Abstract 10106: Atorvastatin and Fenofibrate Enhance Very Low-Density Lipoprotein Apolipoprotein E Catabolism in Men with the Metabolic Syndrome
Background Apolipoprotein (apo) E regulates hepatic and extrahepatic uptake of plasma lipoproteins by binding with high affinity to members of the LDL receptor family. Dysregulated apoE metabolism may, therefore, contribute to dyslipidemia and increased cardiovascular disease risk in the metabolic syndrome (MetS). This study examined the effects of atorvastatin and fenofibrate on very low-density lipoprotein (VLDL) apoE metabolism in MetS
Hypothesis: Atorvastatin and fenofibrate decrease VLDL apoE concentration via increased catabolism.
Methods: 11 men with MetS (mean ± SEM: age 46 ± 2 years, BMI 30.5 ± 0.7 kg/m2, triglyceride 2.4 ± 0.3 mmol/L, HDL cholesterol 0.93 ± 0.04 mmol/L) were studied in a randomized, double-blind, crossover trial of 5 wk intervention periods with placebo, atorvastatin (ATV; 40 mg/d) and micronized fenofibrate (FENO; 200 mg/d), with 2 wks placebo washouts between each period. VLDL apoE kinetics were examined using stable isotope methods and compartmental modelling.
Results: ATV and FENO decreased plasma apoE concentrations compared with placebo (p<0.05). Compared with placebo, ATV decreased VLDL apoE concentration (23.0 ± 2.3 vs 15.4 ± 0.5 mg/l) and increased VLDL apoE fractional catabolic rate (FCR; 4.9 ± 0.2 vs 7.3 ± 0.5 pools/d) (p<0.05). Compared with placebo, FENO decreased VLDL apoE concentration (23.0 ± 2.3 vs 15.4 ± 1.7 mg/l) and production rate (PR; 4.9 ± 0.4 vs 3.4 ± 0.2 mg/kg/d), and increased VLDL apoE FCR (4.9 ± 0.2 vs 6.0 ± 0.4 pools/d) (p<0.05). ATV and FENO had comparable effects on VLDL apoE concentration. Despite this, the increase in VLDL apoE FCR with FENO was 21% less and the decrease in VLDL apoE PR was 24% more than ATV (p<0.05). Change in VLDL apoE FCR was negatively correlated with change in VLDL apoB concentration (r = 0.60, p=0.05) and positively correlated with change in VLDL apoB FCR (r = 0.69, p=0.02) with FENO.
Conclusions: In MetS, ATV decreased plasma and VLDL apoE concentrations chiefly by increasing VLDL apoE catabolism. By contrast, FENO decreased plasma and VLDL apoE concentrations by decreasing VLDL apoE production and increasing VLDL apoE catabolism. The differential effects of ATV and FENO on VLDL apoE kinetics support the use of combination therapy for treatment of dyslipidemia in MetS.
- © 2011 by American Heart Association, Inc.