High plasma glutamate and a low glutamine-to-glutamate ratio are associated with increased risk of heart failure but not atrial fibrillation in the Prevención con Dieta Mediterránea (PREDIMED) Study

Background: Although the association between glutamate and glutamine in relation to cardiometabolic disorders has been evaluated, the role of these metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unknown. Objectives: We examined associations of glutamate, gl...

Full description

Bibliographic Details
Authors: Papandreou, Christopher, Fitó Colomer, Montserrat, Salas Salvadó, Jordi
Format: article
Status:Versión aceptada para publicación
Publication Date:2020
Country:España
Institution:Universitat Pompeu Fabra
Repository:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/53667
Online Access:http://hdl.handle.net/10230/53667
http://dx.doi.org/10.1093/jn/nxaa273
Access Level:Open access
Keyword:PREDIMED
Atrial fibrillation
Glutamate
Glutamine
Heart failure
Description
Summary:Background: Although the association between glutamate and glutamine in relation to cardiometabolic disorders has been evaluated, the role of these metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unknown. Objectives: We examined associations of glutamate, glutamine, and the glutamine-to-glutamate ratio with AF and HF incidence in a Mediterranean population at high cardiovascular disease (CVD) risk. Methods: The present study used 2 nested case-control studies within the PREDIMED (Prevención con Dieta Mediterránea) study. During ∼10 y of follow-up, there were 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma concentrations of glutamate and glutamine were semiquantitatively profiled with LC-tandem MS. ORs were estimated with multivariable conditional logistic regression models. Results: In fully adjusted models, per 1-SD increment, glutamate was associated with a 29% (95% CI: 1.08, 1.54) increased risk of HF and glutamine-to-glutamate ratio with a 20% (95% CI: 0.67, 0.94) decreased risk. Glutamine-to-glutamate ratio was also inversely associated with HF risk (OR per 1-SD increment: 0.80; 95% CI: 0.67, 0.94) when comparing extreme quartiles. Higher glutamate concentrations were associated with a worse cardiometabolic risk profile, whereas a higher glutamine-to-glutamate ratio was associated with a better cardiometabolic risk profile. No associations between the concentrations of these metabolites and AF were observed. Conclusions: Our findings suggest that high plasma glutamate concentrations possibly resulting from alterations in the glutamate-glutamine cycle may contribute to the development of HF in Mediterranean individuals at high CVD risk.This trial was registered at www.isrctn.com as ISRCTN35739639.