title: High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies.
abstract: OBJECTIVE
  This study was designed to assess the relationship of high-density-lipoprotein cholesterol (HDL-C), HDL particle size, and apolipoprotein A-I (apoA-I) with the occurrence of coronary artery disease (CAD), with a focus on the effect of very high values of these parameters.
  
  
  BACKGROUND
  High plasma levels of HDL-C and apoA-I are inversely related to the risk of CAD. However, recent data suggest that this relationship does not hold true for very high HDL-C levels, particularly when a preponderance of large HDL particles is observed.
  
  
  METHODS
  We conducted a post-hoc analysis of 2 prospective studies: the IDEAL (Incremental Decrease in End Points through Aggressive Lipid Lowering; n = 8,888) trial comparing the efficacy of high-dose to usual-dose statin treatment for the secondary prevention of cardiovascular events, and the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk case-control study, including apparently healthy individuals who did (cases, n = 858) or did not (control patients, n = 1,491) develop CAD during follow-up. In IDEAL, only HDL-C and apoA-I were available; in EPIC-Norfolk, nuclear magnetic resonance spectroscopy-determined HDL particle sizes were also available.
  
  
  RESULTS
  In the IDEAL study, higher HDL-C proved a significant major cardiac event risk factor following adjustment for age, gender, smoking, apoA-I, and apoB. A similar association was observed for HDL particle size in EPIC-Norfolk. Increased risk estimates were particularly present in the high ends of the distributions. In contrast, apoA-I remained negatively associated across the major part of its distribution in both studies.
  
  
  CONCLUSIONS
  When apoA-I and apoB are kept constant, HDL-C and HDL particle size may confer risk at very high values. This does not hold true for very high levels of apoA-I at fixed levels of HDL-C and apoB. These findings may have important consequences for assessment and treatment of CAD risk.
authors.affiliation: Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Wim A
authors.initials: WA
authors.lastname: van der Steeg
authors.forename: Ingar
authors.initials: I
authors.lastname: Holme
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
authors.forename: Mogens Lytken
authors.initials: ML
authors.lastname: Larsen
authors.forename: Christina
authors.initials: C
authors.lastname: Lindahl
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
authors.forename: Matti J
authors.initials: MJ
authors.lastname: Tikkanen
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Ole
authors.initials: O
authors.lastname: Faergeman
authors.forename: Anders G
authors.initials: AG
authors.lastname: Olsson
authors.forename: Terje R
authors.initials: TR
authors.lastname: Pedersen
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood* / Q000187:drug effects; D001055:Apolipoproteins B; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood* / Q000187:drug effects; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D015415:Biomarkers; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors