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00925njm 22002777a 4500 dc Razquin, Cristina author Ruiz-Canela, Miguel author Toledo, Estefanía author Clish, Clary B author Guasch-Ferré, Marta author García-Gavilán, Jesús F author Wittenbecher, Clemens author Alonso-Gómez, Angel author Fito, Montserrat author Liang, Liming author Corella, Dolores author Gómez-Gracia, Enrique author Estruch, Ramon author Fiol Sala, Miquel author Santos-Lozano, José Manuel author Serra-Majem, Lluis author Ros, Emilio author Aros, Fernando author Salas-Salvado, Jordi author Hu, Frank B author Martínez-González, Miguel A author 2022-12-23 Effective prevention and risk prediction are important for peripheral artery disease (PAD) due to its poor prognosis and the huge disease burden it produces. Circulating amino acids (AA) and their metabolites may serve as biomarkers of PAD risk, but they have been scarcely investigated. The objective was to prospectively analyze the associations of baseline levels of plasma AA (and their pathways) with subsequent risk of PAD and the potential effect modification by a nutritional intervention with the Mediterranean diet (MedDiet). A matched case-control study was nested in the PREDIMED trial, in which participants were randomized to three arms: MedDiet with tree nut supplementation group, MedDiet with extra-virgin olive oil (EVOO) supplementation group or control group (low-fat diet). One hundred and sixty-seven PAD cases were matched with 250 controls. Plasma AA was measured with liquid chromatography/mass spectrometry at the Broad Institute. Baseline tryptophan, serine and threonine were inversely associated with PAD (ORfor 1 SD increase = 0.78 (0.61-0.99); 0.67 (0.51-0.86) and 0.75 (0.59-0.95), respectively) in a multivariable-adjusted conditional logistic regression model. The kynurenine/tryptophan ratio was directly associated with PAD (ORfor 1 SD increase = 1.50 (1.14-1.98)). The nutritional intervention with the MedDiet+nuts modified the association between threonine and PAD (p-value interaction = 0.018) compared with the control group. However, subjects allocated to the MedDiet+EVOO group were protected against PAD independently of baseline threonine. Plasma tryptophan, kynurenine/tryptophan ratio, serine and threonine might serve as early biomarkers of future PAD in subjects at a high risk of cardiovascular disease. The MedDiet supplemented with EVOO exerted a protective effect, regardless of baseline levels of threonine. Razquin C, Ruiz-Canela M, Toledo E, Clish CB, Guasch-Ferré M, García-Gavilán JF, et al. Circulating Amino Acids and Risk of Peripheral Artery Disease in the PREDIMEDTrial. Int J Mol Sci. 2022 Dec;24(1). https://hdl.handle.net/20.500.13003/18851 https://hdl.handle.net/20.500.12105/23401 36613713 10.3390/ijms24010270 1422-0067 International journal of molecular sciences 2-s2.0-85146040518 915427700001 L2020986074 Circulating Amino Acids and Risk of Peripheral Artery Disease in the PREDIMED Trial