Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure: potential modification effect of Mediterranean diet.

Abstract

BACKGROUND:

The tryptophan-kynurenine pathway is linked to inflammation. We hypothesize that metabolites implicated in this pathway may be associated with the risk of heart failure (HF) or atrial fibrillation (AF) in a population at high risk of cardiovascular disease.

OBJECTIVES:

We aimed to prospectively analyze the associations of kynurenine-related metabolites with the risk of HF and AF and to analyze a potential effect modification by the randomized interventions of the PREDIMED (Prevención con Dieta Mediterránea) trial with Mediterranean diet (MedDiet).

METHODS:

Two case-control studies nested within the PREDIMED trial were designed. We selected 324 incident HF cases and 502 incident AF cases individually matched with ≤3 controls. Conditional logistic regression models were fitted. Interactions with the intervention were tested for each of the baseline plasma metabolites measured by LC-tandem MS.

RESULTS:

Higher baseline kynurenine:tryptophan ratio (OR for 1 SD: 1.20; 95% CI: 1.01, 1.43) and higher levels of kynurenic acid (OR: 1.19; 95% CI: 1.01, 1.40) were associated with HF. Quinolinic acid was associated with AF (OR: 1.15; 95% CI: 1.01, 1.32) and HF (OR: 1.25; 95% CI: 1.04, 1.49). The MedDiet intervention modified the positive associations of kynurenine (Pinteraction = 0.006), kynurenic acid (Pinteraction = 0.008), and quinolinic acid (Pinteraction = 0.033) with HF and the association between kynurenic acid and AF (Pinteraction = 0.02).

CONCLUSIONS:

We found that tryptophan-kynurenine pathway metabolites were prospectively associated with higher HF risk and to a lesser extent with AF risk. Moreover, an effect modification by MedDiet was observed for the association between plasma baseline kynurenine-related metabolites and the risk of HF, showing that the positive association of increased levels of these metabolites and HF was restricted to the control group.

• Authors: Cristina Razquin, Miguel Ruiz-Canela, Estefania Toledo, Pablo Hernández-Alonso, Clary B Clish, Marta Guasch-Ferré, Jun Li, Clemens Wittenbecher, Courtney Dennis, Angel Alonso-Gómez, Montse Fitó, Liming Liang, Dolores Corella, Enrique Gómez-Gracia, Ramon Estruch, Miquel Fiol, Jose Lapetra, Lluis Serra-Majem, Emilio Ros, Fernando Aros, Jordi Salas-Salvadó, Frank B Hu, Miguel A Martínez-González
• Journal: The American journal of clinical nutrition (Am J Clin Nutr) Vol. 114 Issue 5 Pg. 1646-1654 (11 08 2021) ISSN: 1938-3207 [Electronic] United States
• PMID: 34291275 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Chemical References

• Kynurenine
• Tryptophan

Topics

• Aged
• Aged, 80 and over
• Atrial Fibrillation (etiology)
• Case-Control Studies
• Diet, Mediterranean
• Female
• Heart Failure (etiology)
• Humans
• Kynurenine (metabolism)
• Logistic Models
• Male
• Metabolomics
• Middle Aged
• Prospective Studies
• Risk Factors
• Tryptophan (metabolism)