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Title: Metabolites of glutamate metabolism are associated with incident cardiovascular events in the PREDIMED PREvención con DIeta MEDiterránea (PREDIMED) Trial
Authors: Zheng, Yan
Hu, Frank B.
Ruiz-Canela, Miguel
Clish, Clary B.
Dennis, Courtney
Salas-Salvado, Jordi
Hruby, Adela
Liang, Liming
Toledo, Estefania
Corella, Dolores
Ros, Emilio 
Fitó, Montserrat
Gómez-Gracia, Enrique
Arós, Fernando
Fiol, Miquel
Lapetra, José
Serra-Majem, Lluis 
Estruch, Ramón 
Martínez-González, Miguel A.
UNESCO Clasification: 3206 Ciencias de la nutrición
Keywords: Cardiovascular disease
Dietary clinical trial
Glutamate, et al
Issue Date: 2016
Journal: Journal of the American Heart Association 
Abstract: Background: 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 PREvención con DIeta MEDiterránea (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. Clinical Trial Registration: URL: Unique identifier: ISRCTN 35739639.
ISSN: 2047-9980
DOI: 10.1161/JAHA.116.003755
Source: Journal of the American Heart Association [ISSN 2047-9980], v. 5 (9)
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