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Replication of LC-MS untargeted lipidomics results in patients with calcific coronary disease: an interlaboratory reproducibility study
Department of Public Health and Clinical Medicine, Umeå University And Heart Centre, Umeå, Sweden.ORCID iD: 0000-0002-2957-9904
Computational Life Science Cluster, Department of Chemistry, Umeå University, Umeå, Sweden. (Bioinformatics for Life Sciences (BILS) Sweden)
Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
Department of Public Health and Clinical Medicine, Umeå University And Heart Centre, Umeå, Sweden.
2016 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 222, p. 1042-1048Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Recently a lipidomics approach was able to identify perturbed fatty acyl chain (FAC) and sphingolipid moieties that could stratify patients according to the severity of coronary calcification, a form of subclinical atherosclerosis. Nevertheless, these findings have not yet been reproduced before generalising their application. The aim of this study was to evaluate the reproducibility of lipidomics approaches by replicating previous lipidomic findings in groups of patients with calcific coronary artery disease (CCAD).

METHODS: Patients were separated into the following groups based on their calcium score (CS); no calcification (CS: 0; n=26), mild calcification (CS: 1-250; n=27) and severe calcification (CS: >250; n=17). Two serum samples were collected from each patient and used for comparative analyses by 2 different laboratories, in different countries and time points using liquid chromatography coupled to mass spectrometry untargeted lipidomics methods.

RESULTS: Six identical metabolites differentiated patients with severe coronary artery calcification from those with no calcification were found by both laboratories independently. Additionally, relative intensities from the two analyses demonstrated high correlation coefficients. Phosphatidylcholine moieties with 18-carbon FAC were identified in lower intensities and 20:4 FAC in higher intensities in the serum of diseased group. Moreover, 3 common sphingomyelins were detected.

CONCLUSION: This is the first interlaboratory reproducibility study utilising lipidomics applications in general and specifically in patients with CCAD. Lipid profiling applications in patients with CCAD are very reproducible in highly specialised and experienced laboratories and could be applied in clinical practice in order to spare patients diagnostic radiation.

Place, publisher, year, edition, pages
Elsevier , 2016. Vol. 222, p. 1042-1048
Keywords [en]
Lipidomics, Reproducibility, Coronary artery disease, Calcific coronary disease, Metabolomics
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
URN: urn:nbn:se:oru:diva-57882DOI: 10.1016/j.ijcard.2016.07.214ISI: 000384698300219PubMedID: 27543723Scopus ID: 2-s2.0-84982192130OAI: oai:DiVA.org:oru-57882DiVA, id: diva2:1104818
Funder
Swedish Heart Lung FoundationAvailable from: 2016-10-24 Created: 2017-06-01 Last updated: 2020-05-19Bibliographically approved
In thesis
1. Novel and Traditional Risk Factors for Coronary Artery Disease: Role of Coronary Artery Calcium, Lipidomics, Psychosocial Factors and Diet
Open this publication in new window or tab >>Novel and Traditional Risk Factors for Coronary Artery Disease: Role of Coronary Artery Calcium, Lipidomics, Psychosocial Factors and Diet
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: The aim of the research reported in this thesis was to determine the association of novel and traditional risk factors with coronary artery calcium (CAC), a marker of subclinical coronary artery disease (CAD) in healthy individuals. In addition, we investigated the effects of a vegetarian, compared to a meat diet, on novel and traditional risk factors in patients with diagnosed CAD.

Methods: Studies I-II evaluated the inter-laboratory reproducibility of liquid chromatography-mass spectrometry (LC-MS) lipid analysis and the association of serum lipidome with CAC in a cohort of 70 patients. Studies III and IV analysed data of 1067 participants in the pilot study of the Swedish CArdioPulmonary bioImage Study to determine associations of psychosocial (residential area, education, housing, and social support) and traditional risk factors with CAC. Cardiac computed tomography was used to obtain a coronary artery calcium score (CACS) (Studies I–IV). Study V employed a crossover design in which 31 patients with CAD were randomly allocated to a four-week vegetarian diet alternating with four weeks of an isocaloric meat diet. Enzyme-linked immunosorbent assay was used to measure oxidised LDL-cholesterol. Plasma metabolome, including choline, trimethylamine N-oxide, L-carnitine, and acetyl-carnitine, as well as plasma lipidome were determined with LC-MS. Gut microbiota and faecal short- and branched-chain fatty acids were analysed with 16S rRNA gene sequencing and gas chromatography-MS, respectively.

Results: In Study I, two laboratories independently identified six lipids in common that differentiated serum of patients with CACS >250 from that of those with CACS=0. Study II, revealed higher levels of phosphatidylcholine(PC)(16:0/20:4) and lower levels of PC(18:2/18:2), PC(36:3) and phosphatidylethanolamine (PE)(20:0/18:2) in patients with CACS >250 than found in those with CACS=0. Study III showed a CACS >0 prevalence of 46.3% and 36.6% in low and high socioeconomic residential areas, respectively, but the traditional risk factor–adjusted odds ratio for CACS >0 was not significantly higher in subjects living in low socioeconomic areas. In Study III, the traditional risk factor–adjusted odds ratio for CACS >100 relative to CACS=0 was significantly higher in women with low education level and living in a rented apartment. Studies III and IV showed traditional risk factor–adjusted odds ratios for CACS >0 to be significantly higher in women with a family history of premature cardiovascular disease and low social support. No relationship of psychosocial factors with CAC was observed in men. The vegetarian diet implemented in Study V significantly lowered mean oxidized LDL-cholesterol (-2.73 U/L), total cholesterol (-0.13 mmol/L), LDL-cholesterol (-0.10 mmol/L), and body mass index (-0.21 kg/m2), as well as the relative abundance of PCs, PEs, and several microbial genera compared with the meat diet. The effect of the vegetarian diet on oxidized LDL-C was associated with higher relative abundance of Ruminococcaceae genera and of Barnesiella and reduced abundance of Flavonifractor. The vegetarian diet lowered the relative abundance of ceramide(d18:1/16:0) and triacylglycerols with saturated fatty acyl chains and raised the relative abundance of triacylglycerols with high carbon and polyunsaturated fatty acyl chains compared with the meat diet.

Conclusions: Novel and traditional cardiovascular risk factors are associated with subclinical CAD. Psychosocial factors are associated with subclinical CAD in women, but not in men. Short-term intervention with a vegetarian diet in individuals with CAD can positively impact novel and traditional factors that have been associated with risk of future cardiovascular events.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2020. p. 85
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 215
Keywords
Novel risk factors, coronary artery calcium, lipidomics, lipidome, psychosocial factors, vegetarian diet, gut microbiota, metabolome
National Category
General Practice Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-80920 (URN)978-91-7529-342-4 (ISBN)
Public defence
2020-06-12, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2020-03-31 Created: 2020-03-31 Last updated: 2020-05-19Bibliographically approved

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