RELATIONSHIP BETWEEN PLASMA PLASMINOGEN-ACTIVATOR INHIBITOR-1 ACTIVITY AND VLDL TRIGLYCERIDE CONCENTRATION, INSULIN LEVELS AND INSULIN SENSITIVITY - STUDIES IN RANDOMLY SELECTED NORMOTRIGLYCERIDAEMIC AND HYPERTRIGLYCERIDEMIC MEN

Impaired fibrinolytic function secondary to elevated plasma plasminoge n activator inhibitor-1 activity, hypertriglyceridaemia and hyperinsul inaemia are frequent findings in patients with coronary heart disease. It has been debated whether VLDL or insulin is the major regulator of plasma plasminogen activator inhibitor-1 activity. This study examine s the relationships between plasma plasminogen activator inhibitor-1 a ctivity and VLDL trigLyceride concentration, fasting and post-oral glu cose load insulin levels and insulin sensitivity, as estimated by the minimal model method. Subjects studied were randomly selected hypertri gLyceridaemic (n = 65) and age-matched normotriglyceridaemic (n = 61) men, aged 40-50 years, recruited in a population survey. Plasma plasmi nogen activator inhibitor-1 activity was higher in the hypertriglyceri daemic than in the normotriglyceridaemic group (21 +/- 14 vs 10 +/- 8 mU/l; p < 0.01). The hypertriglyceridaemic group had higher serum insu lin, basal as well as 2 h after intake of the oral glucose load, and a lower insulin sensitivity index. In univariate analysis, plasma plasm inogen activator inhibitor-I activity correlated positively with VLDL triglycerides in both the hyper- and normotriglyceridaemic groups (r = 0.43 r = 0.60, respectively) and negatively with the insulin sensitiv ity index (r = -0.35 r = -0.44, respectively). In multivariate analysi s, VLDL triglyceride levels were found to be independently related to plasma plasminogen activator inhibitor-1 activity in both groups, wher eas insulin sensitivity/serum insulin levels were not. An unexpected f inding was that the serum activity of the enzyme gamma glutamyl transp eptidase appeared to influence the relationships for plasma plasminoge n activator inhibitor-1 in the hypertriglyceridaemic group. In conclus ion, this population-based study indicates that VLDL triglyceride conc entration is one of the major determinants of plasma plasminogen activ ator inhibitor-1 activity in both normotriglyceridaemic and hypertrigl yceridaemic men.