Stephen B. Hulley

HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study.

The relation between coronary heart disease (CHD) prevalence and fasting lipid levels was assessed by a case-control study in five populations with a total of 6859 men and women of black, Japanese and white ancestry drawn from subjects aged 40 years and older from populations in Albany, Framingham, Evans County, Honolulu and San Francisco. In each major study group mean levels of high density lipoprotein (HDL) cholesterol were lower in persons with CHD than in those without the disease. The average difference was small - typically 3–4 mg/dl - but statistically significant. It was found in most agerace-sex specific groups. The inverse HDL cholesterol-CHD association was not appreciably diminished when adjusted for levels of low density lipoprotein (LDL) cholesterol and triglyceride. LDL, total cholesterol and triglycerides were directly related to CHD prevalence; surprisingly, these findings were less uniformly present in the various study groups than the inverse HDL cholesterol-CHD association.

CARDIA: study design, recruitment, and some characteristics of the examined subjects.

In 1984, a prospective cohort study, Coronary Artery Risk Development in Young Adults (CARDIA) was initiated to investigate life-style and other factors that influence, favorably and unfavorably, the evolution of coronary heart disease risk factors during young adulthood. After a year of planning and protocol development, 5,116 black and white women and men, age 18-30 years, were recruited and examined in four urban areas: Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota, and Oakland, California. The initial examination included carefully standardized measurements of major risk factors as well as assessments of psychosocial, dietary, and exercise-related characteristics that might influence them, or that might be independent risk factors. This report presents the recruitment and examination methods as well as the mean levels of blood pressure, total plasma cholesterol, height, weight and body mass index, and the prevalence of cigarette smoking by age, sex, race and educational level. Compared to recent national samples, smoking is less prevalent in CARDIA participants, and weight tends to be greater. Cholesterol levels are representative and somewhat lower blood pressures in CARDIA are probably, at least in part, due to differences in measurement methods. Especially noteworthy among several differences in risk factor levels by demographic subgroup, were a higher body mass index among black than white women and much higher prevalence of cigarette smoking among persons with no more than a high school education than among those with more education.

Epidemiology as a guide to clinical decisions. The association between triglyceride and coronary heart disease.

The hypothesis that triglyceride is a cause of coronary heart disease, although unconfirmed and never universally accepted, has nonetheless strongly influenced the practice of preventive medicine. We have examined the epidemiologic association between triglyceride and coronary heart disease to evaluate the validity of inferring that there is a causal relation between the two. Neither the evidence from published studies nor an analysis of data from the Western Collaborative Group Study provides strong support for the causal hypothesis. Information from other scientific disciplines is also meager, contrasting with the coherence of diverse evidence supporting the hypothesis that cholesterol is a cause of coronary heart disease. These arguments fall short of disproving the belief that lowering triglyceride will prevent coronary heart disease, especially since triglyceride and cholesterol are inextricably associated through mutual lipoprotein carriers. But we propose that the ethics of preventive medicine place the burden of proof on the proponents of intervention. We therefore recommend that widespread screening and treatment of healthy persons for hypertriglyceridemia be abandoned until more persuasive evidence becomes available.

Overall and coronary heart disease mortality rates in relation to major risk factors in 325,348 men screened for the MRFIT

The influence of risk factors on CHD and all-cause mortality rates in 35- to 57-year-old men is examined by means of data on 325,348 white men who were screened for the MRFIT. This large data set permits an unusually detailed analysis of factors associated with the 6968 deaths, including 2426 ascribed to CHD, that were detected in the Social Security Administration data set during 6 years of follow-up. Simple cross classification of the data confirms the independent effect of serum cholesterol concentration, diastolic blood pressure, and cigarette smoking as risk factors for CHD and all-cause mortality rates. A distinct escalation of risk is noted for combinations of these risk factors. The strength of the association of each of the risk factors with CHD and all-cause mortality rates diminished with increasing age, although the number of excess deaths attributable to the risk factors increased because of the higher death rates in older men. Comparison of these findings with those observed in the five populations studied in the Pooling Project revealed an overall similarity in the risk relationships. It is estimated that elimination of these risk factors has the potential for reducing the CHD mortality rate by two thirds in 35- to 45-year old men, and by one half in 46- to 57-year-old men.

Effect of Prolonged Bed Rest on Bone Mineral

Abstract Three healthy adult males were restricted to complete bed rest for periods of 30–36 weeks. Urinary calcium excretion was elevated throughout bed rest, averaging 61 mg./day above the base-line value of 193 mg./day. Maximum urine calcium excretion occurred during the seventh week and was 136 mg./day above the base-line value. Fecal calcium excretion was also increased during bed rest. Sweat calcium was unchanged and represented only 2 per cent of calcium output. Mean calcium balances for the three subjects during bed rest were −202, −207, and −254 mg./day. The measured calcium loss during the entire bed rest period averaged 4.2 per cent of the estimated total body calcium. Calcium balance became more normal but remained negative during the three-week period of reambulation. Phosphorus excreted in the urine and phosphorus balance patterns were similar to calcium patterns. Serum calcium and phosphorus levels did not change appreciably during bed rest, but both levels fell during reambulation. Urinary hydroxyproline and pyrophosphate were mildly elevated during bed rest and fell with reambulation. Gamma ray transmission scanning of the os calcis revealed large losses of mineral during bed rest. The decreased mass in the central portion of this bone ranged from 25 per cent to 45 per cent. Mineral reaccumulated in the central os calcis following reambulation at a rate similar to its rate of loss during bed rest. Bone dissolution during bed rest may occur to a greater extent in weight-bearing bones than in the remainder of the skeleton, and the process appears to be reversible.

Effect of serotesting with counselling on condom use and seroconversion among HIV discordant couples in Africa.

OBJECTIVE--To determine whether HIV testing and counselling increased condom use and decreased heterosexual transmission of HIV in discordant couples. DESIGN--Prospective study. SETTING--Kigali, the capital of Rwanda. SUBJECTS--Cohabiting couples with discordant HIV serology results. MAIN OUTCOME MEASURES--Condom use in the couple and HIV seroconversion in the negative partners. RESULTS--60 HIV discordant couples were identified, of whom 53 were followed for an average of 2.2 years. The proportion of discordant couples using condoms increased from 4% to 57% after one year of follow up. During follow up two of the 23 HIV negative men and six of the 30 HIV negative women seroconverted (seroconversion rates of 4 and 9 per 100 person years). The rate among women was less than half that estimated for similar women in discordant couples whose partners had not been serotested. Condom use was less common among those who seroconverted (100% v 5%, p = 0.01 in men; 67% v 25%, p = 0.14 in women). CONCLUSIONS--Roughly one in seven cohabiting couples in Kigali have discordant HIV serological results. Confidential HIV serotesting with counselling caused a large increase in condom use and was associated with a lower rate of new HIV infections. HIV testing is a promising intervention for preventing the spread of HIV in African cities.

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.)

Postmenopausal Hormone Therapy and Risk of Stroke

Background—Observational studies have shown that postmenopausal hormone therapy may increase, decrease, or have no effect on the risk of stroke. To date, no clinical trial has examined this question. To investigate the relation between estrogen plus progestin therapy and risk of stroke among postmenopausal women, we analyzed data collected from the Heart & Estrogen-progestin Replacement Study (HERS), a secondary coronary heart disease prevention trial. Methods and Results—Postmenopausal women (n=2763) were randomly assigned to take conjugated estrogen plus progestin or placebo. Primary outcomes for these analyses were stroke incidence and stroke death during a mean follow-up of 4.1 years. The number of women with strokes was compared with the number of women without strokes. A total of 149 women (5%) had 1 or more strokes, 85% of which were ischemic, resulting in 26 deaths. Hormone therapy was not significantly associated with risk of nonfatal stroke (relative hazard [RH] 1.18; 95% CI 0.83 to 1.66), fatal...

Association between sleep and blood pressure in midlife: the CARDIA sleep study.

BACKGROUND Epidemiological studies have reported an association between self-reported short sleep duration and high blood pressure (BP). Our objective was to examine both cross-sectional and longitudinal associations between objectively measured sleep and BP. METHODS This study is ancillary to the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study. Blood pressure was measured in 2000 and 2001 and in 2005 and 2006. Sleep was measured twice using wrist actigraphy for 3 consecutive days between 2003 and 2005. Sleep duration and sleep maintenance (a component of sleep quality) were calculated. Analyses included 578 African Americans and whites aged 33 to 45 years at baseline. Outcome measures were systolic BP (SBP) and diastolic BP (DBP) levels, 5-year change in BP, and incident hypertension. RESULTS After we excluded the patients who were taking antihypertensive medications and adjusted for age, race, and sex, shorter sleep duration and lower sleep maintenance predicted significantly higher SBP and DBP levels cross-sectionally as well as more adverse changes in SBP and DBP levels over 5 years (all P < .05). Short sleep duration also predicted significantly increased odds of incident hypertension (odds ratio, 1.37; 95% confidence interval, 1.05-1.78). Adjustment for 16 additional covariates, including snoring and daytime sleepiness, slightly attenuated the associations between sleep and BP. Sleep duration appeared to mediate the difference between African Americans and whites in DBP change over time (P = .02). CONCLUSION Reduced sleep duration and consolidation predicted higher BP levels and adverse changes in BP, suggesting the need for studies to investigate whether interventions to optimize sleep may reduce BP.

Condom use in multi-ethnic neighborhoods of San Francisco: the population-based AMEN (AIDS in Multi-Ethnic Neighborhoods) Study.

We examined the prevalence and correlates of condom use in a community-based sample of unmarried heterosexual and gay/bisexual Whites, Blacks, and Hispanics (aged 20 to 44 years) in San Francisco (n = 1229). Only 9% of heterosexual males reported always using condoms, and fewer of those with multiple sexual partners (6%) reported always using condoms compared with those in monogamous relationships (12%). Much higher proportions of gay/bisexual men reported always using condoms (48%). Racial differences in condom use were observed only among women. Sexual communication and the sexual enjoyment value of condoms were consistent correlates of condom use across gender and sexual orientation, while other condom-related beliefs were significant predictors of condom use only for men. In general, condom promotion programs should build sexual communication skills, teach people how to enhance enjoyment with condoms, and reduce psychological barriers to condom acquisition and use.