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Hormone therapy and coronary artery calcification in asymptomatic postmenopausal women: the Rancho Bernardo Study

Barrett-Connor, Elizabeth MD; Laughlin, Gail A. PhDc

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Objective: To determine (1) whether past or current hormone therapy (HT) in postmenopausal women is associated with subclinical coronary artery plaque burden, (2) whether any association is independent of age, body size, blood pressure, lipids, fasting plasma glucose, cigarette smoking, leisure time physical activity, alcohol intake, use of lipid-lowering medications, and socioeconomic status, and (3) whether any association varies by duration of HT or by the use of combined versus unopposed HT.

Design: An observational study, with HT validated and coronary heart disease risk factors determined between 1997 and 1999 in a research clinic, and coronary artery calcium score (CACS) evaluated by electron beam computed tomography in 2001 through 2002. Participants were 204 community-dwelling postmenopausal women from the Rancho Bernardo cohort aged 55 to 78 years with no history of heart disease.

Results: The odds of severe CACS in current estrogen users (n = 127) was 0.40 (95% CI 0.19, 0.82), controlling for all covariates. Past users (n = 40) had intermediate odds (multiply adjusted OR = 0.66, 95% CI = 0.28, 1.58). In subgroup analyses, age-adjusted associations did not differ between the 68 women using unopposed estrogen versus the 59 using an estrogen-progestin regimen. Women who had used HT for at least 10 years (n = 86) had significantly less (P = 0.01) plaque burden than shorter term users (n = 41).

Conclusions: Both the strong association and the duration of use effect independent of lifestyle and social class suggest an antiatherogenic effect of postmenopausal estrogen. Only a clinical trial can completely exclude confounding by social class, lifestyle, and unmeasured covariates.

In this observational study, postmenopausal women currently using standard doses of oral estrogen had a 60% reduced odds of severe coronary atherosclerosis, as estimated from coronary artery calcification. This association was independent of socioeconomic status, lifestyle, and biological heart disease risk factors; it was greater with longer use and was similar with estrogen alone or when used with a progestin. These results point to the need for clinical trials in which coronary atherosclerosis, not cardiac events, is the primary outcome.

From the Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, LA Jolla, CA.

Received January 27, 2003; revised and accepted March 29, 2004.

This work was supported by the American Heart Association Grant 0070088Y, National Institute of Diabetes and Digestive and Kidney Diseases Grant DK31801, and National Institute on Aging Grant AG07181.

Address correspondence to: Elizabeth Barrett-Connor, MD, Department of Family and Preventive Medicine, School of Medicine, Mail Code 0607, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0607. E-mail: ebarrettconnor@ucsd.edu.

©2005The North American Menopause Society