Project

Back to overview

Biomarker signature of stroke aetiology study: The BIOSIGNAL-Study

Applicant Katan Mira
Number 142422
Funding scheme Ambizione
Research institution Neurologische Klinik Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Neurology, Psychiatry
Start/End 01.07.2013 - 31.10.2016
Approved amount 582'629.00
Show all

All Disciplines (2)

Discipline
Neurology, Psychiatry
Cardiovascular Diseases

Keywords (8)

Neuroendocrine; Atrial Fibrillation; Secondary Prevention; Aetiology; Biomarker; Inflammatory ; Stroke; Risk assessment

Lay Summary (German)

Lead
Einer von sechs Schlaganfall-Patienten erleidet innerhalb von 5-Jahre einen erneuten Schlaganfall. Zur Verhinderung eines erneuten Schlaganfalles ist es essentiell die Ursache des stattgehabten Ereignisses schnell und korrekt zu identifizieren. Blut-Biomarker die helfen können die Ursachenfindung zu verbessern wären eine nicht invasive elegante Option die wir in diesem Projekt untersuchen moechten.
Lay summary

Hintergrund: Der Schlaganfall ist die dritt häufigste Todesursache und die häufigste Ursache für schwere Behinderungen weltweit. Mindestens einer von sechs Schlaganfall Patienten erleiden innerhalb der folgenden 5 Jahre einen erneuten Schlaganfall. Für die optimale Therapie zur Verhinderung eines erneuten Schlaganfalles ist es essentiell die Ursache des stattgehabten Ereignisses zu identifizieren. Leider findet man trotz ausführlicher Zusatzdiagnostik auch heute noch in bis zu 39% der Fälle die definitive Ursache nicht, so dass ein Großteil der Patienten nicht optimal behandelt werden kann. Der Gebrauch von Blutbiomarkern die helfen können die Ursachenfindung zu verbessern wäre in diesem Kontext eine nicht invasive elegante Option. Einige vielversprechende Kandidaten Biomarker konnten schon in Pilotprojekten identifiziert werden, wurden bislang jedoch noch nicht in einer geeigneten für diese Fragestellung entworfenen klinischen Studie systematisch untersucht.

 

Inhalt und Ziel des Forschungsprojekts: Mit der geplanten Studie wollen wir die vielversprechendsten Blut Biomarker in einer grossen internationalen multizentrischen Studie mit 3000 Schlaganfall Patienten prospektiv evaluieren. Im Detail werden wir untersuchen ob diese Biomarker assoziiert sind mit dem Auftreten eines erneuten Schlaganfalls und ob Sie assoziiert sind mit den zwei wichtigsten therapierbaren Ursachen eines Schlaganfalls a) dem kardio-embolisch bedingten Schlaganfall und b) dem Schlaganfall bedingt durch Atherosklerose der hirnzuführenden Gefässe.

 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts: Die geplante Studie wird uns beantworten können, ob die ausgewählten Blut Biomarker mit einem erhöhten Risiko einen erneuten Schlaganfall zu erleiden, assoziiert sind, und ob Sie helfen können, die Identifikation derjenigen Patienten, für welche es eine etablierte spezifische Therapie gibt, zu verbessern. Falls diese Assoziation bestätigt werden kann wird es möglich sein mit Hilfe der Messung dieser Blut Biomarker mehr Patienten spezifisch zu behandeln und somit erneute Schlaganfälle zu verhindern. Dies hätte einen grossen Einfluss auf das Überleben und die Lebensqualität von Patienten mit einem Schlaganfall.

Direct link to Lay Summary Last update: 23.01.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
Plasma Apelin Concentrations in Patients With Polyuria-Polydipsia Syndrome.
Urwyler Sandrine Andrea, Timper Katharina, Fenske Wiebke, de Mota Nadia, Blanchard Anne, Kühn Felix, Frech Nica, Arici Birsen, Rutishauser Jonas, Kopp Peter, Stettler Christoph, Müller Beat, Katan Mira, Llorens-Cortes Catherine, Christ-Crain Mirjam (2016), Plasma Apelin Concentrations in Patients With Polyuria-Polydipsia Syndrome., in The Journal of clinical endocrinology and metabolism, 101(5), 1917-23.
Procalcitonin and Midregional Proatrial Natriuretic Peptide as Markers of Ischemic Stroke: The Northern Manhattan Study.
Mira Katan, Yeseon Moon, Myunghee Paik, Beat Mueller, Andreas Huber, Ralph L. Sacco, Mitchell S.V. Elkind (2016), Procalcitonin and Midregional Proatrial Natriuretic Peptide as Markers of Ischemic Stroke: The Northern Manhattan Study., in Stroke, 47(7), 1714-1719.
Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack: a pooled analysis of individual-patient data from cohort studies.
Peter J Kelly, Gregory W Albers, Anastasios Chatzikonstantinou, Gian Marco Demarchis, Julia Ferrari, Paul George, Mira Katan, Michael Knoflach, Jon S Kim, Lixin Li, Eun-Jae Lee, Jean-Marc Olivot, Francisco Purroy, Nicolas Raposo, Peter M Rothwell, Vijay K Sharma, Bo Song, Georgios Tsvgoulis, Cathal Walsh, Yuming Xu, Aine Merwick (2016), Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack: a pooled analysis of individual-patient data from cohort studies., in Lancet Neurology, 15(12), 1238-1247.
Aetiological blood biomarkers of ischaemic stroke.
Sonderer Julian, Katan Kahles Mira (2015), Aetiological blood biomarkers of ischaemic stroke., in Swiss Med Wkly. , 145, 14138.
Collagen Vascular and Infectious Diseases
Gutierrez Jose, Katan Mira, Elkind Mitchell S.V. (2015), Collagen Vascular and Infectious Diseases, in James C. Grotta Gregory W Albers Joseph P Broderick Scott E Kasner Eng H Lo A David Mendelow R (ed.), Elsevier, London, Vereinigtes Königreich, 619-631.
Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study.
Timper Katharina, Fenske Wiebke, Kühn Felix, Frech Nica, Arici Birsen, Rutishauser Jonas, Kopp Peter, Allolio Bruno, Stettler Christoph, Müller Beat, Katan Mira, Christ-Crain Mirjam (2015), Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study., in The Journal of clinical endocrinology and metabolism, 100(6), 2268-74.
Mid-regional pro-atrial natriuretic peptide as independent outcome and aetiological ischemic stroke biomarker: Results from the CORISK Study
De Marchis G. M. D. M. Gian Marco, Schneider J., Weck A. W. Anja, Fluri F. F. Felix, Foerch C. F. Christian, Schuetz P. S. Philipp, Buhl D. B. Daniela, Seiler M. S. Marleen, Morgenthaler N. M. Nils, Mattle H. P. M. Heinrich P., Mueller B. M. Beat, Christ-Crain M. C. C. Mirjam, Arnold M. A. Marcel, Katan M. K. Mira (2015), Mid-regional pro-atrial natriuretic peptide as independent outcome and aetiological ischemic stroke biomarker: Results from the CORISK Study, in European Stroke Organization, European Stroke Organization, European Stroke Organization.
Procalcitonin and midregional pro-atrial natriuretic peptide as markers of silent brain infarcts: The Northern Manhattan Study
Katan M., Moon Y. P., DeRosa J. T., Torres S. A., von Eckardstein A., Spanaus K., Wright C. B., Sacco R. L., Elkind M. S. V. (2015), Procalcitonin and midregional pro-atrial natriuretic peptide as markers of silent brain infarcts: The Northern Manhattan Study, in European Stroke Organization, European Stroke Organization, European Stroke Organization.
BNP but Not s-cTnln is associated with cardioembolic aetiology and predicts short and long term prognosis after cerebrovascular events.
Nigro Nicole, Wildi Karin, Mueller Christian, Schuetz Philipp, Mueller Beat, Fluri Felix, Christ-Crain Mirjam, Katan Mira (2014), BNP but Not s-cTnln is associated with cardioembolic aetiology and predicts short and long term prognosis after cerebrovascular events., in PloS one, 9(7), 102704-102704.
Copeptin for the prediction of recurrent cerebrovascular events after transient ischemic attack: results from the CoRisk study.
De Marchis Gian Marco, Weck Anja, Audebert Heinrich, Benik Steffen, Foerch Christian, Buhl Daniela, Schuetz Philipp, Jung Simon, Seiler Marleen, Morgenthaler Nils G, Mattle Heinrich P, Mueller Beat, Christ-Crain Mirjam, Arnold Marcel, Katan Mira (2014), Copeptin for the prediction of recurrent cerebrovascular events after transient ischemic attack: results from the CoRisk study., in Stroke, 45(10), 2918-23.
Isolated insular strokes and plasma MR-proANP levels are associated with newly diagnosed atrial fibrillation: a pilot study.
Frontzek Karl, Fluri Felix, Siemerkus Jakob, Müller Beat, Gass Achim, Christ-Crain Mirjam, Katan Mira (2014), Isolated insular strokes and plasma MR-proANP levels are associated with newly diagnosed atrial fibrillation: a pilot study., in PloS one, 9(3), 92421-92421.
Lipoprotein-associated phospholipase A2 is associated with atherosclerotic stroke risk: the Northern Manhattan Study.
Katan Mira, Moon Yeseon P, Paik Myunghee C, Wolfert Robert L, Sacco Ralph L, Elkind Mitchell S V (2014), Lipoprotein-associated phospholipase A2 is associated with atherosclerotic stroke risk: the Northern Manhattan Study., in PloS one, 9(1), 83393-83393.
Potential role of blood biomarkers in the management of nontraumatic intracerebral hemorrhage.
Senn Rebecca, Elkind Mitchell S V, Montaner Joan, Christ-Crain Mirjam, Katan Mira (2014), Potential role of blood biomarkers in the management of nontraumatic intracerebral hemorrhage., in Cerebrovascular diseases (Basel, Switzerland), 38(6), 395-409.
The prognostic value of midregional proatrial natriuretic peptide in patients with hemorrhagic stroke.
Fischer Marlene, Katan Mira, Morgenthaler Nils G, Seiler Marleen, Müller Beat, Lackner Peter, Errath Mario, Helbok Raimund, Pfausler Bettina, Beer Ronny, Schmutzhard Erich, Broessner Gregor (2014), The prognostic value of midregional proatrial natriuretic peptide in patients with hemorrhagic stroke., in Cerebrovascular diseases (Basel, Switzerland), 37(2), 128-33.
Copeptin adds prognostic information after ischemic stroke: results from the CoRisk study.
De Marchis Gian Marco, Katan Mira, Weck Anja, Fluri Felix, Foerch Christian, Findling Oliver, Schuetz Philipp, Buhl Daniela, El-Koussy Marwan, Gensicke Henrik, Seiler Marlen, Morgenthaler Nils, Mattle Heinrich P, Mueller Beat, Christ-Crain Mirjam, Arnold Marcel (2013), Copeptin adds prognostic information after ischemic stroke: results from the CoRisk study., in Neurology, 80(14), 1278-86.
Copeptin and risk stratification in patients with ischemic stroke and transient ischemic attack: the CoRisk study.
De Marchis Gian Marco, Katan Mira, Weck Anja, Brekenfeld Caspar, Mattle Heinrich P, Buhl Daniela, Müller Beat, Christ-Crain Mirjam, Arnold Marcel (2013), Copeptin and risk stratification in patients with ischemic stroke and transient ischemic attack: the CoRisk study., in International journal of stroke : official journal of the International Stroke Society, 8(3), 214-8.
Copeptin as a marker for severity and prognosis of aneurysmal subarachnoid hemorrhage.
Fung Christian, De Marchis Gian Marco, Katan Mira, Seiler Marleen, Arnold Marcel, Gralla Jan, Raabe Andreas, Beck Jürgen (2013), Copeptin as a marker for severity and prognosis of aneurysmal subarachnoid hemorrhage., in PloS one, 8(1), 53191-53191.
Infectious burden and cognitive function: the Northern Manhattan Study.
Katan Mira, Moon Yeseon Park, Paik Myunghee Cho, Sacco Ralph L, Wright Clinton B, Elkind Mitchell S V (2013), Infectious burden and cognitive function: the Northern Manhattan Study., in Neurology, 80(13), 1209-15.
Prognostic value of dehydroepiandrosterone-sulfate and other parameters of adrenal function in acute ischemic stroke.
Blum Claudine A, Mueller Cornelia, Schuetz Philipp, Fluri Felix, Trummler Michael, Mueller Beat, Katan Mira, Christ-Crain Mirjam (2013), Prognostic value of dehydroepiandrosterone-sulfate and other parameters of adrenal function in acute ischemic stroke., in PloS one, 8(5), 63224-63224.

Collaboration

Group / person Country
Types of collaboration
Prof. J. Dawson/Glasgow University Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof.J.Montaner/Vall d’Hebron University Hospital, Barcelona Spain (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Industry/business/other use-inspired collaboration
Prof.B.Mueller/ Kantonsspital Aarau Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Industry/business/other use-inspired collaboration
Prof.C.Foerch/Johann Wolfgang Goethe-University, Frankfurt am Main Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Industry/business/other use-inspired collaboration
PD Dr.L.Bonati & PD Dr.GM.Demarchis/University Hospital Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Industry/business/other use-inspired collaboration
Prof.M.Arnold/ Inselspital Bern Switzerland (Europe)
- Publication
- Industry/business/other use-inspired collaboration
Dr. C. Cereda/Ospedale Regionale di Lugano Switzerland (Europe)
- Industry/business/other use-inspired collaboration
Dr.T.Kahles & Prof.K. Nedelchev/Kantonsspital Aarau Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Industry/business/other use-inspired collaboration
Dr. E. Sandset /University of Oslo Norway (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof.G.Ntaios/University Hospital of Larissa Greece (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Industry/business/other use-inspired collaboration
Prof.M.Christ-Crain/University Hospital Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Industry/business/other use-inspired collaboration
Prof.J.C.Sanchez/University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Industry/business/other use-inspired collaboration
Dr.G.Kägi/Kantonsspital St.Gallen Switzerland (Europe)
- Industry/business/other use-inspired collaboration
Prof.P.Michel/University Hospital Lausanne Switzerland (Europe)
- Industry/business/other use-inspired collaboration
Prof.von Eckardstein/University Hospital Zurich/Department of Neurology Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Industry/business/other use-inspired collaboration
Prof.M.Elkind/Columbia University, New York United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
European Stroke organisation Summer School Talk given at a conference Biomarkers In Stroke 14.09.2018 Berlin, Germany Katan Mira;
Personalized Health Technologies and Translational Research Conference Talk given at a conference Improved identification of stroke etiology by using blood biomarkers- a step towards precision medicine 21.06.2018 ETH Zurich 9.00-9.20, Switzerland Katan Mira;
NKO research day Talk given at a conference The role of midregional pro atrial natriuretic peptide in identifying stroke etiology 06.06.2018 Zurich, Switzerland Katan Mira;
European Stroke organization Conference Poster Prognostic value of copeptin dynamics over 5 days after ischemic stroke onset 22.05.2018 Gothenburg, Sweden Katan Mira;
European Stroke organization Conference Talk given at a conference Brain arterial dilatation and midregional proatrial natriuretic peptide as markers of hemodynamic dysfunction: the northern manhattan Study 22.05.2018 Gothenburg, Sweden Katan Mira;
European Stroke Organization Conference Poster The role of C-terminal proEndothelin-1 in predicting ischemic stroke outcome 22.05.2018 Gothenburg, Sweden Katan Mira;
Symposium des Zentrum für Neurowissenschaften Zürich Talk given at a conference Prognostic and aetiologic blood biomarkers in acute ischemic stroke patients 15.09.2016 Zürich, Switzerland Katan Mira;
Symposium des Zentrum für Neurowissenschaften Zürich Poster Serum amyloid A-a novel predictor of stroke associated infections 15.09.2016 Zürich, Switzerland Katan Mira;
Weiterbildung "Clinical Trial Center" Individual talk Wie neuroendocrine Biomarker beim Hirnschlag Einblicke in die Zukunft gewähren 19.05.2016 Zürich, Switzerland Katan Mira;
European Stroke Organization Conference Poster Micro-RNA-150 adds prognostic information after acute ischemic stroke 10.05.2016 Barcelona, Spain Katan Mira;
European Stroke Organization Conference Poster Mid-regional proadrenomedullin is an independent predictor of post stoke mortality 10.05.2016 Barcelona, Spain Katan Mira;
European Stroke Organization Conference Poster “Mid-regional proadrenomedullin is an independent predictor of post stoke mortalit 10.05.2016 Barcelona, Spain Katan Mira;
International Stroke Conference Talk given at a conference Blood and structural biomarkers of atrial dysfunction and stroke risk 17.02.2016 Los Angeles, United States of America Katan Mira;
International Stroke Conference Poster Procalcitonin And Midregional Pro-atrial Natriuretic Peptide As Biomarkers Of subclinical cerebrovascular damage: The Northern Manhattan Study (NOMAS 17.02.2016 Los Angeles, United States of America Katan Mira;
Therapietagung Zuerich-Heidelberg Talk given at a conference Sekundaerprophylaxe Schlaganfall – jenseits der Antikoagulation 23.05.2015 Heidelberg, Germany Katan Mira;
European Stroke Organization Conference Talk given at a conference Midregional Pro-atrial Natriuretic Peptide as indipendent outcome and aetiological ischemic stroke biomarker 17.04.2015 Glasgow, Great Britain and Northern Ireland Katan Mira;
European Stroke Organization Conference Talk given at a conference Update on the BIOSIGNAL-study 17.04.2015 Glasgow, Great Britain and Northern Ireland Katan Mira;
European Stroke Organization Conference Poster Procalcitonin And Midregional Pro-atrial Natriuretic Peptide As Markers Of Silent Brain Infarcts: The Northern Manhattan Study (NOMAS)”, 17.04.2015 Glasgow, Great Britain and Northern Ireland Katan Mira;
Fortbildung fuer praktizierende Aerzte, Highlights in Neurology Talk given at a conference Neues zu den Risiko- und Prognosefaktoren des Schlaganfalls 29.01.2015 Zürich, Switzerland Katan Mira;
Schweizerische Hirnschlag Gesellschaft Talk given at a conference Midregional pro-atrial natriuretic peptide and procalcitonin as markers of ischemic stroke risk: The Northern Manhattan Study 28.01.2015 Genf, Switzerland Katan Mira;
Grand Rounds Proteomics Lab, University of Geneva Individual talk Prognostic blood biomarkers in acute ischemic stroke 12.12.2014 Genf, Switzerland Katan Mira;
Schweizerische Gesellschaft für Endokrinologie und Diabetologie Talk given at a conference Copeptin after Arginine Infusion for the Differential Diagnosis of the Polyuria-Polydipsia-Syndrome ’’The CARGO-Study 27.11.2014 Bern, Switzerland Katan Mira;
International Congress of Endocrinology (ICE) & The Endocrine Society Talk given at a conference Copeptin in the Diagnosis and Differential Diagnosis of Diabetes Insipidus - the Cosip-Study 21.06.2014 Chicago, United States of America Katan Mira;
European Stroke Conference Talk given at a conference Update on the BIOSIGNAL-study“, 05.05.2014 Nizza, France Katan Mira;
International Stroke Conference Talk given at a conference Copeptin, midregional pro-atrial natriuretic peptide and procalcitonin as markers of ischemic stroke risk: The Northern Manhattan Study 12.02.2014 San Diego, United States of America Katan Mira;
Jahrestagung Deutsche Vereinte Gesellschaft für Klinische Chemie und Laboratoriumsmedizin Talk given at a conference Blood biomarkers and stroke 23.10.2013 Dresden, Germany Katan Mira;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
FORUM – Unser Wissen für Sie: Schlaganfall Talk 19.10.2016 Zürich, Switzerland Katan Mira;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions FORUM – Unser Wissen für Sie: Schlaganfall German-speaking Switzerland 2016
Media relations: print media, online media biomarkers in blood International Innovation International 2014

Awards

Title Year
Editorial Board member of the Journal NEUROLOGY, the official Journal of the American Academie of Neurology 2018
Section Editor of the Journal STROKE, the official Journal of the American Stroke and Heart Associaton n(AHA) 2017
Award of the "Morgens and Wilhelm Ellermann-Stiftung" to M.Katan 2016
Fellow of the European Stroke Organization; member of two committees 2016
Chair "research group leaders" of the Medical Faculty of the University Hospital of Zurich 2015
Chair of the "Young Swiss Stroke Physicians" 2015
Dissertation Award of the Faculty of Medicine at the University of Basel to Karl Fronzek (Promotionspreis der medizinischen Fakultät der Universität Basel) 2014
Chair of the IBCD (International Biomarkers in Cerbrovascular Disease)study group 2013

Associated projects

Number Title Start Funding scheme
130982 Inflammation and neuroendocrine dysfunction-related biomarkers: relevance to stroke risk and recurrence 01.06.2010 Fellowships for prospective researchers
182267 MidregiOnal proatrial natriuretic peptide to guide SEcondary Stroke prevention : The MOSES-study 01.04.2019 Project funding (Div. I-III)

Abstract

I SUMMARY: Background: At least 1 in 6 patients who survives a stroke will suffer another stroke within 5 years. For optimal secondary prevention directed at the underlying mechanism, an aetiological classification of stroke is critical. Even with a thorough evaluation, the aetiology of ischemic stroke remains “undetermined” (i.e. classified as cryptogenic stroke according to the classical TOAST criteria) or not evident but only “possible” or “probable” (according to the SSS TOAST-criteria) and thus in 25-39% of patients a specific secondary prevention cannot be initiated. The highest rates of stroke recurrence and mortality are seen in patients with cardioembolic and cryptogenic stroke. Patients initially diagnosed as cryptogenic stroke can, however, later be found to have a detectable cause of stroke, such as paroxysmal atrial fibrillation (AF) or symptomatic atherosclerotic disease (even if stenosis in initial exam was less than 50%). The use of rapidly measurable serum biomarkers for aetiologic diagnostic assessment on admission may enhance aetiologic classification and thus improve the implementation of optimal secondary prevention, patient outcome and benefit-cost ratio. Several promising candidate blood biomarkers have been described recently to be strongly and independently associated with cardioembolic stroke (CE) or large-artery atherosclerotic stroke (LAA). However no study simultaneously assessed the association of these blood biomarkers with the underlying aetiology and the hard endpoint of stroke recurrence as well as their incremental predictive value over existing prognostic and diagnostic clinical information on admission.Personal Research: In the past 5 years, I conducted patient-centered interdisciplinary (Department of Endocrinology and Neurology) clinical outcome studies focusing on neuroendocrine hormones as prognostic and diagnostic biomarkers in stroke patients. We investigated the prognostic value of neuroendocrine markers (e.g. copeptin, MRproANP, TSH, Cortisol etc.) for optimal risk stratification in acute ischemic stroke patients first in a large single center study (COSMOS n>500). Using this study as derivation set we aimed at validating these data and I performed as one of the primary investigators a multicenter study (the CoRisk Study) in over 1000 patients in collaboration with hospitals in Switzerland and Germany. Moreover I currently investigate promising prognostic inflammatory (e.g. LpPLA2) as well as neuroendocrine markers (e.g. Copeptin, MRproANP) and their association with increased risk of stroke also looking at stroke aetiology in one of the largest cohorts of stroke-free participants focused on stroke outcomes worldwide (n>3000; the Northern Manhattan Study, or NOMAS).Approach: We propose to prospectively evaluate the predictive value of the most promising serum biomarkers to identify treatable stroke etiologies on admission and risk of recurrence in 3000 consecutive incident ischemic stroke patients enrolled by 10 centers in Europe and the US. From these 3000 patients we estimate to include at least 750 individuals with a cryptogenic stroke classified according to the original TOAST classification 2 and 120 individuals when classified by the SSS-TOAST classification3. The clinical endpoints of the study are 1) recurrent stroke within one year, 2) all types of AF detected on admission or by prolonged ambulatory cardiac rhythm monitors, 3) presence of cerebrovascular atherosclerosis detected by ultrasound investigations and 4) new silent ischemic brain lesions and progression of chronic cerebral ischemic lesion volume detected by repeated magnetic resonance imaging (MRI and MRA) and (i.e. on admission and after 12 months). Aim 1: To determine whether the proposed biomarkers independently predict recurrent stroke among all patients. Hypothesis 1: Elevated levels of one or more of the proposed biomarkers will independently predict recurrent strokes during trial follow-up, assessed by structured interviews, as well as chart reviews 1 year after the index stroke.Aim 2: To determine whether CE biomarkers are associated with atrial fibrillation among all patients. Hypothesis 2: Baseline values of one or more of the proposed CE biomarkers will be independently associated with AF, including history of AF, AF detection at baseline, or AF detected during the follow up period by 21-day ambulatory cardiac rhythm monitors and structured interviews as well as chart reviews 1 year after the index stroke.Aim 3: To determine whether LAA biomarkers are associated with a) the presence of cerebrovascular atherosclerosis among all patients. Hypothesis 3: Baseline values of one or more of the proposed LAA biomarkers will be independently associated with the presence of extra and intracranial atherosclerosis among patients with ischemic stroke, assessed by duplex sonsography.Aim 4: To determine whether the proposed biomarkers will predict b) new silent strokes and c) progression of chronic cerebral ischemic lesion (white matter hyper-intensity) volume (WMHV) among cryptogenic stroke patients. Hypothesis 4: Baseline values of one or more of the proposed biomarkers will independently predict a) silent stroke b) progression of WMHV, during study follow-up, assessed by repeated magnetic resonance imaging (MRI) (on admission, and 1 year after the index stroke).Significance: Completion of the proposed study will answer the question of whether patients with higher levels of the selected biomarkers are at increased risk for recurrent events after acute ischemic stroke, and if the selected biomarkers can help to improve identifying patients for established effective secondary prevention treatments, allowing us to potentially reduce overall risk of recurrent stroke and thus improve quality of life.
-