Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure : potential modification effect of Mediterranean diet
© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition..
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.
| Errataetall: |
ErratumIn: Am J Clin Nutr. 2022 Jan 11;115(1):310. - PMID 35022667 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:114 |
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| Enthalten in: |
The American journal of clinical nutrition - 114(2021), 5 vom: 08. Nov., Seite 1646-1654 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Razquin, Cristina [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.11.2021 Date Revised 14.02.2023 published: Print ErratumIn: Am J Clin Nutr. 2022 Jan 11;115(1):310. - PMID 35022667 Citation Status MEDLINE |
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| doi: |
10.1093/ajcn/nqab238 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM328362522 |
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| 100 | 1 | |a Razquin, Cristina |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure |b potential modification effect of Mediterranean diet |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 25.11.2021 | ||
| 500 | |a Date Revised 14.02.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a ErratumIn: Am J Clin Nutr. 2022 Jan 11;115(1):310. - PMID 35022667 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition. | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
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| 650 | 4 | |a case–control | |
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