Elsevier

Sleep Medicine

Volume 76, December 2020, Pages 43-47
Sleep Medicine

Original Article
Sleep-disordered breathing and wake-up stroke: a differential association depending on etiologic subtypes

https://doi.org/10.1016/j.sleep.2020.09.030Get rights and content

Highlights

  • Obstructive sleep apnea increases the risk for wake-up stroke in men.

  • Large artery atherosclerosis has a greater risk for wake-up stroke related with snoring.

  • Small vessel occlusion has a greater risk for wake-up stroke related with apnea.

Abstract

Background and purpose

Obstructive sleep apnea (OSA) is a modifiable risk factor for stroke, but there are limited data on which stroke subtypes are associated with OSA. The aim of this study was to assess the risk for wake-up stroke (WUS) associated with OSA according to each etiologic subtype to elucidate the pathophysiologic mechanism of OSA-associated stroke.

Method

We investigated 557 consecutive patients who were admitted with acute ischemic stroke in two regional comprehensive stroke centers using a standardized protocol including the Berlin questionnaire to identify symptoms of OSA prior to stroke. The collected stroke data included the time of onset, risk factors, and etiologic subtype. Stratified analysis according to sex was conducted because sex has been reported to be an effect modifier of OSA on cardiovascular outcomes. The association between preexisting OSA symptoms and WUS depending on etiologic subtypes was assessed using multivariate logistic regression analysis.

Results

Preexisting OSA symptoms were associated with the risk of overall WUS in men. Snoring was associated with WUS in large artery atherosclerosis [adjusted odds ratio, 2.67 (1.15–6.23)], and apnea was associated with WUS in small vessel occlusion [adjusted odds ratio, 8.21 (1.15–58.53)], whereas OSA symptoms were not significantly associated with WUS in cardioembolism. Associations between OSA and WUS were not found in women.

Conclusion

This study demonstrated the differential influences of OSA on WUS depending on etiologic subtypes, suggesting more vulnerability in large artery atherosclerosis and small vessel occlusion. Sex is a significant effect modifier of the association between OSA and WUS.

Introduction

Obstructive sleep apnea (OSA) is a prevalent and modifiable risk factor for stroke [1]. The association between OSA and ischemic stroke may be explained by indirect effects mediated by increases in hypertension, obesity and atrial fibrillation in OSA syndrome as well as the direct effect of OSA events [2]. Recent observational studies have shown that OSA is associated particularly with stroke occurring during sleep, called wake-up stroke (WUS), suggesting that OSA directly contributes to the occurrence of stroke [3,4]. The plausible mechanisms involved in the occurrence of WUS in OSA patients include deoxygenation of brain tissue, fluctuations in cerebral blood flow and velocity, paradoxical embolism induced by apnea events, plaque disruption associated with vibration, and hypercoagulability [[5], [6], [7], [8], [9]].

However, it remains unclear which group is at greater risk for WUS associated with OSA. A differential association between OSA and WUS according to sex was observed in a recent study [10]. There has been no report dealing with the association between OSA and WUS based on the etiologic subtypes of stroke.

The aim of this study was to assess the risk for WUS associated with OSA according to stroke subtypes and to elucidate the pathophysiologic mechanism of WUS in those with OSA.

Section snippets

Methods

We consecutively evaluated adult patients who were admitted with acute ischemic stroke in two regional comprehensive stroke centers (CSCs). The first study was conducted between December 1, 2013, and April 30, 2015, at Kangwon National University Hospital, and an extended study was conducted between July 5, 2017, and March 2, 2018, at Kangwon National University Hospital and between May 22 and February 28, 2018, at Chungbuk National University Hospital. We included patients with acute ischemic

Results

A total of 618 patients met the inclusion criteria during the study period. We could not conduct interviews with the Berlin questionnaire for 41 patients because of early discharge, a critical condition, or no caregiver who could respond. Among the 577 eligible patients, 20 patients could not be categorized into either the WUS or the non-WUS group. Therefore, 557 patients, including 120 (21.5%) with WUS, were included in the final analysis.

Snoring every other day or more was reported in 208

Discussion

This study demonstrated the increased risk of WUS in men with underlying OSA, particularly in LAA and SVO. This result from a large group of patients with acute stroke again raises the possibility that OSA may trigger ischemic stroke. The differential risk of WUS related to OSA depending on the etiologic subtypes is a novel finding.

Previous knowledge of the association between underlying OSA and the occurrence of ischemic stroke subtype is limited. A prospective study demonstrated that

Source of funding

This study was supported by a 2017 Research Grant from the Korean Sleep Research Society.

Ethical standards

All authors of this study understood and observed the ethical standards laid out in the Declaration of Helsinki. All details disclosing the identity of subjects have been omitted from the analyses and this manuscript.

CRediT authorship contribution statement

Jeonghoon Park: Writing - original draft. Minju Yeo: Investigation. Jinsu Kim: Investigation. Seongheon Kim: Resources. Sungok Kwon: Formal analysis. Dong-Ick Shin: Investigation. Sangkil Lee: Resources, Resources. Seo-Young Lee: Project administration, Writing - review & editing, Conceptualization, Investigation.

Acknowledgements

We would like to thank Hee-Jung Nam, RN, of Kangwon National University Hospital and Su-jin Park, RN, of Chungbuk National University Hospital for interviewing patients regarding their OSA symptoms.

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