INTERACTION OF COAGULATION DEFECTS AND CARDIOVASCULAR RISK-FACTORS - INCREASED RISK OF MYOCARDIAL-INFARCTION ASSOCIATED WITH FACTOR-V-LEIDEN OR PROTHROMBIN 20210A

Background-A genetic variation located in the 3'-untranslated region o f the prothrombin gene (prothrombin 20210 G-->A) was recently describe d as a risk factor for venous thrombosis. We examined how the presence of this mutation affected the risk of myocardial infarction in a popu lation-based case-control study. Furthermore, we studied the risk of m yocardial infarction associated with the simultaneous presence of a co agulation defect tie, the 20210 AG genotype of prothrombin or the fact or V Leiden mutation) and major cardiovascular risk factors. Methods a nd Results-Among 560 men with a first myocardial infarction before the age of 70 years, 1.8% were heterozygous carriers of the 20210 variant of the prothrombin gene. The control group consisted of 646 men who w ere frequency matched by age. In the latter group, the frequency of th e 20210 AG genotype was 1.2%. The risk of myocardial infarction in the presence of the AG genotype was increased by 50% (odds ratio, 1.5; 95 % confidence interval [95% CI], 0.6 to 3.8). The risk of myocardial in farction for carriership of factor V Leiden mutation was increased by 40% (odds ratio, 1.4; 95% CI, 0.8 to 2.2). When a coagulation defect w as present tie, the 20210 AG prothrombin genotype or the factor V Leid en mutation), the risk of myocardial infarction for carriers versus no ncarriers was 1.4 (95% CI, 0.9 to 2.2). This risk was substantially in creased when one of the major cardiovascular risk factors of smoking, hypertension, diabetes mellitus, or obesity also was present, with odd s ratios varying between 3 and 6. These risks exceeded those of the si ngle effects of the cardiovascular risk factors tie, in the absence of the coagulation defect). Conclusions-We conclude that in men the 2021 0 G-->A variant of prothrombin is associated with an increased risk of myocardial infarction. The combined presence of major cardiovascular risk factors and carriership of a coagulation defect increases the ris k considerably.