Regulatory Effects of Fenofibrate and Atorvastatin on Lipoprotein A-I and Lipoprotein A-I:A-II Kinetics in the Metabolic Syndrome

doi:10.2337/dc09-0519

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, PHD (Hugh.Barrett{at}uwa.edu.au)¹

1. Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia
2. Lipid Research Group, The Heart Research Institute, Sydney, Australia; Department of Medicine, University of Sydney, Sydney, Australia
3. Bristol-Myers Squibb R & D, Princeton, NJ, USA

Abstract

Objectives- Subjects with the metabolic syndrome (MetS) have reduced HDL concentration and altered metabolism of HDL Lipoprotein (Lp) A-I and LpA-I:A-II particles. In MetS, fenofibrate and atorvastatin may have differential effects on HDL particle kinetics.

Research Design and Methods- Eleven men with MetS were studied in a randomized double-blinded crossover trial of 5-week intervention periods with placebo, fenofibrate (200mg/day) and atorvastatin (40mg/day). LpA-I and LpA-I:A-II kinetics were examined using stable isotopic techniques and compartmental modelling.

Results- Compared with placebo, fenofibrate significantly increased the production of both LpA-I:A-II (+30%, P<0.001) and apoA-II (+43%, P < 0.001), accounting for significant increases of their corresponding plasma concentrations (+10% and +23% respectively), but it did not alter LpA-I kinetics or concentration. Atorvastatin did not significantly alter HDL-cholesterol concentration or the kinetics of HDL particles.

Conclusions- In MetS, fenofibrate, but not atorvastatin, influences HDL metabolism by increasing the transport of LpA-I:A-II particles.