Atorvastatin and Fenofibrate Have Comparable Effects on VLDL–Apolipoprotein C-III Kinetics in Men With the Metabolic Syndrome

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 28; no. 10; pp. 1831 - 1837
• Main Authors: Chan, Dick C., Watts, Gerald F., Ooi, Esther M.M., Ji, Juying, Johnson, Anthony G., Barrett, P Hugh R.
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.10.2008
• Subjects: Adult; Apolipoprotein C-III - blood; Apolipoproteins A - blood; Apolipoproteins B - blood; Atorvastatin; Cholesterol - blood; Cross-Over Studies; Double-Blind Method; Down-Regulation; Dyslipidemias - blood; Dyslipidemias - drug therapy; Fenofibrate - therapeutic use; Gas Chromatography-Mass Spectrometry; Heptanoic Acids - therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypolipidemic Agents - therapeutic use; Kinetics; Lipoproteins, VLDL - blood; Male; Metabolic Syndrome - blood; Metabolic Syndrome - drug therapy; Middle Aged; Models, Biological; Pyrroles - therapeutic use; Treatment Outcome; Triglycerides - blood
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/ATVBAHA.108.170530

OBJECTIVES—The metabolic syndrome (MetS) is characterized by insulin resistance and dyslipidemia that may accelerate atherosclerosis. Disturbed apolipoprotein (apo) C-III metabolism may account for dyslipidemia in these subjects. Atorvastatin and fenofibrate decrease plasma apoC-III, but the underlying mechanisms are not fully understood. METHODS AND RESULTS—The effects of atorvastatin (40 mg/d) and fenofibrate (200 mg/d) on the kinetics of very-low density lipoprotein (VLDL)-apoC-III were investigated in a crossover trial of 11 MetS men. VLDL–apoC-III kinetics were studied, after intravenous d3-leucine administration using gas chromatography-mass spectrometry and compartmental modeling. Compared with placebo, both atorvastatin and fenofibrate significantly decreased (P<0.001) plasma concentrations of triglyceride, apoB, apoB-48, and total apoC-III. Atorvastatin, not fenofibrate, significantly decreased plasma apoA-V concentrations (P<0.05). Both agents significantly increased the fractional catabolic rate (+32% and +30%, respectively) and reduced the production rate of VLDL–apoC-III (−20% and −24%, respectively), accounting for a significant reduction in VLDL–apoC-III concentrations (−41% and −39%, respectively). Total plasma apoC-III production rates were not significantly altered by the 2 agents. Neither treatment altered insulin resistance and body weight. CONCLUSIONS—Both atorvastatin and fenofibrate have dual regulatory effects on VLDL–apoC-III kinetics in MetS; reduced production and increased fractional catabolism of VLDL–apoC-III may explain the triglyceride-lowering effect of these agents.