Plasminogen Activator Inhibitor 1 Is Elevated in the Children of Men with Premature Myocardial Infarction

Abstract

SummaryTo assess whether plasminogen activator inhibitor 1 (PAI-1) activity is elevated in the progeny of young coronary men, 193 young subjects were recruited and divided into two groups. Group A consisted of 104 children whose fathers had suffered a myocardial infarction before the age of 55 (“cases”). Eighty-nine young subjects matched for age, sex, body mass index (BMI) and smoking habits without familial history of coronary artery disease (CAD) served as controls (group B). Children with a family history of diabetes mellitus or hypertension were excluded from both groups. We measured PAI-1 activity, tissue-type plasminogen activator (t-PA) antigen, a2-antiplasmin, fibrinogen, lipids and apolipoproteins in both groups. PAI-1 activity levels were also determined in the men who suffered a premature myocardial infarction 4 months after their discharge. PAI-1 activity levels were higher in cases compared to controls (3.13 ± 1.9 vs 2.17 ± 1.9 U/ml, p = 0.0014). t-PA antigen and a2-antiplasmin did not differ significantly between the two groups, while fibrinogen, total cholesterol, low-den-sity lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) were significantly higher in group A. PAI-1 was positively correlated with triglycerides (r = 0.22, p = 0.024), apolipoprotein B (r = 0.21, p = 0.039) and fibrinogen (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 multiple regression analysis, only apolipoprotein B (p = 0.008) and BMI (p = 0.0014) were significant determinants of PAI-1 activity in cases. There was also a positive correlation between PAI-1 activity levels of the affected fathers and their children (r = 0.30, p = 0.01). The present data support the hypothesis that elevated PAI-1 levels in the offspring of men with premature myocardial infarction impair their fibrinolytic capacity contributing to their familial predisposition to CAD.

Tissue Plasminogen Activator, Fibrin D-Dimer, and Insulin Resistance in the Relatives of Patients With Premature Coronary Artery Disease

“…However, this finding was based on univariate analysis alone and no correlation was found between PAI-1 and tPA. 40 In the present study, we have identified the well reported relationship between the 4G allele of the PAI-1 gene 4G/5G polymorphism and increased PAI-1 levels but found no difference in genotype frequency between relatives and controls. This is in contrast to a study by Margaglione et al 39 which found the 4G/4G genotype to be independently associated with family history of MI.…”

Cardiovascular risk factors in children with obesity, hypertension and diabetes: lipoprotein(a) levels and body mass index correlate with family history of cardiovascular disease

“…Radilis et al [24] determined the activity of PAI-1 in children whose fathers had myocardial infarction before the age of 55 years. In both the children and their fathers, a significant increase in the activity of PAI-1 was found.…”

Maximizing the Cost-effectiveness of Lipid-Lowering Therapy

“…79 Plasminogen activator inhibitor 1 is elevated in the children of men with premature MI, and these elevated plasminogen activator inhibitor 1 levels impair fibrinolytic capacity. 80 Finally, the most recently described risk factor is C-reactive protein, which may act as a marker of "microinflammation," hypothesized to have a role in the initiation and progression of atherosclerosis. In the Physicians' Health Study, this risk factor increased MI and stroke risk almost 3-fold and was independent of lipid and nonlipid risk factors.…”