Abstract 19208: Assessment of Cholesterol Efflux Potential of High-Density Lipoprotein after Treatment with Niacin Extended-Release or Fenofibrate
Background: Niacin and fenofibrate are to date the most effective available HDL-raising therapies. Direct comparison of the capacity of the resulting HDL to affect reverse cholesterol transport through efflux of cholesterol from peripheral cells is still lacking.
Methods: In a multicenter, randomized, open-label, cross-over study, 66 dyslipidemic patients - 24 with low HDL-C (<40 mg/dL) and 42 with normal HDL-C (40-59 mg/dL) - received 6 weeks’ treatment with niacin extended-release (ER) (0.5 g/d then 1 g/d) and fenofibrate (160 mg/d) with 4 weeks’ wash-out between treatments. Plasma lipid, lipoprotein, and apolipoprotein profile was assessed. Whole serum was tested for the ability to promote cholesterol efflux from J774 macrophages or hepatoma cells mediated by passive diffusion, ATP-binding cassette transporters (ABCA1 and ABCG1), and scavenger receptor class B, type I (SR-BI).
Results: Increases in HDL-C and ApoAI were similar with niacin ER (15.9±18.0% and 7.0±11.0%, respectively) and fenofibrate (16.0±20.4% and 7.0±11.0%, respectively). In an initial analysis of a subgroup (n=15) with low HDL-C at baseline (35.9±5.8 mg/dL) fenofibrate increased serum ability to promote passive diffusion (11.4±4.6%; P<0.05 vs baseline) and SR-BI-efflux (13.0±6.1%; P<0.05 vs baseline), whereas a marked decrease in ABCA1-efflux was observed (-50.0±15.0%; P<0.05 vs baseline). No effect was seen in ABCG1-efflux. The changes observed in efflux ability of sera after fenofibrate treatment is consistent with changes in HDL particle size, measured by NMR, showing an increase in large and medium HDL particles. Also, efflux pattern with fenofibrate was comparable to that in a control group (n=18) with high HDL-C (73.4±12.2 mg/dL) and similar HDL distribution at baseline. In the subgroup (n=15) with low baseline HDL-C, niacin ER appeared to be less effective in modifying cholesterol efflux capacity of sera in all measured pathways.
Conclusion: Niacin ER and fenofibrate gave a similar effect on plasma HDL-C levels and HDL distribution. The effects observed for both treatments, and especially for fenofibrate, were paralleled by effects on HDL functionality as assessed by the ability of sera to promote cellular cholesterol efflux.
- © 2010 by American Heart Association, Inc.