Tissue type plasminogen activator, atherosclerosis and the risk of myocardial infarction

Objective: We studied the association of plasma concentrations of tissuetype plasminogen activator (t-PA) and the, until now single documented polymorphism of the t-PA gene, with degree of atherosclerosis and the prevalence of myocardial infarction. Design: Cross-sectional, population-based case control study. Setting: A district of Rotterdam, the Netherlands. Participants: 110 cases of myocardial infarction and 255 controls, free of cardiovascular disease were drawn from the Rotterdam Study, a populationbased cohort study of 7983 subjects of 55 years and older. Subjects using anticoagulant drugs were not selected. Measurements: The ankle to arm blood pressure ratio (AAI), a indicator for atherosclerosis and t-PA antigen and activity (Stabilytc) and the insertion/deletion polymorphism in intron h of the t-PA gene (obtained in blood cells) were determined. Results are adjusted for age and gender. Results: Homoxygosity for the insertion was associated with twice as many cases of myocardial infarction compared to homo/ygosily for the deletion (relative risk 2.24 (95% CI 1.11,4.50). The polymorphism was not associated with plasma concentrations of t-PA antigen or activity. T-PA antigen was positively associated with myocardial infarction, the risk in the upper half of the distribution was 1.61 (95% CI 1.03,2.53) compared to the lower half. When adjusted for total and HDL cholesterol, BMI and blood pressure, the risk markedly attenuated. T-PA activity was not associated with the risk of myocardial infarction. T-PA antigen and activity were both positively associated with decrease in AAI, 2.88 ng/ml (SE 1.67, p = 0.09) and 0.38 IU/ml (SE 0.20, p = 0.06) respectively per unit decrease in AAI. Conclusion: This study provides evidence for an association of the insertion allele of the insertion/deletion polymorphism of the l-PA gene with non-fatal myocardial infarction, independent of plasma levels of t-PA. Increased levels of t-PA antigen and activity may be due to vascular disease.