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 very-low density lipoprotein (VLDL) apoC-III transport in men with the metabolic syndrome.

Research Design and Methods: Twelve men with the metabolic syndrome were studied in a randomized, double-blind, cross-over trial of 5-week intervention periods with placebo, 10mg rosuvastatin or 40mg rosuvastatin, with 2-week placebo wash-outs between each period. VLDL apoC-III kinetics were examined using a stable isotope method and compartmental modeling at the end of each intervention period.

Results: Compared with placebo, there was a significant dose-dependent reduction with rosuvastatin in plasma triglyceride and VLDL apoC-III concentrations. Rosuvastatin significantly (p<0.05) increased VLDL apoC-IIII fractional catabolic rate (FCR) and decreased its production rate, with a significant (p<0.05) dose-related effect. With 40mg rosuvastatin, changes in VLDL apoC-III concentration were positively associated with changes in VLDL apoC-III FCR and inversely associated with VLDL apoC-III PR (p<0.05). Changes in VLDL apoC-III concentration and PR were positively correlated with changes in VLDL apoB concentration and PR, and inversely correlated with VLDL apoB FCR (p<0.05). Similar associations were observed with 10mg rosuvastatin but were either less or not statistically significant.

Conclusions: 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.