The interactive effect of sex and neutrophil-to-lymphocyte ratio on short-term poor outcomes in patients with nonvalvular atrial fibrillation-related acute cardioembolic stroke.

OBJECTIVE: To investigate the association of sex and neutrophil-to-lymphocyte ratio (NLR) differences with short-term adverse outcomes in patients with non-valvular atrial fibrillation (NVAF)-related cardioembolic stroke (CES). METHODS: Patients hospitalized in the Department of Neurology at Hefei Hospital Affiliated to Anhui Medical University between January 2023 and August 2024 with NVAF-related CES were retrospectively enrolled. Outcomes were assessed at the time of discharge or on the 14th day after onset of CES based on the modified Rankin Scale (mRS), with a score ≤ 2 defined as a good outcome and a score > 2 defined as an adverse outcome. NLR was calculated based on laboratory tests performed within 24 h of admission. Multivariable logistic regression analysis was used to identify independent risk factors. Additive interaction models (Relative Excess Risk due to Interaction [RERI], Attributable Proportion [AP], Synergy Index [SI]) and multiplicative interaction models were employed to quantify interaction effects. Bootstrap analysis was used to assess the combined effect risk. RESULTS: A total of 196 patients were enrolled, including 109 females (55.61%). Females were older (82.00 (75.00, 85.00) vs 79.00 (72.00, 83.00) years, P = 0.047) and had lower NLR (5.16 ± 2.93 vs 6.36 ± 5.17, P = 0.057),but a higher risk of adverse outcomes compared to males (55.96% vs 42.53%, P = 0.062). Multivariable logistic regression analysis showed that higher baseline NIHSS score [OR (95%CI) 1.088 (1.023 ~ 1.157)], high NLR[OR (95%CI) 1.279 (1.111 ~ 1.472)], and female[OR (95%CI) 2.288 (1.017 ~ 5.149)] as independent risk factors for short-term adverse outcomes. Additive interaction analysis (Model3: RERI = 0.892, AP = 0.276, SI = 1.665) and multiplicative interaction analysis using continuous NLR [OR (95%CI) 1.688 (1.206 ~ 2.363)] indicated a positive synergistic effect between sex and NLR. Joint effect analysis showed that female patients with higher NLR had a 15.2-fold increased risk of adverse outcomes compared to male patients with lower NLR [OR (95%CI) 15.158 (5.303 ~ 92.832)]. CONCLUSIONS: Baseline NIHSS score, NLR, and female sex are independent predictors for short-term adverse outcomes in NVAF-related CES. Our findings suggest a potential synergistic interaction between sex and NLR, particularly on the multiplicative scale, indicating that the risk of adverse outcomes may be disproportionately higher in female patients with elevated NLR. Further clinical research should focus on monitoring inflammatory status in female patients and exploring personalized interventions.