OBJECTIVES: Gemfibrozil is the most widely used fibric acid for the management of combined hyperlipidaemia. It has beneficial effects in the prevention of coronary heart disease (CHD). The mechanisms by which it exerts this effect are not completely resolved. We studied whether gemfibrozil affects low-density lipoprotein (LDL) size and LDL oxidation parameters in males with a moderate combined hyperlipidaemia at high risk for progressive atherosclerosis. DESIGN: Open treatment with 2 x 600 mg gemfibrozil daily for 12 weeks. SETTING: Outpatient lipid clinic of a tertiary referral centre. SUBJECTS: Twenty-three patients with combined hyperlipidaemia and CHD or a positive family history for both CHD and hyperlipidaemia. MAIN OUTCOME MEASURES: Effects on triglyceride (TG), autoantibodies to oxidized LDL, LDL pattern and resistance to oxidative modification. RESULTS: During treatment with gemfibrozil, plasma TG concentration decreased from 2.83 +/- 0.85 to 2.02 +/- 0.89 mmol L-1 (P < 0.001). All but one patient were shown to have LDL pattern B. The LDL pattern did not change upon treatment with gemfibrozil. The resistance to oxidation, reflected in the lagtime during in-vitro oxidation slightly decreased from 105 +/- 22 to 99 +/- 18 min (P = 0.01). The concentration of autoantibodies against oxidized LDL indicates the rate of LDL oxidation in vivo. This concentration significantly decreased from 14.2 +/- 9.9 to 13.1 +/- 9.2 mg L-1 (P < 0.01). CONCLUSIONS: The beneficial effect of gemfibrozil in reducing CHD may at least in part depend on a decrease of the rate of LDL oxidation in vivo.
OBJECTIVES:Gemfibrozil is the most widely used fibric acid for the management of combined hyperlipidaemia. It has beneficial effects in the prevention of coronary heart disease (CHD). The mechanisms by which it exerts this effect are not completely resolved. We studied whether gemfibrozil affects low-density lipoprotein (LDL) size and LDL oxidation parameters in males with a moderate combined hyperlipidaemia at high risk for progressive atherosclerosis. DESIGN: Open treatment with 2 x 600 mg gemfibrozil daily for 12 weeks. SETTING:Outpatientlipid clinic of a tertiary referral centre. SUBJECTS: Twenty-three patients with combined hyperlipidaemia and CHD or a positive family history for both CHD and hyperlipidaemia. MAIN OUTCOME MEASURES: Effects on triglyceride (TG), autoantibodies to oxidized LDL, LDL pattern and resistance to oxidative modification. RESULTS: During treatment with gemfibrozil, plasma TG concentration decreased from 2.83 +/- 0.85 to 2.02 +/- 0.89 mmol L-1 (P < 0.001). All but one patient were shown to have LDL pattern B. The LDL pattern did not change upon treatment with gemfibrozil. The resistance to oxidation, reflected in the lagtime during in-vitro oxidation slightly decreased from 105 +/- 22 to 99 +/- 18 min (P = 0.01). The concentration of autoantibodies against oxidized LDL indicates the rate of LDL oxidation in vivo. This concentration significantly decreased from 14.2 +/- 9.9 to 13.1 +/- 9.2 mg L-1 (P < 0.01). CONCLUSIONS: The beneficial effect of gemfibrozil in reducing CHD may at least in part depend on a decrease of the rate of LDL oxidation in vivo.