Association of plasma ceramide with stroke-associated pneumonia in acute ischemic stroke

Hao Li¹Mengwen Lu¹Xinyi Ye¹Xinyan Guo¹Tianyu Ma¹Zhouao Zhang¹Mingjin Yang¹Xue Du²Yingying Wang³Huang Xiao-Yu¹Ying Sheng^1,4Yu Bi⁵Yong Zhang^1*

• ¹The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
• ²The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
• ³Suzhou Ninth People's Hospital, Suzhou, China
• ⁴Tongji University School of Medicine, Shanghai, China
• ⁵Fengxian People’s Hospital, Xuzhou, China

Background: Stroke-associated pneumonia (SAP) is a common and severe complication of acute ischemic stroke (AIS), yet its occurrence remains unpredictable. Post-stroke immune dysregulation and systemic inflammatory responses play a crucial role in susceptibility to SAP, highlighting the need for immune-related biomarkers. Ceramide (Cer) is kind of bioactive sphingolipids involved in inflammatory signaling and immune cell regulation, and has been implicated in infection and inflammatory diseases. This study aims to explore the association between Cer and SAP and evaluate the predictive value for SAP occurrence. Methods: This study retrospectively collected a total of 266 eligible patients with AIS and 93 healthy controls. Demographic and clinical data, as well as the concentrations of plasma C16:0-Cer, C18:0-Cer, C24:1-Cer, and C24:0-Cer, were obtained from medical records and were compared before and after propensity score matching. The least absolute shrinkage and selection operator (LASSO) regression was utilized to select variables, and risk factors were detected by multivariate analysis. The predictive values were evaluated by receiver operating characteristic curves. Results: The levels of C16:0-Cer, C18:0-Cer, C24:1-Cer, C24:0-Cer and Coronary Event Risk Test 1 (CERT1) score were higher in patients with AIS than healthy controls, in which C16:0-Cer, C18:0-Cer and CERT1 score significantly elevated in SAP patients compared with non-SAP patients. Patients with minor ischemic stroke had lower levels of C16:0-Cer, C18:0-Cer and CERT1 score with those with moderate and severe ischemic stroke. Meanwhile, levels of C16:0-Cer, C18:0-Cer and CERT1 score were positively correlated with the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) score. The A2DS2 score, C16:0-Cer, high-sensitivity C-reactive protein, and neutrophil-to-lymphocyte ratio were identified as independent risk factors for SAP. C16:0-Cer exhibited a predictive value with an area under curve of 0.725, sensitivity of 74.0%, and specificity of 61.2% for SAP. Conclusion: Plasma C16:0-Cer, C18:0-Cer, and CERT1 scores were significantly elevated in patients with AIS and SAP. Among them, C16:0-Cer served as an independent predictor for SAP in AIS patients. It demonstrated moderate predictive accuracy, suggesting its potential as a novel biomarker for early SAP risk stratification.