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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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We included 7897 individuals aged on average 66 years from six intercontinental cohorts with blood metabolomic profiling (n = 1428 metabolites, of which 168 were present in at least three cohorts with over 80% prevalence) and MI information (1373 cases). We performed a two-stage individual patient 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 &amp;lt; 0.05), and 10 were novel. The largest increased risk was observed for the carbohydrate mannitol\/sorbitol {hazard ratio [HR] [95% confidence interval (CI)] = 1.40 [1.26\u20131.56], P &amp;lt; 0.001}, whereas the largest decrease in risk was found for glutamine [HR (95% CI) = 0.74 (0.67\u20130.82), P &amp;lt; 0.001]. Moreover, the identified metabolites were significantly enriched (corrected P &amp;lt; 0.05) in pathways previously linked with cardiovascular diseases, including aminoacyl-tRNA biosynthesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In the most comprehensive metabolomic 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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvad147","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T15:47:16Z","timestamp":1694706436000},"page":"2743-2754","source":"Crossref","is-referenced-by-count":28,"title":["Predictive metabolites for incident myocardial infarction: a two-step meta-analysis of individual patient data from six cohorts comprising 7897 individuals from the COnsortium of METabolomics Studies"],"prefix":"10.1093","volume":"119","author":[{"given":"Ana","family":"Nogal","sequence":"first","affiliation":[{"name":"Department of Twin Research, King\u2019s College London, St Thomas\u2019 Hospital Campus , Westminster Bridge Road, SE1 7EH London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taryn","family":"Alkis","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, 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