Triglycéride as predictor of both t-PA and PAI-1: Studies in non obese hypertriglyceridemic patients

Impaired fibrinolysis due to high levels of PAI-1 is frequently associated with metabolic conditions i.e. diabetes, obesity, hypertriglyceridemia and insulin resistance. Both triglycéride (TG) and insulin have been proposed as major determinants for PAI-1. In this study we investigated the relationship between levels of metabolic and fibrinolytic variables in 163 fasted subjects attending a Lipid Clinic. 118 of these subjects were hypertriglyceridemic (HTG), 45 normotriglyceridemic (NTG). In HTG a low t-PA and high PAI-1 activity was accompanied by high PAI-1 and t-PA antigen levels in comparison with NTG. Multivariate analysis yielded several significant correlations between fibrinolytic and metabolic variables. In stepwise multiple regression analysis, however only insulin and TG levels were significant and independent predictors of PAI-1 antigen levels (r²=0.22, p <0.0001 ). When patients were grouped in fertiles according to their levels of TG and insulin, PAI-1 antigen levels were found to increase with rising levels of TG in each insulin tenues. Subjects in the lowest fertile of both TG and insulin had the lowest PAI-1 antigen levels, and subjects in the highest tertile of both TG and insulin had the highest levels of PAI-1. Levels of t-PA antigen were higher in HTG than in NTG and multiple stepwise regression analysis identified triglycéride levels as the sole major predictor of t-PA levels (r²=0.13, p <0.00003). In addition the amounts of t-PA antigen released during venous occlusion were greater in HTG patients than in NTG, indicating that endothelial pool of t-PA is larger in hypertriglyceridemic subjects and may represent a compensatory mechanism toward enhanced PAI-1 biosynthesis in the vessel wall.