Relationship of Apolipoproteins A-1 and B, and Lipoprotein(a) to Cardiovascular Outcomes

Abstract

Objectives The aim was 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 Trial. Background Niacin has been reported to lower apoB and Lp(a) and to raise apoA-1. Method Individuals with CV disease and low baseline levels of HDL-C were randomized to simvastatin plus placebo or simvastatin plus extended-release niacin (ERN, 1500–2000 mg/day), with ezetimibe added, as needed, in both groups to maintain an on-treatment LDL-C in the range of 40–80 mg/dL. Hazard ratios (HR) were used to evaluate the relationship between levels of apo A-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+placebo (baseline HR= 1.24, p=0.002 and on-study HR=1.21, p=0.017) and the simvastatin+ERN group (baseline HR=1.25, p=0.001 and on-study HR=1.18 p=0.028). 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.

Lipoprotein(a) Levels and Recurrent Vascular Events After First Ischemic Stroke

“…Three recent studies have linked high Lp(a) to increased residual cardiovascular risk, despite optimal LDL-C reduction. [28][29][30] This supports our finding of high Lp(a) being associated with residual vascular risk after the first-ever ischemic stroke independent of other risk factors, such as LDL-C.…”

Lipoprotein(a) and the Apolipoprotein B/A1 Ratio Independently Associate With Surgery for Aortic Stenosis Only in Patients With Concomitant Coronary Artery Disease

“…Currently, no treatment option has been established for high Lp(a) levels, other than experimental and observational regimes 27, 28, 29, 30, 31, 32, 33. Moreover, to date, no randomized controlled trials have directly evaluated the effect of lowering Lp(a) on cardiovascular outcomes including AS development.…”

Prevalence of Elevated Lp(a) Mass Levels and Patient Thresholds in 532 359 Patients in the United States

“…Interestingly, in secondary prevention settings where patients are generally on maximal secondary prevention measures, such as in the AIM-HIGH 12 (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes) and LIPID 10 trials (Long-Term Intervention with Pravastatin in Ischaemic Disease), the risk of recurrent CVD events was present in the fourth quartiles, which represented Lp(a) >125 nmol/L (or >≈50 mg/dL) and >73.7 mg/dL, respectively. Therefore, setting thresholds and levels at which one might assign risk has to take into account the prevalence of the extent of CVD and that thresholds may need to be different for the general community versus actual patients.…”

“…[1][2][3]9 In secondary prevention populations consisting of patients with prior CVD that are optimally treated with statins and antiplatelet agents, recurrent events seem to begin at values >50 mg/dL. [10][11][12] Lp(a) is composed of apolipoprotein(a) [apo(a)] covalently bound to apolipoprotein B (apoB)-100 of a low-density lipoprotein (LDL)-like particle. It is atherogenic because of the LDL moiety and also from additional proinflammatory and prothrombotic mechanisms from the apo(a) moiety.…”