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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1831.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

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

Dick C. Chan; Gerald F. Watts; Esther M.M. Ooi; Juying Ji; Anthony G. Johnson; P. Hugh R. Barrett

From the Metabolic Research Centre (D.C.C., G.F.W., E.M.M.O., J.J., P.H.R.B.), School of Medicine and Pharmacology, University of Western Australia, Perth; and Bristol-Myers Squibb R&D (A.G.J.), Princeton, NJ.

Correspondence to Professor Gerald F. Watts, School of Medicine and Pharmacology, University of Western Australia, GPO Box X2213 Perth Western Australia 6847 Australia. E-mail gerald.watts{at}uwa.edu.au

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.

Key Words: lipoprotein metabolism • obesity • insulin resistance • cardiovascular disease • statin • fenofibrate

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The complexities of apoC-III metabolism: more exchangeable results?

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ATVB Online, 4 Jul 2009 [Full text]