Elevated phenylalanine has been observed in patients with advanced heart failure (HF) and in community cohorts at risk of HF, and has been shown to have prognostic value. This study aimed to explore the factors associated with elevated phenylalanine in HF patients. Mass spectrometry was performed on blood from 669 participants, including 75 normal controls and 594 HF patients (stages A, B, and C). We measured phenylalanine and associated degradation products on the catecholamine pathway, C-reactive protein, valerylcarnitine, methionine sulfoxide, estimated glomerular filtration rate (eGFR), and B-type natriuretic peptide. Longitudinal analysis was conducted on 61 stage C HF patients who had recovered systolic function after 1 year. Phenylalanine and tyrosine levels increased from normal through stages A, B and C. Cross-sectional analysis in patients at stage C showed that phenylalanine levels were related to total bilirubin, eGFR, valerylcarnitine, methionine sulfoxide, C-reactive protein, and male gender. Longitudinal analysis in the patients at stage C with recovered systolic function after 1 year revealed that phenylalanine, tyrosine, methionine sulfoxide, total bilirubin, and C-reactive protein levels significantly decreased from baseline to 12 months. Based on a generalized estimating equations analysis model with time interaction considered, the only significant factor associated with changes in phenylalanine was changes in C-reactive protein concentrations from baseline to 12 months [B (coefficient) = 0.81, P < 0.001] after adjusting for methionine sulfoxide and total bilirubin levels. In conclusion, phenylalanine levels respond sensitively to HF improvement. Our findings suggest that inflammation plays a pivotal role in the elevation of phenylalanine levels in patients with HF.

已在晚期心力衰竭 (HF) 患者和有 HF 风险的社区队列中观察到苯丙氨酸升高，并已证明具有预后价值。本研究旨在探讨与 HF 患者苯丙氨酸升高相关的因素。对 669 名参与者的血液进行了质谱分析，其中包括 75 名正常对照和 594 名 HF 患者（A、B 和 C 期）。我们测量了苯丙氨酸和儿茶酚胺通路相关的降解产物、C 反应蛋白、戊酰肉碱、甲硫氨酸亚砜、估计的肾小球滤过率 (eGFR) 和 B 型利钠肽。对 61 名 1 年后恢复收缩功能的 C 期 HF 患者进行纵向分析。苯丙氨酸和酪氨酸水平从正常水平通过 A、B 和 C 阶段增加。C 期患者的横断面分析表明，苯丙氨酸水平与总胆红素、eGFR、戊酰肉碱、甲硫氨酸亚砜、C 反应蛋白和男性相关。1 年后收缩功能恢复的 C 期患者的纵向分析显示，苯丙氨酸、酪氨酸、甲硫氨酸亚砜、总胆红素和 C 反应蛋白水平从基线到 12 个月显着下降。基于考虑了时间相互作用的广义估计方程分析模型，与苯丙氨酸变化相关的唯一重要因素是 C 反应蛋白浓度从基线到 12 个月的变化。1 年后收缩功能恢复的 C 期患者的纵向分析显示，苯丙氨酸、酪氨酸、甲硫氨酸亚砜、总胆红素和 C 反应蛋白水平从基线到 12 个月显着下降。基于考虑了时间相互作用的广义估计方程分析模型，与苯丙氨酸变化相关的唯一重要因素是 C 反应蛋白浓度从基线到 12 个月的变化。1 年后收缩功能恢复的 C 期患者的纵向分析显示，苯丙氨酸、酪氨酸、甲硫氨酸亚砜、总胆红素和 C 反应蛋白水平从基线到 12 个月显着下降。基于考虑了时间相互作用的广义估计方程分析模型，与苯丙氨酸变化相关的唯一重要因素是 C 反应蛋白浓度从基线到 12 个月的变化。B（系数）= 0.81，P  < 0.001] 调整甲硫氨酸亚砜和总胆红素水平后。总之，苯丙氨酸水平对 HF 改善敏感。我们的研究结果表明，炎症在 HF 患者苯丙氨酸水平升高中起关键作用。