Effect of gemfibrozil and lovastatin on postprandial lipoprotein clearance in the hypoalphalipoproteinemia and hypertriglyceridemia syndrome.

Eleven men with hypoalphalipoproteinemia (HPAL; fasting plasma high density lipoprotein (HDL) cholesterol level of < 0.9 mmol/l), mild hypertriglyceridemia (HTG; triglycerides (TG) level of 1.75-7.5 mmol/l) and a normal calculated LDL cholesterol level (< 3.7 mmol/l) participated in a randomized, double-blind, double-placebo, crossover trial to compare the effect of two drugs, lovastatin (40 mg once daily) and gemfibrozil (600 mg twice daily), on clearance of postprandial lipoproteins. A 2-week washout period separated drug treatment periods of 6 weeks each. Ten subjects completed each treatment period. After ingestion of a vitamin A fat load, plasma, chylomicron and non-chylomicron retinyl palmitate (RP) and TG responses (areas under curves) were reduced in all subjects on gemfibrozil therapy and in 7 on lovastatin therapy. There was close correlation between change in fasting TG (but not fasting HDL-cholesterol) and change in postprandial RP areas on gemfibrozil but not lovastatin therapy. Postheparin lipoprotein lipase (LPL) and hepatic lipase (HL) activities were increased by gemfibrozil therapy while only a mild elevation in LPL activity alone was seen on lovastatin therapy. These data indicate that improvement in HTG is the main feature associated with improvement in postprandial lipemia and this is likely due to LPL-mediated enhancement of lipolytic hydrolysis. Gemfibrozil is more effective than lovastatin in attenuating postprandial lipemia in the HPAL/HTG syndrome.