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Kushiro K, Hirono H, Ohkoshi S. Platelet-activating cytokines potentially associated with MASLD-induced liver injury significantly decreased following CPAP therapy: A translational study using a fatty liver mouse model. Sleep Med 2025; 130:15-24. [PMID: 40112616 DOI: 10.1016/j.sleep.2025.03.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 02/10/2025] [Accepted: 03/11/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND AND AIM Patients with obstructive sleep apnea (OSA) and metabolic dysfunction associated steatotic liver disease (MASLD) frequently overlap due to the high prevalence of obesity. This translational study aimed to identify cytokines linking these conditions, beginning with an analysis of fatty liver in mice. Serum cytokine levels upregulated in the fatty liver mice were subsequently examined in human OSA serum samples. METHODS Mice were fed a high-fat diet to induce fatty liver. Liver proteins were analyzed using cytokine arrays. Serum samples from seventy (70) OSA patients (with 20 non-MASLD and 50 MASLD, pre- and 6-month post-continuous positive airway pressure [CPAP] therapy) were analyzed for the cytokines identified in the mouse experiment using enzyme-linked immunosorbent assays. RESULTS Four platelet-activation chemokines/cytokines (CCL5/RANTES, P-selectin, CXCL4/PF4, and CXCL5/LIX) were upregulated in mice with fatty liver. While serum levels of these factors were not significantly higher in MASLD-OSA compared to non-MASLD-OSA patients, their levels significantly decreased 6 months after the initiation of CPAP therapy, along with a reduction in mean platelet volume. CPAP compliance was significantly associated with a reduction in CCL5 levels. Additionally, a decrease in ALT levels following 6 months of CPAP therapy was significantly associated with CPAP compliance in MASLD-OSA patients. CONCLUSIONS While platelet-activation cytokines were not directly implicated in liver injury in MASLD-OSA patients, they decreased with CPAP therapy. CPAP compliance may play a key role in ALT reduction in MASLD-OSA patients independently of body weight changes. CCL5/RANTES may be indirectly associated with liver injury in MASLD-OSA, potentially induced through intermittent hypoxia.
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Affiliation(s)
- Kosuke Kushiro
- Clinical Examination, Graduate School of Life Dentistry at Niigata, The Nippon Dental University, Niigata, Japan
| | - Haruka Hirono
- Clinical Examination, Graduate School of Life Dentistry at Niigata, The Nippon Dental University, Niigata, Japan
| | - Shogo Ohkoshi
- Clinical Examination, Graduate School of Life Dentistry at Niigata, The Nippon Dental University, Niigata, Japan.
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2
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Kato M. Recent Insights into the Relationship Between Sleep Disordered Breathing and Cardiovascular Disease. Yonago Acta Med 2025; 68:79-90. [PMID: 40432746 PMCID: PMC12104574 DOI: 10.33160/yam.2025.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Accepted: 02/28/2025] [Indexed: 05/29/2025]
Abstract
Sleep disordered breathing, represented by sleep apnea syndrome, not only significantly reduces the quality of daily life but is also known to contribute to the development of various cardiovascular diseases. Since 2000, sleep apnea syndrome has become widely recognized by the general public. However, the number of suspected patients who seek medical consultation remains low, and even fewer receive a proper diagnosis and treatment. One reason for this is the lack of information that apnea is linked to cardiovascular disease, even among individuals experiencing typical sleep apnea syndrome symptoms such as daytime sleepiness and general fatigue. Additionally, healthcare providers may not be effectively guiding patients while providing sleep hygiene education. Furthermore, the limited number of medical facilities and technicians capable of conducting overnight polysomnography tests for diagnosing sleep disordered breathing is another factor preventing more patients from benefiting from treatment. This article explores the relationship between sleep disordered breathing and the onset of cardiovascular diseases, as well as the latest treatment approaches.
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Affiliation(s)
- Masahiko Kato
- Division of School of Health Science, Department of Pathobiological Science and Technology, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
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Cholidou K, Anagnostopoulos N, Bartziokas K, Vafeiadis K, Bakakos A, Vontetsianos A, Gogou V, Sotiropoulou Z, Anagnostopoulou C, Papasarantou A, Steiropoulos P, Bakakos P, Papaioannou AI. Correlation of mean platelet volume and red blood cell distribution width with obstructive sleep apnoea syndrome severity. Lung India 2025; 42:179-185. [PMID: 40296387 PMCID: PMC12097666 DOI: 10.4103/lungindia.lungindia_422_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/05/2024] [Accepted: 12/17/2024] [Indexed: 04/30/2025] Open
Abstract
INTRODUCTION Mean platelet volume (MPV) and red blood cll distribution width (RDW) have been assosiated with sleep apnea syndrome severity. OBJECTIVE To investigate the correlation of mean platelet volume and red blood cell distribution width with obesity sleep apnoea syndrome (OSAS) severity. METHODS Ninety patients underwent PSG. Patients with an apnoea-hypopnoea index (AHI) <5 were used as controls. Patients with AHI >5 were divided into mild: 5 ≤ AHI <15, moderate: 15≤ AHI <30 and severe OSAS: AHI ≥30. Patients >65 years, with body mass index (BMI) >40, central sleep apnoea syndrome, cardiovascular or other significant comorbidities were excluded. Blood sample collection occurred one day before polysomnography (PSG). RESULTS Sixty-four patients were included in our study. Fifty-seven (89.1%) had OSAS (16% mild, 25% moderate and 48.4% severe) while the remaining 7 (10.1%) were used as controls. MPV was similar among groups [8.1 (7.1, 9.2) vs 7.9 (6.8, 10.1) vs 8.5 (7.4, 9.1) vs 8.4 (7.6, 9.7), P = .930 for control, mild, moderate and severe OSAS, respectively]. RDW did not differ between OSAS patients and control [median (IQR) 14.4 (13.4, 15.3) vs 14.0 (13.5, 16.7), P = .950], while there was no significant difference among different stages of OSAS severity [14.0 (13.5, 16.7) vs 13.9 (11.4, 14.8) vs 14.4 (14.0, 15.3) vs 14.4 (13.3, 15.6), P = .517] for control, mild, moderate and severe OSAS, respectively. CONCLUSION OSAS patients have elevated levels of RDW and MPV compared to controls; however, there was no association between OSAS severity and MPV or RDW.
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Affiliation(s)
- Kyriaki Cholidou
- 1 Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Diseases Hospital, Athens, Greece
| | - Nektarios Anagnostopoulos
- 1 Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Diseases Hospital, Athens, Greece
| | | | - Konstantinos Vafeiadis
- 1 Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Diseases Hospital, Athens, Greece
| | - Agamemnon Bakakos
- 1 Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Diseases Hospital, Athens, Greece
| | - Aggelos Vontetsianos
- 1 Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Diseases Hospital, Athens, Greece
| | - Vasiliki Gogou
- 1 Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Diseases Hospital, Athens, Greece
| | - Zoi Sotiropoulou
- 1 Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Diseases Hospital, Athens, Greece
| | - Christina Anagnostopoulou
- 1 Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Diseases Hospital, Athens, Greece
| | - Anna Papasarantou
- 1 Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Diseases Hospital, Athens, Greece
| | - Paschalis Steiropoulos
- Department of Respiratory Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - Petros Bakakos
- 1 Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Diseases Hospital, Athens, Greece
| | - Andriana I. Papaioannou
- 1 Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Diseases Hospital, Athens, Greece
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Ibrahim A, Högl B, Stefani A. Sleep as the Foundation of Brain Health. Semin Neurol 2025. [PMID: 40139214 DOI: 10.1055/a-2566-4073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2025]
Abstract
Sleep is a vital function, taking about one-third of a human lifetime, and is essential for achieving and maintaining brain health. From homeostatic neurophysiology to emotional and procedural memory processing to clearance of brain waste, sleep and circadian alignment remain paramount. Yet modern lifestyles and clinical practice often dismiss sleep, resulting in profound long-term repercussions. This chapter examines the roles of sleep and circadian rhythms in memory consolidation, synaptic plasticity, and clearance of metabolic waste, highlighting recent advances in neuroscience research. We explore how insufficient and disordered sleep-a public health concern-can impair cognition, escalate neurodegenerative risks, and compromise neurovascular integrity, thereby impacting brain health. These findings underscore the need for comprehensive screening for disturbed sleep and targeted interventions in clinical practice. Emerging interventions and AI-driven technologies may allow early detection and personalized and individualized treatments and improve outcomes. Overall, this chapter reaffirms that healthy sleep is indispensable at any level of neurological disease prevention-on par with the role of diet and exercise in cardiovascular health-and represents the foundation of brain health.
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Affiliation(s)
- Abubaker Ibrahim
- Department of Neurology, Medical University Innsbruck, Innsbruck, Austria
| | - Birgit Högl
- Department of Neurology, Medical University Innsbruck, Innsbruck, Austria
| | - Ambra Stefani
- Department of Neurology, Medical University Innsbruck, Innsbruck, Austria
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Kasai T, Kohno T, Shimizu W, Ando S, Joho S, Osada N, Kato M, Kario K, Shiina K, Tamura A, Yoshihisa A, Fukumoto Y, Takata Y, Yamauchi M, Shiota S, Chiba S, Terada J, Tonogi M, Suzuki K, Adachi T, Iwasaki Y, Naruse Y, Suda S, Misaka T, Tomita Y, Naito R, Goda A, Tokunou T, Sata M, Minamino T, Ide T, Chin K, Hagiwara N, Momomura S. JCS 2023 Guideline on Diagnosis and Treatment of Sleep Disordered Breathing in Cardiovascular Disease. Circ J 2024; 88:1865-1935. [PMID: 39183026 DOI: 10.1253/circj.cj-23-0489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/27/2024]
Affiliation(s)
- Takatoshi Kasai
- Division of School of Health Science, Department of Pathobiological Science and Technology, Faculty of Medicine, Tottori University
| | - Takashi Kohno
- Department of Cardiovascular Medicine, Kyorin University Faculty of Medicine
| | - Wataru Shimizu
- Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School
| | - Shinichi Ando
- Sleep Medicine Center, Fukuokaken Saiseikai Futsukaichi Hospital
| | - Shuji Joho
- Second Department of Internal Medicine, University of Toyama
| | - Naohiko Osada
- Department of Cardiology, St. Marianna University School of Medicine
| | - Masahiko Kato
- Division of School of Health Science, Department of Pathobiological Science and Technology, Faculty of Medicine, Tottori University
| | - Kazuomi Kario
- Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine
| | | | | | - Akiomi Yoshihisa
- Department of Clinical Laboratory Sciences, Fukushima Medical University School of Health Science
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Yoshihiro Fukumoto
- Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine
| | | | - Motoo Yamauchi
- Department of Clinical Pathophysiology of Nursing and Department of Respiratory Medicine, Nara Medical University
| | - Satomi Shiota
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine
| | | | - Jiro Terada
- Department of Respiratory Medicine, Japanese Red Cross Narita Hospital
| | - Morio Tonogi
- 1st Depertment of Oral & Maxillofacial Surgery, Nihon Univercity School of Dentistry
| | | | - Taro Adachi
- Division of Cardiology, Department of Medicine, Showa University School of Medicine
| | - Yuki Iwasaki
- Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School
| | - Yoshihisa Naruse
- Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
| | - Shoko Suda
- Department of Cardiovascular Medicine, Juntendo University School of Medicine
| | - Tomofumi Misaka
- Department of Clinical Laboratory Sciences, Fukushima Medical University School of Health Science
- Department of Cardiovascular Medicine, Fukushima Medical University
| | | | - Ryo Naito
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine
| | - Ayumi Goda
- Department of Cardiovascular Medicine, Kyorin University Faculty of Medicine
| | - Tomotake Tokunou
- Division of Cardiology, Department of Medicine, Fukuoka Dental College
| | - Makoto Sata
- Department of Pulmonology and Infectious Diseases, National Cerebral and Cardiovascular Center
| | | | - Tomomi Ide
- Faculty of Medical Sciences, Kyushu University
| | - Kazuo Chin
- Graduate School of Medicine and Faculty of Medicine, Kyoto University
| | - Nobuhisa Hagiwara
- YUMINO Medical Corporation
- Department of Cardiology, Tokyo Women's Medical University
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He J, Ruan X, Li J. Polycystic ovary syndrome in obstructive sleep apnea-hypopnea syndrome: an updated meta-analysis. Front Endocrinol (Lausanne) 2024; 15:1418933. [PMID: 39247914 PMCID: PMC11377251 DOI: 10.3389/fendo.2024.1418933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 08/06/2024] [Indexed: 09/10/2024] Open
Abstract
Background Obstructive sleep apnea-hypopnea syndrome (OSAHS) is correlated with metabolic deterioration in patients experiencing polycystic ovary syndrome (PCOS). Women diagnosed with PCOS exhibit a heightened prevalence of OSAHS. This meta-analysis aims to assess the morbidity of OSAHS in women affected by PCOS and to examine the differences in metabolism-related indicators between OSAHS-positive and OSAHS-negative in women with PCOS. Methods A comprehensive literature analysis of OSAHS morbidity in women with PCOS was conducted, utilizing databases such as CNKI, EMBASE, PubMed, Web of Science, and Wanfang. A comparison was carried out between patients with OSAHS-positive and those with OSAHS-negative in terms of their clinical characteristics and metabolic differences. The search language included English and Chinese. The acquired data were analyzed by employing RevMan 5.2 and Stata 11.0. Continuous variables with the same units were combined and analyzed through weighted mean differences (WMDs) as effect sizes, while continuous variables with different units were combined and analyzed through standardized mean differences (SMDs) as effect sizes. A conjoint analysis was performed on the basis of I2 value, using either a fixed effect model (I2 ≤ 50%) or a random effect model (I2 > 50%). Results A total of 21 articles met the inclusion criteria for this study. The findings indicated that 20.8% of women with PCOS were found to have comorbid OSAHS. The subjects were categorized into various subgroups for meta-analysis on the basis of race, age, disease severity, body mass index (BMI), and diagnostic criteria of PCOS. The results revealed high morbidity of OSAHS in all subgroups. In addition, most metabolic indicators and parameters of metabolic syndrome were notably worse in women suffering from both PCOS and OSAHS in comparison to their counterparts solely diagnosed with PCOS. Conclusion The current literature indicates higher morbidity of OSAHS among women with PCOS, linking OSAHS with worse metabolic status and obesity in this population. Consequently, clinicians are advised to prioritize the detection and management of OSAHS in women with PCOS. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/#myprospero PROSPERO, identifier (CRD42024528264).
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Affiliation(s)
- Jie He
- Clinical Medical College of Chengdu Medical College, Chengdu, Sichuan, China
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
- Key Laboratory of Geriatric Respiratory Diseases of Sichuan Higher Education Institutes, Chengdu, Sichuan, China
| | - Xia Ruan
- Clinical Medical College of Chengdu Medical College, Chengdu, Sichuan, China
- Department of Rehabilitation, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Jia Li
- Clinical Medical College of Chengdu Medical College, Chengdu, Sichuan, China
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
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7
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Kovbasyuk Z, Ramos‐Cejudo J, Parekh A, Bubu OM, Ayappa IA, Varga AW, Chen M, Johnson AD, Gutierrez‐Jimenez E, Rapoport DM, Osorio RS. Obstructive Sleep Apnea, Platelet Aggregation, and Cardiovascular Risk. J Am Heart Assoc 2024; 13:e034079. [PMID: 39056328 PMCID: PMC11964063 DOI: 10.1161/jaha.123.034079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 05/31/2024] [Indexed: 07/28/2024]
Abstract
BACKGROUND Although related, the precise mechanisms linking obstructive sleep apnea (OSA) and cardiovascular disease (CVD) are unclear. Platelets are mediators of CVD risk and thrombosis and prior studies suggested associations of OSA and platelet activity. The aim of this study is to assess the link between OSA, platelet activity, and CVD-related risk factors. METHODS AND RESULTS We studied the association of OSA-measures and platelet aggregation in participants dually enrolled in the SHHS (Sleep Heart and Health Study) and FHS (Framingham Heart Study). We applied linear regression models with adjustment for demographic and clinical covariates and explored interactions with OSA and CVD-related factors, including age, sex, body mass index, hypertension, OSA diagnosis (apnea-hypopnea index 4%≥5), and aspirin use. Our final sample was of 482 participants (60 years [14.00], 50.4% female). No associations were observed between apnea-hypopnea index 4% and platelet aggregation in the main sample. Stratified analysis revealed an association in aspirin users (n=65) for our primary exposure (apnea-hypopnea index 4%, β=0.523; P<0.001; n=65), and secondary exposures: hypoxic burden (β=0.358; P<0.001), minimum saturation (β=-0.519; P=0.026), and oxygen desaturation index 3% (β=74.672; P=0.002). No associations were detected in nonaspirin users (n=417). CONCLUSIONS No associations were detected between OSA and platelet aggregation in a community sample. Our finding that OSA associates with increased platelet aggregation in the aspirin group, most of whom use it for primary prevention of CVD, suggests that platelet aggregation may mediate the adverse impact of OSA on vascular health in individuals with existing CVD risk, supporting further investigation.
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Affiliation(s)
- Zanetta Kovbasyuk
- Healthy Brain Aging and Sleep CenterDepartment of PsychiatryNew York University Langone Medical CenterNew York CityNY
| | - Jaime Ramos‐Cejudo
- Division of Brain AgingDepartment of PsychiatryNew York University Grossman School of MedicineNew York CityNY
| | - Ankit Parekh
- Division of PulmonaryCritical Care and Sleep MedicineIcahn School of Medicine at Mount SinaiNew York CityNY
| | - Omonigho M. Bubu
- Healthy Brain Aging and Sleep CenterDepartment of PsychiatryNew York University Langone Medical CenterNew York CityNY
| | - Indu A. Ayappa
- Division of PulmonaryCritical Care and Sleep MedicineIcahn School of Medicine at Mount SinaiNew York CityNY
| | - Andrew W. Varga
- Division of PulmonaryCritical Care and Sleep MedicineIcahn School of Medicine at Mount SinaiNew York CityNY
| | - Ming‐Huei Chen
- Population Sciences BranchNational Heart, Lung, and Blood InstituteFraminghamMA
| | - Andrew D. Johnson
- Population Sciences BranchNational Heart, Lung, and Blood InstituteFraminghamMA
| | | | - David M. Rapoport
- Division of Brain AgingDepartment of PsychiatryNew York University Grossman School of MedicineNew York CityNY
| | - Ricardo S. Osorio
- Healthy Brain Aging and Sleep CenterDepartment of PsychiatryNew York University Langone Medical CenterNew York CityNY
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8
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Wu LY, Chai YL, Cheah IK, Chia RSL, Hilal S, Arumugam TV, Chen CP, Lai MKP. Blood-based biomarkers of cerebral small vessel disease. Ageing Res Rev 2024; 95:102247. [PMID: 38417710 DOI: 10.1016/j.arr.2024.102247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 02/12/2024] [Accepted: 02/22/2024] [Indexed: 03/01/2024]
Abstract
Age-associated cerebral small vessel disease (CSVD) represents a clinically heterogenous condition, arising from diverse microvascular mechanisms. These lead to chronic cerebrovascular dysfunction and carry a substantial risk of subsequent stroke and vascular cognitive impairment in aging populations. Owing to advances in neuroimaging, in vivo visualization of cerebral vasculature abnormities and detection of CSVD, including lacunes, microinfarcts, microbleeds and white matter lesions, is now possible, but remains a resource-, skills- and time-intensive approach. As a result, there has been a recent proliferation of blood-based biomarker studies for CSVD aimed at developing accessible screening tools for early detection and risk stratification. However, a good understanding of the pathophysiological processes underpinning CSVD is needed to identify and assess clinically useful biomarkers. Here, we provide an overview of processes associated with CSVD pathogenesis, including endothelial injury and dysfunction, neuroinflammation, oxidative stress, perivascular neuronal damage as well as cardiovascular dysfunction. Then, we review clinical studies of the key biomolecules involved in the aforementioned processes. Lastly, we outline future trends and directions for CSVD biomarker discovery and clinical validation.
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Affiliation(s)
- Liu-Yun Wu
- Memory Aging and Cognition Centre, National University Health System, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yuek Ling Chai
- Memory Aging and Cognition Centre, National University Health System, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Irwin K Cheah
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Neurobiology Programme, Centre for Life Sciences, National University of Singapore, Singapore
| | - Rachel S L Chia
- Memory Aging and Cognition Centre, National University Health System, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Saima Hilal
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Kent Ridge, Singapore
| | - Thiruma V Arumugam
- School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; Centre for Cardiovascular Biology and Disease Research, Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC, Australia
| | - Christopher P Chen
- Memory Aging and Cognition Centre, National University Health System, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Mitchell K P Lai
- Memory Aging and Cognition Centre, National University Health System, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
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9
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Palomares DE, Tran PL, Jerman C, Momayez M, Deymier P, Sheriff J, Bluestein D, Parthasarathy S, Slepian MJ. Vibro-Acoustic Platelet Activation: An Additive Mechanism of Prothrombosis with Applicability to Snoring and Obstructive Sleep Apnea. Bioengineering (Basel) 2023; 10:1414. [PMID: 38136005 PMCID: PMC10741028 DOI: 10.3390/bioengineering10121414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 11/28/2023] [Accepted: 12/08/2023] [Indexed: 12/24/2023] Open
Abstract
Introduction: Obstructive sleep apnea (OSA) and loud snoring are conditions with increased cardiovascular risk and notably an association with stroke. Central in stroke are thrombosis and thromboembolism, all related to and initiaing with platelet activation. Platelet activation in OSA has been felt to be driven by biochemical and inflammatory means, including intermittent catecholamine exposure and transient hypoxia. We hypothesized that snore-associated acoustic vibration (SAAV) is an activator of platelets that synergizes with catecholamines and hypoxia to further amplify platelet activation. Methods: Gel-filtered human platelets were exposed to snoring utilizing a designed vibro-acoustic exposure device, varying the time and intensity of exposure and frequency content. Platelet activation was assessed via thrombin generation using the Platelet Activity State assay and scanning electron microscopy. Comparative activation induced by epinephrine and hypoxia were assessed individually as well as additively with SAAV, as well as the inhibitory effect of aspirin. Results: We demonstrate that snore-associated acoustic vibration is an independent activator of platelets, which is dependent upon the dose of exposure, i.e., intensity x time. In snoring, acoustic vibrations associated with low-frequency sound content (200 Hz) are more activating than those associated with high frequencies (900 Hz) (53.05% vs. 22.08%, p = 0.001). Furthermore, SAAV is additive to both catecholamines and hypoxia-mediated activation, inducing synergistic activation. Finally, aspirin, a known inhibitor of platelet activation, has no significant effect in limiting SAAV platelet activation. Conclusion: Snore-associated acoustic vibration is a mechanical means of platelet activation, which may drive prothrombosis and thrombotic risk clinically observed in loud snoring and OSA.
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Affiliation(s)
- Daniel E. Palomares
- Department of Biomedical Engineering, University of Arizona, Tucson, AZ 85724, USA;
- Arizona Center for Accelerated Biomedical Innovation, University of Arizona, Tucson, AZ 85724, USA; (P.L.T.); (M.M.); (P.D.); (S.P.)
| | - Phat L. Tran
- Arizona Center for Accelerated Biomedical Innovation, University of Arizona, Tucson, AZ 85724, USA; (P.L.T.); (M.M.); (P.D.); (S.P.)
- Department of Medicine, University of Arizona, Tucson, AZ 85724, USA;
| | - Catherine Jerman
- Department of Medicine, University of Arizona, Tucson, AZ 85724, USA;
| | - Moe Momayez
- Arizona Center for Accelerated Biomedical Innovation, University of Arizona, Tucson, AZ 85724, USA; (P.L.T.); (M.M.); (P.D.); (S.P.)
- Department of Mining & Geological Engineering, University of Arizona, Tucson, AZ 85724, USA
| | - Pierre Deymier
- Arizona Center for Accelerated Biomedical Innovation, University of Arizona, Tucson, AZ 85724, USA; (P.L.T.); (M.M.); (P.D.); (S.P.)
- Department of Materials Science & Engineering, University of Arizona, Tucson, AZ 85724, USA
| | - Jawaad Sheriff
- Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA; (J.S.); (D.B.)
| | - Danny Bluestein
- Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA; (J.S.); (D.B.)
| | - Sairam Parthasarathy
- Arizona Center for Accelerated Biomedical Innovation, University of Arizona, Tucson, AZ 85724, USA; (P.L.T.); (M.M.); (P.D.); (S.P.)
- Department of Medicine, University of Arizona, Tucson, AZ 85724, USA;
- Health Sciences Center for Sleep and Circadian Sciences, University of Arizona, Tucson, AZ 85724, USA
| | - Marvin J. Slepian
- Department of Biomedical Engineering, University of Arizona, Tucson, AZ 85724, USA;
- Arizona Center for Accelerated Biomedical Innovation, University of Arizona, Tucson, AZ 85724, USA; (P.L.T.); (M.M.); (P.D.); (S.P.)
- Department of Medicine, University of Arizona, Tucson, AZ 85724, USA;
- Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA; (J.S.); (D.B.)
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10
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Lee-Iannotti JK. Sleep Disorders in Patients with Neurologic Disease. Continuum (Minneap Minn) 2023; 29:1188-1204. [PMID: 37590829 DOI: 10.1212/con.0000000000001270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/19/2023]
Abstract
OBJECTIVE This article provides an overview of the growing body of evidence showing bidirectional relationships between sleep and various neurologic disorders. LATEST DEVELOPMENTS Mounting evidence demonstrates that disrupted sleep can negatively impact various neurologic disease processes, including stroke, multiple sclerosis, epilepsy, neuromuscular disorders including amyotrophic lateral sclerosis, and headache syndromes. Abnormal sleep can also be a precursor to Alzheimer disease and neurodegenerative disease states such as Parkinson disease and dementia with Lewy bodies. Interventions to improve sleep and treat obstructive sleep apnea may play a vital role in preventing neurologic disease development and progression. ESSENTIAL POINTS Sleep disorders are common among patients with neurologic disorders. To provide comprehensive care to patients with neurologic conditions, neurologists must ask patients about sleep issues that may warrant further diagnostic testing, treatment, and sleep medicine referral when indicated.
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Lee G, Dharmakulaseelan L, Muir RT, Iskander C, Kendzerska T, Boulos MI. Obstructive sleep apnea is associated with markers of cerebral small vessel disease in a dose-response manner: A systematic review and meta-analysis. Sleep Med Rev 2023; 68:101763. [PMID: 36805589 DOI: 10.1016/j.smrv.2023.101763] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 01/25/2023] [Accepted: 01/27/2023] [Indexed: 02/10/2023]
Abstract
Cerebral small vessel disease manifests on neuroimaging as white matter hyperintensities, lacunes, cerebral microbleeds, perivascular spaces or subcortical infarcts and is a major contributor to dementia, stroke and incident death. We aimed to determine whether obstructive sleep apnea severity is associated cerebral small vessel disease. A systematic search was conducted for studies examining the association between obstructive sleep apnea and cerebral small vessel disease markers. A random-effects model was used to meta-analyze unadjusted odds ratios derived from event rates. The neuroimaging-derived measures of white matter hyperintensities, lacunes, and cerebral microbleeds were compared against increasing obstructive sleep apnea severity, as measured by apnea-hypopnea indices of <5, 5-15, ≥15 and ≥ 30. Thirty-two observational studies were included: ten reported effect sizes for white matter hyperintensities, nine for lacunes and three for cerebral microbleeds. Compared to patients without obstructive sleep apnea, the odds of possessing white matter hyperintensities were 1.7 [95% confidence interval 0.9-3.6] in mild, 3.9 [2.7-5.5] in moderate-severe and 4.3 [1.9-9.6] in severe obstructive sleep apnea. Moderate-severe obstructive sleep apnea was associated with a higher risk of lacunar infarcts. Obstructive sleep apnea had no association with cerebral microbleeds and an indeterminate association with perivascular spaces and subcortical infarcts due to insufficient data.
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Affiliation(s)
- Grace Lee
- Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Laavanya Dharmakulaseelan
- Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada
| | - Ryan T Muir
- Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada
| | - Carol Iskander
- Faculty of Medicine, The National University of Ireland, Galway, Ireland
| | - Tetyana Kendzerska
- Department of Medicine, Division of Respirology, The Ottawa Hospital/University of Ottawa, Ottawa, Ontario, Canada
| | - Mark I Boulos
- Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada; Sleep Laboratory, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
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12
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Ming X, Cai W, Li Z, Yang X, Yang M, Pan D, Chen X. CD40LG and GZMB were correlated with adipose tissue macrophage infiltration and involved in obstructive sleep apnea related metabolic dysregulation: Evidence from bioinformatics analysis. Front Genet 2023; 14:1128139. [PMID: 36923793 PMCID: PMC10009156 DOI: 10.3389/fgene.2023.1128139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 02/16/2023] [Indexed: 03/03/2023] Open
Abstract
Both obesity and obstructive sleep apnea (OSA) can lead to metabolic dysregulation and systemic inflammation. Similar to obesity, increasing evidence has revealed that immune infiltration in the visceral adipose tissue (VAT) is associated with obstructive sleep apnea-related morbidity. However, the pathological changes and potential molecular mechanisms in visceral adipose tissue of obstructive sleep apnea patients need to be further studied. Herein, by bioinformatics analysis and clinical validation methods, including the immune-related differentially expressed genes (IRDEGs) analysis, protein-protein interaction network (PPI), functional enrichment analysis, a devolution algorithm (CIBERSORT), spearman's correlation analysis, polymerase chain reaction (PCR), Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), we identified and validated 10 hub IRDEGs, the relative mRNA expression of four hub genes (CRP, CD40LG, CCL20, and GZMB), and the protein expression level of two hub genes (CD40LG and GZMB) were consistent with the bioinformatics analysis results. Immune infiltration results further revealed that obstructive sleep apnea patients contained a higher proportion of pro-inflammatory M1 macrophages and a lower proportion of M2 macrophages. Spearman's correlation analysis showed that CD40LG was positively correlated with M1 macrophages and GZMB was negatively correlated with M2 macrophages. CD40LG and GZMB might play a vital role in the visceral adipose tissue homeostasis of obstructive sleep apnea patients. Their interaction with macrophages and involved pathways not only provides new insights for understanding molecular mechanisms but also be of great significance in discovering novel small molecules or other promising candidates as immunotherapies of OSA-associated metabolic complications.
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Affiliation(s)
- Xiaoping Ming
- Department of Otorhinolaryngology, Head, and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Sleep Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Weisong Cai
- Department of Otorhinolaryngology, Head, and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Sleep Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zhen Li
- Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Bariatric and Metabolic Disease Surgery Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xiuping Yang
- Department of Otorhinolaryngology, Head, and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Sleep Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Minlan Yang
- Department of Otorhinolaryngology, Head, and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Sleep Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Dingyu Pan
- Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Bariatric and Metabolic Disease Surgery Center, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xiong Chen
- Department of Otorhinolaryngology, Head, and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.,Sleep Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, China
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Chen M, Wang B, Huang J, Zhao J, Chen J, Chen G. The role of platelet-related parameters for the prediction of NAFLD in OSAHS patients. BMC Pulm Med 2022; 22:487. [PMID: 36566219 DOI: 10.1186/s12890-022-02291-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 12/19/2022] [Indexed: 12/25/2022] Open
Abstract
PURPOSE As the detection of non-alcoholic fatty liver disease (NAFLD) is imperative for the prevention of its complications, we aimed to explore the predictive value of platelet to lymphocyte count ratio (PLR) and white blood cell count to mean platelet volume ratio (WBC/MPV) in relation to the occurrence of NAFLD among patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS This was a cross-sectional study consisting of 351 patients with OSAHS (279 with and 72 without NAFLD). The logistic regression analysis was performed to estimate associations between PLR, WBC/MPV, and NAFLD. Finally, the receiver operating characteristic curve (ROC curve) was used to analyze the efficacy of PLR and WBC/MPV in NAFLD prediction. RESULTS Compared to the OSAHS-only group, there was a rising trend in AHI and TS90% in the OSAHS + NAFLD group. And the logistic regression analysis identified average oxygen saturation (MaSO2), WBC/MPV and PLR as predicted factors (odds ratio [OR] = 1.134, P = 0.031; OR = 7.559, P = 0.018, OR = 0.980, P < 0.001, respectively) for NAFLD in OSAHS patients. Moreover, compared with WBC/MPV, PLR, FLI, and APRI, a combination of WBC/MPV and PLR presented the largest AUC for the detection of NAFLD in BMI < 28 kg/m2 (0.753, 95% CI 0.684-0.822), and in age ≥ 60 years subgroup (0.786, 95% CI 0.692-0.880) in ROC analysis. Meanwhile, a combination of WBC/MPV and PLR presented the second largest AUC for the detection of NAFLD in all subjects (0.743, 95% CI 0.708-0.831), as well as in the age < 60 years subgroup (0.729, 95% CI 0.652-0.806), only ranked after FLI, suggesting the combination of WBC/MPV and PLR has a good predictive value for NAFLD in OSAHS patients. CONCLUSION We confirmed that the levels of WBC/MPV, PLR, and MaSO2 were closely related to the occurrence of NAFLD among OSAHS patients. Furthermore, our results highlighted the clinical combination of WBC/MPV and PLR levels could act as a simple and effective biomarker for screening NAFLD in patients with OSAHS.
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Affiliation(s)
- Menglan Chen
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Fujian Provincial Sleep-Disordered Breathing Clinic Center, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Institute of Respiratory Disease, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Department of Respiratory and Critical Care Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, People's Republic of China
| | - Biying Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Fujian Provincial Sleep-Disordered Breathing Clinic Center, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Institute of Respiratory Disease, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Department of Respiratory and Critical Care Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, People's Republic of China
| | - Jiefeng Huang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Fujian Provincial Sleep-Disordered Breathing Clinic Center, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Institute of Respiratory Disease, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Department of Respiratory and Critical Care Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, People's Republic of China
| | - Jianming Zhao
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Fujian Provincial Sleep-Disordered Breathing Clinic Center, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Institute of Respiratory Disease, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Department of Respiratory and Critical Care Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, People's Republic of China
| | - Jia Chen
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Fujian Provincial Sleep-Disordered Breathing Clinic Center, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Institute of Respiratory Disease, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China.,Department of Respiratory and Critical Care Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, People's Republic of China
| | - Gongping Chen
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China. .,Fujian Provincial Sleep-Disordered Breathing Clinic Center, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China. .,Institute of Respiratory Disease, Fujian Medical University, No. 20, Chazhong Road, Taijiang District, Fuzhou, 350005, Fujian Province, People's Republic of China. .,Department of Respiratory and Critical Care Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, People's Republic of China.
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14
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Advances in Molecular Pathology of Obstructive Sleep Apnea. Molecules 2022; 27:molecules27238422. [PMID: 36500515 PMCID: PMC9739159 DOI: 10.3390/molecules27238422] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 11/22/2022] [Accepted: 11/24/2022] [Indexed: 12/03/2022] Open
Abstract
Obstructive sleep apnea (OSA) is a common syndrome that features a complex etiology and set of mechanisms. Here we summarized the molecular pathogenesis of OSA, especially the prospective mechanism of upper? airway dilator fatigue and the current breakthroughs. Additionally, we also introduced the molecular mechanism of OSA in terms of related studies on the main signaling pathways and epigenetics alterations, such as microRNA, long non-coding RNA, and DNA methylation. We also reviewed small molecular compounds, which are potential targets for gene regulations in the future, that are involved in the regulation of OSA. This review will be beneficial to point the way for OSA research within the next decade.
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Abd El-Razek R, Abou Hagar A, Orabi M, Moawad S, El-Samahy M. Impact of obstructive sleep apnea on platelet activation and development of silent brain infarctions. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2022. [DOI: 10.1186/s41983-022-00575-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Abstract
Background
Obstructive sleep apnea (OSA) is a unique potent predictor for stroke compared to other predictors. By aiding in the adherence of leukocytes and platelets, soluble P-selectin (sP-selectin) contributes to the development of ischemic stroke. The objective of this study was to investigate the independent impact of OSA on platelet activation and development of silent brain infarction. Twenty-four OSA patients and 24 controls were studied in a case–control study, who underwent one-night polysomnography, magnetic resonance imaging for evaluation of silent brain infarctions (SBI), measurement of serum (sP-selectin) levels for assessment of increased platelet activation and C-reactive protein (CRP) serum levels.
Results
Out of 24 patients, 5 (20.8%) had mild OSA and 8 (33.3%) had moderate and 11 (45.8%) had severe OSA. Serum levels of sP-selectin were statistically significantly higher in moderate and severe groups (p < 0.001). Eleven (57.9%) patients in moderate and severe OSA had SBI. Fifty percent of patients with moderate OSA had elevated serum sP-selectin and 25.0% of them had SBI and 81.8% of severe OSA patients had elevated serum sP-selectin and 81.8% of them had SBI. Patients with mild OSA and controls had no SBI and normal serum sP-selectin level. CRP was statistically significantly higher in moderate and severe OSA groups (16.6% and 45.8%) than the mild and control groups (4.1% and 0%) (p < 0.001).
Conclusion
Moderate and severe obstructive sleep apnea were associated independently with elevated serum sP-selectin reflecting increased platelet function, elevated inflammatory marker CRP and an increased risk of silent brain infarctions.
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16
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Zota IM, Adam CA, Marcu DTM, Stătescu C, Sascău R, Anghel L, Boișteanu D, Roca M, Cozma CLD, Maștaleru A, Constantin MML, Moaleș EA, Mitu F. CPAP Influence on Readily Available Inflammatory Markers in OSA-A Pilot Study. Int J Mol Sci 2022; 23:12431. [PMID: 36293288 PMCID: PMC9604000 DOI: 10.3390/ijms232012431] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/07/2022] [Accepted: 10/14/2022] [Indexed: 11/25/2022] Open
Abstract
Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse, chronic hypoxia and a proinflammatory phenotype. The purpose of our study was to evaluate readily available inflammatory biomarkers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), WBC-to-MPV ratio (WMR) and lymphocyte-to-C-reactive protein ratio (LCR)) before and after CPAP in patients with moderate-severe OSA. We performed a prospective study that included patients with newly-diagnosed moderate-severe OSA. The control groups (patients without OSA and with mild OSA) were selected from the hospital polygraphy database. All subjects underwent routine blood panel, which was repeated in moderate-severe OSA patients after 8 weeks of CPAP. Our final study group included 31 controls, 33 patients with mild, 22 patients with moderate and 37 patients with severe OSA. CRP, ESR, NLR and WMR were correlated with OSA severity. After 8-week CPAP therapy, we documented a decrease in weight status, which remained statistically significant in both CPAP-adherent and non-adherent subgroups. Readily available, inexpensive inflammatory parameters can predict the presence of moderate-severe OSA, but are not influenced by short-term CPAP.
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Affiliation(s)
- Ioana Madalina Zota
- Department of Medical Specialties (I), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Cristina Andreea Adam
- Department of Medical Specialties (I), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Dragoș Traian Marius Marcu
- Department of Medical Specialties (I), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Cristian Stătescu
- Department of Medical Specialties (I), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Radu Sascău
- Department of Medical Specialties (I), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Larisa Anghel
- Department of Medical Specialties (I), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Daniela Boișteanu
- Department of Medical Specialties (III), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Mihai Roca
- Department of Medical Specialties (I), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Corina Lucia Dima Cozma
- Department of Medical Specialties (I), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Alexandra Maștaleru
- Department of Medical Specialties (I), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Maria Magdalena Leon Constantin
- Department of Medical Specialties (I), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Elena Andreea Moaleș
- Department of Medical Specialties (III), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Florin Mitu
- Department of Medical Specialties (I), Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
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Nacafaliyev V, Ortan P, Sayin SS. Relationship between obstructive sleep apnoea syndrome and silent brain infarction. Postgrad Med J 2022:7148069. [PMID: 37130819 DOI: 10.1136/pmj-2022-141911] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 09/14/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND The relationship between obstructive sleep apnea syndrome (OSAS) and ischaemic stroke is less known. OBJECTIVES This study aimed to investigate the relationship between OSAS and silent brain infarcts (SBI). METHODS Patients who applied to our clinic with the complaint of snoring, respiratory arrest during sleep, that underwent polysomnography were included. All patients were undergone cranial magnetic resonance imaging to detect SBI. RESULTS SBI was found in 176 (51.5%) of 270 patients in the group with OSAS and 94 (34.8%) patients without OSAS. The patients were evaluated according to their Apnea-Hypopnea Index(AHI) ratio, and those with were found to be significant in terms of SBI. SBI was detected in 56.56% in the moderate and severe (AHI ˃15) stage group and 39.94% in the normal and mild (AHI ≤15) OSAS group (p=0.009). CONCLUSIONS SBI was found to be significantly higher in patients with moderate and severe stage OSAS compared to the normal and mild OSAS group. Desaturations during sleep may influence the formation of these infarcts. Therefore, this study reported that patients with moderate and severe sleep apnea syndrome may have a higher risk of developing ischaemic cerebrovascular disease and that the treatment of these patients should be planned in this respect.
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Affiliation(s)
- Vusal Nacafaliyev
- Department of Neurology, University of Health Sciences Izmir Bozyaka Education and Research Hospital, Izmir, Turkey
| | - Pınar Ortan
- Neurology, University of Health Sciences Izmir Bozyaka Education and Research Hospital, Izmir, Turkey
| | - Sevgi Sidika Sayin
- Department of Neurology, University of Health Sciences Izmir Bozyaka Education and Research Hospital, Izmir, Turkey
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18
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Javaheri S, Peker Y, Yaggi HK, Bassetti CLA. Obstructive sleep apnea and stroke: The mechanisms, the randomized trials, and the road ahead. Sleep Med Rev 2021; 61:101568. [PMID: 34906778 DOI: 10.1016/j.smrv.2021.101568] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 11/02/2021] [Accepted: 11/03/2021] [Indexed: 10/19/2022]
Abstract
When considered separately from cardiovascular disease, stroke is the third leading cause of death in the U.S. and is the leading cause of long-term disability in adults. New approaches that can be offered to the majority of ischemic stroke patients, can be continued throughout post-stroke care, can limit stroke severity, and can complement or even enhance rehabilitation, would transform ischemic stroke recovery. The treatment of obstructive sleep apnea (OSA) in patients with acute ischemic stroke may represent one such approach. This manuscript reviews the epidemiologic studies of the bidirectional association between OSA and stroke, and the mechanisms and molecular signatures of OSA leading to transient ischemic attack and stroke as well as the randomized controlled trials and observational cohort studies examining continuous positive airway treatment efficacy on the impact of stroke outcomes. Finally, the insights these studies provide on future research are also discussed.
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Affiliation(s)
- Shahrokh Javaheri
- Division of Pulmonary and Sleep Medicine, Bethesda North Hospital, Cincinnati, OH, USA; Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Cardiology, The Ohio State University, Columbus, OH, USA.
| | - Yüksel Peker
- Department of Pulmonary Medicine, Koc University School of Medicine, Istanbul, Turkey; Department of Molecular and Clinical Medicine/Cardiology, Sahlgrenska Academy, University of Gothenburg, Sweden; Department of Clinical Sciences, Respiratory Medicine and Allergology, Faculty of Medicine, Lund University, Lund, Sweden; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - H Klar Yaggi
- Department of Medicine, Yale University School of Medicine, New Haven, CT, USA; Clinical Epidemiology Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA
| | - Claudio L A Bassetti
- Department of Neurology, Inselspital, University of Bern, Switzerland; Department of Neurology, Sechenow University Faculty of Medicine, Moscow, Russia
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Ye H, Huang S, Song Y, Liu H, Zhao X, Zhao D, Mi F, Wang X, Zhang X, Du J, Zhu N, Zhang L, Zhao Y. Gene co-expression analysis identifies modules related to insufficient sleep in humans. Sleep Med 2021; 86:68-74. [PMID: 34464880 DOI: 10.1016/j.sleep.2021.08.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 07/12/2021] [Accepted: 08/05/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Insufficient sleep and circadian rhythm disruption may cause cancer, obesity, cardiovascular disease, and cognitive impairment. The underlying mechanisms need to be elucidated. METHOD Weighted gene co-expression network analysis (WGCNA) was used to identify co-expressed modules. Connectivity Map tool was used to identify candidate drugs based on top connected genes. R ptestg package was utilized to detected module rhythmicity alteration. A hypergeometric test was used to test the enrichment of insomnia SNP signals in modules. Google Scholar was used to validate the modules and hub genes by literature. RESULTS We identified a total of 45 co-expressed modules. These modules were stable and preserved. Eight modules were correlated with sleep restriction duration. Module rhythmicity was disrupted in sleep restriction subjects. Hub genes that involve in insufficient sleep also play important roles in sleep disorders. Insomnia GWAS signals were enriched in six modules. Finally, eight drugs associated with sleep disorders were identified. CONCLUSION Systems biology method was used to identify sleep-related modules, hub genes, and candidate drugs. Module rhythmicity was altered in sleep insufficient subjects. Thiamphenicol, lisuride, timolol, and piretanide are novel candidates for sleep disorders.
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Affiliation(s)
- Hua Ye
- Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Shiliang Huang
- Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Yufei Song
- Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Huiwei Liu
- Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Xiaosu Zhao
- Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Dan Zhao
- Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Fangxia Mi
- Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Xinxue Wang
- Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Xuesong Zhang
- Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Jinman Du
- Physical Examination Center, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Na Zhu
- Physical Examination Center, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Liangshun Zhang
- Physical Examination Center, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China
| | - Yibin Zhao
- Department of Anus & Intestine Surgery, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China.
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20
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Two effective clinical prediction models to screen for obstructive sleep apnoea based on body mass index and other parameters. Sleep Breath 2021; 26:923-932. [PMID: 34142269 DOI: 10.1007/s11325-021-02347-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 03/07/2021] [Accepted: 03/09/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND AND OBJECTIVE The diagnosis of obstructive sleep apnea (OSA) relies on polysomnography which is time-consuming and expensive. We therefore aimed to develop two simple, non-invasive models to screen adults for OSA. METHODS The effectiveness of using body mass index (BMI) and a new visual prediction model to screen for OSA was evaluated using a development set (1769 participants) and confirmed using an independent validation set (642 participants). RESULTS Based on the development set, the best BMI cut-off value for diagnosing OSA was 26.45 kg/m2, with an area under the curve (AUC) of 0.7213 (95% confidence interval (CI), 0.6861-0.7566), a sensitivity of 57% and a specificity of 78%. Through forward conditional logistic regression analysis using a stepwise selection model developed from observed data, seven clinical variables were evaluated as independent predictors of OSA: age, BMI, sex, Epworth Sleepiness Scale score, witnessed apnoeas, dry mouth and arrhythmias. With this new model, the AUC was 0.7991 (95% CI, 0.7668-0.8314) for diagnosing OSA (sensitivity, 75%; specificity, 71%). The results were confirmed using the validation set. A nomogram for predicting OSA was generated based on this new model using statistical software. CONCLUSIONS BMI can be used as an indicator to screen for OSA in the community. We created an internally validated, highly distinguishable, visual and parsimonious prediction model comprising BMI and other parameters that can be used to identify patients with OSA among outpatients. Use of this prediction model may help to improve clinical decision-making.
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21
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Mochol J, Gawrys J, Gajecki D, Szahidewicz-Krupska E, Martynowicz H, Doroszko A. Cardiovascular Disorders Triggered by Obstructive Sleep Apnea-A Focus on Endothelium and Blood Components. Int J Mol Sci 2021; 22:5139. [PMID: 34066288 PMCID: PMC8152030 DOI: 10.3390/ijms22105139] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 05/09/2021] [Accepted: 05/10/2021] [Indexed: 12/19/2022] Open
Abstract
Obstructive sleep apnea (OSA) is known to be an independent cardiovascular risk factor. Among arousal from sleep, increased thoracic pressure and enhanced sympathetic activation, intermittent hypoxia is now considered as one of the most important pathophysiological mechanisms contributing to the development of endothelial dysfunction. Nevertheless, not much is known about blood components, which justifies the current review. This review focuses on molecular mechanisms triggered by sleep apnea. The recurrent periods of hypoxemia followed by reoxygenation promote reactive oxygen species (ROS) overproduction and increase inflammatory response. In this review paper we also intend to summarize the effect of treatment with continuous positive airway pressure (CPAP) on changes in the profile of the endothelial function and its subsequent potential clinical advantage in lowering cardiovascular risk in other comorbidities such as diabetes, atherosclerosis, hypertension, atrial fibrillation. Moreover, this paper is aimed at explaining how the presence of OSA may affect platelet function and exert effects on rheological activity of erythrocytes, which could also be the key to explaining an increased risk of stroke.
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Affiliation(s)
| | | | | | | | | | - Adrian Doroszko
- Department of Internal Medicine, Hypertension and Clinical Oncology, Faculty of Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (J.M.); (J.G.); (D.G.); (E.S.-K.); (H.M.)
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22
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Zhu D, Xu Z, Liu T, Li Y. Soluble P-selectin levels in patients with obstructive sleep apnea: a systematic review and meta-analysis. Eur Arch Otorhinolaryngol 2021; 278:4633-4644. [PMID: 33950356 DOI: 10.1007/s00405-021-06831-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 04/17/2021] [Indexed: 12/13/2022]
Abstract
PURPOSE Obstructive sleep apnea (OSA) patients are at increased risk for cardiovascular disease, stroke, atherosclerosis, hypertension, and venous thromboembolism. Elevated soluble P-selectin (sP-selectin) levels are also associated with increased risk of above diseases. But whether sP-selectin levels in OSA patients are higher than their counterparts remain unclear, since previous studies yielded inconsistent results. Therefore, a meta-analysis is warranted. METHODS PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible studies. Studies were included if they reported sP-selectin levels of both OSA patients and non-OSA controls. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to determine the effect sizes. RESULTS Nine eligible studies were finally evaluated. When all the studies were pooled, sP-selectin levels in OSA patients were significantly higher than that in controls (SMD = 0.54, 95% CI 0.29-0.78, I2 = 66%, p < 0.0001). In the subgroup analysis based on BMI matched groups, sP-selectin levels were significantly higher in OSA patients than that in controls (SMD = 0.52, 95% CI 0.27-0.76, I2 = 23%, p < 0.0001). In the subgroup analysis stratified by blood source, either serum sP-selectin levels or plasma sP-selectin levels in OSA patients were higher than that in controls. Moderate-to-severe OSA patients had significant higher sP-selectin levels (SMD = 0.80, 95% CI 0.45-1.15, I2 = 67%, p < 0.00001), while mild OSA patients showed no significant difference with controls. CONCLUSION The pooled results reveal that OSA patients have higher sP-selectin levels than non-OSA controls. This conclusion remains unaltered in all subgroups other than the subgroup of mild OSA patients. Additional studies are warranted to better identify the role of sP-selectin as a potential biomarker in OSA patients.
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Affiliation(s)
- Ding Zhu
- Department of Internal Medicine, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China.,Respiratory Group, Department of Endoscopy, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China.,Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, 310000, China
| | - Zhibo Xu
- Department of Respiratory Medicine, Xixi Hospital of Hangzhou, Hangzhou, 310023, China
| | - Tingting Liu
- Department of Respiratory Medicine, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310005, China
| | - Yaqing Li
- Department of Internal Medicine, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China. .,Respiratory Group, Department of Endoscopy, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, China. .,Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, 310000, China. .,, 1 Banshan East Road, Hangzhou, China.
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23
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Imani MM, Sadeghi M, Farokhzadeh F, Khazaie H, Brand S, Dürsteler KM, Brühl A, Sadeghi-Bahmani D. Evaluation of Blood Levels of C-Reactive Protein Marker in Obstructive Sleep Apnea: A Systematic Review, Meta-Analysis and Meta-Regression. Life (Basel) 2021; 11:life11040362. [PMID: 33921787 PMCID: PMC8073992 DOI: 10.3390/life11040362] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 04/07/2021] [Accepted: 04/10/2021] [Indexed: 01/08/2023] Open
Abstract
(1) Introduction: High sensitivity C-reactive protein (hs-CRP) and CRP are inflammatory biomarkers associated with several inflammatory diseases. In both pediatric and adult individuals with Obstructive Sleep Apnea (OSA) higher hs-CRP and CRP were observed, compared to controls. With the present systematic review, meta-analysis and meta-regression we expand upon previous meta-analyses in four ways: (1) We included 109 studies (96 in adults and 13 in children); (2) we reported subgroup and meta-regression analyses in adults with OSA compared to controls on the serum and plasma levels of hs-CRP; (3) we reported subgroup and meta-regression analyses in adults with OSA compared to controls on the serum and plasma levels of CRP; (4) we reported serum and plasma levels of both hs-CRP and CRP in children with OSA, always compared to controls. (2) Materials and Methods: The PubMed/Medline, Scopus, Cochrane Library, and Web of Science databases were searched to retrieve articles published until 31 May 2020, with no restrictions. The data included basic information involving the first author, publication year, country of study, ethnicity of participants in each study, age, BMI, and AHI of both groups, and mean and standard deviation (SD) of plasma and serum levels of CRP and hs-CRP. (3) Results: A total of 1046 records were retrieved from the databases, and 109 studies were selected for the analysis (96 studies reporting the blood levels of hs-CRP/CRP in adults and 13 studies in children). For adults, 11 studies reported plasma hs-CRP, 44 serum hs-CRP, 9 plasma CRP, and 32 serum CRP levels. For children, 6 studies reported plasma hs-CRP, 4 serum hs-CRP, 1 plasma CRP, and 2 serum CRP levels. Compared to controls, the pooled MD of plasma hs-CRP levels in adults with OSA was 0.11 mg/dL (p < 0.00001). Compared to controls, the pooled MD of serum hs-CRP levels in adults with OSA was 0.09 mg/dL (p < 0.00001). Compared to controls, the pooled MD of plasma CRP levels in adults with OSA was 0.06 mg/dL (p = 0.72). Compared to controls, the pooled MD of serum CRP levels in adults with OSA was 0.36 mg/dL (p < 0.00001). Compared to controls, the pooled MD of plasma hs-CRP, serum hs-CRP, plasma hs-CRP, and serum hs-CRP in children with OSA was 1.17 mg/dL (p = 0.005), 0.18 mg/dL (p = 0.05), 0.08 mg/dL (p = 0.10), and 0.04 mg/dL (p = 0.33), respectively. The meta-regression showed that with a greater apnea-hypapnea index (AHI), serum hs-CRP levels were significantly higher. (4) Conclusions: The results of the present systematic review, meta-analysis and meta-regression showed that compared to healthy controls plasma and serum levels of hs-CRP and serum CRP level were higher in adults with OSA; for children, and compared to controls, just plasma hs-CRP levels in children with OSA were higher.
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Affiliation(s)
- Mohammad Moslem Imani
- Department of Orthodontics, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran;
| | - Masoud Sadeghi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran;
| | - Farid Farokhzadeh
- Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran;
| | - Habibolah Khazaie
- Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran; (H.K.); (D.S.-B.)
| | - Serge Brand
- Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran; (H.K.); (D.S.-B.)
- Center for Affective, Stress and Sleep Disorders (ZASS), Psychiatric University Hospital Basel, 4002 Basel, Switzerland;
- Department of Clinical Research, University of Basel, 4031 Basel, Switzerland
- Department of Sport, Exercise and Health, Division of Sport Science and Psychosocial Health, University of Basel, 4052 Basel, Switzerland
- Substance Abuse Prevention Research Center, Kermanshah University of Medical Sciences, Kermanshah 67146, Iran
- School of Medicine, Tehran University of Medical Sciences, Tehran 25529, Iran
- Correspondence:
| | - Kenneth M. Dürsteler
- Psychiatric Clinics, Division of Substance Use Disorders, University of Basel, 4002 Basel, Switzerland;
- Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, 8001 Zurich, Switzerland
| | - Annette Brühl
- Center for Affective, Stress and Sleep Disorders (ZASS), Psychiatric University Hospital Basel, 4002 Basel, Switzerland;
- Department of Clinical Research, University of Basel, 4031 Basel, Switzerland
| | - Dena Sadeghi-Bahmani
- Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran; (H.K.); (D.S.-B.)
- Center for Affective, Stress and Sleep Disorders (ZASS), Psychiatric University Hospital Basel, 4002 Basel, Switzerland;
- Department of Clinical Research, University of Basel, 4031 Basel, Switzerland
- Substance Abuse Prevention Research Center, Kermanshah University of Medical Sciences, Kermanshah 67146, Iran
- Departments of Physical Therapy, University of Alabama at Birmingham, Birmingham, AL 35209, USA
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Nassir CMNCM, Ghazali MM, Hashim S, Idris NS, Yuen LS, Hui WJ, Norman HH, Gau CH, Jayabalan N, Na Y, Feng L, Ong LK, Abdul Hamid H, Ahamed HN, Mustapha M. Diets and Cellular-Derived Microparticles: Weighing a Plausible Link With Cerebral Small Vessel Disease. Front Cardiovasc Med 2021; 8:632131. [PMID: 33718454 PMCID: PMC7943466 DOI: 10.3389/fcvm.2021.632131] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 01/19/2021] [Indexed: 12/24/2022] Open
Abstract
Cerebral small vessel disease (CSVD) represents a spectrum of pathological processes of various etiologies affecting the brain microcirculation that can trigger neuroinflammation and the subsequent neurodegenerative cascade. Prevalent with aging, CSVD is a recognized risk factor for stroke, vascular dementia, Alzheimer disease, and Parkinson disease. Despite being the most common neurodegenerative condition with cerebrocardiovascular axis, understanding about it remains poor. Interestingly, modifiable risk factors such as unhealthy diet including high intake of processed food, high-fat foods, and animal by-products are known to influence the non-neural peripheral events, such as in the gastrointestinal tract and cardiovascular stress through cellular inflammation and oxidation. One key outcome from such events, among others, includes the cellular activations that lead to elevated levels of endogenous cellular-derived circulating microparticles (MPs). MPs can be produced from various cellular origins including leukocytes, platelets, endothelial cells, microbiota, and microglia. MPs could act as microthrombogenic procoagulant that served as a plausible culprit for the vulnerable end-artery microcirculation in the brain as the end-organ leading to CSVD manifestations. However, little attention has been paid on the potential role of MPs in the onset and progression of CSVD spectrum. Corroboratively, the formation of MPs is known to be influenced by diet-induced cellular stress. Thus, this review aims to appraise the body of evidence on the dietary-related impacts on circulating MPs from non-neural peripheral origins that could serve as a plausible microthrombosis in CSVD manifestation as a precursor of neurodegeneration. Here, we elaborate on the pathomechanical features of MPs in health and disease states; relevance of dietary patterns on MP release; preclinical studies pertaining to diet-based MPs contribution to disease; MP level as putative surrogates for early disease biomarkers; and lastly, the potential of MPs manipulation with diet-based approach as a novel preventive measure for CSVD in an aging society worldwide.
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Affiliation(s)
| | - Mazira Mohamad Ghazali
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Sabarisah Hashim
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Nur Suhaila Idris
- Department of Family Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Lee Si Yuen
- Department of Internal Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Wong Jia Hui
- Neurobiology of Aging and Disease Laboratory, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Haziq Hazman Norman
- Anatomy Unit, International Medical School (IMS), Management and Science University (MSU), Shah Alam, Malaysia
| | - Chuang Huei Gau
- Department of Psychology and Counselling, Faculty of Arts and Social Science, Universiti Tunku Abdul Rahman (UTAR), Kampar, Malaysia
| | - Nanthini Jayabalan
- Translational Neuroscience Lab, University of Queensland (UQ), Centre for Clinical Research, The University of Queensland, Herston, QLD, Australia
| | - Yuri Na
- Center for Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea
| | - Linqing Feng
- Center for Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea
| | - Lin Kooi Ong
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia
- School of Biomedical Sciences and Pharmacy, Priority Research Centre for Stroke and Brain Injury, University of Newcastle, Callaghan, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
- Centre of Research Excellence Stroke Rehabilitation and Brain Recovery, National Health and Medical Research Council (NHMRC), Heidelberg, VIC, Australia
| | - Hafizah Abdul Hamid
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
| | - Haja Nazeer Ahamed
- Crescent School of Pharmacy, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai, India
| | - Muzaimi Mustapha
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia
- Hospital Universiti Sains Malaysia, Jalan Raja Perempuan Zainab II, Kubang Kerian, Malaysia
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25
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Boulos MI, Dharmakulaseelan L, Brown DL, Swartz RH. Trials in Sleep Apnea and Stroke: Learning From the Past to Direct Future Approaches. Stroke 2020; 52:366-372. [PMID: 33349009 DOI: 10.1161/strokeaha.120.031709] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Few randomized controlled trials have evaluated the effectiveness of continuous positive airway pressure (CPAP) in reducing recurrent vascular events and mortality in poststroke obstructive sleep apnea (OSA). To date, results have been mixed, most studies were underpowered and definitive conclusions are not available. Using lessons learned from prior negative trials in stroke, we reappraise prior randomized controlled trials that examined the use of CPAP in treating poststroke OSA and propose the following considerations: (1) Intervention-based changes, such as ensuring that patients are using CPAP for at least 4 hours per night (eg, through use of improvements in CPAP technology that make it easier for patients to use), as well as considering alternative treatment strategies for poststroke OSA; (2) Population-based changes (ie, including stroke patients with severe and symptomatic OSA and CPAP noncompliers); and (3) Changes to timing of intervention and follow-up (ie, early initiation of CPAP therapy within the first 48 hours of stroke and long-term follow-up calculated in accordance with sample size to ensure adequate power). Given the burden of vascular morbidity and mortality in stroke patients with OSA, there is a strong need to learn from past negative trials and explore innovative stroke prevention strategies to improve stroke-free survival.
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Affiliation(s)
- Mark I Boulos
- Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada (M.I.B., L.D., R.H.S.).,Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute (M.I.B., L.D., R.H.S.), Sunnybrook Health Sciences Centre, Toronto, Canada.,Sleep Laboratory (M.I.B., R.H.S.), Sunnybrook Health Sciences Centre, Toronto, Canada
| | - Laavanya Dharmakulaseelan
- Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada (M.I.B., L.D., R.H.S.).,Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute (M.I.B., L.D., R.H.S.), Sunnybrook Health Sciences Centre, Toronto, Canada
| | - Devin L Brown
- Department of Neurology, University of Michigan, Ann Arbor (D.L.B.)
| | - Richard H Swartz
- Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada (M.I.B., L.D., R.H.S.).,Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute (M.I.B., L.D., R.H.S.), Sunnybrook Health Sciences Centre, Toronto, Canada.,Sleep Laboratory (M.I.B., R.H.S.), Sunnybrook Health Sciences Centre, Toronto, Canada
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26
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Bahar Y, Annakkaya AN, Sen C, Oktay M, Aytekin F, Balbay O. Assessment of the frequency of deep venous thromboembolism in obstructive sleep apnea syndrome. Aging Male 2020; 23:1016-1021. [PMID: 31437086 DOI: 10.1080/13685538.2019.1654451] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
The present study aimed to investigate the frequency of deep venous thrombosis (DVT) among patients with obstructive sleep apnea syndrome (OSAS). Patients who referred the preliminary diagnosis of OSAS were included in this study. D-dimer levels of all patients were measured, and D-dimer (+) patients were evaluated by Doppler USG of the lower-extremity. Mean age of the patient group was 52 ± 12 years and 31.8% (76/239) were women. The rate of D-dimer positivity among severe-OSAS cases (15/85) was significantly higher compared to the rest (13/154) (17.6% and 8.4%, respectively; p = 0.034). The risk of D-dimer positivity was elevated by 2.3 folds in severe-OSAS cases (OR: 2,324, 95% confidence interval: 1.048-5.152). Among 28 D-dimer (+) cases, 4 (14.2%) had DVT as demonstrated by USI of the lower-extremity. All four cases with DVT had severe OSAS. D-dimer was positive in 17.6% (15/85) of all severe OSAS cases. DVT was diagnosed in 4.7% (4/85) of severe-OSAS cases. DVT frequency was 26.6% (4/15) in D-dimer (+) severe-OSAS. Findings of this study indicate that severe-OSAS can be a significant risk factor for DVT. Additionally, data obtained in this study underline the benefits of questioning severe-OSAS patients with respect to DVT symptoms, investigating D-dimer levels and evaluating D-dimer (+) severe-OSAS cases for DVT prophylaxis.
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Affiliation(s)
- Yagmur Bahar
- Department of Chest Diseases, Duzce University Medical School, Duzce, Turkey
| | - Ali Nihat Annakkaya
- Department of Chest Diseases, Duzce University Medical School, Duzce, Turkey
| | - Cigdem Sen
- Department of Psychiatric Nursing, Faculty of Health Sciences, Sakarya University, Sakarya, Turkey
| | - Mehtap Oktay
- Department of Radiology, Duzce University Medical School, Duzce, Turkey
| | - Fuat Aytekin
- Department of Chest Diseases, Duzce University Medical School, Duzce, Turkey
| | - Oner Balbay
- Department of Chest Diseases, Duzce University Medical School, Duzce, Turkey
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27
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Liu C, Kang W, Zhang S, Qiao X, Yang X, Zhou Z, Lu H. Mandibular Advancement Devices Prevent the Adverse Cardiac Effects of Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS). Sci Rep 2020; 10:3394. [PMID: 32098974 PMCID: PMC7042252 DOI: 10.1038/s41598-020-60034-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 02/03/2020] [Indexed: 01/21/2023] Open
Abstract
Although considerable research highlights the interactions between obstructive sleep apnea-hypopnea syndrome (OSAHS) and cardiovascular diseases, the effect of mandibular advancement device (MAD) treatment on cardiovascular complications in OSAHS patients remains unclear. We evaluated the effect of OSAHS treatment with MADs on the myocardium. All methods in this study were in accordance with relevant guidelines and regulations of the medical ethics committee in Hospital of Stomatology, Hebei Medical University approved the work. Thirty New Zealand rabbits were randomized into three groups: the control group, Group OSAHS, and Group MAD. Hydrophilic polyacrylamide gel was injected into the soft palate of the rabbits to induce OSAHS. In Group MAD, a MAD was positioned after OSAHS induction. All animals were induced to sleep in a supine position for 4–6 h/day for 8 weeks. Echocardiography was used to determine the structure and function of the heart. The histological changes were detected by optical microscopy and transmission electron microscopy (TEM). The levels of ET-1(endothelin-1) and Ang II (Angiotensin II) in the plasma were measured by an enzyme-linked immunosorbent assay (ELISA). The expression of ET-1 mRNA in heart tissue was detected by RT-PCR. Histological abnormalities, left ventricular hypertrophy, and left ventricular dysfunctions were demonstrated in Group OSAHS, and the abnormities were rescued with MAD treatment. Higher levels of plasma ET-1 and Ang II and elevated expression of ET-1 mRNA in cardiac tissue were detected in Group OSAHS compared with Group MAD and the control group. The blood oxygen saturation was negatively correlated with the levels of ET-1 and Ang II. OSAHS-induced elevated levels of ET-1 and Ang II may be attributed to myocardial structural abnormalities and dysfunction. Early treatment of MADs may play an important role in preventing myocardial damage in OSAHS rabbit model.
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Affiliation(s)
- Chunyan Liu
- Department of Orthodontics, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Shijiazhuang, 050017, P.R. China.,Department of Periodontology and Dental Hygiene, School of Dentistry, University of Detroit Mercy, Detroit, MI, USA
| | - Wenjing Kang
- Department of Orthodontics, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Shijiazhuang, 050017, P.R. China
| | - Shilong Zhang
- Department of Orthodontics, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Shijiazhuang, 050017, P.R. China
| | - Xing Qiao
- Department of Orthodontics, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Shijiazhuang, 050017, P.R. China
| | - Xiuchun Yang
- Department of Cardiology, The Second Hospital of Hebei Medical University; Hebei Province, Shijiazhuang, China
| | - Zheng Zhou
- Department of Periodontology and Dental Hygiene, School of Dentistry, University of Detroit Mercy, Detroit, MI, USA.
| | - Haiyan Lu
- Department of Orthodontics, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Shijiazhuang, 050017, P.R. China.
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28
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Horváth P, Lázár Z, Gálffy G, Puskás R, Kunos L, Losonczy G, Mészáros M, Tárnoki ÁD, Tárnoki DL, Bikov A. Circulating P-Selectin Glycoprotein Ligand 1 and P-Selectin Levels in Obstructive Sleep Apnea Patients. Lung 2020; 198:173-179. [PMID: 31897593 PMCID: PMC7012996 DOI: 10.1007/s00408-019-00299-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 12/02/2019] [Indexed: 02/08/2023]
Abstract
Purpose Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia which induces inflammation in blood vessels leading to the development of cardiovascular comorbidities. Several studies implicated the role of P-selectin in vascular inflammation of OSA. P-selectin glycoprotein ligand 1 (PSGL-1) is the main activator for P-selectin and is involved in immune cell trafficking. However, PSGL-1 has not been analyzed in OSA. The aim of the study was to investigate plasma PSGL-1 and P-selectin levels to have a deeper understanding on their interaction in obstructive sleep apnea. Methods Fifty-one untreated patients with OSA and 42 non-OSA controls were recruited. Plasma PSGL-1 levels were determined in evening and morning samples, P-selectin levels were analyzed in morning samples using commercially available ELISA kits. Polysomnography was performed in all participants. OSA was defined by an apnea–hypopnea index ≥ 5/h. Results PSGL-1 levels did not differ between controls and OSA patients either in the evening or in the morning. Although, there was no difference between controls (16.9/6.8–40.8 ng/ml) and patients with OSA (19.6/8.4–56.8, p = 0.24), patients with severe OSA had increased plasma P-selectin levels (25.6/8.4–56.8 ng/ml) compared to mild OSA patients (14.1/8.5–35.3 ng/ml, p = 0.006) and controls (p = 0.03). Conclusions P-selectin expression relates to disease severity suggesting a pathophysiological role in endothelial cell activation. PSGL-1 levels are unaltered in OSA, suggesting an alternative activation pathway for P-selectin in OSA.
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Affiliation(s)
- P Horváth
- Department of Pulmonology, Semmelweis University, Tömő utca 25-29, Budapest, Hungary.
| | - Z Lázár
- Department of Pulmonology, Semmelweis University, Tömő utca 25-29, Budapest, Hungary
| | - G Gálffy
- Department of Pulmonology, Semmelweis University, Tömő utca 25-29, Budapest, Hungary
| | - R Puskás
- Department of Pulmonology, Semmelweis University, Tömő utca 25-29, Budapest, Hungary
| | - L Kunos
- Department of Pulmonology, Semmelweis University, Tömő utca 25-29, Budapest, Hungary
| | - Gy Losonczy
- Department of Pulmonology, Semmelweis University, Tömő utca 25-29, Budapest, Hungary
| | - M Mészáros
- Department of Pulmonology, Semmelweis University, Tömő utca 25-29, Budapest, Hungary
| | - Á D Tárnoki
- Department of Radiology, Semmelweis University, Budapest, Hungary
| | - D L Tárnoki
- Department of Radiology, Semmelweis University, Budapest, Hungary
| | - A Bikov
- Department of Pulmonology, Semmelweis University, Tömő utca 25-29, Budapest, Hungary
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Circulating P-Selectin and Its Glycoprotein Ligand in Nondiabetic Obstructive Sleep Apnea Patients. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1279:61-69. [PMID: 32170667 DOI: 10.1007/5584_2020_501] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Selectins and their ligands play an important role in atherosclerosis. The role of these adhesion molecules in the pathogenesis of obstructive sleep apnea (OSA) may be of clinical relevance. Therefore, the aim of this study was to assess the serum content of platelet P-selectin (P-SEL) and P-selectin glycoprotein ligand 1 (PSGL-1) in different OSA stages. The study was performed in nondiabetic patients, aged 32-71, in whom OSA was verified by polysomnography. The apnea/hypopnea index (AHI) was used to stratify OSA stages: AHI <5, no sleep pathology (OSA-0); AHI 5-15, (OSA-1); AHI 16-30, (OSA-2); and AHI >30, (OSA-3). There were 16 patients in each group. P-SEL and PSGL-1 were assessed by ELISA kits. There were no appreciable differences in the patients' glucose or high-specificity C-reactive protein content. We found that P-SEL and PSGL-1 significantly increased from OSA-0 to OSA-3. There were the following positive associations in all OSA patients: P-SEL vs. AHI, PSGL-1 vs. AHI, and P-SEL vs. PSGL-1. In addition, the adhesion molecules are associated with the anthropometric parameters, oxygen saturation, and sleep architecture in the OSA-1 group. We conclude that the adhesion molecules consistently increase in the blood of nondiabetic OSA patients, along with progression of disorder severity.
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Chokesuwattanaskul A, Lertjitbanjong P, Thongprayoon C, Bathini T, Sharma K, Mao MA, Cheungpasitporn W, Chokesuwattanaskul R. Impact of obstructive sleep apnea on silent cerebral small vessel disease: a systematic review and meta-analysis. Sleep Med 2019; 68:80-88. [PMID: 32028230 DOI: 10.1016/j.sleep.2019.11.1262] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 10/28/2019] [Accepted: 11/27/2019] [Indexed: 12/28/2022]
Abstract
BACKGROUND Cerebral small vessel disease (CSVD) is a well-known cause of vascular dementia, a leading medical morbidity in the aging population. Obstructive sleep apnea (OSA) has been validated as a cardiovascular risk factor. However, the relationship between these two clinical syndromes is not well established. We aimed to assess the association between OSA and CSVD. METHODS Databases were searched from inception through May 2019. Studies that reported incidence or odd ratios of CSVD in patients with OSA were included. Effect estimates from the individual studies were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS A total of 14 observational studies comprising of 4335 patients were included into the analysis. Compared to patients without OSA, patients with OSA were significantly associated with CSVD magnetic resonance imaging (MRI) findings of white matter hyperintensity (WMH) and asymptomatic lacunar infarction (ALI) with a pooled OR of 2.31 (95% confidence interval [CI], 1.46-3.66, I2 = 79%) and 1.78 (95% CI, 1.06-3.01, I2 = 41%), respectively. However, there was no significant association between OSA and findings of cerebral microbleeds (CMBs), with a pooled odds ratio (OR) of 2.15 (95% CI, 0.64-7.29, I2 = 55%). CONCLUSIONS Our study demonstrated the association between OSA and CSVD MRI findings of white matter hyperintensity (WMH) and asymptomatic lacunar infarction (ALI) when compared to patients without OSA. The absence of an association of CMBs findings with OSA could be due either by a lower sensitivity of neuroimaging techniques utilized to detect CMBs or a potentially different pathogenesis of CMBs.
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Affiliation(s)
- Anthipa Chokesuwattanaskul
- Division of Neurology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand; King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
| | | | | | - Tarun Bathini
- Department of Internal Medicine, University of Arizona, Tucson, AZ, USA
| | - Konika Sharma
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY, USA
| | - Michael A Mao
- Department of Internal Medicine, Mayo Clinic, Jacksonville, FL, 32224, USA
| | | | - Ronpichai Chokesuwattanaskul
- King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
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Obstructive sleep apnea and venous thromboembolism: Overview of an emerging relationship. Sleep Med Rev 2019; 50:101233. [PMID: 31838272 DOI: 10.1016/j.smrv.2019.101233] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 11/05/2019] [Accepted: 11/06/2019] [Indexed: 12/16/2022]
Abstract
Obstructive sleep apnea (OSA) is a risk factor for cardiovascular syndromes. Venous thromboembolism (VTE) is a chronic disease, and pulmonary embolism (PE) is the major expression of VTE and the third most frequent cardiovascular disease. An increasing and emerging number of cross-sectional and longitudinal studies have linked OSA to VTE, and have postulated different putative pathways to explain how OSA might increase the risk of PE. We aim to provide a critical overview of the existing evidence about the complex relationship between these two conditions, with some factors and confounding variables still to be clarified. A global interpretation of the studies shows OSA is highly prevalent in VTE patients. This association represents a major public health burden, given the high prevalence and the mortality rates of both disorders. Although still not proven, OSA may induce a persistent hypercoagulable state that may contribute to increase VTE rate and its recurrence. Coagulant activity, platelet function and fibrinolytic system may improve after continuous positive airway pressure (CPAP) in OSA. However, there is a still a lack of randomized controlled trials to evaluate the potential of CPAP and/or extend oral anticoagulation to reduce PE incidence, recurrence and mortality by PE in patients with OSA.
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Ward SA, Pase MP. Advances in pathophysiology and neuroimaging: Implications for sleep and dementia. Respirology 2019; 25:580-592. [DOI: 10.1111/resp.13728] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 09/02/2019] [Accepted: 10/16/2019] [Indexed: 12/14/2022]
Affiliation(s)
- Stephanie A. Ward
- School of Public Health and Preventive MedicineMonash University Melbourne VIC Australia
- Department of Geriatric MedicinePrince of Wales Hospital Sydney NSW Australia
- Centre for Healthy Brain Ageing (CHeBA), School of PsychiatryUniversity of New South Wales Sydney NSW Australia
| | - Matthew P. Pase
- Melbourne Dementia Research CentreThe Florey Institute of Neuroscience and Mental Health Melbourne VIC Australia
- Faculty of Medicine, Dentistry and Health ScienceThe University of Melbourne Melbourne VIC Australia
- Centre for Human PsychopharmacologySwinburne University of Technology Melbourne VIC Australia
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Huang Y, Yang C, Yuan R, Liu M, Hao Z. Association of obstructive sleep apnea and cerebral small vessel disease: a systematic review and meta-analysis. Sleep 2019; 43:5614282. [PMID: 31696917 DOI: 10.1093/sleep/zsz264] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 08/30/2019] [Indexed: 02/07/2023] Open
Abstract
Abstract
Study Objectives
The objective of the present study was to investigate the association between obstructive sleep apnea (OSA) and the presence of various neuroimaging marker of cerebral small vessel disease (CSVD).
Methods
We systematically searched PubMed, Embase, Web of Science, Scopus, and Cochrane library (from inception to May 2019) for studies evaluating the association between OSA and CSVD, which included white matter hyperintensities (WMH), silent brain infarction (SBI), cerebral microbleeds (CMBs), and perivascular spaces (PVS). Pooled odds ratios (ORs) with 95% confidence interval (CIs) were estimated using random-effects meta-analysis.
Results
After screening 7290 publications, 20 studies were finally included involving 6036 subjects. The sample size ranged from 27 to 1763 (median 158, interquartile range: 67–393). The meta-analysis showed that moderate to severe OSA was positively associated with WMH (13 studies, n = 4412, OR = 2.23, 95% CI = 1.53 to 3.25, I2 = 80.3%) and SBI (12 studies, n = 3353, OR 1.54, 95% CI = 1.06 to 2.23, I2 = 52%). There was no association with CMBs (three studies, n = 342, OR = 2.17, 95% CI = 0.61 to 7.73, I2 = 60.2%) or PVS (two studies, n = 267, OR = 1.56, 95% CI = 0.28 to 8.57, I2 = 69.5%). There was no relationship between mild OSA and CSVD.
Conclusion
Current evidence suggests that moderate to severe sleep apnea is positively related to WMH and SBI, but not CMBs or PVS, which suggests that OSA may contribute to the pathogenesis of CSVD. Further large cohort studies should be prioritized to confirm the findings.
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Affiliation(s)
- Yuhong Huang
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chunsong Yang
- Department of Pharmacy, Evidence-Based Pharmacy Center, West China Second Hospital, Sichuan University, Chengdu, Sichuan China
| | - Ruozhen Yuan
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ming Liu
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zilong Hao
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Improvement of Cognitive Function after Continuous Positive Airway Pressure Treatment for Subacute Stroke Patients with Obstructive Sleep Apnea: A Randomized Controlled Trial. Brain Sci 2019; 9:brainsci9100252. [PMID: 31557935 PMCID: PMC6826775 DOI: 10.3390/brainsci9100252] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 09/23/2019] [Accepted: 09/23/2019] [Indexed: 01/10/2023] Open
Abstract
Background: Obstructive sleep apnea (OSA) is common after stroke. Various studies on continuous positive airway pressure (CPAP) therapy for OSA after stroke have been published. However, there have been no studies from Korea and Asia. The present Korean study aimed to determine whether CPAP treatment during inpatient rehabilitation of stroke patients with sleep disorders, especially OSA, improves function, cognition, sleep quality, and daytime sleepiness. Methods: This single-blind randomized controlled study included 40 stroke patients with OSA between November 2017 and November 2018. The patients were divided into the CPAP treatment group (CPAP and rehabilitation; n = 20) and control group (only rehabilitation; n = 20). The intervention period was 3 weeks. The primary outcomes were function and cognition improvements, and the secondary outcomes were sleep-related improvements. Results: CPAP treatment started at an average of 4.6 ± 2.8 days after admission. Both groups showed improvements in stroke severity, function, and cognition after the 3-week intervention. However, after the intervention, the degree of change in attention and calculation was significantly higher in the CPAP treatment group than in the control group. Additionally, the improvements in sleep quality and daytime sleepiness were greater in the CPAP treatment group than in the control group. Conclusion: CPAP treatment can improve cognitive function, sleep quality, and daytime sleepiness, and it should be considered as part of the rehabilitation program for patients with stroke. Our findings might help in the treatment of stroke patients with OSA in Korea.
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Abstract
Synchronization of molecular, metabolic, and cardiovascular circadian oscillations is fundamental to human health. Sleep-disordered breathing, which disrupts such temporal congruence, elicits hemodynamic, autonomic, chemical, and inflammatory disturbances with acute and long-term consequences for heart, brain, and circulatory and metabolic function. Sleep apnea afflicts a substantial proportion of adult men and women but is more prevalent in those with established cardiovascular diseases and especially fluid-retaining states. Despite the experimental, epidemiological, observational, and interventional evidence assembled in support of these concepts, this substantial body of work has had relatively modest pragmatic impact, thus far, on the discipline of cardiology. Contemporary estimates of cardiovascular risk still are derived typically from data acquired during wakefulness. The impact of sleep-related breathing disorders rarely is entered into such calculations or integrated into diagnostic disease-specific algorithms or therapeutic recommendations. Reasons for this include absence of apnea-related symptoms in most with cardiovascular disease, impediments to efficient diagnosis at the population level, debate as to target, suboptimal therapies, difficulties mounting large randomized trials of sleep-specific interventions, and the challenging results of those few prospective cardiovascular outcome trials that have been completed and reported. The objectives of this review are to delineate the bidirectional interrelationship between sleep-disordered breathing and cardiovascular disease, consider the findings and implications of observational and randomized trials of treatment, frame the current state of clinical equipoise, identify principal current controversies and potential paths to their resolution, and anticipate future directions.
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Affiliation(s)
- John S Floras
- From the University Health Network and Sinai Health System Division of Cardiology, Department of Medicine, University of Toronto, Ontario, Canada.
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36
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Ohta S, Tanaka A, Jinno M, Hirai K, Miyata Y, Yamaguchi M, Homma T, Muramoto M, Watanabe Y, Suzuki S, Yokoe T, Sagara H. Exposure to intermittent hypoxia inhibits allergic airway inflammation in a murine model of asthma. Sleep Breath 2019; 24:523-532. [PMID: 31302837 DOI: 10.1007/s11325-019-01892-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 06/03/2019] [Accepted: 06/29/2019] [Indexed: 10/26/2022]
Abstract
PURPOSE Obesity increases the severity of asthma, and patients with severe asthma are often complicated with obstructive sleep apnea syndrome (OSAS), a concomitant disease of obesity. We investigated whether intermittent hypoxia (IH), which is a physiological feature of OSAS, modifies allergic airway inflammation in a murine model of asthma. METHODS Balb/c mice were sensitized by ovalbumin (OVA) intraperitoneally twice (days 1 and 14) and challenged with intranasal OVA three times (days 21, 22, and 23). The mice were exposed to IH either from days 1 to 24 (long exposure) or only from days 21 to 24 (short exposure). The impact of IH exposure to allergic airway inflammation was investigated using these mice models by histologic, morphometric, and molecular techniques. Additionally, the airway responsiveness to acetylcholine was also assessed. RESULTS OVA-sensitized and OVA-challenged mice exposed to room air (RA) showed increased total cell and eosinophil numbers in the BALF. The levels of interleukin (IL)-5 and IL-13 in the BALF also increased and goblet cell metaplasia was induced. In contrast, both long and short exposure to IH inhibited the increased total cell and eosinophil numbers. The levels of IL-5 and IL-13 in the BALF also decreased on exposure to IH. Moreover, the goblet cell hyperplasia and airway hyperresponsiveness were significantly reduced in mice exposed to IH compared to those exposed to RA. CONCLUSIONS These results suggest that IH may not deteriorate the asthmatic condition in a murine model of asthma.
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Affiliation(s)
- Shin Ohta
- Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan.
| | - Akihiko Tanaka
- Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Megumi Jinno
- Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Kuniaki Hirai
- Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Yoshito Miyata
- Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Munehiro Yamaguchi
- Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Tetsuya Homma
- Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Mayumi Muramoto
- Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Yoshio Watanabe
- Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Shintaro Suzuki
- Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Takuya Yokoe
- Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
| | - Hironori Sagara
- Department of Internal Medicine, Division of Respiratory Medicine and Allergology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
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Moon C, Bendlin BB, Melah KE, Bratzke LC. The association of sleep-disordered breathing and white matter hyperintensities in heart failure patients. Metab Brain Dis 2018; 33:2019-2029. [PMID: 30218440 PMCID: PMC6408271 DOI: 10.1007/s11011-018-0309-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Accepted: 08/26/2018] [Indexed: 01/19/2023]
Abstract
Heart failure patients often manifest white matter hyperintensites on brain magnetic resonance imaging (MRI). White matter hyperintnsities have also been linked with cognitive problems in patients with heart failure. Sleep disordered breathing may contribute to structural brain changes in heart failure. The purpose of this study was to test the extent to which the apnea hypopnea index is associated with global and regional white matter hyperintensities, and is a moderating factor in the relationship between age and white matter hyperintensites. A total of 28 HF patients [mean age (SD) = 67.89 (5.8)] underwent T1-weighted and T2FLAIR MRI and a home sleep monitoring study. The apnea hypopnea index cut off of 10 was used to compare between higher and lower risks of sleep disordered breathing. Regression analysis was used to test the association between apnea hypopnea index and both global and regional white matter hyperintensities. The interaction term was entered to identify the moderation effect. Apnea hypopnea index was associated with higher regional white matter hyperintensities but not global white matter hyperintensities. There was a significant interaction between the apnea hypopnea index and age, such that older participants with the apnea hypopnea index ≥10 showed greater regional white matter hyperintensities than those with the apnea hypopnea index <10. The results of this preliminary study indicate that a higher apnea hypopnea index is associated with more white matter hyperintensities. The age-related white matter hyperintensities appear to be exacerbated by apnea hypopnea index in our individuals with heart failure. Future studies are needed to further investigate the underlying mechanisms.
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Affiliation(s)
- Chooza Moon
- College of Nursing, University of Iowa, 316 CNB, 50 Newton Rd, Iowa City, IA, 52246, USA.
- School of Nursing, University of Wisconsin-Madison, 701 Highland Ave, Madison, WI, 53705, USA.
| | - Barbara B Bendlin
- Wisconsin Alzheimer's Disease Research Center, Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin-Madison, J5/1 Mezzanine CSC, 600 Highland Avenue, Madison, WI, 53792, USA
| | - Kelsey E Melah
- School of Nursing, University of Wisconsin-Madison, 701 Highland Ave, Madison, WI, 53705, USA
| | - Lisa C Bratzke
- School of Nursing, University of Wisconsin-Madison, 701 Highland Ave, Madison, WI, 53705, USA
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Schwarz EI, Furian M, Schlatzer C, Stradling JR, Kohler M, Bloch KE. Nocturnal cerebral hypoxia in obstructive sleep apnoea: a randomised controlled trial. Eur Respir J 2018; 51:13993003.00032-2018. [DOI: 10.1183/13993003.00032-2018] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 04/06/2018] [Indexed: 01/15/2023]
Abstract
Cerebral hypoxia may promote cerebral damage in patients with obstructive sleep apnoea (OSA). We investigated whether OSA patients experience nocturnal cerebral hypoxia that is prevented by continuous positive airway pressure (CPAP).OSA patients using CPAP underwent sleep studies including pulse oximetry (arterial oxygen saturation (SpO2)) and near-infrared spectroscopy to monitor cerebral tissue oxygenation (CTO) at baseline and after 2 weeks on either subtherapeutic or therapeutic CPAP according to randomised allocation. Changes in oxygenation at end of the 2-week intervention were compared between groups.Among 21 patients (mean apnoea/hypopnoea index 50.3 events·h−1), OSA recurred in all nine patients using subtherapeutic CPAP and in none of the patients using therapeutic CPAP: mean (95% CI) between-group differences in changes of oxygen desaturation index from baseline to 2 weeks +40.7 (31.1–50.4) events·h−1 for SpO2 and +37.0 (25.3–48.7) events·h−1 for CTO (both p<0.001). Mean nocturnal SpO2 and CTO decreased more in patients using subtherapeutic versus therapeutic CPAP: −2.4 (−3.4–−1.1)% and −3.8 (−7.4–−0.1)%, respectively; both p<0.03. Severe CTO drops ≥13% associated with cerebral dysfunction in previous studies occurred in four out of nine patients using subtherapeutic CPAP, but in none out of 12 patients using therapeutic CPAP (p=0.01).In patients with OSA, CPAP withdrawal resulted in nocturnal cerebral deoxygenation, suggesting a role of cerebral hypoxia in predisposing untreated OSA patients to cerebral damage.
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Koo DL, Nam H, Thomas RJ, Yun CH. Sleep Disturbances as a Risk Factor for Stroke. J Stroke 2018; 20:12-32. [PMID: 29402071 PMCID: PMC5836576 DOI: 10.5853/jos.2017.02887] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Revised: 01/07/2018] [Accepted: 01/15/2018] [Indexed: 12/30/2022] Open
Abstract
Sleep, a vital process of human being, is carefully orchestrated by the brain and consists of cyclic transitions between rapid eye movement (REM) and non-REM (NREM) sleep. Autonomic tranquility during NREM sleep is characterized by vagal dominance and stable breathing, providing an opportunity for the cardiovascular-neural axis to restore homeostasis, in response to use, distress or fatigue inflicted during wakefulness. Abrupt irregular swings in sympathovagal balance during REM sleep act as phasic loads on the resting cardiovascular system. Any causes of sleep curtailment or fragmentation such as sleep restriction, sleep apnea, insomnia, periodic limb movements during sleep, and shift work, not only impair cardiovascular restoration but also impose a stress on the cardiovascular system. Sleep disturbances have been reported to play a role in the development of stroke and other cardiovascular disorders. This review aims to provide updated information on the role of abnormal sleep in the development of stroke, to discuss the implications of recent research findings, and to help both stroke clinicians and researchers understand the importance of identification and management of sleep pathology for stroke prevention and care.
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Affiliation(s)
- Dae Lim Koo
- Department of Neurology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Hyunwoo Nam
- Department of Neurology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Robert J Thomas
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Chang-Ho Yun
- Department of Neurology, Bundang Clinical Neuroscience Institute, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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The Study of Neurocognitive Outcomes, Radiological and Retinal Effects of Aspirin in Sleep Apnoea- rationale and methodology of the SNORE-ASA study. Contemp Clin Trials 2017; 64:101-111. [PMID: 29097299 DOI: 10.1016/j.cct.2017.10.016] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 10/25/2017] [Accepted: 10/29/2017] [Indexed: 12/29/2022]
Abstract
PURPOSE Sleep disordered breathing (SDB) is highly prevalent in older adults. Increasing evidence links SDB to the risk of dementia, mediated via a number of pathways, some of which may be attenuated by low-dose aspirin. This study will evaluate, in a healthy older cohort, the prospective relationship between SDB and cognitive function, changes in retinal and cerebral microvasculature, and determine whether low-dose aspirin ameliorates the effects of SDB on these outcomes over 3years. DESIGN SNORE-ASA is a sub-study of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised, multi-centre, placebo-controlled trial evaluating the effect of daily 100mg aspirin on disability-free and dementia-free survival in the healthy older adult aged 70 and over. At baseline, 1400 ASPREE participants successfully underwent a home sleep study with a home sleep study screening device for SDB; and 296 underwent both 1.5 Tesla brain magnetic resonance imaging (MRI) and retinal vascular imaging (RVI). Cognitive testing, brain MRI and RVI is being repeated after 3years. PRIMARY OUTCOME MEASURES Change in the modified mini-mental state examination score. Secondary outcome measures are changes in other cognitive tests, and changes in abnormal parameters on RVI and volume of white matter hyper-intensities on brain MRI. CONCLUSION Identifying preventive therapies for delaying the onset of dementia is of paramount importance. The results of this study will help clarify the impact of the SDB on risk of cognitive decline and cerebral small vessel disease, and whether low-dose aspirin can ameliorate cognitive decline in the setting of SDB. SNORE-ASA TRIAL REGISTRATION ACTRN12612000891820: The Principal ASPREE study is registered with the International Standardized Randomized Controlled Trials Register, ASPirin in Reducing Events in the Elderly, Number: ISRCTN83772183 and clinicaltrials.gov Number NCT01038583.
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Hou Y, Yang H, Cui Z, Tai X, Chu Y, Guo X. Tauroursodeoxycholic acid attenuates endoplasmic reticulum stress and protects the liver from chronic intermittent hypoxia induced injury. Exp Ther Med 2017; 14:2461-2468. [PMID: 28962181 PMCID: PMC5609300 DOI: 10.3892/etm.2017.4804] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Accepted: 03/10/2017] [Indexed: 01/14/2023] Open
Abstract
Obstructive sleep apnea that characterized by chronic intermittent hypoxia (CIH) has been reported to associate with chronic liver injury. Tauroursodeoxycholic acid (TUDCA) exerts liver-protective effects in various liver diseases. The purpose of this study was to test the hypothesis that TUDCA could protect liver against CIH injury. C57BL/6 mice were subjected to intermittent hypoxia for eight weeks and applied with TUDCA by intraperitoneal injection. The effect of TUDCA on liver histological changes, liver function, oxidative stress, inflammatory response, hepatocyte apoptosis and endoplasmic reticulum (ER) stress were investigated. The results showed that administration of TUDCA attenuated liver pathological changes, reduced serum alanine aminotransferase and aspartate aminotransferase level, suppressed reactive oxygen species activity, decreased tumor necrosis factor-α and interleukin-1β level and inhibited hepatocyte apoptosis induced by CIH. TUDCA also inhibited CIH-induced ER stress in liver as evidenced by decreased expression of ER chaperone 78 kDa glucose-related protein, unfolded protein response transducers and ER proapoptotic proteins. Altogether, the present study described a liver-protective effect of TUDCA in CIH mice model, and this effect seems at least partly through the inhibition of ER stress.
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Affiliation(s)
- Yanpeng Hou
- Department of Otolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.,Department of Otolaryngology, The 463rd Hospital of The Chinese People's Liberation Army, Shenyang, Liaoning 110042, P.R. China
| | - Huai'an Yang
- Department of Otolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Zeshi Cui
- Science Experiment Center of China Medical University, Shenyang, Liaoning 110001, P.R. China
| | - Xuhui Tai
- Department of Otolaryngology, The 463rd Hospital of The Chinese People's Liberation Army, Shenyang, Liaoning 110042, P.R. China
| | - Yanling Chu
- Department of Otolaryngology, The 463rd Hospital of The Chinese People's Liberation Army, Shenyang, Liaoning 110042, P.R. China
| | - Xing Guo
- Department of Otolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
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de Raaff CA, Gorter-Stam MA, de Vries N, Sinha AC, Jaap Bonjer H, Chung F, Coblijn UK, Dahan A, van den Helder RS, Hilgevoord AA, Hillman DR, Margarson MP, Mattar SG, Mulier JP, Ravesloot MJ, Reiber BM, van Rijswijk AS, Singh PM, Steenhuis R, Tenhagen M, Vanderveken OM, Verbraecken J, White DP, van der Wielen N, van Wagensveld BA. Perioperative management of obstructive sleep apnea in bariatric surgery: a consensus guideline. Surg Obes Relat Dis 2017; 13:1095-1109. [PMID: 28666588 DOI: 10.1016/j.soard.2017.03.022] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 03/21/2017] [Accepted: 03/22/2017] [Indexed: 12/31/2022]
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Chowdhuri S, Quan SF, Almeida F, Ayappa I, Batool-Anwar S, Budhiraja R, Cruse PE, Drager LF, Griss B, Marshall N, Patel SR, Patil S, Knight SL, Rowley JA, Slyman A. An Official American Thoracic Society Research Statement: Impact of Mild Obstructive Sleep Apnea in Adults. Am J Respir Crit Care Med 2017; 193:e37-54. [PMID: 27128710 DOI: 10.1164/rccm.201602-0361st] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Mild obstructive sleep apnea (OSA) is a highly prevalent disorder in adults; however, whether mild OSA has significant neurocognitive and cardiovascular complications is uncertain. OBJECTIVES The specific goals of this Research Statement are to appraise the evidence regarding whether long-term adverse neurocognitive and cardiovascular outcomes are attributable to mild OSA in adults, evaluate whether or not treatment of mild OSA is effective at preventing or reducing these adverse neurocognitive and cardiovascular outcomes, delineate the key research gaps, and provide direction for future research agendas. METHODS Literature searches from multiple reference databases were performed using medical subject headings and text words for OSA in adults as well as by hand searches. Pragmatic systematic reviews of the relevant body of evidence were performed. RESULTS Studies were incongruent in their definitions of "mild" OSA. Data were inconsistent regarding the relationship between mild OSA and daytime sleepiness. However, treatment of mild OSA may improve sleepiness in patients who are sleepy at baseline and improve quality of life. There is limited or inconsistent evidence pertaining to the impact of therapy of mild OSA on neurocognition, mood, vehicle accidents, cardiovascular events, stroke, and arrhythmias. CONCLUSIONS There is evidence that treatment of mild OSA in individuals who demonstrate subjective sleepiness may be beneficial. Treatment may also improve quality of life. Future research agendas should focus on clarifying the effect of mild OSA and impact of effective treatment on other neurocognitive and cardiovascular endpoints as detailed in the document.
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Abstract
Patients with wake-up strokes account for approximately 1 in 5 individuals presenting with an acute ischemic stroke. However, they are commonly excluded from acute stroke treatment. This article reviews the current understanding of wake-up strokes. A comparison of wake-up and awake-onset strokes demonstrated that they are physiologically, clinically, and radiologically similar. Use of advanced CT and MRI techniques may help extend acute stroke treatment options to patients with wake-up stroke.
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Affiliation(s)
- Jenny P Tsai
- Department of Neurology and Neurological Sciences, Stanford University Medical Centre, Stanford, CA
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Sarioglu N, Demirpolat G, Erel F, Kose M. Which Is the Ideal Marker for Early Atherosclerosis in Obstructive Sleep Apnea (OSA) - Carotid Intima-Media Thickness or Mean Platelet Volume? Med Sci Monit 2017; 23:1674-1681. [PMID: 28384127 PMCID: PMC5390721 DOI: 10.12659/msm.900959] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Accepted: 09/19/2016] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Obstructive sleep apnea (OSA) is known to be closely associated with cardiovascular disease. Carotid intima-media thickness (IMT) is widely used for assessment of atherosclerosis. Mean platelet volume (MPV) is a new marker associated with atherothrombosis. In this study, we aimed to detect early atherosclerosis by measuring carotid intima-media thickness and to investigate the relationship between MPV and IMT and OSA severity. MATERIAL AND METHODS The study population consisted of 158 patients who underwent polysomnography and did not have any overt cardiac disease or risk factors. Carotid IMT was measured by ultrasonography. Blood samples were taken for MPV determination. Subjects were divided into 4 groups according to OSA severity: control, mild, moderate, and severe OSA. RESULTS CONCLUSIONS OSA patients appear to have increased carotid IMT suggestive of an atherosclerotic process. Carotid IMT could be a more useful indicator than MPV in these patients. Long-term prospective studies are needed to confirm these results.
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Affiliation(s)
- Nurhan Sarioglu
- Department of Pulmonary Diseases, Faculty of Medicine, Balikesir University, Balikesir, Turkey
| | - Gulen Demirpolat
- Department of Radiology, Faculty of Medicine, Balikesir University, Balikesir, Turkey
| | - Fuat Erel
- Department of Pulmonary Diseases, Faculty of Medicine, Balikesir University, Balikesir, Turkey
| | - Mehmet Kose
- Department of Pulmonary Diseases, Faculty of Medicine, Balikesir University, Balikesir, Turkey
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Physiopathologie du syndrome d’apnées-hypopnées obstructives du sommeil et de ses conséquences cardio-métaboliques. Presse Med 2017; 46:395-403. [DOI: 10.1016/j.lpm.2016.09.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Accepted: 09/05/2016] [Indexed: 01/03/2023] Open
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Bironneau V, Goupil F, Ducluzeau PH, Le Vaillant M, Abraham P, Henni S, Dubois S, Paris A, Priou P, Meslier N, Sanguin C, Trzépizur W, Andriantsitohaina R, Martinez MC, Gagnadoux F. Association between obstructive sleep apnea severity and endothelial dysfunction in patients with type 2 diabetes. Cardiovasc Diabetol 2017; 16:39. [PMID: 28327146 PMCID: PMC5361793 DOI: 10.1186/s12933-017-0521-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2017] [Accepted: 03/15/2017] [Indexed: 12/11/2022] Open
Abstract
Background Obstructive sleep apnea (OSA) and type 2 diabetes (T2D) are associated with endothelial dysfunction a main predictor of late cardiovascular (CV) events. Despite the high prevalence of OSA in patients with T2D, the impact of OSA severity on endothelial function has not been clearly elucidated. The aim of this cross-sectional study was to determine whether increasing OSA severity is associated with poorer endothelial function in patients with T2D. Methods 140 patients with T2D and no overt CV disease underwent polysomnography, peripheral arterial tonometry, clinic blood pressure (BP) measurement, biological assessment for CV risk factors, daytime sleepiness and health related quality of life (HRQL) questionnaires. The following commonly used cut-offs for apnea-hypopnea index (AHI) were used to define 3 categories of disease severity: AHI < 15 (no OSA or mild OSA), 15 ≤ AHI < 30 (moderate OSA), and AHI ≥ 30 (severe OSA). The primary outcome was the reactive hyperemia index (RHI), a validated assessment of endothelial function. Results 21.4% of patients had moderate OSA and 47.6% had severe OSA. Increasing OSA severity and nocturnal hypoxemia were not associated with a significant decrease in RHI. Endothelial dysfunction (RHI < 1.67) was found in 47.1, 44.4 and 39.2% of patients with no OSA or mild OSA, moderate OSA and severe OSA, respectively (p = 0.76). After adjustment for confounders including body mass index, increasing OSA severity was associated with higher systolic BP (p = 0.03), lower circulating levels of adiponectin (p = 0.0009), higher levels of sP-selectin (p = 0.03), lower scores in 3 domains of HRQL including energy/vitality (p = 0.02), role functioning (p = 0.01), and social functioning (p = 0.04). Conclusions Moderate to severe OSA is very common but has no impact on digital micro-vascular endothelial function in patients with T2D.
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Affiliation(s)
| | | | - Pierre Henri Ducluzeau
- Unité d'Endocrinologie-Diabétologie-Nutrition, Pole de Médecine, CHRU de Tours, Tours, France
| | - Marc Le Vaillant
- Centre de Recherche Médecine, Sciences, Santé, Santé mentale, Société, CNRS UMR 8211, INSERM UMR U988-EHESS, Villejuif, France
| | - Pierre Abraham
- Département de Médecine du Sport et Explorations Fonctionnelles Vasculaires, Université Bretagne Loire, CHU d'Angers, Angers, France
| | - Samir Henni
- Département de Médecine du Sport et Explorations Fonctionnelles Vasculaires, Université Bretagne Loire, CHU d'Angers, Angers, France
| | - Séverine Dubois
- Département d'Endocrinologie, Diabétologie, Nutrition, Université Bretagne Loire, CHU d'Angers, Angers, France
| | - Audrey Paris
- Service de Pneumologie, Centre Hospitalier, Le Mans, France
| | - Pascaline Priou
- Université Bretagne Loire, INSERM UMR 1063, Angers, France.,Département de Pneumologie, Université Bretagne Loire, CHU d'Angers, 4 Rue Larrey, 49100, Angers, France
| | - Nicole Meslier
- Université Bretagne Loire, INSERM UMR 1063, Angers, France.,Département de Pneumologie, Université Bretagne Loire, CHU d'Angers, 4 Rue Larrey, 49100, Angers, France
| | - Claire Sanguin
- Service d'Endocrinologie, Diabétologie, Centre Hospitalier, Le Mans, France
| | - Wojciech Trzépizur
- Université Bretagne Loire, INSERM UMR 1063, Angers, France.,Département de Pneumologie, Université Bretagne Loire, CHU d'Angers, 4 Rue Larrey, 49100, Angers, France
| | | | | | - Frédéric Gagnadoux
- Université Bretagne Loire, INSERM UMR 1063, Angers, France. .,Département de Pneumologie, Université Bretagne Loire, CHU d'Angers, 4 Rue Larrey, 49100, Angers, France.
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Koo DL, Kim JY, Lim JS, Kwon HM, Nam H. Cerebral Microbleeds on MRI in Patients with Obstructive Sleep Apnea. J Clin Sleep Med 2017; 13:65-72. [PMID: 27655453 DOI: 10.5664/jcsm.6390] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2016] [Accepted: 08/08/2016] [Indexed: 12/17/2022]
Abstract
STUDY OBJECTIVES Obstructive sleep apnea (OSA) is known to increase the risk of stroke. Cerebral microbleeds (CMBs) are considered one of the precursors to symptomatic stroke. We aimed to clarify the relationship between OSA and CMBs. METHODS We recruited patients who visited our clinic for the evaluation of sleep-disordered breathing. All patients underwent both overnight polysomnography and brain magnetic resonance imaging, which included T2*-weighted gradient-recalled echo images. We applied multivariate logistic regression and partial correlation analysis to estimate the relationship between OSA and CMBs. RESULTS A total of 75 (45 male, 30 female) patients were enrolled. Their mean age was 60.5 years. Patients with CMBs had a significantly higher apneahypopnea index (AHI) compared with those without CMBs. AHI equal to or greater than 15 was a significant independent predictor of CMBs (adjusted odds ratio, 4.51; 95% CI, 1.40-14.58; p = 0.012) in the multivariate regression analysis. In addition, a partial correlation analysis adjusted for age, hypertension, diabetes, and cardiovascular disease revealed a positive relationship between AHI and the number of CMBs (r = 0.585, p = 0.028). CONCLUSIONS Moderate-to-severe OSA can be one of the independent predictors of CMBs which are considered a surrogate marker of overt stroke.
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Affiliation(s)
- Dae Lim Koo
- Department of Neurology, Seoul National University Boramae Hospital, Seoul, Korea
| | - Jun Yup Kim
- Department of Neurology, Seoul National University Boramae Hospital, Seoul, Korea
| | - Jae-Sung Lim
- Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - Hyung-Min Kwon
- Department of Neurology, Seoul National University Boramae Hospital, Seoul, Korea
| | - Hyunwoo Nam
- Department of Neurology, Seoul National University Boramae Hospital, Seoul, Korea
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Song S, Tan J, Miao Y, Zhang Q. Obstructive sleep apnea-hypopnea syndrome and cognitive impairments in the elderly. BIO WEB OF CONFERENCES 2017. [DOI: 10.1051/bioconf/20170801027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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