Author, as appears in the article.: Bulló M; Papandreou C; García-Gavilán J; Ruiz-Canela M; Li J; Guasch-Ferré M; Toledo E; Clish C; Corella D; Estruch R; Ros E; Fitó M; Lee CH; Pierce K; Razquin C; Arós F; Serra-Majem L; Liang L; Martínez-González MA; Hu FB; Salas-Salvadó J

Department: Bioquímica i Biotecnologia

URV's Author/s: Bulló Bonet, Mònica / Salas Salvadó, Jorge

Keywords: Tricarboxylic acid cycle metabolites Predimed Hydroxyglutarate Heart failure Atrial fibrillation Alpha-ketoglutarate profiles predimed plasma mechanisms hydroxyglutarate heart failure failing heart disease dehydrogenase cardiovascular risk cardiomyopathy biomarkers atrial fibrillation

Abstract: Background: Tricarboxylic acid (TCA) cycle deregulation may predispose to cardiovascular diseases, but the role of TCA cycle-related metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unexplored. This study sought to investigate the association of TCA cycle-related metabolites with risk of AF and HF. Methods: We used two nested case-control studies within the PREDIMED study. During a mean follow-up for about 10 years, 512 AF and 334 HF incident cases matched by age (±5 years), sex and recruitment center to 616 controls and 433 controls, respectively, were included in this study. Baseline plasma levels of citrate, aconitate, isocitrate, succinate, malate and D/L-2-hydroxyglutarate were measured with liquid chromatography-tandem mass spectrometry. Multivariable conditional logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for metabolites and the risk of AF or HF. Potential confounders included smoking, family history of premature coronary heart disease, physical activity, alcohol intake, body mass index, intervention groups, dyslipidemia, hypertension, type 2 diabetes and medication use. Results: Comparing extreme quartiles of metabolites, elevated levels of succinate, malate, citrate and D/L-2-hydroxyglutarate were associated with a higher risk of AF [ORQ4 vs. Q1 (95% CI): 1.80 (1.21–2.67), 2.13 (1.45–3.13), 1.87 (1.25–2.81) and 1.95 (1.31–2.90), respectively]. One SD increase in aconitate was directly associated with AF risk [OR (95% CI): 1.16 (1.01–1.34)]. The corresponding ORs (95% CI) for HF comparing extreme quartiles of malate, aconitate, isocitrate and D/L-2-hydroxyglutarate were 2.15 (1.29–3.56), 2.16 (1.25–3.72), 2.63 (1.56–4.44) and 1.82 (1.10–3.04), respectively. These associations were confirmed in an internal validation, except for aconitate and AF. Conclusion: These findings underscore the potential role of the TCA cycle in the pathogenesis of cardiac outcomes.

Thematic Areas: Saúde coletiva Odontología Nutrição Medicina iii Medicina ii Medicina i Interdisciplinar General medicine Farmacia Engenharias ii Enfermagem Endocrinology, diabetes and metabolism Endocrinology & metabolism Endocrinology Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciência de alimentos Biotecnología Antropologia / arqueologia

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: jordi.salas@urv.cat monica.bullo@urv.cat

Author identifier: 0000-0003-2700-7459 0000-0002-0218-7046

Record's date: 2023-02-19

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://pubmed.ncbi.nlm.nih.gov/34678258/

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Metabolism-Clinical And Experimental. 125

APA: Bulló M; Papandreou C; García-Gavilán J; Ruiz-Canela M; Li J; Guasch-Ferré M; Toledo E; Clish C; Corella D; Estruch R; Ros E; Fitó M; Lee CH; Pierce K (2021). Tricarboxylic acid cycle related-metabolites and risk of atrial fibrillation and heart failure. Metabolism-Clinical And Experimental, 125(), -. DOI: 10.1016/j.metabol.2021.154915

Article's DOI: 10.1016/j.metabol.2021.154915

Entity: Universitat Rovira i Virgili

Journal publication year: 2021

Publication Type: Journal Publications