TY - JOUR

T1 - Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure

T2 - potential modification effect of Mediterranean diet

AU - Razquin, Cristina

AU - Ruiz-Canela, Miguel

AU - Toledo, Estefania

AU - Hernández-Alonso, Pablo

AU - Clish, Clary B

AU - Guasch-Ferré, Marta

AU - Li, Jun

AU - Wittenbecher, Clemens

AU - Dennis, Courtney

AU - Alonso-Gómez, Angel

AU - Fitó, Montse

AU - Liang, Liming

AU - Corella, Dolores

AU - Gómez-Gracia, Enrique

AU - Estruch, Ramon

AU - Fiol, Miquel

AU - Lapetra, Jose

AU - Serra-Majem, Lluis

AU - Ros, Emilio

AU - Aros, Fernando

AU - Salas-Salvadó, Jordi

AU - Hu, Frank B

AU - Martínez-González, Miguel A

N1 - © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Atrial Fibrillation/etiology

KW - Case-Control Studies

KW - Diet, Mediterranean

KW - Female

KW - Heart Failure/etiology

KW - Humans

KW - Kynurenine/metabolism

KW - Logistic Models

KW - Male

KW - Metabolomics

KW - Middle Aged

KW - Prospective Studies

KW - Risk Factors

KW - Tryptophan/metabolism

U2 - 10.1093/ajcn/nqab238

DO - 10.1093/ajcn/nqab238

M3 - Journal article

C2 - 34291275

VL - 114

SP - 1646

EP - 1654

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

SN - 0002-9165

IS - 5

ER -