Supplementary Material for: Investigating the Association between Wake-Up Stroke and Obstructive Sleep Apnea: A Meta-Analysis

<b><i>Background:</i></b> Management of wake-up stroke (WUS) is always a challenge as no clear time of onset could be ascertained, and how to choose an appropriate therapy remains unclear. Sleep-disordered breathing (SDB) has been regarded as a potential risk factor to WUS, yet no consensus was achieved. Motivated by the need for a deeper understanding of WUS and its association with sleep apnea, meta-analyses summarizing the available evidence of respiratory events and indices were conducted, and sensitivity analysis was also used for heterogeneity. <b><i>Methods:</i></b> Electronic databases were systematically searched, and cross-checking was done for relevant studies. Collected data included demographic characteristics, and sleep apnea parameters were extracted with stroke patients divided into WUS and NWUS groups. Clinical data of stroke patients accompanied with sleep apnea syndrome (OSA, SAS, and severe SAS) were also extracted for meta-analysis. <b><i>Results:</i></b> A total of 13 studies were included in the analysis. The meta-analysis results showed that OSA, SAS, and severe SAS were significantly higher in WUS patients. A significantly higher AHI (WMD 7.74, 95% CI: 1.38–14.11; <i>p</i> = 0.017) and ODI (WMD of 3.85, 95% CI: 0.261–7.438; <i>p</i> = 0.035) than NWUS patients was also observed in the analysis of respiratory indices. <b><i>Conclusion:</i></b> WUS patients have severer SDB problems compared to NWUS patients suggesting that respiratory events during sleep might be underlying the induction of WUS. Besides, the induction of WUS was significantly associated with men rather than women. Therefore, early diagnosis and management of potential WUS patients should benefit from the detection of SDB status and respiratory effects.

**背景：** 醒后卒中（wake-up stroke, WUS）的临床管理始终是一项挑战，因其发病时间难以明确，且如何选择恰当的治疗方案仍不明确。睡眠呼吸障碍（sleep-disordered breathing, SDB）被认为是醒后卒中的潜在危险因素，但目前尚未达成共识。鉴于亟需深入了解醒后卒中及其与睡眠呼吸暂停的关联，本研究对呼吸事件及相关指标的现有证据开展了荟萃分析，并采用敏感性分析处理研究间异质性。

**方法：** 系统检索电子数据库，并对相关研究进行交叉核查。收集的数据涵盖人口统计学特征，提取睡眠呼吸暂停相关参数，将卒中患者划分为醒后卒中组（WUS组）与非醒后卒中组（NWUS组）。同时提取合并睡眠呼吸暂停综合征（阻塞性睡眠呼吸暂停Obstructive Sleep Apnea, OSA、睡眠呼吸暂停Sleep Apnea, SAS及重度SAS）的卒中患者的临床资料用于荟萃分析。

**结果：** 本分析共纳入13项研究。荟萃分析结果显示，醒后卒中患者的阻塞性睡眠呼吸暂停（Obstructive Sleep Apnea, OSA）、睡眠呼吸暂停（Sleep Apnea, SAS）及重度SAS的发生率显著高于非醒后卒中患者。呼吸指标分析亦表明，醒后卒中患者的呼吸暂停低通气指数（Apnea-Hypopnea Index, AHI）（加权均数差Weighted Mean Difference, WMD 7.74，95%置信区间95% Confidence Interval, 95% CI 1.38~14.11；p=0.017）与氧减指数（Oxygen Desaturation Index, ODI）（加权均数差Weighted Mean Difference, WMD 3.85，95%置信区间95% Confidence Interval, 95% CI 0.261~7.438；p=0.035）均显著高于非醒后卒中患者。

**结论：** 与非醒后卒中患者相比，醒后卒中患者的睡眠呼吸障碍更为严重，提示睡眠期间的呼吸事件可能是诱发醒后卒中的潜在因素。此外，醒后卒中的发生与男性显著相关，而非女性。因此，通过检测潜在醒后卒中患者的睡眠呼吸障碍状态及呼吸功能，可为其早期诊断与管理带来获益。