Published online before print October 13, 2005, doi: 10.1161/01.ATV.0000190700.76493.bb
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© 2005 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Effect of Fenofibrate on Plasma Lipoprotein Composition and Kinetics in Patients With Complete Hepatic Lipase Deficiency
From the Institute on Nutraceuticals and Functional Foods (I.L.R., B.L., J.-F.M.), Laval University, Québec, Canada; the Lipid Research Center (I.L.R., B.L., J.-F.M., P.C.), CHUL Research Center, Québec, Canada; the Department of Medicine and Center for Experimental Therapeutics (K.O.B.), University of Pennsylvania School of Medicine, Philadelphia, Pa; the Hyperlipidemia and Atherosclerosis Research Group (J.S.C.), Clinical Research Institute of Montréal, Canada; and the Cardiovascular Genetics Laboratory (M.M.), Royal Victoria Hospital, McGill University Health Center, Montréal, Canada.
Correspondence to Patrick Couture, MD, PhD, Lipid Research Center, CHUL, 2705 Laurier Blvd, S-102, Québec, G1V 4G2, Canada. E-mail patrick.couture{at}crchul.ulaval.ca; or to Benoît Lamarche, PhD, Institute on Nutraceuticals and Functional Foods, 2440 Hochelaga Blvd, local 2742, Québec, G1K 7P4, Canada. E-mail benoit.lamarche@inaf.ulaval.ca
Objective— The goal of this study was to characterize the effect of microcoated fenofibrate (160 mg/day for 6 months) on plasma lipoprotein composition and kinetics in 2 patients with complete hepatic lipase (HL) deficiency.
Methods and Results— Fenofibrate treatment normalized the plasma lipoprotein profile of patients with complete HL deficiency, as evidenced by significant reductions in the plasma concentration of cholesterol (–49%) and triglycerides (–82%) and a significant increase in low-density lipoprotein (LDL) size (251.5±1.8 versus 263.5±0.7 Å). The in vivo kinetics of very low–density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and LDL apolipoprotein (apo)B-100 and plasma apoA-I and apoA-II were studied using a primed-constant infusion of L-[5,5,5-D3]-leucine for 12 hours in the fasted state. Fenofibrate treatment in complete HL-deficient patients substantially decreased plasma concentrations of VLDL, IDL, and LDL apoB-100 attributable to important increases in VLDL (+325%), IDL (+129%), and LDL (+218%) apoB-100 fractional catabolic rates (FCR). IDL apoB-100 FCR nevertheless remained 60% lower after treatment compared with values obtained in controls (n=5). The kinetics of plasma apoA-I and apoA-II as well as the capacity of total plasma and of high-density lipoprotein particles to efflux cellular cholesterol from normal human skin fibroblasts was not altered by fenofibrate.
Conclusion— Fenofibrate therapy exerts a pronounced antiatherogenic effect on triglyceride-rich lipoproteins even in the complete absence of HL.
Fenofibrate treatment in 2 patients with complete HL deficiency was associated with a marked reduction in plasma triglyceride concentration and an improvement in the composition and metabolism of all apoB-containing lipoproteins, indicating that fenofibrate can have pronounced antiatherogenic effects on plasma lipoprotein metabolism even in the complete absence of HL.
Key Words: lipids • primary prevention • genetics of cardiovascular disease • lipid and lipoprotein metabolism