Tricarboxylic acid cycle related-metabolites and risk of atrial fibrillation and heart failure
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Tricarboxylic acid cycle related-metabolites and risk of atrial fibrillation and heart failure. / 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; Salas-Salvadó, J.
In: Metabolism: clinical and experimental, Vol. 125, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Tricarboxylic acid cycle related-metabolites and risk of atrial fibrillation and heart failure
AU - Bulló, M
AU - Papandreou, C
AU - García-Gavilán, J
AU - Ruiz-Canela, M
AU - Li, J
AU - Guasch-Ferré, M
AU - Toledo, E
AU - Clish, C
AU - Corella, D
AU - Estruch, R
AU - Ros, E
AU - Fitó, M
AU - Lee, CH
AU - Salas-Salvadó, J
PY - 2021
Y1 - 2021
N2 - BackgroundTricarboxylic 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.MethodsWe 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.ResultsComparing 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.ConclusionThese findings underscore the potential role of the TCA cycle in the pathogenesis of cardiac outcomes.
AB - BackgroundTricarboxylic 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.MethodsWe 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.ResultsComparing 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.ConclusionThese findings underscore the potential role of the TCA cycle in the pathogenesis of cardiac outcomes.
U2 - 10.1016/j.metabol.2021.154915
DO - 10.1016/j.metabol.2021.154915
M3 - Journal article
C2 - 34678258
VL - 125
JO - Metabolism: clinical and experimental
JF - Metabolism: clinical and experimental
ER -
ID: 347756259