title: Relationship of lipoproteins to cardiovascular events: the AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes).
abstract: OBJECTIVE
  This study sought to examine the relationship between niacin treatment, lipoproteins, and cardiovascular (CV) outcomes in this secondary analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial.
  
  
  BACKGROUND
  During a 3-year follow-up in 3,414 patients with established CV disease and low high-density lipoprotein cholesterol (HDL-C) levels, combined niacin + low-density lipoprotein cholesterol (LDL-C)-lowering therapy did not reduce CV events compared with LDL-C-lowering therapy alone.
  
  
  METHODS
  Subjects taking simvastatin and/or ezetimibe were randomized to receive extended-release (ER) niacin 1,500 to 2,000 mg or minimal immediate-release niacin (≤ 150 mg) as placebo at bedtime. LDL-C levels in both groups were maintained from 40 to 80 mg/dl. Hazard ratios were estimated by using Cox proportional hazards models for relationships between lipoproteins and the composite endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization.
  
  
  RESULTS
  CV outcomes were not associated with ER niacin in any baseline lipoprotein tertile. In a subset of patients in both the highest triglyceride (≥ 198 mg/dl) and lowest HDL-C (<33 mg/dl) tertiles, ER niacin showed a trend toward benefit (hazard ratio: 0.74, p = 0.073). In-trial LDL-C levels, non-HDL-C levels, and the total cholesterol/HDL-C ratio were positively associated with CV events in the control group, but these relationships were absent in the ER niacin group.
  
  
  CONCLUSIONS
  Baseline lipoprotein tertiles did not predict differential benefit or harm with ER niacin added to LDL-C-lowering therapy, but a small dyslipidemic subgroup may benefit. ER niacin attenuated expected relationships of lipoprotein risk factors with CV events, raising the possibility that nonlipoprotein actions of niacin could affect risk. (Niacin Plus Statin to Prevent Vascular Events [AIM-HIGH]; NCT00120289).
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina. Electronic address: john.guyton@duke.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Guyton
authors.forename: April E
authors.initials: AE
authors.lastname: Slee
authors.forename: Todd
authors.initials: T
authors.lastname: Anderson
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Fleg
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Goldberg
authors.forename: Moti L
authors.initials: ML
authors.lastname: Kashyap
authors.forename: Santica M
authors.initials: SM
authors.lastname: Marcovina
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Nash
authors.forename: Kevin D
authors.initials: KD
authors.lastname: O'Brien
authors.forename: William S
authors.initials: WS
authors.lastname: Weintraub
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.forename: Xue-Qiao
authors.initials: XQ
authors.lastname: Zhao
authors.forename: William E
authors.initials: WE
authors.lastname: Boden
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D008076:Cholesterol, HDL / Q000097:blood*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D014943:Global Health; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage; D011446:Prospective Studies; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D008076:Cholesterol, HDL; D008074:Lipoproteins; D014280:Triglycerides; D009525:Niacin
keywords: CV; ER; G-protein–coupled receptor 109A; GPR109A; HDL-C; HR; LDL-C; TG; cardiovascular; cardiovascular events; clinical trial; extended-release; hazard ratio; high-density lipoprotein cholesterol; lipoproteins; low-density lipoprotein cholesterol; niacin; triglyceride
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