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


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.
Capell
Warren H
WH
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA. warren.capell@uchsc.edu
DeSouza
Christopher A
CA
Poirier
Paul
P
Bell
Melanie L
ML
Stauffer
Brian L
BL
Weil
Kathleen M
KM
Hernandez
Teri L
TL
Eckel
Robert H
RH
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000502:physiology; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy* / Q000503:physiopathology*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D017698:Postmenopause / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012189:Retrospective Studies; D014280:Triglycerides / Q000097:blood* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014280:Triglycerides; D011345:Fenofibrate