title: 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).
abstract: Recent 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.
  
  
  
  In 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 (rp=0.32; P=0.00023) as compared to both total HDL-P (rp=0.27; P=0.0024) and large HDL-P (rp=0.02; P=0.41) measures.
  
  
  
  Small+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.
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA Department of Biostatistics, University of Washington School of Public Health, Seattle, WA.
authors.forename: Daniel Seung
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Biostatistics, University of Washington School of Public Health, Seattle, WA.
authors.forename: Yatong K
authors.initials: YK
authors.lastname: Li
authors.affiliation: Department of Epidemiology, University of Washington School of Public Health, Seattle, WA.
authors.forename: Griffith A
authors.initials: GA
authors.lastname: Bell
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
authors.forename: Amber A
authors.initials: AA
authors.lastname: Burt
authors.affiliation: Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Vaisar
authors.affiliation: Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA TSI Incorporated, Shoreview, MN.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Hutchins
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA.
authors.forename: Clement E
authors.initials: CE
authors.lastname: Furlong
authors.affiliation: LabCorp, Raleigh, NC.
authors.forename: James D
authors.initials: JD
authors.lastname: Otvos
authors.affiliation: Department of Radiology, Tufts University School of Medicine, Boston, MA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Polak
authors.affiliation: Department of Neurology, University of Washington School of Medicine, Seattle, WA.
authors.forename: Martinson Kweku
authors.initials: MK
authors.lastname: Arnan
authors.affiliation: Division of General Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA Department of Epidemiology, University of Washington School of Public Health, Seattle, WA Department of Environmental and Occupational Health Sciences, University of Washington School of Public Health, Seattle, WA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Kaufman
authors.affiliation: Department of Biostatistics, University of Washington School of Public Health, Seattle, WA.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: McClelland
authors.affiliation: Department of Neurology, Wake Forest School of Medicine, Winston-Salem, NC Department of Epidemiology, University of Washington School of Public Health, Seattle, WA.
authors.forename: W T
authors.initials: WT
authors.lastname: Longstreth
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA pair@u.washington.edu.
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
mesh_terms: D000368:Aged; D002340:Carotid Artery Diseases / Q000097:blood* / Q000000981:diagnostic imaging; D059168:Carotid Intima-Media Thickness; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016014:Linear Models; D008075:Lipoproteins, HDL / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL
keywords: antioxidant; carotid intima media thickening; cerebrovascular disease; high‐density lipoprotein cholesterol; high‐density lipoprotein particle concentration; paraoxonase 1