Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/112673
Título: Tricarboxylic acid cycle related-metabolites and risk of atrial fibrillation and heart failure
Autores/as: Bulló, Mònica
Papandreou, Christopher
García-Gavilán, Jesus
Ruiz-Canela, Miguel
Li, Jun
Guasch-Ferré, Marta
Toledo, Estefanía
Clish, Clary
Corella, Dolores
Estruch, Ramon
Ros, Emilio
Fitó, Montserrat
Lee, Chih Hao
Pierce, Kerry
Razquin, Cristina
Arós, Fernando
Serra-Majem, Lluis 
Liang, Liming
Martínez-González, Miguel A.
Hu, Frank B.
Salas-Salvadó, Jordi
Clasificación UNESCO: 320501 Cardiología
Palabras clave: Atrial fibrillation
Heart failure
Hydroxyglutarate
PREDIMED
Tricarboxylic acid cycle metabolites
Fecha de publicación: 2021
Publicación seriada: Metabolism: Clinical and Experimental 
Resumen: 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.
URI: http://hdl.handle.net/10553/112673
ISSN: 0026-0495
DOI: 10.1016/j.metabol.2021.154915
Fuente: Metabolism: Clinical and Experimental [ISSN 0026-0495], n. 125
Colección:Artículos
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