Venous thromboembolic events associated with hormone replacement therapy.
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Biomedical subjects
Publications and source records attributed to S B Hulley.
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In order to measure changes in HIV-related behaviors among heterosexual alcoholics following treatment, we conducted a prospective cohort study of 700 self-identified alcoholics recruited from five public alcohol treatment centers, all of which included HIV risk-reduction counseling. Respondents underwent an HIV antibody test and interviewer-administered questionnaire at entry to alcohol treatment and after a mean of 13 months later. Compared to baseline, at follow-up there was an overall 26% reduction in having sex with an injection-drug-using partner (23% versus 32%, P < .001) and a 58% reduction in the use of injection drugs (15% versus 37%, P < .001), along with smaller improvements in other behaviors. Respondents also showed a 77% improvement in consistent condom use with multiple sexual partners (35% versus 20%, P < .01) and a 23% improvement in partner screening (71% versus 57%, P < .001). Respondents who remained abstinent showed substantially greater improvement than those who continued to drink.
OBJECTIVE: To assess the role of serum lipid levels as screening tests in adults. DESIGN: Pooled analysis of clinical trials, supplemented by analysis of data from the Framingham Heart Study, to estimate the effect of cholesterol reduction in patient groups stratified by cardiac risk. STUDY SELECTION: Published randomized controlled trials of cholesterol reduction, meta-analyses of such trials, prospective cohort studies of the association between cholesterol levels and morbidity and death related to coronary heart disease, and cost-effectiveness analyses of cholesterol reduction. DATA ANALYSIS: Two-stage logistic regression on cardiac risk factors and outcomes in the Framingham Heart Study. The first stage predicted the risk for death from coronary heart disease using standard risk factors but not cholesterol; the second stage predicted the risk for death from coronary heart disease and all causes as functions of age and cholesterol level, stratified by the risk predicted from the first stage. RESULTS: Randomized clinical trials show that cholesterol reduction confers survival benefits in patients with symptomatic coronary disease. In asymptomatic middle-aged men, who are at lower risk for death from coronary disease, cholesterol reduction prevents coronary disease but has not been shown to prolong life. The risk model based on analysis of the data from the Framingham Heart Study is consistent with the randomized trial data and shows that in the demographic groups excluded from trials, the hypothetical benefits of cholesterol reduction are greatest when the underlying risk for coronary disease is greatest. CONCLUSIONS: Screening with total cholesterol levels is most likely to be useful when done in populations at high short-term risk for dying of coronary heart disease, such as survivors of myocardial infarction and middle-aged men with multiple cardiac risk factors. In these populations, cholesterol reduction appears to be both effective and cost-effective. In other populations, the benefits of reduction are much smaller or are uncertain.
OBJECTIVE: To review the findings and implications of studies of rodent carcinogenicity of lipid-lowering drugs. DATA SOURCES: Summaries of carcinogenicity studies published in the 1992 and 1994 Physicians' Desk Reference (PDR), additional information obtained from the US Food and Drug Administration, and published articles identified by computer searching, bibliographies, and consultation with experts. STUDY SAMPLE: We tabulated rodent carcinogenicity data from the 1994 PDR for all drugs listed as "hypolipidemics." For comparison, we selected a stratified random sample of antihypertensive drugs. We also reviewed methods and interpretation of carcinogenicity studies in rodents and results of clinical trials in humans. DATA SYNTHESIS: All members of the two most popular classes of lipid-lowering drugs (the fibrates and the statins) cause cancer in rodents, in some cases at levels of animal exposure close to those prescribed to humans. In contrast, few of the antihypertensive drugs have been found to be carcinogenic in rodents. Evidence of carcinogenicity of lipid-lowering drugs from clinical trials in humans is inconclusive because of inconsistent results and insufficient duration of follow-up. CONCLUSIONS: Extrapolation of this evidence of carcinogenesis from rodents to humans is an uncertain process. Longer-term clinical trials and careful postmarketing surveillance during the next several decades are needed to determine whether cholesterol-lowering drugs cause cancer in humans. In the meantime, the results of experiments in animals and humans suggest that lipid-lowering drug treatment, especially with the fibrates and statins, should be avoided except in patients at high short-term risk of coronary heart disease.
BACKGROUND: Middle-aged black men and women have higher blood pressure, on average, than whites. However, this pattern is inconsistent in children and adolescents. This study explores how differences in lifestyle factors in young adulthood may influence blood pressure patterns in the two races. METHODS AND RESULTS: The Coronary Artery Risk Development in Young Adults (CARDIA) study is an ongoing collaborative investigation of lifestyle and the evolution of cardiovascular disease risk factors in a random sample of young adults ages 18 to 30 years at baseline (1985 to 1986). Data from four examinations over 7 years were analyzed with the use of a method that simultaneously examined cross-sectional and longitudinal relationships of lifestyle factors and blood pressure. This study included 1154 black women, 853 black men, 1126 white women, and 1013 white men. Blacks had higher systolic blood pressure and diastolic blood pressure than whites at every examination. Racial differences were much greater in women than in men and increased over time. Within each sex-race group, average diastolic blood pressure over four examinations was positively associated with baseline age, body mass index, and alcohol intake and negatively associated with physical activity, cigarette use, and intake of potassium and protein. Longitudinal change in diastolic blood pressure was positively associated with changes in body mass index and alcohol intake. After adjustment for obesity and other lifestyle factors, black-white diastolic blood pressure differences were reduced substantially: 21% to 75% for men and 49% to 129% for women. Results for systolic blood pressure were similar. CONCLUSIONS: Differences in obesity and other lifestyle factors in young adults largely explain the higher baseline blood pressure and greater increase over time of blacks relative to whites.
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Cross-sectional associations between self-reported hours of television (TV) viewing per day and cardiovascular risk factors were assessed in a biracial (black and white) study population of 4280 men and women, ages 23 to 35 years, undergoing the year-5 follow-up examination for the Cardiovascular Risk Development in Young Adults (CARDIA) study in 1990 to 1991. Number of hours of TV viewing per day was higher in blacks than in whites and was inversely associated with education and income. Relative to "light" TV viewers (0 to 1 h/d), "heavy" TV viewers (> or = 4 h/d) had a higher prevalence (P < 0.05) of obesity, smoking, and high hostility score in all race/gender groups, and of physical inactivity in all groups except black men. Among whites, "heavy" TV viewers had higher depression scores, and among blacks, reported more alcohol use. TV viewing was not associated with hypertension and lipid abnormalities. Heavy TV viewing is a modifiable behavior that is associated with increased prevalence of several cardiovascular risk factors.
To identify determinants of recent secular trends in lipids and characterize their influence on age-related increases in LDL-cholesterol, we examined a cohort of black and white men and women aged 18-30 in 1985-1986. Secular trends were determined by comparing participants aged 25-30 at baseline with those aged 25-30 at year 7 (2788 and 1395 participants, respectively). LDL-cholesterol was lower among those 25-30 at year 7 (5.9 to 10.2 mg/dL, depending on race-sex group; P < 0.001); weight was higher (8.3 to 12.5 lb; P < 0.001); Keys score was lower (-4.2 to -7.3 units; P < 0.001); and use of oral contraceptives was greater (white women only, P < 0.01). Among 4086 participants followed for 7 years, LDL-cholesterol changed little or decreased, despite substantial weight increases in all groups (11.6 to 19.0 lb; P < 0.001). Keys scores decreased by 6.1 to 8.0 units, and use of oral contraceptives decreased (P < 0.001). Declining secular trends in LDL-cholesterol occurred despite upward trends in weight; the decline was associated with lower dietary fat and cholesterol and offset expected age-related increases in LDL-cholesterol.
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To examine the relation between serum fatty acids and coronary heart disease (CHD), the authors conducted a nested case-control study of 94 men with incident CHD and 94 men without incident CHD who were enrolled in the Usual Care group of the Multiple Risk Factor Intervention Trial between December 1973 and February 1976. After confirming the stability of the stored serum samples, the authors measured serum fatty acid levels by gas-liquid chromatography and examined their association with CHD. In all multivariate models, levels of the cholesterol ester saturated fatty acid palmitic acid (16:0) were directly associated with CHD risk (standardized odds ratio = 1.68; 95% confidence interval 1.10-2.55 in the model that adjusted for total plasma cholesterol level). Levels of the phospholipid omega-3 fatty acid docosapentaenoic acid (22:5) were inversely associated with CHD risk in the two multivariate models that controlled for the effects of total plasma cholesterol level or high density lipoprotein cholesterol to total plasma cholesterol ratio (standardized odds ratio = 0.58; 95% confidence interval 0.38-0.89 in the first model that controlled for total plasma cholesterol level). In contrast to the first two multivariate models, levels of the docosahexaenoic acid (22:6) were inversely associated with CHD risk in a third multivariate model that controlled for the effects of high density lipoprotein cholesterol to low density lipoprotein cholesterol ratio (standardized odds ratio = 0.57; 95% confidence interval 0.36-0.90). These findings are consistent with other evidence indicating that saturated fatty acids are directly correlated with CHD and that omega-3 polyunsaturated fatty acids are inversely correlated with CHD. Because these associations were present after adjustment for blood lipid levels, other mechanisms, such as a direct effect on blood clotting, may be involved.
An Expert Panel convened by the National Cholesterol Education Program has recommended selective screening and treatment of children for high blood cholesterol levels, based on family history of cardiovascular disease or high blood cholesterol. This recommendation is problematic for several reasons. First, the recommended diets are likely to cause only a slight decrease in low-density lipoprotein cholesterol levels, the projected benefits of which will be offset by a similar decrease in high-density lipoprotein cholesterol levels. Lack of efficacy of the recommended diets could lead to use of more restrictive diets or to cholesterol lowering drugs. Second, even under optimistic assumptions, beneficial effects of cholesterol intervention will be small and delayed for many decades. As a result, childhood cholesterol-lowering efforts will not be cost-effective. Third, the Expert Panel's recommendations do not address important gender differences. Girls have higher average cholesterol levels than boys. They will therefore qualify for more dietary and drug treatment despite their lower age-adjusted risk of heart disease and the lack of association between cholesterol levels and cardiovascular mortality in women. Finally, recent evidence from randomized trials, cohort studies, and animal experiments suggests that cholesterol lowering may have serious adverse effects. This evidence was not discussed in the Expert Panel's report. Given current evidence, any screening and treatment of children for high blood cholesterol levels is, at best, premature.
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OBJECTIVE: To measure the prevalence of human immunodeficiency virus (HIV) infection and high-risk behaviors among heterosexuals in alcohol treatment. DESIGN: Cross-sectional survey. SETTING: Five public alcohol treatment centers. SUBJECTS: Consecutive sample of 888 heterosexual clients entering treatment between October 1990 and December 1991. Respondents were 51% black, 10% Hispanic, 33% white, and 76% male. The overall response rate was 68%. MEASUREMENTS: Structured interview and serotesting for HIV antibodies. RESULTS: The overall seroprevalence of HIV infection was 5% (95% confidence interval, 3% to 6%). There were no significant differences in rates of infection by age, gender, or race. The prevalence of infection in heterosexual respondents without a history of injection drug use was 3% in men and 4% in women, several times higher than published estimates from a similar community-based heterosexual sample. Unsafe sexual practices were common: 54% of respondents reported multiple sexual partners in the previous year, 97% of nonmonogamous respondents did not use condoms during all sexual encounters, and few respondents consistently asked new sexual partners about previous high-risk behaviors. CONCLUSIONS: There is a substantial prevalence of HIV infection among heterosexual clients in San Francisco (Calif) alcohol treatment programs, much of which is not associated with injection drug use. Because of this and the high prevalence of unsafe sexual behaviors, there is a relatively high likelihood of heterosexual spread of HIV among the large population of clients seeking treatment for alcohol dependency. Interventions to prevent HIV spread should become a standard part of alcohol treatment programs.
OBJECTIVES: To evaluate HIV testing behavior, validity of self-reported serostatus, and intention to test among alcoholics and drug users entering treatment. DESIGN: Longitudinal cohort study. METHODS: A total of 952 clients voluntarily entering three outpatient and two inpatient public alcohol treatment centers in San Francisco were enrolled. Seventy-six per cent were men, 50% black, 81% had used both alcohol and drugs during the last year, 43% had injected drugs and 9% of the men were homosexual. Subjects completed an interviewer-administered questionnaire and blindly-linked HIV-antibody test at entry and after 1 year (81% follow-up). RESULTS: Fifty-seven per cent of subjects reported that they had previously sought HIV testing. Factors associated with HIV testing included homosexual contact, injecting drug use, having a partner who had been tested, and using condoms. Hispanics were the least likely of all ethnic groups to report testing. Of 60 subjects with HIV antibodies, 47 (78%) said they had already been tested; however, 19 (40%) inaccurately reported that their serostatus was negative and another four (9%) had no collected their test results. Blacks were much more likely than other groups to misreport or be unaware of their HIV status. Only half of the 68% who said they planned to be tested during the following year did so. Five (42%) out of 12 HIV-positive individuals who were unaware of, or misreported their serostatus at baseline, and who sought another HIV test during the follow-up year continued to report themselves as uninfected. CONCLUSIONS: A large proportion of clients attending public alcohol treatment centers report having been HIV tested, much greater than that observed in other populations. However, misreporting of HIV test results was very common among seropositive subjects. Alcohol and drug treatment programs for this high-risk population should include interventions to optimize use of HIV testing for prevention and treatment, and improve understanding of test results.
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