Impaired metabolism predicts coronary artery calcification in women with systemic lupus erythematosus.

Cardiovascular diseases Ceramides Lipidomics Metabolomics Systemic lupus erythematosus

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Oct 2023
Historique:
received: 04 04 2023
revised: 23 08 2023
accepted: 03 09 2023
pubmed: 19 9 2023
medline: 19 9 2023
entrez: 19 9 2023
Statut: ppublish

Résumé

Patients with systemic lupus erythematosus (SLE) exhibit a high risk for cardiovascular diseases (CVD) which is not fully explained by the classical Framingham risk factors. SLE is characterized by major metabolic alterations which can contribute to the elevated prevalence of CVD. A comprehensive analysis of the circulating metabolome and lipidome was conducted in a large cohort of 211 women with SLE who underwent a multi-detector computed tomography scan for quantification of coronary artery calcium (CAC), a robust predictor of coronary heart disease (CHD). Beyond traditional risk factors, including age and hypertension, disease activity and duration were independent risk factors for developing CAC in women with SLE. The presence of coronary calcium was associated with major alterations of circulating lipidome dominated by an elevated abundance of ceramides with very long chain fatty acids. Alterations in multiple metabolic pathways, including purine, arginine and proline metabolism, and microbiota-derived metabolites, were also associated with CAC in women with SLE. Logistic regression with bootstrapping of lipidomic and metabolomic variables were used to develop prognostic scores. Strikingly, combining metabolic and lipidomic variables with clinical and biological parameters markedly improved the prediction (area under the curve: 0.887, p < 0.001) of the presence of coronary calcium in women with SLE. The present study uncovers the contribution of disturbed metabolism to the presence of coronary artery calcium and the associated risk of CHD in SLE. Identification of novel lipid and metabolite biomarkers may help stratifying patients for reducing CVD morbidity and mortality in SLE. INSERM and Sorbonne Université.

Sections du résumé

BACKGROUND BACKGROUND
Patients with systemic lupus erythematosus (SLE) exhibit a high risk for cardiovascular diseases (CVD) which is not fully explained by the classical Framingham risk factors. SLE is characterized by major metabolic alterations which can contribute to the elevated prevalence of CVD.
METHODS METHODS
A comprehensive analysis of the circulating metabolome and lipidome was conducted in a large cohort of 211 women with SLE who underwent a multi-detector computed tomography scan for quantification of coronary artery calcium (CAC), a robust predictor of coronary heart disease (CHD).
FINDINGS RESULTS
Beyond traditional risk factors, including age and hypertension, disease activity and duration were independent risk factors for developing CAC in women with SLE. The presence of coronary calcium was associated with major alterations of circulating lipidome dominated by an elevated abundance of ceramides with very long chain fatty acids. Alterations in multiple metabolic pathways, including purine, arginine and proline metabolism, and microbiota-derived metabolites, were also associated with CAC in women with SLE. Logistic regression with bootstrapping of lipidomic and metabolomic variables were used to develop prognostic scores. Strikingly, combining metabolic and lipidomic variables with clinical and biological parameters markedly improved the prediction (area under the curve: 0.887, p < 0.001) of the presence of coronary calcium in women with SLE.
INTERPRETATION CONCLUSIONS
The present study uncovers the contribution of disturbed metabolism to the presence of coronary artery calcium and the associated risk of CHD in SLE. Identification of novel lipid and metabolite biomarkers may help stratifying patients for reducing CVD morbidity and mortality in SLE.
FUNDING BACKGROUND
INSERM and Sorbonne Université.

Identifiants

DOI: 10.1016/j.ebiom.2023.104802 PMID: 37725854 PMC: PMC10518349
pubmed: 37725854
pii: S2352-3964(23)00368-7
doi: 10.1016/j.ebiom.2023.104802
pmc: PMC10518349
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

104802

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing financial interests.

Auteurs

Fanny Urbain (F)

Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des Anti-phospholipides et Autres Maladies Auto-immunes Rares, Service de Médecine Interne 2, Paris, France.

Maharajah Ponnaiah (M)

Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), ICAN I/O Data Science (MPo), ICAN Omics (FI and ML), 75013, Paris, France.

Farid Ichou (F)

Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), ICAN I/O Data Science (MPo), ICAN Omics (FI and ML), 75013, Paris, France.

Marie Lhomme (M)

Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), ICAN I/O Data Science (MPo), ICAN Omics (FI and ML), 75013, Paris, France.

Clément Materne (C)

Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France.

Sophie Galier (S)

Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France.

Julien Haroche (J)

Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des Anti-phospholipides et Autres Maladies Auto-immunes Rares, Service de Médecine Interne 2, Paris, France.

Eric Frisdal (E)

Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France.

Alexis Mathian (A)

Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des Anti-phospholipides et Autres Maladies Auto-immunes Rares, Service de Médecine Interne 2, Paris, France.

Herve Durand (H)

Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France.

Micheline Pha (M)

Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des Anti-phospholipides et Autres Maladies Auto-immunes Rares, Service de Médecine Interne 2, Paris, France.

Miguel Hie (M)

Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des Anti-phospholipides et Autres Maladies Auto-immunes Rares, Service de Médecine Interne 2, Paris, France.

Anatol Kontush (A)

Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France.

Philippe Cluzel (P)

Cardiovascular and Interventional Radiology Department, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Paris, F-75013, France.

Philippe Lesnik (P)

Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France.

Zahir Amoura (Z)

Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des Anti-phospholipides et Autres Maladies Auto-immunes Rares, Service de Médecine Interne 2, Paris, France; Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 75013, Paris, France.

Maryse Guerin (M)

Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France.

Fleur Cohen Aubart (F)

Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Centre de Référence pour le Lupus, le Syndrome des Anti-phospholipides et Autres Maladies Auto-immunes Rares, Service de Médecine Interne 2, Paris, France. Electronic address: fleur.cohen@psl.aphp.fr.

Wilfried Le Goff (W)

Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France. Electronic address: wilfried.le_goff@sorbonne-universite.fr.

Classifications MeSH