Abstract 322: Effect of Atorvastatin on Very-Low-Density Lipoprotein Triglyceride Kinetics in Obese Men
Background Hypertriglyceridemia is a risk factor for cardiovascular disease. Atorvastatin effectively decreases plasma and VLDL triglyceride concentrations in humans, but the mechanism of action is unknown. This study examined the effect of atorvastatin on VLDL triglyceride (VLDL-TG) metabolism in obese men.
Hypothesis: Atorvastatin decreases VLDL-TG concentrations by increasing VLDL-TG catabolism.
Methods: 25 obese men (mean ± SEM: age 52 ± 3 years, BMI 34.5 ± 1.4 kg/m2, plasma triglyceride 1.9 ± 0.1 mmol/L, HDL cholesterol 1.00 ± 0.05 mmol/L) were studied in a two-arm parallel group study design. Eligible subjects entered a 3 week run-in dietary stabilizing period at the end of which they were randomized to a 6 week treatment period of either atorvastatin 40 mg/day (ATV) or placebo. VLDL-TG kinetics were examined using stable isotope methods and compartmental modelling.
Results: ATV decreased plasma TG, VLDL apoB and VLDL apoC-III concentrations compared with placebo (p<0.05). Compared with placebo, ATV decreased VLDL-TG concentration ( ATV vs. placebo) (-40% vs. +2%, p<0.01) and increased VLDL-TG fractional catabolic rate (FCR; +54 % vs. -7%, p<0.01). ATV did not alter VLDL-TG production rate. Change in VLDL-TG concentration was positively correlated with change in VLDL apoB (r = 0.81, p<0.01) and VLDL apoC-III (r = 0.65, p=0.02) concentrations, and negatively correlated with VLDL-TG FCR (r = -0.54, p=0.05). Change in VLDL-TG FCR was negatively correlated with VLDL apoC-III, but this failed to reach statistical significance (r = -0.53, p=0.06).
Conclusions: In obese men, ATV decreased plasma and VLDL-TG concentrations chiefly by increasing VLDL-TG catabolism, with no appreciable effect on VLDL-TG synthesis. Our data suggest that reduction in apoC-III concentration with ATV may explain, in part, the increase in VLDL-TG catabolism.
- © 2012 by American Heart Association, Inc.