HDL (High-Density Lipoprotein) Cholesterol Efflux Capacity Is Associated With Incident Cardiovascular Disease in the General Population

Abstract

Objective: Focus is shifting from HDL-C (high-density lipoprotein cholesterol) as predictive biomarker for cardiovascular disease (CVD) towards antiatherogenic HDL functionalities. Still, limited data exist on the prospective association of HDL function metrics with CVD events. The current work aimed to determine, if baseline HDL-C efflux capacity (CEC) is associated with future CVD events in the general population. Approach and Results: We performed a prospective study among participants of the PREVEND (Prevention of Renal and Vascular End-stage Disease) cohort (follow-up, 12 years). From the overall n=8592 subjects 325 with previous CVD events were excluded; of the remaining 8267 eligible participants all subjects with new CVD events during follow-up were selected and individually matched to controls for age, sex, smoking status, and HDL-C levels. CEC at baseline was quantified using human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma. Despite identical HDL-C and apoA (apolipoprotein)-I levels between cases (n=351) and controls (n=354) CEC was significantly lower in cases (0.93±0.29 versus 1.01±0.24 arbitrary units; P <0.001). In all subjects combined, CEC correlated positively with HDL-C and apoA-I and negatively with body mass index, hsCRP (high-sensitivity C-reactive protein), and urinary albumin excretion. CEC was inversely associated with incident CVD events, both expressed per quartile and per 1 SD change (odds ratio, 0.73; 95% CI, 0.62–0.86; P <0.001); this association remained significant after adjustments for HDL-C, hsCRP, kidney function, and several other clinical covariates. Conclusions: Combined these data demonstrate that in the general population baseline CEC is significantly associated with the future development of CVD events independent of HDL-C and apoA-I plasma levels.

High-Density Lipoprotein Particles and Their Relationship to Posttransplantation Diabetes Mellitus in Renal Transplant Recipients

“…Besides a key role of the reverse cholesterol transport pathway in atherosclerosis development [51][52][53], HDL-mediated cellular cholesterol efflux (CEC) is considered to be relevant in maintaining β-cell function [54]. Interestingly, CEC from THP1 macrophages to apoB-depleted plasma predicts incident PTDM [55].…”

Association Between Blood Lipid Profile and the Incident CKD in the General Chinese Population: A Retrospective Study

“…In CKD patients, HDL-c was dysfunctional [18,19] and has different composition [20,21]. In CKD patients, HDL reverse cholesterol e ux capacity cannot predict CVD occurrence [22], while in the general population, HDL reverse cholesterol e ux capacity is related to the occurrence of CVD [23]. Accumulating evidence supports the hypothesis that prolonged metabolic imbalance of lipids leads to ectopic fat distribution in the kidney, causing in ammation, endoplasmic reticulum stress, etc.…”

High-Sensitivity CRP is Independently Associated with HDL-Mediated Cholesterol Efflux Capacity and HDL Remodeling in Patients with Coronary Artery Disease

“…The cholesterol e ux assay was performed according to established procedures [9,13]. In brief, murine…”

“…The measurement of CEC requires radiolabeled cholesterol and cultured cells, which is time-consuming and not applicable in clinical settings. It has been consistently observed that CEC was positively correlated with HDL-C levels in healthy populations [9,12,13,16]. However, in patients with CAD, this relationship was inconsistent in different studies.…”

“…A meta-analysis of 11 studies (n = 63,064 patients) has reported that the concentration of HDL particles was inversely related to cardiovascular events [8]. Cholesterol e ux capacity (CEC), a metric re ecting the ability of HDL particles as a cellular cholesterol acceptor, has been demonstrated to be inversely associated with subclinical atherosclerosis [9,10], the incidence of cardiovascular events [11][12][13], and prognosis of CAD [14,15]. The HDL particle numbers and CEC have been considered novel and reliable CAD markers [11] and may be better targets for intervention than HDL-C.…”