Hruby, A. (Adela)

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    Metabolites of glutamate metabolism are associated with incident cardiovascular events in the PREDIMED PREvención con DIeta MEDiterránea (PREDIMED) trial
    (American Heart Association, 2016) Martinez-Gonzalez, M.A. (Miguel Ángel); Fiol, M. (Miquel); Clish, C.B. (Clary B.); Fito, M. (Montserrat); Hu, F.B. (Frank B.); Hruby, A. (Adela); Gomez-Gracia, E. (Enrique); Toledo, E. (Estefanía); Lapetra, J. (José); Zheng, Y. (Yan); Liang, L. (Liming); Ros, E. (Emilio); Ruiz-Canela, M. (Miguel); Dennis, C. (Courtney); Estruch, R. (Ramón); Serra-Majem, L. (Luis); Corella, D. (Dolores); Salas-Salvado, J. (Jordi); Aros, F. (Fernando)
    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 PREvenci on con DIeta MEDiterr anea (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 Plinear 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 (Pinteraction=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.