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J. Clin. Endocrinol. Metab. · Feb 2008
Randomized Controlled TrialDose-dependent regulation of high-density lipoprotein metabolism with rosuvastatin in the metabolic syndrome.
- Esther M M Ooi, Gerald F Watts, Paul J Nestel, Dmitri Sviridov, Anh Hoang, and P Hugh R Barrett.
- Metabolic Research Centre, School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, Perth, Western Australia 6847, Australia.
- J. Clin. Endocrinol. Metab. 2008 Feb 1; 93 (2): 430-7.
BackgroundLow 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 ResultsTwelve 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.ConclusionsRosuvastatin 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.
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