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Nogal, A.* ; Alkis, T.* ; Lee, Y.* ; Kifer, D.* ; Hu, J.* ; Murphy, R.A.* ; Huang, Z.* ; Wang-Sattler, R. ; Kastenmüller, G. ; Linkohr, B. ; Barrios, C.* ; Crespo, M.* ; Gieger, C. ; Peters, A. ; Price, J.* ; Rexrode, K.M.* ; Yu, B.* ; Menni, C.*

Predictive metabolites for incident myocardial infarction: A two-step meta-analysis of individual patient data from six cohorts comprising 7,897 individuals from the the COnsortium of METabolomic Studies.

Cardiovasc. Res. 119, 2743-2754 (2023)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
AIMS: Myocardial infarction (MI) is a major cause of death and disability worldwide. Most metabolomics studies investigating metabolites predicting MI are limited by the participant number and/or the demographic diversity. We sought to identify biomarkers of incident MI in the Consortium of Metabolomics Studies (COMETS). METHODS AND RESULTS: We included 7,897 individuals aged on average 66 years from six intercontinental cohorts with blood metabolomic profiling (n = 1,428 metabolites, of which 168 were present in at least 3 cohorts with over 80% prevalence) and MI information (1,373 cases). We performed a two-stage Individual Patients Data meta-analysis. We first assessed the associations between circulating metabolites and incident MI for each cohort adjusting for traditional risk factors, and then performed a fixed effect inverse-variance meta-analysis to pull the results together. Finally, we conducted a pathway enrichment analysis to identify potential pathways linked to MI.On meta-analysis, 56 metabolites including 21 lipids and 17 amino acids were associated with incident MI after adjusting for multiple testing (false discovery rate, FDR < 0.05), and 10 were novel. The largest increased risk was observed for the carbohydrate mannitol/sorbitol (HR [95% CI] = 1.40[1.26-1.56], p-value < 0.001), whereas the largest decrease in risk was found for glutamine (HR [95% CI] = 0.74[0.67-0.82], p-value < 0.001). Moreover, the identified metabolites were significantly enriched (corrected p-value < 0.05) in pathways previously linked with cardiovascular diseases, including aminoacyl-tRNA biosynthesis. CONCLUSIONS: In the most comprehensive metabolomics study of incident MI to date, 10 novel metabolites were associated with MI. Metabolite profiles might help to identify high-risk individuals before disease onset. Further research is needed to fully understand the mechanisms of action and elaborate pathway findings. TRANSLATIONAL PERSPECTIVE: In the largest meta-analyses covering six international cohorts, we identify 10 novel and 46 known metabolites associated with incident MI, that can be used to identify at-risk individuals before disease onset. Our results improve our understanding of the molecular changes that take place in MI development and provide potential novel targets for clinical prediction and a deeper understanding of causal mechanisms.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 2-step Individual Patient Data Meta-analysis ; Myocardial Infarction ; Amino Acids ; Biomarkers ; Metabolomics; Risk; Disease; Acid
ISSN (print) / ISBN 0008-6363
e-ISSN 1755-3245
Zeitschrift Cardiovascular Research
Quellenangaben Band: 119, Heft: 17, Seiten: 2743-2754 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Great Clarendon St, Oxford Ox2 6dp, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)
Institute of Bioinformatics and Systems Biology (IBIS)
Förderungen We thank all the participants of the contributing cohorts for their time and effort and supporting our research. We also would like to thank Tamara Harris for her contributions.