Homocysteine and hemostatic disorder as a risk factor for myocardial infarction at a young age

Introduction: Hyperhomocysteinemia is a coronary risk factor, but its pathophysiologic mechanism remains unclear. Materials and methods: The importance of hyperhomocystememia in the pathogenesis of early myocardial infarction, was determined in case-control study of 127 men with a first early myocardial infarction :! 45 years and 150 age-matched male controls. We measured plasma concentrations of homocysteine, fibrinogen, antithrombin, tissue factor, tissue factor pathway inhibitor, tissue plasminogen activator, plasminogen activator inhibitor-I, plasminogen, alpha(2)-antiplasmin, lipoprotein(a), protein C, protein S, factor VII, and activated factor VII. Results: Homocysteine concentrations were higher in patients with early myocardial infarction than in controls (11.2+/-5.3 and 8.3+/-5.0 mumol/l, respectively, P<0.001). Hyperhomocysteinemia was associated with early myocardial infarction (odds ratio=2.22, P<0.001) by multivariate logistic regression analysis. Tissue factor, antithrombin, plasminogen, tissue plasminogen activator, plasminogen activator inhibitor-I, lipoprotein(a), diabetes, and smoking also had associations. In a stepwise logistic regression analysis, hyperhomocysteinemia was the strongest predictor of early myocardial infarction (R-2=0.19, p<0.001). Hyperhomocysteinemia also had positive correlations with tissue factor (rho=0.26, P=0.009), tissue factor pathway inhibitor (rho=0.23, P=0.020), and tissue plasminogen activator (rho=0.25, P=0.011) in patients with early myocardial infarction, but not in controls. Conclusions: Hyperhomocysteinemia is an independent risk factor for early myocardial infarction, and is associated with a hypercoagulable state mediated by the extrinsic coagulation cascade. (C) 2003 Elsevier Science Ltd. All rights reserved.