Dataset Information

Tricarboxylic acid cycle related-metabolites and risk of atrial fibrillation and heart failure.

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 [OR_{Q4 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.

SUBMITTER: Bullo M

PROVIDER: S-EPMC9206868 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Tricarboxylic acid cycle related-metabolites and risk of atrial fibrillation and heart failure.

Bulló Mònica M Papandreou Christopher C García-Gavilán Jesus J Ruiz-Canela Miguel M Li Jun J Guasch-Ferré Marta M Toledo Estefanía E Clish Clary C Corella Dolores D Estruch Ramon R Ros Emilio E Fitó Montserrat M Lee Chih-Hao CH Pierce Kerry K Razquin Cristina C Arós Fernando F Serra-Majem Lluís L Liang Liming L Martínez-González Miguel A MA Hu Frank B FB Salas-Salvadó Jordi J

Metabolism: clinical and experimental 20211020

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 34678258

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Dataset Information

Tricarboxylic acid cycle related-metabolites and risk of atrial fibrillation and heart failure.

Background

Methods

Results

Conclusion

Publications

Tricarboxylic acid cycle related-metabolites and risk of atrial fibrillation and heart failure.

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