Threshold of PAGln Changes: Exponential Growth Between Age and Gut Microbiota in Stroke Patients

Yang Liu¹Min Chu²Wang Delong¹Qian Li¹Jixian Lin¹Jing Zhao^1*

• ¹Department of Neurology, Minhang Hospital, Fudan University, Shanghai, Shanghai Municipality, China
• ²Department of Geriatrics, Shanghai Geriatric Medical Center, shanghai, China

Importance PAGln, a gut microbiota-derived metabolite, is linked to increased platelet reactivity and thrombosis risk. However, its relationship with age, particularly the nonlinear patterns in ischemic stroke patients, remains unclear.Objectives To explore the nonlinear relationship between age and plasma PAGln levels in ischemic stroke patients, focusing on identifying exponential growth trends and critical age thresholds.Design, Setting, and Participants 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 nonlinear 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.Main Outcomes and Measures Plasma PAGln levels and their association with age in ischemic stroke patients, evaluated through nonlinear models and regression analysis.Results Significant differences in PAGln levels were found across age quartiles (P=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 nonlinear association between age and PAGln levels was identified (P=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 (P=0.5394), while above 71, a significant exponential increase in PAGln levels was detected (P<0.0001). Subgroup analyses confirmed consistent results across various patient characteristics, with no significant interactions.Conclusions and Relevance A nonlinear 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.