The association of three components of fibrinolysis with fasting insulin and triglycerides: The ARIC study

Background and Aim: The regulation of fibrinolytic activity takes place mainly through the fast-acting inhibitor of the plasminogen activator (PAI-1), but the regulatory mechanisms are not yet established. The aim of the present study was to characterize in a healthy, free-living population the associations of insulin, glucose and triglycerides (Tg) with three parameters of fibrinolysis, D-dimer, tissue plasminogen activator antigen (t-PA:Ag), and PAI-1:Ag. Methods and Results: We performed a cross-sectional analysis of pooled data from a community based case-control study. The study sample included 841 black and white men and women, aged 45 to 64 years, who participated in the Atherosclerosis Risk in Communities (ARIC) Study. Both t-PA:Ag and PAI-1:Ag were significantly and positively correlated with insulin, glucose and Tg, whereas the D-dimer was not. The regression coefficients of insulin, glucose and Tg were in all race-sex groups almost twice as strong for PAI-1:Ag as for t-PA:Ag. In white men, for example, approximately one standard deviation (SD) difference (75%) in plasma insulin was associated with a predicted difference of 15.4% (95% confidence interval 11.7-19.1%) in t-PA:Ag and 32.6% (23.1-42.9%) in PAI-1:Ag. Similar results were obtained for Tg. Thus, the percentage difference in PAI-1:Ag associated with one SD difference in insulin or Tg was significantly greater than the corresponding difference in t-PA:Ag. Furthermore, the relation between t-PA:Ag and PAI-1:Ag depends on the insulin level, especially in white women, thus a given t-PA:Ag value predicted a higher value of PAI-1:Ag in persons with high insulin than in persons with low insulin. Conclusions: In the healthy, free-living population in this study insulin and Tg were significantly associated with t-PA:Ag and PAI-1:Ag, but not with the D-dimer. These associations were approximately similar in white and blacks. Insulin modified the relation between t-PA:Ag and PAI-1:Ag in a way which is consistent with impaired fibrinolysis in persons with high insulin.