TISSUE-PLASMINOGEN ACTIVATOR AND RISK OF MYOCARDIAL-INFARCTION - THE ROTTERDAM STUDY

Background Impaired fibrinolytic capacity, as assessed by euglobulin c lot lysis time or plasma concentration of fibrinolytic parameters, has been associated with an increased risk of myocardial infarction (MI). We studied the association of a polymorphism in the gene for TPA and of plasma concentrations of TPA (antigen and activity) with the preval ence of MI. Methods and Results A case-control study was performed. Su bjects with a history of MI (n=121) and controls (n=250) were drawn fr om the Rotterdam Study, a population-based cohort study of 7983 subjec ts greater than or equal to 55 years old. We determined TPA antigen an d activity in plasma and genotyped all subjects for the Alu repeat ins ertion/deletion polymorphism in intron h in the TPA gene. Homozygosity for the insertion was associated with twice as many cases of MI as wa s homozygosity for the deletion (odds ratio, 2.24; 95% CI, 1.11-4.50). TPA antigen was positively associated with the risk of MI; compared w ith that in the lowest quartile, the relative risks (odds ratio) in th e second, third, and upper quartiles were 1.7 (CI, 0.9-3.3), 2.3 (1.2- 4.4), and 2.0 (1.0-3.8), respectively. When adjusted for body mass ind ex, HDL and total cholesterol, systolic and diastolic blood pressures, and current smoking, the risk associated with TPA antigen concentrati on was attenuated. Increased concentrations of TPA activity tended to be associated with an increased risk of MI. Conclusions This study pro vides evidence for an independent association of the insertion allele of the insertion/deletion polymorphism in the TPA gene with nonfatal M I. Increased TPA antigen is associated with an increased risk of MI; h owever, this association was not independent of cardiovascular disease risk factors.