HDLs comprise a family of heterogeneous particles that vary by size, density, composition, and functionality. Two distinct HDL subfractions, large buoyant HDL2 and small dense HDL3, might exert differential effects on atherosclerosis and display a promising role in CAD risk prediction.
HDL-2 is part of the larger HDL cholesterol family, which is responsible for removing excess cholesterol from the body and transporting it to the liver. HDL-2 is formed when HDL particles in the blood interact with enzymes and acquire more cholesterol.
The large HDL2 is superior to small HDL3 in the assessment of of coronary artery disease risk.
Reduced mean HDL size is associated with cardiovascular disease. Since HDL-C is primarily carried in the circulation by large, lipid-rich HDL particles, the inverse relationship between HDL size and cardiovascular risk can be secondary to those established for plasma levels of HDL particles, HDL-C, and large HDL.
The epidemiological data suggest that the HDL particle number may represent a more relevant therapeutic target as compared to HDL-C.
Very high mean HDL size can be paradoxically associated with elevated cardiovascular risk as observed in the EPIC-Norfolk study after multiple adjustment; this association resembles those reported between cardiovascular disease and very high levels of HDL-C as observed, for example, in the IDEAL study.
References:
Kontush A. HDL particle number and size as predictors of cardiovascular disease. Front Pharmacol. 2015 Oct 5;6:218. doi: 10.3389/fphar.2015.00218. PMID: 26500551; PMCID: PMC4593254.
Pascot A, Lemieux I, Prud'homme D, Tremblay A, Nadeau A, Couillard C, Bergeron J, Lamarche B, Després JP. Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity. J Lipid Res. 2001 Dec;42(12):2007-14. PMID: 11734573.
van der Steeg WA, Holme I, Boekholdt SM, Larsen ML, Lindahl C, Stroes ES, Tikkanen MJ, Wareham NJ, Faergeman O, Olsson AG, Pedersen TR, Khaw KT, Kastelein JJ. High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies. J Am Coll Cardiol. 2008 Feb 12;51(6):634-42. doi: 10.1016/j.jacc.2007.09.060. PMID: 18261682.
van der Steeg WA, Holme I, Boekholdt SM, Larsen ML, Lindahl C, Stroes ES, Tikkanen MJ, Wareham NJ, Faergeman O, Olsson AG, Pedersen TR, Khaw KT, Kastelein JJ. High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies. J Am Coll Cardiol. 2008 Feb 12;51(6):634-42. doi: 10.1016/j.jacc.2007.09.060. PMID: 18261682.
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