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)

John J. Albers, April Slee, Kevin D. O'Brien, Jennifer G. Robinson, Moti L. Kashyap, Peter O. Kwiterovich, Ping Xu, Santica M. Marcovina

Research output: Contribution to journalArticle

Abstract

Objectives 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.

Original languageEnglish (US)
Pages (from-to)1575-1579
Number of pages5
JournalJournal of the American College of Cardiology
Volume62
Issue number17
DOIs
StatePublished - Oct 22 2013

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Lipoprotein(a)
Apolipoprotein A-I
Apolipoproteins B
Niacin
Triglycerides
Simvastatin
Placebos
Global Health
LDL Cholesterol
HDL Cholesterol
Lipoproteins
Cardiovascular Diseases
Therapeutics

Keywords

  • apolipoproteins
  • cardiovascular risk
  • lipoprotein(a)
  • niacin
  • simvastatin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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). / Albers, John J.; Slee, April; O'Brien, Kevin D.; Robinson, Jennifer G.; Kashyap, Moti L.; Kwiterovich, Peter O.; Xu, Ping; Marcovina, Santica M.

In: Journal of the American College of Cardiology, Vol. 62, No. 17, 22.10.2013, p. 1575-1579.

Research output: Contribution to journalArticle

Albers, John J. ; Slee, April ; O'Brien, Kevin D. ; Robinson, Jennifer G. ; Kashyap, Moti L. ; Kwiterovich, Peter O. ; Xu, Ping ; Marcovina, Santica M. / 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). In: Journal of the American College of Cardiology. 2013 ; Vol. 62, No. 17. pp. 1575-1579.
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abstract = "Objectives 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.",
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T1 - Relationship of apolipoproteins A-1 and b, and lipoprotein(a) to cardiovascular outcomes

T2 - The aim-high trial (atherothrombosis intervention in metabolic syndrome with low HDL/high triglyceride and impact on global health outcomes)

AU - Albers, John J.

AU - Slee, April

AU - O'Brien, Kevin D.

AU - Robinson, Jennifer G.

AU - Kashyap, Moti L.

AU - Kwiterovich, Peter O.

AU - Xu, Ping

AU - Marcovina, Santica M.

PY - 2013/10/22

Y1 - 2013/10/22

N2 - Objectives 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.

AB - Objectives 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.

KW - apolipoproteins

KW - cardiovascular risk

KW - lipoprotein(a)

KW - niacin

KW - simvastatin

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