title: Niacin Therapy Increases High-Density Lipoprotein Particles and Total Cholesterol Efflux Capacity But Not ABCA1-Specific Cholesterol Efflux in Statin-Treated Subjects.
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.
  
  
  METHODS
  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.
authors.affiliation: From the Department of Medicine, University of Washington, Seattle.
authors.forename: Graziella E
authors.initials: GE
authors.lastname: Ronsein
authors.affiliation: From the Department of Medicine, University of Washington, Seattle.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Hutchins
authors.affiliation: From the Department of Medicine, University of Washington, Seattle.
authors.forename: Daniel
authors.initials: D
authors.lastname: Isquith
authors.affiliation: From the Department of Medicine, University of Washington, Seattle.
authors.forename: Tomas
authors.initials: T
authors.lastname: Vaisar
authors.affiliation: From the Department of Medicine, University of Washington, Seattle.
authors.forename: Xue-Qiao
authors.initials: XQ
authors.lastname: Zhao
authors.affiliation: From the Department of Medicine, University of Washington, Seattle. heinecke@uw.edu.
authors.forename: Jay W
authors.initials: JW
authors.lastname: Heinecke
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000069059:Atorvastatin / Q000627:therapeutic use*; D001692:Biological Transport; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D002460:Cell Line; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D006224:Cricetinae; D004338:Drug Combinations; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use*; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D008076:Cholesterol, HDL; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009525:Niacin; D002784:Cholesterol; D000069059:Atorvastatin
keywords: atherosclerosis; cardiovascular diseases; macrophages; niacin; triglycerides