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



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.



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).



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.
Hebrew University-Hadassah School of Public Health and Community Medicine, Ein Kerem, Jerusalem, Israel; Mankon Sub-Divisional Hospital, Cameroon.
Chobufo
C
Ditah
LipoScience, Laboratory Corporation of America(®) Holdings, Raleigh, NC, USA.
James
J
Otvos
Cardiology Department, Hadassah Medical Center, Ein Kerem, Jerusalem, Israel.
Hisham
H
Nassar
Imaging Department, Hadassah Medical Center, Ein Kerem, Jerusalem, Israel.
Dorith
D
Shaham
Hebrew University-Hadassah School of Public Health and Community Medicine, Ein Kerem, Jerusalem, Israel.
Ronit
R
Sinnreich
Hebrew University-Hadassah School of Public Health and Community Medicine, Ein Kerem, Jerusalem, Israel. Electronic address: jeremy@mail.huji.ac.il.
Jeremy D
JD
Kark
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D016015:Logistic Models; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009206:Myocardium / Q000473:pathology; D010316:Particle Size; D012307:Risk Factors; D016896:Treatment Outcome
D015415:Biomarkers; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL
Arabs; Coronary calcification; HDL cholesterol; HDL particles; Jews; Large HDL particles; Medium-sized HDL particles; Small HDL particles