Articles producció científica> Bioquímica i Biotecnologia

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

  • Identification data

    Identifier: imarina:9292262
    Authors:
    Santos, JLRuiz-Canela, MRazquin, CClish, CBGuasch-Ferré, MBabio, NCorella, DGómez-Gracia, EFiol, MEstruch, RLapetra, JFitó, MAros, FSerra-Majem, LLiang, LMMartínez, MAToledo, ESalas-Salvadó, JHu, FBMartínez-González, MA
    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 cardiov
  • Others:

    Author, as appears in the article.: Santos, JL; Ruiz-Canela, M; Razquin, C; Clish, CB; Guasch-Ferré, M; Babio, N; Corella, D; Gómez-Gracia, E; Fiol, M; Estruch, R; Lapetra, J; Fitó, M; Aros, F; Serra-Majem, L; Liang, LM; Martínez, MA; Toledo, E; Salas-Salvadó, J; Hu, FB; Martínez-González, MA
    Department: Bioquímica i Biotecnologia
    URV's Author/s: Babio Sánchez, Nancy Elvira / Martínez Rodríguez, María Ángeles / Salas Salvadó, Jorge
    Keywords: Tricarboxylic cycle Stroke Risk factors Middle aged Metabolomics Mediterranean diet Male Malates Humans Female Diet, mediterranean Cohort studies Citric acid cycle Case-control studies Cardiovascular diseases Cardiovascular disease Aged, 80 and over Aged tricarboxylic cycle trial stroke profiles plasma lactate metabolomics heart cardiovascular disease
    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. Clinical trial number: ISRCTN35739639
    Thematic Areas: Serviço social Saúde coletiva Nutrition and dietetics Nutrition & dietetics Nutrição Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar General medicine Farmacia Enfermagem Endocrinology, diabetes and metabolism Endocrinology & metabolism Educação física Ciências biológicas ii Ciências biológicas i Ciências ambientais Cardiology and cardiovascular medicine Cardiac & cardiovascular systems
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: mangeles.martinez@urv.cat jordi.salas@urv.cat nancy.babio@urv.cat
    Author identifier: 0000-0001-8595-3772 0000-0003-2700-7459 0000-0003-3527-5277
    Record's date: 2024-08-03
    Papper version: info:eu-repo/semantics/publishedVersion
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Nutrition Metabolism And Cardiovascular Diseases. 33 (4): 835-843
    APA: Santos, JL; Ruiz-Canela, M; Razquin, C; Clish, CB; Guasch-Ferré, M; Babio, N; Corella, D; Gómez-Gracia, E; Fiol, M; Estruch, R; Lapetra, J; Fitó, M; A (2023). Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study. Nutrition Metabolism And Cardiovascular Diseases, 33(4), 835-843. DOI: 10.1016/j.numecd.2023.01.002
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2023
    Publication Type: Journal Publications
  • Keywords:

    Cardiac & Cardiovascular Systems,Cardiology and Cardiovascular Medicine,Endocrinology & Metabolism,Endocrinology, Diabetes and Metabolism,Medicine (Miscellaneous),Nutrition & Dietetics,Nutrition and Dietetics
    Tricarboxylic cycle
    Stroke
    Risk factors
    Middle aged
    Metabolomics
    Mediterranean diet
    Male
    Malates
    Humans
    Female
    Diet, mediterranean
    Cohort studies
    Citric acid cycle
    Case-control studies
    Cardiovascular diseases
    Cardiovascular disease
    Aged, 80 and over
    Aged
    tricarboxylic cycle
    trial
    stroke
    profiles
    plasma lactate
    metabolomics
    heart
    cardiovascular disease
    Serviço social
    Saúde coletiva
    Nutrition and dietetics
    Nutrition & dietetics
    Nutrição
    Medicine (miscellaneous)
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Interdisciplinar
    General medicine
    Farmacia
    Enfermagem
    Endocrinology, diabetes and metabolism
    Endocrinology & metabolism
    Educação física
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Cardiology and cardiovascular medicine
    Cardiac & cardiovascular systems
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