Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to Atherosclerosis

Background The contribution of high‐density lipoprotein to cardiovascular benefit is closely linked to its role in the cellular cholesterol efflux process; however, various clinical and biochemical variables are known to modulate the overall cholesterol efflux process. The aim of this study was to e...

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Main Authors: Julie Gall, Eric Frisdal, Randa Bittar, Wilfried Le Goff, Eric Bruckert, Philippe Lesnik, Maryse Guerin, Philippe Giral
Format: Article
Language:English
Published: Wiley 2016-12-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.116.004808
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author Julie Gall
Eric Frisdal
Randa Bittar
Wilfried Le Goff
Eric Bruckert
Philippe Lesnik
Maryse Guerin
Philippe Giral
author_facet Julie Gall
Eric Frisdal
Randa Bittar
Wilfried Le Goff
Eric Bruckert
Philippe Lesnik
Maryse Guerin
Philippe Giral
author_sort Julie Gall
collection DOAJ
description Background The contribution of high‐density lipoprotein to cardiovascular benefit is closely linked to its role in the cellular cholesterol efflux process; however, various clinical and biochemical variables are known to modulate the overall cholesterol efflux process. The aim of this study was to evaluate the extent to which clinical and biological anomalies associated with the establishment of the metabolic syndrome modulate cholesterol efflux capacity and contribute to development of atherosclerosis. Methods and Results This study involved patients (n=1202) displaying atherogenic dyslipidemia in primary prevention who were referred to our prevention center. Among these patients, 25% presented at least 3 criteria of the metabolic syndrome, as defined by the National Cholesterol Education Program Adult Treatment Panel III. We measured the capacity of 40‐fold diluted serum to mediate cholesterol efflux from cholesterol‐loaded human THP‐1 macrophages. Cholesterol efflux capacity was reduced progressively by 4% to 11% (P<0.0001) as a function of the increasing number of coexisting criteria for the metabolic syndrome from 1 to 5. This observation was primarily related to reductions in scavenger receptor class B member 1 and ATP binding cassette subfamily G member 1–dependent efflux. Multivariate analyses indicate that serum efflux capacity was significantly associated with established metabolic syndrome (odds ratio 0.45; 95% CI 0.28–0.72; P=0.009) independent of age, low‐density lipoprotein cholesterol, status with regard to lipid‐lowering therapy, smoking status, and alcohol consumption. Conclusions Our study revealed that individual criteria of metabolic syndrome are closely related synergistically to cholesterol efflux capacity. In addition, established metabolic syndrome and cholesterol efflux capacity were independently associated with clinical features of atherosclerosis.
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spelling doaj-art-181069a45cf74f5d81c2ba28fe975f7b2025-08-20T02:44:29ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802016-12-0151210.1161/JAHA.116.004808Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to AtherosclerosisJulie Gall0Eric Frisdal1Randa Bittar2Wilfried Le Goff3Eric Bruckert4Philippe Lesnik5Maryse Guerin6Philippe Giral7INSERM UMRS1166 Hôpital de la Pitié Paris FranceINSERM UMRS1166 Hôpital de la Pitié Paris FranceINSERM UMRS1166 Hôpital de la Pitié Paris FranceINSERM UMRS1166 Hôpital de la Pitié Paris FranceINSERM UMRS1166 Hôpital de la Pitié Paris FranceINSERM UMRS1166 Hôpital de la Pitié Paris FranceINSERM UMRS1166 Hôpital de la Pitié Paris FranceINSERM UMRS1166 Hôpital de la Pitié Paris FranceBackground The contribution of high‐density lipoprotein to cardiovascular benefit is closely linked to its role in the cellular cholesterol efflux process; however, various clinical and biochemical variables are known to modulate the overall cholesterol efflux process. The aim of this study was to evaluate the extent to which clinical and biological anomalies associated with the establishment of the metabolic syndrome modulate cholesterol efflux capacity and contribute to development of atherosclerosis. Methods and Results This study involved patients (n=1202) displaying atherogenic dyslipidemia in primary prevention who were referred to our prevention center. Among these patients, 25% presented at least 3 criteria of the metabolic syndrome, as defined by the National Cholesterol Education Program Adult Treatment Panel III. We measured the capacity of 40‐fold diluted serum to mediate cholesterol efflux from cholesterol‐loaded human THP‐1 macrophages. Cholesterol efflux capacity was reduced progressively by 4% to 11% (P<0.0001) as a function of the increasing number of coexisting criteria for the metabolic syndrome from 1 to 5. This observation was primarily related to reductions in scavenger receptor class B member 1 and ATP binding cassette subfamily G member 1–dependent efflux. Multivariate analyses indicate that serum efflux capacity was significantly associated with established metabolic syndrome (odds ratio 0.45; 95% CI 0.28–0.72; P=0.009) independent of age, low‐density lipoprotein cholesterol, status with regard to lipid‐lowering therapy, smoking status, and alcohol consumption. Conclusions Our study revealed that individual criteria of metabolic syndrome are closely related synergistically to cholesterol efflux capacity. In addition, established metabolic syndrome and cholesterol efflux capacity were independently associated with clinical features of atherosclerosis.https://www.ahajournals.org/doi/10.1161/JAHA.116.004808ABC transporteratherosclerosiscardiovascular riskcholesterol effluxmacrophagemetabolic syndrome
spellingShingle Julie Gall
Eric Frisdal
Randa Bittar
Wilfried Le Goff
Eric Bruckert
Philippe Lesnik
Maryse Guerin
Philippe Giral
Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to Atherosclerosis
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ABC transporter
atherosclerosis
cardiovascular risk
cholesterol efflux
macrophage
metabolic syndrome
title Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to Atherosclerosis
title_full Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to Atherosclerosis
title_fullStr Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to Atherosclerosis
title_full_unstemmed Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to Atherosclerosis
title_short Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to Atherosclerosis
title_sort association of cholesterol efflux capacity with clinical features of metabolic syndrome relevance to atherosclerosis
topic ABC transporter
atherosclerosis
cardiovascular risk
cholesterol efflux
macrophage
metabolic syndrome
url https://www.ahajournals.org/doi/10.1161/JAHA.116.004808
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