Small and medium sized HDL particles are protectively associated with coronary calcification in a cross-sectional population-based sample

• Published in: Atherosclerosis Vol. 251; pp. 124 - 131
• Main Authors: Ditah, Chobufo, Otvos, James, Nassar, Hisham, Shaham, Dorith, Sinnreich, Ronit, Kark, Jeremy D
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.08.2016
• Subjects: Aged; Arabs; Biomarkers - blood; Calcinosis - blood; Cardiovascular; Cholesterol, HDL - blood; Coronary Artery Disease - blood; Coronary calcification; Cross-Sectional Studies; Female; HDL cholesterol; HDL particles; Humans; Jews; Large HDL particles; Lipoproteins, HDL - blood; Logistic Models; Magnetic Resonance Spectroscopy; Male; Medium-sized HDL particles; Middle Aged; Multivariate Analysis; Myocardium - pathology; Particle Size; Risk Factors; Small HDL particles; Treatment Outcome; Large HDL particles; HDL particles; Jews; Medium-sized HDL particles; Arabs; Coronary calcification; Small HDL particles; HDL cholesterol
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2016.06.010

Abstract Background and aims Failure of trials to observe benefits by elevating plasma high-density lipoprotein cholesterol (HDL-C) has raised serious doubts about HDL-C’s atheroprotective properties. We aimed to identify protective HDL biomarkers by examining the association of nuclear magnetic resonance (NMR) measures of total HDL-particle (HDL-P), large HDL-particle, and small and medium-sized HDL-particle (MS-HDL-P) concentrations and average HDL-particle size with coronary artery calcification (CAC), which reflects the burden of coronary atherosclerosis, and compare with that of HDL-C. Methods Using a cross-sectional design, 504 Jerusalem residents (274 Arabs and 230 Jews), recruited by population-based probability sampling, had HDL measured by NMR spectroscopy. CAC was determined by multidetector helical CT-scanning using Agatston scoring. Independent associations between the NMR measures and CAC (comparing scores ≥100 vs. <100) were assessed with multivariable binary logistic models. Results Comparing tertile 3 vs. tertile 1, we observed protective associations of HDL-P (multivariable-adjusted OR 0.42, 95% CI 0.22–0.79, plinear trend  = 0.002) and MS-HDL-P (OR 0.36, 95% CI 0.19–0.69), plinear trend  = 0.006 with CAC, which persisted after further adjustment for HDL-C. HDL-C was not significantly associated with CAC (multivariable-adjusted OR 0.59, 95% CI 0.27–1.29 for tertiles 3 vs. 1, plinear trend  = 0.49). Large HDL-P and average particle size (which are highly correlated; r = 0.83) were not associated with CAC: large HDL-P (OR 0.77, 95% CI 0.33–1.83, plinear trend  = 0.29) and average HDL-P size (OR 0.72, 95% CI 0.35–1.48, plinear trend  = 0.58). Conclusions MS-HDL-P represents a protective subpopulation of HDL particles. HDL-P and MS-HDL-P were more strongly associated with CAC than HDL-C. Based on the accumulating evidence, incorporation of MS-HDL-P or HDL-P into the routine prediction of CHD risk should be evaluated.