Effects of gemfibrozil on very-low-density lipoprotein composition and low-density lipoprotein size in patients with hypertriglyceridemia or combined hyperlipidemia

Chao Yuh Yang, Zi Wei Gu, Yong Hong Xie, Natalya V. Valentinova, Manlan Yang, Daniel Yeshurun, Jun Anthony V. Quion, Antonio M. Gotto

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

To examine the effects of gemfibrozil on very-low-density lipoprotein (VLDL) composition and tow-density lipoprotein (LDL) size, five men with hypertriglyceridemia (HTG) alone and five men with HTG and hypercholesterolemia (combined hyperlipidemia, CHLP) were randomized for 8 weeks to Lopid SR (slow-release gemfibrozil; two 600-mg tablets once per day) or placebo in a crossover study. Drug therapy versus placebo significantly decreased plasma triglyceride (68%), and VLDL (77%), and significantly increased high-density lipoprotein cholesterol (25%); total cholesterol, apolipoprotein B and lipoprotein[a] concentrations did not change significantly. With drug, mean total apoE in plasma was 53% lower in patients with HTG and 39% lower in patients with CHLP. Gemfibrozil significantly affected VLDL composition: protein increased 26%, molar ratio of apoE to apoB reduced 48%, apoC-II increased 19%, and apoC-III decreased 9%. LDL cholesteryl ester significantly increased with drug treatment. VLDL subfractions were separated and classified as heparin binding (VLDL(R), apoE rich) or nonbinding (VLDL(NR-1) and VLDL(NR-2), both apoE poor). All VLDL subfractions were significantly lower with drug therapy, and the differences for total VLDL and for VLDL subfractions were greater in patients with HTG. With placebo, VLDL(R) accounted 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 concentrations of VLDL and alters the apoprotein composition of VLDL in a manner that may favor LDL- and VLDL-receptor-mediated clearance of the apoB-rich VLDL subfraction, thereby reducing TG-rich particle concentrations, and possibly reducing risk for coronary heart disease.

Original languageEnglish (US)
Pages (from-to)105-116
Number of pages12
JournalAtherosclerosis
Volume126
Issue number1
DOIs
StatePublished - Sep 27 1996

Keywords

  • Apolipoprotein E
  • Gemfibrozil
  • Hyperlipidemia
  • LDL size
  • Plasma lipoproteins
  • VLDL composition
  • VLDL subfractions

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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