 10.1. Comparison of Methods to Measure Atherogenic Cholesterol

50th percentile 20th percentile 2nd percentile
LDL Cholesterol (mg/dL) 130 100 70
Non-HDL Cholesterol (mg/dL) 153 119 83
LDL Particle (nmol/L) 1440 1100 720
ApoB (mg/dL) 97 78 54
Adapted from et al. 2009.
Interpretation of the results of these new measurements relative to the tra-

ditional LDL-C test can be challenging. A recent study demonstrates a cross
comparison of these tests from data gleaned from the Framingham study
(Contois et al. 2009). For example, the fiftieth percentile for LDL-C =130 mg/
dl; for non-HDL= 153 mg/dl; for LDL-P = 1440 nmol/L; and for ApoB = 97
mg/dl. The twentieth percentile for LDL-C = 100 mg/dl; for non-HDL = 119
mg/dl; for LDL-P = 1100 nmol/L; for ApoB 78 mg/dl. The second percentile
for LDL-C = 70 mg/dl; for non-HDL= 83 mg/dl; for LDL-P = 720 nmol/L; for
ApoB = 54 mg/dl.
Based on this data, aggressive control of LDL-related risk for those at
highest risk of vascular disease could be accomplished by ensuring that the
following criteria are met: LDL-C <70 mg/dl and ApoB < 60 mg/dl or LDL-P
< 700 nmol/L.
It is likely that future versions of the cholesterol treatment guidelines will
incorporate some measurement of atherogenic particle number for both diag-
nostic purposes, as well as to better define an end point for therapy.
Treatment of Elevated LDL
As previously noted, the cornerstone of prevention in general, including treat-

ment of cholesterol disorders, rests in diet and exercise. When therapy is
required beyond lifestyle measures, a variety of options exist—both prescrip-
tion and over the counter.
Many hundreds of over-the-counter products have been proposed for
reduction of LDL cholesterol. Data for many of these products, however, is
conflicting and demonstrates a modest impact at best. Moreover, some over
the counter products have substantial cholesterol lowering value and may be
an ideal solution under certain circumstances. Therefore, it is incumbent on
the clinician interested in integrative approaches to acquire a thorough under-
standing of the science behind the use of supplements.
As an introduction to this topic, it is important to make note of supple-
ments commonly mentioned for treatment of cholesterol that are not particu-
larly helpful for that purpose. Commonly used supplements with little or no
significant benefit for cholesterol management include garlic (Khoo and Aziz
2009), gugulipid (Szapary et al. 2003), and policosanol (Dulin et al. 2006).
Over-the-counter products shown to have the greatest potency for LDL
reduction include: soluble fiber, plant stanols/sterols, soy, niacin, and red
yeast rice.
FIBER
The water-soluble portion of fiber has been shown to both reduce the intesti-
nal absorption of cholesterol as well as decrease hepatic synthesis. Each daily
gram of soluble fiber intake can decrease LDL-C by 2.2 mg/dL (Brown et al.
1999). Rich dietary sources of soluble fiber include: kidney beans (6 grams/
cup), oatmeal (2 grams/cup), oat bran (2 grams/cup), orange (2 grams/whole
fruit), broccoli 2 grams/cup), and apples (1 gram/whole fruit). Fiber supple-
ments added to dietary sources of fiber can have additional benefit. Twice daily
use of psyllium 5-gram supplement results in a 7 percent reduction in LDL-C,
as well as a reduction in glycemic measures (Anderson et al. 2000).
STANOLS/STEROLS
Mammalian cells contain cholesterol. Plants have no cholesterol but contain

small quantities of phytosterols and their saturated derivatives, plant stanols.
Both sterols and stanols reduce the intestinal absorption of cholesterol by
competing with dietary and biliary sources of cholesterol for production of
micelles. Intake of 1.8 to 2.6 grams per day of stanols supplemented in marga-
rine reduces LDL cholesterol by 14 percent (Miettinen et al. 1995) A single
daily dose of stanols-enriched margarine has been shown to be as effective as
divided doses (Plat et al. 2000). Stanols can be added to ongoing statin therapy
for an additional 10 percent reduction of LDL-C reduction (Blair et al. 2000).
More recently, stanols and sterols have been incorporated into a wide range
of foods. The type of food to which stanols/sterols are added may influence the
degree of cholesterol reduction. One convenient method of enhancing dietary
intake is through stanol-enhanced yogurt. Consumption of 1 g per day of

stanol introduced into a low-fat yogurt resulted in a 13.7 percent reduction in
LDL cholesterol (Mensink et al. 2002). Maximal benefit was noted after one
week of daily intake. Stanols/sterols are also widely available in pill form, but
data is lacking regarding efficacy of stanols and sterols in pill form.
SOY PROTEIN
In a metaanalysis of 38 controlled trials in which soy protein intake averaged

47 g/day (range 17 to 124), soy reduced total cholesterol by 9.3 percent, LDL
by 12.9 percent, and triglycerides by 10.5 percent, with no significant increase
in HDL (Anderson, Johnstone, and Cook-Newell 1995). The mechanism of
benefit is not completely defined, but likely includes an increase in hepatic
LDL receptors (Erdman, 2000). Soy contains isoflavones, a form of phytoe-
strogen. The degree to which isoflavone content in soy contributes to choles-
terol reduction is unclear. A metaanalysis of 10 studies showed no independent
effect of isoflavone concentration on lipid changes (Weggemans and Trautwein
2003). The American Heart Association Nutrition Committee has concluded
that 25 g/day of soy protein is effective for improving lipid profiles (Erdman
2000). Soy intake of 25 to 50 g/day would be expected to lower LDL by 4 to
8 percent (Erdman 2000).
COMBINATION OF FIBER, SOY, ALMONDS,

AND STEROLS (“PORTFOLIO DIET”)
A low-saturated-fat diet concentrated with fiber, soy, sterols, and almonds,

referred to as the “Portfolio Diet,” has been shown in a four-week trial to lower
LDL by 29 percent and C-reactive protein by 28 percent, values similar to those
achieved with a low fat diet and lovastatin 20 mg (Jenkins et al. 2003). The diet
contained approximately 2 g/day of plant sterols from a sterol enhanced marga-
rine, 20 gram per day of soluble fiber from oats, barley, and psyllium, 50 g/day
of soy protein from soy milk and soy meat substitute, and 30 g/day of almonds.
Of note, this was a four-week study in which only 40 percent of the study par-
ticipants judged the Portfolio Diet to be “acceptable.”
NIACIN
Niacin, available over the counter as well as by prescription, is unique in that

it improves a broader range of lipid parameters than with any other lipid
therapy: it lowers LDL, shifts LDL particle size to the more favorable larger
forms, lowers triglycerides, reduces Lp(a), and raises HDL. Niacin reduces the
mobilization of free fatty acids from the periphery, thereby reducing the pro-
duction of VLDL and LDL.
The benefits of niacin are dose-dependent, with LDL reduction in the range
of 3–17 percent with doses ranging from 500 to 2000 mg per day. Reductions
of cardiovascular events with niacin have been reported when used as mono-
therapy (Canner et al. 1986), as well as in combination therapy with other lipid
lowering agents. The combination of over-the-counter niacin and simvastatin
resulted in an 89 percent event reduction in the HDL Atherosclerosis Treatment
Study (Brown et al. 2001).
Be aware that “no-flush” and “flush-free” niacin are ineffective for lipid
management.
Immediate release products (available over the counter) and inter-

mediate release versions (available by prescription) are both effective.
Nonprescription forms are cheaper, and may be preferred by patients seeking
to avoid prescriptions, but have the disadvantage of uncertainty in content.
The major limitation of niacin is the annoying but harmless side effect of
flushing.
Of note, several forms of “no-flush” niacin are available which appear
attractive choices, but should not be used due to poor efficacy. “Flush-free”
and “no-flush” niacin are inositol hexaniacinate, a bound form of niacin, which
requires an esterase for release of the active, free niacin. Because this reaction
is very limited in most individuals, minimal free niacin is produced and, con-
sequently, “no-flush” or “flush-free” niacin are generally ineffective for lipid
management (Meyers et al. 2003).
Successful Strategies for Reducing Flushing Associated with Niacin
1. Take niacin with food—ideally with dinner (avoid taking niacin on

an empty stomach). Alternatively, take niacin with applesauce in the
evening.
2. Take aspirin or a non-steroidal antiinflammatory with niacin.
3. Avoid alcohol and spicy foods at the time niacin is taken
4. Avoid “no-flush” or “flush-free” brands due to poor efficacy.
RED YEAST RICE
Red yeast rice is the most potent over the counter therapy available for reduc-
tion of LDL cholesterol. This is a fermentation product which results from
growing the yeast Monascus purpureus on rice. Red yeast rice contains mona-
colins, constituents that are HMG-CoA reductase inhibitors, or statins.
Analysis of red yeast rice reveals nine monacolins; the one present in greatest
concentration is monacolin K, also known as lovastatin (Heber et al. 1999).
The monacolin content and, therefore, the cholesterol lowering properties,
vary greatly between different brands of red yeast rice (Gordon et al. 2009).
Need for caution exists, as some brands have been found to contain citrinin, a
nephrotoxic substance that should be removed during the fermentation pro-
cess (Gordon et al. 2009).
If red yeast rice is a form of a statin, why recommend it instead of prescription
statins? There are two reasons to consider doing so: 1) patients who are philo-
sophically opposed to taking prescription medication for cholesterol reduc-
tion; 2) patients who have experienced adverse reactions to prescription statins
(particularly myalgias).
A growing body of literature supports the use of red yeast rice. Reductions
in LDL cholesterol season with red yeast rice are typically in the range of 20 to
30 percent (Becker et al. 2009; Heber et al. 1999; Lin, Li, and Lai 2005).
A 12-week study of red yeast rice prescribed at 2400 mg per day resulted in
a decrease in LDL cholesterol of 23 percent, a decrease in triglycerides of
15 percent, and no significant change in HDL cholesterol. Of note, no myalgias
were reported among patients in this study (Heber et al. 1999).
Red yeast rice may be better tolerated than prescription statins; some
patients who have experienced adverse reactions with multiple prescrip-
tion statins, even at low dosages, have been able to take red yeast rice, with
excellent results.
A study of 62 individuals with a history of needing to discontinue therapy

with prescription statins due to severe myalgias were randomized to red yeast
rice at 1800 mg per day or placebo, for 6 months. In the group receiving red
yeast rice, only 2 of 29 (7 percent) of previously statin intolerant patients
needed to discontinue treatment with red yeast rice because of myalgias, with
the benefit of a 21 percent decrease in LDL from baseline at week 24 (Becker
et al. 2009).
Table 10.2. Supplements to Lower LDL

Supplement LDL Reduction
Red yeast rice 20–30%
Niacin 10–20%
Plant stanols/sterols 5–15%
Soluble fiber 5–10%
Soy protein 5–10%
The potency of a nonprescription approach to the patient with dyslipidemia

was demonstrated in a trial comparing a moderate dose of a statin with an
“alternative approach” combining over-the-counter supplements and lifestyle
changes (Becker et al. 2008). In this study, patients were randomized to receive
either receive simvastatin at 40 mg per day along with AHA handouts on diet
and exercise, or a combination of red yeast rice (2400–3600 milligrams per
day), fish oil (3.8 g per day), and weekly lifestyle counseling. At the completion
of the three-month study period, both the prescription and the “alternative”
groups had striking, yet similar, reduction in LDL cholesterol: 40 percent for
the simvastatin group and 42 percent for the alternative group, p=ns. The alter-
native group had a significantly greater reduction in triglycerides, however, of
29 percent versus 9 percent in the simvastatin group, p<0.005.
Most importantly, there is outcomes data with red yeast rice showing
improvement in both cardiovascular end points, as well as total mortality.
A study of 4870 individuals with myocardial infarction randomized to placebo
or red yeast rice 1200 mg per day for 4.5 years demonstrated a 45 percent
decrease in the primary end point of a major coronary event in the group
receiving a red yeast rice. Moreover, a reduction in total mortality of 33 per-
cent in the treatment group was observed (p < 0.0005) (Lu et al. 2008). The red
yeast rice used in this study contained a daily total of lovastatin 10–12 mg, and
the LDL reduction was 18 percent. It is interesting to speculate that other con-
stituents of red yeast rice may contribute to the outcome benefits, which appear
disproportionate to the lipid lowering effect.
Patients with Intolerance or Philosophical

Opposition to Prescription Statins
Managing lipids in patients who are either intolerant of prescriptions statins

or philosophically opposed to their use is one of the most challenging of all
prevention scenarios. Most clinicians have encountered patients who refuse

to take prescription statins. They often avoid medication for fear of adverse
reactions, as well as a general sense that prescriptions are associated with an
increased risk of harm. Others are quite willing to take prescription cholesterol
medication but have been intolerant to them, often despite trying multiple
agents, even at low dosages.
STATIN INTOLERANCE
Although patients often fear liver toxicity from statins, the adverse reaction
most likely to trigger discontinuation of therapy is muscle pain. The package
insert for most prescription statins lists the incidence of myalgias as being
3–5%. Based on personal communications from primary care physicians, this
number is likely a considerable underestimate. Determination of a causal rela-
tionship between statin use and muscle complaints can be perplexing, as
muscle pain is ubiquitous and distinguishing baseline muscle aches and pains
from those related to statin use can be difficult. Relying on serum CK levels to
gauge a cause and effect relationship between myalgias and statins is problem-
atic, as histologically proven muscle inflammation related to statin use may
exist in the absence of elevated circulating CK (Phillips et al. 2002).
Dealing with statin intolerance is frustrating for both patients and medical
providers. Doctors may suspect that adverse reactions are experienced as a
type of “self-fulfilling prophecy,” in which patients, reluctant to have initiated
statins in the first place, seemingly will themselves into an adverse reaction.
In response, many patients report that their complaints of muscle aches after
starting statin therapy are minimized by their health care providers, who often
advise patients to “tough it out” and continue taking their statin.
In order to maximize the chance for patients to distinguish statin-related
myalgias from everyday muscle pain, I always have a discussion with patients
prior to beginning statin therapy. I ask them to make a mental note of muscle
pains they experience from time to time and suggest that similar discomfort
should not trigger alarm after beginning statin therapy. If a new pattern or
increased severity of muscle discomfort should develop, this could be a warn-
ing sign of an adverse reaction and should be considered as a possible adverse
reaction. Based on the severity of symptoms, I advise patients to either lower
the dose or discontinue the statin.
Although psychological factors undoubtedly play a role in some patients
with statin intolerance, there is a growing understanding of the biochemical
basis for statin-related myalgias, including insights into genetic predisposi-
tion. A unique single nucleotide polymorphism has been associated with a
17-fold increase in the risk of statin-related myalgias (Link et al. 2008). A more
complete understanding of genetic determinants of statin-related myalgias
could allow for prediction of individuals best suited for lower dosages or alter-
native treatments.
In patients with statin intolerance, a search should be made for reversible
factors that can predispose individuals to adverse reactions. Metabolic causes
of statin intolerance include: 1) hypothyroidism, and 2) low vitamin D level.
All patients with dyslipidemia should be screened for hypothyroidism, because
it can be a contributing factor in the development of dyslipidemia, as well as
lower the threshold for statin-related myalgias (Antons et al. 2006).
Low-circulating Vitamin D has also been implicated as a trigger for statin
intolerance, with an association noted between statin-related myalgias and
vitamin D 25 (OH) levels below 30 (Duell and Connor 2008) and 32 ng/ml
(Ahmed et al. 2009). Furthermore, statin-related myalgias in patients with
vitamin D deficiency may improve with vitamin D replacement therapy
(Ahmed et al. 2009; Duell and Connor 2008).
Once metabolic impairments have been excluded, tolerance to prescription
statins may be enhanced by changes in the method of statin administration.
Variations in statin administration can include: choosing a different brand of
statin; decreasing the daily dose; or decreasing the dosing frequency. Many
patients intolerant of one or two brands of statins will have no problem with a
different brand. There is a theoretical rationale for believing that the more
lipid-soluble statins may have a lower risk of myalgias, but this relationship has
not been proven. Regardless of the statin chosen, the use of the lowest possible
dose will increase the likelihood of tolerance.
Some of the most potent statins can be given at even one-half or one-quarter
of the lowest pill strength with upward titration as tolerated. For example,
rosuvastatin at a dose of 1 mg, which is less than one-quarter of the lowest
strength tablet available, has been shown to reduce LDL by 34 percent (Olsson
et al. 2001). Appreciation of the potency of even extremely low statin dosages
is enhanced by the knowledge that a 50 percent reduction in dosage would
be expected to reduce LDL cholesterol lowering by only 7 percent (Roberts
1997).
In addition to using a different statin at a lower dose, lengthening the dosing
interval may be useful. Significant LDL reduction has been noted with statin
dosing frequencies ranging from one to three times a week (Gadarla, Kearns,
and Thompson 2008; Mackie et al. 2007; Ruisinger et al. 2009). In the study
of twice a week statin dosing, 40 patients previously intolerant of at least
one statin were given rosuvastatin 5 or 10 mg (Gadarla, Kearns, and Thompson
2008). A 26 percent reduction in LDL cholesterol was observed over the
8-week study period. Over the 8-week study, 80 percent of patients were able
to continue therapy without adverse reactions. Extending the dosing interval

to once-a-week rosuvastatin at a mean dose of 10 mg led to a 23 percent reduc-
tion of LDL, with 74 percent of patients able to continue therapy throughout
the 4-month study (Ruisinger et al. 2009).
If changes to the type, dosage, or frequency of administration of the pre-
scription statin are not successful in avoiding adverse reactions, one might
consider redirecting therapy to include nonprescription options including
soluble fiber, sterols/stanols, and red yeast rice.
COENZYME Q10
Coenzyme Q10 is a fat-soluble substance involved in electron transport in the

mitochondria during oxidative phosphorylation. Supplementing coenzyme
Q10 in patients receiving statins has long been proposed as a treatment to
reduce the risk of adverse reactions from statins. The relationship between
coenzyme Q10 and adverse reactions from statins, however, is controversial.
What is clear is that that the circulating level of coenzyme Q10 is reduced
during therapy with statins (both prescription statins as well as red yeast rice)
(Folkers et al. 1990). As coenzyme Q10 is required for cellular energy produc-
tion, and since levels drop during therapy with statins, it can be logically
concluded that coenzyme Q10 levels should be restored with exogenous sup-
plements during statin treatment.
On the other side of the argument is that fact that the circulating level of
coenzyme Q10 may not reflect the more important tissue level. Of note, reduc-
tion in the blood level of coenzyme Q 10 with statin therapy is largely due
to the fact that up to 50 percent of circulating coenzyme Q 10 is contained in
the LDL particle (Tomasetti et al. 1999). The role of coenzyme Q10 in statin-
related myalgias is further obscured by inconsistency in the impact of statins
on tissue levels, with one study showing no change in skeletal muscle levels
of coenzyme Q10 (Laaksonen et al. 1996), in contrast to other data indicating
as much as a 34 percent reduction in tissue levels (Paiva et al. 2005).
Two randomized clinical trials have evaluated the benefit of coenzyme Q10
on statin-related myalgias. In one study, patients were randomized to coen-
zyme Q10 (200 mg or placebo) and studied for 12 weeks during upward titra-
tion of simvastatin. No improvement in myalgias or tolerance of statins was
observed in the group receiving coenzyme Q10 (Young et al. 2007). In the
second study, after 30 days of treatment with coenzyme Q10 at 100 mg per day,
the severity of muscle pain decreased by 40 percent (p <0.001) and the occur-
rence of pain interfering with daily activities decreased by 38 percent (p <0.02),
with no improvement noted in the placebo group (Caso et al. 2007).
Therefore, although the rationale behind coenzyme Q10 appears sound, the
clinical data regarding improvement of coenzyme Q10 on statin-related myal-
gias is conflicted. Nevertheless, the safety profile of coenzyme Q10 is excellent
(Hathcock and Shao 2006). Based on available information, coenzyme Q10
doses in the range of 100 to 200 mg/day may be considered in an effort to
reduce the risk of myalgias.
The role of coenzyme Q10 in cardiology extends beyond its use in patients
treated with statins, to include patients with congestive heart failure (Molyneux
et al. 2008) and hypertension (Rosenfeldt et al. 2007) as well. These areas are
discussed in detail in the chapters on metabolic cardiology, congestive heart
failure, and hypertension.
Strategies for Statin Intolerance
• Evaluate for hypothyroidism with TSH level.

• Evaluate for vitamin D deficiency with 25 (OH) level. Goal is > 30 ng/ml.
• Add Coenzyme Q10 200 mg per day.
• Switch to a low dose of an alternative statin (ie. rosuvastatin 1.25–2.5 mg,
lovastatin 10 mg, simvastatin 10 mg, or atorvastatin 5 mg) or decrease the
frequency of doses (ranging from every other day to once a week).
• Consider red yeast rice at 1200 to 2400 mg per day.
• Add plant sterols/stanols and soluble fiber for additional LDL lowering.
STRATEGIES FOR THE PATIENT UNWILLING

TO TAKE PRESCRIPTION STATINS
For the patient who is philosophically opposed to the use of prescription cho-
lesterol agents, several approaches may be helpful. Many individuals have an
inordinate fear of the risk associated with statin medications and, on occasion,
a discussion with the patient describing the actual, minor risk of adverse reac-
tions may be helpful. Patients typically fear permanent damage to their liver,
which, fortunately, is extremely rare. For example, in my 20 years of practice, I
have not personally had a single patient experience severe or permanent liver
damage related to cholesterol therapy.
Nevertheless, if patients adamantly refuse to use prescription cholesterol
therapy, over-the-counter products may be considered. For such patients,
the lowest risk (and lowest potency) option could include the addition of sol-
uble fiber, as well as the plant stanols or sterols. This strategy could be expected
to lower LDL cholesterol in the range of 10–20 percent. If additional LDL
lowering is required, red yeast rice could be recommend. The combination

of fiber, plant stanols, and red yeast rice may lower LDL cholesterol between
30 and 40 percent. If HDL cholesterol needs to be increased, over-the-counter
niacin can be added.
Author’s Recommendation
In my experience, most patients who initially express a desire to avoid pre-

scription cholesterol medication are ultimately open to using prescription
medication if initial therapy with diet, exercise, and over-the-counter supple-
ments fail to achieve the desired goal. I believe that many of these patients are
asking nothing more than to be listened to, and to have their preferences incor-
porated into the decision-making process.
Since cholesterol control is rarely required on an urgent basis, I see no reason
not to make at least an initial attempt at therapy that is most congruent with
the patient’s belief system. For example, if a patient is adamant about trying a
nonprescription approach even when I would prefer a more potent prescrip-
tion treatment, I will often express my preference to the patient, but will typi-
cally accede to their wishes if strongly held. In this way, I believe that a true
partnership is established that will keep the patient motivated to engage in a
long-term relationship directed at maximizing opportunities for prevention.
If therapy using a nonprescription approach achieves the desired goals, the
initial strategy can be considered a success. If not, I emphasize to my patients
that I am goal oriented, and that I believe we should move on to a prescription
treatment—often at a low dosage, if appropriate. I have found that most
patients, despite their initial reluctance, will be inclined to proceed with a pre-
scription approach once they feel they have been listened to and that nonpre-
scription alternatives have been exhausted.
The Role of HDL
HDL cholesterol has several beneficial functions, including the “reverse trans-
port” of LDL cholesterol out of the plaque, as well as potent antioxidant capa-
bilities. Low levels of HDL are associated with increased risk of vascular disease.
Interestingly, there are gender differences in normal HDL levels, with higher
values expected in women. Normal values for men are 40–45 mg/dL and for
women, 50–55 mg/dL. Consequently, HDL levels associated with increased
risk are gender dependent: < 40 mg/dL for men and <50 mg/dL for women.
Population studies show an increase in cardiovascular risk for individuals
with low HDL, even if LDL is well controlled (deGoma, Leeper, and Heidenreich
2008).
Relative to our understanding of the benefits of treating LDL, the impact
of HDL-raising therapy is lacking. One prospective HDL-raising trial, the
VA–HIT study, demonstrated an approximately 2 percent lower cardiovascu-
lar risk for each 1 mg/dL increase in HDL (Robins et al. 2001). More studies
are needed to determine the conditions and agents most likely to achieve clin-
ical benefit from raising HDL.
In any effort to optimize HDL, the first strategy is to remove influences
known to depress levels. Factors that decrease HDL include: smoking, high
glycemic load diet, and the use of a wide range of medication including beta
blockers and thiazide diuretics. When such medication is used in those with
low HDL, consideration should be given to determine if acceptable substitutes
are available.
Lifestyle measures are fundamental to raising HDL levels, with particular
impact resulting from reducing glycemic load in the diet, weight loss, and aer-
obic exercise. Carbohydrate intake, especially that contained in high-glycemic-
load food, stimulates a decrease in HDL, paired with an increase in triglycerides
(Liu et al. 2001). Emphasizing low-glycemic-load food choices, as well as foods
rich in monounsaturated fat, can be effective in raising HDL. Reducing the
intake of foods such as bread, chips, rice, potatoes, and sweets and replacing
them with fruit, vegetables, and nuts is a key strategy for raising HDL. These
measures typically have the added benefit of weight loss, which also raises
HDL (Dattilo and Kris-Etherton 1992).
Aerobic exercise can also be useful in raising HDL, but relatively high
amounts are needed for significant improvement. Running for 45 minutes four
days per week, covering 4.5 miles/session, was associated with a 4 mg/dL
increase in HDL (Kraus et al. 2002). Although both intensity and duration of
exercise influence the degree of HDL increase, the number of minutes per
week of exercise appeared to be the strongest determinant of change in HDL.
A metaanalysis suggests that the minimal energy expenditure to raise HDL is
approximately 900 kcal, or 2 hours of exercise per week (Kodama et al. 2007).
The mean increase in HDL observed with exercise was 2.5 mg/dL. A dose-
response relationship was suggested with each additional 10 minutes of exer-
cise per workout session associated with a 1.4 mg/dL increase in HDL. In this
analysis, the total number of minutes exercised per week was more influential
for raising HDL than the frequency or intensity of exercise.
Pharmacologic therapy for HDL includes alcohol, fibrates, niacin, and
insulin-sensitizing agents. Alcohol intake is associated with up to a 55 percent
reduced risk of myocardial infarction in those with the highest consumption
of alcohol (three or more drinks per day) compared to those with less than one
Table 10.3. Strategies to Raise HDL

HDL Increase
Niacin 2000 mg/day 10mg/dL
Low glycemic load diet 6 mg/dL
Alcohol: 1 glass wine/day 5 mg/dL
Pioglitazone 5 mg/dL
Aerobic exercise 3 hrs/week 4 mg/dL
Fibrates 4 mg/dL
alcoholic drink per month (Gaziano et al. 1993). Consumption of 1 glass of

wine every one to two days would be expected to increase HDL by 3 mg/dL in
men and 7 mg/dL in women (Gaziano et al. 1993).
Fibrates, including gemfibrozil and fenofibrate, raise HDL an average of 4
mg/dL, or 10 percent (Birjmohun et al. 2005). Niacin is the most potent agent
available to raise HDL, at an average of 7 mg/dL, or 16 percent (Birjmohun
et al. 2005). The increase in HDL associated with extended-release niacin
(22 percent) and immediate release (23 percent) is greater than that observed
with slow-release niacin (13 percent). As previously noted, “flush-free” or
“no-flush” niacin are bound forms of niacin with minimal therapeutic efficacy.
Therapies that target insulin resistance, especially the thiazolidinedione or
TZD class of agents, are also effective at raising HDL (Deeg et al. 2007)
Pioglitazone has been shown to increase HDL by approximately 5 percent, and
rosiglitazone by approximately 2 percent (Deeg et al. 2007) Statins can raise
HDL, but increases are more modest, generally in the range of 3–10 percent.
The Role of Triglycerides
Although historically controversial, it appears increasingly clear that elevated

triglycerides are an independent risk factor for vascular disease. Interestingly,
elevated levels are more closely linked to risk in women than in men (Hokanson
and Austin 1996). An optimal level for both genders is <100 mg/dL. At a
minimum, fasting levels should be < 150 mg/dL, with levels over 200 mg/dL
considered to be significantly elevated. The mechanism of increased risk
attributed to triglycerides is unclear but appears rooted, in part, to the pre-
dominance of small dense LDL associated with elevated triglycerides (Mudd
et al. 2007).
The initial treatment of elevated triglycerides is to reduce the stimulus for

triglyceride production from other medical conditions or medication. Obesity,
impaired fasting glucose, diabetes, hypothyroidism, and liver disorders can
contribute to elevated triglycerides. B-blockers, thiazides, oral contraceptives,
hormone replacement therapy (oral but not topical), retrovirals and Accutane
(isotretinoin) often lead to elevated triglycerides.
Similar to measures that favorably impact HDL, weight loss, adoption of a
diet with low glycemic load (Liu et al. 2001; Pelkman 2001), and aerobic exer-
cise are all helpful at lowering triglycerides. Of particular note, alcohol is one
of the most potent stimulants for triglycerides; therefore, its use should be
minimized when triglycerides are significantly elevated.
Prescription agents that lower triglycerides include statins (up to 25 percent
reduction), fibrates (55 percent), niacin (35 percent), and fish oil (50 percent).
These agents can be used as monotherapy for patients with isolated hypertrig-
lyceridemia, or in combination with statins for those with mixed dyslipidemia.
FISH OIL
Fish oil has long been associated with cardiovascular health. It has potential
beneficial antiinflammatory, anticoagulant, antihypertensive, and antiarrhyth-
mic properties (Kris-Etherton, Harris, and Appel 2002; Maki et al. 2008). In
addition, fish oil is an extremely effective therapy for reduction of triglycer-
ides, but it is not particularly effective at raising HDL or lowering LDL.
Nevertheless, fish oil is useful in favorably altering the type of LDL, assisting in
the conversion of the more risky small, dense particles into the more desirable
larger, buoyant forms (Maki et al. 2008).
Fish and fish oil have been shown to be protective against cardiac events,
although the data is stronger for secondary than primary prevention. Benefit
of fish for secondary prevention has been shown in the Diet and Reinfarction
Trial (DART), in which men with prior MI who consumed 2–3 fish meals per
week had a 29 percent reduction in all cause mortality, mostly due to a lower
rate of coronary death (Burr et al. 1989). In the GISSI trial, post-MI patients
were randomized to fish oil containing EPA 465 mg and DHA 375 mg (total
EPA and DHA of 840 mg) or placebo, with the result of a 53 percent reduction
in sudden cardiac death by 4 months in the group receiving fish (Marchioli
et al. 2002).
The active ingredients in fish oil are EPA and DHA. Accordingly, recom-
mendation for fish oil dosage should include a specific daily total of EPA
and DHA, as opposed to the total content of omega-3. For prevention, the
recommended daily total of EPA and DHA is 840 mg. For treatment of
elevated triglycerides, a dose range between 1000 and 4000 mg of EPA and
DHA per day may be helpful.
Over-the-counter products vary greatly in their concentration of EPA and
DHA. Despite containing a total omega-3 content of 1000 mg, the total EPA
and DHA per pill can range from 100 to 500 mg. Over-the-counter fish oil
preparations can be excellent choices, as long as they provide the desired daily
total of EPA and DHA. A prescription version of fish oil is also available,
Lovaza™, which contains 840 mg of combined EPA and DHA per tablet, the
exact content of the omega-3 used in the GISSI trial.
Vegetarians can find non-fish sources of DHA in pill form derived from
algae. Flax seed and flax oil are alternative, but less efficient, sources of omega-3.
Flax is rich in alpha linolenic acid but contains no DHA or EPA. Conversion of
alpha-linolenic acid to the active DHA and EPA requires enzymes that function
poorly in most individuals. Therefore, only approximately 5 percent of alpha-
linolenic acid is converted into EPA, and less than 1 percent into DHA (Plourde
and Cunnane 2007).
The active ingredients in fish oil are EPA and DHA. Accordingly, recommenda-
tion for fish oil dosage should include a specific daily total of EPA and DHA
(typically listed on the back of the supplement bottle), as opposed to the total
content of fish oil (listed on the front of the bottle). For prevention purposes,
the recommended daily total of EPA and DHA is 840 mg. For treatment of
elevated triglycerides, a range of 1000 to 4000 mg of EPA and DHA per day
may be helpful.
RISK FACTORS BEYOND LDL: LP(a)
Lp(a) is a glycoprotein that is produced in the liver by combining an LDL mol-

ecule with apo(a). Apo(a) is structurally similar to plasminogen, thereby acting
as a molecular decoy in the coagulation cascade, promoting thrombosis. As
expected, Lp(a), as a dual lipid and procoagulant molecule, has been strongly
correlated with the development of coronary heart disease and stroke (Danesh,
Collings, and Peto 2000; Schaefer et al. 1994).
Lp(a) exists in different sizes, with individual variations dictated by the
number of repeating units, referred to as “kringles” in apo(a). Available immu-
nologic assays target different portions of this molecule, with errors in mea-
surement introduced by some assays that target the kringle repeat regions. The
number of repeat regions also impacts atherogenic risk; those with fewer repeat
units (smaller isoforms) are associated with higher risk (Emanuele et al. 2004;
Kronenberg et al.1999).
Lp(a) can accompany elevated LDL-C or, alternatively, may be markedly
elevated in the face of a desirable appearing standard lipid profile. Clinical
situations where evaluation for Lp(a) may be especially relevant are those in
which the patient has a personal or family history of premature atherosclerotic
disease (Bostom et al. 1996; Genest et al. 1992). The risk of Lp(a) appears to be
linked to the circulating level. Given a reference range of Lp(a) of < 30 mg/dL,
adjusted risk increases from 1.7-fold for levels over 30 mg/dL, to 3.6-fold for
levels in excess of 120 mg/dL (Kamstrup et al. 2008).
Lp(a) levels are not appreciably influenced by diet, exercise, or administration
of statins. Niacin is the only agent in common use for treatment of dyslipidemia
that reduces the level of Lp(a), up to 39% at dose of niacin 2,000 mg per day
(Capuzzi et al. 1998). The highest risk of elevated Lp(a) levels appears to be in
those with concomitant increased levels of LDL-C (Maher et al. 1995; Suk Danik
2006) and, therefore, another approach to treatment is to reduce LDL-C. To date,
however, there has not been a prospective Lp(a) intervention study, and the opti-
mal approach to treatment has not been identified. In high-risk individuals,
some experts suggest intensive treatment of LDL-C (no data to guide how
aggressive to be, but in practice, levels are often reduced to at least< 100 mg/dL,
with more aggressive goals set by some to 60-80 mg/dL). A second approach is
to treat Lp(a) itself with niacin in maximally tolerated doses up to 2,000 mg. The
most aggressive treatment of Lp(a), again without supporting data, is to give a
statin to lower LDL-C to a value between 60–80 mg/dL, in addition to a maxi-
mally tolerated dose of niacin up to 2,000 mg. An alternative approach, for those
who refuse or do not tolerate prescription medication, includes the use of red
yeast rice to lower LDL-C, combined with over-the-counter niacin.
RISK FACTORS BEYOND LDL: hs-CRP
The long-held view of coronary syndromes as evolving from a slow progres-

sion of gradual plaque buildup has been uprooted by the recognition of the
role of inflammation in the development of atherosclerotic plaque. Active ath-
erosclerotic disease appears to be closely related to the degree of local inflam-
matory cell infiltration, as well as circulating measures of inflammation. The
best-studied of the circulating inflammatory markers is high sensitivity
C-Reactive Protein (CRP). CRP is produced in the liver and by vascular
smooth muscle. Incremental risk associated with elevated high sensitivity CRP
has been shown to be in excess of 2-fold (Danesh et al. 2000), and is one of the
strongest predictors of death from coronary disease, even after adjustment for
Framingham risk score (Boekholdt et al. 2006). A link exists between CRP and
the metabolic syndrome, as the level of CRP rises incrementally with the
number of criteria for metabolic syndrome—up to an increase of 6-fold for
individuals with 5 criteria (Rutter et al. 2004).
Levels of high-sensitivity CRP associated with low risk are < 1 mg/L, neu-
tral values between 1.0 and 3.0 mg/L, and elevated levels > 3 mg/L (Yeh and
Willerson 2003).
Although there appears to be an association between high levels of CRP
and the incidence of coronary disease, no studies have been performed to
determine whether CRP reduction, as a goal of therapy, is associated with
improved outcome. Nevertheless, it is interesting to note that lifestyle mea-
sures known to improve cardiovascular outcome also reduce CRP. Diet is one
of the most potent interventions for reducing CRP, with a significant reduction
accompanying weight loss(Selvin, Paynter, and Erlinger 2007). Other dietary
measures associated with reduced CRP include: lower glycemic load diets (Liu
et al. 2002), reduction in trans fats (Lopez-Garcia et al. 2005), and adoption of
a Mediterranean-style diet(Church et al. 2002; Esposito et al. 2004). Aerobic
exercise also leads to reduced markers of inflammation, regardless of body
mass index (Church et al. 2002).
In addition to lifestyle changes, statins also have been known to dramati-
cally decrease CRP, with reductions of 30–40 percent noted with both pre-
scription statins (Ballantyne et al. 2003) as well as with red yeast rice (Li et al.
2005). Other agents that lower CRP include omega-3 fatty acids(Lopez-Garcia
et al. 2004) and probiotics (Kekkonen et al. 2008).
RISK FACTORS BEYOND LDL: HOMOCYSTEINE
Homocysteine has long been linked to the development of atherosclerosis,

with evidence suggesting an association of homocysteine with inflammation,
thrombosis, and endothelial dysfunction. Levels exceeding 10 μmol/liter are
associated with increased risk, with incrementally greater risk associated
with higher levels (Wald, Law, and Morris 2002). Folic acid, vitamin B6,
and vitamin B12 have all been demonstrated to lower homocysteine level.
Therefore, homocysteine-lowering therapy with these nutrients has been
studied to determine if treatment would reduce the risk of cardiovascular
disease.
Large, randomized clinical trials in patients with vascular disease or diabe-
tes have been conducted using high-dose folic acid, vitamin B6, and vitamin
B12, with primary ends point of stroke reduction (Toole et al. 2004) and
reduction of cardiovascular events in the HOPE-2 and NORVIT trials (Bonaa
et al. 2006, Lonn et al. 2006). In each of these studies, combined multivitamin
therapy was successful in lowering homocysteine levels but, paradoxically, no
clinical benefit was observed, and the primary end points were not achieved.
In fact, the NORVIT study of multivitamin therapy in patients with diabetes
or vascular disease demonstrated a trend toward harm in the active treatment
group. Of note, mean plasma homocysteine levels were not severely elevated
at baseline in either the HOPE-2 or NORVIT trials (12.2 and 13.1 μmol/liter,
respectively).
The failure of homocysteine reduction with folic acid, vitamin B6, and
vitamin B12 for secondary prevention is puzzling. Explanations include the
possibility that homocysteine is a marker rather than a trigger for atheroscle-
rosis, as well as the possibility that high-dose multivitamin therapy may have
adverse consequences that offset the benefits of homocysteine reduction. Folic
acid stimulates cell proliferation and, perhaps, accelerates growth of constitu-
ents within the atherosclerotic plaque.
Much remains unknown about the role of homocysteine and its treatment.
Unresolved issues include: the role of vitamin therapy to lower homocysteine
levels for primary prevention; the preventive value of multivitamin therapy in
selected patients with extremely high homocysteine levels; and the potential
benefit of therapies other than folic acid, B6, and B12. Betaine (trimethylgly-
cine) has been shown to reduce homocysteine (Schwab et al. 2002), but no
outcomes data is available using this agent.
Elevated homocysteine is associated with increased cardiovascular risk,

and multivitamin therapy with folic acid, B6, and B12 is effective at reducing
levels. Nevertheless, no studies have demonstrated cardiovascular benefit
from lowering homocysteine. Although there is no support for high-dose folic
acid supplementation, increasing the intake of vegetables rich in folate is
associated with remarkable cardiovascular protection.
At the present time, my own practice is to advise most patients to take no

more than 400 mcg of folic acid in supplements (typically this amount is con-
tained in multivitamins) and to further increase folate intake through increased
consumption of vegetables. Increased intake of green leafy vegetables, rich in
folate, has been linked to reduced cardiovascular events, with each daily serv-
ing of green leafy vegetables associated with a 23 percent reduction in the risk
of coronary heart disease (Joshipura et al. 2001). Exceptional patients, how-
ever, may require individualized assessment, including high-risk individuals
with markedly elevated homocysteine levels.
RISK FACTORS BEYOND LDL: LOW VITAMIN D
There is mounting evidence that low levels of vitamin D contribute to cardio-

vascular disease. Vitamin D receptors are found in both vascular smooth
muscle and in the heart, where activation leads to favorable changes, including
reduced secretion of rennin (Li et al. 2002), suppression of smooth muscle cell
proliferation, and inhibition of cytokine release from lymphocytes(Rigby,
Denome, and Fanger 1987).
Low vitamin D is associated with up-regulation of the renin-angiotensin
system, and restoration of normal levels to individuals with low vitamin D by
either nutritional supplementation or by UVB exposure has been shown to
decrease blood pressure by 6 mmHg (Krause et al. 1998; Li 2003).
Vitamin D deficiency is also linked to insulin resistance and the metabolic
syndrome, with supplementation of 800 IU per day shown to decreased the
risk of type 2 diabetes by one-third (Pittas et al. 2006). Assuring normal
Vitamin D levels in infancy may have profound implications for the future
development of diabetes. A metaanalysis of five observational studies evaluat-
ing the impact of vitamin D supplementation in infancy demonstrated a
29 percent reduction in the development of type I diabetes in infants supple-
mented with vitamin D, compared to those who were not treated (Zipitis and
Akobeng 2008).
Apart from increasing the incidence of atherosclerotic risk factors, mount-
ing clinical evidence suggests an association between low vitamin D and
increased likelihood of cardiovascular disease (Poole et al. 2006; Scragg et al.
1990). Initial observations were confirmed in a larger study of 1,739 individu-
als from the Framingham Offspring Study, in which a 25-OH vitamin D level
<15 ng/ml was associated with a 62 percent increased risk of a cardiovascular
event. This extremely low level of vitamin D is relatively common, with levels
<15 ng/ml found in 28 percent of the study population (Wang et al. 2008).
Increased risk was found primarily in hypertensive individuals, with a 2.1x
hazard ratio in patients with both low Vitamin D and hypertension.
What is the optimal serum level of Vitamin D? Serum levels of 25(OH) D of
> 30 ng/ml are considered ideal (Bischoff-Ferrari et al. 2006). Some experts
suggest that even higher levels are best, but there is general agreement that
a value of at least 30 ng/ml should be targeted. Epidemiologic data suggests
that levels greater than 100 ng/ml are to be avoided, with levels exceeding
150 ng/ml associated with hypercalcemia. Among healthy young adults, the
prevalence of vitamin D inadequacy is 36 percent, and rises to 41 percent in
middle-age and older outpatients (Holick 2006). Factors associated with low
vitamin D levels include: living in cold climates with decreased sun exposure;
darkly pigmented skin; obesity; and advanced age. On average, levels in most
individuals tent to be about one-third lower in the winter compared to the
summer (Tangpricha et al. 2002).
How can Vitamin D levels be increased? The body’s primary source of vita-
min D is internal production stimulated by sun exposure. Exposure of arms
and legs to midday sun for 5 to 30 minutes (depending on skin pigment, age,
and geography) twice a week has been estimated to be sufficient to maintain
healthy vitamin D levels (Holick 2007).
Dietary sources of vitamin D include fish and dairy products. Wild salmon is
among the richest whole food dietary sources of vitamin D, with 360 IU per
3.5 oz serving. Cod liver oil contains 1,360 IU per tablespoon. Vitamin D-fortified
skim milk has approximately 100 IU per cup (2009, Dietary Supplement Fact
Sheet).
Beyond nutritional sources, supplemental vitamin D is often required to
replenish severely depleted levels. Vitamin D can be administered by prescrip-
tion in the form of vitamin D2 50,000 IU pills, which are typically taken once
every one to two weeks. Alternatively, over the counter vitamin D3 can be pre-
scribed in dosages of 1,000 to 5,0000 IU per day. Either strategy is effective, and
vitamin D levels should be checked 2–3 months after beginning therapy.
Mind/Body Interventions
None. That is the amount of time dedicated in my cardiology training to the

study of the impact of thoughts and emotions on heart health. No wonder that
the bidirectional mind–body path remains one that few cardiologists travel.
How could it be otherwise, when physicians have been trained to restrict atten-
tion to “objective” measures that lend themselves to diagnostic studies? Chest
pain may be evaluated with a stress test or even an angiogram, then dismissed
when no “objective” abnormalities are uncovered. The fact that the patient lost
his job, is having a difficult personal relationship, or is feeling sad about his life
situation is often lost in the analysis—yet may be the most critical element of
the evaluation.
Studies are clear on this point: mental stress can induce the same demand
on the heart as physical stress, often with severe consequences. A study of
patients with established heart disease has demonstrated that mental anxiety
can produce scintigraphic evidence of ischemia to a degree indistinguishable
from that produced with exercise (Dimsdale 2008).
The mere act of a health care professional inquiring about, and acknowledg-
ing, the emotional state of the patient during the clinical encounter is healing.
An extreme manifestation of stress on the heart is a newly described

syndrome of stress heart failure, or Takotsubo cardiomyopathy. This cardiac
emergency is a condition in which the development of severe cardiac dysfunc-
tion is triggered by stress. Overdrive of the autonomic system leads to a curi-
ous pattern of left ventricular wall motion abnormalities in which the apical
segments become akinetic with preserved function in basal regions. Cardiac
dysfunction leads to shock and possibly death if not properly supported
(Wittstein et al. 2005).
Interestingly, the antecedent stressors associated with this catastrophic
cardiac condition are often less than dramatic, including stress related to: a
class reunion; a surprise party; public speaking; or fear of a medical procedure
(Wittstein et al. 2005). If these stressors, common to everyone’s life experi-
ences, are capable of evolving into a cardiac emergency, what other less dra-
matic manifestation of cardiac disease may be missed in our daily outpatient
evaluations?
An integrative approach to prevention demands inquiry into emotional
influences that can color, and possibly trigger, a wide range of cardiovascular
conditions, including hypertension, lipid disorders, arrhythmias, angina, heart
failure, and myocardial infarction. It is my belief that the mere act of a health
care professional inquiring about, and acknowledging, the emotional state of
the patient during the clinical encounter is healing. Moreover, emotional dis-
covery is the critical step needed for the health care provider to initiate referral
of patients for appropriate help when stress, anxiety, or depression becomes
problematic.
Conventional options for referral of such patients include psychologists and
psychiatrists—two outstanding choices. An integrative approach to mind–
body interactions in cardiology, however, expands the options for healing.
Additional options within the integrative framework include: Healing Touch;
biofeedback; acupuncture; and Reiki. Matching the patient with the modality
is much more of an art than a science, incorporating the severity of the condi-
tion, the patient’s prior health care experience, personal preference, as well as
local availability and expertise. It is my belief that the inquiry and open explo-
ration is far more important than the particular modality chosen.
The critical area of emotional influences on the heart are more fully
evaluated by John Longhurst in Chapter 6 (Acupuncture in Cardiovascular
Medicine),by Mary Jo Kreitzer in Chapter 7 (Spirituality and Heart Health),
by Kim R. Lebowitz in Chapter 8 (Cardiac Behavioral Medicine: Mind–Body

Approaches to Heart Health), and by Rauni Prittinen King in Chapter 9
(Energy Medicine).
Conclusion
Most of us begin life with a healthy heart. As we enter middle age and beyond,
heart disease becomes so common that we can mistakenly believe it is inevi-
table. To the contrary, heart disease is largely preventable. In this chapter,
I have attempted to illustrate the many ways we can act to maintain heart
health, including the use of strategies that are not often included in physician
training. For example, the fact that nutritional therapy is one of the most
powerful interventions in cardiology is a concept foreign to many. Or, that a
mind–heart pathway, although largely out of view, can frighten us to death if
provoked, or lower our blood pressure and relieve chest pain if soothed.
This chapter has explored a wide range of tools at our disposal for preven-
tion of heart disease including exercise, nutrition, supplements, mind–body
paths, and medication. The integrative practitioner seeks to expand the con-
ventional view and to explore as many opportunities as possible to promote
heart health.
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11
The Integrative Approach to Hypertension
STEPHEN T. SINATRA AND MARK C. HOUSTON
key concepts
■ Oxidative stress initiates and propagates hypertension and

■ Nutrition can prevent, control, and treat hypertension through
numerous vascular biology mechanisms.
■ There is a role for the selected use of nutritional supplements in
the management of hypertension.
■ Exercise and weight reduction are integral components of a
blood pressure treatment program.
■ Mind–body therapies are powerful tools for management of
blood pressure, yet they are often ignored by the mainstream
medical profession.
■
Introduction
O
ptimal nutrition, exercise, weight management, nutraceutical supple-
ments, and management of emotional stress, can prevent, delay the
onset of, and treat hypertension in many patients. An integrative
approach combining these lifestyle suggestions with pharmacologic treatment
will best achieve blood pressure goals, and reduce the likelihood of cardiovas-
cular complications.
224
The Integrative Approach to Hypertension 225
Epidemiology
Hypertension has become a global public health challenge afflicting appro-

ximately one billion individuals worldwide, with the prevalence of hyperten-
sion having increased dramatically in developing countries in recent years
(Chobanian et al. 2003; Gu et al. 2002; Kearney et al. 2005). The consequence
is that hypertension results in a seven-fold increased risk of developing stroke,
triple the risk for coronary heart disease, a six-fold risk of developing conges-
tive heart failure, and an alarming increase in end-stage renal disease (Iseki
et al. 2000). Fortunately, the treatment of moderate to severe hypertension has
resulted in decreased rates of stroke and myocardial infarction (Neaton et al.
1993; Whelton et al. 2002).
THE ROLE OF OXIDATIVE STRESS
Oxidative stress (an imbalance of harmful oxygen species and the antioxidant
defense mechanism) may contribute to the etiology of human hypertension
(Kitiyakara and Wilco 1998; Nayak et al. 2001; Vaziri, Liang, and Ding 1999).
Hypertensive patients have a high level of oxidative stress and a greater than
normal response to oxidative stress (Lacy, O’Connor, and Schmid-Schonbein
1998). In addition, hypertensive patients have an impaired endogenous and
exogenous antioxidant defense mechanism (Kumar and Das 1993; Russo et al.
1998).
An imbalance of vasodilators (such as nitric oxide), vasoconstrictors (such
as angiotension), and radical oxygen species contribute to the initiation and
perpetuation of hypertension (McIntyre, Bohr, and Dominiczak 1999).
STAGED THERAPY OF HYPERTENSION
Patients with blood pressure below 140/90 mmHg who have no risk factors,
target organ disease, or clinical cardiovascular disease may be initially success-
fully treated with lifestyle modifications alone. As many as 50 to 60 percent of
essential hypertensive patients are included in this classification (Houston
1992). Those with more significant hypertension or with end- organ disease will
often require a combination treatment of lifestyle modifications and drugs.
When antihypertensive medication is needed, lifestyle changes potentiate
the effects of antihypertensive drugs, often permitting fewer drugs and/or
lower doses to be used (Houston 1992; Houston, Meador, and Schipani 2000).
In order to obtain optimal results and to keep the patient actively involved in
their care, lifestyle modifications should always be continued following initia-
tion of drug therapy (Houston 1992; Houston, Meador, and Schipani 2000).
Role of Prescription Medication
Although a complete discussion of possible pharmacologic therapy for

hypertension is beyond the scope of this chapter, a brief overview is pro-
vided, to emphasize the importance of balance and integration when treating
hypertension.
Lifestyle recommendations are the first-line treatment for high blood pres-
sure, but some patients must take prescription medication, especially those
whose hearts or lives are compromised, and those who are resistant to making
the lifestyle modifications needed. Blood pressure prescription drugs are
strongly recommended:
1. When a patient’s blood pressure is more than mildly elevated and

immediate action must be taken.
2. When lifestyle modification, weight loss, and exercise have been
unsuccessful or have failed to achieve blood pressure goals.
3. When a patient has evidence of end-organ dysfunction, especially
kidney disease.
Although antihypertensive drugs are effective, the chronic use of these

drugs can cause side effects including impotence, loss of libido, fatigue, drows-
iness, dry cough, lightheadedness and depression. For example, diuretics—
one of the oldest and most commonly used antihypertensives—can cause
muscle cramping, fatigue, weakness, impotence, type 2 diabetes mellitus, and
renal insufficiency.
Several years ago, a report in the Journal of the American Medical Association
noted that properly prescribed medications in a hospital is the fourth leading
cause of death in the United States (Lazaron, Pomeranz, and Corey 1998). At
that time, over 100,000 inpatient deaths were attributed to adverse reactions
to, or drug interactions with, prescription medication.
Even over-the-counter medications can be dangerous. A report from the
Harvard School of Medicine’s ongoing Nurses’ Health Study concluded that
women are at increased risk for high blood pressure if they take daily doses of
non-aspirin painkillers, including acetaminophen and over-the-counter non-
steroidal antiinflammatory agents (Forman, Stampfer, and Curhan 2005).
The Integrative Approach
Patients diagnosed with hypertension frequently leave their physician’s office

with prescriptions, and perhaps some advice to lose weight and cut back on
consumption of salt and fat. Although this is a good start, a better recommen-
dation incorporates an integrative strategy including nutrition, targeted nutri-
tional supplementation, exercise as well as weight management, and mind–body
strategies. Such a structured protocol leads to effective blood pressure lower-
ing and can eventually reduce—and in some cases eliminate—the need for
pharmaceutical drugs.
The Role of Nutrition
Humans have evolved away from pre-agricultural, hunter–gatherer traditions

toward a commercial agriculture and food industry which produces highly
processed foods that impart unnatural and unhealthy nutrition. The human
genetic makeup is 99.9 percent that of our Paleolithic ancestors, who date back
35,000 years, yet our nutrition is vastly different (Eaton, Eaton, and Konner
1997). The macronutrient and micronutrient variations contribute to the
higher incidence of hypertension and other cardiovascular diseases through a
complex nutrient–gene interaction.
The optimal combination of macronutrients and micronutrients signifi-
cantly impacts on vascular health. The landmark study “Dietary Approaches
to Stop Hypertension (DASH)” clearly demonstrated in 1997 that patients
who eat more fruits and vegetables and who switch to low-fat dairy foods are
able to lower their systolic blood pressure by an average of 11.4 points, and
their diastolic pressure by 5.5 points (Appel et al. 1997). This reduction is on
par with that observed with many antihypertensive medications. Moreover,
the DASH participants achieved these gains without losing weight or cutting
back on sodium—two of the most effective non-medical tools for blood pres-
sure lowering.
The average sodium intake in the U.S. is 5,000 mg per day, with people
living in some areas of the country consuming 15,000–20,000 mg per day
(Warner 2000). However, the necessary amount of sodium is probably only
about 500 mg per day (Warner 2000). Epidemiologic, observational, and con-
trolled clinical trials demonstrate that an increased sodium intake is associ-
ated with higher blood pressure (Kotchen and McCarron 1998). A reduction
in sodium intake in hypertensive patients, especially the salt-sensitive patients,
will significantly lower blood pressure by an average of 4–6 mmHg systolic

and 2-3 mmHg diastolic (Sacks et al. 2001). The blood pressure reduction is
proportional to the severity of sodium restriction (Sacks et al. 2001).
The effect of dietary sodium on blood pressure is modulated by other com-
ponents of the diet. Sodium chloride-induced hypertension is augmented by
diets low in potassium (Hamet et al. 1992), calcium, and magnesium (Hamet
et al. 1992; Kotchen and Kotchen 1997) and attenuated by high potassium,
magnesium, and calcium (especially Na+ sensitive). The DASH-II diet is
particularly instructive in this regard (Sacks et al. 2001). Gradual reductions in
sodium from 150 mmol to 100 mmol to 50 mmol per day in association with
a high intake of fruits and vegetables, and intake of low-fat dairy products,
with adequate potassium, calcium, magnesium and fiber intake, was the most
effective in reducing blood pressure.
The average adult consumes the equivalent of nearly two teaspoons of salt a
day—nearly twice the upper limit for good health. The majority of that excess
salt is hidden in processed foods such as canned spaghetti sauces, dill pickles,
packaged soups, salty nuts, crackers, and sauerkraut as well as fast foods.
MAGNESIUM (MG++)
A high dietary intake of magnesium of at least 500–1,000 mg per day reduces

blood pressure in most of the reported epidemiologic, observational, and clin-
ical trials, but the results are less consistent than those seen with Na+ and K+
(Kotchen and McCarron 1998; Warner 2000). In most epidemiologic studies,
there is an inverse relationship between dietary magnesium intake and blood
pressure (Kotchen and McCarron 1998).
PROTEIN
Observational and epidemiologic studies demonstrate a consistent association

between a high protein intake and a reduction in blood pressure (BP)
(Obarzanek, Velletri, and Cutler 1996). The source of that protein is an impor-
tant factor in the BP effect, animal protein being less effective than non-animal
protein for blood pressure lowering (Elliot et al. 2000).
The INTERSALT Study (Stamler et al. 1996) supported the hypothesis that
higher dietary protein intake has favorable influences on blood pressure.
In 10,020 men and women in 32 countries worldwide, the average systolic
blood pressure (SBP) and diastolic blood pressure (DBP) were 3.0 mmHg
and 2.5 mmHg lower, respectively, for those whose dietary protein intake was
30 percent above the overall mean than for those 30 percent below the overall
mean (81 grams/day versus 44 grams/day).
Soy protein at intakes of 25 to 30 grams/day lowers blood pressure and increases
arterial compliance. Soy contains many active compounds that produce these
antihypertensive effects, including isoflavones, amino acids, saponins, phytic acid,
trypsin inhibitors, fiber, and globulins (Hasler CM, Kundrat S, Wool D 2000).
Sardine muscle protein, which contains Valyl-Tyrosine (VAL-TYR), signifi-
cantly lowers blood pressure in hypertensive subjects (Kawasaki et al. 2000).
Kawasaki et al. (2000) treated 29 hypertensive subjects with 3 mg of Valyl-
Tyrosine sardine muscle concentrated extract for four weeks, and lowered BP
9.7 mmHg/5.3 mmHg (p < 0.05). Valyl-Tyrosine is a natural angiotensin con-
verting enzyme inhibitor (ACEI). The antihypertensive effect of sardine may
also be due to its high concentration of both calcium and CoQ10.
OMEGA-3 FATTY ACIDS
Alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexanoic

acid (DHA) comprise the primary members of the omega-3 PUFA family.
Omega-3 fatty acids are found in cold-water fish (herring, haddock, salmon,
trout, tuna, cod, and mackerel), fish oils, flax, flax seed, flax oil, and nuts
(Warner 2000). Omega-3s stimulate the production of nitric oxide, which
relaxes vascular smooth muscle and counteracts the impairment of nitric oxide
production caused by atherosclerotic plaques (Braunwald E 1994). Omega-3
fatty acids also attenuate the vasopressor effects of angiotensin 2 and norepi-
nephrine that affect blood pressure (Lorenz et al. 1983). Omega-3 PUFA was
found to significantly lower blood pressure in observational, epidemiologic,
and in some small prospective clinical trials through a variety of mechanisms
(Lorenz et al. 1983; Mori et al. 1999a; Mori et al. 1999b; Warner 2000).
Mori et al. (1999b) studied sixty-three hypertensive, hyperlipidemic sub-
jects treated with omega-3 PUFA, at 3.65 grams/day for sixteen weeks, and
found significant reductions in blood pressure (P < 0.01). An average systolic
reduction was 5 mmHg. Studies indicate that DHA is more effective in reduc-
ing blood pressure and heart rate than EPA supplementation, possibly due to
greater improvement of DHA on endothelial function (Mori et al. 1999a; Mori
et al. 2000).
Eating cold-water fish three times per week is as effective as high-dose fish
oil in reducing blood pressure in hypertensive patients, and the protein in the
fish may also have antihypertensive effects (Warner 2000).
Plant sources of omega-3 are metabolized to EPA and DHA, but this con-
version is jeopardized in the presence of increased intake of omega-6 fatty
acids, saturated and trans fats, alcohol, and aging via inhibitory effects on delta
desaturase enzymes.
OMEGA-9 FATTY ACIDS
Olive oil is rich in monounsaturated fats (MUFA) predominantly containing

omega 9 fatty acids, which have been associated with blood pressure and lipid
reduction in Mediterranean and other diets (Warner 2000). Ferrara and col-
leagues (2000) studied 23 hypertensive subjects in a double-blind, random-
ized, crossover study for six months comparing MUFA with PUFA. Extra
virgin olive oil (a MUFA) was compared to sunflower oil (a PUFA), abundant
in linoleic acid (W-6 FA). The SBP fell 8 mmHg (p < 0.05) and the DBP fell
6 mmHg (p < 0.01) in the MUFA-treated subjects, compared to the PUFA-
treated subjects. In addition, the need for antihypertensive medications was
reduced by 48 percent in the MUFA group, versus 4 percent in the PUFA
(omega-6 FA) group (p < 0.005).
FIBER
The clinical trials with various types of fiber to reduce blood pressure have
been generally favorable, but inconsistent. Soluble fiber, guar gum, guava,
psyllium, and oat bran lower blood pressure and possibly reduce the need for
antihypertensive treatments (Pereira and Pins 2000; Vuksan et al. 1999).
Vuskan and colleagues (1999) reduced SBP 9.4 mmHg in hypertensive
subjects with the fiber glucomannan. The doses required to achieve these
BP reductions are approximately 60 grams of oatmeal (slightly more than
one-quarter cup) per day, 40 grams of oat bran (dry weight) per day, or 7 grams
a day of psyllium (Stamler et al. 1996).
GARLIC AND ONIONS
Garlic is an outstanding antiinflammatory and antimicrobial agent with a long

history of use in traditional folk medicine. A review of eleven studies in which
hypertensive patients were randomly given garlic or placebo found that garlic
can lower blood pressure as effectively as some pharmaceutical drugs (Ried
et al. 2008).
On average, the metaanalysis demonstrated blood pressure reductions of
8 mmHg systolic, and 7 mm diastolic. The higher a patient’s blood pressure
was at baseline, the more it was reduced with garlic. Dosages taken by the
subjects in the studies ranged from 600 to 900 mg over a period of 3 to

6 months. There is a consistent dose-dependent reduction in BP with garlic
mediated through the RAAS (renin angiotensin aldosterone system) and the
nitric oxide system (Mohamadi et al. 2000).
Approximately 10,000 mcg of allicin per day (the amount contained in
four cloves of garlic, or four grams) is required to achieve a significant blood
pressure lowering effect (McMahon and Vargas 1993; Warner 2000). Garlic
is probably a natural Angiotensin converting enzyme inhibitor (ACEI) that
increases BK and NO-inducing vasodilation, reducing SVR and BP and
improving vascular compliance.
Because they are in the same family as garlic, it is no surprise that onions
have similar effects. Onions, like garlic, contain sulfur and powerful flavonoids,
quercetin being the major health-promoting flavonoid of onions.
NATTO
Natto is a traditional fermented vegetable, a cheese-like food that is a staple in

Japan.
Previous studies have shown that consumption of natto enhances the fibrin-
olytic system while suppressing thrombosis and intimal thickening (Kim et al.
2008; Pais et al. 2006). It also lowers blood pressure by inhibiting plasma renin
activity (Kim et al. 2008).
SEAWEED
Another medicinal food in the Asian diet is wakame seaweed. Wakame

(undaria pinnatifida) is the most popular edible seaweed in Japan (Suetsuna
and Nakano 2000). In humans, 3.3 grams of dried wakame for four weeks
significantly reduced both the SBP 14 + 3 mmHg and the DBP 5 + 2 mmHg
(p < 0.01) (Nakano et al. 1998). The primary effect of wakame appears to be
through its ACEI (Suetsuna and Nakano 2000).
CELERY
Consuming four sticks of celery or eight teaspoons of celery juice three times
daily, or the equivalent in the form of extract of celery seed (1,000 mg twice a
day) or oil (one-half to one teaspoon three times daily in tincture form) seems
to provide an antihypertensive effect in human essential hypertension (Le and
Elliot 1991; Duke 2001).
The Role of Nutritional Supplements
While the diet discussed earlier in this chapter can significantly lower blood
pressure, it is difficult for most patients to consistently adhere to a prescribed
diet. Complementing the diet with targeted nutritional supports may further
support blood pressure lowering.
B VITAMINS
Vitamin B-6 is a readily metabolized and excreted water-soluble vitamin. Six

different B-6 vitamins exist, but pyridoxal 5’ phosphate (PLP) is the primary
and most potent active form. A clinical study by Aybak et al. (1995) demon-
strated that high-dose vitamin B-6 significantly lowered blood pressure. This
study compared nine normotensive men and women with 20 hypertensive sub-
jects, all of whom had significantly higher blood pressure, plasma NE, and HR
compared to control normotensive subjects. Subjects received 5 mg/kg/day
of vitamin B-6 for four weeks. The SBP fell from 167 ± 13 mmHg to 153 ±
15 mmHg, an 8.4% reduction (p < 0.01), and the DBP fell from 108 ± 8.2
mmHg to 98 ± 8.8 mmHg, a 9.3% reduction (p < 0.005).
VITAMIN D
Low levels of vitamin D have been linked to the development of high blood
pressure. In a 2008 case-controlled study involving 1,484 women between the
ages of 32 and 52, plasma levels of vitamin D were found to be lower among
women who developed hypertension. The authors concluded that vitamin D
levels are inversely and independently associated with the risk of developing
hypertension (Forman, Curhan, and Taylor 2008).
In a group of 148 women with low vitamin D levels, the administration
of 1,200 mg calcium, plus 800 IU of vitamin D3, reduced SBP 9.3 percent more
(p < 0.02), compared to 1,200 mg of calcium alone. The HR fell 5.4 percent
(p = 0.02), but DBP was not changed (Pfeifer et al. 2001).
VITAMIN C
Vitamin C, a potent water-soluble antioxidant, not only regenerates tocoph-

erol and supports endothelial cell function; it also enhances the body’s total
antioxidant system by raising levels of glutathione, a polypeptide amino acid

and potent free radical scavenger. The dietary intake of vitamin C or plasma
ascorbate concentration in humans is inversely correlated to SBP, DBP, and
heart rate (Duffy et al. 1999).
Duffy et al. (1999) evaluated 39 hypertensive subjects (DBP 90 mmHg to
110 mmHg) in a placebo-controlled, four-week study. A 2,000-mg loading
dose of vitamin C was given initially, followed by 500 mg per day. The SBP was
reduced 11 mmHg (p = 0.03), DBP decreased by 6 mmHg (p = 0.24), and
MAP fell 10 mmHg (p < 0.02).
COENZYME Q10 (UBIQUINONE)
Coenzyme Q10 is an essential component of the mitochondrial respiratory

chain, and has important functions in oxidative phosphorylation and ATP
production. It is a potent lipid phase antioxidant, free radical scavenger,
cofactor, and coenzyme in mitochondrial energy production that lowers sys-
temic vascular resistance and blood pressure (Cooke 1998; Digiesi et al. 1994;
Langsjoen and Langsjoen 1999; Warner 2000).
In its reduced form, coenzyme Q10 protects membrane phospholipids and
serum LDL from lipid peroxidation. It safeguards mitochondrial membrane
proteins and DNA from free radical-induced oxidative damage (Digiesi et al.
1994; Langsjoen and Langsjoen 1999).
Coenzyme Q10 is commonly found predominantly in animal protein.
Sardines, wild Alaskan salmon, mackerel, and organ meats such as beef heart
and chicken liver are excellent sources. Serum levels of CoQ10 decrease with
age and are lower in patients with diseases characterized by oxidative stress
such as hypertension, CHD, hyperlipidemia, diabetes mellitus, and atheroscle-
rosis. Enzymatic assays showed a deficiency of CoQ10 in 39 percent of
59 patients with essential hypertension, versus only 6 percent deficiency in
controls (p < 0.01) (Digiesi, Cantini, and Brodbeck 1990).
Studies have also demonstrated significant and consistent reductions in
blood pressure in hypertensive subjects following oral administration of 100
mg to 225 mg per day of CoQ10 (Burke, Neustenschwander, and Olson 2001;
Digiesi, Cantini, and Brodbeck 1990; Langsjoen and Langsjoen 1999).
Burke, Neustenschwander, and Olson (2001) conducted a 12-week, random-
ized, double-blind, placebo-controlled trial with 60 mg of oral CoQ10 in 76 sub-
jects with isolated systolic hypertension. The mean reduction in SBP in the treated
group was 17.8 ± 7.3 mmHg (p < 0.01), but DBP did not change. Only 55 percent
of the subjects were responders achieving a reduction in SBP ≥ 4 mmHg, but in
this group the SBP fell 25.9 ± 6.4 mmHg. There was a trend between SBP reduc-
tion and increase in CoQ10 levels. Adverse effects were virtually nonexistent.
CoQ10 has consistent and significant antihypertensive effects in patients

with essential hypertension. The major conclusions from in vitro, animal, and
human clinical trials indicate the following:
1. The bioavailability and delivery of CoQ10 are important consider-

ations when measuring blood levels (Chopra et al. 1998).
2. Compared to normotensive patients, essential hypertensive patients have
a high incidence of CoQ10 deficiency documented by serum levels.
3. Doses of 120 to 300 mg per day of CoQ10, depending on the delivery
method and concomitant ingestion with a fatty meal, are necessary
to achieve a therapeutic level of over 2 ug/ml. This dose is usually
1–2 mg/kg/day of CoQ10. Use of a special delivery system allows
better absorption and lower oral doses. Sicker and more compromised
patients often require larger doses (2–4 mgs/kg/day of CoQ10).
4. Patients with the lowest CoQ10 serum levels may have the best
antihypertensive response to supplementation.
5. The average reduction in SBP is about 15/10 mm Hg based on reported
studies.
6. CoQ10’s favorable impact on blood pressure may be attributed to its
role in reducing oxidative stress in blood vessel tissue, which, in turn,
lowers resistance in the blood vessel.
7. The antihypertensive effect takes time to reach its peak level, usually
at about four weeks; after that blood pressure remains stable. The anti-
hypertensive effect is gone within two weeks after discontinuation of
CoQ10.
8. Some patients with mild hypertension treated with prescription med-
ication who start coenzyme Q10 may be able to lower the dosage of
medication, or possibly eliminate the need for its use.
9. Even high doses (>600 mg/daily) of CoQ10 have no acute or chronic
adverse effects.
HAWTHORN
Hawthorn, a term encompassing many Crataegus species, is traditionally con-

sidered a tonic for the cardiovascular system. Crataegus extract appears to
have multiple antioxidant properties that can inhibit the formation of throm-
boxane A2, a potent inflammatory mediator (Vibes et al. 1994).
Hawthorn exerts a mild hypotensive effect by lowering total peripheral
resistance (Schussler, Holzl, and Fricke 1995). Doses of 1000 to 1500 mg per
day have been used with success.
The Role of Exercise
Physical activity has many positive attributes, including supporting the

maintainance of a healthy weight, as diet alone cannot take and keep weight off
in most cases. Only diet and physical activity together can achieve that.
Research shows that a minimum amount of some form of activity—a mere
30 minutes a day of walking, for instance—yields major protective benefits.
Walking burns approximately 100 calories per mile, and since it is perhaps the
safest form of exercise, it must be considered as a key component in any hyper-
tensive management program. Exercise not only helps to lower blood pressure
through vasodilatory effects, but it also helps reduce weight and decrease insu-
lin resistance.
A review of the “neurobiology” of exercise (Dishman et al. 2006) demon-
strated that regular exercise positively influences brain and nervous system
function. Psychological and emotional stress, especially when they cause height-
ened arousal of the sympathetic nervous system, are major considerations in
the hypertensive syndrome.
The Role of Mind–Body Approaches
Mental stress contributes to hypertension through a sustained increase in

sympathetic nervous activity. Chronic emotional stress has been linked to psy-
chological and cognitive dysfunction (Rozanski A, Blumenthal JA, Kaplan J
1999) resulting from dysregulation of the hypothalamic-pituitary-adrenal
(HPA) network and sympathoadrenal system (Rozanski, Blumenthal, and
Kaplan 1999; Tsigos and Chrousos 2002). Undesirable, dysfunctional affective
states increase the risk of both hypertension and cardiovascular disease
(Todaro et al. 2003).
For example, intense emotional grief and profound sadness can lead to
hypertension (Prigerson et al. 1997; Santić et al. 2006). Researchers looked at
hypertension in family members of soldiers killed in the 1992–1995 war in
Bosnia and Herzegovina. The study involved 1,144 subjects who experienced
a loss and compared them to 582 of their close neighbors who did not. Blood
pressure was recorded in 1996 and again in 2003. At the time of both readings,
the results revealed a significantly higher prevalence of hypertension in the
loss group, which the researchers attributed to the psychological stress of
mourning—even though more than seven years had passed since their family
members had been killed.
Another study related to grief as a predictor of future physical and mental

health problems was conducted in 1997 at the University of Pittsburgh School
of Medicine. Researchers interviewed 150 women and men with terminally ill
spouses. They were first interviewed at the time of their spouses’ hospital
admission and then again after 6 weeks, 6 months, 13 months, and 25 months.
The researchers found that the presence of traumatic grief symptoms at the
6-month mark predicted not only high blood pressure at the 13- and 25-month
interviews, but also other negative health outcomes, such as cancer, heart trou-
ble, suicidal thoughts, and unhealthy eating habits. Assessing grief is of critical
importance in determining which bereaved individuals will be at higher risk
for long-term dysfunction (Prigerson et al. 1997).
Such chronic emotional and psychological stress, or lack of control over
one’s environment, triggers the pituitary release of ACTH (adrenocorticotro-
pic hormone) (Jezova and Duncko 2002). ACTH catalyzes the release of
catecholamines—epinephrine (adrenalin) and norepinephrine (noradrenaline)—
into the bloodstream.
The sustained release of these catecholamines, increases cardiac output and
systemic vascular resistance, and disrupts the equilibrium between the sympa-
thetic and parasympathetic nervous systems (Goldstein 1995). Hypertension,
then, may be viewed as a form of chronic sympathetic overdrive. As people
with a compromised autonomic nervous system often exhibit blood pressure
problems, it follows that balancing the ANS may be an adjunct to blood pres-
sure and stress management.
Manipulating sympathetic nervous activity through mind–body relaxation
techniques helps to assuage emotional stress. Relaxation techniques, such as
Transcendental Meditation (TM), Tai Chi, and yoga, help lower sympathetic
medullary activity, as well as train the body and mind to adapt to stress (Jacobs
2001). Yoga, TM, and Tai Chi are optimal long-term methods of reducing
blood pressure, as they may be regularly practiced anywhere as either group or
individual activities.
All relaxation responses involve reduced stress hormones and central
nervous system activity, measurable through changes in brain wave activity.
TRANSCENDENTAL MEDITATION (TM)
The Transcendental Meditation program, or TM as it is popularly called, has

been the focus of more than 600 scientific studies around the world, including
nine randomized controlled trials in patients with hypertension or high blood
pressure. Anderson, Liu, and Kryscio (2008) at the University of Kentucky
conducted a systematic review and metaanalysis on these randomized trials,
which met strict entry criteria for experimental quality. The random-effects
metaanalysis model for systolic and diastolic blood pressure, respectively,
indicated that TM, compared to control, achieved clinically significant reduc-
tions in blood pressure. The results showed the following changes: systolic
−4.7 mmHg (−7.4 to −1.9 mm) and diastolic −3.2 mmHg (95% CI −5.4 to
−1.3 mmHg). The duration of studies ranged from 8 to 52 weeks, with a median
length of 15 weeks.
In 1987, Orme-Johnson reported on a study of health insurance statistics in
more than 2,000 individuals practicing the TM program over a 5-year period.
He found that those who meditated consistently had less than half the number
of hospitalizations and doctor visits than did other groups with comparable
age, gender, profession, and insurance terms. There were 87 percent fewer hos-
pitalizations for heart disease (Orme-Johnson 1987).
TM was brought to the West in the late 1950s by Maharishi Mahesh Yogi, a
visionary Indian sage trained in physics, who saw meditation as a means of
alleviating stress in individuals and society. His emphasis on scientific research
proved that the timeless practice of meditation was not just an arcane mystical
activity for Himalayan recluses, but rather a mind–body method hugely rele-
vant to and beneficial for modern society.
In 2007, an analysis of 107 studies compared the effects on high blood pres-
sure of multiple stress reduction and relaxation methods. The TM technique
was found to produce a statistically significant reduction in high blood pres-
sure not found with relaxation, biofeedback, or stress management training
(Rainforth et al. 2007).
Therfore, many studies strongly support the inclusion of TM as a major
mind–body tool for blood pressure management, either as the sole or an
adjunctive therapy. Side benefits include reductions in related CVD risk fac-
tors, such as psychological stress, metabolic syndrome, CVD morbidity, and
mortality (Anderson, Liu, and Kryscio 2008; Rainforth et al. 2007).
TAI CHI
Tai Chi, originally a non-competitive form of self-defense, has been referred

to as “meditation in motion.” Consisting of a series of postures and movements
performed slowly and gracefully, Tai Chi focuses on breathing through fluid
movements to induce a state of relaxation and tranquility. As chi is believed
to be the vital force animating the body, Tai Chi aims to circulate chi through-
out the body while fostering a calm mind. Practiced regularly, Tai Chi can
reduce stress while improving flexibility, strength, and energy (Wang, Collet,
and Lau 2004).
Table 11.1. Diet and Lifestyle Recommendations

Nutrition Daily Intake
1. Dash I, Dash II-Na+ and premier diets like

Mediterranean and Asian
2. Sodium restriction Less than 1.5 grams
3. Potassium 100 mEq
4. Potassium/sodium ratio >5:1
5. Protein: total intake (30% total calories) 1.0–1.5 gram/kg

A. Non-animal sources preferred but lean or wild
free- range animal protein in moderation is acceptable
B. Soy protein (fermented is best) 30 grams 1–2 x per week
C. Sardine muscle concentrate extract or 2–3 Sardines 1–2 x per week
D. Cold-water wild fish, i.e., Alaskan salmon, no 4–5 oz, 2–3 x per week
farm-raised fish, fowl, or poultry
6. Fats: 30% total calories

A. Omega-3 fatty acids PUFA 3–4 grams
(DHA, EPA, cold-water fish)
B. Omega-6 fatty acids PUFA Oatmeal 60 grams=>1/4 cup
C. Omega-9 fatty acids MUFA 1–2 tablespoons on
Extra virgin olive oil, Olives steamed veggies or
salad or 3–5 olives
D. Saturated FA (lean, wild animal meat) (30%) <10% total calories
E. P/S ratio (polyunsaturated/saturated_ fats >2.0
F. Omega-3/Omega-6 PUFA, ratio 1:1 – 1:2
G. No trans fatty acids (0%)
(hydrogenated margarines, vegetable oils)
H. Nuts: almonds, walnuts, hazelnuts, macadamia. ¼–½ cup one to two
times a week
7. Carbohydrates 30–40% calories

A. Reduce or eliminate refined sugars and simple
carbohydrates
B. Increase complex carbohydrates and fiber whole grains 3–4 times per week for
(oat, barley, wheat) vegetables, beans, legumes complex carbs
i.e. oatmeal or 60 grams=>1/4 cup
oatbran (dry) or 40 grams, 2–3 times
pr/wk
beta-glucan 3 grams
or psyllium 7 grams
8. Garlic 4 cloves/day
(continued )
Table 11.1. (Continued)

Nutrition Daily Intake
9. Onions 1–2 slices raw/day
10. Wakame seaweed (dried) 3.0–3.5 grams, 2–3

times per week
11. Celery
Celery stalks or 4 stalks/day
Celery juice or 8 teaspoons TID
Celery seed extract 1000 mg BID
Celery Oil (tincture) ½–1 teaspoon TID
12. Natto 100 grams, 2–3 times

per week
Exercise 5 days a week

• Aerobic
• Walk 30–60 minutes daily
• 4200 KJ/week
• Resistance training 3x/week or daily
Weight Loss 3x/week or daily

• To ideal body weight (IBW)
• Lose 1–2 pounds week
• BMI <25
• Waist circumference
<40 inches for male
<35 inches for female
• Total body fat
<16% in males
<22% in females
• Increase lean muscle mass
Alcohol Restriction <20 grams/day

• Wine <10 ounces (preferred-
red wine)3–4 x
per week
• Beer <12 ounces
3–4 x per week
Caffeine None
Tobacco and Smoking None
Avoid drugs and interactions that increase BP Non-steroidals,

acetaminophen
Stress Management Yoga, TM, Tai Chi

In a study of two groups of 76 healthy subjects with high to normal blood

pressure or stage I hypertension, Tai Chi was shown to decrease blood pressure
and anxiety. After subjects practiced 50 minutes of Tai Chi three times per
week for 12 weeks, the treatment group demonstrated a 15.6 mmHg decrease
in systolic blood pressure and a 8.8 mmHg decrease in diastolic blood pressure
(Tsai et al. 2003).
YOGA
The practice of yoga can help reduce weight and lower blood pressure as an
adjunctive means of treating hypertension, most favorably in conjunction with
a healthy diet, exercise, and pharmaceutical treatment (Yang 2007).
In studies of adults with high blood pressure, with and without coronary
disease, reductions in medication requirements have been observed among
those participants completing a yoga-based intervention, as compared to con-
trolled counterparts receiving usual care (Yang 2007; Yogendra et al. 2004).
For example, in a study of thirteen hypertensive individuals aged 41–60,
practicing one hour of yoga per day, six days per week, resulted in a significant
drop in blood pressure: systolic dropped from 141.7 to 127.9 mmHg by the
third week and then to 120.7 mmHg by the fourth week (Yang 2007). Even
30 minutes of daily yoga has been shown to decrease blood pressure in studies
involving hypertensive individuals (Selvamurthy et al. 1998)
Table 11.2 Nutritional Supplements for Hypertension

Supplements Daily Intake
Coenzyme Q10 120–150 mg 2x a day
Fish Oil 3–4 grams a day
Nattokinase (NSK-SD) 50–100 mg if dietary natto is not consumed
Magnesium 400–800 mg a day
Organic Garlic 1000 mg if not taken in diet
Hawthorn 1000 to 1500 mg per day
Quercetin 500–1000 mg per day 2x a day
Vitamin D3 2000 units per day
Vitamin B6 100 mg 1–2x a day
Vitamin C 250–500 mg 2x a day

In addition to their antihypertensive effects, mind–body interventions pro-

vide patients with a proactive process through which they may manage their
health, as opposed to passively taking pills. As lack of control over various
aspects of life creates stress, empowerment derived from harnessing control
over blood pressure and health through such lifestyle modification techniques
ultimately improves patients’ blood pressure, health, and longevity.
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12
MIMI GUARNERI AND CHRISTOPHER SUHAR
key concepts
■ The causes of cardiovascular disease are multifactorial, ranging

from inflammation and lipid abnormalities to stress, depression,
anger, and social isolation.
■ An integrative holistic approach to cardiovascular disease
entails healing the whole person: mind, body, emotions, and
spirit.
■ A growing understanding of the science of the human genome,
nutraceuticals, and mind–body medicine is paving the way to
a multidisciplinary approach to individual risk that is personal-
ized, predictive, proactive, and preventive.
■
Introduction
C
ardiovascular disease (CVD) is one of the major progressive lifelong
diseases in the modern era, affecting the lives of one out of two men
and one out of three women. The disease begins silently in adolescence
and slowly progresses in middle age. It results in clinical events starting
after 55 years of age in men and after 65 years of age in women. The Interheart
Study defined the relative risks for acute myocardial infarction of the various
cardiovascular risk factors in a population of 29,972 individuals from fifty-two
different countries (Ogden et al. 2006). Nine risk factors were found to account
for 90 percent of the populations’ attributable risk in men, and 94 percent of
the risk in women (see Table 12.1).
247
Table 12.1. Results of the Interheart Study

Cardiovascular Risk Factor Relative Risk
Smoking 2.87
Elevated Apo B/Apo A1 3.25
Hypertension 1.91
Diabetes 2.37
Abdominal obesity 1.12
Psychosocial factors 2.67
Daily consumption of fruit and vegetables 0.7
Regular alcohol consumption (≥3/week) 0.91
Regular physical activity 0.86
Although Western allopathic medicine excels in the area of acute care, such
as treating heart attacks and providing lifesaving surgeries, it falls short in its
treatment of chronic disease management and prevention. It is in the arena of
prevention and chronic disease management that integrative cardiology has
the opportunity to complete the circle of care, addressing all of the risk factors
for cardiovascular disease from a holistic perspective.
Lifestyle Change Intervention
The causes of CVD are multifactorial, and treatment almost always requires
lifestyle changes and mind–body interventions. Almost all cardiac risk factors
are dependent on lifestyle and environment. Prevention is the best interven-
tion for CVD, yet in a recent survey of primary care physicians and cardiolo-
gists, it was found that discussions of lifestyle including nutrition, exercise,
and psychosocial stressors continue to be poorly addressed (Mosca et al. 2005;
Vogel and Krucoff 2007).
Almost all CVD is closely related to and affected by inflammation, which is
a direct result of obesity, poor nutrition, sedentary lifestyle, and maladaptive
responses to stress and tension. In fact, poor nutrition and physical inactivity
are identified as probably the true leading “actual” causes of death in the
U.S. (Mokdad, 2004). Increasing BMI has been linked to an increasing risk of
diabetes mellitus, hyperlipidemia, and hypertension. Conversely, as the BMI is
lowered, so is the prevalence of all risk factors. Multiple avenues of research
Integrative Approaches to Cardiovascular Disease 249
have shown that lifestyle intervention alone can alter the course of disease. For
example, in the Diabetes Prevention Study, type 2 diabetes was prevented in
high-risk individuals who underwent individualized counseling on weight
loss and physical activity alone, when compared to appropriately matched
controls and patients taking metformin alone (Tuomilehto et al. 2001).
An integrative approach to cardiovascular care broadens the traditional
diagnosis and treatment of disease, utilizing both Western-based diagnostic
tests and pharmaceuticals along with an aggressive focus on all aspects of
health, including nutrition, exercise, and psychosocial stress. In almost all
cases, a comprehensive lifestyle change approach is necessary.
From Hippocrates we learned that “food is medicine.” In fact, a single high-
fat meal transiently impairs endothelial function and blood flow (Vogel,
Corretti, and Plotnick 1997). A very large epidemiologic study evaluated the
effect of nutrition on disease in rural China and the United States. In this study
of over 10,000 individuals, the U.S. fat intake was twice as high, fiber intake
was three times lower, animal protein intake was 90 percent higher. The heart
disease death rate was 16.7-fold greater for men and 5.6-fold greater for
women. The incidence of other diseases were also higher in the U.S. including
cancer, osteoporosis, diabetes, and hypertension (Chen et al. 1990). Importantly,
Asian immigrants to the U.S. reached the American level of heart disease and
cancer deaths within two generations.
In order to fully understand the nutritional status of my patients, a three-
day food diary is used to assess the quantity and quality of calories consumed.
The Department of Agriculture reported an 8 percent increase in food con-
sumption from 1990 to 2000, and the CDC reports that the doubling of
the prevalence of obesity between 1971 and 2000 correlated with a 22 percent
increase in calorie consumption for women and a 9 percent increase for men
(Ogden et al. 2006). Interestingly, despite indications that the percentage of
calories consumed as fat is decreasing, surveys indicate that we are consuming
more calories overall (Eckel and Krauss 1998). Reduction in total caloric intake
and exercise should be emphasized as a first-line approach to weight loss.
Determination of the basal metabolic rate allows a more precise estimate of
calories needed, along with exercise and stress management, to achieve an
ideal body weight.
Simple handouts to guide patients on nutrition choices can be extremely
valuable. It is important to teach patients about the glycemic index; you might
consider providing handouts that label food choices as high, moderate,
and low on the glycemic index. Patients should be taught to eliminate liquid
calories, most notably soda and fruit juice. Our patients are also taught to
eliminate high-fructose corn syrup and trans fatty acids. If sweeteners are
necessary, organic agave nectar or stevia can be used. A plant-based vegetarian
diet is preferred. For those individuals who consume fish, options are sug-
gested that are high in omega-3 fatty acids, low in mercury, and not farm
raised, such as wild salmon and sardines. Foods high in antioxidants are
strongly recommended. Functional foods, which have bioactive properties as
well as nutrient value, are incorporated into the nutrition program. These
include almonds, chocolate, tea, soy, and viscous fibers such as eggplant, oats.
and psyllium. Tea and chocolate are able to reduce free radicals due to their
high concentration of flavonoids. We recommend five cups of green tea daily
to reduce cardiovascular mortality and to lower cholesterol (Kuriyama et al.
2006). Flavonoids, especially those found in green tea, have been shown to
have antithrombotic effects (Son et al. 2004). Consumption of black tea is asso-
ciated with a reduction in acute myocardial infarction (Geleijnse 2002), and
improved endothelial relaxation (Duffy 2001).Supplements, like nutrition and
exercise, play an important role in the prevention of CVD. In my integrative
cardiology practice I use omega-3 fish oil, CoQ10, red yeast rice, vitamin D,
and niacin on a daily basis. I believe that disorders determine treatment and
that a supplement regimen should be tailored to the individual. For example,
those individuals with low HDL and/or high triglycerides will be placed on a
low glycemic index diet, a daily exercise program, omega-3 fish oil, and niacin.
An individual with high LDL may be placed on a low- saturated-fat diet, red
yeast rice, plant stanols, soluble fiber, statin therapy (if indicated), and omega-3
fish oil. Green tea, soluble fiber, exercise, low glycemic/antiinflammatory diets,
and stress management are universal recommendations for health.
Vitamin E and Antioxidants
The Nurses’ Health Study, which was observational in design, concluded a

34 percent reduction in cardiovascular events in subjects taking vitamin E
supplementation (Lopez-Garcia et al. 2004). Since that initial observation,
multiple studies have attempted to evaluate vitamin E in the primary and
secondary prevention of cardiovascular disease. In the primary prevention
project, 4,495 patients were followed for 3.6 years on 300 IU of vitamin E sup-
plementation without demonstrating improvement in cardiovascular morbid-
ity (Sacco et al. 2003). Multiple secondary prevention studies, including HOPE
(Yusef et al. 2000) and GISSI-P (GISSI-Prevenzione Investigators 1999), failed
to demonstrate benefit from vitamin E supplementation. HATS compared
treatment regimens of lipid-modifying therapy and antioxidant-vitamin
therapy, alone and together (Brown et al. 2001). The three-year, double-blind
trial included 160 patients with coronary disease, low levels of HDL-C,
and normal levels of LDL-C. Patients were assigned to one of four treatment
regimens: simvastatin (10-20 mg/day) plus niacin (2-4 g/day); antioxidants;

simvastatin (10-20 mg/day) plus niacin (2-4 g/day) plus antioxidants; or pla-
cebo. The primary end points were arteriographic evidence of change in coro-
nary stenosis, and the occurrence of a first cardiovascular event (fatal/nonfatal
MI, stroke, or revascularization). The average stenosis progressed with placebo
(3.9 percent), antioxidants (1.8 percent), and simvastatin plus niacin plus anti-
oxidants (0.7 percent). There was a 0.4 percent regression with simvastatin plus
niacin alone (p<0.001). In conclusion, the combination of simvastatin plus
niacin greatly reduced the rate of major coronary events (60–90 percent) and
substantially slowed progression of coronary atherosclerosis in patients with
low HDL-C. While HATS further supported the use of niacin for raising HDL
and reducing plaque formation in combination with statin therapy, no further
advantage was seen in the group receiving antioxidants and combination statin–
niacin therapy. These studies did not attempt to assess the inflammatory and
oxidative state of subjects prior to initiation and following therapy.
In a randomized double-blind placebo control trial, subjects received
1600 IU of RRR-alpha tocopherol versus placebo and followed for six months
(Devaraj et al. 2007). Subjects taking the vitamin E had a statistically signifi-
cant reduction in hs-CRP and urinary F2 isoprostanes and monocyte superox-
ide anion and tumor necrosis factor release, compared with baseline and
placebo. Despite this reduction in oxidative and inflammatory markers, no
change was seen in carotid intimal-medial thickness. Multiple trial design
concerns have been raised to explain the inconsistency of the observational
and randomized study data (Blumberg and Frei 2007). These include:
1. Not using the right type of supplement formulation;

2. Not using the correct dosage;
3. Not using a complex antioxidant mixture;
4. Not choosing the right study population; and
5. Not looking at functional biomarkers.
One of the important variables missing from all of these studies is nutri-
tional status. Until biomarkers and nutritional status are included with these
research variables, it is premature to conclude that antioxidants offer no ben-
efit in cardiovascular disease prevention.
Exercise
Exercise is one of the most powerful methods for decreasing cardiac risk and
enhancing health. Looking at patients after myocardial infarction, percutaneous
coronary intervention (PCI), or coronary artery bypass graft (CABG) surgery,

those who participate in a comprehensive exercise rehabilitation program have
a six-fold decrease in cardiac death, as compared to those patients not undergo-
ing cardiac rehabilitation (Taylor et al. 2004). Despite these and many other
findings showing the benefits of exercise, physicians reported spending an
average of eight minutes counseling their patients on lifestyle change at routine
annual visits. Furthermore, less than 5 percent of physicians advise patients to
engage in physical activity at least six days per week, as recommended by
national guidelines.
A provocative study looking at exercise versus angioplasty in patients with
coronary artery disease (CAD) determined by >75% stenosis on angiography
showed that daily exercise over a 12-month period had a lower cardiovascular
event-free survival and equal angina symptom improvement (Hambrecht 2004).
Group exercise also provides a valuable social network, which is one of the most
powerful interventions available to prevent and treat cardiovascular disease.
Invasive Therapies and Statin Therapy
INVASIVE THERAPIES FOR CAD
Coronary artery bypass grafting is an extremely common procedure, yet the

relative gains of its use are limited. The Coronary Artery Surgery Study (CASS)
randomized patients with chronic CAD into a bypass group and a medical
therapy group. In the long-term follow-up of CASS, only 2.1 percent of
bypasses yield improved mortality when compared to medical therapy.
Specifically, this was in patients with left main and left main equivalent disease
(Caracciolo et al. 1995). It is important to note that the medical therapies avail-
able when this study began were nowhere near as comprehensive as currently
available medical treatment including a lack of availability of statins. The rela-
tive gains of medical therapy, if this study were done today, may be found to
be even greater.
STATIN THERAPY
Multiple studies have shown substantial reductions in mortality and proce-

dure rates using statin medications. The Scandinavian Simvastatin Survival
Study (4S) was one of the largest of these studies. The trial enrolled 4,444
patients with known CAD and treated them with Simvastatin. This treatment
alone decreased revascularization procedures by 37 percent; cardiac death
rates and event rates were lowered by 50 percent in the treatment group as well
(Pederson et al. 1994).
STATIN THERAPY VS. INVASIVE PROCEDURES
Multiple studies have shown that there is a benefit in using aggressive lipid
lowering therapy instead of angioplasty in patients with chronic stable angina
(Boden, 2007; Pitt et al. 1999). The AVERT study used 80 mg of Atorvastatin
compared to PTCA for chronic stable angina. The Atorvaststin group had
fewer ischemic events, including stroke, and a longer time period until a first
event (Pitt et al. 1999), thus showing lipid therapy to be preferable in this pop-
ulation. With this and other related studies demonstrating treatment benefit
with medication and lifestyle change, the AHA and ACC made the following
statement: “Based on the data available from randomized trials comparing
medical therapy with PTCA, it seems prudent to consider medical therapy for
the initial management of most patients with Canadian Cardiovascular Society
Classification Class I and II and reserve PTCA and CABG for those patients
with more severe symptoms and ischemia” (Smith et al. 2001).
While statins alone may be preferable to invasive procedures for the patient
with chronic stable angina or CAD without ischemia, statin therapy only
manages one aspect of coronary disease—the lipids. If you take a truly holistic
approach and address diet, exercise, and the patient’s emotional health, the
gains are far greater.
Coronary Artery Disease Reversal
Multiple studies have been done demonstrating that comprehensive lifestyle

change can reverse cardiac atherosclerotic lesions. The majority of this work has
been done by Dean Ornish and his colleagues using the Lifestyle Modification
Program. This program consists of a very low-fat, (10 percent of total calories
consumed) plant-based diet, exercise, yoga, and group support participation.
The following abstracts and comments summarize that work.
Effects of stress management training and dietary

changes in treating ischemic heart disease
This study evaluated the short-term effects of the Lifestyle Modification

Program in patients with coronary heart disease. The study compared the
cardiovascular status of 23 patients who received this intervention with a

randomized control group of 23 patients who did not. After 24 days, patients
in the experimental group demonstrated a 44 percent mean increase in dura-
tion of exercise, a 55 percent mean increase in total work performed, signifi-
cantly improved left ventricular regional wall motion during peak exercise,
and a net change in the left ventricular ejection fraction from rest to maximum
exercise of +6.4%. Also, there was a 20.5 percent mean decrease in plasma
cholesterol levels and a 91 percent mean reduction in frequency of anginal
episodes. In this selected sample, short-term improvements in cardiovascular
status seem to result from these adjuncts to conventional treatment of coro-
nary heart disease (Ornish et al. 1983).
Can lifestyle changes reverse coronary heart disease?

The Lifestyle Heart Trial
In a prospective, randomized, controlled trial to determine whether compre-

hensive lifestyle changes affect coronary atherosclerosis after one year, patients
were assigned to an experimental group asked to follow the Lifestyle
Modification Program or to a usual-care control group. One hundred ninety-
five coronary artery lesions were analyzed by quantitative coronary angiogra-
phy. The average percentage diameter stenosis regressed from 40.0 (SD 16.9)
percent to 37.8 (16.5) percent in the experimental group, yet progressed from
42.7 (15.5) percent to 46.1 (18.5) percent in the control group. When only
lesions greater than 50 percent stenosed were analyzed, the average percentage
diameter stenosis regressed from 61.1 (8.8) percent to 55.8 (11) percent in the
experimental group, and progressed from 61.7 (9.5) percent to 64.4 (16.3) per-
cent in the control group. Overall, 82 percent of experimental-group patients
had an average change toward regression. In summary, comprehensive life-
style changes may be able to bring about regression of even severe coronary
atherosclerosis after only one year, without the use of lipid-lowering drugs
(Ornish et al. 1990).
Gould et al. (1995) conducted a study to quantify changes in size and sever-
ity of myocardial perfusion abnormalities by PET in patients with coronary
artery disease after five years of risk factor modification. The size and severity
of perfusion abnormalities on dipyridamole PET images decreased (improved)
after risk factor modification in the experimental group compared with an
increase (worsening) of size and severity in controls. The percentage of left-
ventricle perfusion abnormalities outside 2.5 SDs of those of normal persons
(based on 20 disease-free individuals) on the dipyridamole PET image of
normalized counts worsened in controls (mean +/- SE, + 10.3% +/- 5.6%) and
improved in the experimental group (mean +/- SE, -5.1% +/ 4.8%) (p=0.02);
the percentage of left ventricle with activity less than 60 percent of the maxi-
mum activity on the dipyridamole PET image of normalized counts worsened
in controls (+13.5% +/ 3.8%) and improved in the experimental group (-4.2%
+/- 3.8%) (p=0.002); and the myocardial quadrant on the PET image with the
lowest average activity expressed as a percentage of maximum activity wors-
ened in controls (-8.8% +/- 2.3%) and improved in the experimental group
(+4.9% +/- 3.3%) (p=0.001). The size and severity of perfusion abnormalities
on resting PET images were also significantly improved in the experimental
group as compared with controls. The relative magnitude of change in size and
severity of PET perfusion abnormalities was comparable to or greater than the
magnitude of changes in percent diameter stenosis, absolute stenosis lumen
area, or stenosis flow reserve documented by quantitative coronary arteriogra-
phy. These studies, though small in size, provide the most insight into the power
of lifestyle change, particularly in coronary artery disease progression.
Additional Cardiovascular Therapies for Consideration
ENHANCED EXTERNAL COUNTERPULSATION (EECP)
EECP uses an inflatable suit that surrounds the lower limbs and expands to
compress the extremities during diastole. In doing so, it mimics the effects
of intra-aortic balloon counterpulsation. This reduces loading conditions in
systole, while increasing coronary perfusion pressures in diastole.
In multiple studies, EECP has been shown to be beneficial in lowering
chronic stable angina by one class, while improving quality of life by 50 per-
cent at a two-year follow-up (Michaels et al. 2004). It has also been shown to
improve exercise tolerance and decrease anti-anginal medication utilization
(Arora et al. 1999; Linnemeier et al. 2003).
An EECP patient registry based on nation-wide data collection demon-
strated the following (Bonetti et al. 2003):
• 69 percent of patients improved by at least 1 Canadian Cardiovascular

Society (CCS) angina class immediately after EECP
• 72 percent had sustained improvement at one-year follow-up.
• Those with the most severe coronary artery disease and those who
had previously undergone a surgical revascularization procedure
(89 percent of patients in the registry) seemed to benefit the most.
• In the long-term follow-up:

EECP improves coronary perfusion and left ventricular systolic
unloading that occurs during a treatment session.

EECP increases blood nitric oxide within one week of treatment
(nitric oxide has important vasodilatory, antiplatelet, antithrom-
botic, and antiinflammatory properties).
It is believed that the sheer force induced by EECP may influence athero-
genesis and angiogenesis by up-regulating the production of growth factors
such as vascular endothelial growth factor and platelet-derived growth factor
(Bonetti et al. 2003).
CHELATION FOR CAD
Chelation is an intravenous therapy with ethylenediaminetetra-acetic acid

(EDTA). The theory is that components of the plaque can be reabsorbed with
treatment. Most practitioners use chelation therapy in combination with life-
style change and supplements. One randomized controlled trial has been con-
ducted to evaluate chelation therapy in coronary artery disease. In that study,
84 patients, with CAD proven by angiography or a documented MI and stable
angina, were randomly assigned to receive infusion with either: weight-
adjusted (40 mg/kg) EDTA chelation therapy (n = 41) or placebo (n = 43). The
treatments were three hours in length per treatment, twice weekly for 15 weeks
and once per month for an additional three months. There was a 27-week fol-
low-up. In this study, there were no differences between chelation and placebo,
in time to ischemia on treadmill testing, exercise capacity, or quality of life
(Knudtson et al. 2002).
Based on this study and other related studies, the AHA presented the
following statement: The American Heart Association has reviewed the
available literature on using chelation to treat arteriosclerotic heart disease.
We found no scientific evidence to demonstrate any benefit from this form of
therapy.
A multicenter NHLBI and NCCAM Trial to Assess Chelation Therapy
(TACT) was started in 2002. This is a placebo-controlled, double-blind
study which will involve 2,372 participants age 50 years and older who
have documented coronary artery disease. This larger trial will enhance
our understanding of chelation therapy as a treatment for coronary artery
disease.
Psychological Risk
Studies by Blumenthal et al. (2005), Dusseldorp et al. (1999), and Schneider et al.
(2005) demonstrated the impact of stress reduction on cardiovascular mortality.
Blumenthal and colleagues (2005) demonstrated, in a five-year follow-up
study, that stress management significantly reduced the risk of cardiovascular
events compared to controls. One hundred and thirty-four patients with CVD
participated in sixteen 1.5-hour sessions on stress management and exercise.
Patients were instructed in biofeedback, a cognitive-social learning model,
and progressive muscle relaxation. For patients with stable ischemic heart dis-
ease (IHD), exercise and stress management training reduced emotional dis-
tress and improved markers of cardiovascular risk more than usual medical
care alone.
Randomized controlled trials on stress reduction with the Transcendental
Meditation technique show reductions in CVD risk factors, morbidity and
mortality (Barnes and Orme-Johnson, 2006; Walton et al. 2004). A systematic
review and metaanalysis of 107 well-designed trials on stress reducing meth-
ods for high blood pressure found that the Transcendental Meditation pro-
gram was associated with significant reductions in systolic and diastolic blood
pressure (Rainforth et al. 2007). This was confirmed by a later metaanalysis
(Anderson et al. 2008) Other meta-analyses have reported reductions in
psychosocial stress factors, smoking and alcohol abuse with Transcendental
Meditation practice (Orme-Johnson and Walton 1998). A series of NIH-
supported RCTs of Transcendental Meditation compared to health education
reported improvements in insulin resistance and autonomic tone in CHD
patients and reduced atherosclerosis, measured by carotid intima-media
thickness [Castillo-Richmond, 2000; Paul-Labrador et al. 2006]. A pooled
analysis of long-term trials with an average follow up of 8 years demonstrated
30% reduction in cardiovascular mortality in patients randomized to
Transcendental Meditation program compared to controls [Schneider et al.
2005]. The Transcendental Meditation program may be a useful adjunctive
therapy in heart failure based on a pilot trial that reported improved func-
tional capacity, reduced depression and enhanced quality of life in the
Transcendental Meditation subjects compared to controls [Jayadevappa et al.
2007].
These clinical results are consistent with cost analysis studies that have
shown that the practice of Transcendental Meditation lowered health insur-
ance utilization, hospital inpatient days, hospital admissions and hospital
outpatient visits, including an 80% reducition in hospitalization rates for

cardiovascular disorders (Orme-Johnson 1987; Herron et al. 2000).
I routinely teach my patients two simple stress management techniques.
The first technique utilizes a simple five-second-in and five-second-out breath
to shift the autonomic nervous system to a more parasympathetic state. Patients
are taught to disengage from stress and to not engage in the stress of others.
Emphasis is placed on changing one’s response to and perception of events.
They are also taught to use a mantra on a daily basis to settle their mind.
Patients are taught to use their mantra when they need it and when they
do not. A list of possible mantras is offered such as “shalom,” “Jesus prince
of peace,” “Om Namo Narayani,” depending on the individual’s religious and
personal preferences. I personally encourage all of my patients to learn to
meditate, as I believe meditation is one of the true paths to transformation.
The form of meditation varies with the individual.
Guided imagery is a therapeutic technique that allows an individual to use
his or her own imagination to achieve desirable outcomes, such as decreased
pain perception and reduced anxiety. Imagery has been successfully used as
an intervention in patients with pain, cancer, insomnia, post-traumatic stress
disorder, and surgery. Guided imagery has been studied as a pre- and post-
surgical intervention. A study conducted by the Cleveland Clinic with cardio-
thoracic surgery patients demonstrated that both pain and anxiety decreased
significantly with guided imagery (Kshettry et al. 2006). In addition, by
augmenting pain treatment, guided imagery decreased the length of hospital-
ization by two days on average.
Qigong and Tai Chi
Qigong is a form of traditional Chinese medicine that implements coordina-

tion of different breathing patterns with a variety of physical postures
and body motions. It is a very safe, low-impact form of exercise which can be
performed by almost anyone, including patients with exercise-limiting dis-
eases or conditions. This practice can be implemented at home on a daily basis.
While Qigong is often taught for general health maintenance purposes, it also
can be used as a therapeutic intervention where the effectiveness has been
studied for disorders such as congestive heart failure, chronic respiratory dis-
eases, hypertension, and generalized stress and anxiety. In an NIH-sponsored
pilot trial (Yeh et al. 2004), 30 patients with stable chronic heart failure
(ejection fraction <40% and New York heart association class 2) were random-
ized to receive either 12 weeks of Tai Chi training or usual care. The patients
receiving Tai Chi had a statistically significant increase in quality-of-life scores,
six-minute walk distances, and a reduction in serum B-type natriuretic

peptide levels.
Biofeedback
Biofeedback is a mind–body therapy which involves monitoring and display-

ing physiological function such as muscle tension, skin temperature, and heart
rate. Patients are taught relaxation techniques including deep breathing and
muscle relaxation. Biofeedback provides an objective measurement of the
impact of these therapies on the autonomic nervous system and is useful to
optimize results. Lehrer, Vaschillo, and Vaschillo (2000) demonstrated
that training subjects to maximize peak heart rate differences via biofeedback
could increase homeostatic reflexes, lower blood pressure, and improve lung
function. In cardiovascular patients, biofeedback has been used for stress
reduction, blood pressure control and increase in heart rate variability.
Biofeedback has been studied in patients with essential hypertension and
shown to effectively lower both systolic and diastolic blood pressure (Nakao
et al. 1997; Nakao et al. 2000). Where low heart rate variability is an indepen-
dent risk factor for sudden cardiac death, all-cause death, and cardiac event
recurrence, studies support the use of biofeedback and breathing retraining as
a treatment to reverse the decrease in heart rate variability that which occurs
with heart disease (Bigger et al. 1993; Kleiger et al. 1987). We examined the use
of biofeedback in patients with coronary artery disease and found that this
technique increases heart rate variability, thus supporting biofeedback as a
possible tool for improving cardiac morbidity and mortality (Del Pozo et al.
2004).
Conclusion
Western allopathic medicine excels at treating advanced disease through the

use of diagnostic testing, surgery, and pharmaceuticals. Although all of these
interventions may be life-saving, they are focused on a diseased care model in
which intervention is initiated after the ensuing event. Integrative medicine
offers cardiologists the chance to combine the best of Western allopathic med-
icine with equally strong interventions that focus on lifestyle change. Patients
are evaluated from a holistic perspective with all risk factors addressed from a
physical, emotional, mental, and spiritual perspective. The ability to motivate
patients and empower them with knowledge to take responsibility for their
health in partnership with their healthcare provider is at the core of integrative
medicine philosophy. As we screen patients for dyslipidemia, inflammation,

diabetes, and hypertension we need to add depression, stress, anger, anxiety,
and social isolation to the list. Once we identify people at risk we need to have
programs and centers of excellence that can guide an individual in proper
nutrition counseling, the use of dietary supplements, exercise, and mind–body
interventions.
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13
Integrative Approaches to Heart Failure
ELIZABETH KABACK , LEE LIPSENTHAL
AND MIMI GUARNERI
key concepts
■ Coronary artery disease is the number-one cause of congestive

heart failure. The development of coronary artery disease
and, therefore, congestive heart failure is preventable through
lifestyle change.
■ Nutrition, nutraceuticals, exercise, and changing one’s response
to stress and tension are key components in coronary disease
prevention.
■ Psychosocial factors such as anger, stress, and social isolation
are important determinants of cardiovascular events.
■
Introduction
A
n estimated 550,000 individuals are diagnosed with heart failure each
year. More than 5 million Americans suffer from heart failure, which
is the leading cause of hospitalizations in the United States. In the
year 2007, it was estimated by the American Heart Association that approxi-
mately 432 billion dollars was spent on cardiovascular disease. An estimated
33 billion dollars was spent on heart failure alone. While the mortality rate for
acute myocardial infarction has decreased, it has increased for heart failure,
because more people are living with chronic heart problems that result in heart
failure. The mortality statistics for heart failure are frightening. An astounding
percentage (80 percent of men and 70 percent of women under the age of 65)
diagnosed with heart failure will die within eight years (Rosamond et al. 2007).
265
It is therefore not surprising that a diagnosis of heart failure has a detrimental

impact on a patient. Just the term—heart failure—is terrifying for patients
and their families. We try to avoid this term whenever possible, choosing
instead words like heart recovery and heart health. We have changed the name
of the Scripps Heart Failure Clinic to the Heart Recovery Clinic. The latter
confers a sense of hope, which is crucial to the healing process.
Heart failure is the final common pathway of varying etiologies, including
coronary artery disease, hypertension, obesity, diabetes, congenital cardiomy-
opathies, idiopathic dilated cardiomyopathies, valvular heart disease, preg-
nancy, viral or bacterial infections, inborn errors of metabolism, and drug and
alcohol abuse. In simple terms, it is a condition whereby the heart is unable to
pump enough oxygenated blood to meet the body’s demand. In technical
terms this is described as an oxygen/demand mismatch. This leads to a con-
stellation of symptoms including fatigue, shortness of breath, fluid retention,
and in many instances, kidney dysfunction.
Given the number of patients diagnosed with heart failure each year, there
is a need to address both secondary as well as primary prevention. Risk factors
contributing to disease development include hypertension, diabetes, dyslipi-
demia, obesity, smoking, aging, stress, genes, valvular abnormalities, and
toxins. If addressed early, the development of disease may be slowed or entirely
avoided by simple lifestyle change recommendations, in most cases.
Fortunately, there are many treatments for heart failure that have been
shown to improve quality of life. Conventional treatments include renin-
angiotensin-aldosterone system antagonists, adrenergic blockers (commonly
referred to as beta blockers), diuretics, nitrates, ionotropes, as well as sodium
and volume restriction. Complementary approaches include herbal or botani-
cal supplementation, minerals, vitamins, amino acids, fish oil, meditation
or guided imagery, and Tai Chi. Goals common to both integrative and con-
ventional therapies include nutritional counseling, weight management, and
exercise.
The patient–physician relationship is crucial and can have a tremendous
impact on the health and well-being of the patient. Patients who are cared for,
feel supported by, and trust the medical judgment of their physician will almost
always have better outcomes. Setting short-, medium- and long-term goals is
also very helpful. They can aid in the setting or resetting of expectations of a
patient, the patient’s family, and the physician. These goals should be individu-
alized depending on the patient’s functional status and willingness to change.
The medical management of the patient who is acutely sick is different than
the management of one who is chronically well compensated. The acutely ill
patient requires conservative traditional therapies. Short-term goals are clearly
defined and may include aggressive diuresis and intravenous ionotropic support.
Integrative Approaches to Heart Failure 267
Once beyond the acute care period, a shift in focus to other issues harnessing
mind–body interactions is helpful, including Healing Touch. Healing touch
treatments are ideal for patients with heart failure because they promote a state
of deep relaxation, which decreases stress hormones. The Healing Touch treat-
ments allow for healing on all levels: emotional, mental, spiritual, and physical,
providing a great complement to Western allopathic methods. Once dis-
charged from the hospital, an integrative approach to heart failure like coro-
nary artery disease gives a person the greatest opportunity to achieve optimum
health, well-being and healing. Long-term goal setting might include conven-
tional medications, herbs, and supplements, as well as dietary and lifestyle
changes including exercise, Tai Chi or guided imagery and meditation.
Pathophysiology
The pathophysiology of heart failure is multifactorial, including coronary artery

disease, hypertension, genetic factors, idiopathic, and post-viral syndromes just
to mention a few causes. Overlaying all of these cardiac insults is prolonged
exposure of the heart to stress hormones. Calcium influx into myocytes is
triggered, the cells of the heart hypertrophy, and interstitial fibrosis ensues. In
ischemic heart disease, scar tissue and fibrosis result in left ventricular remodel-
ing and dysfunction. Myocardial energy demands increase, cardiac output
decreases, and sodium and water retention occurs due to the kidneys’ response to
perceived hypovolemia. The kidneys activate the renin-angiotensin-aldosterone
system (RAAS); catecholamines and inflammatory cytokines such as tumor
necrosis factor-alpha (TNF-a) increase. This leads to additional salt and water
retention, resulting in congestion of the capillaries of the lung, in turn causing
leakage of fluid into the alveolar spaces and poor gas exchange, otherwise
known as pulmonary edema or congestive heart failure.
Classification of Heart Failure
There are two classification systems of heart failure. The first is the New York
Heart Association (NYHA) system which classifies patients based on func-
tional capacity (Table 13.1). Many patients do not come to medical attention
until they are Class II, and often times Class III. This is easily understood, as a
person with Class I heart failure is asymptomatic, having no physical limita-
tions. In Class II, a person has slight limitation of physical activity. They are
comfortable with normal daily physical activity, but moderate exercise such as
walking long distances or inclines or climbing two flights of stairs is limited by
Table 13.1. New York Heart Association Functional Classification (ACC/AHA, 2005)
Class Patient Symptoms
Class I No limitation of physical activity. Ordinary physical activity does not cause
(Mild) undue fatigue, palpitation, or dyspnea (shortness of breath).
Class II Slight limitation of physical activity. Comfortable at rest, but ordinary

(Mild) physical activity results in fatigue, palpitation, or dyspnea.
Class III Marked limitation of physical activity. Comfortable at rest, but less than
(Moderate) ordinary activity causes fatigue, palpitation, or dyspnea.
Class IV Unable to carry out any physical activity without discomfort. Symptoms of
(Severe) cardiac insufficiency at rest. If any physical activity is undertaken,
discomfort is increased.
shortness of breath (or dyspnea), resulting in fatigue. Marked limitation of

normal daily physical activity—such as walking short distances on level
ground, walking a short flight of stairs, or grocery shopping—by fatigue and
dyspnea places a patient in Class III. Lastly, symptoms of shortness of breath
with minimal activity such as simply getting dressed or bathing is considered
Class IV. This classification system falls short in the detection of early disease;
it does not allow for primary prevention as it identifies those who already have
significant secondary symptoms.
In an attempt to better define the progression of disease, the American
Heart Association (AHA) and American College of Cardiology (ACC) devel-
oped a new classification system (Table 13.2). This classification enables the
physician to identify patients who are at risk of disease development, allowing
for earlier intervention and primary prevention in the hope of intervening
before disease has occurred. For example, a Stage A patient may have a history
of hypertension, diabetes mellitus, coronary artery disease, and\or family
history of cardiomyopathy with no symptoms of heart failure. Stage B would
be an individual who has structural heart disease (myocardial infarction, left
ventricular dysfunction, or valvular heart disease) and no symptoms of heart
failure. Those with structural heart disease and symptoms of heart failure
including shortness of breath, dyspnea on exertion, fatigue, and exercise
intolerance would be included in Stage C. Lastly, those who have significant
symptoms at rest or with activity despite maximal medical therapy fall into
Stage D. The two different classification systems are often used together to
provide insight into functional capacity as well as diagnostic and therapeutic
intervention.
An integrative approach to heart failure should be primarily directed at
prevention. There are many forms of heart failure including systolic, diastolic,
Table 13.2. American College of Cardiology/American Heart Association

Classification of Chronic Heart Failure (ACC/AHA, 2005)
Stage Description
A—high risk for developing At risk of HF but without structural heart disease or
heart failure HF symptoms
B—asymptomatic heart failure Structural heart disease but without signs or

symptoms of HF
C—symptomatic heart failure Structural heart disease with prior or current

symptoms of HF
D—refractory end-stage Refractory HF requiring specialized intervention

heart failure
HF = Heart Failure
a combination of systolic and diastolic, acute, chronic, and left- or right-sided.

This chapter is written specifically with systolic heart failure in mind, where
the left ventricular ejection fraction (the volume of blood ejected from the
heart with each beat) is ≤45%.
Conventional Medicines
DIGITALIS
Digoxin is a botanical isolated from the foxglove plant (Digitalis purpurea),

which is typically used in the conventional setting to treat heart failure. Many
studies demonstrate that digoxin decreases hospital readmission rates and, if
discontinued, is associated with worsening heart failure symptoms (Adams
et al. 1997; Packer et al. 1993; Uretsky et al. 1993). Fewer studies have demon-
strated the effects of digoxin discontinuation on mortality and morbidity.
Ahmed et al. (2007) retrospectively used multivariable Cox-regression
analysis to determine the effect of discontinuation of digoxin versus various
serum digoxin levels on all-cause mortality and hospitalization within the first
40 months in the original DIG study (Digitalis Investigation Group 1997).
Thirty-eight percent of patients whose long-term digoxin therapy was discon-
tinued, 32 percent of patients in the low-serum digoxin concentration group,
and 45 percent of patients in the high-serum digoxin concentration group
died of all-cause mortality. All-cause hospitalization occurred in 70 percent
of patients in the digoxin discontinuation group, in 66 percent of patients in
the low-serum digoxin concentration group, and 69 percent of those in the

high serum digoxin concentration group (Ahmed et al. 2007).
ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS
ACE inhibitors suppress the renin-angiontensin-aldosterone system by inhib-

iting the conversion of angiotensin I to angiotensin II. Numerous studies
have shown that ACE inhibitors slow progression of heart disease, favorably
affect left-ventricular remodeling, and improve overall prognosis, including
morbidity and mortality (CONSENSUS Trial Study Group 1987; Pfeffer MA,
et al. 1992; Garg and Yusuf 1995; SOLVD Investigators 1991). Typically
used agents include captopril, enalapril, fosinopril, lisinopril, ramipril, tran-
dolapril, and quinapril. Side effects are many and include, but are not limited
to, worsening kidney function (increase in creatinine), electrolyte disturbances
(hyperkalemia), hypotension, angioedema, and ACE-induced cough (second-
ary to increased bradykinin levels). Cough, however, should be evaluated to
rule out congestive heart failure exacerbation. ACE inhibitors are considered
a mainstay in conventional practice and should be used in all cases of heart
failure except when contraindicated, as described above.
ANGIOTENSIN RECEPTOR BLOCKERS (ARB)
ARBs provide additional inhibition of the renin-angiontensin-aldosterone

system through the binding of the angiotensin II receptor. Similar to ACE
inhibition, ARBs improve morbidity and mortality, favorably affect left ventric-
ular remodeling, and have been shown to increase cardiac output. Importantly,
they do not cause the cough sometimes associated with ACE inhibition. Side
effects are similar to those for ACE inhibitors, and include renal dysfunction
(increase in creatinine), electrolyte disturbance (hyperkalemia), hypotension,
angioedema, and a drop in white blood cell counts (Cohn and Tognoni 2001;
McKelvie et al. 1999; Pitt et al. 2000; Young et al. 2004). In general ARBs are
well tolerated; examples include candesartan, eprosartan, irbesartan, losartan,
olmesartan, telmisartan, and valsartan.
ALDOSTERONE ANTAGONISTS
Spironolactone (nonselective) and eplerenone (selective) are aldosterone

antagonists. Both have been shown to reduce the readmission rates and risk of
sudden death when added to other conventional heart failure medications.

Although usage has been demonstrated to be safe, due to potential electrolyte
abnormalities, caution is advised when starting these drugs. Renal function
should be evaluated prior to the initiation, and all potassium supplementation
discontinued, as both can promote hyperkalemia (Ezekowitz and McAlister
2009; Pitt et al. 1999; Pitt et al. 2003; Pitt et al. 2006; Pitt et al. 2008; RALES
Investigators 1996).
BETA-BLOCKADE
In the past, treatment of heart failure with beta-blockade was contraindicated.

However, in the mid- to late 1990s, beta-blockade alone, or when added to
ACE or ARB, was shown to be beneficial and is now considered standard of
care in the treatment of heart failure. Beta-blockers favorably affect morbidity
and mortality (decreasing the incidence of sudden death), decrease hospital
readmission rates, and improve cardiac output and quality of life. They rees-
tablish neurohormonal balance, blunting the ill effects (improving left-ven-
tricular function) of catecholamine bombardment on the heart. Beta-blockage
usage in Class IV/Stage D, or decompensated chronic heart failure, is con-
traindicated due to the possibility of further worsening heart failure. However,
once an acute CHF exacerbation has resolved, one can consider introducing
beta-blockade. Beta-blockers that have been shown to be beneficial include
metoprolol succinate extended release, carvedilol, and bisoprolol. Some more
common side effects include worsening heart failure, bradycardia, hypoten-
sion, and fatigue (CAPRICORN Investigators 2001; MERIT-HF Study Group
1999; Packer et al. 1996; Packer et al. 2001; Packer et al. 2002; Poole-Wilson
et al. 2003; Shibata, Flather, and Wang 2001).
Supplements in CHF
HAWTHORN
Hawthorn (Crataegus monogyna or Crataegus laevigata) is a popular herb

used as an adjuvant treatment in mild heart failure. The flower and leaf are
considered to be the most therapeutic parts of the plant and recommended for
use by the German Commission E. Active constituents are considered to be
flavonoids and oligomeric proanthocyanidins. Cardiovascular effects include
positive inotropic effects, negative chronotropic effects, vasodilatory proper-
ties (both increasing coronary artery blood flow and decreasing peripheral
vascular resistance), antioxidant properties, angiotensin converting enzyme

inhibition, and antiarrhythmic activity (Chang et al. 2002; Loew 1997). Lastly,
immunomodulatory effects have also been implicated, but not clearly estab-
lished (Bleske et al. 2007).
Two metanalyses suggest that hawthorn is superior to placebo as adjuvant
treatment in NYHF class I-III heart failure. The first of the two studies included
eight (totaling 632 patients) and the second 14 (totaling 855 patients) small
randomized, double-blind, placebo-controlled trials. In both metanalyses,
all included studies were required to use a monopreparation of hawthorn,
although the dosage used varied between 600–1800 mg/day. Primary end
points were not the same in all studies. Some used maximum workload as a
primary end point, while others used the six-minute walk test or a combina-
tion. The authors concluded in both metanalyses that there was a trend toward
significance in favor of hawthorn (Pittler, Schmidt, and Ernst 2003; Tauchert,
2002). While Pittler et al. in their metaanalysis concluded that there was a
favorable trend toward significance in heart failure symptoms and left-ventric-
ular ejection fraction (LVEF), authors of the primary studies felt hawthorn did
not have a measurable substantial benefit on submaximal exercise capacity, LV
function, or quality of life in patients with heart failure (Liu, Konstam, and
Force 2005). Still, in a second original trial called SPICE (Survival and
Prognosis: Investigation of Crataegus Extract WS 1442 in CHF), the authors
concluded a neutral effect on heart failure outcome. The primary end point
was defined as a composite of sudden cardiac death, death due to progressive
heart failure, fatal MI, nonfatal MI, or hospitalization due to HF progression.
The primary end point was measured at 24 months in patients treated with
conventional heart failure medications plus hawthorn, versus conventional
medications and no hawthorn. The results were not found to be significant,
revealing rates of 28 percent for actively treated patients versus 29 percent
for controls. It was concluded, however, that hawthorn could safely be added
to standard heart failure medications without negative effect (Holubarsch
et al. 2000).
Hawthorn was reasonably well tolerated, with the most commonly reported
side effects being dizziness, vertigo, and nausea. However, gastrointestinal
complaints, fatigue, sweating, rash, palpitations, headache, sleeplessness, agi-
tation, and circulatory disturbances have been reported as well (Pittler,
Schmidt, and Ernst 2003; Tauchert, 2002). Hawthorn has the potential to cause
hypotension and should be used with caution with conventional medications
that lower blood pressure. Potential adverse drug–herb interactions may exist
between hawthorn and conventionally used pharmaceuticals including
anticoagulants, cardiac glycosides, and antihypertensives (Chang et al. 2002).
Until further double-blind prospective randomized controlled trials have been
completed, the usage of hawthorn with conventional heart failure medications

should be undertaken with care.
L-CARNITINE
L-Carnitine (or Propionyl L-Carnitine [PLC]) is a key player in cellular energy

production. It functions to shuttle free fatty acids from the cytoplasm to the
mitochondria, where beta oxidation to adenosine tri-phosphate (ATP) occurs
(Arseian M.A.,1997), and cellular energy. L-carnitine is most highly concen-
trated in the heart and skeletal muscle—organs with high fatty acid metabo-
lism and energy requirements. It has been suggested that chronic administration
of PLC improves left-ventricular function, improves exercise time and lowers
peripheral vascular resistance (Mancini M., 1992; The Investigators of the
Study on Propionyl-L-Carnitine in Chronic Heart Failure., 1999; Soukoulis
et al. 2009). In the acute setting it has been shown to decrease pulmonary
artery and pulmonary wedge pressures (Anand I., et al. 1998). PLC is a reason-
able adjunct to other therapies with no known side effects. The recommended
dose is 1–3 gm/day.
D-RIBOSE
D-Ribose is a pentose sugar. It is a substrate involved in the salvage and de

novo biochemical pathways that are involved in the synthesis of ATP. It has
been shown that the infusion of D-ribose following an ischemic event improves
recovery of heart function in a rat model (Pasque et al. 1982). A prospective
feasibility study examined quality of life, functional capacity, and echocardio-
graphic parameters that assessed myocardial function of D-ribose in heart
failure patients. Quality of life and myocardial function were statistically
shown to be improved. In particular, diastolic dysfunction (the relaxation
phase or filling phase of the heart) was improved (Omran et al. 2003). Larger
studies are warranted.
COENZYME Q10
Coenzyme Q10 (CoQ10), a ubiquinone, is a constituent of the respiratory chain

in the mitochondrial cell membrane. It plays a key role in oxidative phosphory-
lation, assisting in the mitochondrial synthesis of adenosine triphosphate,
or cellular energy. It is also a potent antioxidant, acting at both the cellular
and subcellular levels. Lastly, it has been shown to stabilize cell membranes.
On the basis of its antioxidant properties and its role in energy production,
CoQ10 has been used to treat a wide variety of cardiovascular disorders.
There is conflicting evidence for the benefits of CoQ10 in the treatment of
heart failure, hypertension, and ischemic heart disease. The mechanism of
these effects is multifaceted, with increased energy production, protection
against lipid peroxidation, and attenuation of ischemic injury all contributing
to potential improvements following CoQ10 therapy. CoQ10 is decreased in
the myocardial cells of patients with heart failure. The extent of cellular defi-
ciency has been correlated with the clinical severity of heart failure (Folkers
et al. 1985; Mortensen 1993). Plasma CoQ10 concentrations have been shown
to be an independent predictor of survival in patients with acute congestive
heart failure exacerbation. The implication that CoQ10 deficiency may be
detrimental to the outcome of patients with CHF suggests that there is reason
to examine the possible benefits of supplementation with intervention trials
(Molyneux et al. 2008). A small randomized, double-blind, placebo-controlled
trial compared the effects of oral CoQ10 (200 mg/d) versus placebo over
six months. Parameters examined included left-ventricular ejection fraction,
peak oxygen consumption, and exercise duration in patients with New York
Heart functional class (NYHF class) III-IV symptoms. No benefit was observed
in the CoQ10-treated group (Khatta et al. 2000). In direct contrast, a second
study with a similar patient population reported an improvement in ejec-
tion fraction following the administration of 100 mg CoQ10 (Langsjoen,
Vadhanavikit, and Folkers 1985). A third study involving NYHF class II-III
patients in a double-blind, placebo-controlled cross-over design used oral
CoQ10 at 100 mg three times daily. Exercise training, peak oxygen consump-
tion, left-ventricular contractility as measured by systolic wall thickening
score (SWTI), and endothelial dependent relaxation were examined. Exercise
capacity, LV contractility, and endothelial function were shown to improve
(Belardinelli et al. 2006). Still other studies have noted improvement in pul-
monary capillary wedge pressure (Munkholm et al. 1999), improvement in
NYHA functional class (Keogh et al. 2003) and decreased hospitalization as
well as decrease in life threatening pulmonary edema (Morisco et al. 1993)
Of note, ejection fraction and outcome measures examined were different in
each study. These inconsistencies may explain the controversial results noted
in the literature, and support the need for large standardized double-blind
randomized control trials to further elucidate the true efficacy of CoQ10 in
heart failure. Trials involving CoQ10 supplementation use doses ranging from
60-300mg/day (Soukoulis et al. 2009).
In general, CoQ10 is well tolerated. Its side effect profile is relatively benign.
No major adverse side effects have been reported in the literature. Minor side
effects reported include: gastric upset (including diarrhea, nausea, vomiting,

appetite suppression, and epigastric discomfort in < 1 percent of cases) and
rash. Side effects appear to occur at larger doses (Pittler, Schmidt, and Ernst
2003; Tauchert, 2002; see also www.naturaldatabase.com). Based on available
data, the cost–benefit ratio appears reasonably in favor of its use in patients
with congestive heart failure.
MAGNESIUM
Magnesium is used to treat and prevent hypomagnesemia. It is used to treat

heart failure for a number of reasons, the first of which is simply poor dietary
intake. Loop diuretics used in the treatment of heart failure increase the
urinary excretion of magnesium, resulting in low blood levels. Magnesium
is effective in the treatment of arrhythmias that are often seen in heart failure,
including ventricular tachycardia. One study demonstrated that replacing
magnesium alleviated these arrhythmias (Ceremuzyński et al. 2000).
Aldosterone antagonist diuretics, such as spironolactone, have been shown to
increase plasma and erythrocyte magnesium concentrations and decrease
magnesium transport out of the cell. This was shown to decrease heart rate
and premature ventricular contractions, and lower the risk of atrial fibrilla-
tion and atrial flutter (Gao et al. 2007). Without sufficient magnesium
levels the heart cannot pump adequately, as magnesium is intimately involved
in the production of ATP, or cellular energy. One small study examined
the influence of micronutrients (including magnesium) on left ventricular
function, proinflammatory cytokine levels (TNF-alpha and its soluble recep-
tors), and quality of life. In a double-blind, randomized fashion, patients
received either placebo or micronutrient for nine months. Left ventricular
function and quality of life was shown to improve, while inflammatory cytokine
levels were not significantly changed (Witte et al. 2005). Although further
research is necessary to fully understand the effects of magnesium, in our clin-
ical practice it is a key micronutrient supplement in patients with normal renal
function.
THIAMINE
Thiamine is a water-soluble vitamin. It is also known as vitamin B1. Dietary

sources include nuts, citrus fruits, rice, seeds, beef, pork, legumes, brewer’s
yeast, and whole grains. Very little thiamine is stored in the body, and there-
fore it can be depleted within a couple of weeks. Chronic severe thiamine
deficiency can result in cardiovascular, skeletal muscle, gastrointestinal, brain,

and nervous system pathology. “Wet” beriberi affects the cardiovascular
system, causing heart failure through peripheral vasodilation and activation of
the rennin-angiotensin-aldoserone system. Studies have shown that loop
diuretics (such as furosemide) lead to the depletion of thiamine (Seligmann
et al. 1991; Zenuk, 2003). In fact patients with NYHF functional class III/IV
heart failure have significantly higher thiamine deficiencies than those with
NYHF functional class I/II heart failure (Soukoulis et al. 2009). Ironically, the
very treatment used to treat heart failure (diuretic therapy) is possibly contrib-
uting to left ventricular dysfunction. Heart failure patients tend to have poor
nutrition, and it would logically follow that supplementation with thiamine
would improve function (Wooley 2008). Additional large studies are needed to
examine the potential beneficial effects of thiamine replacement in patients
with heart failure.
POLYUNSATURATED FREE FATTY ACIDS (PUFA)
Omega-3 Fatty Acids
Several studies have demonstrated the favorable effects of omega-3 fatty acids
in treating cardiovascular disease, including dyslipidemia, coronary artery
disease, sudden death due to arrhythmia, and most recently heart failure.
Consuming two servings of fatty fish per week seems to reduce the risk of
developing cardiovascular disease in primary prevention (Ascherio et al.
1995). Cold-water fish such as salmon, sardine, trout, herring, kipper, mack-
erel, and to a lesser extent shellfish including scallops, oysters, and shrimp
contain omega-3 fatty acid or n-3 polyunsaturated fatty acids (PUFA).
Specifically, these fatty acids include eicosapentaenoic acid (EPA) and docosa-
hexaenoic acid (DHA). Consuming 1gm/day of omega-3 fatty acids (three
ounces of fatty fish) seems to decrease the risk of recurrent myocardial infarc-
tion, sudden death, stroke, and progression of atherosclerotic disease (second-
ary prevention) (Burr et al. 1989; GISSI-Prevenzione Investigators 1999).
A recent large-scale, double-blind, placebo-controlled multicenter trial (the
GISSI-HF trial) showed mortality benefit in heart failure—specifically with
NYHF class II-IV patients who took 1gm of omega-3 fatty acids daily. It was
demonstrated that 56 patients needed to be treated for a median of 3.9 years to
avoid one death, or 44 patients required treatment to avoid one major cardio-
vascular event such as death or a cardiac-induced hospital admission
(GISSI-HF Investigators et al. 2008).
Omega-3 fatty acids inhibit platelet activity (but to a lesser degree than
aspirin) by inhibiting platelet aggregation, and cause modest vasodilation by
inhibiting the synthesis of thromboxane A2 and increasing the production of
prostacyclin. Omega-3s are well known for their potent antiinflammatory
effects, as they suppress the expression of proinflammatory cytokines and
leukotrienes and are used in many inflammatory states, including cardiovas-
cular disease. They have additional immuno-modulating effects by inhibiting
cell adhesion molecules, resulting in decreased endothelial cell activation.
The vasodilatory and positive endothelial cell effects may contribute to the
increased survival noted in heart failure. However, stabilization of the myocar-
dial cell membrane by the incorporation of omega-3s is likely to have reduced
electrical excitability of the myocyte. This in turn decreases the incidence of
arrhythmic death.
Fish oil by oral administration is in general well tolerated. The most common
side effects include belching, halitosis, heartburn, nausea, loose stool and rash.
Taking supplements that are frozen or with meals has been reported to decrease
the incidence of belching (Harris, 2004). There is potential for increased bleed-
ing, bruising, and possible hemorrhagic stroke with 3 gm/day or more of ome-
ga-3 due to platelet inhibition (Pedersen et al. 1999). The potential for platelet
inhibition is greatly affected by conventional medications such as aspirin and
Plavix. We routinely use fish oil as an antiinflammatory/antiarrhythmic agent
and for hypertriglyceridemia. Fish oil is also added to statin therapy at 1800
mg EPA following the results of the JELIS trial, which demonstrated a 19%
reduction in cardiovascular events (Yokoyama, 2003).
L-ARGININE
Studies examining the effects of the amino acid L-arginine on heart failure are
small but the results are promising, and certainly suggest the need for further
research. Given the activation of the renin-angiotensin-aldosterone axis in
heart failure and resultant endothelial cell dysfunction, it is not surprising that
l-arginine would be effective. L-arginine is the substrate for nitric oxide syn-
thetase, whose end product nitric oxide—otherwise known as endothelium-
derived relaxation factor (EDRF)—is a potent vasodilator. Studies have
demonstrated that positive vasodilatory effects may increase coronary artery
blood flow and decrease peripheral vascular resistance, resulting in increased
cardiac output and improved organ perfusion. The exact cellular mechanism by
which this occurs is unknown, but may be secondary to increased production
of nitric oxide (EDRF), resulting in vasodilation or reducing the concentration
of circulating endothelin, a potent vasoconstrictor (Rector et al. 1996). It has

been shown that the production of EDRF is impaired in patients with heart
failure (Katz et al. 1999). Presumably because of the positive effects of l-argin-
ine on EDRF production, the following clinical effects have been shown:
1. Improved kidney function (Watanabe, Tomiyama, and Doba 2000).

2. Improved exercise capacity (Bednarz et al. 2004; Rector et al. 1996).
3. Increased cardiac output and stroke volume.
4. Decreased heart rate and systemic vascular resistance (Bocchi et al.
2000; Koifman et al. 1995).
L-arginine doses of 3–8 gm/day in general do not cause significant gastro-

intestinal side effects. However, at higher doses side effects include abdominal
pain, bloating, and diarrhea (Grimble 2007). L-arginine can also exacerbate
gout and asthma and cause other allergic reactions resulting in airway inflam-
mation (King et al. 2004; Resnick et al. 2002; Sapienza et al. 1998). Bioavailability
may vary between preparations.
DIURETICS
Dandelion (Taraxacum Officinale) has been used in heart failure for its diuretic
effect. It has been studied in animal models with mixed results, and further
evaluation in humans is needed. It has been traditionally used for gastro-
intestinal maladies as well as for its antiinflammatory properties. Other natu-
ral medicines used in heart failure but not yet proven to be effective or safe
include corn silk and stinging nettle (see www.naturaldatabase.com; www.
nlm.nih.gov).
Nutrition
Multiple diets have been tested in patients with coronary artery disease (CAD)
to evaluate the relative benefits in risk factor reduction and cardiovascular
adverse events. Preventing CAD is the best way to prevent congestive heart
failure.
The relationship between incident heart failure (death or hospitalization)
and intake of seven food categories (whole grains, fruits and vegetables,
fish, nuts, high-fat dairy, eggs, and red meat) were investigated in the
Atherosclerosis Risk in Communities (ARIC) Study, an observational cohort
of 14,153 African-American and Caucasian adults, age 45 to 64 years, sampled
from four American communities. Between baseline (1987–1989) and Exam 3

(1993–1995), dietary intake was based on responses to a 66-item food fre-
quency questionnaire. During a mean of 13 years, 1,140 heart failure hospital-
izations were identified. After multivariable adjustment (energy intake,
demographics, lifestyle factors, prevalent cardiovascular disease, diabetes,
hypertension), heart failure risk was lower with greater whole-grain intake
(0.93 [0.87, 0.99]), but heart failure risk was higher with greater intake of eggs
(1.23 [1.08, 1.41]) and high-fat dairy (1.08 [1.01, 1.16]). These associations
remained significant independent of intakes of the five other food categories,
which were not associated with heart failure. The authors concluded that
whole-grain intake was associated with lower heart failure risk, whereas intake
of eggs and high-fat dairy were associated with greater heart failure risk, after
adjustment for several confounders (Nettleton 2008).
Decreasing salt intake, often in the range of 2 grams of sodium per day, is
felt to be beneficial (Hunt S. A., et al. 2001). In addition, the patient with isch-
emic cardiomyopathy and resultant heart failure should follow a low-saturat-
ed-fat, antiinflammatory diet. Of note, when a person is on a low-fat diet, a
natriuresis typically occurs, which may decrease the intensive need for salt
restriction in some patients.
Exercise
In counseling a patient with coronary artery disease (CAD) and congestive

heart failure (CHF) who is seeking to decrease their body weight, it is
important to remember that weight loss without physical activity can lead to
“yo-yo” dieting. This is due to the loss of muscle mass early in the dieting pro-
cess. As muscle mass contributes significantly to the body’s metabolism, its loss
decreases metabolism, and thus the ability to lose weight. This is one of the
main causes for plateaus in weight reduction after three to four weeks on any
diet. Yo-yo dieting actually increases cardiovascular risk over time (Klein et al.
2004).
A study of the relative benefits of exercise and lean weight in 22,000 par-
ticipants, who were followed for eight years, showed that physical activity was
a better predictor of cardiovascular outcomes than percentage body fat. Lean,
unfit individuals had a higher morbidity and mortality than obese fit people
(Lee, Blair, and Jackson 1999). Exercise also has particular value for the patient
with CHF. Exercise training improves autonomic balance and decreases ven-
tricular remodeling in CHF patients. Exercise attenuates the rate of progres-
sion of CHF, while reducing the risk of hospitalization and death (Belardinelli
et al. 1999; Orenstein, Parker, and Butany 1995).
How much exercise is the right amount? General recommendations have

been increasing over time. The recommendations vary from a minimum of
40 minutes of aerobic exercise daily to one hour daily. This should be com-
bined with muscle building activity at least three times per week (Thompson
2003). However, many patients may not be physically able to start at this level.
Blair and colleagues (1998) showed that modest exercise, such as walking daily,
decreased heart disease deaths by 50 percent in both men and women. Certified
cardiac rehabilitation programs are an excellent way to conduct safe graded
exercise.
Mind–Body Interactions
Stress remains one of the most important triggers for a CHF exacerbation and
decompensation. Most notably, the stress hormones aldosterone, epinephrine,
and cortisol set up a cascade of events that lead to salt and water retention, coro-
nary vasoconstriction, platelet adhesion, and arrhythmia. All of these events,
plus the activation of inflammatory cytokines and the renin- angiotensin-
aldosterone system, can rapidly lead to clinical decompensation. Many of the
medications prescribed for the treatment of CHF target the stress hormones
(beta-blockers block adrenaline, aldactone blocks salt and water retention,
ACE inhibitors and ARBs block the renin-angiotensin-aldosterone axis).
To further combat the effects of stress, harnessing mind–body interactions
such as meditation, yoga, Tai Chi and biofeedback maybe helpful. Tai Chi has
been shown to enhance the quality of life, exercise capacity, and sleep stability
in patients with New York Heart Functional Class I-IV heart failure (Yeh et al.
2004; Yeh, Wayne, and Phillips 2008). An 18-week study of biofeedback in
29 patients with New York Heart Functional Class I-III heart failure showed
an increase in exercise tolerance (p = 0.05) in patients with left-ventricular
ejection fraction >31% (Swanson et al. 2009).
These techniques have the potential to modulate the effects of stress on
the sympathetic nervous system and neurohormonal bombardment of the
cardiovascular system by stimulating the autonomic nervous system.
Enhanced External Counterpulsation (EECP) and CHF
Enhanced External Counterpulsation (EECP) may be a useful adjunct in

patients with CHF. EECP improved exercise tolerance and quality of life for
patients with New York Heart Functional class II-III heart failure (average ejec-
tion fraction of 23 percent), secondary to ischemic or dilated cardiomyopathy
without significant adverse events (Soran et al. 2002). The use of EECP in heart
failure is suggestive. A study using EECP for seven weeks demonstrated modest
improvements in heart failure symptoms and exercise duration, but no changes
in peak oxygen consumption, suggesting a possible placebo effect (Feldman
et al. 2006).
Mechanical Devices and Percutaneous

and Surgical Approaches
The treatment of heart failure with biventricular pacemakers for cardiac resyn-
chronization therapy has been shown to improve quality of life, decrease the
combined risk of death of any cause or first hospitalization, and when com-
bined with an AICD, decrease mortality (Bristow, Saxon, and Boehmer 2004;
Young et al. 2003). In addition, automatic implantable cardiac defibrillators, in
comparison to medications alone, are now well-established to improve mor-
tality in all patients with heart failure and ejection fractions ≤ 35–40% (Bardy
et al. 2005; Buxton et al. 1999; Moss et al. 1996; 2002). In end-stage heart fail-
ure, where life expectancy is limited, left ventricular assist devices (external
mechanical circulatory-support devices) have been shown to prolong survival,
improve quality of life, functional capacity and have been used as bridges to
cardiac transplantation. (Rose E.A., et al. 2001; Rogers J.G., et al. 2007;
Slaughter M.S., et al. 2009). Percutaneous coronary artery intervention and
surgical revascularization may improve heart failure due to coronary artery
disease. Similarly, left-ventricular dysfunction caused by underlying valvular
pathology, as in aortic stenosis, can be significantly improved by valve replace-
ment. Following percutaneous intervention or surgery, left-ventricular func-
tion often returns to normal and symptoms of heart failure resolve.
Conclusion
It is important to explain the causes of congestive heart failure and to develop

an individualized, personalized plan to decrease risk and recurrent events.
Frequently this plan includes conventional pharmaceuticals combined with
nutraceuticals, nutritional guidance, and mind–body interventions. The role
of stress, anger, social isolation, and depression must be considered with the
same level of importance as blood pressure control and food choices.
Conventional treatments shown to improve quality of life and mortality are
in general well-studied, with evidence from double-blind randomized control
trials to prove efficacy. However, in the outpatient setting, conventional
treatments often fall short, as they only address symptoms related to the
physical body in what we feel is a myopic manner. Eliminating the term
heart failure and replacing it with heart recovery or heart health offers the
opportunity to shift the underlying message we give our patients from one of
defeat to hope.
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14
A Brief Note About Arrhythmias
THOMAS B. GRABOYS
Editors’ Note
The treatment of cardiac arrhythmias has become extraordinarily complex.

Practitioners are faced with a rapidly expanding—and often bewildering—set of
options, including a growing armamentarium of medications, as well as invasive
therapies, including catheter-based procedures and surgery.
A detailed examination of specific treatments for these conditions is not the
subject of this chapter. Instead, we chose to step back and explore some basic
concepts that underlie an integrative approach to arrhythmia management.
We asked Dr. Thomas B. Graboys, a distinguished Harvard cardiologist and pres-
ident emeritus of the Lown Cardiovascular Research Foundation in Brookline,
Massachusetts, to distill this complex field down to a few clinical pearls.
Dr. Graboys, while battling a chronic decline in his own health, has graciously
responded to our request and shares his clinical wisdom in the following insight-
ful axioms, which speak to the core of integrative practice.
key concepts:
■ Overriding principle of arrhythmia management: try simple

measures first before considering drug therapy.
■ Be the patient’s advocate.
■ Minimize tests, especially invasive tests in the elderly.
■ Maintain a sense of humor and optimism.
■
289
Key Factors in Treating Arrhythmias
1. Diet: Changes in diet may play a role in the development of arrthyth-

mias. Food allergies have been reported as a trigger of arrhythmia.
Comorbid eating disorders may also be a factor.
2. Hydration: Check the patient’s level of hydration. Many patients are
chronically dehydrated. I have seen a number of patients whose
arrhythmia “disappeared” after adequate hydration was restored.
3. Stress: Assess whether the patient is experiencing psychosocial stres-
sors. As William Harvey wrote in 1628, “Every affection of the mind
that is attended with either pain or pleasure, hope or fear, is the cause
of an agitation whose influence extends to the heart” (pp. 73). I fre-
quently ask the patient precisely when his or her symptoms began,
which may allow us to identify a “trigger” which defines and unlocks
the problem without the use of medication (Graboys 1984). Since stress
has a direct bearing on sympathetic tone, which raises blood pressure
and pulse, these simple vital signs may offer some insight into your
patient’s level of stress.
4. Medication-Induced Nutritient Depletion: Determine if the patient
is currently taking any medications (including vitamins and supple-
ments) that could impact on arrhythmias. Many medications and sup-
plements lead to nutrient depletion, which can trigger arrhythmias.
Polypharmacy is an essential risk factor to be considered.
Principles to Guide Treatment
1. Are we treating the patient—or ourselves? When in doubt, do not

treat the patient with any medication unless there is compelling evi-
dence to do so. It is not uncommon for a patient to be prescribed
medications simply due to the physician’s own anxiety.
2. Is the problem frequent or severe enough to treat? Renowned cardi-
ologist Samuel A. Levine chastised us: “It hardly seems wise to institute
a course of drug therapy for rare spells” (Graboys 1985, pp. 64).
3. What is the impact of treatment on the patient’s quality of life? The
physician should take care not to diminish life’s pleasures when there
is no sound reason to do so (Graboys 1983).
4. Care of the patient with a chronic rhythm problem requires patience,
perseverance, and enthusiasm.
A Brief Note About Arrhythmias 291
REFERENCES
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308: 835–37.
Graboys, T. B. 1984. Stress and the aching heart. N Eng J Me, 311: 594–95.
Graboys, T. B. 1985. The treatment of supraventricular tachycardias. N Eng J Med 312:
62–64.
Harvey, W. 1628. On the motion of the heart and blood in animals. Translated by Robert
Willis. New York: P.F. Collier & Son Company 1909.
15
Integrative Approach to Patients
Undergoing Cardiac Surgery
GULSHAN K. SETHI
key concepts
■ Despite significant improvements in drug therapy, technology,

and reduction of risk factors for cardiovascular diseases, a select
group of patients require cardiac surgery.
■ Coronary artery bypass grafting (CABG) is one of the most
common operations performed in the world.
■ Surgery is always a stressful event, for patients and families
alike.
■ Various therapies drawn from complementary and alternative
medicine (CAM) have been shown to reduce pain, anxiety, and
stress associated with surgery.
■ The American College of Cardiology (ACC) and the American
Heart Association (AHA) have published guidelines for care of
patients undergoing CABG.
■ Combining ACC/AHA guidelines with various CAM therapies
will provide more comprehensive care to patients undergoing
cardiac surgery.
■
D
espite significant improvements in drug therapy, in technology, and
in reduction of risk factors for cardiovascular events, heart disease
remains the leading cause of death for both men and women. For a
select group of patients, heart surgery is and will remain a viable therapeutic
option. Though the frequency of percutaneous coronary interventions have
dramatically increased over the past few years, coronary artery bypass grafting
(CABG) is still one of the most common operations performed in the world.
292
Integrative Approach to Patients Undergoing Cardiac Surgery 293
It accounts for more resource expenditure than any other single surgical
procedure. For patients with valvular heart disease, heart valve repair and
replacement are frequently performed.
For a select group of patients with end-stage heart disease, a heart transplant
provides excellent long-term results. But for patients with end-stage heart dis-
ease who are not candidates for either a conventional surgical procedure or a
heart transplant, implantation of a ventricular assist device as destination ther-
apy may be necessary (Park, Tector, and Piccionis 2005). As the population
ages, the demand for cardiac procedures will obviously continue to grow. The
outcome after cardiac surgery is steadily improving, even though an increasing
number of patients undergoing this surgery are much older, with a higher
rate of coexisting morbid conditions. The improvement in cardiac anesthesia,
operative techniques, cardiopulmonary bypass technology, myocardial preser-
vation techniques, and postoperative care has resulted in very low operative
mortality and morbidity rates after CABG. The widespread use of the left inter-
nal mammary artery for a graft, postoperative pharmacologic intervention
with antiplatelet therapy and lipid-lowering drugs, aggressive measures to
control diabetes, smoking cessation, behavioral modification, and cardiac reha-
bilitation programs has significantly improved long-term survival after CABG.
Other improvements include the ability to perform CABG without using
a heart-lung machine (beating heart, or off-pump coronary artery bypass), with
minimally invasive techniques, and with robotics. Other technological advances
include mechanical suture devices and graft to coronary and aortic connectors.
Even though these newer modalities are still relatively controversial, well-
designed studies will help determine their efficacy in the very near future.
Integrative medicine is healing-oriented medicine that takes into account
the person as a whole: mind, body, and spirit. It combines mainstream medical
therapies with complementary and alternative medicine (CAM), as long as
scientific evidence supports the particular CAM therapy’s safety and effective-
ness. Patients take an active role in choosing various CAM practices that may
aid their healing. Increasing evidence suggests that the integrative approach
may lead to better short-term and long-term outcomes (Ai, Peterson, and
Koenig 2002; Charlson and Isom 2003; Halpin et al. 2002; Kshettry et al. 2006;
Tusek, Cwynar, and Cosgrove 1999).
Surgery is always a stressful time, for patients and families alike. Pain,
anxiety, fear, helplessness, and uncertainty are common concerns before any
operation. Like any other surgical procedure, cardiac procedures are associ-
ated with significant pain, which peaks within the first few days postopera-
tively and then gradually diminishes, and finally dissipates. If this pain is
not adequately controlled, it causes stress and dissatisfaction and can compro-
mise recovery. Pain also compromises patients’ ability to breathe deep, thus
exposing them to postoperative pulmonary complications, infections, and

cardiac arrhythmias.
Various complementary therapies have been shown to reduce pain, anxiety,
and stress by evoking the relaxation response through stimulation of the para-
sympathetic nervous system. They also complement patients’ natural healing
ability. Examples include guided imagery, music therapy, breathing exercises,
massage therapy, meditation, yoga, and hypnotherapy. Nowadays, a few car-
diac surgical centers offer some or all of these complementary therapies to
patients undergoing cardiac surgery.
CABG is a palliative procedure that treats the manifestations of coronary
artery disease. It does not cure the disease itself. Rather, it provides symptom-
atic relief of angina for most patients; for some, it has been proven to prolong
life (Caracciolo et al. 1995; Takaro et al.1982; Yusuf et al.1994).
The American College of Cardiology (ACC), in association with the
American Heart Association (AHA), has published guidelines for the care
of patients undergoing CABG and for the management of various risk factors
after revascularization (Eagle et al. 2004). The Agency for Healthcare Research
and Quality (AHRQ) has also published recommendations for cardiac
surgical patients, including that they undergo cardiac rehabilitation, exer-
cise training, education, counseling, and behavioral modification (Wenger
et al. 1995).
However, awareness is growing of the importance of providing a more
patient-centered and holistic health care experience. The use of CAM thera-
pies has steadily increased over the years. A recent survey by the National
Center for Complementary and Alternative Medicine, of the National Institutes
of Health, showed that four out of 10 Americans had used some form of CAM
therapy in the past 12 months (Barnes, Bloom, and Nahin 2008). Ernst (2003)
also reported that about half of the populations in the developed countries use
CAM therapies.
According to Lui and colleagues (2000), patients undergoing cardiac
surgery use CAM therapies as frequently as the general population, even if
such patients do not discuss this use with their physicians. Patients who used
CAM therapies believed that they were helpful. Patients also indicated that
mental attitude was an integral part of the healing process.
Recently, Kshettry et al. (2006) reported that they were quite easily able to
incorporate their CAM therapy protocol in treating their patients. This inte-
gration in no way compromised the safety of their patients. On the contrary, it
helped alleviate their concerns and appeared to reduce pain and tension during
early recovery.
This evidence suggests that following ACC/AHA guidelines and AHRQ
recommendations and implementing various CAM therapies may provide
Table 15.1. Integrative Approaches for Patients Undergoing Cardiac Surgery

Preoperative Strategies Postoperative Strategies
Prepare Patient and Family for Surgery Use Pharmacologic and Behavioral
Interventions
Develop Social Support Take Aspirin and other Platelet

Inhibiting Drugs
Manage Depression Make Use of Beta-Blockers
Stop Smoking Make Use of ACE Inhibitors
Use CAM Therapies to Reduce Stress and Make Use of Lipid-Lowering Drugs
Anxiety, Including:
Guided Imagery Control Diabetes
Music Therapy Control Hypertension
Breathing Exercises Make Lifestyle Changes
Religious Belief and Prayer Manage Depression
Massage Therapy Undergo Cardiac Rehabilitation
Meditation Make Use of Laughter Therapy
Yoga
Hypnotherapy
Laughter Therapy
more comprehensive care to cardiac surgery patients, empowering them with

various tools to improve their physical, mental, and spiritual health.
Table 15.1 summarizes the integrative approach to patients undergoing
coronary artery bypass surgery.
Preoperative Preparation
Increasing evidence suggests that discussing decisions and treatment options

with patients during preoperative visits influences early postoperative recov-
ery as well as later outcome. Patients who perceive themselves as having strong
social support have fewer depressive symptoms and less functional impair-
ment postoperatively. For this reason, while waiting for surgery, patients
should be encouraged to develop a healthy support system if they do not have
one already. They should also be encouraged to bring family members and
friends to pre- and postoperative visits (Oxman and Hull 1997). Depression
affects almost half of all patients undergoing CABG and is a strong predictor
of an adverse outcome; it increases operative mortality, decreases late survival,
and may undermine quality of life even after technically successful surgery.
Blumenthal et al. (1997) reported that patients who adopt various approaches
to manage stress have a significantly reduced incidence of cardiac events
and an improved quality of life. In the preoperative care of patients under-
going cardiac surgery, it is well worth the effort to incorporate techniques
to manage stress, depression, lack of social support, and anxiety. As a result,
short- and long-term clinical outcome improves in terms of an increase in
patient satisfaction, a better quality of life, and a decrease in later cardiac
events.
SMOKING CESSATION
Smoking is, by far, the single most important risk factor for preventable pre-
mature cardiac mortality (Wasley et al. 1997). It is also associated with an
increased incidence of postoperative pulmonary complications. All smokers
should receive educational counseling. Patients who quit smoking not only
are less likely to develop postoperative pulmonary complications, but also tend
to have a lower incidence of recurrent angina or myocardial infarction and
are less likely to require reoperations (Charlson et al. 1999; Wasley et al. 1997).
CAM therapies such as acupuncture, guided imagery, and hypnotherapy have
been very effective as smoking cessation tools.
In some patients, drug therapy may be necessary. For patients who are
unable to quit smoking by behavioral modification or CAM therapies, trans-
dermal nicotine patches and nicotine gum, which have been used widely with
excellent results, should be considered (Kornitzer et al. 1995). For smokers
who quit, bupropion, a sustained-release antidepressant, may help reduce the
nicotine craving and anxiety. However, for patients with acute myocardial
infarction, bupropion should be used with caution.
CAM Therapies
GUIDED IMAGERY
Guided imagery is a simple and non-pharmacologic but effective and power-

ful tool that can reduce stress and anxiety. It involves a deliberate daydream of
positive sensory images encompassing sight, sound, smell, and taste. The goal
is to teach patients to use their own imagination to influence their psychological

and physiologic state. This form of relaxation can help overcome the anxiety,
irritability, pain, and insomnia associated with stressful situations, such as
open-heart surgery (Halpin et al. 2002; Tusek, Cwynar, and Cosgrove 1999).
It may also reduce the requirement for postoperative narcotics, which are asso-
ciated with hallucination, nausea, vomiting, and constipation. Use of guided
imagery in this population may reduce the length of hospital stay as well
(Tusek, Church, and Fazio 1997).
Guided imagery requires a minimal financial investment, yet its benefits
are enormous. The equipment includes a headset, an audiocassette player, and
cassettes. The cassettes are readily available; their contents vary, but usually
include simple relaxation exercises, soothing music, and a general description
of what will happen during the cardiac surgery procedure—reinforcing for
patients that their physicians and caregivers are extremely competent, skilled,
and experienced.
Guided imagery can be introduced to patients in various ways. The preop-
erative evaluation is an ideal time to ask patients if they would like to partici-
pate in the guided imagery program. Those who wish to do so are given a set
of guided imagery cassettes specially designed for patients undergoing cardiac
surgery. They are asked to listen to them preoperatively till the day of surgery,
and then for a week or two postoperatively.
Patients with a very high level of anxiety may be helped by a session or two
with a health care professional who is well trained in guided imagery and sur-
gical preparation. The more relaxed and stress-free patients are, the better their
outcome and the faster their recovery.
Many patients and even many health care providers are unaware of the
value and benefits of guided imagery; they need to be educated about this very
potent tool to prepare patients for cardiac surgery.
MUSIC THERAPY
Recommendations for pain management by the AHRQ include cognitive

behavioral interventions such as relaxation, distraction, imagery, and music
therapy (Wenger et al. 1995). Music can distract patients, diverting their atten-
tion away from anxiety and pain and toward something more pleasant and
relaxing, thus producing a happier emotional state. For patients with angina
and myocardial infarction, music therapy is associated with a decrease in heart
rate, respiratory rate, blood pressure, and myocardial oxygen demand, result-
ing in a decrease in the frequency of cardiac complications (Sendelbach et al.
2006).
BREATHING EXERCISES
Because of postoperative pain, anxiety, and the prescription of narcotics,

patients who have undergone cardiac surgery hesitate to take deep breaths. This
shallow breathing may result in atelectasis and other pulmonary complications.
Incentive spirometery is widely used to prevent atelectatsis. Various breathing
exercises, with emphasis on the rhythmic control of breath (pranayama, in the
yogic tradition), are relaxing and may help decrease postoperative pulmonary
complications.
RELIGIOUS BELIEF AND PRAYER
Religion, prayer, and touch have been used as traditional healing therapy
for centuries. Involvement in religious and communal activities has been pos-
itively related to all dimensions of social support and to a decreased likelihood
of depression. The social network also reduces emotional distress and anxiety,
aiding postoperative recovery and resulting in better physical health and
longer survival time. Many studies have shown that stress, anger, hostility, and
social isolation increase the risks for heart disease and impair recovery after
myocardial infarction. Optimistic, relaxed, and confident patients seem to
come through cardiac operations better than those who are anxious and
depressed. Faith-based, positive coping styles may protect the psychological
well-being of patients and have been associated with improved short-term
postoperative overall functioning after heart surgery (Ai et al. 2002).
The role of spirituality and prayer for patients undergoing myocardial
revascularization has not been fully evaluated. We do not know why some
patients with a low surgical risk die while others with a high risk survive. Is it
because of prayers, spirituality, willpower, supernatural power, luck, or a com-
bination of all of these? The effect of prayers on patients with heart disease is
controversial. A couple of notable studies reported a beneficial effect of prayer
for patients in coronary care units (Byrd 1988; Harris et al. 1999).
Two excellent studies recently evaluated the efficacy of intercessory prayer
for patients with coronary artery disease undergoing percutaneous interven-
tion or surgery. Krucoff et al. (2004) did not find any benefit of intercessory
prayer for patients undergoing percutaneous coronary intervention. Benson
et al. (2006) studied the therapeutic effects of intercessory prayer for patients
undergoing coronary artery bypass. The major postoperative events and
the 30-day mortality were similar across the groups. However, complication
rates were higher in patients who were certain (vs. noncertain) of receiving
intercessory prayer than those who were uncertain of receiving it. Benson et al.
had no explanation for their surprising findings. In any case, it seems reason-
able to encourage patients who want to use their faith for coping to do so.
MASSAGE THERAPY
Massage therapy is a beneficial healing art that provides comfort to patients

undergoing cardiac surgery. While helping to reduce postoperative pain, stress,
anxiety, and tension, it also enhances patients’ circulation, range of motion,
and overall sense of well-being. Anderson and Cutshall (2007) reported that,
for patients undergoing cardiac surgery, 20 minutes of massage therapy a day
resulted in less discomfort, increased mobility, improved sleep, satisfaction
with pain management, and a shorter hospital stay.
MEDITATION
Meditation is a form of conscious relaxation that makes the mind calm and
peaceful. It teaches patients to reach a state of serenity, creating an inner mental
space for clarity. In mindful meditation, the person sits comfortably and
silently for 10 to 15 minutes, centering attention by focusing awareness on an
object or process (such as on breathing or on a mantra). The practical purpose
of focusing on breathing or on a mantra (which entails silent internal mental
repetition of a word, phrase, or sound) is to deflect the mind from bothersome
situations, leading to calmness and new insights. Meditation can lead to a
decrease in blood pressure, heart rate, and stress.
YOGA
Yoga aims to create balance in the body through developing strength and
flexibility. It involves meditation, spiritual discipline, stretching, diet, and the
rhythmic control of breathing. It develops flexibility and muscular endurance
by allowing muscles to be stretched and strengthened. It can decrease blood
pressure, heart rate, and anxiety; it can increase agility and muscle relaxation.
HYPNOTHERAPY
Hypnotherapy produces an altered state of consciousness, inducing relaxation,

guiding the imagination, and fostering the experience of being on a different
plane of consciousness. It is a collection of methods that allows a person to

access the mind–body connection and promotes self-healing. Hypnotherapy
has been shown to be effective in smoking cessation, weight loss and pain
management.
LAUGHTER THERAPY
Laughter therapy consists of three parts. These include a series of breathing

exercises and stretching, a period of laughter exercises (unconditional laugh-
ter), followed by guided relaxation.
The laughter in laughter therapy is more than a vocal and muscular behav-
ior. It is accompanied by a variety of physiological and neural manifestations.
Various studies (in such areas as cardiac rehabilitation, pain perception, dis-
comfort threshold, stress coping, and immune system enhancement) have
shown measurable benefits of humor and laughter for patients. The mirthful
laughter brings about reduced serum levels of cortisol, dopac, epinephrine,
norepinephrin, and growth hormone (Berk et al.1989). It also increases natu-
ral killer cell activity and other immune markers (Berk et al. 2001; Takahashi
et al. 2001).
One notable study found that people who fail to smile or laugh in stressful
or uncomfortable situations may be more prone to heart problems. They inter-
viewed 150 patients who had either suffered a myocardial infarction or had
undergone aortocoronary bypass surgery. These patients’ attitudes were com-
pared with that of 150 age-matched controls. Each study participant was asked
how he or she would react to a number of uncomfortable everyday situations.
Miller et al. (2006) concluded that people with cardiac problems were more
likely to get angry or hostile, rather than to laugh or use humor, in order to
overcome the embarrassment or difficulty of the situation. In addition, people
with cardiac problems were less likely to recognize humor or use it as an adap-
tive mechanism; they generally showed less ability to laugh, even in positive
situations. Another finding was that brachial artery blood flow increased in
study participants who watched movie clips that evoked humor and laughter,
but decreased in those who watched movie clips that caused mental stress.
Tan, Tan, and Berk (1997) followed two groups of patients who had suffered
a myocardial infarction in their cardiac rehabilitation program. Both groups
were matched for pertinent patient characteristics, but the experimental group
was allowed to view self-selected humorous movies for 30 minutes every day
as an adjunct to standard therapy. The experimental group experienced fewer
episodes of arrhythmias, lower blood pressure, lower urinary and plasma cat-
echolamine levels, a lower incidence of beta-blocker and nitroglycerine use,
and a lower incidence of recurrent myocardial infarction, as compared with

the control group).
In a similar study, the same investigators assigned 20 adults with type II
diabetes to either the control group or the laughter group. All 20 patients had
hypertension and elevated cholesterol levels and were taking standard medica-
tion for diabetes, hypertension, and elevated cholesterol levels. At their one-
year follow-up appointment, patients in the laughter group had a mean increase
in their HDL cholesterol level of 26 percent (as compared with 3 percent in the
control group), as well as a mean decrease in their C-reactive protein level of
66 percent (as compared with 22 percet in the control group); both differences
were statistically significant (Tan, Tan, and Berk 2009).
Some investigators have raised the theoretical concern that, during laugh-
ter, the increase in heart rate and blood pressure could have a detrimental
effect in patients with heart disease. However, given the lack of medical litera-
ture on myocardial infarction provoked by mirthful laughter, Fry (1994) sug-
gested that a physiologic “sparing mechanism” in the body is associated with
mirth and laughter.
Holistic and alternative approaches to patient care, which were first devel-
oped in the 1950s, stimulated interest in the use of humor in healing, though
not specifically as a therapeutic modality per se. The humor therapy move-
ment was not ignited until the late 1970s, with the publication of Norman
Cousins now-classic book, Anatomy of an Illness as Perceived by the Patient, in
which he detailed his personal experience of relieving pain due to ankylosing
spondylitis with humor. In 1995, Kataria founded the Laughter Yoga Clubs in
India; since then, they have mushroomed all over the world.
At the University of Arizona, we have modified Kataria’s laughter yoga pro-
tocol and incorporated it into a program that consists of three parts:
• Part I: A series of breathing and stretching exercises to energize the

body (5 minutes).
• Part II: Laughter exercises (unconditional laughter), along with
chanting and clapping, followed by stretching and deep breathing
(15 minutes).
• Part III: Breathing exercises and guided relaxation (10 minutes).
Laughter therapy can be used safely with all patients with heart disease.
Postoperatively, before initiating the laughter therapy, the patients should
have no incisional discomfort and they should also check with their physician
and surgeon.
It is obvious that more research needs to be done in this field to make laugh-
ter therapy more acceptable to the public and caregivers alike.
Postoperative Care
PHARMACOLOGICAL INTERVENTIONS TO IMPROVE OUTCOMES
Aspirin and Other Platelet-inhibiting Drugs
Late postoperative results after CABG surgery depend on graft patency. Early
postoperative administration of aspirin improves the graft patency rate for
saphenous vein grafts and reduces the incidence of death, myocardial infarc-
tion, stroke, renal failure, and bowel necrosis (Goldman et al. 1990; Mangano
et al. 2002). To achieve optimal results, aspirin should be administered within
six hours postoperatively, either through the nasogastric (NG) tube or rectally;
however, if the patient is bleeding, aspirin may be delayed for 24 hours. Aspirin
therapy should be continued indefinitely. In case of aspirin allergy, Clopidogrel,
a very effective platelet inhibitor that can be used.
Beta-Blockers
The perioperative use of beta-blockers is very effective in preventing postop-

erative arterial fibrillation. Their use has also been shown to improve survival
in patients undergoing CABG after myocardial infarction (Chen et al. 2000).
Angiotensin-Cnverting Enzyme (ACE) Inhibitors
The use of ACE inhibitors is recommended for patients with left ventricular
dysfunction (left ventricular ejection fraction, below 40 percent), hyperten-
sion, diabetes, or chronic renal disease. Their use has been shown to decrease
the rates of myocardial infarction, stroke, and death in patients with coronary
artery disease (Talbot 2000).
Lipid-Lowering Drugs
Elevated levels of serum triglyceride, low level of high-density lipoprotein

(HDL), and elevated levels of low-density lipo-protein (LDL) are independent
risk factors for coronary artery disease. Abundant evidence shows that all
patients undergoing CABG should receive lipid-lowering therapy, unless
otherwise contraindicated (Grundy et al. 2004). All individuals who have

undergone CABG should aim for LDL levels at least below 100 mg/DL.
Recently, the National Cholesterol Education Program recommended consid-
eration of targeting LDL levels below 70mg/DL for people with a very high
risk for coronary artery disease. These individuals are those with presence
of established cardiovascular disease plus other risk factors, especially diabe-
tes, \ poorly controlled risk factors, especially continued smoking or metabolic
syndrome, or patients with acute coronary syndrome or elevated level of
C-reactive protein (Post Coronary Artery Bypass Group Trial Investigators.
1997, Maron, Ridker, and Grundy 2008). The Post Coronary Artery Bypass
Graft Trial also showed that patients aggressively treated with lipid-lowering
agents (who achieved LDL levels below 100ml/DL) had lower atherosclerotic
disease progression in their saphenous vein grafts and required fewer repeat
revascularization procedures (Brown et al. 2006).
CONTROL OF DIABETES
Diabetic (vs. nondiabetic) patients tend to have higher rates of operative mor-
tality, deep sternal wound infections, and strokes. They also have longer hospi-
tal stays and are at high risk for subsequent cardiovascular events (Estrada et al.
2003). Perioperative hyperglycemia, with or without diabetes, is associated with
increased resource use for patients undergoing CABG (Furnary et al. 2003).
Meticulous control of hyperglycemia with continuous intravenous infusion of
insulin preoperatively has been shown to reduce the incidence of sternal wound
infections, death, and morbidity (Hoogwerf et al. 1999). It is extremely impor-
tant to aggressively control diabetes and have the patient take lipid-lowering
drugs in order to achieve good long-term results (Domanski et al. 2000).
CONTROL OF HYPERTENSION
Hypertension is associated with cardiovascular diseases and stroke. It is well

known that controlling blood pressure also reduces the extent of progression
of atherosclerosis in patients who have undergone CABG with saphenous vein
grafts (Goyal et al. 2005).
LIFESTYLE CHANGES
Lifestyle changes to reduce cardiovascular risks are extremely important after

CABG. Patients should be encouraged to follow a heart-healthy diet. They should
be advised to eat ample amounts of fruits, vegetables, and whole grains.

Emphasis should be on reducing consumption of saturated fats and trans-fatty
acids, cholesterol, and simple sugars. Fish consumption and supplementation
with omega-3 fatty acids appear to promote cardiovascular health and espe-
cially to protect against sudden death. Being overweight and inactive tends to
increase LDL levels and total cholesterol levels and to decrease HDL levels.
Exercise and weight control are very important, especially for patients with
metabolic syndrome.
MANAGEMENT OF DEPRESSION
Depression is associated with alterations in autonomic, neuroendocrine,

immune, and platelet function. It is a risk factor for both the development of
and the worsening of coronary artery disease. Major depressive disorders (as
noted preoperatively) are related to subsequent mortality and morbidity as well
as to less improvement in quality of life postoperatively (Musselman, Evans,
and Nemeroff 1998). Depressed patients are also less physically active, less med-
ically compliant, and more likely to engage in health-damaging behavior.
The incidence of preoperative major depression in cardiac patients ranges
from 16 percent to 48 percent. Postoperatively, 18 percent of patients who were
not depressed preoperatively develop significant depression. These newly
depressed patients are at a higher risk for long-term cardiac events and death,
as compared with patients who are not depressed (Peterson et al. 2002;
Wellenius et al. 2008). Depressive symptoms are associated with atheroscle-
rotic progression in patients’ saphenous vein grafts; such patients have a sig-
nificantly higher risk of cardiovascular events and of mortality related to heart
disease (Miller 1998).
Preoperative education (aimed at helping patients better understand their
illness, its treatment, and its effects) may reduce their psychological distress
and improve their future well-being; depression may undermine their quality
of life, despite successful cardiac surgery.
Potential Risks Associated with CAM Therapies
A large proportion of the American population uses CAM therapies, yet many
patients do not disclose their use of CAM to physicians, even when they
are prompted. Liu and colleagues (2000) surveyed 376 patients (mostly well-
educated) undergoing cardiac surgery at Columbia-Presbyterian Medical
Center in New York. Excluding prayer or the use of vitamins, 44 percent had
tried some type of CAM therapy. Of those patients, only 17 percent said that
they discussed their use of CAM therapy with their physicians, while 48 per-
cent admitted that they did not want to discuss this topic with anyone
This lack of communication is potentially dangerous. Herbal medications,
for example, possess significant pharmacologic activity; consequently, they
may have potentially adverse effects and interact in harmful ways with other
drugs. Some can speed up or slow down the heart rate, inhibit blood clotting,
alter the immune system, or change the effect and duration of anesthesia.
Several herbs directly affect platelet aggregation and bleeding time, while
others interact with anticoagulation medications. Fish oil, garlic, onion, and
vitamin E inhibit platelet aggregation. Feverfew, ginkgo biloba, coenzyme
Q10, ginger, ginseng, and St. John’s wort interact with warfarin. Hawthorn
berry, kyusin, licorice, plantain, uzara root, ginseng, and St. John’s wort inter-
act with digoxin. St. John’s wort also alters the metabolism of cyclosporine and
increases the risk of rejection in heart transplant recipients.
Because of the extensive use of CAM therapies by the general population,
physicians and patients must be open in their discussions, and bring up any
use of such therapies. The surgeon should specifically ask patients about any
herbal medications used, in order to prevent perioperative complications. The
American Society of Anesthesiologists recommends that patients stop taking
all herbal medication two weeks before undergoing cardiac surgery. Herbal
medications may be resumed postoperatively, if they will not potentially inter-
act with other prescribed drugs.
Conclusion
Despite improvements in drug therapy, percutaneous coronary interventions,

and reduction of risk factors for cardiac diseases, many patients still need
CABG either to resolve their symptomatic relief or to prolong their lives.
The ACC/AHA guidelines for care of patients undergoing CABG should be
followed. Patients who prepare for surgery psychologically have less discom-
fort, fewer complications, and shorter hospital stays. Various CAM therapies
have been shown to reduce pain, anxiety, stress, and depression, thereby fur-
ther enhancing patients’ natural healing abilities. Combining the ACC/AHA
guidelines with various CAM therapies will provide more comprehensive care
to patients, and empower them with an array of tools to improve their physi-
cal, mental, and spiritual health.
A large proportion of cardiac patients also take herbal medicine and dietary
supplements. These may have adverse effects and may interact in harmful ways
with other drugs. To avoid potential complications during surgery, all herbal
medicines and dietary supplements should be discontinued before surgery

and then closely monitored postoperatively.
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ADDITIONAL RESOURCES
O
n behalf of all the chapter authors, we hope that this volume has been
helpful to those seeking to incorporate aspects of integrative cardiol-
ogy into clinical care and research. Adopting this new approach can
be challenging, however, as it involves a data set not typically part of current
medical training. Furthermore, since the field is relatively new, reliable refer-
ence material may be difficult to identify.
For these reasons, we have compiled a focused list of resources that the
authors have found to be most useful.
Continuing Education
AMERICAN COLLEGE OF CARDIOLOGY
The report of the American College of Cardiology Foundation task force,

titled “Integrating Complementary Medicine Into Cardiovascular Medicine”
is an excellent overview of research involving integrative approaches to cardio-
vascular disease. This document can be found at: http://content.onlinejacc.
org/cgi/reprint/46/1/184.pdf.
311
312 Additional Resources
FELLOWSHIP PROGRAM IN INTEGRATIVE MEDICINE

AT THE UNIVERSITY OF ARIZONA
The two-year fellowship program in Integrative Medicine offered by the

University of Arizona Center for Integrative Medicine combines distance
learning with three weeks of activities in Tucson. The program is designed for
physicians, nurse practitioners, and physician assistants in all stages of their
careers. More information is available at http://integrativemedicine.arizona.
edu/education/fellowship/.
NATIONAL INSTITUTES OF HEALTH: THE NATIONAL CENTER FOR

COMPLEMENTARY AND ALTERNATIVE MEDICINE
The Web site of the National Center for Complementary and Alternative
Medicine, sponsored by the National Institute of Health, contains reference
material as well as information about government-funded research opportuni-
ties: www.nccam.nih.gov.
Journals
The authors have found the following journals to be especially helpful and
informative:
• Alternative Therapies in Health and Medicine

• Explore: The Journal of Science & Healing
• Journal of Alternative and Complementary Medicine
Nutritional Supplements
CONSUMERLAB
This group provides an independent laboratory analysis of the content and purity
of various supplements. Many practitioners find this information to be helpful in
the selection of the brand of supplement to recommend. This service is available
for a fee. More information is available at: http://www.consumerlab.com.
Additional Resources 313
NATURAL MEDICINES DATABASE
This resource, available online and in hard copy, is a highly useful reference
for learning about the science and practical use of supplements including
mechanism of action, dose, and interactions with drugs and supplements.
This service is available for a fee. More information is available at: www.
naturaldatabase.com.
NATURAL STANDARD
This searchable database of supplements (which requires a fee for access) includes
a ranking of the quality of supporting evidence: www.naturalstandard.com.
OFFICE OF DIETARY SUPPLEMENTS
This Web site provides dietary supplement fact sheets and a link to the
International Bibliographic Information on Dietary Supplements (IBIDS). It
can be accessed for free at: http://ods.od.nih.gov/.
HERBAL GRAM
The Web site is sponsored by the American Botanical Council, a nonprofit

organization that provides reference material on herbal medicine. It contains
an Herb Clip section which summarizes current research on herbal prepara-
tions. Some content is free content, but a fee is required for full access: www.
herbalgram.org.
INDEX
Note: Page numbers followed by “f ” and “t” denote figures and tables, respectively.
ACLS certification, 43 Aldosterone antagonists, 270–71

ACTH (adrenocorticotropic hormone), 236 Alpha-linolenic acid (ALA), 229
Actin-myosin complexes, 21 American College of Cardiology (ACC),
Acupuncture, 101–2, 109–10, 171–72 253, 311
acupoints, 110, 102f American College of Cardiology (ACC)/
for cholesterol, 106–7 American Heart Association
clinical application, 110–11 (AHA)
future research, 111–12 exercise guidelines, 189–90
for hypertension, 105–6 guidelines for CABG patients care, 294
mechanism of action, 103–5 American Diabetic Association (ADA), 35
for myocardial ischemia, 108 American Heart Association (AHA), 24,
for obesity, 107 43, 159, 253
for peripheral vascular disease, 109 American Heart Association (AHA)/
for smoking cessation, 107 American College of Cardiology
Adenosine diphosphate (ADP), 79f, 80 (ACC)
Adenosine monophosphate (AMP), 81 heart failure classification, 268–69, 269t
Adenosine triphosphate (ATP), 21, 79f, American Holistic Nurses Association
80–84 (AHNA), 178
Aerobic exercise, 31, 158, 189, 203 Anaerobic glycolysis, 21
African traditional medicine, 63 Angina pectoris, 108
Agency for Healthcare Research and Angiotensin-converting enzyme (ACE)
Quality (AHRQ), 294 inhibitors [ACEI], 229, 231,
Alcohol, 203–4, 205 270, 302
315
316 INDEX
Antidepressants, 152–53 Betaine, 209

Anti-hypertensive herbs, 60 Bilberry (Vaccinium myrtillis), 65
Anti-inflammatory and antimicrobial Bioenergetics, 78–79
agent, 230 Biofeedback, 259
Anti-inflammatory diet, 11–14 Bishop’s weed (Ammi visnaga), 62
calorie, 7–8 Botanical medicine, 55–57
carbohydrates, 8 anti-hypertensive herbs, 60
fat, 8–9 cardiac tonics, 62–63
fiber, 9 cardioactive herbs, 61
phytonutrients, 9–10 diuretics, 63
protein, 9 hypolipidemic plant products, 63–64
vitamins and minerals, 10 nervine relaxants, 64–65
water, 10–11 quality of, 57
Antioxidants, 6, 14, 250–51 safety of, 58–59
Anxiety, 143–44 vascular tonics, 65
avoidance, 146–47 Web sites, 66–67
mechanisms of action, 147–48 Brain natriuretic peptide (BNP), 88
panic, 144–46 Brain wave activity, 170
worry, 147 Breathing exercises, 172, 259, 294–95, 298,
Apolipoprotein B (ApoB), 191 300–301
l-Arginine, 277–78 Buddhism, 128
Arjuna (Terminalia arjuna), 62
Arrhythmias, treatment C-Reactive Protein (CRP), 207–8
key factors, 290 Calcium, 10
principles, 290 Calorie-restricted diets, 6
Art, 125 Carbohydrate, 8, 203
Artichoke (Cynara scolymus), 63 Cardiac behavioral medicine, 135–37
Asian mushrooms, cooked, 12 anxiety, 143–48
Aspirin, 70–72, 302 cognitive behavioral therapy, 153–55
complications of, 72 depression. See Depression
contraindications to, 72–73 education, 155–56
dosage, 73–74 exercise, 158
drug resistance, 74–75 improving coping strategies,
indications for therapy, 75 156–57
Atherosclerosis Risk in Communities pharmacotherapy, 152–53
(ARIC) Study, 278 protecting healthy behaviors, 156
Atherosclerosis, 4 relaxation, 157–58
Atorvastatin, 88 role of the medical team: (SERF),
ATP. See Adenosine triphosphate (ATP) 159–62
Ayurveda, 57, 62 stress. See Stress
treatment modalities, 151–59
B vitamins. See also Vitamins Cardiac energetics, 85
for hypertension, 232 Cardiac energy metabolism, 78–82
Beans, 13 Cardiac glycosides, 61
Benzodiazepines, 152 Cardiac mortality, 29
Beta-blockers, 271, 302 Cardiac physiology, 23–24
INDEX 317
Cardiac resynchronization therapy Comorbidity, 27f

(CRT), 85 Congestive heart failure (CHF), 56
Cardiac surgery, 292–95 ConsumerLab, 64, 67, 312
CAM therapies. See CAM therapies CoQ10, serum 233
postoperative care, 302–4 Coronary artery bypass grafting (CABG),
preoperative preparation, 295–96 252, 253, 292–93, 294
smoking cessation, 296 Coronary artery disease (CAD), 136,
Cardiac tonics, 62–63 150, 152
Cardioactive herbs, 61 and anxiety, 144, 148
Cardiomyocytes, 88 chelation for, 256
Cardiomyopathy, 90 and depression, 137, 141, 142
Cardiovascular prevention, 44–46 invasive therapies for, 252
Cardiovascular rehabilitation programs, 43 nutrition, 278
Carnitine shuttle, 91 risk factors for, 139–41
l-Carnitine (or Propionyl l-Carnitine statin therapy for, 88, 252–53
[PLC]), 91, 273 and stress, 150–51
Carotenoids, 10 and worry, 147
Celery Coronary Artery Surgery Study
for hypertension, 231 (CASS), 252
Cellular mechanisms, 83 Coronary care unit (CCU), 177
Central adaptations, 25 Coronary heart disease (CHD), 24
Certified Healing Touch Practitioner CREATE trial, 155
(CHTP), 178 Creatine kinase, 21
Chakras, 174t Cretaceous extract, 234
properties of, 170 Crossover observational studies, 28
self-healing with, 175–76t
Chelation, 256 Dairy products, 211
Trial to Assess Chelation Therapy Dandelion (Taraxacum officinale), 278
(TACT), 256 Dehydrogenase, 86
Cholesterol, 106–7, 190–92 Department of Agriculture, 249
Christianity, 129 Depression, 137–39
Chronic emotional stress, 235 and coronary artery disease, 141
Chronic sympathetic overdrive, 236 diabetes, 140
Chronic venous insufficiency, 65 management of, 304
Circuit training, 31 mechanisms of action, 142–43
Citalopram, 152 non-adherence to medical
Clinical depression (Major Depressive recommendations, 139
Disorder [MDD]), 137 obesity, 140
Coenzyme A (Co A), 91 as predictor of morbidity and mortality,
Coenzyme Q10 (ubiquinone), 88–91, 141–42
200–201, 273–75 smoking, 139
in metabolic cardiology, 88-90, 94-96 and spirituality, 121
for hypertension, 233–34 DHA. See Docosahexanoic acid (DHA)
for patients treated with statins, Diabetes, 34, 36
200–201 control of, 303
Cognitive behavioral therapy, 153–55 type 2, 18, 85
318 INDEX
Diabetes Prevention Study, 249 Energy flow, 171

Diastolic blood pressure (DBP), 228 Energy healing, 177–78
Diastolic dysfunction, 84 Energy medicine, 169–71
Dicumarol, 71 acupuncture. See Acupuncture
Diet. See also Nutrition Healing Touch, 170, 171, 174–76, 267
anti-inflammatory diet, 11–14 preoperative and postoperative, 176–77
calorie, 7–8 Qi Gong, 172–73, 258–59
carbohydrates, 8 referrals, 178
fat, 8–9 Reiki, 173
fiber, 9 spiritual crises, death, and dying,
phytonutrients, 9–10 177–78
protein, 9 Tai Chi, 172–73, 237–40, 258–59, 280
vitamins and minerals, 10 vascular disease, 177
water, 10–11 Energy tracts (meridians), 174
calorie-restricted diets, 6 Enhanced external counterpulsation
Japanese diet, 4 (EECP), 255–56
low-fat diet, 4 and CHF, 280–81
Mediterranean diet, 6–7, 185–88 ENRICHD trial, 152, 155, 257
North American diet, 5–6 EPA, 205–6, 229, 238, 276–77
Okinawan diet, traditional, 4–5 Eplerenone, 271
portfolio diet, 194 European Society of Cardiology, 40
supplements, 14 European Stroke Prevention Study, 73
ultra-low-fat diets, 4, 6 Exercise, 17–18
yo yo diet, 279 benefits, 26–29
Diet and Reinfarction Trial (DART), 205 cardiac physiology, 23–24
Dietary Approaches to Stop Hypertension for cardiovascular disease, 24–29,
(DASH), 227 251–52
Digitalis, 61, 269–70 for cardiovascular prevention, 44–46,
Digoxin, 56 188–90
Diuretics, 63, 278 for diabetes mellitus, 34–36
Docosahexanoic acid (DHA), 205–6, 229, in elderly, 40
238, 276 for heart failure, 279–80
Doctor of Naturopathy (ND), 178 hemostatic effects, 36–37
Doctor of Oriental Medicine (OMD), 178 for hypertension, 30–31, 235
Double-blind trial, 250–51 lipids, 32–33
DSM-IV-TR symptoms of depressive peripheral muscle and vasculature,
episode, 138t 19–22
physiologic changes with exercise,
ECG abnormalities, 40 25–26
EDTA, 256 physiology, 18–24
Eicosapentaenoic acid (EPA), 229 pre-exercise evaluation, 42–44
Electroacupuncture, 103, 104–5, 111 prescription of, 40–41
Endothelial function, 25 pulmonary contribution to exercise
Endothelium-derived relaxation factor tolerance, 22–23
(EDRF), 277–78 risk, 41–42
Energy centers (chakras), 174 in women, 37
Energy fields (auras), 174 in young, 37–40
INDEX 319
Exercise-induced ST segment deviation, 28 Harvard Alumni Study, 26, 29

Exercise stress test, 35 HATS trial, 250
Hawthorn (Crataegus spp), 56, 62, 271–72
Fatigue-resistant type 1 fibers, 20 for hypertension, 234
Fellowship Program in Integrative HbA1C, 31, 34
Medicine at the University of HDL Atherosclerosis Treatment
Arizona, 312 Study, 195
Fennel (Foeniculum vulgare), 63 Healing Touch, 170, 171, 174–76, 267
Fenofibrate, 204 preoperative, 176
Fiber, 9, 202 Healing Touch International, 178
for hypertension, 230 Healing Touch Program, 178
Fibrates, 204 Health Professionals Follow-Up Study,
FICA interview guide, 122 186, 189
Finnish Twin Cohort study, 27 Heart failure, 265–67
Fish and fish oil, 12, 205–6, 211 aldosterone antagonists, 270–71
Flat dose-response curve, 31 ACE inhibitors, 270
Flavonoids, 57 ARB270
Folic acid, 10, 209 l-arginine, 277–78
Food and Drug Administration (FDA), 57 beta-blockade, 271
Four-quadrant model, physician–patient l-carnitine, 273
interactions, 127 classification of, 267–69
Foxglove (Digitalis purpurea), 56, 61 coenzyme Q10, 273–75
Framingham Heart Study, 27, 28, 144 digitalis, 269–70
Framingham Offspring Study, 210 diuretics, 278
Frank-Starling principle, 23 EECP and CHF, 280–81
Fruits, 5, 14, 188 exercise, 279–80
Functional foods, 250 hawthorn, 271–72
magnesium, 275
Garlic (Allium sativum), 57, 60, 63, 193 mind–body interactions, 280
for hypertension, 230–31 nutrition, 278–79
Gemfibrozil, 204 pathophysiology, 267
German Commission E., 61, 63, 271 polyunsaturated free fatty acids
Ginkgo (Ginkgo biloba), 65 (PUFA), 276–77
GISSI trial, 205, 206 d-ribose, 273
Glucose, serum, 35 thiamine, 275–76
Glucose intolerance, 34 Heart rate, 25
Glucose-6-phosphate dehydrogenase, 86 Hepatic triglyceride lipase (HTGL), 33
Glycine propionyl l-carnitine (GPLC), 93 Herbal Gram, 313
Glycolytic, 20 Herbal medicine. See Botanical medicine
Good manufacturing guidelines Herbs and spices, 11
(GMP), 57 Hibiscus (Hibiscus sabdariffa), 57, 60, 63
Grains, 13, 186, 188 High-density lipoprotein (HDL), 32–33,
Grief, and mental health problems, 236 33f, 195, 202–4
Guggul (Commiphora mukul), 63 High-tech cardiac care, side effects of,
Gugulipid, 193 xiii–xiv
Guided imagery technique, 176, 258, Homocysteine, 208–9
296–97 Hope tool, 122–23
320 INDEX
HOPE-2 trial, 208–9, 250 Left ventricular end-diastolic volume

Horsetail (Equisetium spp), 63 (LVEDP), 23
hs-CRP, 207–8, 251 Left ventricular hypertrophy, 84
Hypercholesterolemia, 140 Legumes, 13
Hypertension Leonurine, 64
control of, 303 Levocarnitine (l-carnitine or carnitine),
epidemiology, 225–26 91–93
exercise, 235 Life expectancy (LE), 27f
integrative approach, 227 Lifestyle changes, 208, 248–50, 254–55,
mind–body approaches, 235–41 303–4
nutrition, 227–31 Lifestyle Modification Program,
nutritional supplements, 232–34 253–54
prescription medication, 226 Lifestyle recommendations, 229
role of oxidative stress, 225 Lily-of-the valley (Convallaria majalis), 61
staged therapy of, 225–26 Linden flower (Tilia platyphllos), 60
Hypertensive heart disease, 30, 85, 90 Lipid-lowering drugs, 302–3
Hypertrophied heart, 84 Lipids, 32–33
Hypnotherapy, 299–300 Lipoprotein lipase (LPL) activity, 33
Hypolipidemic plant products, 63–64 Lipoproteins, 32
Hypomagnesemia, 93 Lovastatin, 196
Hypothyroidism, 199 Low-circulating vitamin D, 199
Low-density lipoprotein (LDL), 32, 33, 33f,
Imagery technique, 258 63–64, 190–97
Inorganic phosphate (Pi), 79f particle size 195
Insulin resistance, 34, 204 Low-fat diet, 4
Insulin-responsive glucose transporter, Low-glycemic-load food, 203
GLUT 4, 34 Lp(a), 195, 206–7
Integrative medicine, definition, xiv–xv Lyon Diet Heart Study, 185–87
Interheart Study, 247, 248t
International Olympic Committee, 40 Macronutrient and micronutrient
INTERSALT Study, 228 variations, 227
Invasive therapies, for CAD, 252 Magnesium
vs. statin therapy, 253 for hypertension, 228
Massage therapy, 299
Japanese diet, 4 Meditation, 125, 299. See also
JELIS trial, 277 Transcendental Meditation (TM)
Journal of the American Medical Mediterranean diet, 6–7, 185–88
Association, 229 Mental-stress induced ischemia, 150
Journals, 312 Metabolic cardiology, 78
cardiac energy metabolism, 78–82
Krebs cycle, 21 coenzyme Q10, 88–91
energy nutrients for congestive heart
Lactate threshold, 21–22 failure, 85–87
LaPlace’s law, 84 energy starvation, 83–85
Laughter therapy, 300–301 levocarnitine (l-carnitine or carnitine),
Lavandulifolioside, 64 91–93
INDEX 321
magnesium, 93–94 for hypertension, 227–31, 240t

d-ribose (ribose), 85–87 for heart failure, 278–79
Metabolic energy defects, 84
Metabolic equivalents (METs), 19, 26 Obesity, 107, 140
Mind/body approaches, 211–13, 235–41. Office of Dietary Supplements, 313
See also Cardiac behavioral Okinawan diet, traditional, 4–5
medicine Olive oil, 230
Mistletoe (Viscum album), 60 Olive oil, extra virgin, 230
Mitral valve prolapse (MVP), 93 Omega-3 fatty acids, 62–63, 229
Monacolin K, 196 for hypertension, 229–30
Monascus purpureus, 64 Omega-9 fatty acids
Monounsaturated fats (MUFA), 57, 230 for hypertension, 230
Motherwort (Leonurus cardiaca), 64–65 Onions
MR FIT Trial (Multiple Risk Factor for hypertension, 230–31
Intervention Trial), 26 Ornish’s Lifestyle Heart Trial, 121
Multicultural “bioenergy” healings, 171 Oxidative phosphorylation, 84, 88,
Music therapy, 125, 297 21–22
Myocardial infarction, 4 Oxidative, 20
Myocardial ischemia, 108
Panic, 144–46
National Center for Complementary and Parsley (Petroselinum sativum), 63
Alternative Medicine Parsley seed, 57
(NCCAM), 173 Pasta, 13
National Center for Health Statistics, 173 Peripheral adaption, 25
National Institute of Health (NIH), 172 Peripheral circulation, 22
Natto Pharmacologic therapy, 152–53, 229
for hypertension, 231 Phosphocreatine (PCr), 21, 80
Natural Medicines Database, 313 6-Phosphogluconate, 86
Natural Standard, 313 5-Phosphoribosyl-1-pyrophosphate
Nervine relaxants, 64–65 (PRPP), 82, 86
Neurobiology of exercise, 235 Physician spirituality, 126
New York Heart Association (NYHA), and compassion, 128–29
heart failure classification, and physician–patient relationship,
267–68, 268t 127–28
Niacin, 194–95, 202, 204 and professional satisfaction, 129–30
Niacin, “flush-free” or “no-flush”, Physician’s Health Study, 42
195, 204 Physiologic homeostasis, 23
Nitric oxide, 277–78 Phytonutrients, 9–10
Nitric-oxide mediated vasodilation, 22 Phytosterols, 63
North American diet, 5–6 Phytotherapy. See Botanical medicine
NORVIT trial, 208, 209 Pinus pinaster ssp. Atlantica, 65
Nurses’ Health Study, 27, 37, 186, 226, Pioglitazone, 204
229, 250 Plant stanols, 193–94, 201, 202
Nutrient–gene interaction, 227 Plant sterols, 56, 63–64, 193–94, 201
Nutrition. See also Diet Plasma CoQ10, 90
for heart health, 185–88 Policosanol, 63, 193
322 INDEX
Polyunsaturated free fatty acids (PUFA), Reiki, 173

276–77 Relative intensity, 44
Portfolio diet, 194 Relative risk, 42
Post Coronary Artery Bypass Graft Relaxation, 157–58
Trial, 303 Religious well-being, 123. See also
Prayer, 125 Spirituality
Preventive cardiology, 183–85 Reserpine, 56, 60
cholesterol, 190–92 with thiazide diuretic, 60
coenzyme Q10, 200–201 Resistance training (pure isometric
exercise, 188–90 exercise), 31, 34
fiber, 193 Retinopathy, 36
HDL, 202–4 d-Ribose (ribose), 85–87, 273
mind/body interventions, 211–13 D-Ribose-5-phosphate, 82
niacin, 194–95 Risk, absolute, 42
nutrition for heart health, Rosiglitazone, 204
185–88 Running, 203
portfolio diet, 194
red yeast rice, 196–97 Sardine muscle protein, 229
soy protein, 194 Saturated fat, 3–5, 8, 185, 194, 230, 238,
stanols/sterols, 193–94 250, 304
statin intolerance, 198–200 Scandinavian Simvastatin Survival Study
statins-avoiding patients, strategies for, (4S), 252–53
201–2 Schumann resonance, 170
triglycerides. See Triglycerides Seafood, 12
Project PACE, 41 Seaweed
Protein, 9, 11–12 for hypertension, 231
for hypertension, 228–29 Selective serotonin reuptake inhibitor
Psychotherapy, 153 (SSRI), 152
Psyllium (Plantago ovata), 63, 64 Selenium, 10
PTCA, 253 Serenity, 123
Pycnogenol, 65 Serenity Scale, 123
Pyridoxal 5′ phosphate (PLP), 232 Serological assays, 32
Sertraline, 152
Qi Gong, 172–73, 258–59 Sertraline Antidepressant Heart
Attack Randomized Trial
RAAS (renin angiotensin aldosterone (SADHART), 152
system), 231 SHARP Trial (Stop Hypertension
Randomized double-blind placebo control with Acupuncture Research
trial, 251 Trial), 106
Rauwolfia serpentina, 56, 60 Simvastatin, 197, 252
Red or “slow” fibers (twitch type 1), 20 Single motor neuron, 19–20
Red wine, 11 Smoking cessation, 107, 139, 296
Red yeast rice (Monascus purpureus), 57, Soluble fiber, 201
63, 64, 202 Soy foods, 12
for preventive cardiology, 196–97 Soy protein, 194, 229
INDEX 323
Spergularia purpurea, 63 Takotsubo cardiomyopathy, 212

Spiritual crises, death, and dying, Tea, 11
177–78 Thiamine, 275–76
Spiritual direction or counseling, Thiazolidinedione, 204
125–26 Tocopherols, 10
Spiritual self-care practices, 125 Traditional Chinese Medicine,
Spiritual Well-Being Scale 57, 101–2, 172
(SWBS), 123 acupuncture. See Acupuncture
Spirituality, 117–19, 130–31 Transcendental Meditation (TM), 257
addressing, 123–26 for hypertension, 236–37
assessing, 122–23 Transcutaneous electrical stimulation
barriers to and facilitators of spiritual (TENS), 106, 108,
care, 124–25 109, 112
characteristics of, 120t Traumatic grief symptoms, 236
defining, 119–20 Triglycerides, 32, 196, 197, 204–5
and health outcomes, relationship fish oil, 205–6
between, 120–21 homocysteine, 208–9
of physicians. physician hs-CRP, 207–8
spirituality low vitamin D, 210–11
Spironolactone, 270, 275 Lp(a), 206–7
Starling’s Law, 84 Trimethylglycine, 209
Statin intolerance
metabolic causes of, 199 Ultra-low-fat diets, 4, 6
strategies for, 201
Statin-related myalgias, 199 Valerian (Valeriana officinalis),
and coenzyme Q10, 200–201 64–65
Statin therapy, for CAD, 88, 252–53 Valyl-Tyrosine (VAL-TYR), 229
vs. invasive procedures, 253 Varicose veins, 65
Statins, 204 Vascular tonics, 65
Strength training, 31 Vasoconstriction, 22
Stress, 148–49, 280 Vegetables, 13–14
acute stress and cardiac events, Vibrational medicine. See Energy
149–50 medicine
chronic stress and CAD, 150–51 Vitamin B-6, 232
mechanisms of action, 151 Vitamin C, 10
management, 254 for hypertension, 232–33
Stress heart failure, 212 Vitamin D
Supplements, dietary, 14 for hypertension, 232
Sweets, healthy, 11–14 low, 210–11
Sympathetic nervous system, 149f Vitamin E, 10, 250–51
Systemic vascular resistance (SVR), 22
Systolic blood pressure (SBP), 228 Wakame seaweed (undaria
pinnatifida), 231
Tai Chi, 172–73, 258–59, 280 Walking, 189
for hypertension, 237–40 labyrinth, 125
324 INDEX
Water, 10–11 Whole wheat bread, 7

Western allopathic medicine, 248 Women’s Health Initiative Observational
Western-based diagnostic tests and Study, 37, 189
pharmaceuticals, 249 Worry, 147
White or “fast” fibers (twitch
type 2), 20 Yoga, 240, 299
White squill (Urginea for hypertension, 240–41
maritima), 61 Yo-yo dieting, 279

Integrative Cardiology

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Integrative Cardiology

Weil Integrative Medicine Library

Donald I. Abrams and Andrew T. Weil: Integrative Oncology

James E. Dalen, MD, MPH, FACC

Oxford New York

Copyright © 2011 by Oxford University Press.

Published by Oxford University Press, Inc.

Oxford is a registered trademark of Oxford University Press

Library of Congress Cataloging-in-Publication Data

SECTION I: The Foundations of Integrative Cardiology

8. Cardiac Behavioral Medicine: Mind–Body

SECTION II: Integrative Approaches to Cardiovascular Disease

Additional Resources 311

James E. Dalen, MD, MPH, FACC Mimi Guarneri, MD, FACC

Mary Jo Kreitzer, PhD, RN Stephen T. Sinatra, MD, FACC,

John Longhurst, MD, PhD Christopher Suhar, MD

Gulshan K. Sethi, MD, FACC

What Is Integrative Medicine?

Integrative medicine is the intelligent combination of conventional medicine

Prevention is the cornerstone of integrative medicine. In Chapter 10,

■ The mainstream North American diet promotes the develop-

• It provides too much of the unhealthy fats: saturated fat (especially

• It is top-heavy in animal foods, especially beef. Diets high in animal

The Antiinﬂammatory Diet

• Aim for variety.

• On a 2,000-calorie-a-day diet, adult women should eat about 160 to

• On a 2,000-calorie-a-day diet, 600 of those calories can come from

• Include in your diet avocados and nuts–especially walnuts, cashews,

• On a 2,000-calorie-a-day diet, daily intake of protein should be

• To get maximum natural protection against age-related diseases,

• Eat cruciferous (cabbage-family) vegetables regularly.

VITAMINS AND MINERALS

The following chart offers practical suggestions for how to incorporate

Healthy Herbs & Spices

Other Sources of Protein

Healthy choices: Natural cheeses, natural yogurt, omega-3 enriched eggs,

Cooked Asian Mushrooms

Whole Soy Foods

Fish & Seafood

Whole & Cracked Grains

Pasta (al dente)

Beans & Legumes

de groof, R. Remodeling of age- and diabetes-related changes in extracellular matrix.

■ Physical inactivity is one of the most prevalent modifiable risk

surgeon general and various medical organizations, many individuals have

increases (up to 50x) in skeletal muscle metabolism and work performed

PERIPHERAL MUSCLE AND VASCULATURE

The peripheral, or skeletal, muscles performing the work of exercise are

Table 2.1. Examples of Common Physical Activities for Healthy US Adults by

Walking slowly/strolling Walking briskly (3–4 mph) Walking briskly uphill or

Cycling, stationary (<50 W) Cycling for pleasure or Cycling, fast or racing

Swimming, slow treading Swimming, moderate effort Swimming, fast treading

Stretching exercises/yoga General calisthenics Cross-country skiing/

∗∗∗ Racket sports/table tennis Singles tennis/

Golf, power cart Golf, pulling cart/carrying clubs ∗∗∗

Bowling ∗∗∗ ∗∗∗

Fishing, sitting Fishing, standing/casting Fishing in stream

Home care, carpet Home care, general cleaning Moving furniture