title: High-Density Lipoprotein Subclasses and Noncardiovascular, Noncancer Chronic Inflammatory-Related Events Versus Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis.
abstract: BACKGROUND
  High-density lipoprotein (HDL) particles have properties beyond reverse cholesterol transport. We hypothesized that their protection extends to inflammation-related disease. The predictive value of HDL particle subclasses and inflammatory markers was studied for noncardiovascular, noncancer chronic inflammation-related death and hospitalization, and for incident cardiovascular disease (CVD).
  
  
  RESULTS
  A multiethnic, multicenter, prospective observational study was conducted in 6475 men and women (aged 45 to 84 years) free of known CVD at baseline with median follow-up of 10.1 years. Fasting venous samples were analyzed for baseline lipid profile and lipoprotein particles. We focused on the HDL family of variables (small-, medium-, and large-diameter HDL particles and HDL cholesterol). Analyses identified the sum of small- plus medium-diameter HDL particles as important. Small- plus medium-diameter HDL particles were inversely associated with diagnostic code-based noncardiovascular, noncancer chronic inflammation-related death and hospitalization (n=1054) independent of covariates: relative risk per SD 0.85 (95% CI: 0.79 to 0.91, P<0.0001). Small- plus medium-diameter HDL particles were also associated with adjudicated fatal and nonfatal coronary heart disease events (n=423): relative risk per SD 0.88 (95% CI 0.77 to 0.98, P=0.02).
  
  
  CONCLUSIONS
  Small- plus medium-diameter HDL particles are an independent predictor for noncardiovascular, noncancer chronic inflammation-related death and hospitalization and for coronary heart disease events in subjects initially free of overt CVD. These findings support the hypothesis that smaller HDL particles of diameter <9.4 nm have anti-inflammatory properties in the general population.
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN (D.A.D.).
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Duprez
authors.affiliation: Laboratory Corporation of America, Burlington, NC (J.O.).
authors.forename: James
authors.initials: J
authors.lastname: Otvos
authors.affiliation: Department of Pathology, University of Vermont, Colchester, VT (R.P.T.).
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: Department of Medicine, VA Medical Center, University of California San Francisco, San Francisco, CA (K.R.F.).
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Feingold
authors.affiliation: Institute for Public Health and Medicine, Northwestern University, Chicago, IL (P.G.).
authors.forename: Philip
authors.initials: P
authors.lastname: Greenland
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN (M.D.G.).
authors.forename: Myron D
authors.initials: MD
authors.lastname: Gross
authors.affiliation: Department of Medicine/Radiology, John Hopkins University, Baltimore, MD (J.C.L.).
authors.forename: Joao A C
authors.initials: JA
authors.lastname: Lima
authors.affiliation: Department of Epidemiology, University of Pittsburgh, PA (R.H.M.).
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Mackey
authors.affiliation: Department of Biostatistics, University of Minnesota, Minneapolis, MN (J.D.N.).
authors.forename: James D
authors.initials: JD
authors.lastname: Neaton
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN (O.A.S., D.R.J.).
authors.forename: Otto A
authors.initials: OA
authors.lastname: Sanchez
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN (O.A.S., D.R.J.).
authors.forename: David R
authors.initials: DR
authors.lastname: Jacobs
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology / Q000401:mortality; D018450:Disease Progression; D005260:Female; D006760:Hospitalization; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology / Q000401:mortality; D018836:Inflammation Mediators / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D011379:Prognosis; D011446:Prospective Studies; D065840:Protective Factors; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D018836:Inflammation Mediators; D008075:Lipoproteins, HDL
keywords: Multi‐Ethnic Study of Atherosclerosis; cardiovascular events; high‐density lipoprotein; lipoprotein particles; noncardiovascular, noncancer chronic inflammation–related death and hospitalization