The expression changes endothelial and fibrinolytic biomarkers in acute ischemic stroke patients with OSA

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Methods Data were gathered from 80 patients with AIS who were admitted to the First Hospital of Jilin University between January 2023 and December 2023. Out of these, 60 patients completed the NIHSS Scale, ESS Scale, STOP-Bang Scale, and underwent polysomnography within a week of symptom onset. Based on the apnea-hypopnea index (AHI) score, patients were categorized into three groups: 15 in the non-exposed group (AHI 15). Serum levels of fibrinogen, E-selectin, and t-PA were determined using enzyme-linked immunosorbent assay. Results Polysomnography results indicated AIS with OSA had an increased arousal index and oxygen desaturation index (P < 0.001). Additionally, serum levels of fibrinogen, E-selectin, and t-PA were markedly elevated in the moderately-severely exposed group compared to the non-exposed group (P < 0.001), and these levels positively correlated with the severity of OSA. ROC curves showed the sensitivities of serum of fibrinogen, E-selection, and t-PA was 84.4%, 80%, and 82.2%, respectively, and the specificities of 60%, 66.7%, and 66.7%, compared with that of PSG respectively. Conclusion The expression of serum fibrinogen, E-selectin, and t-PA is elevated in AIS with OSA and correlates with the severity of OSA. obstructive sleep apnea syndrome acute ischemic stroke fibrinogen E-selectin tissue-type plasminogen activator Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Acute ischemic stroke (AIS) is an acute focal neurological impairment caused by cerebrovascular ischemia. Globally, it is one of the major causes of disability and death, with approximately 3.29 million deaths annually[ 1 ]. Patients with AIS face a high risk of recurrence within five years, highlighting the critical need for research and intervention in modifiable risk factors. Sleep-disordered breathing (SDB) is a prevalent chronic condition affecting nearly 936 million people globally, with 425 million experiencing moderate to severe obstructive sleep apnea (OSA)[ 2 ]. OSA is marked by repeated episodes of partial (hypopnea) or complete (apnea) blockage of airflow during sleep, causing intermittent hypoxia and fragmented sleep. These disruptions result in daytime drowsiness, fatigue, irritability, lack of concentration, and even cognitive impairment[ 3 ]. The severity of OSA is determined using the apnea-hypopnea index (AHI). This classification is broken down into three categories: mild (AHI between 5 and 15), moderate (AHI between 15 and 30), and severe (AHI 30 or higher)[ 4 ]. Seiler et al. discovered that the incidence of sleep apnea in patients with AIS is 71%, nearly four times that of the masses[ 5 ]. Not only does OSA directly increase the risk of stroke as an independent risk factor, but it also worsens other cardiovascular risk factors, such as high blood pressure and arrhythmias, significantly impacting stroke prognosis[ 6 ]. Although polysomnography is the definitive test for the diagnosis of OSA, its complexity, requirement for extensive medical personnel, and high cost can delay diagnosis and treatment. Advancements in biomarker research have shown that specific biomarkers in OSA patients could be crucial for predicting diagnosis, disease severity, and response to therapy[ 7 – 9 ]. However, studies on endothelial function and the fibrinolytic system in AIS patients with OSA are relatively scarce. This study aims to investigate the expression of serum t-PA, E-selectin, and fibrinogen in AIS with OSA and assess their diagnostic value for AIS combined with OSA. Methods The study was approved by the ethics committee of the First Hospital of Jilin University and was conducted in accordance with the Declaration of Helsinki (Approval No. 24K042-001). All participants and their guardians gave informed consent. Participants We recruited 80 acute ischemic stroke (AIS) patients who were enrolled in the Department of Neurology of the First Hospital of Jilin University between January 2023 to December 2023. Finally, 60 patients underwent polysomnography (PSG) within a week of symptom onset. Given the frequency of OSA in AIS patients (71%) [5], the patients were collected in a 1:3 ratio and categorized into two groups: 15 patients in the non-exposed group (AIS without OSA) and 45 patients in the exposed group (AIS with OSA). The exposed group was further divided into mildly exposed (5 ≤ AHI ≤ 15; n=15) and moderately-severely exposed (AHI > 15; n=30) according to the apnea-hypopnea index (AHI) score. Inclusion and Exclusion Criteria The inclusion criteria included: 1. Non-exposed group: age, gender, cerebral infarction site matched with exposed group, and no sleep disorder in PSG. 2. Exposed group: (1) Diagnosed with OSA according to the International Classification of Sleep Disorders (ICSD), 3rd edition; (2) aged between 18 and 65 years; (3) and having a cerebral infarction located in the region dominated by the internal carotid artery system with a maximum infarct lesion diameter greater than 20 mm. The exclusion criteria included: (1) Patients with TIA or acute ischemic stroke undergoing endovascular therapy or intravenous thrombolysis; (2) Patients with sleep disorders excluding OSA; (3) Patients with comorbid respiratory conditions, including acute respiratory infections, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), lung infections, bronchiectasis, and bronchial asthma; (4) recent use of medications affecting sleep breathing (benzodiazepines, sedative antidepressants, opioids, etc.); (5) Generalized Anxiety Disorder-7 (GAD-7) score ≥ 9 or Patient Health Questionnaire-9 (PHQ-9) score ≥ 5. Clinical Data All patients underwent comprehensive clinical data collection on admission, including age, sex, height, weight calculated body mass index (BMI), Epworth Sleepiness Scale (ESS) assessment, National Institutes of Health Stroke Scale (NIHSS) assessment, STOP-Bang questionnaire, past medical history, neurologic examination, and head imaging of stroke site and maximum infarct lesion diameter. Polysomnography Polysomnography (PSG) was used to monitor all patients for at least 8 hours at our hospital's sleep center (Compumedics, Australia). Results of the PSG have been scored by certified PSG technologists., following the American Academy of Sleep Medicine's revised interpretation criteria for sleep stages and related events, version 2.6. Apnea was diagnosed as a fall in peak temperature sensor excursion of ≥ 90% of baseline, lasting for at least two respiratory cycles. Hypopnea was considered as ≥ 30% decline in nasal pressure signal excursion from pre-event baseline, lasting at least two breathing cycles, with ≥ 3% desaturation in blood oxygen saturation or associated arousal. The apnea-hypopnea index (AHI) was computed as the mean number of apnea and/or hypopnea events per hour of sleep. Oximetric measures derived from PSG channels included the oxygen desaturation index (ODI), minimum oxygen saturation of arterial blood (Min SaO 2 ), and mean oxygen saturation of arterial blood (Mean SaO 2 ). ODI was calculated as the number of events per hour in which the decrease in oxygen saturation was ≥ 3% from baseline. Fibrinogen, E-selection, and t-PA Serum Level Detection Blood samples were taken from all patients the following morning after an 8-hour fast on enrolment and processed by centrifugation at 3000 rpm for 10 minutes. Serum was kept at -80°C until the time of testing. Serum levels of fibrinogen, E-selectin, and tissue-type plasminogen activator (t-PA) were detected using enzyme-linked immunosorbent assay (ELISA) kits (Jianglai Biotechnology Co., Ltd., Shanghai, China). Statistical Analysis IBM SPSS Statistics for Windows version 26.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. The Shapiro-Wilk test was used to examine the normal distribution of continuous variables. Data with a normal distribution were expressed as mean ± standard deviation, while data with a skewed distribution were expressed as median with interquartile range. Categorical data were presented as absolute values and percentages. Differences between multiple groups of independent samples were compared using one-way analysis of variance (ANOVA) or the Kruskal-Wallis H test, for data distribution. The Pearson correlation test was employed to examine the relationship between the apnea-hypopnea index and serum levels of fibrinogen, E-selectin, and t-PA. Receiver operating characteristic (ROC) curves were generated to calculate the sensitivity, specificity, and cut-off points for fibrinogen, E-selectin, and t-PA serum levels in predicting OSA, based on the Youden index. Results Baseline Characteristics Sixty patients were included in this study, divided into three groups: 15 in the non-exposed group, 15 in the mildly exposed group and 30 in the moderately-severely exposed group. There were no significant differences among the groups in terms of age, gender, NIHSS score, smoking history, drinking history, hypertension, diabetes mellitus, and hyperlipidemia. However, BMI (P = 0.001), ESS scores (P = 0.003), and STOP-Bang scores (P < 0.001) were significantly higher in the moderately-severely exposed group compared to the non-exposed group (Tables 1 and 2). Table 1 Clinical characteristics of acute ischemic stroke among different groups Control group (15) Mildly exposed group (15) Moderately-Severely exposed group (30) P-value Age, years 61.67±9.28 58.40±9.57 57.49±9.09 0.344 Male, n (%) 10(66.7) 7(70.0) 27(77.1) 0.720 BMI, kg/m 2 22.79±2.25 25.43±4.06 27.26±4.06 0.001 Smoke, n (%) 5(33.3) 7(70.0) 17(48.6) 0.200 Drink, n (%) 2(13.3) 5(50.0) 13(37.1) 0.124 Hypertension, n (%) 13(86.7) 5(50.0) 26(74.3) 0.158 Hyperlipidemia, n (%) 3(20.0) 3(30.0) 14(40.0) 0.377 Diabetes, n (%) 4(26.7) 2(20.0) 16(45.7) 0.215 Abbreviation: BMI, body mass index. Table 2 The scale of NIHSS、ESS、STOP-Bang in different groups Non-exposed group (15) Mildly exposed group (15) Moderately-Severely exposed group (30) P-value NIHSS 3.67±2.41 4.30±3.02 4.49±2.59 0.601 ESS 6.13±2.53 5.20±3.39 9.69±4.87 0.003 STOP-Bang 3.20±0.78 3.30±1.64 5.11±1.57 ＜0.001 Abbreviation: NIHSS, National Institute of Health stroke scale, ESS, Epworth Sleepiness Scale. Polysomnography Parameters Polysomnography (PSG) parameters showed that AIS patients with OSA had a higher proportion of stage N1 sleep (P = 0.002) and a lower proportion of stage N3 sleep (P < 0.001). Additionally, these patients exhibited an increased arousal index and oxygen desaturation index (ODI) (P < 0.001), and decreased minimum and mean oxygen saturation levels (P < 0.001) (Table 3). Table 3 The PSG parameters of acute ischemic stroke in different groups Non-exposed group (15) Mildly exposed group (15) Moderately-Severely exposed group (30) P-value TST, min 400.07±45.39 399.05±42.33 395.19±69.31 0.978 Sleep Efficiency (%) 75.99±11.11 70.22±20.84 71.51±10.22 0.439 Stage N1, % 29.30±8.93 31.98±10.13 46.31±19.46 0.002 Stage N2, % 39.14±11.94 42.66±9.20 34.92±16.58 0.291 Stage N3, % 13.13±4.26 5.43±4.95 2.71±2.78 ＜0.001 REM, % 17.95±4.57 19.94±7.22 16.09±6.24 0.186 AHI, episodes/h 4.04±0.78 11.95±2.88 44.77±22.08 ＜0.001 ODI, episodes/h 0.58±0.50 2.78±2.47 22.58±19.45 ＜0.001 Min SaO 2 , % 91.73±2.84 85.10±7.20 80.29±10.52 ＜0.001 Mean SaO 2 , % 96.53±0.74 95.60±1.65 94.03±2.35 ＜0.001 Arousal index, episodes/h 1.81±1.04 2.27±0.49 17.21±17.56 ＜0.001 Abbreviation: TST, total sleep time; REM, rapid eye movement; N, non-rapid eye movement; Min SaO2, minimum oxygen saturation of arterial blood; Mean SaO2, mean oxygen saturation of arterial blood; ODI, oxygen desaturation index. AHI, apnea-hypopnea index. Serum Levels of Fibrinogen, E-Selectin, and t-PA The serum levels of fibrinogen, E-selectin, and t-PA were markedly increased in the moderately-severely exposed group in comparison to the non-exposed group (P < 0.001), while there were no significant differences between the mildly exposed and non-exposed groups. These biomarkers' levels increased with the severity of OSA (Table 4, Figure 1). Table 4 Comparison of fibrinogen, E-selectin, and t-PA in different groups Non-exposed group (15) Mildly exposed group (15) Moderately-Severely exposed group (30) P-value Fibrinogen, g/L 2.39±0.75 2.96±0.88 3.50±0.83 0.001 E-selectin, ng/ml 8.30±1.52 9.71±1.57 10.99±2.22 0.001 t-PA, ng/ml 8.14±2.12 9.46±1.51 10.67±1.86 0.001 Abbreviation: tissue-type plasminogen activator. Correlation Analysis Pearson correlation analysis revealed that AHI values in stroke patients were positively correlated with serum levels of fibrinogen (r = 0.409, P = 0.001), E-selectin (r = 0.591, P < 0.001), and t-PA (r = 0.622, P < 0.001) (Figure 2). Diagnostic Performance of Biomarkers Receiver operating characteristic (ROC) curve analysis demonstrated that the areas under the curve (AUCs) for fibrinogen, E-selectin, and t-PA were 0.792 (95% CI: 0.67 to 0.92, P = 0.001), 0.813 (95% CI: 0.70 to 0.93, P = 0.001), and 0.796 (95% CI: 0.70 to 0.92, P = 0.001), respectively. The cutoff values for fibrinogen, E-selectin, and t-PA were 2.475 g/L, 8.7 ng/mL, and 8.65 ng/mL, with sensitivities of 84.4%, 80%, and 82.2%, and specificities of 60%, 66.7%, and 66.7%, respectively (Figure 3). Discussion In our study, we found that AIS patients with OSA exhibited increased light sleep (percentage of stage N1), decreased deep sleep (percentage of stage N3), higher arousal index, and higher ODI, along with reduced minimum and mean oxygen saturation levels. OSA, a sleep-related breathing disorder, is associated with intermittent hypoxemia and sleep fragmentation, with intermittent hypoxemia thought to be a contributing factor in the development of OSA-related complications [10, 11]. Therefore, the increase in light sleep and decrease in deep sleep observed in these patients may be attributed to OSA-induced sleep fragmentation and frequent awakenings, which lead to decreased sleep quality and further impact stroke recovery. The ODI, definition as the number of times per hour of sleep that oxygen saturation drops more than 3% from baseline, was notably higher in AIS patients with OSA. This increase in ODI indicates more frequent and severe episodes of hypoxemia, which can exacerbate the underlying stroke pathology and hinder recovery. Intermittent hypoxemia triggers a cascade of pathophysiologic responses, including abnormal lipid metabolism, systemic inflammation, oxidative stress, endothelial dysfunction, and hypercoagulability[12]. These conditions collectively impair vascular health and elevate the risk of further ischemic events. A reduction in minimum oxygen saturation highlights the most severe hypoxic episodes during sleep, while a decrease in mean oxygen saturation indicates a persistent overall deficiency in oxygen supply. Sustained low blood oxygen levels can promote thrombosis by increasing blood viscosity, further contributing to hypoxia and impairing neurological recovery[13, 14]. Gottlieb et al. observed a decline in the proportion of deep sleep and a compensatory increase in non-rapid eye movement (NREM) sleep stages 1-2 in patients with chronic-phase ischemic stroke combined with moderate-to-severe OSA, in comparison to healthy controls. [15]. Additionally, Xu et al. found that the ODI, the proportion of time with oxygen saturation below 90%, and the respiration-related arousal index were significantly higher, while the lowest oxygen saturation (LSaO 2 ) was considerably lower in the stroke with OSA group than in the stroke alone group[16]. Consequently, continuous positive airway pressure (CPAP) therapy for OSA has been proved to improve the prognosis of AIS patients in specific circumstances [17]. Early diagnosis and intervention of OSA in AIS patients suspected of having comorbid OSA is crucial for improving clinical outcomes[18]. Our study also found that BMI, ESS scores, and STOP-Bang scores were significantly higher in acute ischemic stroke patients with moderate -severe OSA than in patients without OSA. BMI is a critical measure of obesity, which increases fat deposition in the upper airways, leading to airway narrowing and the development of OSA[19]. Given that overweight is a common risk factor for both AIS and OSA, AIS patients with OSA typically have a higher BMI. Frequent nocturnal apneas and arousals in OSA patients result in sleep fragmentation and reduced sleep efficiency, causing significant daytime somnolence and affecting daytime cognitive functions in AIS patients[20]. Consequently, AIS patients with OSA exhibited higher degrees of sleepiness as reflected by the ESS score. The STOP-Bang questionnaire, which assesses the risk of OSA by evaluating eight indicators (snoring, fatigue, witnessed apnea, hypertension, BMI, age, neck circumference, and gender) [21], indicated that AIS patients with OSA had substantially elevated STOP-Bang scores compared to those without OSA due to the accumulation of these risk factors. Reuter et al. discovered that stroke patients often lack the typical signs and symptoms of OSA, thereby limiting the effectiveness of common screening tools (e.g., ESS, STOP-Bang, and Berlin Questionnaire) in stroke patients, resulting in the underdiagnosis and undertreatment of severe OSA[22]. Blood biomarkers are key to detection of patients at high risk of OSA, primarily due to the pathophysiologic mechanisms underlying the condition[23]. These mechanisms include abnormal lipid metabolism, systemic inflammation, oxidative stress, endothelial dysfunction, and blood hypercoagulability[3]. Our study found that serum levels of fibrinogen, E-selectin and t-PA were markedly higher in acute ischemic stroke patients with moderate-severe OSA versus those without OSA. Moreover, these biomarkers gradually raised with the severity of OSA. E-selectin, specifically expressed on endothelial cells, mediates the rolling of leukocytes on endothelial cells, facilitating the recruitment of neutrophils, monocytes, and T cells to sites of inflammation. This process can lead to endothelial dysfunction and inflammatory responses[24]. Sun et al. reported that various cellular adhesion molecules, including E-selectin, were markedly increased in OSA patients versus healthy controls. Furthermore, multivariate linear regression analysis indicated a significant correlation between elevated E-selectin levels and OSA severity[25]. Richard et al. found that E-selectin levels within 6 hours of acute stroke onset independently predicted the 3-month prognostic outcome[26]. Additionally, in a mouse model of ischemic stroke, the expression of E-selectin was upregulated in cerebral blood vessels damaged by reperfusion ischemia. Increased E-selectin levels may induce the migration of leukocytes or neutrophils into brain tissue, further contributing to cytokine release and free radical-mediated injury[27]. Our team's preliminary research discovered that ApoB-100 levels were raised in the serum of OSA patients in comparison to healthy controls [28]. Consequently, OSA can also impact endothelial function through lipid metabolism abnormalities. ApoB-100 has a powerful stimulatory influence on cholesterol esterification in macrophages, promoting foam cell formation and affecting endothelial function[29]. These findings underscore the complex interplay between OSA, endothelial dysfunction, and stroke pathophysiology. Fibrinogen is primarily synthesized and secreted by hepatocytes, playing a crucial role in the coagulation process and platelet aggregation by forming fibrin monomers under the action of thrombin. T-PA is a serine protease, and is secreted primarily by the endothelial cells of blood vessels and converts plasminogen to plasmin, which degrades fibrinogen and various coagulation factors. Bikov et al. found that OSA induces a hypercoagulable state, activating the fibrinolytic system, and Overactivation of this system can lead to thrombus formation and vascular occlusion, one of the mechanisms by which OSA raises risk of cerebrovascular disease[30]. Qiu et al. observed increased levels of fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and D-dimer in OSA patients, suggesting a reduced capacity of the fibrinolytic system to degrade fibrinogen[31]. Our study demonstrated that AIS patients with moderate-to-severe OSA have elevated levels of fibrinogen and t-PA. The increase in t-PA may represent a compensatory response to the hypercoagulable state induced by OSA, aiming to mitigate the impact of elevated fibrinogen on blood hypercoagulability. Steffanina et al. reported significant elevations in both PAI-1 and t-PA in OSA patients in comparison to healthy controls [32], indicating an imbalance in the fibrinolytic system. This imbalance is further evidenced by the fact that elevated PAI-1 counteracts the effects of t-PA. Consequently, the suppressive role of elevated PAI-1 on t-PA exceeds the ability of t-PA to degrade fibrinogen, resulting in elevated levels of both fibrinogen and t-PA (Figure 4). The major diagnostic criteria for acute ischemic stroke (AIS) with OSA are currently based on polysomnography (PSG). However, PSG is complex and expensive to perform. Biomarkers, being objective and quantifiable indicators, offer a promising alternative. Our study employed ROC curves to validate that fibrinogen, E-selectin, and t-PA have the potential to serve as alternative serologic tests to PSG for diagnosing OSA. The sensitivity of these three biomarkers exceeded 80%, and their positive rates for diagnosing stroke combined with OSA were high, suggesting their value in the management and follow-up of AIS with OSA. Early identification and management of OSA are crucial for improving the prognosis of AIS patients. By comprehensively assessing fibrinogen, E-selectin, and t-PA levels, we can effectively screen and manage this high-risk population, ultimately improving their quality of life and long-term health conditions for AIS patients. Nevertheless, our study has limitations. Firstly, the relatively small size of the sample may lead to random error. Secondly, we did not investigate whether the levels of these biomarkers decreased following OSA treatment or track their trends with the recovery of cerebral infarction. Future studies should address these aspects to provide a more comprehensive understanding. Conclusion Acute ischemic stroke (AIS) patients with OSA exhibit disrupted sleep architecture, characterized by a prolonged light sleep (N1), a shortened deep sleep (N3), and an increased arousal index. In these patients, serum levels of fibrinogen, E-selectin, and t-PA are elevated, showing a linear correlation with the severity of OSA. These serological markers may thus be valuable in diagnosing OSA in AIS patients. Declarations Conflict Of Interest Huang Zhencan, Zhang Yanan, Sun Qingqing, and Wang Zan have no conflicts of interest to disclose. Author Contribution All authors contributed to the study conception and design. Z.H: drafting the original manuscript. Q.S: data collection and analysis. Y.Z: conception and design of the study. Z.H and Y.Z: material preparation. Z.H and Z.W: critical revision of the manuscript. All authors reviewed the manuscript. 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Cite Share Download PDF Status: Published Journal Publication published 27 Feb, 2025 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 13 Nov, 2024 Editor assigned by journal 11 Nov, 2024 Submission checks completed at journal 11 Nov, 2024 First submitted to journal 07 Nov, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5410234","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":377756885,"identity":"4800b4b4-a375-489d-b6c9-4a373375ac11","order_by":0,"name":"Zhencan Huang","email":"","orcid":"","institution":"First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Zhencan","middleName":"","lastName":"Huang","suffix":""},{"id":377756887,"identity":"55ab0ee8-d7c1-495b-93b6-982c6a3a02b1","order_by":1,"name":"Yanan Zhang","email":"","orcid":"","institution":"First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Yanan","middleName":"","lastName":"Zhang","suffix":""},{"id":377756888,"identity":"9f1e64a8-1ef7-4ed5-9f61-5ab15084ed16","order_by":2,"name":"Qingqing Sun","email":"","orcid":"","institution":"First Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Qingqing","middleName":"","lastName":"Sun","suffix":""},{"id":377756890,"identity":"130d7209-b727-4052-a13e-1d8d69013a5f","order_by":3,"name":"Zan Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIiWNgGAWjYBADOcZ2EMVGghZjxmZStSQ2MBOrxeD42cMvf9TcSW9u5jFg+FB2mIF/dgMBLWfy0iwkjj3LbQRqYZxx7jCDxJ0D+LWYHcgxMzBgOwzWwszbdpjBQCKBgJbzb8wMEv4dTmcEaflLlJYbOcYPDrYdTgBrYSRGi/2NN2aMjX2HDRub2QoO9pxL55G4QUCLZH+O8ccf3w7LG7Y3b3zwo8xajn8GAS1AwCYBIg0bGBgOAGkeguqBgPkDiJQnRukoGAWjYBSMTAAAftVD9lk/A6UAAAAASUVORK5CYII=","orcid":"","institution":"First Hospital of Jilin University","correspondingAuthor":true,"prefix":"","firstName":"Zan","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-11-07 13:24:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5410234/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5410234/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12883-025-04084-w","type":"published","date":"2025-02-27T15:57:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":71562998,"identity":"c35b9c90-5ab5-45bc-b5e4-b399b2bf0bf9","added_by":"auto","created_at":"2024-12-16 17:14:52","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":149573,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of fibrinogen (FIB), E-selectin, and t-PA serum levels in mildly exposed group，moderately-severely exposed group, and non-exposed group.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5410234/v1/df51e25d32bba81896de9f04.jpg"},{"id":71561825,"identity":"7a7282fb-37cd-4432-bcd0-7154c07b6af0","added_by":"auto","created_at":"2024-12-16 17:06:52","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":182522,"visible":true,"origin":"","legend":"\u003cp\u003eRelations between apnea-hypopnea index (AHI) and the serum levels of fibrinogen (A), E-selectin (B), and t-PA (C).\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5410234/v1/693aba5b631f1ba021364cec.jpg"},{"id":71561829,"identity":"5e4f5fdd-869d-4629-bd25-12ca7e91a45c","added_by":"auto","created_at":"2024-12-16 17:06:52","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":260710,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver operating characteristic (ROC) curve for fibrinogen (A), E-selectin(B), and t-PA(C) of stroke with OSA. Each panel shows the area under the curve (AUC), cutoff value, sensitivity, and specificity values.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5410234/v1/ecabe70e69da46c14e0a2ed4.jpg"},{"id":71561827,"identity":"5ef8085f-0281-47ca-a44f-14e447e64ca3","added_by":"auto","created_at":"2024-12-16 17:06:52","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":209037,"visible":true,"origin":"","legend":"\u003cp\u003eDiagram of the mechanism by which hypoxia leads to elevated secretion of E-selectin, fibrinogen, and t-PA by vascular endothelial cells.\u003c/p\u003e\n\u003cp\u003eAbbreviation:t-PA: tissue-type plasminogen activator; PAI-1: plasminogen activator inhibitor-1.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5410234/v1/bf51de3b2446095ac5400572.jpg"},{"id":77622679,"identity":"02746624-c715-49d0-bf8a-68537d685e11","added_by":"auto","created_at":"2025-03-03 16:09:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1415653,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5410234/v1/bc8bd690-0d3f-40b3-baf7-23662461752a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The expression changes endothelial and fibrinolytic biomarkers in acute ischemic stroke patients with OSA","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute ischemic stroke (AIS) is an acute focal neurological impairment caused by cerebrovascular ischemia. Globally, it is one of the major causes of disability and death, with approximately 3.29\u0026nbsp;million deaths annually[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Patients with AIS face a high risk of recurrence within five years, highlighting the critical need for research and intervention in modifiable risk factors. Sleep-disordered breathing (SDB) is a prevalent chronic condition affecting nearly 936\u0026nbsp;million people globally, with 425\u0026nbsp;million experiencing moderate to severe obstructive sleep apnea (OSA)[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. OSA is marked by repeated episodes of partial (hypopnea) or complete (apnea) blockage of airflow during sleep, causing intermittent hypoxia and fragmented sleep. These disruptions result in daytime drowsiness, fatigue, irritability, lack of concentration, and even cognitive impairment[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The severity of OSA is determined using the apnea-hypopnea index (AHI). This classification is broken down into three categories: mild (AHI between 5 and 15), moderate (AHI between 15 and 30), and severe (AHI 30 or higher)[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeiler et al. discovered that the incidence of sleep apnea in patients with AIS is 71%, nearly four times that of the masses[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Not only does OSA directly increase the risk of stroke as an independent risk factor, but it also worsens other cardiovascular risk factors, such as high blood pressure and arrhythmias, significantly impacting stroke prognosis[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Although polysomnography is the definitive test for the diagnosis of OSA, its complexity, requirement for extensive medical personnel, and high cost can delay diagnosis and treatment.\u003c/p\u003e \u003cp\u003eAdvancements in biomarker research have shown that specific biomarkers in OSA patients could be crucial for predicting diagnosis, disease severity, and response to therapy[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, studies on endothelial function and the fibrinolytic system in AIS patients with OSA are relatively scarce. This study aims to investigate the expression of serum t-PA, E-selectin, and fibrinogen in AIS with OSA and assess their diagnostic value for AIS combined with OSA.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe study was approved by the ethics committee of the First Hospital of Jilin University and was conducted in accordance with the Declaration of Helsinki (Approval No. 24K042-001). All participants and their guardians gave informed consent.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eParticipants\u003c/h2\u003e\n\u003cp\u003eWe recruited 80 acute ischemic stroke (AIS) patients who were enrolled in the Department of Neurology of the First Hospital of Jilin University between January 2023 to December 2023. \u0026nbsp;Finally, 60 patients underwent polysomnography (PSG) within a week of symptom onset. Given the frequency of OSA in AIS patients (71%) [5], the patients were collected in a 1:3 ratio and categorized into two groups: 15 patients in the non-exposed group (AIS without OSA) and 45 patients in the exposed group (AIS with OSA). The exposed group was further divided into mildly exposed (5 \u0026le; AHI \u0026le; 15; n=15) and moderately-severely exposed (AHI \u0026gt; 15; n=30) according to the apnea-hypopnea index (AHI) score.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eInclusion and Exclusion Criteria\u003c/h2\u003e\n\u003cp\u003eThe inclusion criteria included:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1. Non-exposed group:\u0026nbsp;\u003c/strong\u003eage, gender, cerebral infarction site matched with exposed group, and no sleep disorder in PSG.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2. Exposed group:\u003c/strong\u003e (1) Diagnosed with OSA according to the International Classification of Sleep Disorders (ICSD), 3rd edition; (2) aged between 18 and 65 years; (3) and having a cerebral infarction located in the region dominated by the internal carotid artery system with a maximum infarct lesion diameter greater than 20 mm.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe exclusion criteria included:\u003cins cite=\"mailto:苗宏伟\" datetime=\"2024-07-09T14:43\"\u003e\u0026nbsp;\u003c/ins\u003e\u003c/p\u003e\n\u003cp\u003e(1) Patients with TIA or acute ischemic stroke undergoing endovascular therapy or intravenous thrombolysis; (2) Patients with sleep disorders excluding OSA; (3) Patients with comorbid respiratory conditions, including acute respiratory infections, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), lung infections, bronchiectasis, and bronchial asthma; (4) recent use of medications affecting sleep breathing (benzodiazepines, sedative antidepressants, opioids, etc.); (5) Generalized Anxiety Disorder-7 (GAD-7) score \u0026ge; 9 or Patient Health Questionnaire-9 (PHQ-9) score \u0026ge; 5.\u003c/p\u003e\n\u003ch2\u003eClinical Data\u003c/h2\u003e\n\u003cp\u003eAll patients underwent comprehensive clinical data collection on admission, including age, sex, height, weight calculated body mass index (BMI), Epworth Sleepiness Scale (ESS) assessment, National Institutes of Health Stroke Scale (NIHSS) assessment, STOP-Bang questionnaire, past medical history, neurologic examination, and head imaging of stroke site and maximum infarct lesion diameter.\u003c/p\u003e\n\u003ch2\u003ePolysomnography\u003c/h2\u003e\n\u003cp\u003ePolysomnography (PSG) was used to monitor all patients for at least 8 hours at our hospital\u0026apos;s sleep center (Compumedics, Australia). Results of the PSG have been scored by certified PSG technologists., following the American Academy of Sleep Medicine\u0026apos;s revised interpretation criteria for sleep stages and related events, version 2.6.\u003c/p\u003e\n\u003cp\u003eApnea was diagnosed as a fall in peak temperature sensor excursion of \u0026ge; 90% of baseline, lasting for at least two respiratory cycles. Hypopnea was considered as \u0026ge; 30% decline in nasal pressure signal excursion from pre-event baseline, lasting at least two breathing cycles, with \u0026ge; 3% desaturation in blood oxygen saturation or associated arousal. The apnea-hypopnea index (AHI) was computed as the mean number of apnea and/or hypopnea events per hour of sleep. Oximetric measures derived from PSG channels included the oxygen desaturation index (ODI), minimum oxygen saturation of arterial blood (Min SaO\u003csub\u003e2\u003c/sub\u003e), and mean oxygen saturation of arterial blood (Mean SaO\u003csub\u003e2\u003c/sub\u003e). ODI was calculated as the number of events per hour in which the decrease in oxygen saturation was \u0026ge; 3% from baseline.\u003c/p\u003e\n\u003ch2\u003eFibrinogen, E-selection, and t-PA Serum Level Detection\u003c/h2\u003e\n\u003cp\u003eBlood samples were taken from all patients the following morning after an 8-hour fast on enrolment and processed by centrifugation at 3000 rpm for 10 minutes. Serum was kept at -80\u0026deg;C until the time of testing. Serum levels of fibrinogen, E-selectin, and tissue-type plasminogen activator (t-PA) were detected using enzyme-linked immunosorbent assay (ELISA) kits (Jianglai Biotechnology Co., Ltd., Shanghai, China).\u003c/p\u003e\n\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\n\u003cp\u003eIBM SPSS Statistics for Windows version 26.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. The Shapiro-Wilk test was used to examine the normal distribution of continuous variables. Data with a normal distribution were expressed as mean \u0026plusmn; standard deviation, while data with a skewed distribution were expressed as median with interquartile range. Categorical data were presented as absolute values and percentages. Differences between multiple groups of independent samples were compared using one-way analysis of variance (ANOVA) or the Kruskal-Wallis H test, for data distribution. The Pearson correlation test was employed to examine the relationship between the apnea-hypopnea index and serum levels of fibrinogen, E-selectin, and t-PA. Receiver operating characteristic (ROC) curves were generated to calculate the sensitivity, specificity, and cut-off points for fibrinogen, E-selectin, and t-PA serum levels in predicting OSA, based on the Youden index.\u003c/p\u003e"},{"header":"Results","content":"\u003ch2\u003eBaseline Characteristics\u003c/h2\u003e\n\u003cp\u003eSixty patients were included in this study, divided into three groups: 15 in the non-exposed group, 15 in the mildly exposed group and 30 in the moderately-severely exposed group. There were no significant differences among the groups in terms of age, gender, NIHSS score, smoking history, drinking history, hypertension, diabetes mellitus, and hyperlipidemia. However, BMI (P = 0.001), ESS scores (P = 0.003), and STOP-Bang scores (P \u0026lt; 0.001) were significantly higher in the moderately-severely exposed group compared to the non-exposed group (Tables 1 and 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003eClinical characteristics of acute ischemic stroke among different groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eControl group (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003eMildly exposed group (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003eModerately-Severely exposed group\u0026nbsp;(30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e61.67\u0026plusmn;9.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e58.40\u0026plusmn;9.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e57.49\u0026plusmn;9.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.344\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e10(66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e7(70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e27(77.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.720\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e22.79\u0026plusmn;2.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e25.43\u0026plusmn;4.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e27.26\u0026plusmn;4.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003eSmoke, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e5(33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e7(70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e17(48.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003eDrink, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2(13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e5(50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e13(37.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003eHypertension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e13(86.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e5(50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e26(74.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.158\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003eHyperlipidemia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e3(20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e3(30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e14(40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.377\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003eDiabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e4(26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e2(20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e16(45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.215\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviation: BMI, body mass index.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u0026nbsp;\u003c/strong\u003eThe scale of NIHSS、ESS、STOP-Bang \u0026nbsp;in \u0026nbsp;different \u0026nbsp; groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eNon-exposed group\u0026nbsp;(15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eMildly exposed\u0026nbsp;group (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003eModerately-Severely exposed\u0026nbsp;group (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eNIHSS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e3.67\u0026plusmn;2.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e4.30\u0026plusmn;3.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e4.49\u0026plusmn;2.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.601\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eESS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e6.13\u0026plusmn;2.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e5.20\u0026plusmn;3.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e9.69\u0026plusmn;4.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eSTOP-Bang\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e3.20\u0026plusmn;0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e3.30\u0026plusmn;1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e5.11\u0026plusmn;1.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviation: NIHSS, National Institute of Health stroke scale, ESS, Epworth Sleepiness Scale.\u003c/p\u003e\n\u003ch2\u003ePolysomnography Parameters\u003c/h2\u003e\n\u003cp\u003ePolysomnography (PSG) parameters showed that AIS patients with OSA had a higher proportion of stage N1 sleep (P = 0.002) and a lower proportion of stage N3 sleep (P \u0026lt; 0.001). Additionally, these patients exhibited an increased arousal index and oxygen desaturation index (ODI) (P \u0026lt; 0.001), and decreased minimum and mean oxygen saturation levels (P \u0026lt; 0.001) (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003eThe PSG parameters of acute ischemic stroke in different groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eNon-exposed group\u0026nbsp;(15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eMildly exposed\u0026nbsp;group (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003eModerately-Severely exposed\u0026nbsp;group (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eTST, min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e400.07\u0026plusmn;45.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e399.05\u0026plusmn;42.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e395.19\u0026plusmn;69.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.978\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eSleep Efficiency (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e75.99\u0026plusmn;11.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e70.22\u0026plusmn;20.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e71.51\u0026plusmn;10.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.439\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eStage N1, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e29.30\u0026plusmn;8.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e31.98\u0026plusmn;10.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e46.31\u0026plusmn;19.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eStage N2, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e39.14\u0026plusmn;11.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e42.66\u0026plusmn;9.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e34.92\u0026plusmn;16.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.291\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eStage N3, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e13.13\u0026plusmn;4.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e5.43\u0026plusmn;4.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e2.71\u0026plusmn;2.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eREM, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e17.95\u0026plusmn;4.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e19.94\u0026plusmn;7.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e16.09\u0026plusmn;6.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.186\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eAHI, episodes/h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e4.04\u0026plusmn;0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e11.95\u0026plusmn;2.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e44.77\u0026plusmn;22.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eODI, episodes/h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0.58\u0026plusmn;0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2.78\u0026plusmn;2.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e22.58\u0026plusmn;19.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eMin SaO\u003csub\u003e2\u003c/sub\u003e, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e91.73\u0026plusmn;2.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e85.10\u0026plusmn;7.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e80.29\u0026plusmn;10.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eMean SaO\u003csub\u003e2\u003c/sub\u003e, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e96.53\u0026plusmn;0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e95.60\u0026plusmn;1.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e94.03\u0026plusmn;2.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eArousal index, episodes/h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.81\u0026plusmn;1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2.27\u0026plusmn;0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e17.21\u0026plusmn;17.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviation: TST, total sleep time; REM, rapid eye movement; N, non-rapid eye movement; Min SaO2, minimum oxygen saturation of arterial blood; Mean SaO2, mean oxygen saturation of arterial blood; ODI, oxygen desaturation index. AHI, apnea-hypopnea index.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSerum Levels of Fibrinogen, E-Selectin, and t-PA\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe serum levels of fibrinogen, E-selectin, and t-PA were markedly increased in the moderately-severely exposed group in comparison to the non-exposed group (P \u0026lt; 0.001), while there were no significant differences between the mildly exposed and non-exposed groups. These biomarkers\u0026apos; levels increased with the severity of OSA (Table 4, Figure 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u0026nbsp;\u003c/strong\u003eComparison of\u0026nbsp;fibrinogen, E-selectin, and t-PA in different\u0026nbsp;groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003eNon-exposed group\u0026nbsp;(15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eMildly exposed\u0026nbsp;group (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003eModerately-Severely exposed\u0026nbsp;group (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003eFibrinogen, g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e2.39\u0026plusmn;0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e2.96\u0026plusmn;0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e3.50\u0026plusmn;0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003eE-selectin, ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e8.30\u0026plusmn;1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e9.71\u0026plusmn;1.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e10.99\u0026plusmn;2.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003et-PA, ng/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e8.14\u0026plusmn;2.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e9.46\u0026plusmn;1.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 153px;\"\u003e\n \u003cp\u003e10.67\u0026plusmn;1.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviation: tissue-type plasminogen activator.\u003c/p\u003e\n\u003ch2\u003eCorrelation Analysis\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003ePearson correlation analysis revealed that AHI values in stroke patients were positively correlated with serum levels of fibrinogen (r = 0.409, P = 0.001), E-selectin (r = 0.591, P \u0026lt; 0.001), and t-PA (r = 0.622, P \u0026lt; 0.001) (Figure 2).\u003c/p\u003e\n\u003ch2\u003eDiagnostic Performance of Biomarkers\u003c/h2\u003e\n\u003cp\u003eReceiver operating characteristic (ROC) curve analysis demonstrated that the areas under the curve (AUCs) for fibrinogen, E-selectin, and t-PA were 0.792 (95% CI: 0.67 to 0.92, P = 0.001), 0.813 (95% CI: 0.70 to 0.93, P = 0.001), and 0.796 (95% CI: 0.70 to 0.92, P = 0.001), respectively. The cutoff values for fibrinogen, E-selectin, and t-PA were 2.475 g/L, 8.7 ng/mL, and 8.65 ng/mL, with sensitivities of 84.4%, 80%, and 82.2%, and specificities of 60%, 66.7%, and 66.7%, respectively (Figure 3).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our study, we found that AIS patients with OSA exhibited increased light sleep (percentage of stage N1), decreased deep sleep (percentage of stage N3), higher arousal index, and higher ODI, along with reduced minimum and mean oxygen saturation levels. OSA, a sleep-related breathing disorder, is associated with intermittent hypoxemia and sleep fragmentation, with intermittent hypoxemia thought to be a contributing factor in the development of OSA-related complications [10, 11]. Therefore, the increase in light sleep and decrease in deep sleep observed in these patients may be attributed to OSA-induced sleep fragmentation and frequent awakenings, which lead to decreased sleep quality and further impact stroke recovery.\u003c/p\u003e\n\u003cp\u003eThe ODI, definition as the number of times per hour of sleep that oxygen saturation drops more than 3% from baseline, was notably higher in AIS patients with OSA. This increase in ODI indicates more frequent and severe episodes of hypoxemia, which can exacerbate the underlying stroke pathology and hinder recovery. Intermittent hypoxemia triggers a cascade of pathophysiologic responses, including abnormal lipid metabolism, systemic inflammation, oxidative stress, endothelial dysfunction, and hypercoagulability[12]. These conditions collectively impair vascular health and elevate the risk of further ischemic events. A reduction in minimum oxygen saturation highlights the most severe hypoxic episodes during sleep, while a decrease in mean oxygen saturation indicates a persistent overall deficiency in oxygen supply. Sustained low blood oxygen levels can promote thrombosis by increasing blood viscosity, further contributing to hypoxia and impairing neurological recovery[13, 14].\u003c/p\u003e\n\u003cp\u003eGottlieb et al. observed a decline in the proportion of deep sleep and a compensatory increase in non-rapid eye movement (NREM) sleep stages 1-2 in patients with chronic-phase ischemic stroke combined with moderate-to-severe OSA, in comparison to healthy controls. [15]. Additionally, Xu et al. found that the ODI, the proportion of time with oxygen saturation below 90%, and the respiration-related arousal index were significantly higher, while the lowest oxygen saturation (LSaO\u003csub\u003e2\u003c/sub\u003e) was considerably lower in the stroke with OSA group than in the stroke alone group[16]. Consequently, continuous positive airway pressure (CPAP) therapy for OSA has been proved to improve the prognosis of AIS patients in specific circumstances [17]. Early diagnosis and intervention of OSA in AIS patients suspected of having comorbid OSA is crucial for improving clinical outcomes[18].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study also found that BMI, ESS scores, and STOP-Bang scores were significantly higher in acute ischemic stroke patients with moderate -severe OSA than in patients without OSA. BMI is a critical measure of obesity, which increases fat deposition in the upper airways, leading to airway narrowing and the development of OSA[19]. Given that overweight is a common risk factor for both AIS and OSA, AIS patients with OSA typically have a higher BMI. Frequent nocturnal apneas and arousals in OSA patients result in sleep fragmentation and reduced sleep efficiency, causing significant daytime somnolence and affecting daytime cognitive functions in AIS patients[20]. Consequently, AIS patients with OSA exhibited higher degrees of sleepiness as reflected by the ESS score. The STOP-Bang questionnaire, which assesses the risk of OSA by evaluating eight indicators (snoring, fatigue, witnessed apnea, hypertension, BMI, age, neck circumference, and gender) [21], indicated that AIS patients with OSA had substantially elevated STOP-Bang scores compared to those without OSA due to the accumulation of these risk factors. Reuter et al. discovered that stroke patients often lack the typical signs and symptoms of OSA, thereby limiting the effectiveness of common screening tools (e.g., ESS, STOP-Bang, and Berlin Questionnaire) in stroke patients, resulting in the underdiagnosis and undertreatment of severe OSA[22].\u003c/p\u003e\n\u003cp\u003eBlood biomarkers are key to detection of patients at high risk of OSA, primarily due to the pathophysiologic mechanisms underlying the condition[23]. These mechanisms include abnormal lipid metabolism, systemic inflammation, oxidative stress, endothelial dysfunction, and blood hypercoagulability[3]. Our study found that serum levels of fibrinogen, E-selectin and t-PA were markedly higher in acute ischemic stroke patients with moderate-severe OSA versus those without OSA. Moreover, these biomarkers gradually raised with the severity of OSA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eE-selectin, specifically expressed on endothelial cells, mediates the rolling of leukocytes on endothelial cells, facilitating the recruitment of neutrophils, monocytes, and T cells to sites of inflammation. This process can lead to endothelial dysfunction and inflammatory responses[24]. Sun et al. reported that various cellular adhesion molecules, including E-selectin, were markedly increased in OSA patients versus healthy controls. Furthermore, multivariate linear regression analysis indicated a significant correlation between elevated E-selectin levels and OSA severity[25]. Richard et al. found that E-selectin levels within 6 hours of acute stroke onset independently predicted the 3-month prognostic outcome[26]. Additionally, in a mouse model of ischemic stroke, the expression of E-selectin was upregulated in cerebral blood vessels damaged by reperfusion ischemia. Increased E-selectin levels may induce the migration of leukocytes or neutrophils into brain tissue, further contributing to cytokine release and free radical-mediated injury[27]. Our team\u0026apos;s preliminary research discovered that ApoB-100 levels were raised in the serum of OSA patients in comparison to healthy controls\u0026nbsp;[28]. Consequently, OSA can also impact endothelial function through lipid metabolism abnormalities. ApoB-100 has a powerful stimulatory influence on cholesterol esterification in macrophages, promoting foam cell formation and affecting endothelial function[29]. These findings underscore the complex interplay between OSA, endothelial dysfunction, and stroke pathophysiology.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFibrinogen is primarily synthesized and secreted by hepatocytes, playing a crucial role in the coagulation process and platelet aggregation by forming fibrin monomers under the action of thrombin. T-PA is a serine protease, and is secreted primarily by the endothelial cells of blood vessels and converts plasminogen to plasmin, which degrades fibrinogen and various coagulation factors. Bikov et al. found that OSA induces a hypercoagulable state, activating the fibrinolytic system, and Overactivation of this system can lead to thrombus formation and vascular occlusion, one of the mechanisms by which OSA raises risk of cerebrovascular disease[30]. Qiu et al. observed increased levels of fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and D-dimer in OSA patients, suggesting a reduced capacity of the fibrinolytic system to degrade fibrinogen[31]. Our study demonstrated that AIS patients with moderate-to-severe OSA have elevated levels of fibrinogen and t-PA. The increase in t-PA may represent a compensatory response to the hypercoagulable state induced by OSA, aiming to mitigate the impact of elevated fibrinogen on blood hypercoagulability. Steffanina et al. reported significant elevations in both PAI-1 and t-PA in OSA patients in comparison to healthy controls [32], indicating an imbalance in the fibrinolytic system. This imbalance is further evidenced by the fact that elevated PAI-1 counteracts the effects of t-PA. Consequently, the suppressive role of elevated PAI-1 on t-PA exceeds the ability of t-PA to degrade fibrinogen, resulting in elevated levels of both fibrinogen and t-PA (Figure 4).\u003c/p\u003e\n\u003cp\u003eThe major diagnostic criteria for acute ischemic stroke (AIS) with OSA are currently based on polysomnography (PSG). However, PSG is complex and expensive to perform. Biomarkers, being objective and quantifiable indicators, offer a promising alternative. Our study employed ROC curves to validate that fibrinogen, E-selectin, and t-PA have the potential to serve as alternative serologic tests to PSG for diagnosing OSA. The sensitivity of these three biomarkers exceeded 80%, and their positive rates for diagnosing stroke combined with OSA were high, suggesting their value in the management and follow-up of AIS with OSA. Early identification and management of OSA are crucial for improving the prognosis of AIS patients. By comprehensively assessing fibrinogen, E-selectin, and t-PA levels, we can effectively screen and manage this high-risk population, ultimately improving their quality of life and long-term health conditions for AIS patients.\u003c/p\u003e\n\u003cp\u003eNevertheless, our study has limitations. Firstly, the relatively small size of the sample may lead to random error. Secondly, we did not investigate whether the levels of these biomarkers decreased following OSA treatment or track their trends with the recovery of cerebral infarction. Future studies should address these aspects to provide a more comprehensive understanding.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAcute ischemic stroke (AIS) patients with OSA exhibit disrupted sleep architecture, characterized by a prolonged light sleep (N1), a shortened deep sleep (N3), and an increased arousal index. In these patients, serum levels of fibrinogen, E-selectin, and t-PA are elevated, showing a linear correlation with the severity of OSA. These serological markers may thus be valuable in diagnosing OSA in AIS patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict Of Interest\u003c/h2\u003e\n\u003cp\u003eHuang Zhencan, Zhang Yanan, Sun Qingqing, and Wang Zan have no conflicts of interest to disclose.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Z.H: drafting the original manuscript. Q.S: data collection and analysis. Y.Z: conception and design of the study. Z.H and Y.Z: material preparation. Z.H and Z.W: critical revision of the manuscript. All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFan J, Li X, Yu X, Liu Z, Jiang Y, Fang Y, et al. Global Burden, Risk Factor Analysis, and Prediction Study of Ischemic Stroke, 1990-2030. Neurology. 2023;101:e137\u0026ndash;50.\u003c/li\u003e\n\u003cli\u003eBenjafield AV, Ayas NT, Eastwood PR, Heinzer R, Ip MSM, Morrell MJ, et al. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019;7:687\u0026ndash;98.\u003c/li\u003e\n\u003cli\u003eBaillieul S, Dekkers M, Brill A-K, Schmidt MH, Detante O, P\u0026eacute;pin J-L, et al. Sleep apnoea and ischaemic stroke: current knowledge and future directions. Lancet Neurol. 2022;21:78\u0026ndash;88.\u003c/li\u003e\n\u003cli\u003eBerry RB, Brooks R, Gamaldo C, Harding SM, Lloyd RM, Quan SF, et al. AASM Scoring Manual Updates for 2017 (Version 2.4). J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2017;13:665\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eSeiler A, Camilo M, Korostovtseva L, Haynes AG, Brill A-K, Horvath T, et al. Prevalence of sleep-disordered breathing after stroke and TIA: A meta-analysis. Neurology. 2019;92:e648\u0026ndash;54.\u003c/li\u003e\n\u003cli\u003eBassetti CLA, Randerath W, Vignatelli L, Ferini-Strambi L, Brill A-K, Bonsignore MR, et al. EAN/ERS/ESO/ESRS statement on the impact of sleep disorders on risk and outcome of stroke. Eur Respir J. 2020;55:1901104.\u003c/li\u003e\n\u003cli\u003eCederberg KLJ, Hanif U, Peris Sempere V, H\u0026eacute;dou J, Leary EB, Schneider LD, et al. Proteomic Biomarkers of the Apnea Hypopnea Index and Obstructive Sleep Apnea: Insights into the Pathophysiology of Presence, Severity, and Treatment Response. Int J Mol Sci. 2022;23:7983.\u003c/li\u003e\n\u003cli\u003eNiżankowska-Jędrzejczyk A, Almeida FR, Lowe AA, Kania A, Nastałek P, Mejza F, et al. Modulation of inflammatory and hemostatic markers in obstructive sleep apnea patients treated with mandibular advancement splints: a parallel, controlled trial. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2014;10:255\u0026ndash;62.\u003c/li\u003e\n\u003cli\u003eJurado-Gamez B, Gomez-Chaparro JL, Mu\u0026ntilde;oz-Calero M, Serna Sanz A, Mu\u0026ntilde;oz-Cabrera L, Lopez-Barea J, et al. Serum proteomic changes in adults with obstructive sleep apnoea. J Sleep Res. 2012;21:139\u0026ndash;46.\u003c/li\u003e\n\u003cli\u003eDewan NA, Nieto FJ, Somers VK. Intermittent hypoxemia and OSA: implications for comorbidities. Chest. 2015;147:266\u0026ndash;74.\u003c/li\u003e\n\u003cli\u003eYeghiazarians Y, Jneid H, Tietjens JR, Redline S, Brown DL, El-Sherif N, et al. Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2021;144:e56\u0026ndash;67.\u003c/li\u003e\n\u003cli\u003eChang JL, Goldberg AN, Alt JA, Mohammed A, Ashbrook L, Auckley D, et al. International Consensus Statement on Obstructive Sleep Apnea. Int Forum Allergy Rhinol. 2023;13:1061\u0026ndash;482.\u003c/li\u003e\n\u003cli\u003eLee H, Heo J, Lee IH, Kim YD, Nam HS. Association between blood viscosity and early neurological deterioration in lacunar infarction. Front Neurol. 2022;13:979073.\u003c/li\u003e\n\u003cli\u003eToraldo DM, Peverini F, De Benedetto M, De Nuccio F. Obstructive sleep apnea syndrome: blood viscosity, blood coagulation abnormalities, and early atherosclerosis. Lung. 2013;191:1\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eGottlieb E, Khlif MS, Bird L, Werden E, Churchward T, Pase MP, et al. Sleep architectural dysfunction and undiagnosed obstructive sleep apnea after chronic ischemic stroke. Sleep Med. 2021;83:45\u0026ndash;53.\u003c/li\u003e\n\u003cli\u003eXu YN, Li J, Huang JY, Zhu C, Mao CJ, Shen Y, et al. [Effect of obstructive sleep apnea on sleep architecture of acute ischemic stroke patients]. Zhonghua Yi Xue Za Zhi. 2017;97:920\u0026ndash;4.\u003c/li\u003e\n\u003cli\u003eGupta A, Shukla G, Afsar M, Poornima S, Pandey RM, Goyal V, et al. Role of Positive Airway Pressure Therapy for Obstructive Sleep Apnea in Patients With Stroke: A Randomized Controlled Trial. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2018;14:511\u0026ndash;21.\u003c/li\u003e\n\u003cli\u003eDom\u0026iacute;nguez-Mayoral A, Guti\u0026eacute;rrez C, S\u0026aacute;nchez-G\u0026oacute;mez J, P\u0026eacute;rez-S\u0026aacute;nchez S, Fouz N, Guerrero-Zamora P, et al. Benefits in quality of life following an obstructive sleep apnea screening and treatment program in patients with acute ischemic stroke. Rev Neurol. 2023;76:117\u0026ndash;25.\u003c/li\u003e\n\u003cli\u003eDempsey JA, Veasey SC, Morgan BJ, O\u0026rsquo;Donnell CP. Pathophysiology of sleep apnea. Physiol Rev. 2010;90:47\u0026ndash;112.\u003c/li\u003e\n\u003cli\u003eLal C, Weaver TE, Bae CJ, Strohl KP. Excessive Daytime Sleepiness in Obstructive Sleep Apnea. Mechanisms and Clinical Management. Ann Am Thorac Soc. 2021;18:757\u0026ndash;68.\u003c/li\u003e\n\u003cli\u003eChung F, Abdullah HR, Liao P. STOP-Bang Questionnaire: A Practical Approach to Screen for Obstructive Sleep Apnea. Chest. 2016;149:631\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eReuter H, Herkenrath S, Treml M, Halbach M, Steven D, Frank K, et al. Sleep-disordered breathing in patients with cardiovascular diseases cannot be detected by ESS, STOP-BANG, and Berlin questionnaires. Clin Res Cardiol Off J Ger Card Soc. 2018;107:1071\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eKapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, et al. Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2017;13:479\u0026ndash;504.\u003c/li\u003e\n\u003cli\u003eTelen MJ. Cellular adhesion and the endothelium: E-selectin, L-selectin, and pan-selectin inhibitors. Hematol Oncol Clin North Am. 2014;28:341\u0026ndash;54.\u003c/li\u003e\n\u003cli\u003eSun H, Du Y, Zhang L, Yu H, Jiao X, Lv Q, et al. Increasing circulating ESM-1 and adhesion molecules are associated with early stage atherosclerosis in OSA patients: A cross-sectional study. Sleep Med. 2022;98:114\u0026ndash;20.\u003c/li\u003e\n\u003cli\u003eRichard S, Lagerstedt L, Burkhard PR, Debouverie M, Turck N, Sanchez J-C. E-selectin and vascular cell adhesion molecule-1 as biomarkers of 3-month outcome in cerebrovascular diseases. J Inflamm Lond Engl. 2015;12:61.\u003c/li\u003e\n\u003cli\u003eMa X-J, Cheng J-W, Zhang J, Liu A-J, Liu W, Guo W, et al. E-selectin deficiency attenuates brain ischemia in mice. CNS Neurosci Ther. 2012;18:903\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eZhang Y, Wu X, Sun Q, Tang Q, Guo Z-N, Wang Z, et al. Biomarkers and Dynamic Cerebral Autoregulation of Obstructive Sleep Apnea-Hypopnea Syndrome. Nat Sci Sleep. 2021;13:2019\u0026ndash;28.\u003c/li\u003e\n\u003cli\u003eChyu K-Y, Zhao X, Zhou J, Dimayuga PC, Lio NW, Cercek B, et al. Immunization using ApoB-100 peptide-linked nanoparticles reduces atherosclerosis. JCI Insight. 2022;7:e149741.\u003c/li\u003e\n\u003cli\u003eBikov A, Meszaros M, Schwarz EI. Coagulation and Fibrinolysis in Obstructive Sleep Apnoea. Int J Mol Sci. 2021;22:2834.\u003c/li\u003e\n\u003cli\u003eQiu Y, Li X, Zhang X, Wang W, Chen J, Liu Y, et al. Prothrombotic Factors in Obstructive Sleep Apnea: A Systematic Review With Meta-Analysis. Ear Nose Throat J. 2022;101:NP412\u0026ndash;21.\u003c/li\u003e\n\u003cli\u003eSteffanina A, Proietti L, Antonaglia C, Palange P, Angelici E, Canipari R. The Plasminogen System and Transforming Growth Factor-\u0026beta; in Subjects With Obstructive Sleep Apnea Syndrome: Effects of CPAP Treatment. Respir Care. 2015;60:1643\u0026ndash;51.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"obstructive sleep apnea syndrome, acute ischemic stroke, fibrinogen, E-selectin, tissue-type plasminogen activator","lastPublishedDoi":"10.21203/rs.3.rs-5410234/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5410234/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo assess the expression changes of serum fibrinogen, E-selectin, and tissue-type plasminogen activator (t-PA) in acute ischemic stroke (AIS) patients with varying degrees of obstructive sleep apnea syndrome (OSA), and evaluate their value in diagnosing AIS with OSA.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eData were gathered from 80 patients with AIS who were admitted to the First Hospital of Jilin University between January 2023 and December 2023. Out of these, 60 patients completed the NIHSS Scale, ESS Scale, STOP-Bang Scale, and underwent polysomnography within a week of symptom onset. Based on the apnea-hypopnea index (AHI) score, patients were categorized into three groups: 15 in the non-exposed group (AHI\u0026thinsp;\u0026lt;\u0026thinsp;5), 15 in the mildly exposed group (5\u0026thinsp;\u0026le;\u0026thinsp;AHI\u0026thinsp;\u0026le;\u0026thinsp;15), and 30 in the moderately to severely exposed group (AHI\u0026thinsp;\u0026gt;\u0026thinsp;15). Serum levels of fibrinogen, E-selectin, and t-PA were determined using enzyme-linked immunosorbent assay.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePolysomnography results indicated AIS with OSA had an increased arousal index and oxygen desaturation index (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, serum levels of fibrinogen, E-selectin, and t-PA were markedly elevated in the moderately-severely exposed group compared to the non-exposed group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and these levels positively correlated with the severity of OSA. ROC curves showed the sensitivities of serum of fibrinogen, E-selection, and t-PA was 84.4%, 80%, and 82.2%, respectively, and the specificities of 60%, 66.7%, and 66.7%, compared with that of PSG respectively.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe expression of serum fibrinogen, E-selectin, and t-PA is elevated in AIS with OSA and correlates with the severity of OSA.\u003c/p\u003e","manuscriptTitle":"The expression changes endothelial and fibrinolytic biomarkers in acute ischemic stroke patients with OSA","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-16 17:06:47","doi":"10.21203/rs.3.rs-5410234/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-13T15:49:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-11T15:40:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-11T15:40:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2024-11-07T13:16:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"27222719-36ea-4de3-a65f-5f79b31032e0","owner":[],"postedDate":"December 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-03-03T16:05:07+00:00","versionOfRecord":{"articleIdentity":"rs-5410234","link":"https://doi.org/10.1186/s12883-025-04084-w","journal":{"identity":"bmc-neurology","isVorOnly":false,"title":"BMC Neurology"},"publishedOn":"2025-02-27 15:57:06","publishedOnDateReadable":"February 27th, 2025"},"versionCreatedAt":"2024-12-16 17:06:47","video":"","vorDoi":"10.1186/s12883-025-04084-w","vorDoiUrl":"https://doi.org/10.1186/s12883-025-04084-w","workflowStages":[]},"version":"v1","identity":"rs-5410234","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5410234","identity":"rs-5410234","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}