Supplementary Material for: Diverging trends in survival and functional outcome between males and females after intracerebral hemorrhage

Background
Compared to ischemic stroke, sex differences in patient outcome following intracerebral hemorrhage (ICH) is underreported. We aimed to determine sex differences in mortality and functional outcome in a large, unselected Swedish cohort.

Methods
In this observational study, data on 22789 patients with spontaneous ICH registered in the Swedish Stroke Register between 2012–2019 were used to compare sex differences in 90-day mortality and functional outcome using multivariable Cox and logistic regression analyses, adjusting for relevant confounders. Multiple imputation was used to impute missing data.

Results
The crude 90-day mortality rate was 36.7% in females (3820/10405) and 31.7% in males (3929/12384) (female Hazard Ratio (HR) 1.20 95%CI: 1.15–1.25). In multivariable analysis, the HR for 90-day mortality following ICH in females was 0.89 (95%CI: 0.85–0.94). Age was an important driving factor for the effect of sex on mortality. After adjustment for age, vascular risk factors, and stroke severity, 90-day functional outcome in prestroke independent patients was worse in females compared to males (OR 1.27 95%CI: 1.16–1.40).

Conclusion
In this large observational study, despite a lower 90-day mortality, female sex was independently associated with a worse functional outcome compared to males after ICH, even after adjusting for significant covariates. These diverging trends have not been previously reported for ICH. Given the observational design, our findings should be interpreted with caution, thus further external validation is warranted.

研究背景
相较于缺血性脑卒中（ischemic stroke），脑出血（intracerebral hemorrhage, ICH）后患者预后的性别差异相关研究报道仍较为不足。本研究旨在针对一个大型、未经筛选的瑞典队列，明确脑出血后患者死亡率与功能预后的性别差异。

研究方法
本项观察性研究纳入了2012年至2019年间瑞典脑卒中登记库中登记的22789例自发性脑出血患者数据，通过多变量Cox回归与logistic回归分析，并校正相关混杂因素，对比分析90天死亡率与功能预后的性别差异。本研究采用多重插补法对缺失数据进行补全。

研究结果
本研究中，女性患者的粗90天死亡率为36.7%（3820/10405），男性患者为31.7%（3929/12384），女性的风险比（Hazard Ratio, HR）为1.20，95%置信区间（95%CI：1.15–1.25）。经多变量分析后，女性脑出血患者90天死亡率的HR为0.89（95%CI：0.85–0.94）。年龄是性别对死亡率影响的重要驱动因素。在校正年龄、血管危险因素及脑卒中严重程度后，卒中前已具备独立生活能力的患者中，女性的90天功能预后较男性更差（优势比OR=1.27，95%CI：1.16–1.40）。

研究结论
本项大型观察性研究结果显示，尽管女性脑出血患者的90天死亡率更低，但在校正重要协变量后，与男性相比，女性性别仍与更差的功能预后独立相关。此类相悖的趋势此前尚未见针对脑出血的相关报道。鉴于本研究为观察性设计，解读研究结果时需谨慎，因此仍需开展进一步的外部验证。