OBJECTIVE:To evaluate the association between estrogen therapy and cardiovascular disease risk among women with type 2 diabetes. RESEARCH DESIGN AND METHODS:A retrospective, case-cohort study was conducted among 6017 women aged 45-80 years with type 2 diabetes from 1 January 1986 to 31 December 1992 at the Group Health Cooperative in Washington state. Cardiovascular outcomes, including nonfatal myocardial infarction (n = 215), coronary revascularization (n = 253), and cardiovascular deaths (n = 229), were ascertained through 31 December 1998. Use of estrogen and progestin was derived from automated pharmacy records and modeled as a time-dependent variable. Median follow-up was 6.8 years. Multivariable-adjusted relative risk (RR) and 95% CI were calculated using Cox proportional hazard models for case-cohort analyses. RESULTS:Current use of estrogen with (RR 0.43, 95% CI 0.22-0.85) or without (0.48, 0.30-0.78) progestin was associated with a decreased risk of cardiovascular events compared with never having used estrogen. Risk of cardiovascular events associated with a first episode of estrogen use (with or without progestin) of <25 months' duration (1.12, 0.49-2.54), first episode of use >or=25 months' duration (0.32, 0.06-1.70), and current use that was not the first episode of use (0.42, 0.42-0.67) indicated that recent initiation was not associated with an increase or decrease in risk. CONCLUSIONS:These results show an association of estrogen therapy, with or without progestin, with decreased risk of cardiovascular events among women with type 2 diabetes. This association should be further investigated in large randomized, controlled trials.

Background Premature ventricular contractions (PVCs) predict heart failure and death. Data regarding modifiable risk factors for PVCs are scarce. Methods and Results We studied 1424 Cardiovascular Health Study participants randomly assigned to 24-hour Holter monitoring. Demographics, comorbidities, habits, and echocardiographic measurements were examined as predictors of PVC frequency and, among 845 participants, change in PVC frequency 5 years later. Participants exhibited a median of 0.6 (interquartile range, 0.1-7.1) PVCs per hour. Of the more directly modifiable characteristics and after multivariable adjustment, every SD increase in systolic blood pressure was associated with 9% more PVCs (95% confidence interval [CI], 2%-17%; P=0.01), regularly performing no or low-intensity exercise compared with more physical activity was associated with ≈15% more PVCs (95% CI, 3-25%; P=0.02), and those with a history of smoking exhibited an average of 18% more PVCs (95% CI, 3-36%; P=0.02) than did never smokers. After 5 years, PVC frequency increased from a median of 0.5 (IQR, 0.1-4.7) to 1.2 (IQR, 0.1-13.8) per hour ( P<0.0001). Directly modifiable predictors of 5-year increase in PVCs, described as the odds per each quintile increase in PVCs, included increased diastolic blood pressure (odds ratio per SD increase, 1.16; 95% CI, 1.02-1.31; P=0.02) and a history of smoking (OR, 1.31; 95% CI, 1.02-1.68; P=0.04). Conclusions Enhancing physical activity, smoking cessation, and aggressive control of blood pressure may represent fruitful strategies to mitigate PVC frequency and PVC-associated adverse outcomes.

We investigated the association between hormone replacement therapy (HRT), primarily conjugated estrogens with or without medroxyprogesterone acetate, and colon cancer risk in a nested case-control study among women ages 55-79 years enrolled in Group Health Cooperative, a health maintenance organization in Washington state. Cases were diagnosed between 1984 and 1993. We selected controls randomly from enrollment files. HRT use was ascertained from a computerized database containing virtually all prescriptions dispensed since 1977. Among subjects with at least 5 years of pharmacy database information before reference date (1 year before diagnosis date), there were 341 cases of incident colon cancer and 1,679 controls. Estrogen use during the 5 years before reference date was not associated with risk of colon cancer [odds ratio (OR) = 0.85 and 95% confidence interval (CI) = 0.57-1.27 for 1-749 estrogen tablets; OR = 0.97 and 95% CI = 0.68-1.40 for > or =750 estrogen tablets]. An analysis including only women with at least 10 years of pharmacy database coverage found no association with use during the 10 years before reference date [OR = 1.07 (95% CI = 0.61-1.86) for 1-749 estrogen tablets; OR = 1.11 (95% CI = 0.69-1.80) for 750 or more estrogen tablets]. These results do not support the hypothesis that recent HRT use substantially reduces risk of colon cancer.

AIMS:Premature atrial contractions (PACs) are known to trigger and predict atrial fibrillation (AF). We sought to identify the determinants of PACs and the degree to which PACs mediate the effects of established risk factors for AF. METHODS AND RESULTS:Predictors of baseline PAC frequency were examined using a Holter Study among 1392 participants in the Cardiovascular Health Study, a community-based cohort of individuals aged ≥65 years. Participants were then followed for their first diagnosis of AF. Independent predictors of PACs were identified, and the extent to which PACs might mediate the relationship between those predictors and AF was determined. The median hourly frequency of PACs was 2.7 (interquartile range 0.8-12.1). After multivariable adjustment, increasing age, increasing height, decreasing body mass index, and a history of myocardial infarction were each associated with more PACs. Regarding modifiable predictors, participants using beta-blockers had 21% less [95% confidence interval (95% CI) 9-30%, P = 0.001] and those performing at least moderate intensity exercise vs. lower intensity exercisers had 10% less (95% CI 1-18%, P = 0.03) PACs. Higher PAC frequency explained 34% (95% CI 22-57%, P < 0.0001) of the relationship between increasing age and AF risk and 27% (95% CI 10-75%, P = 0.004) of the relationship between taller height and AF risk. CONCLUSION:Enhancing physical activity and use of beta-blockers may represent fruitful strategies to mitigate PAC frequency. A substantial proportion of the excess risk of AF due to increasing age and taller height may be explained by an increase in PAC frequency.

Background

Though it is a widely held belief that caffeinated beverages predispose individuals to arrhythmias, it is not clear whether regular coffee consumption is associated with development of atrial fibrillation (AF).

Objective

We examined the association between long-term coffee consumption and development of AF in both habitual (≥0.5 cups of daily coffee) and nonhabitual (<0.5 cups/day) drinkers.

Methods

A total of 5,972 men and women, aged 45-84 years and without a history of cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA) were followed from 2000 to 2014 for incident AF with baseline coffee consumption assessed in 2000-2002 via a Food Frequency Questionnaire and divided into quartiles of 0 cups/day, >0 to <0.5 cups/day, ≥0.5 to 1.5 cups/day, and ≥1.5 cups/day.

Results

Out of the 828 incident cases of AF, intermittent coffee consumption (>0 to 0.5 cups of daily coffee) was associated with a greater risk of incident AF (HR 1.22, 95% CI 1.01-1.48) relative to 0 cups/day in multivariable Cox proportional hazards models after adjustment for numerous AF risk factors. This relation was particularly pronounced in men (adjusted HR=1.36, 95% CI 1.04-1.77). Higher coffee consumption was not associated with AF risk (HR 1.03, 95%CI 0.93-1.14 for ≥0.5 to 1.5 cups/day and 1.05, 95%CI 0.97-1.13 for ≥1.5 cups/day).

Conclusions

While there appears to be no dose-response association between habitual coffee intake and AF risk, we found evidence that intermittent, but not habitual, coffee consumption is associated with a modestly increased risk of incident AF that deserves further study.

Introduction

Epidemiological studies generally have not found plasma total fibrinogen to be a risk factor for venous thromboembolism (VTE), but several have reported associations between variants in the fibrinogen gamma gene (FGG) and VTE. A case-control study in whites suggested plasma γ' fibrinogen concentration may be associated inversely with VTE, but this was not replicated in African Americans.

Objective

To examine the prospective association between γ' fibrinogen concentrations and occurrence of VTE.

Methods

We used the Longitudinal Investigation of Thromboembolism Etiology (LITE), involving two pooled population-based cohorts in the United States including 16,234 participants. The cohorts comprised white and African American men and women, aged 50years and older at study onset in the early 1990s. We identified VTEs during follow-up and documented they met standardized diagnostic criteria.

Results

During two decades of follow-up, neither γ' fibrinogen nor total fibrinogen nor their ratio was associated with VTE overall (n=521 VTEs), in subgroups defined by race, or in other subgroups. In both race groups, the minor allele of FGG rs2066865 was associated with lower γ' fibrinogen concentrations, but this allele was not associated with VTE.

Conclusions

A lower plasma concentration of γ' fibrinogen in healthy adults does not appear to increase VTE risk.

Inaccurate self-reported data on medication exposure lead to less reliable study findings. From 2013 to 2015, we assessed the validity of information on medication use collected via a mailed medication inventory among 223 Women's Health Initiative participants who were members of a health-care delivery system. Self-reported information on medication use was compared with pharmacy records for statins, calcium channel blockers, β-blockers, and bisphosphonates. We assessed sensitivity, specificity, and positive predictive value (PPV) for current medication use. We assessed agreement on duration of use (<2, 2, 3, 4, or ≥5 years) by means of the weighted κ statistic. The mean age of participants was 77 years. Statins, β-blockers, and calcium channel blockers were each reported by over 15% of women, and bisphosphonates were reported by 4.5%. Compared with pharmacy records, the sensitivity, specificity, and PPV for self-reported use of statins, β-blockers, and calcium channel blockers were all 95% or greater. The sensitivity and PPV for bisphosphonate use were both 80% (95% confidence interval: 44, 97), and specificity was 99% (95% confidence interval: 97, 100). The κ statistic for duration of use was 0.87 or greater for all 4 medication classes. Compared with pharmacy records, self-reported information on current medication use and duration of use collected via mailed medication inventory among older women had almost perfect agreement for use of statins, β-blockers, and calcium channel blockers.

The effects of estrogen replacement therapy on prognosis in women with established coronary disease remain uncertain. The authors conducted a retrospective cohort study of 726 women (mean age, 66.2 years) who survived first myocardial infarction to hospital discharge from 1980 through 1991, while enrolled at Group Health Cooperative of Puget Sound in western Washington State. Estrogen replacement therapy after myocardial infarction (122 women) was ascertained from computerized pharmacy records. Reinfarctions (n = 135) and deaths (n = 183) through 1993 were identified, and relative risks were calculated. The relative risk for reinfarction associated with current estrogen replacement therapy after myocardial infarction, adjusting for age and time since infarction, was 0.64 (95% confidence interval (CI) 0.32-1.30), and that for past estrogen replacement therapy was 0.90 (95% CI 0.62-1.31). The relative risk for all-cause mortality associated with current estrogen replacement therapy was 0.50 (95% CI 0.25-1.00), and that for past estrogen replacement therapy was 0.79 (95% CI 0.56-1.09). While estrogen users were less likely than nonusers to have a history of diabetes or congestive heart failure, adjustment for these and additional prognostic factors altered risk estimates only slightly. Estrogen replacement therapy after first myocardial infarction was not associated with increased risk of reinfarction or mortality. This study provides reassurance regarding the safety of estrogen replacement therapy after myocardial infarction in women.

OBJECTIVE: Obesity and dysmetabolism are major risk factors for atrial fibrillation (AF). Fasting and postload levels of glucose and non-esterified fatty acids (NEFAs) reflect different facets of metabolic regulation. We sought to study their respective contributions to AF risk concurrently. METHODS: We assessed levels of fasting and postload glucose and NEFA in the Cardiovascular Health Study to identify associations with AF incidence and, secondarily, with ECG parameters of AF risk available at baseline. Linear and Cox regressions were performed. RESULTS: The study included 1876 participants (age 77.7±4.4). During the median follow-up of 11.4 years, 717 cases of incident AF occurred. After adjustment for potential confounders, postload glucose showed an association with incident AF (HR per SD increment of postload glucose=1.11, 95% CI 1.02 to 1.21, p=0.017). Both glucose measures, but not NEFA, were positively associated with higher P wave terminal force in V1 (PTFV1); the association remained significant only for postload glucose when the two measures were entered together (β per SD increment=138 μV·ms, 95% CI 15 to 260, p=0.028). Exploratory analyses showed significant interaction by sex for fasting NEFA (pinteraction=0.044) and postload glucose (pinteraction=0.015) relative to AF, with relationships stronger in women. For postload glucose, the association with incident AF was observed among women but not among men. CONCLUSIONS: Among older adults, postload glucose was positively associated with incident AF, with consistent findings for PTFV1. In exploratory analyses, the relationship with AF appeared specific to women. These findings require further study but suggest that interventions to address postprandial dysglycaemia late in life might reduce AF.

Objective

Hysterectomy and bilateral salpingo-oophorectomy (BSO) are associated with changes in endogenous hormone levels, yet the risk of venous thrombosis (VT) associated with hysterectomy and BSO is incompletely characterized. This study evaluated the risk of incident VT among postmenopausal women associated with combined prior hysterectomy/oophorectomy status and current use of hormone therapy (HT).

Methods

In a case-control study, we identified incident VT cases (n = 1,623) among postmenopausal Group Health Cooperative enrollees without reproductive cancer, defining their "index date" as their VT diagnosis date (1995-2010). Matched controls had not experienced a prior VT (n = 4,480). Multiple logistic regression models estimated adjusted relative risks for VT associated with combinations of prior hysterectomy/oophorectomy status and HT use at the index date.

Results

Compared with women with an intact uterus who were not using HT, there was no suggestion of greater VT risk in women with prior hysterectomy without BSO, whether they were (adjusted odds ratio [aOR] = 0.80 [95% CI: 0.57, 1.12]) or were not using HT (aOR = 1.09 [95% CI: 0.89, 1.35]). Women with prior hysterectomy and BSO who were using HT were not at a greater VT risk (OR = 1.00 [95% CI: 0.78, 1.27]), but there was evidence of a 25% greater risk associated with prior hysterectomy with BSO and no current HT use (OR = 1.25 [95% CI: 1.05, 1.49]).

Conclusions

Collectively, these and prior data do not suggest a substantial impact of hysterectomy, with or without BSO, on the risk of VT among postmenopausal women.