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. 2014 Jun 25;3(3):e000902.
doi: 10.1161/JAHA.114.000902.

HDL-3 is a superior predictor of carotid artery disease in a case-control cohort of 1725 participants

Daniel Seung Kim  1 , Amber A Burt  2 , Elisabeth A Rosenthal  2 , Jane E Ranchalis  2 , Jason F Eintracht  3 , Thomas S Hatsukami  4 , Clement E Furlong  1 , Santica Marcovina  5 , John J Albers  5 , Gail P Jarvik  1
Affiliations

HDL-3 is a superior predictor of carotid artery disease in a case-control cohort of 1725 participants

Daniel Seung Kim et al. J Am Heart Assoc. .

Abstract

Background: Recent data suggest that high-density lipoprotein cholesterol (HDL-C) levels are likely not in the causative pathway of atheroprotection, shifting focus from HDL-C to its subfractions and associated proteins. This study's goal was to determine which HDL phenotype was the better predictor of carotid artery disease (CAAD).

Methods and results: HDL-2 and HDL-3 were measured in 1725 participants of European ancestry in a prevalent case-control cohort study of CAAD. Stratified analyses were conducted for men (n=1201) and women (n=524). Stepwise linear regression was used to determine whether HDL-C, HDL-2, HDL-3, or apolipoprotein A1 was the best predictor of CAAD, while adjusting for the confounders of censored age, diabetes, and current smoking status. In both men and women, HDL-3 was negatively associated with CAAD (P=0.0011 and 0.033 for men and women, respectively); once HDL-3 was included in the model, no other HDL phenotype was significantly associated with CAAD. Addition of paraoxonase 1 activity to the aforementioned regression model showed a significant and independent (of HDL-3) association with CAAD in men (P=0.001) but not in the smaller female subgroup.

Conclusions: This study is the first to contrast the associations of HDL-2 and HDL-3 with CAAD. We found that HDL-3 levels were more predictive of CAAD status than HDL-2, HDL-C, or apolipoprotein A1. In addition, for men, paraoxonase 1 activity improved the overall model prediction for CAAD independently and additively with HDL-3 levels. Further investigation into the molecular mechanisms through which HDL-3 is associated with protection from CAAD is warranted.

Keywords: atherosclerosis; carotid arteries; high‐density lipoprotein; lipids; lipoproteins.

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Figures

Figure 1.
Figure 1.
Correlation matrix for plasma lipid measurements. Values inside each box represent r, the pairwise correlation coefficient, unadjusted for covariates. apoA1 indicates apolipoprotein A1; HDL‐C, high‐density lipoprotein cholesterol; PON1, paraoxonase 1.
See this image and copyright information in PMC

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