PLASMINOGEN-ACTIVATOR INHIBITOR-1 IS ELEVATED IN THE CHILDREN OF MEN WITH PREMATURE MYOCARDIAL-INFARCTION

To assess whether plasminogen activator inhibitor 1 (PAI-1) activity i s elevated in the progeny of young coronary men, 193 young subjects we re recruited and divided into two groups. Group A consisted of 104 chi ldren whose fathers had suffered a myocardial infarction before the ag e of 55 (''cases''). Eighty-nine young subjects matched for age, sex, body mass index (BMT) and smoking habits without familial history of c oronary artery disease (CAD) served as controls (group B). Children wi th a family history of diabetes mellitus or hypertension were excluded from both groups. We measured PAT-I activity, tissue-type plasminogen activator (t-PA) antigen, a2-antiplasmin, fibrinogen, lipids and apol ipoproteins in both groups. PAI-I activity levels were also determined in the men who suffered a premature myocardial infarction 4 months af ter their discharge. PAI-1 activity levels were higher in cases compar ed to controls (3.13 +/- 1.9 vs 2.17 +/- 1.9 U/ml, p = 0.0014). t-PA a ntigen and a2-antiplasmin did not differ significant ly between the tw o groups, while fibrinogen, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) were significantly h igher in group A. PAI-I was positively correlated with triglycerides ( r = 0.22, p = 0.024), apolipoprotein B (r = 0.21, p = 0.039) and fibri nogen (r = 0.22, p = 0.029) in cases and with BMI in both cases (r = 0 .37, p = 0.0003) and controls (r = 0.23, p = 0.044). In stepwise multi ple regression analysis, only apolipoprotein B (p = 0.008) and BMI (p = 0.0014) were significant determinants of PAI-1 activity in cases. Th ere was also a positive correlation between PAI-1 activity levels of t he affected fathers and their children (r = 0.30, p = 0.01). The prese nt data support the hypothesis that elevated PAI-1 levels in the offsp ring of men with premature myocardial infarction impair their fibrinol ytic capacity contributing to their familial predisposition to CAD.