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

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

CONCLUSION

These findings underscore the potential role of the TCA cycle in the pathogenesis of cardiac outcomes.

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest ER has received grants for research through his institution from the California Walnut Commission (CWC), as well as fees for lectures and participation in the CWC's Health Research Advisory Group, and support for travel and accommodation. He is also a non-paid member of the Scientific Advisory Council of the CWC. He has also received honoraria for Advisory Board, lectures and support for travel and accommodation from Alexion; honoraria for lectures and support for travel and accommodation from Danone; and honoraria for lectures from Amarin. JS-S is a non-paid member of the Scientific Committee of the International Nut and Dried Fruit Foundation. He has received grants/research support from the American Pistachio Growers and International Nut and Dried Fruit Foundation through his Institution. He has received honoraria from Instituto Danone Spain and Eroski. He is a member of the executive committee of Instituto Danone Spain and non-paid member of International Danone Institute. None of the other co-authors has potential conflicts of interest to disclose relevant to the subject matter or materials included in this work.