The effects of gemfibrozil upon the hypercoagulable state in dyslipidaemic patients with chronic renal failure

BACKGROUND: The dyslipidaemia of chronic renal disease could contribute to a hypercoagulable state by activation of blood coagulation and/or impairment of fibrinolysis, thereby increasing cardiovascular disease (CVD) risk. METHODS: We measured the coagulation activation marker prothrombin fragment F1 + 2 (F1 + 2), fibrinogen, plasminogen activator inhibitor-1 activity (PAI1), interleukin-6 (IL6), insulin, lipids and lipoprotein(a) (Lp(a)), in 12 patients with chronic renal disease before and after gemfibrozil. RESULTS: Gemfibrozil significantly reduced triglycerides by 44% and increased HDL-cholesterol by 31% without significant change in LDL cholesterol. Before treatment, patients had increased F1 + 2, fibrinogen and IL6, but similar PAI1 compared with the controls, consistent with a hypercoagulable and persistent inflammatory state. Following treatment, F1 + 2 decreased to within the normal range and this reduction correlated with the decrease in triglycerides and inversely with the increase in HDL-cholesterol. A non-significant decrease in fibrinogen was inversely correlated with a significant increase in albumin. However, Lp(a) and PAI1 activity significantly increased whilst insulin and IL6 were unchanged. CONCLUSIONS: Gemfibrozil improved the uraemic dyslipidaemia and hypercoagulable state by reduction in activation of blood coagulation, indirectly suggesting a reduction in lipid-dependent extrinsic pathway activity which should contribute to reduced risk of thrombosis and CVD. Reduced fibrinogen and increased albumin are consistent with a reduction in the acute phase response. Increased PAI1 and Lp(a) could impair fibrinolysis and potentially increase CVD risk, although the mechanism for these effects is uncertain but does not appear related to cytokine or insulin mediated mechanisms and requires further study. Large prospective studies are required to determine if gemfibrozil can reduce CVD events in uraemia.