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

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dc.catalogadorgjm
dc.contributor.authorSantos Martín, José Luis
dc.contributor.authorRuiz-Canela, Miguel
dc.contributor.authorRazquin, Cristina
dc.contributor.authorClish, Clary B.
dc.contributor.authorGuasch-Ferré, Marta
dc.contributor.authorBabio, Nancy
dc.contributor.authorCorella, Dolores
dc.contributor.authorGómez-Gracia, Enrique
dc.contributor.authorFiol, Miquel
dc.contributor.authorEstruch, Ramón
dc.contributor.authorLapetra, José
dc.contributor.authorFitó, Montserrat
dc.contributor.authorAros, Fernando
dc.contributor.authorSerra-Majem, Lluis
dc.contributor.authorLiang, Liming
dc.contributor.authorMartínez, María Ángeles
dc.contributor.authorToledo, Estefanía
dc.contributor.authorSalas-Salvadó, Jordi
dc.contributor.authorHu, Frank B.
dc.contributor.authorMartínez-González, Miguel A.
dc.date.accessioned2024-01-19T14:48:18Z
dc.date.available2024-01-19T14:48:18Z
dc.date.issued2023
dc.description.abstractBackground 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.
dc.fechaingreso.objetodigital2024-06-06
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.numecd.2023.01.002
dc.identifier.urihttps://doi.org/10.1016/j.numecd.2023.01.002
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/80693
dc.identifier.wosidWOS:000994906500001
dc.information.autorucEscuela de Medicina; Santos Martín, José Luis; 0000-0003-2895-0369; 1005923
dc.language.isoen
dc.nota.accesoContenido completo
dc.rightsacceso abierto
dc.subjectCitric acid cycle
dc.subjectTricarboxylic cycle
dc.subjectMetabolomics
dc.subjectCardiovascular disease
dc.subjectStroke
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleCirculating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study
dc.typeartículo
sipa.codpersvinculados1005923
sipa.trazabilidadORCID;2024-01-08
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