Supplementary Material for: Sex Differences in Long-Term Functional Decline after Ischemic Stroke: A Longitudinal Observational Study from the Fukuoka Stroke Registry

<b><i>Introduction:</i></b> Data on sex differences in poststroke functional status for a period longer than 1 year based on large cohorts are sparse. This study aimed to determine whether there are sex differences in long-term functional decline after ischemic stroke. <b><i>Methods:</i></b> We tracked functional status for 5 years among 3-month survivors of acute ischemic stroke and compared outcomes between women and men using a large-scale hospital-based stroke registry in Fukuoka, Japan. Functional status was assessed using the modified Rankin Scale (mRS). Functional dependency was defined as an mRS score of 3, 4, or 5. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals of outcomes after adjusting for possible confounders. <b><i>Results:</i></b> A total of 8,446 patients (71.9 ± 12.5 years, 3,377 (40.0%) female patients) were enrolled in this study. Female sex was associated with a higher risk of functional dependency at 5 years poststroke even when adjusting for age, 3-month mRS score, and other confounding factors (multivariable-adjusted OR vs. men, 1.56 [95% confidence interval, 1.26–1.93]). This significant association of female sex with higher dependency at 5 years was also found among patients who were independent at 3 months poststroke. Subgroup analysis showed that increased risk of functional dependency in female patients was more marked in patients aged ≥75 years than in those aged &lt;75 years (<i>p</i> for heterogeneity = 0.02). Conversely, female sex was associated with a lower risk of death. No sex difference was observed in stroke recurrence during 5 years poststroke. <b><i>Discussion/Conclusion:</i></b> This longitudinal observational study suggests that female sex was independently associated with an increased risk of functional decline in the chronic phase of stroke, especially in older patients. There was no sex difference in 5-year stroke recurrence, and thus, other factors might be involved in more significant deterioration of functional status in female survivors of ischemic stroke. Further studies are needed to elucidate underlying causes of sex differences in long-term functional decline after stroke.

**引言**：基于大型队列的卒中后1年以上功能状态性别差异相关数据较为匮乏。本研究旨在明确缺血性卒中患者长期功能衰退是否存在性别差异。
**方法**：依托日本福冈市大型医院卒中登记库，对急性缺血性卒中发病后存活满3个月的患者开展为期5年的功能状态追踪，对比女性与男性的转归结局。采用改良Rankin量表（modified Rankin Scale, mRS）评估功能状态，以mRS评分3、4、5分定义为功能依赖。通过logistic回归分析校正潜在混杂因素后，估算结局的比值比（OR）及95%置信区间（CI）。
**结果**：本研究共纳入8446例患者（年龄71.9±12.5岁，女性3377例，占比40.0%）。在校正年龄、发病3个月时的mRS评分及其他混杂因素后，女性性别仍与卒中后5年更高的功能依赖风险相关（多因素校正OR相较于男性为1.56，95%置信区间1.26~1.93）。在卒中后3个月时功能独立的患者亚组中，同样观察到女性与5年更高功能依赖风险存在显著关联。亚组分析显示，年龄≥75岁的女性患者，其功能依赖风险的升高幅度较年龄<75岁者更为显著（组间异质性检验P值为0.02）。与之相反，女性性别与更低的死亡风险相关。卒中后5年内的卒中复发率未观察到性别差异。
**讨论与结论**：这项纵向观察性研究表明，女性性别与卒中慢性期功能衰退风险升高独立相关，这一关联在老年患者中尤为显著。5年卒中复发率未发现性别差异，因此缺血性卒中女性幸存者功能状态更显著恶化可能与其他因素有关。未来仍需开展进一步研究以阐明卒中后长期功能衰退存在性别差异的潜在机制。