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 for therapy of hyperlipidemia, (75 [27%] on estrogen replacement therapy [ERT]), our specific aim was to determine whether ERT-mediated thrombophilia and heterozygosity for the thrombophilic 20210 G/A prothrombin gene mutation interacted as risk factors for atherothrombotic cardiovascular disease (ATCVD). Of the 275 women, 100 (36%) had ATCVD; 10 (3.6%) were heterozygous for the 20210 G/A prothrombin gene mutation. In women without the 20210 G/A prothrombin 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 [CI], 1.4 to 30.2; P =.021) and a 20210 G/A prothrombin 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 (ERT minus [-] and 20210 G/A prothrombin gene mutation -) or (ERT plus [+] and 20210 G/A prothrombin gene mutation +), P =.004. Other positive explanatory variables for ATCVD events included age (P =.004), triglycerides (P =.012), lipoprotein (a) (P =.03), and homocysteine (P =.032). ERT may be protective against ATCVD when the thrombophilic 20210 G/A prothrombin gene mutation is absent, whereas the 20210 G/A prothrombin gene mutation may increase risk for ATCVD, particularly in the presence of ERT. We suggest that the 20210 G/A prothrombin gene mutation be measured in all women on ERT or before beginning ERT to identify those heterozygous for the thrombophilic prothrombin gene mutation (4%) in whom ERT is contraindicated because of increased risk for ATCVD and thromboembolism, and a second, much larger group of women without the 20210 G/A prothrombin gene mutation (96%) in whom ERT may possibly reduce risk for ATCVD.
Glueck
C J
CJ
Cholesterol Center, Jewish Hospital, Cincinnati, OH, USA.
Wang
P
P
Fontaine
R N
RN
Sieve-Smith
L
L
Lang
J E
JE
D000368:Aged; D001161:Arteriosclerosis / Q000235:genetics* / Q000517:prevention & control; D000075202:Contraindications; D003430:Cross-Sectional Studies; D015914:Estrogen Replacement Therapy; D005260:Female; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000502:physiology*; D011516:Prothrombin / Q000235:genetics*; D019851:Thrombophilia / Q000235:genetics*; D013927:Thrombosis / Q000235:genetics* / Q000517:prevention & control
D011516:Prothrombin