{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T16:55:20Z","timestamp":1781801720492,"version":"3.54.5"},"reference-count":29,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pulse"],"abstract":"<jats:p>Introduction: Biological rather than chronological age (C-age) drives deviation from healthy aging. This study aimed to identify a plasma metabolomic signature indicative of age-related cardiovascular risk (pMTB-age) predicting vascular morbidity and mortality. Methods: Nuclear magnetic resonance identified 38 plasma metabolites in two population cohorts: the Flemish cohort examined as discovery (N = 719 [2005\u20132010]) and internal replication cohort (N = 580\/719 [2009\u20132013]) and the external replication Spanish Hortega cohort (N = 811 [2001]). Results: The trained model (pMTB-age), relating C-age to the plasma metabolome derived by elastic net regression, included 18 metabolites (six amino acids) and explained from 28.6% to 22.9% of C-age in the discovery and replication data. Feature importance of the retained metabolites derived by SHapley Additive exPlanation showed large interindividual variability in the relation between C-age and pMTB-age. In Flemish and Spanish, cardiovascular risk factors were significantly associated with C-age, pMTB-age, and pMTB-age uncorrelated from C-age (pMTB-age-R). In Flemish (median follow-up 12.3 years) and Spanish (18.8 years), mortality and cardiovascular complications correlated with C-age and pMTB-age. In Flemish, cardiac endpoints (hazard ratio [95% CI] 1.28 [1.00\u20131.63]) and its components kept significance in relation to pMTB-age-R. The pathway analysis revealed overrepresentation of glycine, serine, and threonine. Conclusions: pMTB-age is a multidimensional biomarker, which identifies individuals with accelerated vascular aging with high precision and combined with the pathway analysis highlights the role of amino acids in vascular disease. Therefore, pMTB-age can guide risk stratification and the personalized and timely prevention and treatment tailored to an individual\u2019s unique pMTB-age profile.<\/jats:p>","DOI":"10.1159\/000551883","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T16:00:54Z","timestamp":1775232054000},"page":"62-77","source":"Crossref","is-referenced-by-count":0,"title":["Plasma Metabolomic Signature Predicting Deviation from Healthy Vascular Aging in Two European Cohorts"],"prefix":"10.1159","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0551-971X","authenticated-orcid":false,"given":"Dong-Yan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7893-3642","authenticated-orcid":false,"given":"Dries 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