HDL Measures, Particle Heterogeneity, Proposed Nomenclature, and Relation to Atherosclerotic Cardiovascular Events

Abstract

BACKGROUND A growing body of evidence from epidemiological data, animal studies, and clinical trials supports HDL as the next target to reduce residual cardiovascular risk in statin-treated, high-risk patients. For more than 3 decades, HDL cholesterol has been employed as the principal clinical measure of HDL and cardiovascular risk associated with low HDL-cholesterol concentrations. The physicochemical and functional heterogeneity of HDL present important challenges to investigators in the cardiovascular field who are seeking to identify more effective laboratory and clinical methods to develop a measurement method to quantify HDL that has predictive value in assessing cardiovascular risk. CONTENT In this report, we critically evaluate the diverse physical and chemical methods that have been employed to characterize plasma HDL. To facilitate future characterization of HDL subfractions, we propose the development of a new nomenclature based on physical properties for the subfractions of HDL that includes very large HDL particles (VL-HDL), large HDL particles (L-HDL), medium HDL particles (M-HDL), small HDL particles (S-HDL), and very-small HDL particles (VS-HDL). This nomenclature also includes an entry for the pre-β-1 HDL subclass that participates in macrophage cholesterol efflux. SUMMARY We anticipate that adoption of a uniform nomenclature system for HDL subfractions that integrates terminology from several methods will enhance our ability not only to compare findings with different approaches for HDL fractionation, but also to assess the clinical effects of different agents that modulate HDL particle structure, metabolism, and function, and in turn, cardiovascular risk prediction within these HDL subfractions.

A review of paraoxonase 1 properties and diagnostic applications

“…is associated with high density lipoproteins (HDLs). Human HDLs are a heterogeneous group of lipoproteins which may be classified according to their increasing size: HDL 3 c, HDL 3 b, HDL 3 a, HDL 2 a, HDL 2 b (Rosenson et al 2011). In healthy individuals the highest PON1 serum activity, using ultracentrifugation and automated fractionation methods, was found in the HDL subfraction with density ranging from 1.175-1.185 kg/L, with a maximum activity at 1.18 kg/L.…”

Epidemiology: Disease Associations and Modulators of HDL-Related Biomarkers

“…However, the nomenclature has varied and it is generally quite difficult to compare HDL subclasses separated by different methods. Recently, a unified nomenclature for a simplified differentiation into 5 subclasses according to particle size (very small, small, medium, large, and very large HDL) has been proposed (Rosenson et al 2011).…”

High-Density Lipoprotein

“…15 Molar differences in the content of major proteins and lipid constituents of HDL, that is apoA-I, phosphatidylcholine, sphingomyelin, cholesterol, and cholesteryl esters, cause considerable heterogeneity of HDL as delineated by electron microscopy (shape), ultracentrifugation (density), gel filtration, polyacrylamide gel electrophoresis, nuclear magnetic resonance spectroscopy (size), charge (agarose gel electrophoresis), or affinity (apolipoprotein composition). 16 Unfortunately, there is only limited overlap between the proposed HDL subclasses defined by the various isolation methods. To facilitate communication and application in clinical studies, a consensus group has suggested 5 HDL subclasses according to size (small, very small, medium, large, very large).…”

“…To facilitate communication and application in clinical studies, a consensus group has suggested 5 HDL subclasses according to size (small, very small, medium, large, very large). 16 To date, clinical and epidemiological studies have come to discrepant conclusions on the prognostic performance of HDL subclasses. [16][17][18] This macroheterogeneity is further increased by different quantities of proteins or lipids, some of which may contribute to the pleiotropic functions of HDL.…”

“…16 To date, clinical and epidemiological studies have come to discrepant conclusions on the prognostic performance of HDL subclasses. [16][17][18] This macroheterogeneity is further increased by different quantities of proteins or lipids, some of which may contribute to the pleiotropic functions of HDL. HDL particles carry >80 different proteins [19][20][21] and hundreds of lipid species.…”