Summary

This study examines the relationship between plasmaPlasminogen Activator Inhibitor-1 (PAI-1) activity and the PAI-14G/5G polymorphism, and their association with the risk ofmyocardial infarction (MI). Furthermore, this study exploreswhether a high level of PAI-1 or whether the PAI-1 4G/5Gpolymorphism synergistically interacts with any establishedenvironmental risk factor for MI. This case-referent study ofsubjects aged 45-70 and living in Stockholm includes 851 menand 361 women with first-time MI and 1051 men and 505women who were randomly chosen as referents from a populationregister.The adjusted odds ratio (OR) of MI was 1.9 (95%confidence interval [CI] 1.4-2.8) for men with a plasma PAI-1activity level greater than the 90th percentile value of referents. The corresponding OR for women was 1.5 (95% CI 0.9-2.5).Astrong indication of synergistic interaction was found in menfor the co-exposure to high plasma PAI-1 activity and currentsmoking, an adjusted synergy index score of 3.9 (95% CI 1.2-13.2). In women, the 4G allele was associated slightly with anincreased risk of MI, OR 1.4 (95% CI 1.0-1.9). This associationwas not found in men. There were no clear indications ofsynergistic interaction effects involving the PAI-1 4G/5Gpolymorphism and the environmental exposures considered(cigarette smoking, physical inactivity, overweight, diabetesmellitus, hypercholesterolaemia, hypertension, high C-reactiveprotein and hypertriglyceridaemia).