Dose-Dependent Effect of Rosuvastatin on VLDL-Apolipoprotein C-III Kinetics in the Metabolic Syndrome

<b>OBJECTIVE</b> - 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-III transport in men with the metabolic syndrome.<br/> <b>RESEARCH DESIGN AND METHODS</b> - Twelve men with the metabolic syndrome were studied in a randomized 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-III kinetics were examined using a stable isotope method and compartmental modeling at the end of each intervention period.<br/> <b>RESULTS</b> - Compared with placebo, there was a significant dose-dependent reduction with rosuvastatin in plasma triglyceride and VLDL apoC-III concentrations. Rosuvastatin significantly (<I>P</I> < 0.05) increased VLDL apoC-III fractional catabolic rate (FCR) and decreased its production rate, with a significant (<I>P</I> < 0.05) dose-related effect. With 40 mg rosuvastatin, changes in VLDL apoC-III concentration were inversely associated with changes in VLDL apoC-III FCR and positively associated with VLDL apoC-III production rate (<I>P</I> < 0.05). Changes in VLDL apoC-III concentration and production rate were positively correlated with changes in VLDL apoB concentration and production rate and inversely correlated with VLDL apoB FCR (<I>P</I> < 0.05). Similar associations were observed with 10 mg rosuvastatin but were either less or not statistically significant.<br/> <b>CONCLUSIONS</b> - In this study, rosuvastatin decreased the production and increased the catabolism of VLDL apoC-III, a mechanism that accounted for the significant reduction in VLDL apoC-III and triglyceride concentrations. This has implications for the management of cardiometabolic risk in obese subjects with the metabolic syndrome.<br/>