A multi-metabolite signature robustly predicts long-term mortality in the PREDIMED trial and several US cohorts

Metabolome-based biomarkers contribute to identify mechanisms of disease and to a better understanding of overall mortality. In a long-term follow-up subsample (n = 1878) of the PREDIMED trial, among 337 candidate baseline plasma metabolites repeatedly assessed at baseline and after 1 year, 38 plasm...

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Detalles Bibliográficos
Autores: Fernández-Duval, Gonzalo, Razquin, Cristina, Wang, Fenglei, Yun, Huan, Hu, Jie, Guasch-Ferré, Marta, Rexrode, Kathryn, Balasubramanian, Raji, García-Gavilán, Jesús, Ruiz-Canela, Miguel, Clish, Clary B., Corella, Dolores, Gómez-Gracia, Enrique, Fiol Sala, Miquel, Estruch, Ramón, Lapetra, José, Fitó, Montse, Serra-Majem, Luis, Ros, Emilio, Liang, Liming, Dennis, Courtney, Asensio, Eva M, Castañer-Niño, Olga, Planes, Francisco J, Salas-Salvadó, Jordi, Hu, Frank B, Toledo, Estefanía, Martínez-González, Miguel A
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/25512
Acceso en línea:https://hdl.handle.net/20.500.13003/25512
Access Level:acceso abierto
Palabra clave:Biomarkers
Metabolomics
Biomarcadores
Metabolómica
All-cause mortality
Metabolomic
Metabolomic signature
Plasma metabolites
Descripción
Sumario:Metabolome-based biomarkers contribute to identify mechanisms of disease and to a better understanding of overall mortality. In a long-term follow-up subsample (n = 1878) of the PREDIMED trial, among 337 candidate baseline plasma metabolites repeatedly assessed at baseline and after 1 year, 38 plasma metabolites were identified as predictors of all-cause mortality. Gamma-amino-butyric acid (GABA), homoarginine, serine, creatine, 1-methylnicotinamide and a set of sphingomyelins, plasmalogens, phosphatidylethanolamines and cholesterol esters were inversely associated with all-cause mortality, whereas plasma dimethylguanidino valeric acid (DMGV), choline, short and long-chain acylcarnitines, 4-acetamidobutanoate, pseudouridine, 7-methylguanine, N6-acetyllysine, phenylacetylglutamine and creatinine were associated with higher mortality. The multi-metabolite signature created as a linear combination of these selected metabolites, also showed a strong association with all-cause mortality using plasma samples collected at 1-year follow-up in PREDIMED. This association was subsequently confirmed in 4 independent American cohorts, validating the signature as a consistent predictor of all-cause mortality across diverse populations.