Systemic Inflammation Mediates the Association Between Admission Hyperglycemia and Pulmonary Infection or Prognosis...

Hyperglycemia frequently occurs after the onset of acute ischemic stroke (AIS) and the distinct effects and mechanisms of long-term or transient hyperglycemia on stroke outcome are incompletely revealed. We aimed to investigate the potential mediating role of systemic inflammation in admission glycemia status with clinical outcome.

A total of 2233 eligible AIS patients were enrolled from January 2018 to February 2024 and followed up for 12 months. Patients were stratified into three groups: normoglycemia (NG, n = 1341), persistent hyperglycemia (PHG, n = 588) and stress-induced transient hyperglycemia (SIH, n = 304). Systemic immune-inflammation index (SII), systemic inflammation response index (SIRI) were calculated from baseline blood cell counts. The primary outcomes were in-hospital stroke-associated pneumonia (SAP) and poor functional outcome (modified Rankin Scale [mRS] >2) at 12 months.

Among the included patients, 26.3% had PHG and 13.6% developed SIH. The rates of SAP and poor prognosis were highest in SIH group, intermediate in the PHG group and lowest in the NG group. Patients in SIH group exhibited highest systemic inflammatory levels (C-reactive protein [CRP], hsCRP, lnSII, SIRI, and neutrophil-to-lymphocyte [NLR]). After adjusting for confounders identified by LASSO regression, both tertile 3 of lnSII and SIRI were significantly associated with higher risk of SAP independent of admission glycemia status. While higher lnSII and SIRI were significantly associated with poor prognosis at 12-month only in SIH group. Mediation analysis demonstrated that lnSII partially mediated the association between glycemic status and clinical outcomes (mediation proportion: 16.7% for SAP; 10.8% for prognosis), with a similar effect observed for SIRI. The prediction model incorporating clinical variables and lnSII or SIRI yielded an AUC around 0.90 for SAP and 0.84 for 12-month prognosis.

Admission hyperglycemia, particularly SIH, notably affected the incidence of SAP and poor prognosis. Systemic inflammation partially mediated the effect of hyperglycemia on clinical outcome in AIS.