Search

Background: To our knowledge, the risk of sudden cardiac death (SCD) and the assessment of risk factors in prediction models have not been evaluated in women with coronary artery disease (CAD). We sought to evaluate the incidence of SCD as well as its risk factors and their predictive accuracy among a population of women with CAD., Methods: The Heart and Estrogen/progestin Replacement Study evaluated the effects of hormone replacement therapy on cardiovascular events among 2763 postmenopausal women with CAD. Sudden cardiac death was defined as death resulting from a cardiac origin that occurred within 1 hour of symptom onset. The associations between candidate predictor variables and SCD were evaluated in a Cox proportional hazards model. The C-index was used to compare the predictive value of the clinical risk factors with left ventricular ejection fraction (LVEF) alone and in combination. The net reclassification improvement was also computed., Results: Over a mean follow-up of 6.8 years, SCD comprised 136 of the 254 cardiac deaths. The annual SCD event rate was 0.79% (95% confidence interval, 0.67-0.94). The following variables were independently associated with SCD in the multivariate model: myocardial infarction, heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes. The incidences of SCD among women with 0 (n = 683), 1 (n = 1224), 2 (n = 610), and 3 plus (n = 246) risk factors at baseline were 0.3%, 0.5%, 1.2%, and 2.9% per year, respectively. The combination of clinical risk factors and LVEF (C-index, 0.681) were better predictors of SCD than LVEF alone (C-index, 0.600) and resulted in a net reclassification improvement of 0.20 (P < .001)., Conclusions: Sudden cardiac death comprised the majority of cardiac deaths among postmenopausal women with CAD. Independent predictors of SCD, including myocardial infarction, congestive heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m(2), atrial fibrillation, physical inactivity, and diabetes, improved SCD prediction when they were considered in addition to LVEF.

Background: Dyslipidemia causes coronary heart disease in middle-aged and elderly adults, but the consequences of lipid exposure during young adulthood are unclear., Objective: To assess whether nonoptimal lipid levels during young adulthood cause atherosclerotic changes that persist into middle age., Design: Prospective cohort study., Setting: 4 cities in the United States., Participants: 3258 participants from the 5115 black and white men and women recruited at age 18 to 30 years in 1985 to 1986 for the CARDIA (Coronary Artery Risk Development in Young Adults) study., Measurements: Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides, and coronary calcium. Time-averaged cumulative exposures to lipids between age 20 and 35 years were estimated by using repeated serum lipid measurements over 20 years in the CARDIA study; these measurements were then related to coronary calcium scores assessed later in life (45 years [SD, 4])., Results: 2824 participants (87%) had nonoptimal levels of LDL cholesterol (>or=2.59 mmol/L [>or=100 mg/dL]), HDL cholesterol (<1.55 mmol/L [<60 mg/dL]), or triglycerides (>or=1.70 mmol/L [>or=150 mg/dL]) during young adulthood. Coronary calcium prevalence 2 decades later was 8% in participants who maintained optimal LDL levels (<1.81 mmol/L [<70 mg/dL]), and 44% in participants with LDL cholesterol levels of 4.14 mmol/L (160 mg/dL) or greater (P < 0.001). The association was similar across race and sex and strongly graded, with odds ratios for coronary calcium of 1.5 (95% CI, 0.7 to 3.3) for LDL cholesterol levels of 1.81 to 2.56 mmol/L (70 to 99 mg/dL), 2.4 (CI, 1.1 to 5.3) for levels of 2.59 to 3.34 mmol/L (100 to 129 mg/dL), 3.3 (CI, 1.3 to 7.8) for levels of 3.37 to 4.12 mmol/L (130 to 159 mg/dL), and 5.6 (CI, 2.0 to 16) for levels of 4.14 mmol/L (160 mg/dL) or greater, compared with levels less than 1.81 mmol/L (<70 mg/dL), after adjustment for lipid exposure after age 35 years and other coronary risk factors. Both LDL and HDL cholesterol levels were independently associated with coronary calcium after participants who were receiving lipid-lowering medications or had clinically abnormal lipid levels were excluded., Limitation: Coronary calcium, although a strong predictor of future coronary heart disease, is not a clinical outcome., Conclusion: Nonoptimal levels of LDL and HDL cholesterol during young adulthood are independently associated with coronary atherosclerosis 2 decades later., Primary Funding Source: National Heart, Lung, and Blood Institute.

Background: High blood pressure in middle age is a well-established risk factor for cardiovascular disease, but the consequences of low-level elevations during young adulthood are unknown., Objective: To measure the association between prehypertension exposure before age 35 years and coronary calcium later in life., Design: Prospective cohort study., Setting: Four communities in the United States., Participants: Black and white men and women age 18 to 30 years recruited for the CARDIA (Coronary Artery Risk Development in Young Adults) Study in 1985 through 1986 who were without hypertension before age 35 years., Measurements: Blood pressure trajectories for each participant were estimated by using measurements from 7 examinations over the course of 20 years. Cumulative exposure to blood pressure in the prehypertension range (systolic blood pressure of 120 to 139 mm Hg, or diastolic blood pressure of 80 to 89 mm Hg) from age 20 to 35 years was calculated in units of mm Hg-years (similar to pack-years of tobacco exposure) and related to the presence of coronary calcium measured at each participant's last examination (mean age, 44 years [SD, 4])., Results: Among 3560 participants, the 635 (18%) who developed prehypertension before age 35 years were more often black, male, overweight, and of lower socioeconomic status. Exposure to prehypertension before age 35 years, especially systolic prehypertension, showed a graded association with coronary calcium later in life (coronary calcium prevalence of 15%, 24%, and 38% for 0, 1 to 30, and >30 mm Hg-years of exposure, respectively; P < 0.001). This association remained strong after adjustment for blood pressure elevation after age 35 years and other coronary risk factors and participant characteristics., Limitation: Coronary calcium, although a strong predictor of future coronary heart disease, is not a clinical outcome., Conclusion: Prehypertension during young adulthood is common and is associated with coronary atherosclerosis 20 years later. Keeping systolic pressure below 120 mm Hg before age 35 years may provide important health benefits later in life.

Background: Previous studies suggest that beta-adrenergic receptor (betaAR) single nucleotide polymorphisms (SNPs) are associated with out-of-hospital sudden cardiac death (SCD) and overall mortality, but did not specifically examine risk of ventricular arrhythmias (VA)., Objective: This study examined the effects of functional SNPs of beta1AR and beta2AR on the risk of VA and SCD in patients with coronary artery disease (CAD)., Methods: beta1AR (Ser49Gly, Arg389Gly) and beta2AR (Gly16Arg, Gln27Glu) SNPs were genotyped in a case-control study comparing 107 patients with CAD and aborted SCD due to VA with 287 CAD control subjects and 101 healthy control subjects. These variants were also examined in the Heart and Estrogen Replacement Study (HERS) cohort of women with CAD followed for SCD (n = 66) and nonfatal VA (NFVA) (n = 33) over 6.8 years., Results: In the case-control study, no statistically significant association was observed for the odds of SCD with any of the SNPs or haplotypes tested. Similarly, HERS revealed null effects for these SNPs and haplotypes in relation to risk of SCD, SCD + NFVA, and all-cause mortality. Point estimates and confidence intervals for risk of SCD associated with beta2AR27 were similar in both populations (Glu27 carriers vs Gln27 homozygotes: adjusted odds ratio 1.23 [95% confidence interval 0.75 to 2.03, P = .41] in the case-control study, and adjusted relative risk (RR) 1.18 [95% confidence interval 0.69 to 2.00, P = .55] in HERS). These null findings trend in the opposite direction and differ from previous published estimates (P = .01 and .07, respectively)., Conclusion: We did not find an increase in risk of SCD associated with any of these common betaAR polymorphisms.

Objectives: We sought to determine whether early adult levels of cardiovascular risk factors predict subsequent coronary artery calcium (CAC) better than concurrent or average 15-year levels and independent of a 15-year change in levels., Background: Few studies have used multiple measures over the course of time to predict subclinical atherosclerosis., Methods: African American and white adults, ages 18 to 30 years, in 4 U.S. cities were enrolled in the prospective CARDIA (Coronary Artery Risk Development in Young Adults) study from 1985 to 1986. Risk factors were measured at years 0, 2, 5, 7, 10, and 15, and CAC was assessed at year 15 (n = 3,043)., Results: Overall, 9.6% adults had any CAC, with a greater prevalence among men than women (15.0% vs. 5.1%), white than African American men (17.6% vs. 11.3%), and ages 40 to 45 years than 33 to 39 years (13.3% vs. 5.5%). Baseline levels predicted CAC presence (C = 0.79) equally as well as average 15-year levels (C = 0.79; p = 0.8262) and better than concurrent levels (C = 0.77; p = 0.019), despite a 15-year change in risk factor levels. Multivariate-adjusted odds ratios of having CAC by ages 33 to 45 years were 1.5 (95% confidence interval [CI] 1.3 to 1.7) per 10 cigarettes, 1.5 (95% CI 1.3 to 1.8) per 30 mg/dl low-density lipoprotein cholesterol, 1.3 (95% CI 1.1 to 1.5) per 10 mm Hg systolic blood pressure, and 1.2 (95% CI 1.1 to 1.4) per 15 mg/dl glucose at baseline. Young adults with above optimal risk factor levels at baseline were 2 to 3 times as likely to have CAC., Conclusions: Early adult levels of modifiable risk factors, albeit low, were equally or more informative about odds of CAC in middle age than subsequent levels. Earlier risk assessment and efforts to achieve and maintain optimal risk factor levels may be needed.

Background: Cocaine use is associated with myocardial ischemia and infarction, but it is unclear whether this is only because of the acute effects of cocaine on heart rate, blood pressure, and vasomotor tone or whether accelerated atherosclerosis from long-term exposure to cocaine also contributes., Methods: We sought to measure the association between cocaine exposure and coronary calcification, a marker for atherosclerosis, among participants in the CARDIA Study who received computed tomography scanning and answered questions about illicit drug use at the year 15 examination in 2000-2001., Results: Among 3038 CARDIA participants (age 33-45 years, 55% women and 45% black), past cocaine exposure was reported by 35% and was more common among men, smokers, drinkers, and participants with less education. Powdered cocaine exposure was more common among whites, crack cocaine among blacks. Before adjustment, cocaine exposure was strongly associated with coronary calcification. After adjusting for age, sex, ethnicity, socioeconomic status, family history, and habits, however, these associations disappeared: adjusted odds ratios for coronary calcification were 0.9 (95% CI 0.6-1.3) for 1 to 10, 1.2 (95% CI 0.8-1.7) for 11 to 99, and 1.0 (95% CI 0.6-1.6) for > or =100 lifetime episodes of cocaine use, in comparison with none. Sex, tobacco, and alcohol use appeared to be primarily responsible for the confounding we observed in unadjusted models., Conclusion: We found no evidence of a causal relationship between long-term exposure to cocaine and coronary calcification and conclude that acute nonatherogenic mechanisms probably explain most cocaine-associated myocardial infarction.

It is unclear to what extent the apparently beneficial cardiovascular effects of moderate alcohol consumption are mediated by protection against atherosclerosis. Alcohol consumption, coronary heart disease risk factors, and coronary calcification (a marker of atherosclerosis) were measured during 15 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (1985-2001). Among 3,037 participants aged 33-45 years after follow-up (55% women, 45% Black), the prevalence of coronary calcification was 8% for consumption of 0 drinks/week (n = 1,435), 9% for 1-6 drinks/week (n = 1,023), 13% for 7-13 drinks/week (n = 341), and 19% for > or = 14 drinks/week (n = 238) (p < 0.001 for trend). Calcification was also more common among binge drinkers (odds ratio = 2.1, 95% confidence interval: 1.6, 2.7). These associations persisted after adjustment for potential confounders (age, gender/ethnicity, income, physical activity, family history, body mass index, smoking) and intermediary factors (lipids, blood pressure, glucose, C-reactive protein, and fibrinogen). Stratification showed the dose-response relation most clearly in Black men; only heavier alcohol consumption (> or = 14 drinks/week) was associated with coronary calcification in other race/sex subgroups. These surprising findings suggest the presence of proatherogenic effects of alcohol in young adults, especially Black men, which may counterbalance high density lipoprotein cholesterol elevation and other possible benefits of alcohol consumption.

Randomized, controlled trial data from the Heart and Estrogen-progestin Replacement Study were used to evaluate the effect of estrogen plus progestin use on all-cause mortality in women with heart failure and coronary disease. Over the 4.1-year follow-up, estrogen plus progestin use had no effect on all-cause mortality (hazard ratio 1.0, 95% confidence interval 0.7 to 1.4, p = 0.8) in women with heart failure and coronary disease.

Ascorbic acid is an antioxidant nutrient possibly related to the development of atherosclerosis. To examine the relation between ascorbic acid and coronary artery calcium, an indicator of subclinical coronary disease, the authors analyzed data from 2,637 African-American and White men and women aged 18-30 years at baseline who were enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (1985-2001). Participants completed diet histories at enrollment and year 7, and plasma ascorbic acid levels were obtained at year 10. Coronary artery computed tomography was performed at year 15. The authors calculated odds ratios in four biologically relevant plasma ascorbic acid categories, adjusting for possible confounding variables. When compared with men with high plasma ascorbic acid levels, men with low levels to marginally low levels had an increased prevalence of coronary artery calcium (multivariate odds ratio = 2.68, 95% confidence interval: 1.31, 5.48). Among women, the association was attenuated and nonsignificant (multivariate odds ratio = 1.50, 95% confidence interval: 0.58, 3.85). Ascorbic acid intakes from diet alone and diet plus supplements were not associated with coronary artery calcium. Low to marginally low plasma ascorbic acid levels were associated with a higher prevalence of coronary artery calcium among men but not among women.