Regulatory effects of fenofibrate and atorvastatin on lipoprotein A-I and lipoprotein A-I:A-II kinetics in the metabolic syndrome.
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.


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.
Chan
Dick C
DC
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
Watts
Gerald F
GF
Ooi
Esther M M
EM
Rye
Kerry-Anne
KA
Ji
Juying
J
Johnson
Anthony G
AG
Barrett
P Hugh R
PH
D000069059:Atorvastatin; D018592:Cross-Over Studies; D004311:Double-Blind Method; D011345:Fenofibrate / Q000627:therapeutic use*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007700:Kinetics; D017270:Lipoprotein(a) / Q000097:blood* / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000097:blood / Q000187:drug effects; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D009391:Nephelometry and Turbidimetry / Q000379:methods; D010919:Placebos; D011758:Pyrroles / Q000627:therapeutic use*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D017270:Lipoprotein(a); D008075:Lipoproteins, HDL; D010919:Placebos; D011758:Pyrroles; C106575:lipoprotein A-II; C078260:lipoprotein A-I; D000069059:Atorvastatin; D011345:Fenofibrate