title: Metabolites of Glutamate Metabolism Are Associated With Incident Cardiovascular Events in the PREDIMED PREvención con DIeta MEDiterránea (PREDIMED) Trial.
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.
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.affiliation: Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain IDISNA (Instituto de Investigación Sanitaria de Navarra), Pamplona, Spain CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Ruiz-Canela
authors.affiliation: Broad Institute of MIT and Harvard University, Cambridge, MA.
authors.forename: Clary B
authors.initials: CB
authors.lastname: Clish
authors.affiliation: Broad Institute of MIT and Harvard University, Cambridge, MA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Dennis
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain Human Nutrition Department, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Salas-Salvado
authors.affiliation: Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA.
authors.forename: Adela
authors.initials: A
authors.lastname: Hruby
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA.
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain IDISNA (Instituto de Investigación Sanitaria de Navarra), Pamplona, Spain CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Estefania
authors.initials: E
authors.lastname: Toledo
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain Department of Preventive Medicine, University of Valencia, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain Lipid Clinic, Departments of Endocrinology and Nutrition, Institut d'Investigacions Biomediques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Ros
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Fitó
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain Department of Preventive Medicine, University of Malaga, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Gómez-Gracia
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain Department of Cardiology, University Hospital of Alava, Vitoria, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Arós
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain Palma Institute of Health Research (IdISPa), Hospital Son Espases, Palma de Mallorca, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Fiol
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain Research Unit, Department of Family Medicine, Distrito Sanitario Atencion Primaria Sevilla, Sevilla, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Lapetra
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Las Palmas, Spain.
authors.forename: Lluis
authors.initials: L
authors.lastname: Serra-Majem
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain Department of Internal Medicine, Institut d'Investigacions Biomediques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Estruch
authors.affiliation: Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain IDISNA (Instituto de Investigación Sanitaria de Navarra), Pamplona, Spain CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain mamartinez@unav.es.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martínez-González
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism / Q000401:mortality* / Q000517:prevention & control; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D038441:Diet, Mediterranean; D050171:Dyslipidemias / Q000097:blood / Q000453:epidemiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000378:metabolism; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D013030:Spain / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology* / Q000378:metabolism; D000073869:Tobacco Smoking
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005973:Glutamine; D018698:Glutamic Acid
keywords: cardiovascular disease; diet; dietary clinical trial; epidemiology; glutamate; glutamine; incidence; stroke