Interaction of Coagulation Defects and Cardiovascular Risk Factors

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Abstract
Background —A genetic variation located in the 3′-untranslated region of the prothrombin gene (prothrombin 20210 G→A) was recently described as a risk factor for venous thrombosis. We examined how the presence of this mutation affected the risk of myocardial infarction in a population-based case-control study. Furthermore, we studied the risk of myocardial infarction associated with the simultaneous presence of a coagulation defect (ie, the 20210 AG genotype of prothrombin or the factor V Leiden mutation) and major cardiovascular risk factors. Methods and 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 were frequency matched by age. In the latter group, the frequency of the 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 infarction 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 was present (ie, the 20210 AG prothrombin genotype or the factor V Leiden mutation), the risk of myocardial infarction for carriers versus noncarriers was 1.4 (95% CI, 0.9 to 2.2). This risk was substantially increased when one of the major cardiovascular risk factors of smoking, hypertension, diabetes mellitus, or obesity also was present, with odds ratios varying between 3 and 6. These risks exceeded those of the single effects of the cardiovascular risk factors (ie, in the absence of the coagulation defect). Conclusions —We conclude that in men the 20210 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 risk considerably.