Regulatory Effects of Fenofibrate and Atorvastatin on Lipoprotein A-I and Lipoprotein A-I:A-II Kinetics in the Metabolic Syndrome
- Dick C. Chan, PHD1,
- Gerald F. Watts, MD, DSC1,
- Esther M.M. Ooi, PHD1,
- Kerry-Anne Rye, PHD2,
- Juying Ji, PHD1,
- Anthony G. Johnson, MD3 and
- P. Hugh R. Barrett, PHD1
- 1Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia;
- 2Lipid Research Group, the Heart Research Institute, Sydney, Australia, and the Department of Medicine, University of Sydney, Sydney, Australia;
- 3Bristol-Myers Squibb R&D, Princeton, New Jersey.
- Corresponding author: P.H.R. Barrett, hugh.barrett{at}uwa.edu.au.
Abstract
OBJECTIVE Subjects with the metabolic syndrome have reduced HDL cholesterol concentration and altered metabolism of high-density lipoprotein (Lp)A-I and LpA-I:A-II particles. In the metabolic syndrome, fenofibrate and atorvastatin may have differential effects on HDL particle kinetics.
RESEARCH DESIGN AND METHODS Eleven men with metabolic syndrome were studied in a randomized, double-blind, crossover trial of 5-week intervention periods with placebo, fenofibrate (200 mg/day), and atorvastatin (40 mg/day). LpA-I and LpA-I:A-II kinetics were examined using stable isotopic techniques and compartmental modeling.
RESULTS Compared with placebo, fenofibrate significantly increased the production of both LpA-I:A-II (30% increase; P < 0.001) and apoA-II (43% increase; P < 0.001), accounting for significant increases of their corresponding plasma concentrations (10 and 23% increases, respectively), but it did not alter LpA-I kinetics or concentration. Atorvastatin did not significantly alter HDL concentration or the kinetics of HDL particles.
CONCLUSIONS In the metabolic syndrome, fenofibrate, but not atorvastatin, influences HDL metabolism by increasing the transport of LpA-I:A-II particles.
Footnotes
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Clinical trial reg. no. NCT00632840, clinicaltrials.gov.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received March 16, 2009.
- Accepted July 24, 2009.
- © 2009 by the American Diabetes Association.
