doi: 10.1161/01.CIR.0000115525.92645.16
(Circulation. 2004;109:722-725.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Abnormal Coronary Vasomotion as a Prognostic Indicator of Cardiovascular Events in Women
Results From the National Heart, Lung, and Blood Institute–Sponsored Women’s Ischemia Syndrome Evaluation (WISE)
From the University of Florida College of Medicine (G.O.v.M., C.B.A., T.R.W., S.P.M., K.M.S., E.H., C.J.P., R.A.K.), Division of Cardiovascular Medicine, Gainesville, Fla; the Division of Cardiology (C.N.B.M.), Department of Medicine, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, Los Angeles, Calif; Rhode Island Hospital (B.L.S.), Division of Cardiology, Providence, Rhode Island; the Cardiovascular Institute and Department of Epidemiology (M.B.O., B.D.J.), University of Pittsburgh Medical Center, Pittsburgh, Pa; and the Division of Heart and Vascular Disease (G.S.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
Reprint requests to Carl J. Pepine, MD, Chief, Division of Cardiovascular Medicine, University of Florida College of Medicine, PO Box 100277, Gainesville, FL 32610-0277. E-mail pepincj{at}medicine.ufl.edu
Received December 17, 2003; accepted December 17, 2003.
Background— Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women.
Methods and Results— As part of the Women’s Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less change in coronary cross-sectional area (
CSA) in response to acetylcholine (P=0.0006) and nitroglycerin (P=0.04). In addition, women with abnormal coronary dilator response to acetylcholine had less time free from cardiovascular events (P=0.004). In multivariable analysis, after controlling for age, hypertension, diabetes, dyslipidemia, tobacco use, and CAD severity, %CSA with acetylcholine (P=0.001) independently predicted events. When the outcome was restricted to only death, myocardial infarction, congestive heart failure, and stroke, %CSA with acetylcholine remained a significant predictor (P=0.006).
Conclusions— In women in this study, impaired coronary vasomotor response to acetylcholine was independently linked to adverse cardiovascular outcomes regardless of CAD severity.
Key Words: coronary disease • endothelium • acetylcholine • prognosis • women
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