Christopher Papandreou1,2,3,4, Pablo Hernández-Alonso1,2,3,4, Mònica Bulló1,2,3,4, Miguel Ruiz-Canela3,5,6, Jun Li7,8, Marta Guasch-Ferré1,2,7,9, Estefanía Toledo3,5,6, Clary Clish10, Dolores Corella3,11, Ramon Estruch3,12,13, Montserrat Cofán3,13,14, Montserrat Fitó3,15, Cristina Razquin3,5,6, Fernando Arós3,16, Miquel Fiol3,17, José M Santos-Lozano3,18, Lluís Serra-Majem3,19, Liming Liang8,20, Miguel A Martínez-González3,5,6,7, Frank B Hu7,9,8, Jordi Salas-Salvadó1,2,3,4. 1. Biochemistry and Biotechnology Department, Human Nutrition Unit, Rovira i Virgili University, Reus, Spain. 2. Pere i Virgili Health Research Institute (IISPV), Reus, Spain. 3. CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain. 4. Human Nutrition Unit, University Hospital of Sant Joan de Reus, Reus, Spain. 5. Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain. 6. Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. 7. Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA. 8. Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA. 9. Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 10. Broad Institute of MIT and Harvard University, Cambridge, MA, USA. 11. Department of Preventive Medicine, University of Valencia, Valencia, Spain. 12. Department of Internal Medicine, Hospital Clinic, University of Barcelona,, Barcelona, Spain. 13. August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain. 14. Lipid Clinic, Department of Endocrinology and Nutrition, Hospital Clinic, University of Barcelona, Barcelona, Spain. 15. Cardiovascular and Nutrition Research Group, Hospital del Mar Medical Research Institute, Barcelona, Spain. 16. Department of Cardiology, University Hospital of Alava, Vitoria, Spain. 17. Institute of Health Sciences IUNICS, Health Research Institute of the Balearic Islands, Son Espases Hospital, Palma de Mallorca, Spain. 18. Department of Family Medicine, Seville Primary Care Health District, San Pablo Health Center, Seville, Spain. 19. Research Institute of Biomedical and Health Sciences IUIBS, University of Las Palmas de Gran Canaria, Las Palmas, Spain. 20. Department of Statistics, Harvard TH Chan School of Public Health, Boston, MA, USA.
Abstract
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.
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.
Authors: Ramón Estruch; Emilio Ros; Jordi Salas-Salvadó; Maria-Isabel Covas; Dolores Corella; Fernando Arós; Enrique Gómez-Gracia; Valentina Ruiz-Gutiérrez; Miquel Fiol; José Lapetra; Rosa M Lamuela-Raventos; Lluís Serra-Majem; Xavier Pintó; Josep Basora; Miguel A Muñoz; José V Sorlí; J Alfredo Martínez; Montserrat Fitó; Alfredo Gea; Miguel A Hernán; Miguel A Martínez-González Journal: N Engl J Med Date: 2018-06-13 Impact factor: 91.245
Authors: Daniel R Sappington; Eric R Siegel; Gloria Hiatt; Abhishek Desai; Rosalind B Penney; Azemat Jamshidi-Parsian; Robert J Griffin; Gunnar Boysen Journal: Biochim Biophys Acta Date: 2016-01-26