(Circulation. 1999;99:354-360.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Vascular Effects of Estrogen and Cholesterol-Lowering Therapies in Hypercholesterolemic Postmenopausal Women
From the Cardiology Branch (K.K.K., C.C., M.N.B., L.H., J.A.P., R.O.C.) and the Office of Biostatistics Research (M.A.W.), National Heart, Lung, and Blood Institute, and the Clinical Pathology Department (G.C.), Clinical Center, National Institutes of Health, Bethesda, Md.
Correspondence to Dr Richard O. Cannon III, National Institutes of Health, Building 10, Room 7B15, 10 Center Dr MSC-1650, Bethesda, MD 20892-1650. E-mail cannonr{at}gwgate.nhlbi.nih.gov
Background—Lipoproteins affect endothelium-dependent vasomotor responsiveness. Because lipoprotein effects of estrogen and cholesterol-lowering therapies differ, we studied the vascular responses to these therapies in hypercholesterolemic postmenopausal women.
Methods and Results—We randomly assigned 28 women to conjugated
equine estrogen (CE) 0.625 mg, simvastatin 10 mg, and their
combination daily for 6 weeks. Compared with respective baseline
values, simvastatin alone and combined with CE reduced LDL
cholesterol to a greater extent than CE alone (both
P<0.05). CE alone and combined with
simvastatin raised HDL cholesterol and lowered
lipoprotein(a) to a greater extent than simvastatin alone
(all P<0.05). Flow-mediated dilation of the brachial
artery (by ultrasonography) improved (all P<0.001
versus baseline values) on CE (4.0±2.6% to 10.2±3.9%),
simvastatin (4.3±2.4% to 10.0±3.9%), and CE combined
with simvastatin (4.6±2.0% to 9.8±2.6%), but similarly
among therapies (P=0.507 by ANOVA). None of the
therapies improved the dilator response to
nitroglycerin (all P
0.184). Only
therapies including CE lowered levels of plasminogen
activator inhibitor type 1 and the cell
adhesion molecule E-selectin (all P<0.05 versus
simvastatin).
Conclusions—Although estrogen and statin therapies have differing effects on lipoprotein levels, specific improvement in endothelium-dependent vasodilator responsiveness is similar. However, only therapies including estrogen improved markers of fibrinolysis and vascular inflammation. Thus, estrogen therapy appears to have unique properties that may benefit the vasculature of hypercholesterolemic postmenopausal women, even if they are already on cholesterol-lowering therapy.
Key Words: lipoproteins • endothelium • hormones • cell adhesion molecules • fibrinolysis
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