Dose-dependent regulation of high-density lipoprotein metabolism with rosuvastatin in the metabolic syndrome

J Clin Endocrinol Metab. 2008 Feb;93(2):430-7. doi: 10.1210/jc.2007-0854. Epub 2007 Nov 20.


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.

Methods and 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein A-I / blood
  • Apolipoprotein A-II / blood
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Fluorobenzenes / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Lipoproteins, HDL / blood*
  • Male
  • Metabolic Syndrome / blood*
  • Metabolic Syndrome / drug therapy
  • Middle Aged
  • Particle Size
  • Pyrimidines / therapeutic use*
  • Rosuvastatin Calcium
  • Sulfonamides / therapeutic use*
  • Triglycerides / blood


  • Apolipoprotein A-I
  • Apolipoprotein A-II
  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, HDL
  • Pyrimidines
  • Sulfonamides
  • Triglycerides
  • Rosuvastatin Calcium