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

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 asses...

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Autores principales: Riggs, Kayla A., Joshi, Parag H., Khera, Amit, Singh, Kavisha, Akinmolayemi, Oludamilola, Ayers, Colby R., Rohatgi, Anand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947609/
https://www.ncbi.nlm.nih.gov/pubmed/31817053
http://dx.doi.org/10.3390/jcm8122137
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author Riggs, Kayla A.
Joshi, Parag H.
Khera, Amit
Singh, Kavisha
Akinmolayemi, Oludamilola
Ayers, Colby R.
Rohatgi, Anand
author_facet Riggs, Kayla A.
Joshi, Parag H.
Khera, Amit
Singh, Kavisha
Akinmolayemi, Oludamilola
Ayers, Colby R.
Rohatgi, Anand
author_sort Riggs, Kayla A.
collection PubMed
description 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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spelling pubmed-69476092020-01-13 Impaired HDL Metabolism Links GlycA, A Novel Inflammatory Marker, with Incident Cardiovascular Events Riggs, Kayla A. Joshi, Parag H. Khera, Amit Singh, Kavisha Akinmolayemi, Oludamilola Ayers, Colby R. Rohatgi, Anand J Clin Med Article 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. MDPI 2019-12-03 /pmc/articles/PMC6947609/ /pubmed/31817053 http://dx.doi.org/10.3390/jcm8122137 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Riggs, Kayla A.
Joshi, Parag H.
Khera, Amit
Singh, Kavisha
Akinmolayemi, Oludamilola
Ayers, Colby R.
Rohatgi, Anand
Impaired HDL Metabolism Links GlycA, A Novel Inflammatory Marker, with Incident Cardiovascular Events
title Impaired HDL Metabolism Links GlycA, A Novel Inflammatory Marker, with Incident Cardiovascular Events
title_full Impaired HDL Metabolism Links GlycA, A Novel Inflammatory Marker, with Incident Cardiovascular Events
title_fullStr Impaired HDL Metabolism Links GlycA, A Novel Inflammatory Marker, with Incident Cardiovascular Events
title_full_unstemmed Impaired HDL Metabolism Links GlycA, A Novel Inflammatory Marker, with Incident Cardiovascular Events
title_short Impaired HDL Metabolism Links GlycA, A Novel Inflammatory Marker, with Incident Cardiovascular Events
title_sort impaired hdl metabolism links glyca, a novel inflammatory marker, with incident cardiovascular events
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947609/
https://www.ncbi.nlm.nih.gov/pubmed/31817053
http://dx.doi.org/10.3390/jcm8122137
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