title: Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes).
abstract: OBJECTIVE
  This study sought to examine the relationship between baseline and on-study apolipoproteins (apo) A-1 and B and lipoprotein(a) [Lp(a)] levels and the development of subsequent cardiovascular (CV) events in the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes) trial.
  
  
  BACKGROUND
  Niacin has been reported to lower apoB and Lp(a) and to raise apoA-1.
  
  
  METHODS
  Individuals with CV disease and low baseline levels of high-density lipoprotein cholesterol were randomized to simvastatin plus placebo or simvastatin, plus extended-release niacin ([ERN], 1,500 to 2,000 mg/day), with ezetimibe added as needed, in both groups, to maintain an on-treatment low-density lipoprotein cholesterol in the range of 40 to 80 mg/dl. Hazard ratios (HRs) were used to evaluate the relationship between levels of apoA-1, apoB, and Lp(a), and CV events in each treatment group.
  
  
  RESULTS
  Baseline apoB and the apoB/apoA-I ratio were significantly predictive of CV events only for the placebo group (HR: 1.17 [p = 0.018] and HR: 1.19 [p = 0.016]). Baseline and on-study Lp(a) were predictive of CV events in both simvastatin plus placebo (baseline HR: 1.24 [p = 0.002] and on-study HR: 1.21 [p = 0.017]) and the simvastatin plus ERN group (baseline HR: 1.25 [p = 0.001] and on-study HR: 1.18 [p = 0.028]). The ERN modestly increased 1-year apoA-1 (7%), decreased apoB (13%), decreased the ApoB/ApoA-1 ratio (19%), and decreased Lp(a) 21%, but did not reduce CV events.
  
  
  CONCLUSIONS
  Lp(a) was associated with increased CV risk in both treatment groups indicating that it contributes to residual CV risk. However, there was no evidence that ERN reduced CV risk, despite favorable lipoprotein changes.
authors: Northwest Lipid Metabolism and Diabetes Research Laboratories, Department of Medicine, University of Washington, Seattle, Washington.
authors: John J
authors: JJ
authors: Albers
authors: April
authors: A
authors: Slee
authors: Kevin D
authors: KD
authors: O'Brien
authors: Jennifer G
authors: JG
authors: Robinson
authors: Moti L
authors: ML
authors: Kashyap
authors: Peter O
authors: PO
authors: Kwiterovich
authors: Ping
authors: P
authors: Xu
authors: Santica M
authors: SM
authors: Marcovina
mesh_terms: D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood*; D001055:Apolipoproteins B / Q000097:blood*; 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; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D052456:Hypoalphalipoproteinemias / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D017270:Lipoprotein(a) / 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; D019821:Simvastatin / Q000008:administration & dosage; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D015415:Biomarkers; D008076:Cholesterol, HDL; D017270:Lipoprotein(a); D014280:Triglycerides; D009525:Niacin; D019821:Simvastatin
keywords: Apo; CV; ELISA; ERN; HDL-C; HR; LDL; LDL-C; Lp(a); apolipoprotein; apolipoproteins; cardiovascular; cardiovascular risk; enzyme-linked immunoadsorbent assay; extended-release niacin; hazard ratio; high-density lipoprotein cholesterol; lipoprotein(a); low-density lipoprotein; low-density lipoprotein cholesterol; niacin; simvastatin
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