Published online before print April 11, 2002, doi: 10.1161/01.ATV.0000018301.91721.94
© 2002 American Heart Association, Inc.
Thrombosis |
Factor V Leiden, Hormone Replacement Therapy, and Risk of Venous Thromboembolic Events in Women With Coronary Disease
From the Department of Internal Medicine, Sections on Cardiology (D.M.H., D.A.M.), Medical Genetics (T.D.H.), and Hematology and Oncology (J.O.), and the Departments of Public Health Sciences (D.M.R.) and Biochemistry (D.B.), Wake Forest University School of Medicine, Winston-Salem, NC; the Department of Epidemiology and Biostatistics (E.V., J.A.S., D.G., S.B.H.), University of California, San Francisco; and the Department of Medicine (V.B.), University of Alabama at Birmingham.
Reprint requests to David M. Herrington, MD, MHS, Department of Internal Medicine/Cardiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040. E-mail dherring{at}wfubmc.edu
Abstract— Oral contraceptive use in women with factor V Leiden is associated with increased rates of venous thromboembolic events (VTEs). However, the effects of hormone replacement therapy (HRT) in postmenopausal women with factor V Leiden are not known. A nested case-control study was conducted among women with established coronary disease enrolled in 2 randomized clinical trials of HRT, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Estrogen Replacement and Atherosclerosis (ERA) trial. The Leiden mutation was present in 8 (16.7%) of 48 cases with VTE compared with only 7 (6.3%) of 112 controls (odds ratio [OR]Leiden 3.3, 95% CI 1.1 to 9.8; P=0.03). In women without the factor V Leiden mutation, risk associated with HRT use was significantly increased (ORHRT 3.7, 95% CI 1.4 to 9.4; P<0.01). On the other hand, in women with the factor V Leiden mutation, the estimated risk associated with HRT was increased nearly 6-fold, although the CIs were wide and included unity (ORHRT 5.7, 95% CI 0.6 to 53.9; P=0.13). The OR for women with the Leiden mutation who were also assigned to HRT compared with wild-type women assigned to placebo was 14.1 (95% CI 2.7 to 72.4, P=0.0015). In women with the factor V Leiden mutation who were treated with HRT, the estimated absolute incidence of VTE was 15.4 of 1000 per year compared with 2.0 of 1000 per year in women without the mutation who were taking a placebo (P=0.0015). On the basis of these data, in women with coronary disease, the estimated number needed to screen for factor V Leiden to avoid an HRT-associated VTE during 5 years of treatment is 376. If factor V Leiden genotyping becomes less expensive, it could be cost effective to screen for the presence of the mutation before instituting HRT in women with coronary disease.
Key Words: cardiology • risk factors for stroke • genetics • thrombosis risk factors
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