Research Article
Concentration of Smaller High‐Density Lipoprotein Particle (HDL‐P) Is Inversely Correlated With Carotid Intima Media Thickening After Confounder Adjustment: The Multi Ethnic Study of Atherosclerosis (MESA)
Daniel Seung Kim, Yatong K. Li, Griffith A. Bell, Amber A. Burt, Tomas Vaisar, Patrick M. Hutchins, Clement E. Furlong, James D. Otvos, Joseph F. Polak, Martinson Kweku Arnan, Joel D. Kaufman, Robyn L. McClelland, W. T. Longstreth, Gail P. Jarvik
Published:
May 20, 2016
DOI:
10.1161/JAHA.115.002977
License:
© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Abstract
BackgroundRecent studies have failed to establish a causal relationship between high‐density lipoprotein cholesterol levels (HDL‐C) and cardiovascular disease (CVD), shifting focus to other HDL measures. We previously reported that smaller/denser HDL levels are protective against cerebrovascular disease. This study sought to determine which of small+medium HDL particle concentration (HDL‐P) or large HDL‐P was more strongly associated with carotid intima‐media thickening (cIMT) in an ethnically diverse cohort.Methods and ResultsIn cross‐sectional analyses of participants from the Multi Ethnic Study of Atherosclerosis (MESA), we evaluated the associations of nuclear magnetic resonance spectroscopy–measured small+medium versus large HDL‐P with cIMT measured in the common and internal carotid arteries, through linear regression. After adjustment for CVD confounders, low‐density lipoprotein cholesterol (LDL‐C), HDL‐C, and small+medium HDL‐P remained significantly and inversely associated with common (coefficient=−1.46 μm; P=0.00037; n=6512) and internal cIMT (coefficient=−3.82 μm; P=0.0051; n=6418) after Bonferroni correction for 4 independent tests (threshold for significance=0.0125; α=0.05/4). Large HDL‐P was significantly and inversely associated with both cIMT outcomes before HDL‐C adjustment; however, after adjustment for HDL‐C, the association of large HDL‐P with both common (coefficient=1.55 μm; P=0.30; n=6512) and internal cIMT (coefficient=4.84 μm; P=0.33; n=6418) was attenuated. In a separate sample of 126 men, small/medium HDL‐P was more strongly correlated with paraoxonase 1 activity (r p=0.32; P=0.00023) as compared to both total HDL‐P (r p=0.27; P=0.0024) and large HDL‐P (r p=0.02; P=0.41) measures.ConclusionsSmall+medium HDL‐P is significantly and inversely correlated with cIMT measurements. Correlation of small+medium HDL‐P with cardioprotective paraoxonase 1 activity may reflect a functional aspect of HDL responsible for this finding.