Metabolites of Glutamate Metabolism Are Associated With Incident Cardiovascular Events in the PREDIMED PREvencion con DIeta MEDiterranea (PREDIMED) Trial
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:...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2016 |
| Country: | España |
| Institution: | Instituto de Salud Carlos III (ISCIII) |
| Repository: | Repisalud |
| Language: | English |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/20240 |
| Online Access: | http://hdl.handle.net/20.500.12105/20240 |
| Access Level: | Open access |
| Keyword: | Cardiovascular disease Diet Dietary clinical trial Epidemiology Glutamate Glutamine Incidence Stroke Dieta Mediterránea Incidencia Modelos de Riesgos Proporcionales Ácido Glutámico Accidente Cerebrovascular LDL-Colesterol Femenino Infarto del Miocardio Fumar Tabaco HDL-Colesterol Masculino Glutamina Hipertensión Fumar Factores de Riesgo Dislipidemias Humanos Persona de Mediana Edad Anciano Anciano de 80 o más Años Diabetes Mellitus Tipo 2 Enfermedades Cardiovasculares Ensayos Clínicos Controlados Aleatorios como Asunto España Cardiovascular Diseases Diabetes Mellitus, Type 2 |
| Summary: | 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 PREvencion con DIeta MEDiterranea (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 P-linear 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 (P-interaction=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. |
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