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This version published online on January 8, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-0425
A more recent version of this article appeared on April 1, 2008
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Submitted on February 23, 2007
Accepted on December 31, 2007

Post-Menopausal 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 (NHLBI) – Sponsored Women's Ischemia Syndrome Evaluation (WISE)

Leslee J. Shaw PhD*, C. Noel Bairey Merz MD, Ricardo Azziz MD, MPH, Frank Z. Stanczyk PhD, George Sopko MD, Glenn D. Braunstein MD, Sheryl F. Kelsey PhD, Kevin E. Kip PhD, Rhonda M. Cooper-DeHoff PharmD, B. Delia Johnson PhD, Viola Vaccarino MD, PhD, Steven E. Reis MD, Vera Bittner MD, MSPH, T. Keta Hodgson RN, William Rogers MD, and Carl J. Pepine MD

From Division of Cardiology, Department of Medicine, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, Los Angeles, California; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California; University of Southern California, Los Angeles, California; National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania; Division of Cardiology, Department of Medicine, University of Florida, Gainesville, Florida; Division of Cardiology, Department of Medicine, Emory University School of Medicine; Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama

* To whom correspondence should be addressed. 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 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 (T; ≥30.9 ng/dl), or free T (≥4.5 pg/ml). Cox proportional hazard model was fit to estimate CV death or myocardial infarction (MI) (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 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) versus 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 coronary artery disease 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.
Key words: Polycystic ovary syndrome • cardiovascular disease • prognosis • menopause




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