Summary of Study ST002732

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001696. The data can be accessed directly via it's Project DOI: 10.21228/M8GM73 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002732
Study TitleImpaired metabolism predicts coronary artery calcification in women with systemic lupus erythematosus
Study SummaryBackground. Patients with systemic lupus erythematosus (SLE) exhibit a high risk for cardiovascular diseases which is not fully explained by the classical Framingham risk factors. SLE is characterized by major metabolic alterations which could contribute to the elevated prevalence of CVD. In order to address this hypothesis, 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 (CT) scan for quantification of coronary artery calcium (CAC), a robust predictor of coronary heart disease (CHD). Results. Beyond traditional risk factors, including age and hypertension, disease activity and duration were independent risk factor for developing CAC in women with SLE. The presence of coronary calcium was associated with major alterations of circulating lipidome dominated by a high abundance of circulating ceramides with very long chain fatty acids. Alteration in multiple metabolic pathways, including purine metabolism, arginine and proline metabolism, and microbiota-derived metabolites, were also associated with CAC in women with SLE. Backward stepwise logistic regression models of lipidomic and metabolomic variables were used to develop prognostic scores. Strikingly, combining metabolic and lipidomic variables to 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. Conclusion. The present study uncovers the contribution of disturbed metabolism in the presence of coronary artery calcium and the prediction of CHD in SLE. The identification of these novel lipid and metabolite biomarkers may help to stratify patients for reducing CVD morbidity and mortality in SLE.
Institute
INSERM
Last NameLe Goff
First NameWilfried
Address91, bd de l'Hopital
Emailwilfried.le_goff@sorbonne-universite.fr
Phone+33140779638
Submit Date2023-06-07
Num Groups3
Total Subjects228
Raw Data AvailableYes
Raw Data File Type(s)wiff
Analysis Type DetailLC-MS
Release Date2023-06-25
Release Version1
Wilfried Le Goff Wilfried Le Goff
https://dx.doi.org/10.21228/M8GM73
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001696
Project DOI:doi: 10.21228/M8GM73
Project Title:Impaired metabolism predicts coronary artery calcification in women with systemic lupus erythematosus
Project Type:Clinical study
Project 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. In order to address this hypothesis, 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). Results. Beyond traditional risk factors, including age and hypertension, disease activity and duration were independent risk factor 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. Backward stepwise logistic regression models 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. Conclusion. The present study uncovers the contribution of disturbed metabolism to the presence of coronary artery calcium and the prediction of CHD in SLE. Identification of novel lipid and metabolite biomarkers may help stratifying patients for reducing CVD morbidity and mortality in SLE.
Institute:INSERM
Last Name:Lhomme
First Name:Marie
Address:Bd de l'hopital, Paris, Ile de France, 75013, France
Email:m.lhomme@ihuican.fr
Phone:+33184827767

Subject:

Subject ID:SU002838
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Group
SA274792P_207High
SA274793P_97High
SA274794P_107High
SA274795P_93High
SA274796P_67High
SA274797P_158High
SA274798P_153High
SA274799P_57High
SA274800P_60High
SA274801P_3High
SA274802P_15High
SA274803P_205High
SA274804P_49High
SA274805P_134High
SA274806P_20High
SA274807P_119High
SA274808P_131High
SA274809P_32High
SA274810P_95High
SA274811P_192High
SA274812P_77Med
SA274813P_208Med
SA274814P_55Med
SA274815P_190Med
SA274816P_16Med
SA274817P_143Med
SA274818P_24Med
SA274819P_47Med
SA274820P_129Med
SA274821P_133Med
SA274822P_101Med
SA274823P_169Med
SA274824P_167Med
SA274825P_111Med
SA274826P_64Med
SA274827P_165Med
SA274828P_178Med
SA274829P_100Med
SA274830P_166Med
SA274831P_7Med
SA274832P_17Med
SA274833P_113Med
SA274834P_159Med
SA274835P_132Med
SA274836P_14Med
SA274837P_141Med
SA274838P_186Med
SA274839P_56Med
SA274840P_210Med
SA274841P_155Med
SA274842P_147Med
SA274843P_172Med
SA274844P_149Med
SA274845P_80Med
SA274846P_127Med
SA274847P_83Med
SA274848P_130Med
SA274849P_146Med
SA274850P_88Med
SA274851P_170Med
SA274852P_115Med
SA274853P_145Med
SA274854P_138Med
SA274855P_86Med
SA274856P_125Med
SA274857P_85Med
SA274858P_211Med
SA274859P_176Null
SA274860P_173Null
SA274861P_195Null
SA274862P_157Null
SA274863P_164Null
SA274864P_175Null
SA274865P_200Null
SA274866P_151Null
SA274867P_177Null
SA274868P_41Null
SA274869P_197Null
SA274870P_162Null
SA274871P_201Null
SA274872P_191Null
SA274873P_188Null
SA274874P_161Null
SA274875P_206Null
SA274876P_209Null
SA274877P_182Null
SA274878P_148Null
SA274879P_154Null
SA274880P_21Null
SA274881P_152Null
SA274882P_189Null
SA274883P_184Null
SA274884P_204Null
SA274885P_181Null
SA274886P_29Null
SA274887P_198Null
SA274888P_179Null
SA274889P_183Null
SA274890P_171Null
SA274891P_193Null
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Collection:

Collection ID:CO002831
Collection Summary:Patients included in this study (211 female subjects with median age of 43.5 years [range 19-78 years]) were followed at the French National Reference Center for SLE (Pitié-Salpêtrière Hospital, Paris, France) between January 2014 and December 2017. SLE was defined according to international guidelines (ACR) 19. Antiphospholipid syndrome (APS) was defined according to the revised Sapporo criteria 20. Each patient underwent a multi-detector CT scan (Siemens syngo.CT CaScoring) and CAC was quantified by means of the previously described Agatston scoring method 21. Duration of the disease, clinical involvements (skin, seritis, hematology, joints and nervous system), treatment regimens (steroids, methotrexate and hydroxychloroquine) and SLE variables (C3, anti-dsDNA, anti-nuclear and antiphospholipid (aPL) antibodies) are presented in Table 1. Disease activity was estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. The presence of cardiovascular risk factors, including hypertension, hypercholesterolemia, diabetes, obesity, smoking status, family or previous personal history of cardiovascular events and inflammation (US-CRP) was determined for all patients (Table 1). Patients were classified into 3 groups of coronary heart disease (CHD) risk according to the calcium score as defined by the Multi-Ethnic Study of Atherosclerosis (MESA) study 22 (low, CAC=0; moderate, 0 < CAC < 100, and high, CAC > 100).
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR002847
Treatment Summary:A blood sample was collected at the day of the CT scan for each patient by venipuncture from the antecubital vein into sterile BD Vacutainer tubes containing clot activator. Serum was separated immediately by low-speed centrifugation at 2500 rpm for 20 min at 4°C and was stored at -80°C until use.

Sample Preparation:

Sampleprep ID:SP002844
Sampleprep Summary:Serum lipids were extracted using a modified Folch method 26. Briefly, 10 µl serum supplemented with a mixture of internal standards were extracted using 1600 μl of acidified methanol:0.05N HCl (1:1 v/v) and 800 μl chloroform in the presence of an antioxidant, butylated hydroxytoluene. The lower organic phase was dried and lipids were reconstituted into 40µl of LC-MS compatible solvent and were quantified by LC-MS/MS.

Combined analysis:

Analysis ID AN004429 AN004430
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Shimadzu 20AD Shimadzu 20AD
Column Phenomenex Kinetex HILIC (150 x 3mm,2.6um) Phenomenex Kinetex HILIC (150 x 3mm,2.6um)
MS Type ESI ESI
MS instrument type Triple quadrupole Triple quadrupole
MS instrument name ABI Sciex 4000 QTrap ABI Sciex 4000 QTrap
Ion Mode POSITIVE POSITIVE
Units relative difference relative difference

Chromatography:

Chromatography ID:CH003328
Instrument Name:Shimadzu 20AD
Column Name:Phenomenex Kinetex HILIC (150 x 3mm,2.6um)
Column Temperature:45
Flow Gradient:-
Flow Rate:300ul/min
Solvent A:100% water; 0.2% acetic acid; 30mM ammonium acetate
Solvent B:100% acetonitrile; 0.2% acetic acid
Chromatography Type:HILIC

MS:

MS ID:MS004176
Analysis ID:AN004429
Instrument Name:ABI Sciex 4000 QTrap
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:MRM acquisition of low abundant phospho- and sphingolipid classes: PS, PA, LPC, LPE, cer, PG, PI, PE, PE-P this acquisition is called "short"
Ion Mode:POSITIVE
  
MS ID:MS004177
Analysis ID:AN004430
Instrument Name:ABI Sciex 4000 QTrap
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:MRM acquisition of abundant lipids following 100fold dilution for PC and SM analysis. This acquisition is called "short10x"
Ion Mode:POSITIVE
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