Dose-dependent effect of rosuvastatin on VLDL-apolipoprotein C-III kinetics in the metabolic syndrome

Abstract

OBJECTIVE-Dysregulated apolipoprotein (apo)C-III metabolism may account for hypertriglyceridemia and increased cardiovascular risk in the metabolic syndrome. This study investigated the dose-dependent effect of rosuvastatin on VLDL apoC-1II transport in men with the metabolic syndrome.RESEARCH DESIGN AND METHODS-Twelve men with the metabolic syndrome were studied in arandomized double-blind crossover trial of 5-week intervention periods with placebo, 10 mg rosuvastatin,or 40 mg rosuvastatin, with 2-week placebo washouts between each period. VLDL apoC-IlI kinetics were examined using a stable isotope method and compartmental modeling at the end ofeachintervention period.RESULTS-Compared with placebo, there was a significant dose-dependent reduction with rosuvastatinin plasma triglyceride and VLDL apoC-III concentrations. Rosuvastatin significantly (P < 0.05) increasedVLDL apoC-I1I fractional catabolic rate (FCR) and decreased its production rate, with a significant (P <0.05) dose-related effect. With 40 mg rosuvastatin, changes in VLDL apoC-I1I concentration wereinversely associated with changes in VLDL apoC-IIl FCR and positively associated with VLDL apoC-1IIproduction rate (P < 0.05). Changes in VLDL apoC-1II concentration and production rate were positivelycorrelated with changes in VLDL apoS concentration and production rate and inversely correlated with VLDL apoB FCR (P < 0.05). Similar associations were observed with 10 mg rosuvastatin but were either less or not statistically significant.CONCLUSIONS-In this study, rosuvastatin decreased the production and increased the catabolism of VLDL apoC-IIl, a mechanism that accounted for the significant reduction in VLDL apoC-llI and triglyceride concentrations. This has implications for the management of cardiometabolic risk in obese subjects with the metabolic syndrome.