High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: Significance for cardiovascular risk - The IDEAL and EPIC-Norfolk studies

Wim A. van der Steeg, Ingar Holme, S. Matthijs Boekholdt, Mogens Lytken Larsen, Christina Lindahl, Erik S. G. Stroes, Matti J. Tikkanen, Nicholas J. Wareham, Ole Faergeman, Anders G. Olsson, Terje R. Pedersen, Kay-Tee Khaw, John J. P. Kastelein

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Objectives 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
Original languageEnglish
Pages (from-to)634-642
JournalJournal of the American College of Cardiology
Issue number6
Publication statusPublished - 2008

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