Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure: potential modification effect of Mediterranean diet
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Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure : potential modification effect of Mediterranean diet. / Razquin, Cristina; Ruiz-Canela, Miguel; Toledo, Estefania; Hernández-Alonso, Pablo; Clish, Clary B; Guasch-Ferré, Marta; Li, Jun; Wittenbecher, Clemens; Dennis, Courtney; Alonso-Gómez, Angel; Fitó, Montse; Liang, Liming; Corella, Dolores; Gómez-Gracia, Enrique; Estruch, Ramon; Fiol, Miquel; Lapetra, Jose; Serra-Majem, Lluis; Ros, Emilio; Aros, Fernando; Salas-Salvadó, Jordi; Hu, Frank B; Martínez-González, Miguel A.
In: American Journal of Clinical Nutrition, Vol. 114, No. 5, 2021, p. 1646-1654.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 351043319