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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:307.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

From the Departments of Medicine (W.H.C., P.P., B.L.S., K.M.W., T.L.H., R.H.E.) and Preventive Medicine and Biometrics (M.L.B.), University of Colorado Health Sciences Center, Denver and Department of Kinesiology and Applied Physiology (C.A.D.), University of Colorado, Boulder, Colo.

Correspondence to Warren H. Capell, MD, UCHSC, Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, 4200 East 9th Ave, Box B-151, Denver, CO 80262. E-mail warren.capell{at}uchsc.edu

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.

Key Words: endothelial function • postprandial lipemia • free fatty acids • lipoprotein lipase • metabolic syndrome

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