Wearable Cardioverter-Defibrillator after Myocardial Infarction.

BACKGROUND: Despite the high rate of sudden death after myocardial infarction among patients with a low ejection fraction, implantable cardioverter-defibrillators are contraindicated until 40 to 90 days after myocardial infarction. Whether a wearable cardioverter-defibrillator would reduce the incidence of sudden death during this high-risk period is unclear. METHODS: We randomly assigned (in a 2:1 ratio) patients with acute myocardial infarction and an ejection fraction of 35% or less to receive a wearable cardioverter-defibrillator plus guideline-directed therapy (the device group) or to receive only guideline-directed therapy (the control group). The primary outcome was the composite of sudden death or death from ventricular tachyarrhythmia at 90 days (arrhythmic death). Secondary outcomes included death from any cause and nonarrhythmic death. RESULTS: Of 2302 participants, 1524 were randomly assigned to the device group and 778 to the control group. Participants in the device group wore the device for a median of 18.0 hours per day (interquartile range, 3.8 to 22.7). Arrhythmic death occurred in 1.6% of the participants in the device group and in 2.4% of those in the control group (relative risk, 0.67; 95% confidence interval [CI], 0.37 to 1.21; P=0.18). Death from any cause occurred in 3.1% of the participants in the device group and in 4.9% of those in the control group (relative risk, 0.64; 95% CI, 0.43 to 0.98; uncorrected P=0.04), and nonarrhythmic death in 1.4% and 2.2%, respectively (relative risk, 0.63; 95% CI, 0.33 to 1.19; uncorrected P=0.15). Of the 48 participants in the device group who died, 12 were wearing the device at the time of death. A total of 20 participants in the device group (1.3%) received an appropriate shock, and 9 (0.6%) received an inappropriate shock. CONCLUSIONS: Among patients with a recent myocardial infarction and an ejection fraction of 35% or less, the wearable cardioverter-defibrillator did not lead to a significantly lower rate of the primary outcome of arrhythmic death than control. (Funded by the National Institutes of Health and Zoll Medical; VEST ClinicalTrials.gov number, NCT01446965 .).

Impact of wearable cardioverter-defibrillator compliance on outcomes in the VEST trial: As-treated and per-protocol analyses.

BACKGROUND: Vest Prevention of Early Sudden Death Trial did not demonstrate a significant reduction in arrhythmic death with the wearable cardioverter-defibrillator (WCD), but compliance with the device may have substantially affected the results. ThePletcher influence of WCD compliance on outcomes has not yet been fully evaluated. METHODS: Using linear and pooled logistic models, we performed as-treated analyses omitting person-time in the hospital and adjusted for correlates of WCD compliance. To assess the impact of early stopping of WCD, we performed a per-protocol Kaplan-Meier analysis, censoring after the last day the WCD was worn. Interactions of potential effect modifiers with treatment assignment and WCD compliance on outcomes were investigated. Finally, we used linear models to identify predictors of WCD compliance. RESULTS: A per-protocol analysis demonstrated a significant reduction in total (P < .001) and arrhythmic (P = .001) mortality. Better WCD compliance was independently predicted by cardiac arrest during index myocardial infarction (MI), higher Cr, diabetes, prior heart failure, EF ≤ 25%, Polish enrolling center and number of WCD alarms, while worse compliance was predicted by being divorced, Asian race, higher body mass index, prior percutaneous coronary intervention, or any WCD shock. Neither excluding time in hospital from the as-treated analysis nor adjustment for factors affecting WCD compliance materially changed the results. No variable demonstrated a significant interaction in either the intention-to-treat or as-treated analysis. CONCLUSION: Robust sensitivity analyses of as-treated and per-protocol analyses suggest that the WCD is protective in compliant patients with ejection fraction less than or equal to 35% during the first 3 months post-MI.

Racial differences in incident heart failure among young adults.

BACKGROUND: The antecedents and epidemiology of heart failure in young adults are poorly understood. METHODS: We prospectively assessed the incidence of heart failure over a 20-year period among 5115 blacks and whites of both sexes who were 18 to 30 years of age at baseline. Using Cox models, we examined predictors of hospitalization or death from heart failure. RESULTS: Over the course of 20 years, heart failure developed in 27 participants (mean [+/-SD] age at onset, 39+/-6 years), all but 1 of whom were black. The cumulative incidence of heart failure before the age of 50 years was 1.1% (95% confidence interval [CI], 0.6 to 1.7) in black women, 0.9% (95% CI, 0.5 to 1.4) in black men, 0.08% (95% CI, 0.0 to 0.5) in white women, and 0% (95% CI, 0 to 0.4) in white men (P=0.001 for the comparison of black participants and white participants). Among blacks, independent predictors at 18 to 30 years of age of heart failure occurring 15 years, on average, later included higher diastolic blood pressure (hazard ratio per 10.0 mm Hg, 2.1; 95% CI, 1.4 to 3.1), higher body-mass index (the weight in kilograms divided by the square of the height in meters) (hazard ratio per 5.7 units, 1.4; 95% CI, 1.0 to 1.9), lower high-density lipoprotein cholesterol (hazard ratio per 13.3 mg per deciliter [0.34 mmol per liter], 0.6; 95% CI, 0.4 to 1.0), and kidney disease (hazard ratio, 19.8; 95% CI, 4.5 to 87.2). Three quarters of those in whom heart failure subsequently developed had hypertension by the time they were 40 years of age. Depressed systolic function, as assessed on a study echocardiogram when the participants were 23 to 35 years of age, was independently associated with the development of heart failure 10 years, on average, later (hazard ratio for abnormal systolic function, 36.9; 95% CI, 6.9 to 198.3; hazard ratio for borderline systolic function, 3.5; 95% CI, 1.2 to 10.2). Myocardial infarction, drug use, and alcohol use were not associated with the risk of heart failure. CONCLUSIONS: Incident heart failure before 50 years of age is substantially more common among blacks than among whites. Hypertension, obesity, and systolic dysfunction that are present before a person is 35 years of age are important antecedents that may be targets for the prevention of heart failure. (ClinicalTrials.gov number, NCT00005130.)

Nonoptimal lipids commonly present in young adults and coronary calcium later in life: the CARDIA (Coronary Artery Risk Development in Young Adults) study.

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.

Cross-sectional and longitudinal associations between objectively measured sleep duration and body mass index: the CARDIA Sleep Study.

Numerous studies have found an association between shorter sleep duration and higher body mass index (BMI) in adults. Most previous studies have been cross-sectional and relied on self-reported sleep duration, which may not be very accurate. In the Coronary Artery Risk Development in Young Adults (CARDIA) Sleep Study (2000-2006), the authors examine whether objectively measured sleep is associated with BMI and change in BMI. They use several nights of wrist actigraphy to measure sleep among participants in an ongoing cohort of middle-aged adults. By use of linear regression, the authors examine whether average sleep duration or fragmentation is associated with BMI and 5-year change in BMI, adjusting for confounders. Among 612 participants, sleep duration averaged 6.1 hours and was grouped into 4 categories. Both shorter sleep and greater fragmentation were strongly associated with higher BMI in unadjusted cross-sectional analysis. After adjustment, BMI decreased by 0.78 kg/m(2) (95% confidence interval: -1.6, -0.002) for each increasing sleep category. The association was very strong in persons who reported snoring and weak in those who did not. There were no longitudinal associations between sleep measurements and change in BMI. The authors confirmed a cross-sectional association between sleep duration and BMI using objective sleep measures, but they did not find that sleep predicted change in BMI. The mechanism underlying the cross-sectional association is not clear.

Prehypertension during young adulthood and coronary calcium later in life.

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.

C-reactive protein concentration and incident hypertension in young adults: the CARDIA study.

BACKGROUND: There is increasing evidence that C-reactive protein (CRP) concentration, a measure of inflammation, is an independent risk factor for the development of hypertension in older adults. However, it is unknown whether a similar relationship exists in younger individuals. METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study was initiated in 1985-1986 to determine the factors that are associated with coronary risk development in young adults. C-reactive protein concentrations were measured in 3919 African American and white men and women enrolled in CARDIA using blood specimens from the year 7 examination (1992-1993), when the age of the cohort was 25 to 37 years, and the year 15 examination (2000-2001). RESULTS: In unadjusted analyses, CRP concentrations greater than 3 mg/L, compared with those less than 1 mg/L, was associated with a 79% greater risk of incident hypertension (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.40-2.28). However, CRP concentration did not predict risk of incident hypertension after adjusting for year 7 body mass index (BMI) (OR, 1.14; 95% CI, 0.86-1.53) or year 7 BMI and other potential confounders (OR, 1.13; 95% CI, 0.83-1.52). In addition, year 7 CRP concentration was not associated with change in systolic or diastolic blood pressure after adjusting for BMI (P = .10 and P = .70, respectively). These findings were similar within each of the race- and sex-specific groups. CONCLUSION: C-reactive protein is associated with hypertension in young adults, but in contrast to the finding in older populations, the association is no longer present after adjusting for BMI.

Marijuana use, diet, body mass index, and cardiovascular risk factors (from the CARDIA study).

Marijuana use has been associated with increased appetite, high caloric diet, acute increase in blood pressure, and decreases in high-density lipoprotein cholesterol and triglycerides. Marijuana is the most commonly used illicit drug in the United States, but its long-term effects on body mass index (BMI) and cardiovascular risk factors are unknown. Using 15 years of longitudinal data from 3,617 black and white young adults participating in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we assessed whether marijuana use was associated with caloric intake, BMI, and cardiovascular risk factors. Of the 3,617 participants, 1,365 (38%) reported ever using marijuana. Marijuana use was associated with male gender, tobacco smoking, and other illicit drug use. More extensive marijuana use was associated with a higher caloric intake (2,746 kcal/day in never users to 3,365 kcal/day in those who used marijuana for > or = 1,800 days over 15 years) and alcohol intake (3.6 to 10.8 drinks/week), systolic blood pressure (112.7 to 116.5 mm Hg), and triglyceride levels (84 to 100 mg/dl or 0.95 to 1.13 mmol/L, all p values for trend < 0.001), but not with higher BMI and lipid and glucose levels. In multivariate analysis, the associations between marijuana use and systolic blood pressure and triglycerides disappeared, having been mainly confounded by greater alcohol use in marijuana users. In conclusion, although marijuana use was not independently associated with cardiovascular risk factors, it was associated with other unhealthy behaviors, such as high caloric diet, tobacco smoking, and other illicit drug use, which all have long-term detrimental effects on health.

Phenotypic predictors of response to simvastatin therapy among African-Americans and Caucasians: the Cholesterol and Pharmacogenetics (CAP) Study.

Although statins are effective lipid-lowering agents, the phenotypic and demographic predictors of such lowering have been less well examined. We enrolled 944 African-American and white men and women who completed an open-label, 6-week pharmacogenetics trial of 40 mg of simvastatin. The phenotypic and demographic variables were examined as predictors of the change in lipids and lipoproteins using linear regression analysis. On average, treatment with simvastatin lowered low-density lipoprotein (LDL) cholesterol by 54 mg/dl and increased high-density lipoprotein (HDL) cholesterol by 2 mg/dl. Compared with African-Americans, whites had a 3-mg/dl greater LDL reduction and a 1-mg/dl higher HDL elevation, independent of other variables, including baseline lipoprotein levels (p <0.01). Multivariate analyses revealed moderate subgroup differences, with older participants having a larger decrease in LDL cholesterol and apolipoprotein B levels compared with younger participants (p <0.001), women having larger increases in HDL than men (p <0.01), nonsmokers having larger decreases in LDL and triglyceride levels compared with smokers (p <0.05), those with hypertension having smaller decreases in apolipoprotein B than those without hypertension (p <0.05), and those with a larger waist circumference having a diminished lowering of triglycerides in response to treatment with simvastatin (p <0.01). In conclusion, treatment with simvastatin produced favorable lipid and lipoprotein changes among all participants. The magnitude of the lipid and lipoprotein responses, however, differed among participants according to a number of phenotypic and demographic characteristics.

Randomized trial of medical treatment versus hysterectomy for abnormal uterine bleeding: resource use in the Medicine or Surgery (Ms) trial.

OBJECTIVE: This study was undertaken to compare resource use outcomes for participants in the Medicine or Surgery (Ms) randomized trial. STUDY DESIGN: In a randomized controlled trial, we compared resources used during a 24-month follow-up period by women with abnormal uterine bleeding who were randomly assigned to either expanded medical treatment or hysterectomy. RESULTS: Women randomly assigned to hysterectomy used significantly more resources (medicine = $4479, hysterectomy = $6777; P = .03), with almost all the difference caused by the hysterectomy procedure. Fifty-three percent of women randomly assigned to medicine had a hysterectomy during the follow-up period; women who were able to continue on medical therapy had mean total resource use of $2595 compared with $6128 for medicine patients who eventually had surgery. CONCLUSION: For women with abnormal uterine bleeding refractory to cyclic medroxyprogesterone acetate, compared with expanded medical treatment, hysterectomy increases resource use significantly and results in better clinical and 6-month quality-of-life outcomes.

Incidence and antecedents of nonmedical prescription opioid use in four US communities. The Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study.

BACKGROUND: Nonmedical use of prescription opioids has emerged as a major public health problem during the last decade, but direct measures of incidence and predisposing factors are lacking. METHODS: We prospectively measured incidence and antecedents of nonmedical prescription opioid use in The Coronary Artery Risk Development in Young Adults study among 28-40-year-old African- and European-American men and women with no prior history of nonmedical opioid use. RESULTS: Among 3163 participants, 23 reported new nonmedical prescription opioid use in 2000-2001 (5-year incidence 0.7%; 95%CI: 0.4-1.0%). All 23 had previously reported marijuana use (p<0.001). Five-year incidence was significantly higher among European-American men (OR=3.3; 95%CI: 1.3-8.3), and among participants reporting a history of amphetamine use (OR=24; 95%CI: 6.9-83) or medical opioid use for treatment of pain (OR=8.6; 95%CI: 2.5-30). These associations remained strong when examined among marijuana users and after adjusting for demographics, social factors, and other antecedent substance use. Amphetamine use was the best single predictor of future nonmedical use (sensitivity 87%, specificity 79%). CONCLUSIONS: Initiation of nonmedical prescription opioid use is generally rare in 28-40-year-old adults, but is observed to be more common with a previous history of substance abuse and legal access to opioids through prescription by a physician.

Impaired fasting glucose and cardiovascular outcomes in postmenopausal women with coronary artery disease.

BACKGROUND: Type 2 diabetes increases risk for cardiovascular disease. Persons with impaired fasting glucose levels may also have increased risk. OBJECTIVE: To evaluate the association between glucose status and cardiovascular outcomes and the effect of lowering the fasting glucose level criterion for impaired fasting glucose from a lower limit of 6.1 mmol/L (110 mg/dL) to 5.6 mmol/L (100 mg/dL). DESIGN: Prospective cohort study. SETTING: 20 U.S. clinical centers. PATIENTS: 2763 postmenopausal women with established coronary heart disease (CHD) who were followed for 6.8 years. MEASUREMENTS: Any CHD event (nonfatal myocardial infarction or CHD death), stroke or transient ischemic attack (TIA), congestive heart failure (CHF) hospitalization, and any cardiovascular event. RESULTS: During follow-up, 583 women had a CHD event, 329 women had a stroke or TIA, and 348 women were hospitalized for CHF. Women with diabetes were at an approximately 75% increased risk for each outcome compared with normoglycemic women. The 218 women with impaired fasting glucose according to the 1997 definition (fasting glucose level, 6.1 to 6.9 mmol/L [110 to 125 mg/dL]) had increased risk for any CHD event (hazard ratio, 1.37 [95% CI, 1.08 to 1.74]), while the 698 women with impaired fasting glucose according to the 2003 definition (fasting glucose level, 5.6 to 6.9 mmol/L [100 to 125 mg/dL]) were not at increased risk (hazard ratio, 1.09 [CI, 0.90 to 1.34]). Most of the women (n = 480) with fasting glucose levels between 5.6 mmol/L (100 mg/dL) and 6.0 mmol/L (109 mg/dL) had no increased risk for CHD (hazard ratio, 0.90 [CI, 0.73 to 1.12]). Women with impaired fasting glucose according to either definition were not at increased risk for stroke or TIA or CHF. LIMITATIONS: These findings may not be generalizable to men or women without existing heart disease. CONCLUSIONS: Among postmenopausal women with coronary artery disease, the 2003 definition for impaired fasting glucose was not associated with increased risk for new CHD, stroke or TIA, or CHF.

Predictors of heart failure among women with coronary disease.

BACKGROUND: Although heart failure is common among women with coronary disease, the risk factors for developing heart failure have not been well studied. We determined the risk factors for developing heart failure among postmenopausal women with established coronary disease. METHODS AND RESULTS: This is a prospective cohort study using data from the Heart and Estrogen/progestin Replacement Study (HERS), a randomized, blinded, placebo-controlled trial of 4.1 years' duration, and subsequent open-label observational follow-up for 2.7 years (HERS II), performed at 20 US clinical centers between 1993 and 2000. Of the 2763 postmenopausal women with established coronary disease in the HERS trial, we studied the 2391 women with no heart failure at baseline by self-report and physical examination. The primary outcome of this analysis was incident heart failure defined by hospital admission or death from heart failure. During the 6.3+/-1.4-year follow-up, 237 women (10%) developed heart failure. Nine predictors were identified: diabetes (defined as a self-reported history of diabetes on treatment), atrial fibrillation, myocardial infarction, creatinine clearance <40 mL/min, systolic blood pressure >120 mm Hg, current smoking, body mass index >35 kg/m2, left bundle-branch block, and left ventricular hypertrophy. Randomization to estrogen/progestin was not associated with heart failure (hazard ratio=1.0; 95% CI, 0.7 to 1.3). Diabetes was the strongest risk factor (adjusted hazard ratio=3.1; 95% CI, 2.3 to 4.2). Diabetic women with elevated body mass index or depressed creatinine clearance were at highest risk, with annual incidence rates of 7% and 13%, respectively. Among diabetic women, hyperglycemia was associated with heart failure risk (adjusted hazard ratio=3.0; 95% CI, 1.2 to 7.5 for fasting glucose >300 mg/dL compared with fasting glucose 80 to 150 mg/dL). CONCLUSIONS: We identified 9 predictors of heart failure in postmenopausal women with coronary disease. Diabetes was the strongest risk factor, particularly when poorly controlled or with concomitant renal insufficiency or obesity.

Subgroup interactions in the Heart and Estrogen/Progestin Replacement Study: lessons learned.

BACKGROUND: The Heart and Estrogen/Progestin Replacement Study (HERS) showed no overall benefit of postmenopausal hormone treatment in women with coronary heart disease (CHD). We analyzed the HERS data to determine whether there were specific subgroups of women who responded differently to treatment, either during the first year or in the overall study. METHODS AND RESULTS: In the search for significant treatment interactions, we analyzed a total of 86 subgroups defined by baseline characteristics. These included demographics and lifestyle factors, laboratory and physical examination variables, medical history and symptoms by self-report, medication use, and prior CHD history by chart review. We examined within-subgroup treatment effects for baseline variables that significantly interacted with treatment assignment. Under the null hypothesis, 4 (5%) of the 86 interactions would be expected to be nominally significant (P<0.05) by chance alone at each time point. Six of the interaction values were P<0.05 at 1 year, and 3 were P<0.05 at trial completion. The findings are discussed in the context of known mechanisms of action and prior scientific knowledge. Use of digitalis and history of myocardial infarction emerged as 2 possible modifiers of the effect of hormone therapy during the first year, and lipoprotein(a) emerged as a possible modifier during the overall study. CONCLUSIONS: Extensive post hoc analyses did not identify any subgroup of HERS participants in which postmenopausal hormone treatment was clearly beneficial or harmful, but several possibilities emerged for testing in future trials.

Cocaine and coronary calcification in young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

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.

Effect of hormone therapy on mortality rates among women with heart failure and coronary artery disease.

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.

Sexual activity and function in postmenopausal women with heart disease.

OBJECTIVE: To examine the prevalence and correlates of sexual activity and function in postmenopausal women with heart disease. METHODS: We included baseline self-reported measures of sexual activity and the sexual problem scale from the Medical Outcomes Study in the Heart and Estrogen/Progestin Replacement Study (HERS), a study of 2,763 postmenopausal women, average age 67 years, with coronary disease and intact uteri. We used multivariable linear and logistic regression to identify independent correlates of sexual activity and dysfunction. RESULTS: Approximately 39% of the women in HERS were sexually active, and 65% of these reported at least 1 of 5 sexual problems (lack of interest, inability to relax, difficulty in arousal or in orgasm, and discomfort with sex). In multivariable analysis, factors independently associated with being sexually active included younger age, fewer years since menopause, being married, better self-reported health, higher parity, moderate alcohol use, not smoking, lack of chest discomfort, and not being depressed. Among the 1,091 women who were sexually active, lower sexual problem scores were associated with being unmarried, being better educated, having better self-reported health, and having higher body mass index. CONCLUSION: Many women with heart disease continue to engage in sexual activity into their 70s, and two thirds of these report discomfort and other sexual function problems. Physicians should be aware that postmenopausal patients are sexually active and address the problems these women experience. LEVEL OF EVIDENCE: II-2.

Postmenopausal hormone therapy: does it cause incontinence?

OBJECTIVE: To estimate the effect of hormone therapy on risk of stress and urge urinary incontinence. METHODS: The Heart Estrogen/progestin Replacement Study was a randomized, placebo-controlled, double-blinded trial to evaluate daily oral conjugated estrogen (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) therapy for the prevention of heart disease events in women with established heart disease. The 1,208 participants in Heart Estrogen/progestin Replacement Study who reported no loss of urine in the previous 7 days at baseline are included in this analysis. RESULTS: During 4.2 years of treatment, 64% of women randomly assigned to hormone therapy compared with 49% of those assigned to placebo reported weekly incontinence (P < .001). The higher risk of incontinence in the hormone group was evident at 4 months, persisted throughout the treatment period, and was independent of the age of the women. The odds ratios for weekly incontinence among women on hormone therapy compared with placebo were 1.5 for urge incontinence (95% confidence interval [CI] 1.2-1.8; P < .001) and 1.7 for stress incontinence (95% CI 1.5-2.1; P < .001). Four years of treatment with hormone therapy caused an excess risk of 12% for weekly urge incontinence and 16% for weekly stress incontinence; the corresponding numbers needed to harm were 8.6 (95% CI 5.8-16.6) and 6.2 (95% CI 4.6-9.4). CONCLUSION: Estrogen plus progestin therapy increases risk of urge and stress incontinence within 4 months of beginning treatment. LEVEL OF EVIDENCE: I.

Sexual functioning after total compared with supracervical hysterectomy: a randomized trial.

OBJECTIVE: To compare sexual functioning and health-related quality-of-life outcomes of total abdominal hysterectomy (TAH) and supracervical hysterectomy (SCH) among women with symptomatic uterine leiomyomata or abnormal uterine bleeding refractory to hormonal management. METHODS: We randomly assigned 135 women scheduled to undergo abdominal hysterectomy in 4 U.S. clinical centers to either a total or supracervical procedure. The primary outcome was sexual functioning at 2 years, as assessed by the Medical Outcomes Study Sexual Problems Scale. Secondary outcomes included specific aspects of sexual functioning and health-related quality-of-life at 6 months and 2 years. RESULTS: Sexual problems improved dramatically in both randomized groups during the first 6 months and plateaued by 1 year. Health-related quality-of-life scores also improved in both groups. At 2 years, both groups reported few problems with sexual functioning (mean score on the Sexual Problems Scale for SCH group 82, TAH group 80, on a 0-to-100 scale with 100 indicating an absence of problems; difference = +2.95% confidence interval -8 to +11), and there were no significant differences between groups. CONCLUSION: Supracervical and total abdominal hysterectomy result in similar sexual functioning and health-related quality of life during 2 years of follow-up. This information can help guide physicians as they discuss surgical options with their patients.

Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease.

Oral contraceptive use in women with factor V Leiden is associated with increased rates of venous thromboembolic events (VTEs). However, the effects of hormone replacement therapy (HRT) in postmenopausal women with factor V Leiden are not known. A nested case-control study was conducted among women with established coronary disease enrolled in 2 randomized clinical trials of HRT, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Estrogen Replacement and Atherosclerosis (ERA) trial. The Leiden mutation was present in 8 (16.7%) of 48 cases with VTE compared with only 7 (6.3%) of 112 controls (odds ratio [OR](Leiden) 3.3, 95% CI 1.1 to 9.8; P=0.03). In women without the factor V Leiden mutation, risk associated with HRT use was significantly increased (OR(HRT) 3.7, 95% CI 1.4 to 9.4; P<0.01). On the other hand, in women with the factor V Leiden mutation, the estimated risk associated with HRT was increased nearly 6-fold, although the CIs were wide and included unity (OR(HRT) 5.7, 95% CI 0.6 to 53.9; P=0.13). The OR for women with the Leiden mutation who were also assigned to HRT compared with wild-type women assigned to placebo was 14.1 (95% CI 2.7 to 72.4, P=0.0015). In women with the factor V Leiden mutation who were treated with HRT, the estimated absolute incidence of VTE was 15.4 of 1000 per year compared with 2.0 of 1000 per year in women without the mutation who were taking a placebo (P=0.0015). On the basis of these data, in women with coronary disease, the estimated number needed to screen for factor V Leiden to avoid an HRT-associated VTE during 5 years of treatment is 376. If factor V Leiden genotyping becomes less expensive, it could be cost effective to screen for the presence of the mutation before instituting HRT in women with coronary disease.