HYPERINSULINEMIA PREDICTS LOW TISSUE-PLASMINOGEN ACTIVATOR ACTIVITY IN A HEALTHY POPULATION - THE NORTHERN SWEDEN MONICA STUDY

Fibrinogen levels predict atherothrombotic disease, and impaired fibri nolysis has been proposed as a risk factor for myocardial infarction. Fibrinolysis is mainly dependent on the activity of tissue plasminogen activator (tPA) and its inhibitor plasminogen activator inhibitor typ e-1 (PAI-1). Oral glucose tolerance tests were performed in 318 random ly selected healthy men and 324 women aged 25 to 64 years. tPA activit y was strongly predicted by fasting insulin in both univariate analysi s (r = -.37 and -.34 in men and women, respectively) and multivariate analysis with age, anthropometric measurements, lipids, and blood pres sure included. Fasting insulin was the strongest predictor of PAI-1 ac tivity (r = .49 and .51). In women, the influence of fasting insulin l evel on tPA and PAI-1 activity was consistently stronger after than be fore menopause, and a threshold effect was seen with distinctly lower fibrinolytic activity in the highest quartile of insulin (27.0 mU/L). In men, the relation between insulin and fibrinolytic variables was li near. Fibrinogen levels were not related to insulin or glucose levels after adjustment for age and other risk factors in a multiple regressi on. Subjects with previously unknown diabetes or impaired glucose tole rance tended to have elevated fibrinogen and PAI-1 activity and decrea sed tPA activity. Our data support previous findings of a strong corre lation between insulin and PAI-1 activity in small highly selected gro ups, and extend them to randomly selected population samples. The stro ng inverse relation between endogenous insulin levels and tPA activity has not previously been demonstrated in a healthy population. Copyrig ht (C) 1994 by W.B. Saunders Company