Assessment of HDL Cholesterol Removal Capacity: Toward Clinical Application

Abstract

While there is a controversy regarding the causal relationship between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD), recent studies have demonstrated that the cholesterol efflux capacity (CEC) of HDL is associated with the incidence of CVD. However, there are several limitations to current assays of CEC. First, CEC measurements are not instantly applicable in clinical settings, because CEC assay methods require radiolabeled cholesterol and cultured cells, and these procedures are time consuming. Second, techniques to measure CEC are not standardized. Third, the condition of endogenous cholesterol donors would not be accounted for in the CEC assays. Recently, we established a simple, high-throughput, cell-free assay system to evaluate the capacity of HDL to accept additional cholesterol, which is herein referred to as "cholesterol uptake capacity (CUC)". We demonstrated that CUC represents a residual cardiovascular risk in patients with optimal low-density lipoprotein cholesterol control independently of traditional risk factors, including HDL-C. Establishing reproducible approaches for the cholesterol removal capacity of HDL is required to validate the impact of dysfunctional HDL on cardiovascular risk stratification in the "real world".

Keywords: Cardiovascular disease; Cholesterol efflux capacity (CEC); Cholesterol uptake capacity (CUC); HDL cholesterol (HDL-C); High-density lipoprotein (HDL).

Fig. 1.

Post-transcriptional modification of apoAI and CEC

Fig. 2.

The procedural schema of CEC and CUC

Fig. 3.

Varied systems to measure CEC Adapted from Ref. (Progress in Lipid Research 2018; 69: 21–32).

Fig. 4.

Differences in concept between CEC and CUC ABCA1: ATP-binding cassette transporter A1; ABCG1: ATP-binding cassette transporter G1; SR-BI: scavenger receptor class B type I; LCAT: Lecithin:cholesterol acyltransferase; PLTP: phospholipid transfer protein; HL: hepatic lipase; EL: endothelial lipase; sPLA2: secreted phospholipase A2.

Fig. 5.

Correlations between CUC and HDL particle concentration (HDL-P) Small (diameter range: 7.3–8.2 nm) and large (diameter range: 9.4–14 nm) HDL-P were determined at LipoScience/LabCorp (Burlington, NC) using nuclear magnetic resonance spectroscopy and the LipoProfile-3 algorithm.