Dose-dependent regulation of high-density lipoprotein metabolism with rosuvastatin in the metabolic syndrome.
BACKGROUND
Low plasma concentration of high-density lipoprotein (HDL) cholesterol is a risk factor for cardiovascular disease and a feature of the metabolic syndrome. Rosuvastatin has been shown to increase HDL cholesterol concentration, but the mechanisms remain unclear.


RESULTS
Twelve men with the metabolic syndrome were studied in a randomized, double-blind, crossover trial of 5-wk therapeutic periods with placebo, 10 mg/d rosuvastatin, or 40 mg/d rosuvastatin, with 2-wk placebo washout between each period. Compared with placebo, there was a significant dose-dependent increase in HDL cholesterol, HDL particle size, and concentration of HDL particles that contain apolipoprotein A-I (LpA-I). The increase in LpA-I concentration was associated with significant dose-dependent reductions in triglyceride concentration and LpA-I fractional catabolic rate, with no changes in LpA-I production rate. There was a significant dose-dependent reduction in the fractional catabolic rate of HDL particles containing both apolipoprotein A-I and A-II (LpA-I:A-II), with concomitant reduction in LpA-I:A-II production rate, and hence no change in LpA-I:A-II concentration.


CONCLUSIONS
Rosuvastatin dose-dependently increased plasma HDL cholesterol and LpA-I concentrations in the metabolic syndrome. This could relate to reduction in plasma triglycerides with remodeling of HDL particles and reduction in LpA-I fractional catabolism. The findings contribute to understanding mechanisms for the HDL-raising effect of rosuvastatin in the metabolic syndrome with implications for reduction in cardiovascular disease.
Ooi
Esther M M
EM
Metabolic Research Centre, School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, Perth, Western Australia 6847, Australia.
Watts
Gerald F
GF
Nestel
Paul J
PJ
Sviridov
Dmitri
D
Hoang
Anh
A
Barrett
P Hugh R
PH
D016632:Apolipoprotein A-I / Q000097:blood; D016633:Apolipoprotein A-II / Q000097:blood; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000188:drug therapy; D008875:Middle Aged; D010316:Particle Size; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D011743:Pyrimidines; D013449:Sulfonamides; D014280:Triglycerides; D000068718:Rosuvastatin Calcium