A Mediation Analysis of the Association Between Systemic Inflammation Response Index, in-Hospital Complications, and Poor Long-Term Functional Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage: Insights from a Large Prospective Cohort Study

Tu Li,1 Runting Li,1 Fa Lin,1 Xiaolin Chen1– 3 1Department of Neurosurgery, Beijing Tiantan Hospital, Beijing, People’s Republic of China; 2Stroke Center, Beijing Institute for Brain Disorders, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xiaolin Chen, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Beijing, Fengtai District, 100070, People’s Republic of China, Email chenxiaolin@bjtth.orgPurpose: Early systemic inflammatory changes are increasingly recognized as factors influencing outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Systemic inflammation response index (SIRI), an inflammation biomarker, was thought to be associated with adverse outcomes in many other diseases. However, in aSAH, research on SIRI remains limited. Thus, our objective was to investigate the association between SIRI and poor long-term functional outcomes while evaluating the mediating role of in-hospital complications in this association.Patients and Methods: SIRI was defined as neutrophil count × monocyte count/lymphocyte count. Patients were categorized according to SIRI quartiles. Stabilized inverse probability of treatment weighting (sIPTW) was utilized to minimize group differences. The association between SIRI and in-hospital complications as well as poor 90-day functional outcomes (mRS 3– 6) was estimated by multivariable logistic regression analyses. Mediation analysis was performed to investigate the relationship between SIRI and poor functional outcomes mediated by in-hospital complications.Results: A total of 650 patients were prospectively included. After sIPTW, compared to the lowest quartile, an elevated SIRI was associated with delayed cerebral ischemia (DCI) (OR 2.12, 95% CI 1.20– 3.74), post-operative pneumonia (POP) (OR 2.16, 95% CI 1.29– 3.62) and poor 90-day functional outcomes (OR 3.03, 95% CI 1.55– 5.91). In-hospital complications including DCI (mediation proportion, 18.18% before sIPTW and 20.0% after sIPTW) and POP (mediation proportion, 18.18% before sIPTW and 26.7% after sIPTW) partially mediated the association between SIRI and poor 90-day functional outcomes. Mediation analysis yielded comparable results in subgroups stratified by age and sex.Conclusion: In this study, SIRI was associated with poor long-term functional outcomes in aSAH, which was partially mediated by DCI and POP with a mediation proportion exceeding 18%. Our findings might underscore the potential utility of SIRI in prompting physicians to address systemic inflammatory status timely to prevent in-hospital complications, including DCI and POP, and ultimately improve long-term functional outcomes.Keywords: aneurysmal subarachnoid hemorrhage, systemic inflammation response index, complications, functional outcomes, mediation analysis