Author, as appears in the article.: Bullo, Monica; Papandreou, Christopher; Garcia-Gavilan, Jesus; Ruiz-Canela, Miguel; Li, Jun; Guasch-Ferre, Marta; Toledo, Estefania; Clish, Clary; Corella, Dolores; Estruch, Ramon; Ros, Emilio; Fito, Montserrat; Lee, Chih-Hao; Pierce, Kerry; Razquin, Cristina; Aros, Fernando; Serra-Majem, Lluis; Liang, Liming; Martinez-Gonzalez, Miguel A; Hu, Frank B; Salas-Salvado, Jordi
Department: Bioquímica i Biotecnologia
URV's Author/s: Bulló Bonet, Mònica / García Gavilán, Jesús Francisco / Salas Salvadó, Jorge
Keywords: Tricarboxylic acid cycle metabolites Succinic acid Risk Predimed Middle aged Malic acid Male Malates Isocitric acid Isocitrates Incidence Hydroxyglutarate Humans Heart failure Glutarates Female Citric acid cycle Citric acid Case-control studies Atrial fibrillation Alpha-ketoglutarate Alpha-hydroxyglutarate Aged Aconitic acid 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: jesusfrancisco.garcia@urv.cat jesusfrancisco.garcia@urv.cat monica.bullo@urv.cat jordi.salas@urv.cat
Author identifier: 0000-0002-0218-7046 0000-0003-2700-7459
Record's date: 2024-10-12
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://pubmed.ncbi.nlm.nih.gov/34678258/
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Metabolism-Clinical And Experimental. 125 154915-
APA: Bullo, Monica; Papandreou, Christopher; Garcia-Gavilan, Jesus; Ruiz-Canela, Miguel; Li, Jun; Guasch-Ferre, Marta; Toledo, Estefania; Clish, Clary; Cor (2021). Tricarboxylic acid cycle related-metabolites and risk of atrial fibrillation and heart failure. Metabolism-Clinical And Experimental, 125(), 154915-. 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
Repositori URV