Abstract 16056: Ezetimibe Increases Reverse Cholesterol Transport in Humans
Introduction: Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. Although ezetimibe reduces LDL, it also lowers intestinal cholesterol absorption but the exact effects on fecal endogenous cholesterol excretion and turnover of cholesterol pools are not known.
Hypothesis: Ezetimibe increases fecal endogenous cholesterol excretion and increases turnover of rapidly-mixing plasma cholesterol pool.
Methods: In a randomized, double-masked parallel trial in 24 healthy subjects with LDL 100-190 mg/dL, we measured cholesterol metabolism before and after a 4-week treatment with either ezetimibe 10 mg/day or placebo. For each test, 40 mg cholesterol-d7 solubilized in Intralipid®, prepared using Current Good Manufacturing Practices, was infused intravenously as a bolus to label endogenous cholesterol. After 2 weeks cholesterol-d5 and sitostanol-d4 solubilized in oil were given orally to label dietary cholesterol and stool was collected on a metabolic kitchen diet controlling cholesterol and phytosterol intake.
Results: Ezetimibe reduced intestinal cholesterol absorption efficiency by 30 ± 11.2% (SD, P < 0.0001) relative to baseline, and LDL cholesterol by 19.8 ± 9.8% (P = 0.0001). Fecal excretion of both endogenous (72.4 ± 30.9%, P < 0.0001) and unabsorbed dietary cholesterol (52.0 ± 21.6%, P < 0.0001) was increased. Fecal excretion of bile acids was not increased and the rapidly-mixing body cholesterol pool size was similar. However, turnover of cholesterol plasma d7 enrichment post-treatment was increased (28.1 ± 13.5%, P = 0.0065) by ezetimibe.
Conclusions: Ezetimibe moderately reduced LDL but had substantial effects on measures of reverse cholesterol transport including cholesterol absorption efficiency, fecal excretion of endogenous and dietary cholesterol, and turnover of the rapid cholesterol pool. The ability of ezetimibe to increase reverse cholesterol transport is quantitatively larger than the effect on LDL. More data are needed on the relation of reverse cholesterol transport or its related biomarkers to CHD outcomes.
Author Disclosures: X. Lin: None. S.B. Racette: None. L. Ma: None. M. Wallendorf: None. R.E. Ostlund: None.
- © 2016 by American Heart Association, Inc.