Impaired metabolism predicts coronary artery calcification in women with systemic lupus erythematosusResearch in context
Fanny Urbain,
Maharajah Ponnaiah,
Farid Ichou,
Marie Lhomme,
Clément Materne,
Sophie Galier,
Julien Haroche,
Eric Frisdal,
Alexis Mathian,
Herve Durand,
Micheline Pha,
Miguel Hie,
Anatol Kontush,
Philippe Cluzel,
Philippe Lesnik,
Zahir Amoura,
Maryse Guerin,
Fleur Cohen Aubart,
Wilfried Le Goff
Affiliations
Fanny Urbain
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
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
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
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
Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France
Sophie Galier
Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France
Julien Haroche
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
Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France
Alexis Mathian
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
Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France
Micheline Pha
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
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
Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France
Philippe Cluzel
Cardiovascular and Interventional Radiology Department, Sorbonne Université, Assistance Publique–Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Paris, F-75013, France
Philippe Lesnik
Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France
Zahir Amoura
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
Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France
Fleur Cohen Aubart
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; Corresponding author. Service de Médecine Interne 2, Groupe Hospitalier Pitié-Salpêtrière, 47-83, Boulevard de l’Hôpital, 75013, Paris, France.
Wilfried Le Goff
Sorbonne Université, INSERM, Foundation for Innovation in Cardiometabolism and Nutrition (IHU ICAN), UMR_S1166, F-75013, Paris, France; Corresponding author. INSERM UMR_S1166, Faculté de médecine Sorbonne Université, 91, Boulevard de l’Hôpital, 75013, Paris, France.
Summary: 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: 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: 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: 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: INSERM and Sorbonne Université.
