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

TLDR

Epidemiological, animal, and clinical evidence supports targeting HDL to reduce residual cardiovascular risk in statin‑treated high‑risk patients, yet the long‑standing use of HDL‑cholesterol as a single marker and the heterogeneity of HDL particles complicate risk assessment. The study critically evaluates existing physical and chemical HDL characterization methods and proposes a unified nomenclature for HDL subfractions based on particle size. The authors introduce a nomenclature that classifies HDL into very large, large, medium, small, very‑small, and pre‑β‑1 subfractions according to physical properties. Adopting this uniform nomenclature is expected to facilitate cross‑method comparisons and improve evaluation of therapeutic agents that alter HDL subfraction structure, metabolism, and function for better cardiovascular risk prediction.

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.