Estrogen replacement therapy, thrombophilia, and atherothrombosis.

In a consecutive case series, cross-sectional study of 401 women referred for hyperlipidemia therapy, (110 [27%] on estrogen replacement therapy [ERT]), we assessed whether ERT-mediated thrombophilia and heritable thrombophilia (20210 G-->A prothrombin gene [PTG], Factor V Leiden gene mutation [FV]) interacted as risk factors for atherothrombotic cardiovascular disease (ATCVD). Thirty-eight percent of women (152/401) had > or = 1 ATCVD event, 57 (14%) had > or = 2 ATCVD events. Fifteen women (3.7%) were PTG heterozygotes, 24 (6.0%) were FV heterozygotes, (there was 1 double heterozygote [0.25%]); 363 (91%) were wild-type normal for both genes. Of the 152 women with > or = 1 ATCVD event, 21 (14%) had > or = 1 thrombophilic gene mutation, versus 17/249 (7%) without events (X(2) = 5.4, P =.02). In women on ERT and with both genes wild-type normal, 23 of 96 (24%) had > or = 1 ATCVD event versus 8 of 14 (57%) on ERT and with > or = 1 thrombophilic mutation, X(2) = 6.6, P =.01. By stepwise logistic regression, in 401 women (152 with > or = 1 ATCVD event, 249 no events), positive explanatory variables for ATCVD included FV and/or PTG (risk odds ratio, 2.59, 95% confidence interval [CI] 1.26 to 5.36, P =.01) and a PTG*ERT interaction term (risk odds ratio, 2.27, 95% CI 1.36 to 3.79, P =.0017). After deleting 23 FV heterozygotes and 14 PTG heterozygotes and 1 double heterozygote from the 401 women, ERT was protective against ATCVD events, with a risk odds ratio of 0.50 and 95% CI of 0.29 to 0.87 P =.014. PTG and FV may increase risk for ATCVD, particularly in the presence of ERT, whereas ERT may be protective against ATCVD when PTG and FV are absent. Copyright 2002, Elsevier Science (USA). All rights reserved.