Beneficial Effect of Gemfibrozil on LDL Chemicophysical Characteristics and Oxidizability

Abstract

Previous reports have shown that administration of fibrates can reduce coronary events and also improve plasma lipids. Oxidative modification of low density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis, and the resistance of LDL to in vitro oxidation has been found to be correlated with the extent of atherosclerosis. We performed a double-blind, placebo-controlled intervention trial to establish whether gemfibrozil could improve resistance of LDL to oxidation in patients with hyperlipidemia. Patients were randomly assigned to treatment with gemfibrozil (450 mg, twice a day, n=10) or placebo (n=9) for 8 weeks. Gemfibrozil administration significantly reduced total plasma cholesterol and triglyceride levels and changed the LDL from small, dense particles (pattern B, ≤ 25.5 nm) to larger, more buoyant particles (pattern A, > 25.5 nm). Gemfibrozil significantly increased the lag time of LDL oxidation in vitro by 18.2 % from 45.5 ± 8.0 min at week 0 to 53.4 ± 11.4 min at week 8, but did not change LDL vitamin E concentrations. Moreover, gemfibrozil significantly decreased LDL lipid peroxides by-33.1 % and increased the LDL vitamin E/ lipid peroxide ratio by 67.6 %. These results demonstrate that gemfibrozil treatment can render LDL less susceptible to oxidative modification while reducing plasma cholesterol and triglyceride levels, and improving LDL subclass pattern. This antioxidative effect of gemfibrozil on LDL may be one of factors which could delay the progression of atherosclerosis.