Open Access Review

Article DOI: 10.7759/cureus.29480

Obesity and Coronary Artery Disease: An Updated

Systematic Review 2022
Received 08/15/2022
Mohana Priya Manoharan 1 , Rabab Raja 2 , Aneeque Jamil 1 , Denise Csendes 1 , Sai Dheeraj Gutlapalli 1 ,
Review began 08/26/2022 Keerthana Prakash 1 , Kiran Maee Swarnakari 1 , Meena Bai 2 , Darshi M. Desai 3 , Aditya Desai 4, 5 , Sai Sri
Review ended 09/14/2022 Penumetcha 6, 7
Published 09/23/2022

© Copyright 2022 1. Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA 2. Medicine,
Manoharan et al. This is an open access California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA 3. Division of Research & Academic
article distributed under the terms of the Affairs, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA 4. Internal Medicine Clinical
Creative Commons Attribution License CC-
Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA 5. Internal Medicine,
BY 4.0., which permits unrestricted use,
University of California Riverside School of Medicine, Riverside, USA 6. General Medicine, California Institute of
distribution, and reproduction in any
medium, provided the original author and Behavioral Neurosciences & Psychology, Fairfield, USA 7. General Medicine, Chalmeda Anand Rao Institute of Medical
source are credited. Sciences, Karimnagar, IND

Corresponding author: Mohana Priya Manoharan , [email protected]

Abstract
The primary goal is to identify the pathogenesis of cardiovascular illnesses in obese patients. Articles were
extracted using the MeSH search approach from PubMed and Google Scholar databases. Inclusion and
exclusion criteria were used, and duplicates were eliminated. Eight publications were finally included in this
research study after two authors independently completed the quality check appraisal. Seven observational
studies and one narrative review were found in our search. The publications evaluated the risk of coronary
artery disease in metabolically healthy obese people with that of unhealthy obese adults and evaluated the
effects of adipose tissue-mediated inflammation. Additionally, they offered several explanations for the
obesity problem. Studies have indicated that adipocytokines and their pro-inflammatory cytokines have
significantly affected the development of cardiovascular disease in obese subjects. The relationship between
metabolically unhealthy people with increased risk for coronary artery disease (CAD) is unclear. It has also
been shown that metabolically healthy obese persons are still at risk for developing coronary artery disease
(CAD), as explained in certain studies in which inflammation plays a vital role in obese people. There hasn't
been much data on the advantages of being physically active in overweight people, but obese people have to
change their lifestyle as a first measure.

Categories: Cardiology, Internal Medicine, Pathology

Keywords: overweight, weight loss, metabolic syndrome, body mass index, adipocytokines, metabolic phenotypes,
obesity paradox, metabolically healthy obesity, coronary artery disease, obesity

Introduction And Background

Obesity and overweight play a key role in the development of cardiovascular disease or myocardial ischemia,
particularly today, as does their relationship to traditional and non-traditional risk factors [1]. In this
modern society, a new threat to health is the obesity epidemic [2]. The most common cause of death
worldwide is cardiovascular disease [2], and obesity is the most critical factor in the development of
coronary heart disease [3]. It is believed that the global spread of unhealthy lifestyle factors such as smoking,
overweight, inactivity, and type 2 diabetes mellitus can partially explain this increasing change in the global
epidemiological pattern [4]. As known, obesity is one of the most significant threats the world is facing, and
it’s increasing progressively over the past decades [4]. The first wave of the obesity pandemic has already
occurred in some high-income countries, and the second wave has hit some low- and middle-income
countries [4]. More than 25% of the adult population in some middle-income nations, including Mexico,
Argentina, Libya, Jordan, Egypt, and South Africa, are reported to be obese today. This is a significant
change from only two decades ago [4].

Obesity is the increased storage of body fat and its pathogenesis involving multiple factors [5]. A tool used to
assess obesity is the body mass index of ≥30 kg/m2 [4]. This statement has limitations, such as fit people
with greater muscle mass can have the same body mass index (BMI) as unfit people with larger fat mass [4].
Other measures of obesity that have been suggested are waist-to-hip ratio, waist-to-height ratio, and waist
circumference [4]. The risks of developing CAD increased by 40% with every 10 cm rise in waist
circumference, with an odds ratio of 1.04 (95% CI: 1.01-1.07, P = 0.013) for a 1 cm increment [4]. The obesity
paradox has been seen in some patient populations, but the pathophysiologic mechanisms causing it are not
fully understood [6]. Metabolically healthy obesity (MHO) is one type of obesity without any cardiometabolic
risk factors such as hypertension, dyslipidemia, insulin resistance, and type 2 diabetes mellitus [7]. It appears
that those who exhibit the metabolically healthy obesity (MHO) phenotype do not have an increased risk of
developing atherosclerosis [8].

Certain studies have suggested that metabolically healthy obese will progress to metabolically unhealthy

How to cite this article

Manoharan M, Raja R, Jamil A, et al. (September 23, 2022) Obesity and Coronary Artery Disease: An Updated Systematic Review 2022. Cureus
14(9): e29480. DOI 10.7759/cureus.29480
 obese [8]. Also, the previous results have concluded that, compared to non-obese people, people with MHO
are at increased risk for atherosclerosis [8]. Although previous studies have recommended that obesity
increases the risk of coronary artery disease, the connection between body mass index (BMI) and age of
presentation of symptomatic coronary artery disease (CAD) has not been well explained [3].

Management has been outlined and found effective for coronary artery disease [8]. However, obese patients
exhibit myocardial ischemia even in the absence of occlusion of large coronary arteries [9], which can be due
to any alterations in the coronary microcirculation [9].On a generalized note, in subjects with type 2
Diabetes mellitus, the coronary microvascular disease is recognized by small artery vasospasm and
microvascular obstruction [9], but in obese people before the development of hyperglycemia, it is quite rare
for these morphological changes to be observed in the microvessels [9]. Certain studies have observed that
myocardial perfusion is reduced in obese people, and others have stated that myocardial perfusion is not
altered in obesity [9]. Reduced myocardial perfusion is a claim that may be caused by coronary microvascular
capillary’s impaired ability to act as vasodilators, which is a result of some significant cardiovascular risk
factors that contribute to the pathogenesis of obesity [9].

The main objective is to conduct a systematic review to ascertain the connection between the obesity
paradox, how individuals with metabolic syndrome and obesity are more likely to experience cardiac
complications like coronary artery disease, the underlying pathophysiology, and the effects of weight loss on
obesity.

Review
Methods
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines;
the MeSH strategy was obtained after finalizing the topic and selecting keywords such as obesity, coronary
vascular disease, and myocardial infarction. Articles were accessed from PubMed, and the inclusion and
exclusion criteria were applied. The reports relevant to the topic present within the last 10 years and the
papers available in the English language alone are selected. Once we obtained the results, duplicates were
removed. The documents were also searched manually and obtained from Google Scholar. After this, the
articles were screened by topic name and by reading the abstracts. After doing this, full-text papers for the
remaining articles were downloaded, and the research articles were further redefined after applying the
eligibility criteria (inclusion and exclusion). The next step, quality appraisal or quality check, was done by
two authors independently. The quality appraisal tool used was the SANRA checklist; based on this, the
articles were included in the final review of the study. Below is Table 1, which shows the search strategy
obtained by MeSH. Table 2, which lists the inclusion and exclusion criteria applied, and Figure 1 [10], below
explains our search strategy and the literature review process through a PRISMA flow diagram.

SEARCH STRATEGY

Obesity ( "Obesity/complications"[Majr] OR "Obesity/etiology"[Majr] OR "Obesity/pathology"[Majr] OR "Obesity/physiology"[Majr] OR

"Obesity/physiopathology"[Majr] ) AND Coronary Heart Disease OR Myocardial Infarction( "Coronary Disease/complications"[Majr] OR
"Coronary Disease/etiology"[Majr] OR "Coronary Disease/pathology"[Majr] OR "Coronary Disease/physiology"[Majr] OR "Coronary
Disease/physiopathology"[Majr] )

TABLE 1: MeSH Search Strategy

Inclusion criteria Exclusion criteria

Articles associated with the data Articles not associated with the data

Articles from the last 10 years Articles more than 10 years

Articles in the English language Articles that were not in the English language

TABLE 2: Applied Inclusion and Exclusion Criteria

2022 Manoharan et al. Cureus 14(9): e29480. DOI 10.7759/cureus.29480 2 of 9

 FIGURE 1: PRISMA Flow Diagram
Ref: [10]

Results
From a preliminary screening of 13631 papers, eight articles were chosen for participation in the study.
Seven of the eight items in this collection were full-text free downloads from PubMed, while one was from
Google Scholar. These articles describe how obesity affects coronary artery syndrome and contrast the risks
of developing coronary artery disease (CAD) in obese people with and without metabolic abnormalities. The
finalized articles are included in Table 3 below, along with their intended audience.

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 Year of
Author Purpose of study Intervention studied Result/ conclusion
publication

Metabolically healthy obese

To compare coronary artery
subjects have a higher incidence of
Yoosoo calcium scores in metabolically
2014 Coronary artery calcium scores subclinical coronary artery
Chang [11] healthy obese individuals and
atherosclerosis when compared to
normal-weight individuals.
normal-weight individuals.

The release of adipokines and

To find the involvement of proinflammatory cytokines from
Zsolt bagi
2014 adipose tissue mediated Role of adipokines adipose tissue plays an important
[9]
inflammatory response role in coronary microvascular
inflammation

Obesity increases the risk of CAD

Eiman through changes in the endothelial
The relationship between obesity
Jahangir 2014 Risk factors of the obesity paradox function and other inflammatory
and coronary artery disease
[12] responses and also alters the lipid
profile

levels of serum resistin and leptin,

Increased levels of leptin and CRP,
To evaluate the relationship C-reactive protein (CRP), lipid
Farzaneh (p < 0.001), cholesterol (p < 0.05),
between serum resistin and profile and cardiac enzyme tests,
Montazerifar 2012 triglyceride (p < 0.01), and WC (p <
leptin levels with obesity and and calculating of body mass index
[13] 0.05) is found in CAD patients
coronary artery disease (CAD) (BMI), and waist circumference
compared to healthy controls.
(WC)

MHO subjects have a lower risk of

To assess the cardiometabolic diabetes, stroke, and CHD when
Fangjian Used indices of blood pressure,
2016 risk in metabolically healthy compared to unhealthy subjects but
Guo [14] blood glucose, and blood lipids
obesity and unhealthy obesity diabetes risk is higher when
compared with healthy lean people

Diana A. To determine abdominal obesity Assess between metabolic Waist circumference cut-off points
2020
Chirinos [15] as a risk factor for CAD syndrome and abdominal obesity determining the risk of CAD

To determine the influence of

isolated overweight and obesity Metabolically healthy subjects have
Eva
on carotid intima-media Metabolic phenotypes and carotid greater carotid intima-media
Talavera- 2016
thickness and also whether it is artery ultrasound thickness when compared to
Garcia [16]
associated with metabolic metabolically healthy subjects
abnormalities

Further need to evaluate the

Tiffany M. To determine the influence of
Invasive and non-invasive mechanisms for obesity-related
Powell- 2021 obesity on cardiovascular
diagnostic tests cardiac dysfunction and
Wiley [17] disease
management options

TABLE 3: Study Characteristics

Discussion
Pathophysiology of Obesity in Coronary Artery Disease (CAD)

The pathological role and management of atherogenic dyslipidemia in the development of obesity-related
coronary artery disease are well known [9]. Adipocytokines have a significant role in the incidence of
cardiovascular diseases [13]. The hormones like peptides and other molecules secreted from the adipose
tissue likely act as pro-atherogenic markers [13]. Adipokines released from adipocytes consist of
adiponectin, leptin, resistin, vascular endothelial growth factor (VEGF), and pro-inflammatory cytokines,
such as TNF, IL-1, IL-6, and monocyte chemoattractant protein-1 (MCP-1) [9]. In obesity, the endocrine
function of adipocytes is changed, with decreased adiponectin [9] and increased levels of leptin, resistin, IL-
6, and tumor necrosis factor (TNF) [9]. During the prolonged follow-up periods, it was observed that patients
who had been obese at baseline stayed obese and infrequently turned lean. This was true for both young
adults and young-older adults who were obese [14]. The prognosis of CAD can sometimes be evaluated with
the serum level of adipokines, which is used in screening, diagnosing, and predicting atherosclerosis [13].

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 Increased body mass leads to increased metabolic requirements [9]. In "uncomplicated" obesity, enlarged left
ventricular mass might be an early adaptation of cardiac function, compensating for the greater
hemodynamic and metabolic demand in obesity [9]. Inflammatory processes linked to obesity occur in both
vascular and non-vascular tissues, and endothelial cells are activated by the vasoactive chemicals secreted
by adipocytes, such as resistin and leptin [13].

Role of Adiponectin, Resistin, and Leptin

In general, adiponectin is found to have a protective effect on the heart and safeguards from ischemia-
reperfusion injury via a combination of AMP kinase- and cyclooxygenase-2-dependent mechanisms [9]. In
obesity, this effect declines because of low adiponectin levels [9]. Also, it raises nitrous oxide (NO)
bioavailability, producing vasodilation [9]. It contributes to the loss of vasodilator properties in obese people
with metabolic syndrome [9]. Insulin resistance diabetes develops in obese individuals as a result of low
levels of adiponectin, which is the primary consequence of the insulin-sensitizing hormone [9]. Adiponectin
has a trimeric, hexameric, and high molecular weight structure in serum and cells. A defect in adiponectin
multimerization affects the protein's stability and secretion, which is linked to insulin resistance [9].

The role of an appetite-regulating hormone known as leptin is weight reduction by acting through
hypothalamic neurons, activating the catabolic pathway, and inhibiting the anabolic pathway [9]. Therefore,
lower leptin levels were associated with increased weight gain in healthy individuals [9]. In contrast, obese
people were found to have higher leptin levels denoting leptin resistance rather than inadequate leptin
production [9]. Additionally, elevated levels of leptin also modify the vasomotor function in obesity [9]. With
leptin, there is greater endothelial NO synthase (eNOS) expression with low intracellular L-arginine levels
contributing to the uncoupling of eNOS and production of superoxide and peroxynitrite production [9]. But
the overall contribution of adipocyte-derived leptin to coronary artery dysfunction remains unclear [9].

Resistin plays a vital role in metabolic homeostasis and is found to be elevated in obesity [9]. The known
potent vasoconstrictor endothelin -1 expression is increased by resistin [9]; glucose and glucocorticoids have
a significant role in the induction of resistin, whereas insulin and TNF inhibit the resistin expression [9];
greater plasma resistin levels are interrelated with inflammatory markers such as TNF receptor-2, IL-6,
lipoprotein-associated phospholipase A2 and with higher coronary calcium score which measures the
severity of coronary sclerosis [9]. In the secretory vesicles found in adipocytes, leptin and resistin are
grouped into each secretory vesicle, where its secretion is modulated by the cellular level of cAMP and
protein kinase A as well as insulin/glycolytic substrates [9]. In patients with symptomatic coronary artery
disease, a correlation was discovered with resistin [9].

Certain studies have also concluded that adipokines such as resistin, leptin, and adiponectin have adverse
effects on coronary arteriolar dilation in obesity which in turn is related to the development of coronary
artery disease [9]. These effects are supported by the loss of NO and increased reactive oxygen species (ROS)
production in the coronary arteries of obese subjects [9]. Obesity is connected with inflammation, evidenced
by increased C-Reactive protein (CRP) levels [13]. Studies have proved that inflammation associated with
elevated levels of resistin and leptin has a significant role at the beginning of the mechanism of
inflammation and leads to the advancement of atherosclerotic disease [13], as a known factor that CRP is an
important marker determining the degree of inflammation, this elevated levels of resistin and leptin, in
turn, induces the production of CRP in coronary endothelial cells and this CRP promotes vascular
thrombosis that might be involved in the acute coronary syndrome pathophysiology process [13]. In that
same study, it has shown that leptin and resistin are linked with coronary artery disease regardless of CRP
[13].

Cardiometabolic Criteria

Wildman has formulated cardiometabolic abnormalities [16]. Guidelines defined by CDC/AHA contain blood
pressure more than 130/85 or currently using any antihypertensive drug, Triglycerides more than or equal to
150mg/dl, fasting blood sugar more than 100 mg/dl [16], or on any anti-diabetic treatment, high-density
lipoprotein (HDL) less than 40 mg/dl in men or less than 50 mg/dl in women, or lipid-lowering treatment is
used, insulin resistance more than 2.6 and CRP more than 3mg/dl [16].

Metabolic Phenotypes

Metabolically healthy normal weight includes BMI < 25 and two metabolic criteria [16]. Metabolically sick
normal weight has BMI <25 and more than or equal to two metabolic measures [16]. Metabolically healthy
overweight includes BMI ranging between 25 to 30 and less than two metabolic criteria [16]. Metabolically
sick overweight has BMI between 25 to 30 and more than or equal to two metabolic measures [16].
Metabolically healthy obese include a BMI of more than 30 and less than two metabolic criteria, whereas
metabolically sick obese includes more than or equal to two metabolic standards and a BMI of more than 30
[16].

Components of Metabolic Syndrome

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 Obesity and overweight are the major determinants of metabolic syndrome and contribute to the
development of cardiovascular diseases [18]. Obesity is also a significant risk factor for both DM and
metabolic syndrome, and increased cases of obesity have been seen due to the prevalence of DM [12].
Metabolic syndrome constitutes a combination of anthropometric, hemodynamic, and metabolic alterations
[15]. In 2009, a clinical diagnosis of metabolic syndrome was released by a joint interim statement issued by
several organizations [15]. This statement compromises a cluster of components such as central obesity,
elevated blood pressure and triglycerides, low high-density cholesterol, and altered glucose metabolism [15].
Metabolic syndrome has a stronger association with developing atherosclerotic cardiovascular disease
[19] both genetic and acquired factors are involved in the pathogenesis of metabolic syndrome, which in
turn leads to the final pathway of inflammation contributing to coronary vascular disease [16]. Weight (kg)
divided by height (m2) can be used to calculate BMI [7]. The World Health Organization defined obesity as
having a BMI of 30 kg/m2, overweight as having a BMI of 25, and average weight as having a BMI of 18.5
kg/m2 [7]. When the metabolic syndrome is identified early, patients should be actively encouraged to make
lifestyle changes, and physicians can take steps to reduce the risk of type 2 diabetes mellitus [15]. The
management of patients already diagnosed with T2DM-associated metabolic syndrome is crucial because it
helps to overcome the known cardiac complications associated with T2DM [15].

Metabolically Healthy and Unhealthy Obesity

Metabolically healthy subjects can be stated as not having any metabolic risk factors such as elevated blood
pressure, triglycerides, not using any drugs for hypertriglyceridemia, and decreased HDL cholesterol levels
[20]. Metabolically unwell people are those who have one or more of the aforementioned risk factors. [20].
Evaluation of metabolic health status has been demonstrated to help predict the result of cardiovascular risk
status [14]. Additionally, it has been noted that obese individuals, even those without metabolic syndrome,
have a higher risk of myocardial infarction [14]. Modified metabolic syndrome has been predicted based on
glycemic statuses, such as self-reported diabetes mellitus (DM), registry-documented diabetes diagnosis,
antidiabetic therapy, and/or nonfasting plasma glucose level greater than 200 mg/dl. [14]. In the CARDIA
study over 20 years, 67.3% of baseline overweight participants and 17.5% of baseline lean subjects both
converted to obesity at the year 20 evaluation [14]. In comparison to younger patients in CARDIA, fewer
older patients in ARIC transitioned from being lean to being obese or from being overweight to being obese,
suggesting that BMI status was more stable over 10 years in subjects in their sixth and seventh decade than
it was in middle-aged adults [14]. The rate of glucose tolerance alone in a metabolically unhealthy subject,
apart from other components of metabolic syndrome, has a greater effect on CAD [20]. Metabolically healthy
obese people seem to have higher coronary artery calcium scores [11]. Also, obese people might have
fibrinolysis impaired and increased hypercoagulability [11] because atherogenesis is mediated by interleukin
- 6 and tumor necrosis factor-alpha released from adipose tissue [11]. Studies have concluded that
metabolically unhealthy subjects have an increased risk for CAD compared to people with metabolically
healthy obesity [14].

On the other hand, metabolically healthy obese (MHO) people have an increased risk of becoming
‘metabolically unhealthy obese [21]. Significantly, metabolically healthy individuals have reduced quality of
life because of the prevalence of other obesity-related comorbidities such as psychological abnormalities,
osteoarthritis, respiratory distress, gynecologic abnormalities, and skin problems [21]. When compared to
metabolically unhealthy obese people, metabolically healthy obese subjects have more abdominal
subcutaneous adipose tissue, lower visceral fat mass, and less fat accumulation in liver and skeletal muscle
with more adipocytes, less macrophage infiltration, and inflammation which, in turn, concludes that MHO
subjects having good inflammatory profile [21].

The Obesity Paradox

As discussed above from various studies, although there is a greater risk of acquiring CVD in obese people,
recently, it has been stated that once CVD gets established in overweight or obese individuals [12], they have
lower mortality when compared with normal-weight people, which is termed as ‘obesity paradox’ [12]. This
paradox has been explained in many cardiovascular diseases, such as CAD, atrial fibrillation, and heart
failure [12]. Mortality rates for overweight and obese men were comparable to those of the highly fit normal-
weight reference group [12]. Patients with high levels of fitness typically have lower mortality rates than
those with lower levels, and adding fitness to other conventional risk factors seems to reduce cardiovascular
mortality [12]. Defining obesity based on BMI might be one of the reasons for this paradox, as it does not
take into consideration lean mass [22]. It has been proposed that before a CVD event, positive caloric
balance causing adiposity leads to pathologic changes in the adipose tissue causing metabolic diseases [12].
Alternatively, the improved clinical outcome has been observed with negative caloric balance as it may occur
during a CV event where adipose tissue responds with enhanced function [12]. Increased muscle strength in
obesity has also been associated with a better prognosis [12].In this evaluation of the obesity paradox, BMI is
a protective factor in both lower and higher CRP groups [23]. In obese people with CAD, endogenous
regenerative capacity can be measured by using cell progenitor counts, which also explains this obesity
paradox [6]. The relation of obesity with adverse outcomes in CAD is indirectly proportional to those with a
preserved endogenous regenerative capacity which is higher cell progenitor cell counts [6]. The analysis of
this paradoxical association finding remains unclear, and also, many theories have been proposed to support
this obesity paradox [22].

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 Obesity as a Risk Factor for Coronary Artery Disease (CAD)

In the past two decades, the global epidemic affecting both children and adult populations has been obesity
[24]. The adverse effects of obesity are due to pathogenesis involving psychosocial, biological,
environmental, and socioeconomic factors [17]. The association between obesity and cardiovascular diseases
has been exclusively studied, but the particular question is still not understood and remains complex [24].
Obesity with comorbidities such as hypertension, dyslipidemia, and glucose intolerance increases the risk of
coronary vascular diseases [24]. When compared to BMI, the measurement of waist circumference was also
found to be a marker for cardiometabolic risk [25]. Obesity can cause CAD, and researchers are looking into
the genes that contribute to the development of obesity to see if there is a link to CAD development [5]. one
of the molecular mechanisms responsible for early life obesity is an epigenetic modification of genes through
methylation, histone modification, chromatin remodeling, and non-coding RNA alterations [26]. This
epigenetic modification increases the risk of getting adult obesity and which can be transmitted to future
generations, thereby responsible for the obesity epidemic [26]. While certain types of obesity are brought on
by solitary mutations, the majority of cases are polygenic and come about as a result of a complicated
interaction between the environment and the genotype [5]. The degree of calcification in the coronary
arteries can be measured using CT, known as coronary artery calcium scores (CACS) [27]. This CACS score is
one of the indicators of atherosclerosis [27], a positive association between high BMI and risk of CAD has
been demonstrated, which showed that every 1kg/m2 increase in BMI led to a 5%-7% increase in the
incidence of CAD across all BMI categories [28]. For very muscular people, BMI may sometimes overestimate
body fat, and for those who have lean muscle mass, BMI may underestimate body fat [28]. A BMI of more
than 30kg/m2 is used to measure general adiposity, and a waist-hip ratio of more than 0.90 for males and
0.85 for males is used to measure central adiposity and its association with CAD [28]. Another study that
used G-estimation for the assessment of obesity and CHD has concluded that a shorter survival rate for CHD
is mainly linked with greater levels of abdominal obesity, either predicted through waist circumference or
waist-to-hip ratio [29]. In G-estimation, three criteria were used to calculate the impact of obesity on CHD
and compare it to accelerated failure time models. All indices of obesity were associated with an elevated
risk of CHD in the first model that was adjusted for baseline variables while removing metabolic mediators
of obesity [29]. Additional adjustments in the second model to account for metabolic mediators and the third
model to account for time-varying factors revealed minimal hazard ratios [29]. Based on waist circumference
and waist-to-hip ratio, respectively, the hazard ratios derived by G-estimation for general obesity were 1.15
(95%CI: 0.83-1.47), 1.65 (95%CI: 1.35-1.92), and 1.38 (95%CI: 1.13-1.99) for abdominal obesity, indicating
that abdominal obesity enhanced the risk of coronary heart disease [29].

Methods Used for Assessment of Coronary Artery Disease (CAD) in Obesity

ECG is extensively available and cheap, but its sensitivity and specificity are found to be low [17]. The ECG
findings for obese people are displacement of the heart with an elevation of the diaphragm in the supine
position, greater cardiac workload, and the distance between the heart and the recording electrodes are
increased [17]. Clinically significant changes in ECG include increased heart rate, increased QRS and QT
interval [17]. In obese people, treadmill stress test performance is limited, and their aerobic capacity is
lowered due to pulmonary dysfunction, orthopedic limitations and left ventricular diastolic dysfunction [17].
These obese people may sometimes stop the stress test because of fatigue, leg pain and dyspnea [17], and
the systolic and diastolic blood pressure are elevated while performing the stress test [17]. Single-photon
emission CT is used in patients with lower-weight individuals, and it is usually avoided in patients whose
BMI is more than 35 kg/m2 [17]. To generate better images in obese subjects, sometimes technetium
sestamibi is used as a marker [17]. Because of the limitation in this single photon emission CT, an alternate
imaging modality used for myocardial ischemia is positron emission tomography [17]. The assessment of
perfusion defects in left ventricular ejection fraction and the detection of scar can be obtained using a
technique called stress cardiac MRI with the use of gadolinium [17]. PET rubidium is faster than single-
photon emission CT [17]. And has advantages like good quality images, less exposure to radiation and better
diagnostic precision but the availability of these tests is limited [17]. In all obese individuals, PET is linked to
fewer cardiac fatalities if myocardial perfusion imaging results are normal. [17]. The quantification of both
coronary and non-coronary calcified plaque can be evaluated by CT coronary angiography [17]. Plaque
characterization and quantification and luminal stenosis evaluation can be done using this CT coronary
angiography, whereas CAC allows only risk stratification and assessment of plaque burden [17]. The two
invasive evaluations are coronary angiography and invasive coronary ultrasound [17].

Impact on Weight Loss

With regular physical activity and aerobic exercise, the risk factors of CAD can be moderately reduced,
evidenced by low body fat and body mass, low blood pressure, low triglycerides, and increased high-density
cholesterol [30]. Improves insulin sensitivity and endothelial function regardless of weight loss [17]. The
general idea of this weight loss management is to reduce body weight so as to prevent further weight gain
and maintain a lower body weight [17]. The overweight or obese individuals with weight loss targets of 5% to
10% have been shown to significantly improve the health outcome of obesity-associated complications [31].
Losing weight can aid in the prevention of T2D in people who are obese and have prediabetes, and it has a
favorable long-term effect on cardiovascular mortality [31]. The efficacy of weight loss treatment can be
determined by measuring BMI and WC [17]. Also, there is no evidence that studies demonstrate a reduction

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 of coronary vascular disease or mortality with lifestyle modification such as exercise alone [17]. The degree
of weight loss obtained (5-10 kg with medical weight loss versus 10-40 kg with surgery) and the reduction in
risk factors seen with bariatric surgery are likely the causes of the discrepancies between the outcomes of
weight loss trials using medical and surgical methods [17]. But what is certain is that for obese patients with
CAD, fitness seems to improve prognosis, and therefore, physical activity and exercise training are
recommended as it is accompanied by purposeful weight loss [12].

Limitations
There are several limitations included in this study. The articles included are mainly observational studies, as
it does not mean to prove causation. Since the sample size varies in each study, the outcomes that have been
discussed cannot be applied to all age groups. This study was also conducted with articles taken from the
English language, so the conclusions in other language articles were not known.

Conclusions
With a sedentary lifestyle becoming more prevalent nowadays, the relationship between obesity and the
development of coronary artery disease has been explained by the pathophysiology involved. Adipokines
from adipose tissue, such as resistin, leptin, adiponectin, and TNF, play a vital role in the inflammation
process, which is the main reason for the development of atherosclerosis. Obesity is a significant component
of metabolic syndrome. With six types of metabolic phenotypes present, a greater risk of CAD is associated
with metabolically unhealthy people when compared to metabolically healthy subjects. Additionally, a
paradox exists that says obese people with CAD are associated with decreased mortality. This research has
also yet again shown that inflammation is the major culprit, which plays an important role in the
development of coronary artery disease. The articles that were shortlisted and included in this study have a
common association that inflammation and further endothelial damage caused by the release of pro-
inflammatory cytokines play a vital role in the development of coronary artery disease in obese people, and
further, these articles show that metabolically unhealthy obese people have a greater risk of coronary artery
disease when compared to metabolically healthy obese people. Additionally, it has been proven that obese
people can benefit from losing weight. Even though so many studies have supported the notion put forth
above, the relationship between obesity and CAD is still not clear. Future research should take this into
account, and more randomized controlled trials should be conducted because the majority of studies
currently available are only observational studies.

Additional Information
Disclosures
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the
following: Payment/services info: All authors have declared that no financial support was received from
any organization for the submitted work. Financial relationships: All authors have declared that they have
no financial relationships at present or within the previous three years with any organizations that might
have an interest in the submitted work. Other relationships: All authors have declared that there are no
other relationships or activities that could appear to have influenced the submitted work.

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