Short-term triglyceride lowering with fenofibrate improves vasodilator function in subjects with hypertriglyceridemia

Warren H. Capell, Christopher A. DeSouza, Paul Poirier, Melanie L. Bell, Brian L. Stauffer, Kathleen M. Weil, Teri L. Hernandez, Robert H. Eckel

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Objective - The objective of this study was to investigate the effects of lowering plasma triglycerides (TGs) on endothelial function and gain insight into the role played by free fatty acids (FFAs) in hypertriglyceridemia-associated vascular dysfunction. Methods and Results - Eleven hypertriglyceridemic subjects without coronary artery disease, diabetes, elevated low-density lipoprotein cholesterol, tobacco use, or hypertension were studied using a randomized, double-blinded, crossover design (fenofibrate and placebo, 14 days). After each regimen, forearm blood flow was assessed by plethysmography in response to arterial acetylcholine, nitroprusside, and verapamil infusion. Hourly plasma TGs, FFA, glucose, and insulin were measured during a 24-hour feeding cycle to characterize the metabolic environment. Changes in plasma FFA after intravenous heparin were used to estimate typical FFA accumulation in the luminal endothelial microenvironment. Fenofibrate lowered plasma TG (P<0.001), total cholesterol (P<0.01), and apolipoprotein B (P<0.01) without altering high-density lipoprotein or low-density lipoprotein cholesterol concentrations. Forearm blood flow in response to acetylcholine (P<0.0001), nitroprusside (P<0.001), and verapamil (P<0.0001) improved after fenofibrate. Fenofibrate lowered 24-hour (P<0.0001) and post-heparin (P<0.001) TG and tended to lower 24-hour (P=0.054) and post-heparin (P=0.028) FFA. Conclusions - Vascular smooth muscle function significantly improves after lowering plasma TG without changes in confounding lipoproteins or insulin resistance. The data raise additional questions regarding the role of FFA in hypertriglyceridemia-associated vascular dysfunction.

Original languageEnglish (US)
Pages (from-to)307-313
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume23
Issue number2
DOIs
StatePublished - Feb 1 2003

Keywords

  • Endothelial function
  • Free fatty acids
  • Lipoprotein lipase
  • Metabolic syndrome
  • Postprandial lipemia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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