Synergistic effects of prothrombotic polymorphisms and atherogenic factorson the risk of myocardial infarction in young males

Several recent studies evaluated a possible effect of the prothrombotic pol ymorphisms such as 5,10 methylenetetrahydrofolate reductase (MTHFR) nt 677C --> T,factor V (F V) nt 1691G -->A (F V Leiden), and factor II (F II) nt 2 0210 G --> A on the risk of myocardial infarction. In the present study, we analyzed the effect of these prothrombotic polymorphisms, as well as apoli poprotein (Apo) E4, smoking, hypertension, diabetes mellitus, and hyperchol esterolemia. on the risk of myocardial infarction in young males. We conduc ted a case-control study of 112 young males with first acute myocardial inf arction (AMI) before the age of 52 and 187 healthy controls of similar age. The prevalences of heterozygotes for F V G1691A and F II G20210A were not significantly different between cases and controls (6.3% v 6.4% and 5.9% v 3.4% among cases and controls, respectively). In contrast, the prevalence o f MTHFR 677T homozygosity and the allele frequency of Apo E4 were significa ntly higher among patients (24.1% v 10.7% and 9.4% v 5.3% among cases and c ontrols, respectively). Concomitant presence of hypertension, hypercholeste rolemia, or diabetes and one or more of the four examined polymorphisms inc reased the risk by almost ninefold (odds ratio [OR] = 8.66; 95% confidence interval [CI], 3.49 to 21.5) and concomitant smoking by almost 18-fold (OR = 17.6; 95% CI, 6.30 to 48.9). When all atherogenic risk factors were analy zed simultaneously by a logistic model, the combination of prothrombotic an d Apo E4 polymorphisms with current smoking increased the risk 25-fold (OR = 24.7; 95% CI, 7.17 to 84.9). The presented data suggest a synergistic eff ect between atherogenic and thrombogenic risk factors in the pathogenesis o f AMI, as was recently found in a similar cohort of women. (C) 1999 by The American Society of Hematology.