Zheng, YanHu, Frank BRuiz-Canela, MiguelClish, Clary BDennis, CourtneySalas-Salvado, JordiHruby, AdelaLiang, LimingToledo, EstefaníaCorella, DoloresRos, EmilioFito, MontserratGomez-Gracia, EnriqueAros, FernandoLapetra, JoseSerra-Majem, LluisEstruch, RamonMartinez-Gonzalez, Miguel A2024-07-092024-07-092016-09Zheng Y, Hu FB, Ruiz-Canela M, Clish CB, Dennis C, Salas-Salvado J, et al. Metabolites of Glutamate Metabolism Are Associated With Incident Cardiovascular Events in the PREDIMED PREvencion con DIeta MEDiterranea (PREDIMED) Trial. J Am Heart Assoc. 2016 Sep;5(9):e003755.2047-9980http://hdl.handle.net/20.500.13003/17180http://hdl.handle.net/20.500.12105/20240Background: Glutamate metabolism may play a role in the pathophysiology of cardiometabolic disorders. However, there is limited evidence of an association between glutamate-related metabolites and, moreover, changes in these metabolites, and risk of cardiovascular disease (CVD). Methods and Results: Plasma levels of glutamate and glutamine were measured at baseline and 1-year follow-up in a case-cohort study including 980 participants (mean age 68 years; 46% male) from the PREvencion con DIeta MEDiterranea (PREDIMED) randomized trial, which assessed a Mediterranean diet intervention in the primary prevention of CVD. During median 4.8 years of follow-up, there were 229 incident CVD events (nonfatal stroke, nonfatal myocardial infarction, or CVD death). In fully adjusted models, per 1-SD, baseline glutamate was associated with 43% (95% CI: 16% to 76%) and 81% (39% to 137%) increased risk of composite CVD and stroke alone, respectively, and baseline glutamine-to-glutamate ratio with 25% (6% to 40%) and 44% (25% to 58%) decreased risk of composite CVD and stroke alone, respectively. Associations appeared linear for stroke (both P-linear trend <= 0.005). Among participants with high baseline glutamate, the interventions lowered CVD risk by 37% compared to the control diet; the intervention effects were not significant when baseline glutamate was low (P-interaction=0.02). No significant effect of the intervention on year-1 changes in metabolites was observed, and no effect of changes themselves on CVD risk was apparent. Conclusions: Baseline glutamate was associated with increased CVD risk, particularly stroke, and glutamine-to-glutamate ratio was associated with decreased risk. Participants with high glutamate levels may obtain greater benefits from the Mediterranean diet than those with low levels.enghttp://creativecommons.org/licenses/by-nc/4.0/Cardiovascular diseaseDietDietary clinical trialEpidemiologyGlutamateGlutamineIncidenceStrokeCardiovascular DiseasesDiabetes Mellitus, Type 2research articleAttribution-NonCommercial 4.0 International2763339159e00375510.1161/JAHA.116.003755Journal of the American Heart Associationopen accessDieta MediterráneaIncidenciaModelos de Riesgos ProporcionalesÁcido GlutámicoAccidente CerebrovascularLDL-ColesterolFemeninoInfarto del MiocardioFumar TabacoHDL-ColesterolMasculinoGlutaminaHipertensiónFumarFactores de RiesgoDislipidemiasHumanosPersona de Mediana EdadAncianoAnciano de 80 o más AñosDiabetes Mellitus Tipo 2Enfermedades CardiovascularesEnsayos Clínicos Controlados Aleatorios como AsuntoEspaña2-s2.0-85016728658386716900037L618953066