Sex Modifies the Association Between Neutrophil Percentage-to-Albumin Ratio and Stroke-Associated Pneumonia in Acute Ischemic Stroke.

BACKGROUND: Stroke-associated pneumonia (SAP) is a common and serious complication in patients with acute ischemic stroke (AIS), leading to prolonged hospitalization and poor prognosis. The neutrophil percentage-to-albumin ratio (NPAR), a novel inflammatory biomarker, has been linked to stroke-associated infections; however, no prior study has characterized the dose-response relationship between NPAR and SAP or explored potential sex-based effect modification. METHODS: This retrospective cohort study included 1008 patients with AIS. NPAR was calculated as neutrophil percentage divided by serum albumin level (g/L) at admission. SAP was defined as pneumonia occurring within 7 days of stroke onset. Multivariable logistic regression models were constructed to evaluate the association between NPAR and SAP, with NPAR analyzed both as a continuous variable (per 0.1-unit increase) and as tertiles. Restricted cubic spline (RCS) analysis was performed to assess the dose-response relationship. Subgroup analyses with interaction tests were conducted to explore potential effect modification, including by sex. RESULTS: Among 1008 AIS patients (mean age 62.18 years; 68.25% male), 90 (8.93%) developed SAP. After full adjustment, each 0.1-unit increase in NPAR was independently associated with SAP (OR = 1.22; 95% CI: 1.13-1.32; P < 0.001), with a linear dose-response relationship (P for nonlinearity = 0.80). Patients in the highest NPAR tertile had approximately 5-fold higher odds of SAP compared with the lowest tertile (OR = 5.18; P < 0.001). A significant sex-based interaction was identified (P = 0.01): the association was prominent in males (OR = 1.38; P < 0.001) but non-significant in females (OR = 1.11; P = 0.09). Sex-stratified ROC analysis further confirmed this difference, with a significantly higher AUC in males (0.77) than in females (0.58; DeLong P < 0.05). CONCLUSION: Higher NPAR is independently and linearly associated with an increased risk of SAP in AIS patients, with a significant dose-response relationship. This association is significantly stronger in males than in females. NPAR may serve as a readily accessible and cost-effective candidate biomarker for early risk stratification of SAP, particularly in male AIS patients, pending external validation in prospective, multi-center studies.