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

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  • dc.contributor.author Santos-Lozano, José
  • dc.contributor.author Ruiz-Canela, Miguel
  • dc.contributor.author Razquin, Cristina
  • dc.contributor.author Clish, Clary B.
  • dc.contributor.author Guasch Ferré, Marta
  • dc.contributor.author Babio, Nancy
  • dc.contributor.author Corella, Dolores
  • dc.contributor.author Gómez-Gracia, Enrique
  • dc.contributor.author Fiol, Miquel
  • dc.contributor.author Estruch, Ramón
  • dc.contributor.author Lapetra, José
  • dc.contributor.author Fitó Colomer, Montserrat
  • dc.contributor.author Arós, Fernando
  • dc.contributor.author Serra-Majem, Luis
  • dc.contributor.author Liang, Liming
  • dc.contributor.author Martínez, María Ángeles
  • dc.contributor.author Toledo, Estefania
  • dc.contributor.author Salas Salvadó, Jordi
  • dc.contributor.author Hu, Frank B.
  • dc.contributor.author Martínez-González, Miguel Ángel, 1957-
  • dc.date.accessioned 2024-05-08T06:56:10Z
  • dc.date.available 2024-05-08T06:56:10Z
  • dc.date.issued 2023
  • dc.description.abstract 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.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Santos JL, Ruiz-Canela M, Razquin C, Clish CB, Guasch-Ferré M, Babio N, et al. Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study. Nutr Metab Cardiovasc Dis. 2023 Apr;33(4):835-43. DOI: 10.1016/j.numecd.2023.01.002
  • dc.identifier.doi http://dx.doi.org/10.1016/j.numecd.2023.01.002
  • dc.identifier.issn 0939-4753
  • dc.identifier.uri http://hdl.handle.net/10230/60065
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Nutr Metab Cardiovasc Dis. 2023 Apr;33(4):835-43
  • dc.rights © 2023 The Author(s). Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Citric acid cycle
  • dc.subject.keyword Tricarboxylic cycle
  • dc.subject.keyword Metabolomics
  • dc.subject.keyword Cardiovascular disease
  • dc.subject.keyword Stroke
  • dc.title Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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