Hypertriglyceridemia is linked to impaired fibrinolytic function, and
lipid-lowering treatment with
fibric acid derivatives could hypothetically improve fibrinolysis in this condition. We therefore conducted a double-blind, placebo-controlled, crossover study of
gemfibrozil treatment on fibrinolytic function in 21 men with combined
hyperlipoproteinemia. Measurements were performed at rest and during mental stress and after venous occlusion. The patients had clearly disturbed fibrinolytic function, with elevated
plasminogen activator inhibitor-1 (PAI-1) activity at rest ( approximately 25 U/mL; reference, <15 U/mL).
Gemfibrozil reduced plasma total and
VLDL cholesterol as well as all
triglyceride fractions, whereas
HDL cholesterol increased (P <.001 for all). Total
triglyceride levels were reduced by 57 +/- 4% (from 5.3 to 2.1 mmol/L). Fasting serum
insulin levels were not altered by
gemfibrozil treatment. Plasma levels of
PAI-1 activity and
tissue-type plasminogen activator (TPA) activity or
antigen were unaffected by
gemfibrozil treatment 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 treatment (P=.28 and P=.17, respectively), but treatment effects did not differ by ANOVA on delta values (ie, stress minus rest). Venous occlusion 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
hyperlipoproteinemia despite marked reduction of plasma
triglyceride levels. It seems unlikely that improved fibrinolysis explains the primary preventive effect of
gemfibrozil.