色氨酸-犬尿氨酸降解途径的代谢组学与心房颤动和心力衰竭风险：地中海饮食的潜在修饰作用。
Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure: potential modification effect of Mediterranean diet.
机构信息
Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
Navarra Health Research Institute (IdiSNA), Pamplona, Spain.
出版信息
Am J Clin Nutr. 2021 Nov 8;114(5):1646-1654. doi: 10.1093/ajcn/nqab238.
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.
背景
色氨酸-犬尿氨酸途径与炎症有关。我们假设该途径中的代谢物与心血管疾病高危人群中心力衰竭（HF）或心房颤动（AF）的风险相关。
目的
我们旨在前瞻性分析犬尿氨酸相关代谢物与 HF 和 AF 风险的关系，并分析地中海饮食（MedDiet）干预的 PREDIMED（Prevención con Dieta Mediterránea）试验的随机干预对其的潜在影响。
方法
设计了嵌套在 PREDIMED 试验中的两项病例对照研究。我们选择了 324 例新发 HF 病例和 502 例新发 AF 病例，分别与≤3 例对照进行匹配。通过 LC-串联 MS 测量的基础血浆代谢物，采用条件逻辑回归模型进行拟合。为每个基线血浆代谢物测试了与干预的相互作用。
结果
较高的基础犬尿氨酸：色氨酸比值（OR 为 1 SD：1.20；95%CI：1.01，1.43）和较高的犬尿氨酸酸水平（OR：1.19；95%CI：1.01，1.40）与 HF 相关。喹啉酸与 AF（OR：1.15；95%CI：1.01，1.32）和 HF（OR：1.25；95%CI：1.04，1.49）相关。MedDiet 干预改变了犬尿氨酸（Pinteraction=0.006）、犬尿氨酸酸（Pinteraction=0.008）和喹啉酸（Pinteraction=0.033）与 HF 的正相关，以及犬尿氨酸酸与 AF 的相关性（Pinteraction=0.02）。
结论
我们发现色氨酸-犬尿氨酸途径代谢物与 HF 风险呈前瞻性相关，与 AF 风险的相关性较低。此外，MedDiet 的影响修饰作用观察到了基础血浆犬尿氨酸相关代谢物与 HF 风险之间的关系，表明这些代谢物水平升高与 HF 呈正相关，仅限于对照组。
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