CLINICAL INVESTIGATION Cardiovascular mortality

A cohort of 2270 white women, aged 40-69 years at baseline, were followed for an average of 8.5 years in the Lipid Research Clinics Program Follow-up Study. There were 44 deaths due to cardiovascular disease among the 1677 nonusers of estrogens and six cardiovascular disease deaths among the 593 estrogen users. The age-adjusted relative risk (RR) of cardiovascular disease deaths in users compared with nonusers was 0.34 (95% confidence limits 0.12 to 0.81). After multivariable adjustment for potential confounding factors (age, blood pressure, and smoking), the estimated RR for estrogen use was 0.37 (95% confidence limits 0.16 to 0.88). Analyses were done to explore whether these results could be due to selection bias for estrogen use. However, the prevalence of cardiovascular disease at baseline was slightly higher in estrogen users (12%) than in nonusers (10%); furthermore, the exclusion of all women with prevalent cardiovascular disease at baseline did not alter the apparent protective effect of estrogen use on cardiovascular disease mortality (RR = 0.42, 95% confidence limits 0.13 to 1.10). Additional analyses examining the complex association between estrogen use, lipoprotein levels, and cardiovascular disease mortality suggest that the protective effect of estrogen is substantially mediated through increased high-density lipoprotein levels. Circulation 75, No. 6, 1102-1109, 1987. THE ASSOCIATION between exogenous estrogen use and cardiovascular disease is controversial. Clinical trials of estrogen use in men1`3 and case-control studies of oral contraceptive use in women4-7 are frequently cited as evidence that exogenous estrogen use increases the risk of cardiovascular disease. Recently, the Framingham Study has reported that use of noncontraceptive estrogens increases the risk of cardiovascular disease in postmenopausal women.8 From the Oklahoma Medical Research Foundation and Departments of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City; Department of Community Medicine, Division of Epidemiology, University of California at San Diego, La Jolla; Department of Community and Preventive Medicine, College of Medicine, University of Iowa, Iowa City; Departments of Biostatistics and Epidemiology, University of North Carolina, Chapel Hill; and National Institutes of Health, National Heart, Lung, and Blood Institute, Lipid Metabolism-Atherogenesis Branch, Bethesda, MD. This work was supported by National Heart, Lung, and Blood Institute contracts NOI-HV12159, NOI-HV12156, NOI-HV12160, NOI-HV22914, YOI-HV30010, NOI-HV22913, N01-HV12158, NOI-HV12161, NOI-HV22915, N01-HV22932, NOI-HV22917, NOI-HV12157, NOI-HV12243, NOI-HV32961, and N01-HV62941. Address for correspondence: Basil M. Rifkind, M.D., F.R.C.P., National Institutes of Health, National Heart, Lung, and Blood Institute, Lipid Metabolism-Atherogenesis Branch, Federal Bldg., Room 401, Bethesda, MD 20892 Received Oct. 21, 1986; revision accepted Feb. 25, 1987 1102 In contrast to the above-mentioned studies, other reports have suggested that estrogen use protects against the development of cardiovascular disease. Evidence from animal9"11 and autopsy studies12-14 shows that exogenous estrogens may inhibit the development of atherosclerotic coronary lesions. Furthermore, the majority of studies of noncontraceptive estrogen use in women suggest that estrogens either protect against or do not increase the risk of cardiovascular disease."5-25 Given the conflicting evidence on exogenous estrogen use and cardiovascular disease risk, our purpose in this analysis is to examine prospectively the association of estrogen use and subsequent cardiovascular disease mortality in a cohort of women.