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Postmenopausal Women with a History of Irregular Menses and Elevated Androgen Measurements at High Risk for Worsening Cardiovascular Event-Free Survival: Results from the National Institutes of Health—National Heart, Lung, and Blood Institute Sponsored Women’s Ischemia Syndrome Evaluation

Division of Cardiology, Department of Medicine (L.J.S., C.N.B.M.), Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048; Department of Obstetrics and Gynecology (R.A.), Cedars-Sinai Medical Center, Los Angeles, California 90048; University of Southern California (F.Z.S.), Los Angeles, California 90089; National Heart, Lung, and Blood Institute (G.S.), NIH, Bethesda, Maryland 20814; Department of Medicine (G.D.B., T.K.H.), Cedars-Sinai Medical Center, Los Angeles, California 90048; Department of Epidemiology (S.F.K., K.E.K., B.D.J.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; Division of Cardiology (R.M.C.-D., C.J.P.), Department of Medicine, University of Florida, Gainesville, Florida 32611; Division of Cardiology (V.V.), Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322; Cardiovascular Institute (S.E.R.), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213; and Division of Cardiovascular Disease (V.B., W.R.), Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294

Address all correspondence and requests for reprints to: Leslee J. Shaw, Ph.D., c/o WISE Coordinating Center, University of Pittsburgh, 127 Parran Hall, Graduate School of Public Health, 130 DeSoto Street, Pittsburgh, Pennsylvania 15261. E-mail: lshaw3{at}emory.edu.

Background: Women with polycystic ovary syndrome (PCOS) have a greater clustering of cardiac risk factors. However, the link between PCOS and cardiovascular (CV) disease is incompletely described.

Objective: The aim of this analysis was to evaluate the risk of CV events in 390 postmenopausal women enrolled in the National Institutes of Health–National Heart, Lung, and Blood Institute (NIH-NHLBI) sponsored Women’s Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS.

Methods: A total of 104 women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia. Hyperandrogenemia was defined as the top quartile of androstenedione (701 pg/ml), testosterone (30.9 ng/dl), or free testosterone (4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (n = 55).

Results: Women with clinical features of PCOS were more often diabetic (P < 0.0001), obese (P = 0.005), had the metabolic syndrome (P < 0.0001), and had more angiographic coronary artery disease (CAD) (P = 0.04) compared to women without clinical features of PCOS. Cumulative 5-yr CV event-free survival was 78.9% for women with clinical features of PCOS (n = 104) vs. 88.7% for women without clinical features of PCOS (n = 286) (P = 0.006). PCOS remained a significant predictor (P < 0.01) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD as covariates.

Conclusion: Among postmenopausal women evaluated for suspected ischemia, clinical features of PCOS are associated with more angiographic CAD and worsening CV event-free survival. Identification of postmenopausal women with clinical features of PCOS may provide an opportunity for risk factor intervention for the prevention of CAD and CV events.

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