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Association of an HDL Apolipoproteomic Score With Coronary Atherosclerosis and Cardiovascular Death
Authors:Pradeep Natarajan  Tim S. Collier  Zhicheng Jin  Asya Lyass  Yiwei Li  Nasrien E. Ibrahim  Renata Mukai  Cian P. McCarthy  Joseph M. Massaro  Ralph B. D’Agostino  Hanna K. Gaggin  Cory Bystrom  Marc S. Penn  James L. Januzzi
Affiliation:1. Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts;2. Department of Medicine, Harvard Medical School, Boston, Massachusetts;3. Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts;4. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts;5. Cleveland Heart Lab, Cleveland, Ohio;6. Baim Institute for Clinical Research, Boston, Massachusetts;7. Department of Mathematics & Statistics, Boston University, Boston, Massachusetts;8. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts;9. Summa Health Heart and Vascular Institute, Summa Health, Akron, Ohio
Abstract:

Background

Concentrations of circulating apolipoproteins are strongly linked to risk for coronary artery disease (CAD). The relative importance of the additional knowledge of apolipoprotein concentrations within specific lipoprotein species for CAD risk prediction is limited.

Objectives

This study sought to evaluate the performance of a high-density lipoprotein (HDL) apolipoproteomic score, based on targeted mass spectrometry of HDL-associated apolipoproteins, for the detection of angiographic CAD and outcomes.

Methods

HDL-associated apolipoprotein (apo) A-1, apoC-1, apoC-2, apoC-3, and apoC-4 were measured in 943 participants without prevalent myocardial infarction (MI) referred for coronary angiography in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study. A composite HDL apolipoproteomic score (pCAD) was associated with likelihood of obstructive CAD (≥70% lesion in ≥1 vessel) and with incident cardiovascular outcomes over 4-year follow-up.

Results

There were 587 (62.2%) patients with coronary stenosis. The pCAD score was associated with the presence of obstructive CAD (odds ratio: 1.39; 95% confidence interval [CI]: 1.14 to 1.69; p < 0.001), independently of conventional cardiovascular risk factors including circulating plasma apoA-1 and apoB. The C-index for pCAD was 0.63 (95% CI: 0.59 to 0.67) for the presence of obstructive CAD. Although pCAD was not associated with cardiovascular mortality among all individuals (hazard ratio: 1.24; 95% CI: 0.93 to 1.66; p = 0.15), there was evidence of association for individuals with obstructive CAD (hazard ratio: 1.48; 95% CI: 1.07 to 2.05; p = 0.019).

Conclusions

An HDL apolipoproteomic score is associated with the presence of CAD, independent of circulating apoA-1 and apoB concentrations and other conventional cardiovascular risk factors. Among individuals with CAD, this score may be independently associated cardiovascular death. (The CASABLANCA Study: Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA]; NCT00842868)
Keywords:coronary artery disease  HDL  lipids  prevention  proteomics  ANOVA  analysis of variance  CAD  coronary artery disease  CI  confidence interval  HDL  high-density lipoprotein  HDL-C  high-density lipoprotein cholesterol  hsCRP  high-sensitivity C-reactive protein  LDL-C  low-density lipoprotein cholesterol  MI  myocardial infarction  OR  odds ratio
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