Background Low plasma concentration of high-density lipoprotein (HDL) cholesterol is a risk factor for cardiovascular disease (CVD) 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 five-week therapeutic periods with placebo, 10 mg/day rosuvastatin or 40 mg/day rosuvastatin, with two weeks placebo wash-out between each period. Compared with placebo, there was a significant dose-dependent increase in HDL cholesterol, HDL particle size and LpA-I concentration. The increase in LpA-I concentration was associated with significant dose-dependent reductions in triglyceride concentration and LpA-I fractional catabolic rate (FCR), with no changes in LpA-I production rate (PR). There was a significant dose-dependent reduction in LpA-I:A-II FCR with concomitant reduction in LpA-I:A-II PR, 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 CVD.