Association of an HDL Apolipoproteomic Score With Coronary Atherosclerosis and Cardiovascular Death

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: HDL; coronary artery disease; lipids; prevention; proteomics.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Central Illustration:. HDL Apolipoproteomic Score and Coronary Artery Disease.

Top.Schematic of affinity enrichment of apolipoprotein A-1 associated lipoproteins and subsequent apolipoproteomic analysis. Bottom. Association of quantiles of an HDL apolipoproteomic score (pCAD) with angiographic coronary artery disease, adjusted for age, sex, history of myocardial infarction, statin use, hypertension, current smoking, diabetes mellitus, plasma apolipoprotein A-1, and plasma apolipoprotein B.

Figure 1.. Intercorrelation of HDL proteins and plasma lipoprotein biomarkers.

Each cell represents pairwise Pearson correlation for magnitude of correlation through color and r correlation coefficient. White cells have P>0.05/91 pairwise tests=5.5×10−4, and r correlation coefficients are still presented. Variables are arranged through hierarchical clustering. Clusters of positively correlated variables are represented with black squares.

Figure 2.. pCAD distributions by plasma apoA-1 quantile and presence of angiographic obstructive CAD.

Boxplots of pCAD scores separated by plasma apoA-1 quantile and presence of obstructive CAD by angiography are depicted. For each box, the middle line represents the 50th quantile (Q2), and lower and upper box edges represent the 25th (Q1) and 75th (Q3) quantiles, respectively. The lower whisker extends to the smallest observation ≥ Q1 − 1.5 * IQR (where IQR = Q3 − Q1). The upper whisker extends to the largest observation ≤ Q3 + 1.5 * IQR. Depicted points represent values extending beyond the whiskers.

Figure 3.. Comparisons of C-statistics for obstructive CAD across clinical variables, plasma apolipoproteins, and pCAD.

Individual C-statistics and 95% confidence intervals were computed for CAD in the present study across CAD clinical risk factors, apoB, apoA-1, and an HDL apolipoproteomic score (pCAD). Horizontal lines represent the upper and lower bounds of the 95% confidence interval for pCAD. The y-axis is truncated to allow for comparisons across the individual variables assessed. Variables are ordered along the x-axis by C-statistic estimation.