The association of hormone replacement therapy and coronary calcium as determined by electron beam tomography

Background: Observational studies have shown that hormone replacement therapy (HRT) is associated with lower coronary heart disease (CHD), and animal studies demonstrate potent antiatherosclerotic estrogen effects. Paradoxically, recent clinical trials have not demonstrated a protective effect. This paradox may be explained by a healthy woman effect bias. Women using HRT have improved health outcomes unrelated to underlying atherosclerotic burden. Examination of the association between coronary calcium (CC), a marker of atherosclerotic plaque burden, and the use of HRT in postmenopausal women may help address this paradox. Methods: The study population comprised 641 asymptomatic postmenopausal women, 425 (66%) of whom were taking HRT. Data obtained from a self-administered questionnaire and blood samples were analyzed. Electron beam tomography (EBT) for CC was performed on each subject. Analysis of variance (ANOVA) was used to evaluate adjusted means. Results: Independent t tests found that age, low-density lipoproteins (LDL), high-density lipoproteins (HDL), body mass index (BMI), vitamin use, coronary calcium score (CCS), coronary calcified volume (CCV), and the number of coronary calcium lesions (CCL) were significantly different between the HRT group and the non-HRT group. However, after controlling for potential confounders, no significant differences were observed in CCS, CCV, or the number of CCL between the HRT and non-HRT groups. Stratifying by BMI shows that obese/overweight women taking HRT have lower adjusted CCS and fewer CCL than the obese/overweight women not taking HRT. Conclusions: These findings demonstrate no association between HRT use and CCS, CCV, and CCL after adjusting for measurable confounders in postmenopausal women. Our failure to demonstrate an independent association between HRT use and a marker of atherosclerotic plaque burden suggests that a healthy woman effect may explain the beneficial association between HRT use and CHD in observational studies.