EFFECTS OF GEMFIBROZIL ON VERY-LOW-DENSITY LIPOPROTEIN COMPOSITION AND LOW-DENSITY-LIPOPROTEIN SIZE IN PATIENTS WITH HYPERTRIGLYCERIDEMIA OR COMBINED HYPERLIPIDEMIA

To examine the effects of gemfibrozil on very-low-density lipoprotein (VLDL) composition and low-density lipoprotein (LDL) size, five men wi th hypertriglyceridemia (HTG) alone and five men with HTG and hypercho lesterolemia (combined hyperlipidemia, CHLP) were randomized for 8 wee ks to Lopid SR (slow-release gemfibrozil; two 600-mg tablets once per day) or placebo in a crossover study. Drug therapy versus placebo sign ificantly decreased plasma triglyceride (68%), and VLDL (77%), and sig nificantly increased high-density lipoprotein cholesterol (25%); total cholesterol, apolipoprotein B and lipoprotein[a] concentrations did n ot change significantly. With drug, mean total apoE in plasma was 53% lower in patients with HTG and 39% lower in patients with CHLP. Gemfib rozil significantly affected VLDL composition: protein increased 26%, molar ratio of apoE to apoB reduced 48%, apoC-II increased 19%, and ap oC-III decreased 9%. LDL cholesteryl ester significantly increased wit h drug treatment. VLDL subfractions were separated and classified as h eparin binding (VLDL(R), apoE rich) or nonbinding (VLDL(NR-1) and VLDL (NR-2), both apoE poor). All VLDL subfractions were significantly lowe r with drug therapy, and the differences for total VLDL and for VLDL s ubfractions were greater in patients with HTG. With placebo, VLDL, acc ounted for 41.8% of VLDL in HTG and 49.0% of VLDL in CHLP, reduced to 27.6% and 38.6%, respectively, with gemfibrozil. Taken together, these results suggest that treatment with gemfibrozil reduces plasma concen trations of VLDL and alters the apoprotein composition of VLDL in a ma nner that may favor LDL- and VLDL-receptor-mediated clearance of the a poE-rich VLDL subfraction, thereby reducing TG-rich particle concentra tions, and possibly reducing risk for coronary heart disease.