Niacin Therapy Increases High-Density Lipoprotein Particles and Total Cholesterol Efflux Capacity But Not ABCA1-Specific Cholesterol Efflux in Statin-Treated Subjects. Issue 2 (February 2016)

• Record Type: Journal Article
• Authors: Ronsein, Graziella E.; Hutchins, Patrick M.; Isquith, Daniel; Vaisar, Tomas; Zhao, Xue-Qiao; Heinecke, Jay W.
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 36:Issue 2(2016)
• Publication Date: 2016-02
• Subjects: atherosclerosis -- cardiovascular diseases -- macrophages -- niacin -- triglycerides; Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.115.306268
• Languages: English
• ISSNs: 1079-5642

Abstract

Abstract : Objective—: We investigated relationships between statin and niacin/statin combination therapy and the concentration of high-density lipoprotein particles (HDL-P) and cholesterol efflux capacity, 2 HDL metrics that might better assess cardiovascular disease risk than HDL-cholesterol (HDL-C) levels. Approach—: In the Carotid Plaque Composition Study, 126 subjects with a history of cardiovascular disease were randomized to atorvastatin or combination therapy (atorvastatin/niacin). At baseline and after 1 year of treatment, the concentration of HDL and its 3 subclasses (small, medium, and large) were quantified by calibrated ion mobility analysis (HDL-PIMA ). We also measured total cholesterol efflux from macrophages and ATP-binding cassette transporter A1 (ABCA1)–specific cholesterol efflux capacity. Results—: Atorvastatin decreased low-density lipoprotein cholesterol by 39% and raised HDL-C by 11% ( P =0.0001) but did not increase HDL-PIMA or macrophage cholesterol efflux. Combination therapy raised HDL-C by 39% ( P <0.0001) but increased HDL-PIMA by only 14%. Triglyceride levels did not correlate with HDL-PIMA ( P =0.39), in contrast to their strongly negative correlation with HDL-C ( P <0.0001). Combination therapy increased macrophage cholesterol efflux capacity (16%, P <0.0001) but not ABCA1-specific efflux. ABCA1-specific cholesterol efflux capacity decreased significantly ( P =0.013) in statin-treated subjects, with or without niacin therapy. Conclusions—: Statin therapy increased HDL-C levels but failed to increase HDL-PIMA . It also reduced ABCA1-specific cholesterol efflux capacity. Adding niacin to statin therapy increased HDL-C and macrophage efflux, but had much less effect on HDL-PIMA . It also failed to improve ABCA1-specific efflux, a key cholesterol exporter in macrophages. Our observations raise the possibility that niacin might not target the relevant atheroprotective population of HDL. Abstract : Supplemental Digital Content is available in the text.