GEMFIBROZIL TREATMENT OF COMBINED HYPERLIPOPROTEINEMIA - NO IMPROVEMENT OF FIBRINOLYSIS DESPITE MARKED REDUCTION OF PLASMA TRIGLYCERIDE LEVELS

Hypertriglyceridemia is linked to impaired fibrinolytic function, and lipid-lowering treatment with fibric acid derivatives could hypothetic ally improve fibrinolysis in this condition. We therefore conducted a double-blind, placebo-controlled, crossover study of gemfibrozil treat ment on fibrinolytic function in 21 men with combined hyperlipoprotein emia. Measurements were performed at rest and during mental stress and after venous occlusion. The patients had clearly disturbed fibrinolyt ic function, with elevated plasminogen activator inhibitor-1 (PAI-1) a ctivity at rest (approximate to 25 U/mL; reference, <15 U/mL). Gemfibr ozil reduced plasma total and VLDL cholesterol as well as all triglyce ride fractions, whereas HDL cholesterol increased (P<.001 for all). To tal triglyceride levels were reduced by 57 +/- 4% (from 5.3 to 2.1 mmo l/L). Fasting serum insulin levels were not altered by gemfibrozil tre atment. Plasma levels of PAI-1 activity and tissue-type plasminogen ac tivator (TPA) activity or antigen were unaffected by gemfibrozil treat ment both at rest and during the provocations. The levels of D-dimer, plasmin/antiplasmin complex, and fibrinogen were also uninfluenced by gemfibrozil treatment. Mental stress elevated plasma TPA (P=.0036) and lowered PAI-1 (P=.0012) activity during placebo but not gemfibrozil t reatment (P=.28 and P=.17, respectively), but treatment effects did no t differ by ANOVA on h values (ie, stress minus rest). Venous occlusio n reduced PAI-1 activity, whereas TPA and plasmin/antiplasmin complex increased during both treatments. Thus, gemfibrozil treatment did not improve fibrinolysis or lower fibrinogen levels in men with combined h yperlipoproteinemia despite marked reduction of plasma triglyceride le vels. It seems unlikely that improved fibrinolysis explains the primar y preventive effect of gemfibrozil.