Niacin Therapy Increases High-Density Lipoprotein Particles and Total Cholesterol Efflux Capacity But Not ABCA1-Specific Cholesterol Efflux in Statin-Treated Subjects

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 36; no. 2; pp. 404 - 411
• Main Authors: Ronsein, Graziella E., Hutchins, Patrick M., Isquith, Daniel, Vaisar, Tomas, Zhao, Xue-Qiao, Heinecke, Jay W.
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.02.2016
• Subjects: Animals; Atorvastatin Calcium - therapeutic use; ATP Binding Cassette Transporter 1 - genetics; ATP Binding Cassette Transporter 1 - metabolism; Biological Transport; Carotid Artery Diseases - blood; Carotid Artery Diseases - diagnosis; Carotid Artery Diseases - drug therapy; Cell Line; Cholesterol - blood; Cholesterol, HDL - blood; Cricetinae; Drug Combinations; Dyslipidemias - blood; Dyslipidemias - diagnosis; Dyslipidemias - drug therapy; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Middle Aged; Niacin - therapeutic use; Time Factors; Transfection; Treatment Outcome; atherosclerosis; niacin; macrophages; cardiovascular diseases; triglycerides
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/ATVBAHA.115.306268

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.