Center for Microbiome and Human Health, Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA.
Eur J Heart Fail. 2024 Feb;26(2):233-241. doi: 10.1002/ejhf.3111. Epub 2024 Jan 25.
Phenylacetylglutamine (PAGln) is a phenylalanine-derived metabolite produced by gut microbiota with mechanistic links to heart failure (HF)-relevant phenotypes. We sought to investigate the prognostic value of PAGln in patients with stable HF.
Fasting plasma PAGln levels were measured by stable-isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patients with stable HF from two large cohorts. All-cause mortality was assessed at 5-year follow-up in the Cleveland cohort, and HF, hospitalization, or mortality were assessed at 3-year follow-up in the Berlin cohort. Within the Cleveland cohort, median PAGln levels were 4.2 (interquartile range [IQR] 2.4-6.9) μM. Highest quartile of PAGln was associated with 3.09-fold increased mortality risk compared to lowest quartile. Following adjustments for traditional risk factors, as well as race, estimated glomerular filtration rate, amino-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, left ventricular ejection fraction, ischaemic aetiology, and HF drug treatment, elevated PAGln levels remained predictive of 5-year mortality in quartile comparisons (adjusted hazard ratio [HR] [95% confidence interval, CI] for Q4 vs Q1: 1.64 [1.07-2.53]). In the Berlin cohort, a similar distribution of PAGln levels was observed (median 3.2 [IQR 2.0-4.8] μM), and PAGln levels were associated with a 1.92-fold increase in 3-year HF hospitalization or all-cause mortality risk (adjusted HR [95% CI] for Q4 vs Q1: 1.92 [1.02-3.61]). Prognostic value of PAGln appears to be independent of trimethylamine N-oxide levels.
High levels of PAGln are associated with adverse outcomes independent of traditional cardiac risk factors and cardio-renal risk markers.
苯乙酰谷氨酰胺（PAGln）是一种由肠道微生物群产生的苯丙氨酸衍生代谢物，与心力衰竭（HF）相关表型有机制联系。我们试图研究稳定型 HF 患者中 PAGln 的预后价值。
通过稳定同位素稀释液质联用（LC-MS/MS）测定了来自两个大型队列的稳定型 HF 患者的空腹血浆 PAGln 水平。在克利夫兰队列中进行了 5 年随访的全因死亡率评估，在柏林队列中进行了 3 年随访的 HF、住院或死亡率评估。在克利夫兰队列中，PAGln 中位数为 4.2（四分位距 [IQR] 2.4-6.9）μM。与最低四分位数相比，最高四分位数的 PAGln 与死亡率风险增加 3.09 倍相关。在调整传统危险因素以及种族、估算肾小球滤过率、氨基末端 pro-B 型利钠肽、高敏 C 反应蛋白、左心室射血分数、缺血病因和 HF 药物治疗后，在四分位比较中，升高的 PAGln 水平仍然预测 5 年死亡率（Q4 与 Q1 的调整后危险比 [HR] [95%置信区间，CI]：1.64 [1.07-2.53]）。在柏林队列中，观察到类似的 PAGln 水平分布（中位数 3.2 [IQR 2.0-4.8]μM），并且 PAGln 水平与 3 年 HF 住院或全因死亡率风险增加 1.92 倍相关（Q4 与 Q1 的调整后 HR [95%CI]：1.92 [1.02-3.61]）。PAGln 的预后价值似乎独立于三甲胺 N-氧化物水平。
高水平的 PAGln 与传统心脏危险因素和心肾风险标志物无关，与不良结局相关。
