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Published on: September 22, 2023
Impaired metabolism predicts coronary artery calcification in women with systemic lupus erythematosus
Fanny Urbain1, Maharajah Ponnaiah2, Farid Ichou2
1Sorbonne 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.
Insights
Systemic lupus erythematosus (SLE) patients have high cardiovascular disease (CVD) risk due to metabolic alterations. Novel lipid and metabolite biomarkers improve coronary artery calcium prediction in SLE, aiding patient stratification and reducing CVD risk.
Area of Science:
- Cardiovascular research
- Metabolomics
- Rheumatology
Background:
- Systemic lupus erythematosus (SLE) patients face elevated cardiovascular disease (CVD) risk, not fully explained by traditional factors.
- SLE involves significant metabolic changes contributing to CVD prevalence.
Purpose of the Study:
- To investigate the association between metabolic and lipidomic alterations and coronary artery calcium (CAC) in SLE patients.
- To identify novel biomarkers for predicting CVD risk in SLE.
Main Methods:
- Comprehensive analysis of circulating metabolome and lipidome in 211 women with SLE.
- Coronary artery calcium (CAC) quantified using multi-detector computed tomography.
- Logistic regression with bootstrapping to develop prognostic scores.
Main Results:
- SLE disease activity and duration were independent risk factors for CAC.
- CAC presence correlated with altered lipidome (elevated very long-chain fatty acid ceramides) and metabolic pathways (purine, arginine, proline).
- Combining metabolic/lipidomic data with clinical factors improved CAC prediction (AUC: 0.887).
Conclusions:
- Disturbed metabolism significantly contributes to coronary artery calcium and coronary heart disease (CHD) risk in SLE.
- Novel lipid and metabolite biomarkers can help stratify SLE patients for targeted CVD risk reduction.
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.
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