Hormone replacement therapy, prothrombotic mutations, and the risk of incident nonfatal myocardial infarction in postmenopausal women

Context Estrogens are known to be prothrombotic, and findings from the Hear t and Estrogen/progestin Replacement Study suggest that in women with clini cally recognized heart disease, hormone replacement therapy (HRT) may be as sociated with early harm and late benefit in terms of coronary events. Objective To assess whether, as hypothesized, prothrombotic mutations modif y the association between HRT use and incidence of first myocardial infarct ion (MI). Design and Setting Population-based, case-control study conducted in a Seat tle-based health maintenance organization. Participants Cases were 232 postmenopausal women aged 30 to 79 years who ha d their first nonfatal MI between 1995 and 1998. Controls were a stratified random sample of 723 postmenopausal women without MI who were frequency-ma tched to cases by age. calendar year, and hypertension status. Main Outcome Measure Risk of first nonfatal MI based on current use of HRT and the presence or absence of coagulation factor V Leiden and prothrombin 20210 G-->A variants among cases and controls, stratified by hypertension. Results One hundred eight MI cases and 387 controls had hypertension and 12 4 MI cases and 336 controls did not. Among hypertensive women, the prothrom bin variant was a risk factor for MI (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.52-12.1) and, in this stratum, there was also a significa nt interaction between use of HRT and presence of the prothrombin variant o n risk of Mi. Compared with nonusers of HRT with wild-type genotype, women who were current users and who had the prothrombin variant (n=8) had a near ly Ii-fold increase in risk of a nonfatal MI (OR, 10.9; 95% CI, 2.15-55.2). The interaction with the prothrombin variant was more pronounced in analys es assuming 100% compliance than in those assuming 80% compliance with HRT, The interaction was absent among nonhypertensive women and was less pronou nced if hypertensive and nonhypertensive women were combined into 1 group. No interaction was found for factor V Leiden in either hypertensive or nonh ypertensive women. Among hypertensive women, the estimates were affected on ly in trivial ways by adjustment, and the interaction with the prothrombin variant was specific to HRT. Conclusions Our results suggest that among postmenopausal hypertensive wome n, the association between HRT use and MI risk differed between those with and without. the prothrombin 20210 G-->A variant. If these findings are con firmed in other studies. screening for the prothrombin variant may permit a better assessment of the risks and benefits associated with HRT in postmen opausal women.