Prognostic Usefulness of Serum Cholesterol Efflux Capacity in Patients With Coronary Artery Disease

Objective To investigate the association between serum cholesterol efflux capacity and all-cause and cardiovascular mortality in patients with coronary artery disease. Design Prospective cohort study. Setting Guangdong Coronary Artery Disease Cohort, established in 2008-2011. Participants 1 765 patients with coronary artery disease were followed-up for a median of 3.9 years. Main outcome measures Primary outcome was the association of baseline serum cholesterol efflux capacity with the risks of all-cause and cardiovascular mortality. Results: During 6 778 person-years of follow-up, 170 deaths were registered, 126 of which were caused by cardiovascular diseases. After multivariate adjustment for factors related to cardiovascular diseases, the hazard ratios (95% confidence intervals) across quartiles of serum cholesterol efflux capacity were 1.00, 0.75 (0.51-1.10), 0.51 (0.33-0.81) and 0.43 (0.25-0.73) for all-cause mortality ( P = 0.003), and 1.00, 0.76 (0.49-1.18), 0.37 (0.21-0.65), and 0.25 (0.12-0.52) for cardiovascular mortality ( P < 0.001). Adding serum cholesterol efflux capacity to a model containing traditional cardiovascular risk factors significantly increases its discriminatory power and predictive ability for all-cause (area under receiver operating characteristic curve 0.68 versus 0.61, P < 0.001; net reclassification improvement 14.5%, P = 0.001) and cardiovascular (area under receiver operating characteristic curve 0.71 versus 0.63, P < 0.001; net reclassification improvement 18.4%, P < 0.001) death, respectively. Conclusions: Serum cholesterol efflux capacity may serve as an independent measure for predicting all-cause and cardiovascular mortality in patients with coronary artery disease.

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

10.21203/rs.3.rs-66204/v1 ◽

2020 ◽

Author(s):

Xiaoyu Tang ◽

Ling Mao ◽

Jin Chen ◽

Tianhua Zhang ◽

Shuwei Weng ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Nmr Spectroscopy ◽

Cholesterol Efflux ◽

High Sensitivity ◽

Proton Nuclear Magnetic Resonance ◽

Control Group ◽

Cholesterol Efflux Capacity ◽

Hdl Function ◽

Artery Disease

Abstract Background: Cholesterol efflux capacity (CEC), a crucial atheroprotective function of high-density lipoprotein (HDL), has proven to be a reliable predictor of cardiovascular risk. Inflammation can damage CEC, but few studies have focused on the relationship between the systemic inflammation marker high-sensitivity C-reactive protein (hsCRP) and CEC in patients with coronary artery disease (CAD). Methods: Thirty-six CAD patients and sixty-one non-CAD controls were enrolled in this observational, cross-sectional study. CEC was measured using a [3H] cholesterol loading Raw 264.7 cell model with apolipoprotein B-depleted plasma (a surrogate for HDL). Proton nuclear magnetic resonance (NMR) spectroscopy was used to assess HDL components and subclass distribution. hsCRP was measured with a latex particle, enhanced immunoturbidimetric assay.Results: CEC was impaired in CAD patients compared to controls (11.9±2.3% vs. 13.0±2.2%, p=0.022). In the control group, CEC was positively correlated with enzymatically measured HDL cholesterol (HDL-C) levels (r=0.358, p=0.006) or NMR-determined HDL-C levels (r=0.416, p=0.001). However, in the CAD group, the significance of correlation disappeared (enzymatic method: r=0.216, p=0.206; NMR spectroscopy: r=0.065, p=0.708). Instead, we found that the level of hsCRP was negatively correlated with CEC (r=-0.351, p=0.036), and this relationship was not modified by CAD risk factors, HDL-C, and HDL subclasses. NMR showed that HDL particles shifted to larger ones in patients with high hsCRP levels, and this phenomenon was accompanied by decreased CEC. Conclusions: In patients with CAD, the level of HDL-C cannot reflect HDL function, but hsCRP is independently associated with HDL dysfunction. The impaired correlation between HDL-C and CEC is possibly due to an inflammation-induced HDL subclass remodeling. Trial registration: Chinese Clinical Trial Registry, ChiCTR1900020873. Registered on 21 January 2019 - Retrospectivelyregistered.

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Development and Validation of Apolipoprotein AI-Associated Lipoprotein Proteome Panel for the Prediction of Cholesterol Efflux Capacity and Coronary Artery Disease

Clinical Chemistry ◽

10.1373/clinchem.2018.291922 ◽

2019 ◽

Vol 65 (2) ◽

pp. 282-290 ◽

Cited By ~ 9

Author(s):

Zhicheng Jin ◽

Timothy S Collier ◽

Darlene L Y Dai ◽

Virginia Chen ◽

Zsuzsanna Hollander ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

High Throughput ◽

Cholesterol Efflux ◽

Case Control Study ◽

Case Control ◽

Inverse Association ◽

Cholesterol Efflux Capacity ◽

Artery Disease ◽

Control Study

Abstract BACKGROUND Cholesterol efflux capacity (CEC) is a measure of HDL function that, in cell-based studies, has demonstrated an inverse association with cardiovascular disease. The cell-based measure of CEC is complex and low-throughput. We hypothesized that assessment of the lipoprotein proteome would allow for precise, high-throughput CEC prediction. METHODS After isolating lipoprotein particles from serum, we used LC-MS/MS to quantify 21 lipoprotein-associated proteins. A bioinformatic pipeline was used to identify proteins with univariate correlation to cell-based CEC measurements and generate a multivariate algorithm for CEC prediction (pCE). Using logistic regression, protein coefficients in the pCE model were reweighted to yield a new algorithm predicting coronary artery disease (pCAD). RESULTS Discovery using targeted LC-MS/MS analysis of 105 training and test samples yielded a pCE model comprising 5 proteins (Spearman r = 0.86). Evaluation of pCE in a case–control study of 231 specimens from healthy individuals and patients with coronary artery disease revealed lower pCE in cases (P = 0.03). Derived within this same study, the pCAD model significantly improved classification (P < 0.0001). Following analytical validation of the multiplexed proteomic method, we conducted a case–control study of myocardial infarction in 137 postmenopausal women that confirmed significant separation of specimen cohorts in both the pCE (P = 0.015) and pCAD (P = 0.001) models. CONCLUSIONS Development of a proteomic pCE provides a reproducible high-throughput alternative to traditional cell-based CEC assays. The pCAD model improves stratification of case and control cohorts and, with further studies to establish clinical validity, presents a new opportunity for the assessment of cardiovascular health.

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Roles of cholesterol efflux capacity in the occurrence and prognosis coronary artery disease

10.21203/rs.2.17179/v1 ◽

2019 ◽

Author(s):

Huiming Ye ◽

Guiyu Xu ◽

Lihui Ren ◽

Jianjun Peng

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Cholesterol Efflux ◽

Cochrane Library ◽

Cholesterol Efflux Capacity ◽

Coronary Syndrome ◽

Increased Risk ◽

Myocardial Infraction ◽

Artery Disease ◽

Related Mortality

Abstract Background The association between cholesterol efflux capacity (CEC) with the occurrence and prognosis of coronary artery disease (CAD) remains unrevealed. In our study, a systematic review was performed to quantitively analyze the association between CEC and the risk of CAD and follow-up endpoint events of the patients with CAD.Methods A systematic search of electronic databases (PubMed, EMBASE, OVID, Web of Science and Cochrane Library) for studies published until September 2019 was performed. Cohort, case-control studies, and randomized controlled trials that examined the effect of CEC on risk and prognosis of CAD were included.Results Eighteen studies involving a total of 12615 subjects that met the inclusion criteria were included. Among them, 14 studies reported the CEC levels in control and CAD group and 8 of them analyzed the association of CEC with risk of CAD. Four studies reported the prognosis of CAD or acute coronary syndrome (ACS). From the pooled analyses, significantly decreased CEC level was shown in patients with stable CAD in comparison with the control. It was also true in subgroup analysis of the patients with ACS. The decreased CEC was significantly associated with increased risk of CAD (OR=0.65, 95% CI: 0.55-0.75, P<0.001). Decreased CEC level predicted higher all-cause (OR= 0.39, 95% CI: 0.20-0.77, P=0.007) and cardiovascular related mortality (OR= 0.34, 95% CI: 0.13-0.90, P=0.03) risk in patients with CAD. However, CEC levels failed to predict the occurrence of stroke and myocardial infraction in patients with CAD.Conclusions Decreased cholesterol efflux capacity is an independent risk factor for the occurrence of CAD patients, and its level predicts all-cause and cardiovascular related mortality risk in patients with CAD. Prospective studies should further investigate whether CEC control might improve outcomes in CAD patients.

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