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.

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.

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.

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.

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.

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.

Causes and demographic, medical, lifestyle and psychosocial predictors of premature mortality: the CARDIA study.

We examined the 16-year mortality experience among participants in the baseline examination (1985-86) of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a U.S. cohort of 5115 urban adults initially 18-30 years old and balanced by sex and race (black and whites) in the USA. We observed 127 deaths (annual mortality of 0.15%). Compared to white women, the rate ratio (95% confidence interval) of all-cause mortality was 9.3 (4.4, 19.4) among black men, 5.3 (2.5, 11.4) among white men and 2.7 (1.2, 6.1) among black women. The predominant causes of death, which also differed greatly by sex-race, were AIDS (28% of deaths), homicide (16%), unintentional injury (10%), suicide (7%), cancer (7%) and coronary disease (7%). The significant baseline predictors of all-cause mortality in multivariate analysis were male sex, black race, diabetes, self-reported liver and kidney disease, current cigarette smoking and low social support. Two other factors, self-reported thyroid disease and high hostility, were significant predictors in analyses adjusted for age, sex and race. In conclusion, we found striking differences in the rates and underlying cause of death across sex-race groups and several independent predictors of young adult mortality that have major implications for preventive medicine and social policies.

Depressive symptoms, unemployment, and loss of income: The CARDIA Study.

BACKGROUND: Previous studies have suggested an association between depression and low socioeconomic status, but few have empirically examined the effect of depressive symptoms on income and employment over time. OBJECTIVE: To determine whether depressive symptoms are associated with subsequent unemployment or loss of family income. METHODS: We performed a prospective cohort study of 5115 adults aged 18 to 30 years. These participants included approximately equal numbers of African Americans and whites and men and women from 4 cities in the United States who completed the 1990-1991 examination of the Coronary Artery Risk Development in Young Adults (CARDIA) study. For this analysis, we included 2334 participants who were employed full or part time and who reported an annual family income of $25 000 or more. Participants completed the Center for Epidemiologic Studies Depression Scale and were considered to have depressive symptoms if they scored 16 or higher on the 60-point scale. We evaluated self-reported unemployment and annual family income during 5 years of follow-up. RESULTS: Thirty-three percent (118/354) of participants with depressive symptoms (Center for Epidemiologic Studies Depression Scale score >/=16) in 1990-1991 and 21% (335/1581) of participants without substantial depressive symptoms (Center for Epidemiologic Studies Depression Scale score <16) reported new unemployment during the subsequent 5 years (odds ratio, 1.9; 95% confidence interval, 1.4-2.4; P<.001). This association remained strong after adjusting for potential confounding variables, including marital status, education, history of unemployment, current part-time (vs full-time) employment, and cigarette smoking (odds ratio, 1.6; 95% confidence interval, 1.2-2.0; P =.001). Seventeen percent (62/371) of participants with depressive symptoms and 7% (113/1631) of participants without substantial depressive symptoms in 1990-1991 reported that their family income had decreased below $25 000 by 1995-1996 (odds ratio, 2.7; 95% confidence interval, 1.9-3.8; P<.001). This association also remained strong after adjusting for potential confounding variables (odds ratio, 1.9; 95% confidence interval, 1.3-2.7; P<.001). CONCLUSIONS: Depressive symptoms are associated with subsequent unemployment and loss of family income among working young adults. Socioeconomic indicators, such as income and employment, should be considered in evaluating the potential benefits of treatment for patients with depressive symptoms.

Fracture and the risk of coronary events in women with heart disease.

BACKGROUND: Osteoporosis is associated with aortic calcification and cardiovascular mortality. However, whether skeletal fractures predict the risk of coronary events is unknown. METHODS: We used Cox proportional hazards models to determine whether postmenopausal fracture was associated with the risk of coronary heart disease events among the 2763 postmenopausal women with known coronary disease enrolled in the Heart and Estrogen/progestin Replacement Study. Because fractures occurred before enrollment (in 615 women) and during follow-up (in 276 women), we treated incident fracture as a time-dependent covariate in our models. RESULTS: During a mean follow-up of 4.1 years, 361 women had coronary heart disease events. The risk of these events was 25% lower in women who sustained fractures than in those without fractures (hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.57 to 0.96; P = 0.02). This association was not confounded by physical activity or by factors associated with both fracture and coronary heart disease events (HR = 0.75; 95% CI: 0.57 to 0.98; P = 0.04). CONCLUSION: Postmenopausal women with heart disease who had skeletal fractures had a reduced risk of subsequent coronary events. This unexpected association, if confirmed in future studies, could influence risk-related treatment strategies for cardiovascular disease.

Lipid changes on hormone therapy and coronary heart disease events in the Heart and Estrogen/progestin Replacement Study (HERS).

BACKGROUND: Despite the effect of lowering low-density lipoprotein cholesterol (LDL-C) levels and raising high-density lipoprotein cholesterol (HDL-C) levels, combination hormone therapy did not reduce the incidence of coronary heart disease (CHD) events in the Heart and Estrogen/progestin Replacement Study (HERS). To explore possible mechanisms, we examined the association between lipid changes and CHD outcomes among women assigned to hormone therapy. METHODS: HERS participants were postmenopausal women with previously diagnosed CHD who were randomly assigned to receive conjugated estrogens and medroxyprogesterone or identical placebo and then followed-up for an average of 4.1 years. Among women assigned to hormone therapy, associations between baseline-to-year-1 lipid level changes and CHD events were compared with the associations observed for baseline lipids using multivariate proportional hazards models. RESULTS: Among women assigned to hormone therapy, CHD events were independently predicted by baseline LDL-C levels (relative hazard [RH] 0.94 per 15.6 mg/dL decrease, 95% CI 0.88-1.01) and HDL-C levels (RH 0.89 per 5.4 mg/dL increase, 95% CI 0.81-0.99), but not by triglyceride levels (RH 1.01 per 13.2 mg/dL increase, 95% CI 0.97-1.06). CHD events were marginally associated with first-year reductions in LDL-C levels (RH 0.95 per 15.6 mg/dL decrease, 95% CI 0.86-1.04), and were not associated with increases in HDL-C levels ( RH 1.03 per 5.4 mg/dL increase, 95% CI 0.91-1.16) or triglyceride levels (RH 1.01 per 13.2 mg/dL increase, 95% CI 0.98-1.05). CONCLUSION: Changes in lipid levels with hormone therapy are not predictive of CHD outcomes in women with heart disease in the HERS trial.

Physical and sexual function in women with chronic kidney disease.

BACKGROUND: Cross-sectional studies suggest an association between functional status and chronic kidney disease (CKD). Whether physical function deteriorates with progression of CKD is unknown. METHODS: To determine associations among CKD, physical function, and sexual function in women, we conducted cross-sectional and longitudinal analyses of 2,761 women enrolled in the Heart and Estrogen/Progestin Replacement Study. Physical and sexual function were evaluated using the Duke Activity Status Index (DASI) and the Sexual Problems Scale of the Medical Outcomes Study, respectively. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease regression equation. In addition to analyses across the spectrum of GFR, CKD was categorized as mild (estimated GFR, 45 to 60 mL/min/1.73 m2), moderate (estimated GFR, 30 to 44 mL/min/1.73 m2), and severe (estimated GFR, <30 mL/min/1.73 m2) according to a modification of recently established classification guidelines. RESULTS: Mean age of study participants was 67 +/- 7 years, and mean estimated GFR was 61 +/- 14 mL/min/1.73 m2. In unadjusted analyses, mean baseline DASI score was 10 points lower in women with an estimated GFR less than 30 mL/min/1.73 m2 than in women with an estimated GFR of 60 mL/min/1.73 m2 or greater (P < 0.0001). Estimated GFR remained significantly associated with DASI score after multivariable adjustment. In longitudinal analyses, a decline in estimated GFR was associated with a significant decline in DASI score independent of baseline estimated GFR and other factors. There were no significant associations between estimated GFR and psychosocial aspects of sexual function. CONCLUSION: CKD is associated with impaired physical function, and a decline in estimated GFR is associated with a decline in physical function.

Positional change in blood pressure and 8-year risk of hypertension: the CARDIA Study.

OBJECTIVE: To assess the relationship between positional blood pressure change and 8-year incidence of hypertension in a biracial cohort of young adults. SUBJECTS AND METHODS: Participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study with complete data from year 2 (1987-1988), year 5 (1990-1991), year 7 (1992-1993), and year 10 (1995-1996) examinations were included (N = 2781). Participants were classified into 3 groups based on their year 2 systolic blood pressure response to standing: drop, a decrease in systolic blood pressure of more than 5 mm Hg; same, a change of between -5 and +5 mm Hg; and rise, more than 5-mm Hg increase. RESULTS: The number of participants in each group was as follows: drop, 741; same, 1590; and rise, 450. The 8-year incidence of hypertension was 8.4% in the drop group, 6.8% in the same group, and 12.4% in the rise group (P < .001). Adjusted odds ratios for developing hypertension during the follow-up period in the rise group vs the same group were as follows: in black men, 2.85 (95% confidence interval [CI], 1.43-5.69), in black women, 2.47 (95% CI, 1.19-5.11), in white men, 2.17 (95% CI, 1.00-4.73), and in white women, 4.74 (95% CI, 1.11-20.30). CONCLUSIONS: A greater than 5-mm Hg increase in blood pressure on standing identified a group of young adults at increased risk of developing hypertension within 8 years. These findings support a physiologic link between sympathetic nervous system reactivity and risk of hypertension in young adults.

A randomized comparison of total or supracervical hysterectomy: surgical complications and clinical outcomes.

OBJECTIVE: To compare surgical complications and clinical outcomes after total versus supracervical abdominal hysterectomy for control of abnormal uterine bleeding, symptomatic uterine leiomyomata, or both. METHODS: We conducted a randomized intervention trial in four US clinical centers among 135 patients who had abdominal hysterectomy for symptomatic uterine leiomyomata, abnormal uterine bleeding refractory to hormonal treatment, or both. Patients were randomly assigned to receive a total or supracervical hysterectomy performed using the surgeon's customary technique. Using an intention-to-treat approach, we compared surgical complications and clinical outcomes for 2 years after randomization. RESULTS: Sixty-eight participants were assigned to supracervical hysterectomy (SCH) and 67 to total abdominal hysterectomy (TAH). Hysterectomy by either technique led to statistically significant reductions in most symptoms, including pelvic pain or pressure, back pain, urinary incontinence, and voiding dysfunction. Patients randomly assigned to (SCH) tended to have more hospital readmissions than those randomized to TAH, but this difference was not statistically significant. There were no statistically significant differences in the rate of complications, degree of symptom improvement, or activity limitation. Participants weighing more than 100 kg at study entry were twice as likely to be readmitted to the hospital during the 2-year follow-up period (relative risk [RR] 2.18, 95% confidence interval [CI] 1.06, 4.48, P=.034). CONCLUSION: We found no statistically significant differences between (SCH) and TAH in surgical complications and clinical outcomes during 2 years of follow-up.