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

  1. Esther M.M. Ooi, PHD1,
  2. Gerald F. Watts, MD, DSC1,
  3. Dick C. Chan, PHD1,
  4. Meifania M. Chen, BSC1,
  5. Paul J. Nestel, MD2,
  6. Dmitri Sviridov, MD, PHD2 and
  7. P. Hugh R. Barrett, PHD1
  1. 1Metabolic Research Centre, School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, Perth, Western Australia
  2. 2Baker Heart Research Institute, Melbourne, Victoria, Australia
  1. Corresponding author: P. Hugh R. Barrett, hugh.barrett{at}uwa.edu.au

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-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 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.

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-III 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-III concentration were inversely associated with changes in VLDL apoC-III FCR and positively associated with VLDL apoC-III production rate (P < 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 (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-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.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 28 May 2008.

    Clinical trial reg. no. NCT00240305, clinicaltrials.gov.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received February 18, 2008.
    • Accepted May 14, 2008.
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  1. Published online before print May 28, 2008, doi: 10.2337/dc08-0358 Diabetes Care August 2008 vol. 31 no. 8 1656-1661
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