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Sleep apnea and acute ischemic stroke: clinical and pathophysiological implications

English title Sleep apnea and acute ischemic stroke: clinical and pathophysiological implications
Applicant Bassetti Claudio L.
Number 125069
Funding scheme Project funding (Div. I-III)
Research institution Universitätsklinik für Neurologie Inselspital Universität Bern
Institution of higher education University of Zurich - ZH
Main discipline Neurology, Psychiatry
Start/End 01.09.2009 - 31.12.2012
Approved amount 415'000.00
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Keywords (17)

sleep apnea; stroke; cardiovascular risk factors; outcome; blood pressure; oxidative stress; endothelial function; neuroimaging; cerebral hemodynamics; humoral factors; near-infrared spectrophotometry; magnetic resonance imaging; pulse wave analysis; Cerebrovascular events; Continuous Positive Airway Pressure; CPAP; Sleep disordered breathing

Lay Summary (English)

Lead
Lay summary
Prof. Dr. Claudio Bassetti, Neurocentre of Southern Switzerland, Ospedale Civico, Via Tesserete 46, 6900 Lugano Lead Sleep disordered breathing is an independent risk factor for cardiovascular morbidity and mortality and is frequent in patients with acute cerebrovascular events. In this study we observe the association between sleep disordered breathing, hypertension, stroke and the evolution of blood markers for atherosclerosis as well as the efficacy of Continuous Positive Airway Pressure treatment in patients with acute or subacute cerebrovascular events.BackgroundSleep disordered breathing (SDB) is characterized by repetitive apnoeas and/or hypopnoeas during sleep, associated with oxygen desaturations and sleep disruption. Acute stroke may cause a new-onset of sleep disordered breathing or worsen a pre-existing one. Sleep disordered breathing may adversely affect clinical evolution after acute ischemic stroke. A strong association exists between SDB and both hypertension and stroke. Their relationship, however, remains poorly known. There is a growing evidence for a direct pathophysiological link between obstructive SDB, cardiovascular diseases and atherosclerosis /atherogenesis. Endothelial function was shown to be impaired in patients with hypertension and atherosclerosis, and was suppressed in patients with obstructive SDB. Increased serum levels of circulating inflammatory markers were documented in patients with sleep disordered breathing. These inflammatory markers play a role in the development and progression of atherosclerosis in patients with obstructive SDB.ObjectivesThe SAS CARE 1 study is planned to verify whether or not sleep disordered breathing has a detrimental 3 months effect on cardiovascular functions and markers after acute cerebrovascular events. The SAS CARE 2 study is designed to address whether or not the treatment of sleep disordered breathing with CPAP reduces the combined rate of mortality, stroke, cardiovascular events (myocardial infarction/revascularisation/instable angina/ hospitalisation for heart insufficiency) over a 24 months period in patients after acute cerebrovascular events.SignificanceThe SAS CARE study will add to our understanding of the clinical implications of sleep disordered breathing in patients with acute cerebrovascular events and of the feasibility/efficacy of Continuous Positive Airway Pressure treatment in terms of cardio-cerebrovascular prevention and influence on outcome in stroke patients.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Endothelial Dysfunction and Arterial Stiffness in Ischemic Stroke : The Role of Sleep-Disordered Breathing
Cereda Carlo W, Tamisier Renaud, Manconi Maudo, Andreotti Jennifer, Frangi Jane, Pifferini Valeria, Bassetti Claudio L (2013), Endothelial Dysfunction and Arterial Stiffness in Ischemic Stroke : The Role of Sleep-Disordered Breathing, in Stroke, 44, 1175-1178.
Cerebral hemodynamic changes in stroke during sleep-disordered breathing
Pizza Fabio, Biallas Martin, Kallweit Ulf, Wolf Martin, Bassetti Claudio L (2012), Cerebral hemodynamic changes in stroke during sleep-disordered breathing, in Stroke, 43(7), 1951-1953.
Sleep-disordered breathing in acute ischemic stroke and transient ischemic attack: effects on short- and long-term outcome and efficacy of treatment with continuous positive airways pressure--rational
Cereda Carlo W, Bassetti Claudio L (2012), Sleep-disordered breathing in acute ischemic stroke and transient ischemic attack: effects on short- and long-term outcome and efficacy of treatment with continuous positive airways pressure--rational, in Int J Stroke, 7(7), 597-603.
Sleep and stroke
Bassetti Claudio L, Hermann Dirk M (2011), Sleep and stroke, in P. Montagna and S. Chokroverty Editors (ed.), 1051-1072.
Nocturnal cerebral hemodynamics in snorers and in patients with obstructive sleep apnea: a near-infrared spectroscopy study
Pizza Fabio, Biallas Marin, Wolf Martin, Werth Esther, Bassetti Claudio L (2010), Nocturnal cerebral hemodynamics in snorers and in patients with obstructive sleep apnea: a near-infrared spectroscopy study, in Sleep, 33(2), 205-210.
Integrating the Review of Gottlieb et al. With the SAS-CARE Study
Mauro Manconi, Ott Sebastian R, Bassetti Claudio L, Integrating the Review of Gottlieb et al. With the SAS-CARE Study, in Sleep.
Longitudinal Polysomnographic Assessment from Acute to Subacute Phase in Infra- vs Supratentorial Stroke
Manconi Mauro, Zavalko Irina, Cereda Carlo, Pisarenco Iraida, Ott Sebastian R, Fulda Stephany, Bassetti Claudio L, Longitudinal Polysomnographic Assessment from Acute to Subacute Phase in Infra- vs Supratentorial Stroke, in Cerebrovascular Diseases .

Collaboration

Group / person Country
Types of collaboration
University of Haifa, Paretz Lavie Israel (Asia)
- Research Infrastructure
Ospedale S. Giovanni, Bellinzona / Sanor Györig Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Neurocentro EOC, Lugano / Carlo Cereda Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Universitätsklinikum Münster / Peter Young Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Ospedale Niguarda, Milan / Lino Nobili Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Universitätsspital Bern / Sebastian Ott Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
20. Jahrestagung der Deutschen Gesellschaft für Schlafforschung und Schlafmedizin Talk given at a conference 06.12.2012 Berlin, Germany Bassetti Claudio L.;
8. Jahresmeeting der Klinischen Neurowissenschaften Bern Poster 04.12.2012 Bern, Switzerland Bassetti Claudio L.;
8. Jahresmeeting der Klinischen Neurowissenschaften Bern Poster 04.12.2012 Bern, Switzerland Bassetti Claudio L.;
8. Jahresmeeting der Klinischen Neurowissenschaften Bern Poster 04.12.2012 Bern, Switzerland Baracchi Francesca; Bassetti Claudio L.;
8. Jahresmeeting der Klinischen Neurowissenschaften Bern Poster 04.12.2012 Bern, Switzerland Bassetti Claudio L.;
8. Jahresmeeting der Klinischen Neurowissenschaften Bern Poster 04.12.2012 Bern, Switzerland Bassetti Claudio L.;
8. Jahresmeeting der Klinischen Neurowissenschaften Bern Poster 04.12.2012 Basel, Switzerland Bassetti Claudio L.; Baracchi Francesca;
188. Jahrestagung Schweizerische Neurologische Gesellschaft Talk given at a conference 08.11.2012 Basel, Switzerland Bassetti Claudio L.;
188. Jahrestagung Schweizerische Neurologische Gesellschaft Talk given at a conference 08.11.2012 Basel, Switzerland Bassetti Claudio L.;
188. Jahrestagung Schweizerische Neurologische Gesellschaft Poster 08.11.2012 Basel, Switzerland Bassetti Claudio L.;
188. Jahrestagung Schweizerische Neurologische Gesellschaft Poster 08.11.2012 Basel, Switzerland Bassetti Claudio L.;
188. Jahrestagung Schweizerische Neurologische Gesellschaft Poster 08.11.2012 Basel, Switzerland Bassetti Claudio L.; Pisarenco Iraida;
188. Jahrestagung Schweizerische Neurologische Gesellschaft Poster 08.11.2012 Basel, Switzerland Bassetti Claudio L.; Baracchi Francesca;
188. Jahrestagung Schweizerische Neurologische Gesellschaft Talk given at a conference 08.11.2012 Basel, Switzerland Bassetti Claudio L.; Baracchi Francesca;
Simposio della Fondazione Sir John Eccles Talk given at a conference 27.10.2012 Ascona, Switzerland Bassetti Claudio L.;
Symposium on Sleep Disorders 28th Dr. Janez Faganel Memorial Lecture Talk given at a conference 05.10.2012 Ljublijana, Slovenia Bassetti Claudio L.;
85. Kongress der Deutschen Gesellschaft für Neurologie Talk given at a conference 26.09.2012 Hamburg, Germany Bassetti Claudio L.;
Simposio Sonno 2012 in onore del Prof. Claudio L. Bassetti Talk given at a conference 13.09.2012 Lugano, Switzerland Bassetti Claudio L.;
World Association of Sleep Medicine: 4th Int. Congress on Sleep Medicine Poster 10.09.2012 Quebec, Canada Bassetti Claudio L.;
21st Congress of the European Sleep Research Society Talk given at a conference 07.09.2012 Paris, France Bassetti Claudio L.;
Colloque Interville Lugano-Bern Talk given at a conference 15.06.2012 Lugano Ospedale civico, Switzerland Bassetti Claudio L.;
American Accademy of Neurology (AAN) Annual Meeting Poster 22.04.2012 New Orleans, United States of America Bassetti Claudio L.;
187. Jahrestagung Schweizerische Neurologische Gesellschaft Poster 03.11.2011 St. Gallen, Switzerland Bassetti Claudio L.;
187. Jahrestagung Schweizerische Neurologische Gesellschaft Poster 03.11.2011 St. Gallen, Switzerland Bassetti Claudio L.;
XXI Congresso Nazinale AIMS (Associazioneitaliana di Medicina del Sonno) Poster 02.10.2011 Pavia, Italy Petrini-Klieber Liliane; Kuen Doris; Frangi Jane; Bassetti Claudio L.;
European Neurological Society Talk given at a conference 28.05.2011 Lisbon, Portugal Bassetti Claudio L.;
63rd AAN Annual Meeting der American Academy of Neurology Talk given at a conference 09.04.2011 Hawaii, United States of America Bassetti Claudio L.;
First SFCNS Congress Swiss Federation of Clinical Neuro-Societies Talk given at a conference 02.10.2010 Basel, Switzerland Bassetti Claudio L.;
USZ, Tag der Forschung Talk given at a conference 08.04.2010 Zürich, Switzerland Bassetti Claudio L.;


Self-organised

Title Date Place
16. Berner Schlaf-Wach-Symposium 25.10.2012 Bern, Switzerland
Sleep disordered breathing (SDB) 13.10.2011 Lugano, Switzerland
Giornata della ricerca clinica della Svizzera Italiana 25.03.2011 Lugano, Switzerland

Awards

Title Year
Premio Crivelli awarded to Carlo Cereda 2011
Pisa Sleep Award 2010

Associated projects

Number Title Start Funding scheme
166827 Early Sleep Apnea Treatment in Stroke: A Randomized, Rater-Blinded, Clinical Trial of Adaptive Servo-Ventilation 01.06.2016 Investigator Initiated Clinical Trials (IICT)

Abstract

Background: Sleep apnea (SA) has been recognized as independent risk factor for cardiovascular morbidity and mortality and is very frequent (more than 50%) in patients with acute stroke. Preliminary observations suggested that 1) stroke may cause (or worsen pre-existing) SA; 2) SA may adversely affect outcome of ischemic stroke. Possible mechanisms leading to this detrimental effect include cerebral hemodynamic, oxygen saturation, humoral (endothelial, coagulatory, metabolic and inflammatory) changes. It remains unclear how a) stroke may cause (or worsen) SA, and b) to what extent any by which mechanisms SA may affect outcome of ischemic stroke.Working Hypotheses: 1) Ischemic stroke leads to new-onset or worsening of pre-existing SA; 2) SA has a detrimental effect on MRI evolution (in the first hours after stroke onset) and clinical outcome of acute ischemic stroke (within the first 3 months); 3) These detrimental effects are related to changes in blood pressure/heart rate, cerebral hemodynamics/tissue oxygenation, endothelial function, and humoral factors.Specific aims: The four major specific aims of the project are to assess 1) the impact of topography and severity of acute stroke on SA; 2) the impact of SA on the evolution of the ischemic penumbra (as assessed by MRI) and on the clinical outcome of stroke in the first 3 months after its onset; 3) the effect of SA on cardiovascular variables (blood pressure/heart rate, cerebral hemodynamics, endothelial function, humoral factors) in the first 3 months after stroke.Experimental design/Methods: In this prospective cohort study 200 consecutive patients with acute ischemic stroke admitted within 48 hours after symptoms onset will be assessed. In the first week after stroke investigations will include: 1) clinical assessments (stroke severity, etiology outcome), 2) diffusion/perfusion and conventional brain MRI (at admission and 36h later), 3) registration of nocturnal breathing (including pCO2), 4) registration of blood pressure/heart rate, 5) measurements of oxygen, oxyhemoglobin and deoxyhemoglobin concentrations in the brain (near-infrared spectrophotometry), 6) a test of endothelial function (pulse wave analysis, PWA), 7) measurements of serum oxidative/inflammatory markers. Three months later the following investigations will be repeated: 1) clinical assessment (stroke outcome), 2) registration of nocturnal breathing, 3) registration of blood pressure/heart rate, 4) PWA, 5) measurements of serum oxidative/inflammatory markers.Expected Value of the proposed Project: This project will improve our understanding of the clinical relevance and pathophysiological implications of SA in acute stroke. The results of this prospective cohort study will offer the opportunity to identify a subpopulation of patients with acute stroke and SA at high risk for neurological/cardiovascular complications in whom early treatment may be considered.
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