Supplementary Material for: Cerebrovascular Accident Risk in a Population with Periodic Limb Movements of Sleep: A Preliminary Meta-Analysis

<b><i>Background and Purpose:</i></b> Periodic limb movements of sleep (PLMS) are usually comorbid with hypertension, tachycardia, and coronary arterial diseases, which are also risk factors for cerebrovascular accidents (CVA). However, evidence about the relationship between CVA and PLMS is still weak. The aim of this study was to investigate (1) the prevalence of CVA in patients with PLMS, and (2) the severity of PLMS in patients with or without CVA through a meta-analysis. <b><i>Methods:</i></b> The electronic databases of PubMed, Embase, ScienceDirect, ClinicalKey, Cochrane Library, ProQuest, Web of Science, and ClinicalTrials.gov were searched. The inclusion criteria were (1) articles investigating comorbidity between PLMS and CVA, and (2) clinical trials in humans. <b><i>Results:</i></b> This meta-analysis included (1) 9,823 patients with PLMS and 9,416 controls from 5 studies to analyze the prevalence of CVA in PLMS, and (2) 158 patients with PLMS with CVA and 88 PLMS controls without CVA from 3 studies to analyze the severity of PLMS with and without CVA. The results showed (1) significantly higher comorbidity rates of CVA in the patients with PLMS than in the controls without PLMS (OR 1.267, <i>p</i> = 0.019), and (2) higher PLM index in the patients with CVA than in the controls (Hedges’ <i>g</i> = 0.860, <i>p</i> = 0.001; means difference: 4.435, <i>p</i> = 0.016). <b><i>Conclusions:</i></b> The results revealed (1) a worse severity of PLMS in the patients with CVA, and (2) increased prevalence of CVA in the patients with PLMS. Based on our results, the patients had a higher prevalence of CVA within 8 years of a diagnosis of PLMS compared to those without PLMS by about 1.3-fold. Whether (1) patients with PLMS receiving treatment have a similar incidence of stroke to those without PLMS, and (2) secondary stroke prevention can lower the severity of PLMS or whether those with severe PLMS have a higher risk of stroke is still inconclusive. Future studies investigating the prevalence of CVA in patients with PLMS should use a follow-up period of over 8 years.

**背景与目的：** 睡眠周期性肢体运动（Periodic Limb Movements of Sleep, PLMS）常与高血压、心动过速及冠状动脉疾病共病，而上述疾病亦为脑血管意外（Cerebrovascular Accidents, CVA）的危险因素。然而，目前关于CVA与PLMS之间关联的研究证据仍较为薄弱。本研究旨在通过荟萃分析完成两项目标：其一，明确PLMS患者中CVA的患病率；其二，对比伴或不伴CVA的患者的PLMS严重程度。
**方法：** 检索PubMed、Embase、ScienceDirect、ClinicalKey、Cochrane图书馆、ProQuest、Web of Science及ClinicalTrials.gov等电子数据库。纳入标准为：（1）探讨PLMS与CVA共病关系的研究；（2）针对人类的临床试验。
**结果：** 本项荟萃分析共纳入两项分析：（1）来自5项研究的9823名PLMS患者与9416名对照者，用于分析PLMS患者的CVA患病率；（2）来自3项研究的158名伴CVA的PLMS患者与88名不伴CVA的PLMS对照者，用于分析伴或不伴CVA的PLMS患者的病情严重程度。结果显示：（1）PLMS患者的CVA共病率显著高于无PLMS的对照人群（比值比（Odds Ratio, OR）=1.267，p=0.019）；（2）伴CVA患者的PLM指数显著高于对照人群（赫奇斯g值（Hedges’ g）=0.860，p=0.001；均数差=4.435，p=0.016）。
**结论：** 本研究结果表明：（1）伴CVA患者的PLMS严重程度更高；（2）PLMS患者的CVA患病率有所升高。基于本研究结果，相较于无PLMS的人群，PLMS确诊后8年内的CVA患病率约高出1.3倍。目前仍存在两个尚未明确的问题：其一，接受治疗的PLMS患者的卒中发病率是否与无PLMS人群相当；其二，卒中二级预防是否可降低PLMS的严重程度，抑或重度PLMS患者的卒中风险是否更高。未来针对PLMS患者CVA患病率的研究，应采用8年以上的随访周期。