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

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 DESIG...

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Main Authors: Ooi, E., Watts, G., Chan, D., Chen, Meifania, Nestel, P., Sviridov, D., Barrett, H.
Format: Journal Article
Published: American Diabetes Association ADA 2008
Online Access:http://hdl.handle.net/20.500.11937/32130
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author Ooi, E.
Watts, G.
Chan, D.
Chen, Meifania
Nestel, P.
Sviridov, D.
Barrett, H.
author_facet Ooi, E.
Watts, G.
Chan, D.
Chen, Meifania
Nestel, P.
Sviridov, D.
Barrett, H.
author_sort Ooi, E.
building Curtin Institutional Repository
collection Online Access
description 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.
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publishDate 2008
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spelling curtin-20.500.11937-321302017-09-13T15:56:36Z Dose-dependent effect of rosuvastatin on VLDL-apolipoprotein C-III kinetics in the metabolic syndrome Ooi, E. Watts, G. Chan, D. Chen, Meifania Nestel, P. Sviridov, D. Barrett, H. 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. 2008 Journal Article http://hdl.handle.net/20.500.11937/32130 10.2337/dc08-0358 American Diabetes Association ADA fulltext
spellingShingle Ooi, E.
Watts, G.
Chan, D.
Chen, Meifania
Nestel, P.
Sviridov, D.
Barrett, H.
Dose-dependent effect of rosuvastatin on VLDL-apolipoprotein C-III kinetics in the metabolic syndrome
title Dose-dependent effect of rosuvastatin on VLDL-apolipoprotein C-III kinetics in the metabolic syndrome
title_full Dose-dependent effect of rosuvastatin on VLDL-apolipoprotein C-III kinetics in the metabolic syndrome
title_fullStr Dose-dependent effect of rosuvastatin on VLDL-apolipoprotein C-III kinetics in the metabolic syndrome
title_full_unstemmed Dose-dependent effect of rosuvastatin on VLDL-apolipoprotein C-III kinetics in the metabolic syndrome
title_short Dose-dependent effect of rosuvastatin on VLDL-apolipoprotein C-III kinetics in the metabolic syndrome
title_sort dose-dependent effect of rosuvastatin on vldl-apolipoprotein c-iii kinetics in the metabolic syndrome
url http://hdl.handle.net/20.500.11937/32130