Interaction of estrogen replacement therapy with the thrombophilic 20210 G/A prothrombin gene mutation for atherothrombotic vascular disease: A cross-sectional study of 275 hyperlipidemic women

In a consecutive case series, cross-sectional study of 275 women referred f or therapy of hyperlipidemia, (75 [27%] on estrogen replacement therapy [ER T]), our specific aim was to determine whether ERT-mediated thrombophilia a nd heterozygosity for the thrombophilic 20210 G/A prothrombin gene mutation interacted as risk factors for atherothrombotic cardiovascular disease (AT CVD). Of the 275 women. 100 (36%) had ATCVD; 10 (3.6%) were heterozygous fo r the 20210 G/A prothrombin gene mutation. In women without the 20210 G/A p rothrombin gene mutation, 15 of 71 (21%) on ERT had ATCVD versus 78 of 194 (40%) not on ERT (X-2 = 8.31, P =.004). BY stepwise logistic regression, in 261 women with ATCVD risk factor data, positive explanatory variables for ATCVD included the 20210 G/A prothrombin mutation (risk odds ratio, 5.8; 95 % confidence intervals [Cl], 1.4 to 30.2; P =.021) and a 20210 G/A prothrom bin gene mutation*ERT interaction term (risk odds ratio, 2.70; 95% CI. 1.4 to 5.4; P =.004). ATCVD events were more likely in 2 subgroups of women (ER T minus [-] and 20210 G/A prothrombin gene mutation -) or (ERT plus [+] and 20210 G/A prothrombin gene mutation +), P =.004. Other positive explanator y variables for ATCVD events included age (P =.004), triglycerides (P =.012 ), lipoprotein (a) (P =.03), and homocysteine (P =.032). ERT may be protect ive against ATCVD when the thrombophilic 20210 G/A prothrombin gene mutatio n is absent, whereas the 20210 G/A prothrombin gene mutation may increase r isk for ATCVD, particularly in the presence of ERT. We suggest that the 202 10 G/A prothrombin gene mutation be measured in all women on ERT or before beginning ERT to identify those heterozygous for the thrombophilic prothrom bin gene mutation (4%) in whom ERT is contraindicated because of increased risk for ATCVD and thromboembolism, and a second, much larger group of wome n without the 20210 G/A prothrombin gene mutation (96%) in whom ERT may pos sibly reduce risk for ATCVD. Copyright (C) 2001 by W.B. Saunders Company.