Abstract 111: A Novel Assay that Incorporates Measurement of Ex Vivo LCAT Activity with Measurement of Cholesterol Efflux Capacity - Assessment of Two Biomarkers of Serum HDL Function

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Heidi L Collins ◽  
Anthony C Sulpizio ◽  
Seanna M Unruh ◽  
Steven J Adelman
Keyword(s):  
Cholesterol Efflux ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Inverse Correlation ◽  
Hdl Cholesterol ◽  
Cholesterol Esterification ◽  
High Density Lipoproteins ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
Artery Disease

Atheroprotective properties of high-density lipoproteins (HDL) may be due to the ability to remove lipids from peripheral cells to the liver for excretion during reverse cholesterol transport (RCT). Assays that measure functionality of serum HDL are needed to evaluate the therapeutic potential of treatments targeting HDL metabolism. Recent work shows an inverse correlation between cholesterol efflux capacity of serum HDL and coronary artery disease, demonstrating the value of measuring HDL functionality. Another function of HDL that promotes RCT is the capacity for esterification of cholesterol by lecithin:cholesterol acyltransferase (LCAT). A novel assay was developed that in addition to measurement of serum HDL efflux capacity incorporates measuring the capacity for esterification of HDL-cholesterol by LCAT. Assay methodology includes measurement of global cholesterol efflux via all known pathways (ABCA1, SR-BI, ABCG1 and passive diffusion) from J774 macrophage cells to serum HDL, and measurement of the proportion of cholesterol transferred to serum HDL that is esterified by LCAT over 4h. Assay validation included assessment of intra-assay repeatability, inter-assay precision, linearity, LOQ and specificity. Results showed the intra-assay variability (%CV) from six independent preparations of serum HDL is ≤10% for both the % efflux and the % esterification of cholesterol. Inter-assay variability between four separate assays is ≤13% for both the % efflux and the % esterification of cholesterol. Cholesterol efflux is linear up to concentrations of 2.8% serum HDL and cholesterol esterification is linear up to concentrations of 4% serum. The LOQ for the assay is 0.15% cholesterol efflux and 0.40% cholesterol esterification. Global cholesterol efflux was determined to be specific for known cholesterol acceptors such as serum HDL (p≤0.0001 versus media blank). The cholesterol esterification measured was determined to be specific for the action of LCAT because the presence of LCAT inhibitor decreased the % ester by 86-97% (p≤0.0009). This novel assay allows the measurement of two functional aspects of an individual subject’s serum HDL, the capacities for both cholesterol efflux and for esterification of cholesterol by LCAT.

scholarly journals Cholesterol Efflux Capacity Associates with the Ankle-Brachial Index but Not All-Cause Mortality in Patients with Peripheral Artery Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1407
Author(s):  
Robert K. Clemens ◽  
Monika Hunjadi ◽  
Andreas Ritsch ◽  
Lucia Rohrer ◽  
Thomas O. Meier ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cholesterol Efflux ◽  
Ankle Brachial Index ◽  
Mortality Rates ◽  
High Density Lipoproteins ◽  
Peripheral Artery ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
All Cause Mortality ◽  
Artery Disease

Background: Cholesterol efflux is an important mechanism by which high-density lipoproteins (HDLs) protect against cardiovascular disease. As peripheral artery disease (PAD) is associated with high mortality rates, mainly due to cardiovascular causes, we investigated whether cholesterol efflux capacity (CEC) of apolipoprotein B (apoB)-depleted plasma, a widely used surrogate of HDL function, may serve as a predictive marker for mortality in this patient population. Methods: In this prospective single-center study (median follow-up time: 9.3 years), apoB-containing lipoproteins were precipitated from plasma of 95 patients with PAD and incubated with J744-macrophages, which were loaded with radiolabeled cholesterol. CEC was defined as the fractional radiolabel released during 4 h of incubation. Results: Baseline CEC was lower in PAD patients that currently smoked (p = 0.015) and had a history of myocardial infarction (p = 0.011). Moreover, CEC showed a significant correlation with HDL-cholesterol (p = 0.003) and apolipoprotein A-I levels (p = 0.001) as well as the ankle-brachial index (ABI, p = 0.018). However, CEC did not differ between survivors and non-survivors. Neither revealed Kaplan–Meier and Cox regression analyses any significant association of CEC with all-cause mortality rates. Conclusion: Taken together, CEC is associated with ABI but does not predict all-cause mortality in patients with PAD.

scholarly journals Prolonged bedrest reduces plasma high-density lipoprotein levels linked to markedly suppressed cholesterol efflux capacity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Athina Trakaki ◽  
Hubert Scharnagl ◽  
Markus Trieb ◽  
Michael Holzer ◽  
Helmut Hinghofer-Szalkay ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Oxidative Capacity ◽  
High Density ◽  
High Density Lipoproteins ◽  
Cholesterol Efflux Capacity ◽  
Vibration Exercise ◽  
Amyloid A ◽  
Hdl Function

Abstract Recent observations strongly connect high-density lipoproteins (HDL) function and levels with coronary heart disease outcomes and risk for infections and sepsis. To date, our knowledge of factors determining this connection is still very limited. The immobility associated with prolonged bedrest is detrimental to health, affecting several systems, including the cardiovascular, pulmonary, gastrointestinal, musculoskeletal and urinary. Effects of prolonged bedrest on the composition and functional properties of HDL remain elusive. We evaluated metrics of HDL composition and function in healthy male volunteers participating in a randomized, crossover head-down bedrest study. We observed that HDL cholesterol efflux capacity was profoundly decreased during bedrest, mediated by a bedrest associated reduction in plasma levels of HDL-cholesterol and major apolipoproteins (apo) apoA-I and apoA-II. Paraoxonase activity, plasma anti-oxidative capacity and the activities of lecithin-cholesterol acyltransferase and cholesteryl ester transfer protein were not affected. No change was observed in the content of HDL-associated serum amyloid A, a sensitive marker of inflammation. Resistive vibration exercise countermeasure during bedrest did not correct impaired cholesterol efflux capacity and only tended to increase arylesterase activity of HDL-associated paraoxonase. In conclusion, prolonged bedrest reduces plasma HDL levels linked to markedly suppressed HDL cholesterol efflux capacity. Resistive vibration exercise during bedrest did not correct HDL levels and impaired cholesterol efflux capacity.

Abstract 19753: Hdl Cholesterol Efflux Capacity is Inversely Associated With Incident Chd Events Independent of Hdl-c and Apoa-i Concentrations

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Danish Saleheen ◽  
Robert Scott ◽  
Sunda Javad ◽  
Wei Zhao ◽  
Amrith Rodrigues ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Ex Vivo ◽  
Control Sample ◽  
Hdl Cholesterol ◽  
P Value ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
Chd Risk ◽  
A Prospective Study ◽  
Nested Case Control

Background: Although plasma HDL-C levels are strongly associated with risk of coronary heart disease (CHD), interventions that raise HDL-C have not been shown to reduce CHD risk. A prototypical measure of HDL function, namely HDL cholesterol efflux capacity, has been shown to be associated with prevalent CHD even after adjusting for HDL-C, but its association with incident CHD events remains uncertain. Methods: We measured HDL cholesterol efflux capacity and assessed its relationship to incident CHD events in a nested case control sample within a prospective study (EPIC-Norfolk) of 25,639 individuals aged 40-79 years examined in 1993-1997 and followed up to 2009. We quantified efflux capacity in 1895 incident CHD cases and 2474 control participants free of any cardiovascular disorders, by using a validated ex-vivo radiotracer assay that involved incubation of J774 macrophages with apoB-depleted serum from the study participants. Results: HDL cholesterol efflux capacity was positively correlated with HDL-C levels (r2=0.27; P-value<5x10-5) and apoA-I (r2=0.24;P-value< 5x10-5). In analyses comparing top versus bottom third, cholesterol efflux capacity was significantly inversely associated with incident CHD, independent of age, sex, diabetes, hypertension, smoking and alcohol use, waist-to-hip ratio, BMI, LDL-C levels and even after controlling for HDL-C or apoA-I (OR: 0.75 [0.53, 0.97];P-value:9.1x10-3) (Figure). Conclusions: HDL cholesterol efflux capacity is significantly and inversely associated with incident CHD events, independent of established vascular risk factors and after adjusting for HDL-C and apoA-I levels.

scholarly journals Whole egg consumption compared with yolk-free egg increases the cholesterol efflux capacity of high-density lipoproteins in overweight, postmenopausal women

2019 ◽  
Vol 110 (3) ◽  
pp. 617-627 ◽  
Author(s):  
Lisa Sawrey-Kubicek ◽  
Chenghao Zhu ◽  
Allison S Bardagjy ◽  
Christopher H Rhodes ◽  
Romina Sacchi ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Cholesterol Efflux ◽  
Ldl Cholesterol ◽  
Disease Risk ◽  
Hdl Cholesterol ◽  
High Density Lipoproteins ◽  
Cvd Risk ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
Whole Egg

ABSTRACTBackgroundPostmenopausal women are at higher risk for cardiovascular disease (CVD) than their younger counterparts. HDL cholesterol is a biomarker for CVD risk, but the function of HDL may be more important than HDL cholesterol in deciphering disease risk. Although diet continues to be a cornerstone of treatment and prevention of CVD, little is known about how diet affects the functionality of HDL.ObjectivesThe aim of this study was to characterize the effects of whole eggs compared with yolk-free eggs on HDL function and composition in overweight, postmenopausal women and determine how changes in HDL composition are related to HDL functional parameters.MethodsThe study was a 14-wk, single-blind, randomized crossover dietary trial with two 4-wk intervention periods in 20 overweight, postmenopausal women. The crossover treatments were frozen breakfast meals containing 100 g of liquid (∼2) whole eggs compared with 100 g of (∼2) yolk-free eggs per day, separated by a 4-wk washout. Fasting blood samples were taken at the beginning and end of each treatment period to determine the effects on HDL composition and function.ResultsCholesterol efflux capacity increased in the whole-egg treatment (mean ± SD percentage change: +5.69% ± 9.9%) compared with the yolk-free egg treatment (−3.69% ± 5.3%) (P < 0.01), but there were no other significant changes in HDL functions or antioxidant or inflammatory markers. ApoA-I, total cholesterol (TC), LDL cholesterol, and HDL cholesterol also did not change in response to the egg treatment.ConclusionsThe consumption of 2 whole eggs/d by overweight, postmenopausal women showed a significant increase in cholesterol efflux capacity. This increase in cholesterol efflux capacity was seen without significant changes in apoA-I, TC, LDL cholesterol, or HDL cholesterol, supporting the idea that HDL function rather than HDL cholesterol should be addressed in this population. This trial was registered at clinicaltrials.gov as NCT02445638.

scholarly journals Serum cholesterol efflux capacity is associated with coronary plaque progression in patients with coronary heart disease

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
X Q Wang ◽  
S Feng ◽  
X Y Shu ◽  
C D Yang ◽  
R Y Zhang
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Coronary Angiography ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Coronary Plaque ◽  
Plaque Progression ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function

Abstract Background Coronary plaque progression is a major risk factor of adverse cardiac events in patients with coronary heart disease (CHD). Emerging evidence showed that attenuated high-density lipoprotein (HDL) function measured by cholesterol efflux capacity (CEC) was associated with development of atherosclerosis independent of HDL cholesterol level. In this study, we sought to investigate whether CEC is a predictor for coronary plaque progression in CHD patients. Methods We consecutively enrolled CHD patients from January 2017 to August 2019 in our Hospital who underwent elective percutaneous coronary intervention and had at least one non-target coronary lesion. Follow-up coronary angiography were performed at around 12 months. Fluorescence-labeled cholesterol and J774 macrophages were used to measure the CEC of ApoB-depleted serum sample from all patients. Quantitative coronary angiography (QCA) was performed both at baseline and follow-up to analyze the plaque progression. Results A total of 430 CHD patients with 586 non-target coronary lesions were included in the final analysis. During a mean follow-up time of 381.04±59.52 days, patients with decreased CEC presented more severe plaque progression (net luminal loss in highest to lowest CEC quartile: 0.22±0.42mm vs 0.20±0.41mm vs 0.13±0.36mm vs 0.11±0.34mm, p=0.035). In multivariate analysis, baseline CEC was independently associated with coronary plaque progression after adjustment for traditional risk factors including HDL cholesterol and ApoA-I, no matter treated as categorical variable (OR: 0.382 [95% CI 0.180–0.781] for highest to lowest quartile) or continuous variable (OR: 0.522 [95% CI 0.373–0.714] for per SD increase]. Furthermore, CEC demonstrated a better power in predicting coronary plaque progression compared with HDL cholesterol concentration (AUC=0.644 vs 0.514). Conclusions This study suggests that HDL function reflected by serum CEC is an independent predictor for coronary plaque progression in CHD patients. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China, Shanghai Municipal Commission of Health and Family Planning

Plasma high density lipoproteins phospholipds as an indirect indicator of their cholesterol efflux capacity — new suspected atherosclerosis risk factor

2021 ◽  
Vol 67 (2) ◽  
pp. 119-129
Author(s):  
Yu.A. Tereshkina ◽  
L.V. Kostryukova ◽  
T.I. Torkhovskaya ◽  
Yu.Yu. Khudoklinova ◽  
E.G. Tikhonova
Keyword(s):  
Risk Factor ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
High Density ◽  
The Body ◽  
High Density Lipoproteins ◽  
Clinical Effects ◽  
Cholesterol Efflux Capacity ◽  
Atherosclerosis Risk ◽  
Atherosclerosis Risk Factor

High density lipoproteins (HDL) are a unique natural structure, protecting the body from the development of atherosclerotic vascular lesions and cardiovascular diseases due to this ability to remove cholesterol from cells. Plasma HDL level estimated by their cholesterol content, is a common lipid parameter, and its decrease is considered as an established atherosclerosis risk factor. However, a number of studies have shown the absence of positive clinical effects after drug-induced increase in HDL cholesterol. There is increasing evidence that not only HDL concentration, but also HDL properties, considered in this review are important. Many studies showed the decrease of HDL cholesterol efflux capacity in patients with coronary heart diseases and its association with disease severity. Some authors consider a decrease of this HDL capacity as a new additional risk factor of atherosclerosis. The review summarizes existing information on various protein and lipid components of HDL with a primary emphasis on the HDL. Special attention is paid to correlation between the HDL cholesterol efflux capacity and HDL phospholipids and the ratio “phospholipids/free cholesterol”. The accumulated information indicates importance of evaluation in the HDL fraction not only in terms of their cholesterol, but also phospholipids. In addition to the traditionally used lipid criteria, this would provide more comprehensive information about the activity of the reverse cholesterol transport process in the body and could contribute to the targeted correction of the detected disorders.

scholarly journals HDL functions and their interaction in patients with ST Elevation Myocardial Infarction: a case control study

2020 ◽  
Author(s):  
Himani Thakkar ◽  
Vinnyfred Vincent ◽  
Ambuj Roy ◽  
Sandeep Singh ◽  
Lakshmy Ramakrishnan ◽  
...  
Keyword(s):  
Acute Phase ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Pon1 Activity ◽  
Cholesterol Efflux Capacity ◽  
Coronary Syndrome ◽  
Hdl Function ◽  
Apolipoprotein A ◽  
The Mean

Abstract Background : Recent studies emphasize the importance of HDL function over HDL cholesterol measurement, as an important risk for cardiovascular diseases (CVD). We compared the HDL function of patients with Acute Coronary Syndrome (ACS) and healthy controls. Methods : We measured cholesterol efflux capacity of HDL using THP-1 macrophages labelled with fluorescently tagged (BODIPY) cholesterol. Paraoxonase and arylesterase activity of PON1 enzyme were assessed by spectrophotometric methods. Results : We recruited 151 ACS patients and 110 controls. The HDL function of all patients during acute phase and at six month follow-up was measured. The mean age of the patients and controls was 51.7 and 43.6 years respectively. The mean HDL cholesterol/apolipoprotein A-I levels (ratio) of patients during acute phase, follow-up and of controls were 40.2 mg/dl/ 112.5 mg/dl (ratio= 0.36), 38.3 mg/dl/ 127.2 mg/dl (ratio= 0.30) and 45.4 mg/dl/ 142.1 mg/dl (ratio=0.32) respectively. The cholesterol efflux capacity (CEC) of HDL was positively correlated with apolipoprotein A-I levels during acute phase (r = 0.19, p = 0.019), follow-up (r = 0.26, p = 0.007) and of controls (r = 0.3, p = 0.0012) but not with HDL-C levels (acute phase: r = 0.07, p = 0.47; follow-up: r = 0.1 , p = 0.2; control: r = 0.02, p = 0.82). Higher levels of cholesterol efflux capacity, PON1 activity and apolipoprotein A-I were associated with lower odds of development of ACS. We also observed that low CEC is associated with higher odds of having ACS if PON1 activity of HDL is also low and vice versa. Conclusion : ACS is associated with reduced HDL functions which improves at follow-up. The predicted probability of ACS depends upon individual HDL functions and the interactions between them.

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

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.

scholarly journals HDL Cholesterol Efflux Capacity is Impaired in Severe Short-Term Hypothyroidism Despite Increased HDL Cholesterol

2020 ◽  
Vol 105 (9) ◽  
pp. e3355-e3362
Author(s):  
Trynke van der Boom ◽  
Congzhuo Jia ◽  
Joop D Lefrandt ◽  
Margery A Connelly ◽  
Thera P Links ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Particle Concentration ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Antioxidative Capacity ◽  
Short Term ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
Particle Characteristics ◽  
The Impact

Abstract Context Severe hypothyroidism has profound effects on lipoprotein metabolism including high-density lipoprotein (HDL) cholesterol elevations but effects on HDL function metrics are unknown. Objective To determine the impact of severe short-term hypothyroidism on HDL particle characteristics, HDL cholesterol efflux capacity (CEC), and HDL antioxidative capacity. Design Observational study with variables measured during severe short-term hypothyroidism (median TSH 81 mU/L) and after 20 weeks of thyroid hormone supplementation (median TSH 0.03 mU/L) (Netherlands Trial Registry ID 7228). Setting University hospital setting in The Netherlands. Patients Seventeen patients who had undergone a total thyroidectomy for differentiated thyroid carcinoma. Main outcome measures HDL particle characteristics (nuclear magnetic resonance spectrometry), CEC (human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma), and HDL anti-oxidative capacity (inhibition of low-density lipoprotein oxidation). Results During hypothyroidism plasma total cholesterol, HDL cholesterol and apolipoprotein A-I were increased (P ≤ 0.001). HDL particle concentration was unchanged, but there was a shift in HDL subclasses toward larger HDL particles (P &lt; 0.001). CEC was decreased (P = 0.035), also when corrected for HDL cholesterol (P &lt; 0.001) or HDL particle concentration (P = 0.011). HDL antioxidative capacity did not change. Conclusion During severe short-term hypothyroidism CEC, an important antiatherogenic metric of HDL function, is impaired. HDL cholesterol and larger HDL particles are increased but HDL particle concentration is unchanged. Combined, these findings suggest that HDL quality and quantity are not improved, reflecting dysfunctional HDL in hypothyroidism.

scholarly journals Impaired HDL Metabolism Links GlycA, A Novel Inflammatory Marker, with Incident Cardiovascular Events

2019 ◽  
Vol 8 (12) ◽  
pp. 2137 ◽  
Author(s):  
Kayla A. Riggs ◽  
Parag H. Joshi ◽  
Amit Khera ◽  
Kavisha Singh ◽  
Oludamilola Akinmolayemi ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Inflammatory Marker ◽  
Coronary Revascularization ◽  
Hdl Cholesterol ◽  
High Sensitivity ◽  
High Density Lipoproteins ◽  
Acute Phase Reactants ◽  
Hdl Function ◽  
Hs Crp ◽  
The Impact

High-density lipoproteins (HDL) exert anti-atherosclerotic effects via reverse cholesterol transport, yet this salutary property is impaired in the setting of inflammation. GlycA, a novel integrated glycosylation marker of five acute phase reactants, is linked to cardiovascular (CV) events. We assessed the hypothesis that GlycA is associated with measures of impaired HDL function and that dysfunctional HDL may contribute to the association between GlycA and incident CV events. Baseline measurements of HDL cholesterol (HDL-C), HDL particle concentration (HDL-P), apoliprotein A1 (Apo A1), cholesterol efflux capacity, GlycA and high-sensitivity C-reactive protein (hs-CRP) were obtained from the Dallas Heart Study, a multi-ethnic cohort of 2643 adults (median 43 years old; 56% women, 50% black) without cardiovascular disease (CVD). GlycA was derived from nuclear magnetic resonance imaging. Participants were followed for first nonfatal MI, nonfatal stroke, coronary revascularization, or CV death over a median of 12.4 years (n = 197). The correlation between GlycA and hs-CRP was 0.58 (p < 0.0001). In multivariate models with HDL-C, GlycA was directly associated with HDL-P and Apo A1 and inversely associated with cholesterol efflux (standardized beta estimates: 0.08, 0.29, -0.06, respectively; all p ≤ 0.0004) GlycA was directly associated with incident CV events (adjusted hazard ratio (HR) for Q4 vs. Q1: 3.33, 95% confidence interval (CI) 1.99, 5.57). Adjustment for cholesterol efflux mildly attenuated this association (HR for Q4 vs. Q1: 3.00, 95% CI 1.75 to 5.13). In a multi-ethnic cohort, worsening inflammation, as reflected by higher GlycA levels, is associated with higher HDL-P and lower cholesterol efflux. Impaired cholesterol efflux likely explains some of the association between GlycA and incident CV events. Further studies are warranted to investigate the impact of inflammation on HDL function and CV disease.

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