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

The fibrinolytic system is regulated by the balance between the levels of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1). A positive correlation between PAI-1 and triglyceride (TG) or insulin levels was found in obesity, CHD, diabetes, hypertriglyceridemia and hyperinsulinemia, all considered proatherothrombotic conditions. It is still open the question whether triglycerides and/or insulin are the major physiologycal 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 plasma levels of PAI-1 antigen correlated positively and significantly with insulin, TG, body mass index, total cholesterol and blood glucose. At the stepwise multiple regression analysis, insulin and logTG were the only significant and independent predictor of PAI-1 antigen levels, (r squared= 0.21, p<0.0001). In order to better investigate the role of triglycerides and insulin as determinants of PAI-1, the subjects were categorized in tertiles according to their levels of TG and insulin and PAI-1 compared within strata of these two 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 tertile of TG and insulin had the 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 triglyceride and insulin as determinants of plasminogen activator inhibitor-1 levels was suggested.