Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study

Background and aim: Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association...

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Detalles Bibliográficos
Autores: Santos, José L, Ruiz-Canela, Miguel, Razquin, Cristina, Clish, Clary B, Guasch-Ferré, Marta, Babio, Nancy, Corella, Dolores, Gómez-Gracia, Enrique, Fiol Sala, Miquel, Estruch, Ramon, Lapetra, José, Fito, Montserrat, Aros, Fernando, Serra-Majem, Lluis, Liang, Liming, Martínez, María Ángeles, Toledo, Estefanía, Salas-Salvado, Jordi, Hu, Frank B, Martínez-González, Miguel A
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/23614
Acceso en línea:https://hdl.handle.net/20.500.12105/23614
Access Level:acceso abierto
Palabra clave:Dieta Mediterránea
Estudios de Cohortes
Malatos
Femenino
Masculino
Factores de Riesgo
Humanos
Persona de Mediana Edad
Ciclo del ácido Cítrico
Anciano
Anciano de 80 o más Años
Enfermedades Cardiovasculares
Estudios de Casos y Controles
Cardiovascular Diseases
Aged, 80 and over
Aged
Case-Control Studies
Citric Acid Cycle
Humans
Middle Aged
Male
Malates
Female
Risk Factors
Diet, Mediterranean
Cohort Studies
Descripción
Sumario:Background and aim: Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions. Methods and results: Case-cohort study from the PREDIMED trial involving participants aged 55-80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20-1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12-1.58) for fumarate and 1.47 (95%CI:1.21-1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32-1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention. Conclusion: Plasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk. Clinical trial number: ISRCTN35739639.

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