Liu Yang, Chu Min, Wang Delong, Li Qian, Lin Jixian, Zhao Jing
Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China.
Institute of Science and Technology for Brain-Inspired Intelligence (ISTBI), Fudan University, Shanghai, China.
Front Neurol. 2025 May 21;16:1576777. doi: 10.3389/fneur.2025.1576777. eCollection 2025.
phenylacetylglutamine (PAGln), a gut microbiota-derived metabolite, is linked to increased platelet reactivity and thrombosis risk. However, its relationship with age, particularly the non-linear patterns in ischemic stroke patients, remains unclear.
To explore the non-linear relationship between age and plasma PAGln levels in ischemic stroke patients, focusing on identifying exponential growth trends and critical age thresholds.
This single-center, prospective cohort study was conducted at the Department of Neurology, Minhang Hospital, Fudan University, from January 2022 to December 2023. A total of 121 patients with ischemic stroke were consecutively enrolled. Demographic information, lifestyle factors, stroke characteristics, and comorbidities were systematically collected. Plasma PAGln levels were measured using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry. Generalized additive models and smoothing curve fitting were applied to assess non-linear relationships between age and PAGln levels, with threshold effect analysis used to identify age breakpoints. Multivariable regression models were applied to adjust for confounders, and subgroup analyses tested the robustness of findings.
Plasma PAGln levels and their association with age in ischemic stroke patients, evaluated through non-linear models and regression analysis.
Significant differences in PAGln levels were found across age quartiles ( = 0.004), rising from 186.87 ± 95.49 μmol/L in the youngest quartile (35-54 years) to 433.11 ± 474.03 μmol/L in the oldest quartile (69-87 years). A non-linear association between age and PAGln levels was identified ( = 0.0006). Smoothing curve fitting revealed an exponential increase in PAGln levels with age. A threshold effect analysis pinpointed a breakpoint at 71 years. Below this age, no significant association between age and PAGln was observed ( = 0.5394), while above 71, a significant exponential increase in PAGln levels was detected ( < 0.0001). Subgroup analyses confirmed consistent results across various patient characteristics, with no significant interactions.
A non-linear exponential relationship exists between age and plasma PAGln levels in ischemic stroke patients, with a marked increase after 71 years. Elevated PAGln levels in elderly patients suggest significant metabolic dysregulation, potentially raising thrombosis risk. Monitoring PAGln levels in stroke patients over 71 years could provide valuable insights for personalized interventions to reduce thrombotic complications.
苯乙酰谷氨酰胺（PAGln）是一种源自肠道微生物群的代谢产物，与血小板反应性增加和血栓形成风险相关。然而，其与年龄的关系，尤其是缺血性中风患者中的非线性模式，仍不清楚。
探讨缺血性中风患者年龄与血浆PAGln水平之间的非线性关系，重点是识别指数增长趋势和关键年龄阈值。
设计、地点和参与者：本单中心前瞻性队列研究于2022年1月至2023年12月在复旦大学附属闵行医院神经内科进行。共连续纳入121例缺血性中风患者。系统收集人口统计学信息、生活方式因素、中风特征和合并症。使用快速分辨率液相色谱-四极杆飞行时间质谱法测量血浆PAGln水平。应用广义相加模型和平滑曲线拟合来评估年龄与PAGln水平之间的非线性关系，并使用阈值效应分析来识别年龄断点。应用多变量回归模型调整混杂因素，并进行亚组分析以检验研究结果的稳健性。
通过非线性模型和回归分析评估缺血性中风患者的血浆PAGln水平及其与年龄的关联。
在不同年龄四分位数中发现PAGln水平存在显著差异（P = 0.004），从最年轻四分位数（35 - 54岁）的186.87±95.49μmol/L上升至最年长四分位数（69 - 87岁）的433.11±474.03μmol/L。确定了年龄与PAGln水平之间的非线性关联（P = 0.0006）。平滑曲线拟合显示PAGln水平随年龄呈指数增加。阈值效应分析确定了71岁为断点。在这个年龄以下，未观察到年龄与PAGln之间的显著关联（P = 0.5394），而在71岁以上，检测到PAGln水平显著呈指数增加（P < 0.0001）。亚组分析证实了在各种患者特征中的一致结果，没有显著的相互作用。
缺血性中风患者年龄与血浆PAGln水平之间存在非线性指数关系，71岁后显著增加。老年患者中PAGln水平升高表明存在明显的代谢失调，可能会增加血栓形成风险。监测71岁以上中风患者的PAGln水平可为减少血栓并发症的个性化干预提供有价值的见解。
