Metabolites of Glutamate Metabolism Are Associated With Incident Cardiovascular Events in the PREDIMED PREvencion con DIeta MEDiterranea (PREDIMED) Trial

Identifier:  imarina:2448446

Handle: https://hdl.handle.net/20.500.11797/imarina2448446

Authors:  Zheng Y, Hu FB, Ruiz-Canela M, Clish CB, Dennis C, Salas-Salvado J, Hruby A, Liang L, Toledo E, Corella D, Ros E, Fitó M, Gómez-Gracia E, Arós F, Fiol M, Lapetra J, Serra-Majem L, Estruch R, Martínez-González MA

Abstract:
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).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.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.URL: www.controlled-trials.com. Unique identifier: ISRCTN 35739639.© 2016 The Authors and The Broad Institute. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.