Additive effect of triglyceride and insulin as determinants of plasminogen activator inhibitor-1 levels in normo and hypertriglyceridemic subjects

Impaired fibrinolytic function, secondary to elevated levels of PAI-1, is frequently observed in patients with CHD, obesity, diabetes, hypertriglyceridemia, hyperinsulinemia and insulin-resistance syndrome. A direct correlation between PAI-1, triglyceride (TG) and/or insulin levels was found in normal subjects and in patients at risk of atherothrombotic disease. It is still open the question whether triglycerides and/or insulin are, among others, the major physiological regulators of PAI-1 plasma levels. In this study we have investigated the relationship between fasting levels of insulin, lipids and PAI-1 antigen in normo and hyperlipidemic subjects (n=163). 44 subjects were characterized by TG levels below 150 mg/dl, 60 by TG levels between 151-350 mg/dl and 59 by TG levels higher than 351 mg/dl. In the overall group, PAI-1 plasma levels correlated positively and significantly with insulin, TG, body mass index, total cholesterol and blood glucose. At the stepwise multiple regression analysis, insulin and log transformed TG were the only significant and independent predictors of PAI-1 antigen levels (r2=0.21, p<0.0001 ). To better investigate the role of triglycerides and insulin as determinants of PAI-1, the subjects were categorized in tertiles according to TG and insulin levels and PAI-1 compared within strata of these parameters. PAI-1 antigen levels gradually increased with rising levels of TG within all strata of insulin. In contrast, the increase of PAI-1 with rising of insulin levels was evident in the highest tertile of triglycerides only. In addition, subjects in the lowest tertiles of TG and insulin had lowest PAI•1 antigen levels, while subjects in the highest tertiles of TG and insulin had the highest levels of PAI-1. In conclusion, an additive effect of triglycerides and insulin as determinants of plasminogen activator inhibitor-1 levels is suggested.