Heterogeneity of the Cardioprotective Effect of HRT
Jay M. Sullivan, M.D.*
Affiliation : * Chief, Division of Cardiovascular Diseases, University of Tennessee, UT Coli of Med, 951 Court Ave. Room 353D, Memphis 38163, U.S.A.
In 1993, more women than men died of cardiovascular disease in the United States. There has been a decline in the death rate from cardiovascular disease (CVD) and stroke. Studies show that in postmenopausal women the rate of CVD increases regardless of the age at which menopause takes place. Hospital-based and population-based case-control studies of the effect of estrogen replacement therapy (ERT) on CVD have yielded incon- sistent results, while prospective cohort studies have found a protective effect. The Nurses Health Study demonstrated a reduction in the relative risk of cadiovascular disease to 0.56 (0.40-0.80) in current users of ERT. In a separate study of corornary artery stenosis, estrogen use was reported by fewer postmenopausal women with positive coronary angio- grams. Analysis showed that ERT had an independent protective effect against coronary atherosclerosis. Generally, studies have found that the apparent cardioprotection in estrogen users is relatively greater in women with cardiovascular risks. One of the beneficial effects of estrogen involves lipids. After menopause, serum HDL levels fall as LDL levels rise. Studies demonstrate that ERT reverses this pattern, although when a progestational agent is used, the elevation of HDL is less than that with estrogen alone. It was initially suggested that the effect of ERT on cardiovascular events was associated solely with the effect on HDL. However, recent analyses suggest that changes in HDL cholesterol account for no more than 33% to 50% of the reductions in CV events. Other studies comparing ERT and HMG-CoA reductase inhibitors report that the effect of estrogen on HDL was equal to or greater than that of a statin, but the statins were more potent LDL-lowering agents. Statins lower triglycerides, while estrogen increases triglycerides. Importantly, estrogen lowers LP(a), while the statins do not. There is increasing evidence that estrogens directly affect blood vessel walls by other mechanisms, such as increasing fibrinolysis and decreasing fibrinogen and plasminogen activator inhibitor.
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