Nonlinear association between hematocrit and 3-month outcome after acute ischemic stroke: identification of threshold effects in males

Objective Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Hematocrit (HCT), the proportion of blood volume occupied by red blood cells, has been associated with outcome in AIS patients, but the relationship remains controversial. This study aimed to investigate the association between HCT levels and 3-month adverse outcome in South Korean patients with AIS, with a focus on potential sex differences. Methods This secondary analysis utilized data from an existing South Korean prospective cohort study involving 1,896 AIS patients. HCT was assessed both as a continuous variable and categorized into quartiles. The outcome was 3-month adverse outcome, defined as a modified Rankin Scale score ≥ 3. Logistic regression models were employed to evaluate the relationship between HCT and adverse outcome in both the overall population and sex-stratified subgroups. Nonlinear associations were explored using generalized additive models and two-piecewise linear regression analysis. Results Our study included 1,896 AIS patients, comprising 1,163 males (61.34%) and 733 females (38.66%). The age distribution was as follows: < 60 years (22.89%), 60–70 years (26.53%), 70–80 years (35.07%), and ≥ 80 years (15.51%). The probability of adverse outcome was 28.53%. Females were more likely to experience unfavorable outcome (35.20%) compared to males (24.33%). A nonlinear relationship was identified in the overall population, with HCT levels below 34.4% demonstrating a 15% risk reduction per 1% increase (OR = 0.85, 95% CI 0.78–0.92, P = 0.0001). In males, a similar nonlinear relationship was observed, with HCT levels below 36.4% (95% CI 32.2–38.6%) associated with a 19% risk reduction per 1% increase (OR = 0.81, 95% CI 0.74–0.88, P < 0.0001). However, no significant association was found in female patients. Conclusion This study revealed a nonlinear, sex-specific relationship between HCT and 3-month outcome in AIS patients. In male patients, HCT levels below the threshold were inversely associated with adverse outcome, while no significant association was observed in female patients.