TY - JOUR
T1 - A multi-metabolite signature robustly predicts long-term mortality in the PREDIMED trial and several US cohorts
AU - Fernández-Duval, Gonzalo
AU - Razquin, Cristina
AU - Wang, Fenglei
AU - Yun, Huan
AU - Hu, Jie
AU - Guasch-Ferré, Marta
AU - Rexrode, Kathryn
AU - Balasubramanian, Raji
AU - García-Gavilán, Jesús
AU - Ruiz-Canela, Miguel
AU - Clish, Clary B.
AU - Corella, Dolores
AU - Gómez-Gracia, Enrique
AU - Fiol, Miquel
AU - Estruch, Ramón
AU - Lapetra, José
AU - Fitó, Montse
AU - Serra-Majem, Luis
AU - Ros, Emilio
AU - Liang, Liming
AU - Dennis, Courtney
AU - Asensio, Eva M.
AU - Castañer, Olga
AU - Planes, Francisco J.
AU - Salas-Salvadó, Jordi
AU - Hu, Frank B.
AU - Toledo, Estefanía
AU - Martínez-González, Miguel A.
N1 - Publisher Copyright:
© 2025 Elsevier Inc.
PY - 2025
Y1 - 2025
N2 - 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.
AB - 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.
KW - All-cause mortality
KW - Biomarkers
KW - Metabolomic
KW - Metabolomic signature
KW - Plasma metabolites
U2 - 10.1016/j.metabol.2025.156195
DO - 10.1016/j.metabol.2025.156195
M3 - Journal article
C2 - 40107652
AN - SCOPUS:105001960454
SN - 0026-0495
VL - 170
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
M1 - 156195
ER -