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

Abstract

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.

• Authors: Esther M M Ooi, Gerald F Watts, Paul J Nestel, Dmitri Sviridov, Anh Hoang, P Hugh R Barrett
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 93 Issue 2 Pg. 430-7 (Feb 2008) ISSN: 0021-972X [Print] United States
• PMID: 18029469 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, drug therapy)
• Middle Aged
• Particle Size
• Pyrimidines (therapeutic use)
• Rosuvastatin Calcium
• Sulfonamides (therapeutic use)
• Triglycerides (blood)