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1. Sex-specific association of cardiovascular drug doses with adverse outcomes in atrial fibrillation

Author: David Conen, Stefan Osswald, Tobias Reichlin, Michael Kuhne, Christine Baumgartner, Nicolas Rodondi, Richard Kobza, Giorgio Moschovitis, Carole Clair, Jeanne Moor, Carole Elodie Aubert, Angelo Auricchio, Juerg H Beer, Seraina Netzer, and Leo Bonati
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Objectives Sex differences occur in atrial fibrillation (AF), including age at first manifestation, pathophysiology, treatment allocation, complication rates and quality of life. However, optimal doses of cardiovascular pharmacotherapy used in women with AF with or without heart failure (HF) are unclear. We investigated sex-specific associations of beta-blocker and renin–angiotensin system (RAS) inhibitor doses with cardiovascular outcomes in patients with AF or AF with concomitant HF.Methods We used data from the prospective Basel Atrial Fibrillation and Swiss Atrial Fibrillation cohorts on patients with AF. The outcome was major adverse cardiovascular events (MACEs), including death, myocardial infarction, stroke, systemic embolisation and HF-related hospitalisation. Predictors of interest were spline (primary analysis) or quartiles (secondary analysis) of beta-blocker or RAS inhibitor dose in per cent of the maximum dose (reference), in interaction with sex. Cox models were adjusted for demographics, comorbidities and comedication.Results Among 3961 patients (28% women), MACEs occurred in 1113 (28%) patients over a 5-year median follow-up. Distributions of RAS inhibitor and beta-blocker doses were similar in women and men. Cox models revealed no association between beta-blocker dose or RAS inhibitor dose and MACE. In a subgroup of patients with AF and HF, the lowest hazard of MACE was observed in women prescribed 100% of the RAS inhibitor dose. However, there was no association between RAS dose quartiles and MACE.Conclusions In this study of patients with AF, doses of beta-blockers and RAS inhibitors did not differ by sex and were not associated with MACE overall.
Published: 2024
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2. Patients on vitamin K treatment: is switching to direct-acting oral anticoagulation cost-effective? A target trial on a prospective cohort

Author: Stefanie Aeschbacher, David Conen, Stefan Osswald, Andreas Mueller, Tobias Reichlin, Christian Sticherling, Michael Kuhne, Matthias Schwenkglenks, Eva Blozik, Nicolas Rodondi, Giorgio Moschovitis, Carola A Huber, Michael Coslovsky, Marcello Di Valentino, Thomas D Szucs, Maria Luisa De Perna, Giulio Conte, Juerg H Beer, Miquel Serra-Burriel, Leo Bonati, Manuel Blum, Helena Aebersold, Stefan Felder, Rebecca E Paladini, Annina Stauber, and Fabienne Foster-Witassek
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Aims Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment.Methods The target trial approach was applied to the prospective observational Swiss-AF cohort, which enrolled 2415 AF patients from 2014 to 2017. Clinical data, healthcare resource utilisation and EQ-5D-based utilities representing quality of life were collected in yearly follow-ups. Health insurance claims were available for 1024 patients (42.4%). Overall survival, quality-of-life, costs from the Swiss statutory health insurance perspective and cost-effectiveness were estimated by emulating a target trial in which patients were randomly assigned to switch to DOAC or maintain VKA treatment.Results 228 patients switching from VKA to DOAC compared with 563 patients maintaining VKA treatment had no overall survival advantage over a 5-year observation period (HR 0.99, 95% CI 0.45, 1.55). The estimated gain in quality-adjusted life years (QALYs) was 0.003 over the 5-year period at an incremental costs of CHF 23 033 (€ 20 940). The estimated incremental cost-effectiveness ratio was CHF 425 852 (€ 387 138) per QALY gained.Conclusions Applying a causal inference method to real-world data, we could not demonstrate switching to DOACs to be cost-effective for AF patients with at least 1 year of VKA treatment. Our estimates align with results from a previous randomised trial.
Published: 2024
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3. Sex differences in functional outcomes of intravenous thrombolysis among patients with lacunar stroke

Author: Patrizia Wueger, Roberta Noseda, Alberto Pagnamenta, Giovanni Bianco, David Seiffge, Patrik Michel, Krassen Nedeltchev, Leo Bonati, Georg Kägi, Julien Niederhauser, Thomas Nyffeler, Andreas Luft, Susanne Wegener, Ludwig Schelosky, Friedrich Medlin, Biljana Rodic, Nils Peters, Susanne Renaud, Marie Luise Mono, Emmanuel Carrera, Urs Fischer, Gian Marco De Marchis, and Carlo W. Cereda
Subjects: lacunar stroke, intravenous thrombolysis, sex differences, functional outcome, cohort study, Neurology. Diseases of the nervous system, RC346-429
Abstract: BackgroundThis study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS).MethodsConsecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke.ResultsA total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th–75th percentiles 67–84 years versus 70 years, 25th–75th percentiles 60–80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01–2.19, value of p 0.044).ConclusionThis study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.
Published: 2024
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4. Real-time video analysis allows the identification of large vessel occlusion in patients with suspected stroke: feasibility trial of a 'telestroke' pathway in Northwestern Switzerland

Author: Sebastian Thilemann, Christoph Kenan Traenka, Fabian Schaub, Lukas Nussbaum, Leo Bonati, Nils Peters, Joachim Fladt, Christian Nickel, Patrick Hunziker, Marc Luethy, Sabine Schädelin, Axel Ernst, Stefan Engelter, Gian Marco De Marchis, and Philippe Lyrer
Subjects: telestroke, telemedicine, LVO, stroke, pre-hospital, triage, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background and aimLoss of time is a major obstacle to efficient stroke treatment. Our telestroke path intends to optimize prehospital triage using a video link connecting ambulance personnel and a stroke physician. The objectives were as follows: (1) To identify patients suffering a stroke and (2) in particular large vessel occlusion (LVO) strokes as candidates for endovascular treatment. We have chosen the Rapid Arterial Occlusion Evaluation (RACE) scale for this purpose.MethodsThis analysis aimed to verify the feasibility of prehospital stroke identification by video assessment. In this prospective telestroke cohort study, we included 97 subjects, in which the RACE score (items: facial palsy, arm and leg motor function, head and gaze deviation, and aphasia or agnosia) was applied, and the assessment videotaped by a trained member of the Emergency Medical Services (EMS) in the field using a mobile device. Each recorded patient video was independently assessed by three experienced stroke physicians from a certified stroke center and compared to the neuroimaging gold standard. Within this feasibility study, the stroke code was not altered by the outcome of the RACE assessment, and all patients underwent the standard procedures within the emergency unit.ResultsWe analyzed 97 patients (median age 78 years, 53% women), of whom 51 (52.6%) suffered an acute stroke, 12 (23.5%) of which were due to an LVO and 46 patients had symptoms mimicking a stroke. The sensitivity of stroke identification was 77.8%, and specificity was 53.6%. In regard to the identification of an LVO, sensitivity was 69.4% and specificity was 84.3%. The inter-rater agreement in the RACE-score assessment was ICC = 0.82 (intraclass-correlation coefficient).ConclusionThese results confirm our hypothesis that the local telestroke concept is feasible. It allows correct (i) stroke and (ii) LVO identification in the majority of the cases and thus has the potential to assist in efficient prehospital triage.
Published: 2023
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5. Estimating the cost impact of atrial fibrillation using a prospective cohort study and population-based controls

Author: Stefanie Aeschbacher, David Conen, Stefan Osswald, Andreas Mueller, Tobias Reichlin, Christian Sticherling, Matthias Schwenkglenks, Eva Blozik, Beat Brüngger, Nicolas Rodondi, Michael Kuehne, Giorgio Moschovitis, Jürg-Hans Beer, Giulio Conte, Anne Springer, Miquel Serra-Burriel, Leo Bonati, Manuel Blum, Thomas Szucs, Helena Aebersold, Stefan Felder, Rebecca E Paladini, Annina Stauber, Fabienne Foster-Witassek, and Carola Huber
Subjects: Medicine
Abstract: Aims Atrial fibrillation (AF) costs are expected to be substantial, but cost comparisons with the general population are scarce. Using data from the prospective Swiss-AF cohort study and population-based controls, we estimated the impact of AF on direct healthcare costs from the Swiss statutory health insurance perspective.Methods Swiss-AF patients, enrolled from 2014 to 2017, had documented, prevalent AF. We analysed 5 years of follow-up, where clinical data, and health insurance claims in 42% of the patients were collected on a yearly basis. Controls from a health insurance claims database were matched for demographics and region. The cost impact of AF was estimated using five different methods: (1) ordinary least square regression (OLS), (2) OLS-based two-part modelling, (3) generalised linear model-based two-part modelling, (4) 1:1 nearest neighbour propensity score matching and (5) a cost adjudication algorithm using Swiss-AF data non-comparatively and considering clinical data. Cost of illness at the Swiss national level was modelled using obtained cost estimates, prevalence from the Global Burden of Disease Project, and Swiss population data.Results The 1024 Swiss-AF patients with available claims data were compared with 16 556 controls without known AF. AF patients accrued CHF5600 (EUR5091) of AF-related direct healthcare costs per year, in addition to non-AF-related healthcare costs of CHF11100 (EUR10 091) per year accrued by AF patients and controls. All five methods yielded comparable results. AF-related costs at the national level were estimated to amount to 1% of Swiss healthcare expenditure.Conclusions We robustly found direct medical costs of AF patients were 50% higher than those of population-based controls. Such information on the incremental cost burden of AF may support healthcare capacity planning.
Published: 2023
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6. Omega-3 Fatty Acids and Markers of Thrombosis in Patients with Atrial Fibrillation

Author: Martin F. Reiner, Daniela A. Bertschi, Laura Werlen, Andrea Wiencierz, Stefanie Aeschbacher, Pratintip Lee, Nicolas Rodondi, Elisavet Moutzouri, Leo Bonati, Tobias Reichlin, Giorgio Moschovitis, Jonas Rutishauser, Michael Kühne, Stefan Osswald, David Conen, and Jürg H. Beer
Subjects: atrial fibrillation, beta-thromboglobulin, D-dimer, omega-3 fatty acids, stroke, Nutrition. Foods and food supply, TX341-641
Abstract: Omega-3 fatty acids (n-3 FAs) are associated with a lower risk of ischemic stroke in patients with atrial fibrillation (AF). Antithrombotic mechanisms may in part explain this observation. Therefore, we examined the association of n-3 FAs with D-dimer and beta-thromboglobulin (BTG), markers for activated coagulation and platelets, respectively. The n-3 FAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA) were determined via gas chromatography in the whole blood of 2373 patients with AF from the Swiss Atrial Fibrillation cohort study (ClinicalTrials.gov Identifier: NCT02105844). In a cross-sectional analysis, we examined the association of total n-3 FAs (EPA + DHA + DPA + ALA) and the association of individual fatty acids with D-dimer in patients with detectable D-dimer values (n = 1096) as well as with BTG (n = 2371) using multiple linear regression models adjusted for confounders. Median D-dimer and BTG levels were 0.340 ug/mL and 448 ng/mL, respectively. Higher total n-3 FAs correlated with lower D-dimer levels (coefficient 0.94, 95% confidence interval (Cl) 0.90–0.98, p = 0.004) and lower BTG levels (coefficient 0.97, Cl 0.95–0.99, p = 0.003). Likewise, the individual n-3 FAs EPA, DHA, DPA and ALA showed an inverse association with D-dimer. Higher levels of DHA, DPA and ALA correlated with lower BTG levels, whereas EPA showed a positive association with BTG. In patients with AF, higher levels of n-3 FAs were associated with lower levels of D-dimer and BTG, markers for activated coagulation and platelets, respectively. These findings suggest that n-3 FAs may exert antithrombotic properties in patients with AF.
Published: 2024
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7. Early Minimally Invasive image-guided eNdoscopic Evacuation of iNTracerebral haemorrhage: A pilot trial (EMINENT-ICH Pilot Trial)

Author: Tim Hallenberger, Leo Bonati, Urs Fischer, Raphael Guzman, and Jehuda Soleman
Subjects: Neurology. Diseases of the nervous system, RC346-429
Published: 2023
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8. Sex differences of vascular brain lesions in patients with atrial fibrillation

Author: Christian Müller, Leo H Bonati, Pascal Meyre, Steffen Blum, Stefanie Aeschbacher, David Conen, Stefan Osswald, Urs Fischer, Manuel R Blum, Simon Jung, Jens Wuerfel, Christian Sticherling, Michael Kuhne, Philipp Krisai, Matthias Schwenkglenks, Luise Adam, Elisavet Moutzouri, Martin Feller, Nathalie Schwab, Claudio Schneider, Drahomir Aujesky, Nicolas Rodondi, Karl-Olof Lovblad, Michael Amann, Richard Kobza, Marie Méan, Andreas Müller, Giorgio Moschovitis, Fabienne Witassek, Silke Küest, Sonja Meier, Jürg-Hans Beer, Damiana Rakovic, Michael Coslovsky, Tiziano Moccetti, Ramun Schmid, Augusto Gallino, Carole Elodie Aubert, Georg Ehret, Angelo Auricchio, Giulio Conte, Daniel Hayoz, Benjamin Berte, Nathalie Lauriers, Peter Ammann, François Regoli, Dipen Shah, Laurent Roten, Marco Düring, Pascal Benkert, Simone Evers-Dörpfeld, Elisa Hennings, Ceylan Eken, Selinda Ceylan, Anne Springer, Heinrich Mattle, Tim Sinnecker, Leo Bonati, Anna Altermatt, Manuel Blum, Sacha Niederberger, Chloé Auberson, Simone Evers-Doerpfeld, Marc Girod, Elena Herber, Vasco Iten, Mirko Lischer, Christine Meyer-Zürn, Andreas U Monsch, Thomas Szucs, Gian Völlmin, Juerg Fuhrer, Axel Loewe, Tanja Flückiger, Cindy Groen, Lukas Ehrsam, Sven Hellrigl, Alexandra Nuoffer, Rylana Wenger, Christopher Beynon, Roger Dillier, Michèle Deubelbeiss, Franz Eberli, Christine Franzini, Isabel Juchli, Claudia Liedtke, Jacqueline Nadler, Thayze Obst, Jasmin Roth, Fiona Schlomowitsch, Xiaoye Schneider, Katrin Studerus, Noreen Tynan, Dominik Weishaupt, Simone Fontana, Karin Scheuch, Denise Hischier, Nicole Bonetti, Alexandra Grau, Jonas Villinger, Eva Laube, Philipp Baumgartner, Mark Filipovic, Marcel Frick, Giulia Montrasio, Stefanie Leuenberger, Franziska Rutz, Adriana Anesini, Cristina Camporini, Maria Luce Caputo, Roman Brenner, David Altmann, Michaela Gemperle, Mathieu Firmann, Sandrine Foucras, Martine Rime, Virgina Justi, Frauke Kellner-Weldon, Brigitta Mehmann, Myriam Roth, Andrea Ruckli-Kaeppeli, Ian Russi, Kai Schmidt, Mabelle Young, Melanie Zbinden, Luisa Vicari, Hervé Gallet, Elise Guillermet, Francois Lazeyras, Patrick Perret, Philippe Tavel, Cheryl Teres, Sandrine Salzmann, Jürg Schläpfer, Andrea Grêt, Jan Novak, Sandra Vitelli, Frank-Peter Stephan, Jane Frangi-Kultalahti, Marcello Di Valentino, Jens Würfel, Petra Huber, Esther Ruberte, Vanessa Zuber, Gilles Dutilh, Milica Markovic, Pia Neuschwander, and Patrick Simon
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Objective To examine sex differences in prevalence, volume and distribution of vascular brain lesions on MRI among patients with atrial fibrillation (AF).Methods In this cross-sectional analysis, we included 1743 patients with AF (27% women) from the multicentre Swiss Atrial Fibrillation study (SWISS-AF) with available baseline brain MRI. We compared presence and total volume of large non-cortical or cortical infarcts (LNCCIs), small non-cortical infarcts, microbleeds (MB) and white matter hyperintensities (WMH, Fazekas score ≥2 for moderate or severe degree) between men and women with multivariable logistic regression. We generated voxel-based probability maps to assess the anatomical distribution of lesions.Results We found no strong evidence for an association of female sex with the prevalence of all ischaemic infarcts (LNCCI and SNCI combined; adjusted OR 0.86, 95% CI 0.67 to 1.09, p=0.22), MB (adjusted OR 0.91, 95% CI 0.68 to 1.21, p=0.52) and moderate or severe WMH (adjusted OR 1.15, 95% CI 0.90 to 1.48, p=0.27). However, total WMH volume was 17% larger among women than men (multivariable adjusted multiplicative effect 1.17, 95% CI 1.01 to 1.35; p=0.04). Lesion probability maps showed a right hemispheric preponderance of ischaemic infarcts in both men and women, while WMH were distributed symmetrically.Conclusion Women had higher white matter disease burden than men, while volume and prevalence of other lesions did not differ. Our findings highlight the importance of controlling risk factors for cerebral small vessel disease in patients with AF, especially among women.
Published: 2022
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9. Treatment and Postinterventional Management of a Fusiform Intracranial Aneurysm in a Professional Soccer Player: A Case Report

Author: Manina Maja Etter, Leo Bonati, Ioannis Tsogkas, Gregor Hutter, Kristine Blackham, Raphael Guzman, and Marios-Nikos Psychogios
Subjects: intracranial aneurysms, professional athletes, endovascular treatment, dual antiplatelet therapy, case report, Neurology. Diseases of the nervous system, RC346-429
Abstract: IntroductionWhile intracranial aneurysms are common lesions affecting between 1 and 5% of the general population, the prevalence in professional athletes remains unknown. The result is uncertainty and lack of guidelines on appropriate treatment of these patients.Case PresentationA 29-year-old professional soccer player presented in our hospital with an incidentally found intracranial aneurysm. After detailed depiction of the aneurysm and interdisciplinary discussion, endovascular treatment using a flow diverter was chosen to be the best treatment modality. Postinterventional medication consisted of dual antiplatelet therapy with aspirin and clopidogrel. The main challenge in managing the case of our patient was the combination of the dual antiplatelet treatment regime with his professional career in a contact sport.ConclusionDue to lack of literature or similar reports regarding the management of professional athletes with intracranial aneurysms, the optimal treatment strategy remains unclear. Even though decisions should be made dynamically and case-adapted to each situation, developing a registry could help provide guidance and new ideas for similar cases in the future.
Published: 2022
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10. Differences Between Anticoagulated Patients With Ischemic Stroke Versus Intracerebral Hemorrhage

Author: Fabian Schaub, Alexandros A. Polymeris, Sabine Schaedelin, Lisa Hert, Louisa Meya, Sebastian Thilemann, Christopher Traenka, Benjamin Wagner, David Seiffge, Henrik Gensicke, Gian Marco De Marchis, Leo Bonati, Stefan T. Engelter, Nils Peters, and Philippe Lyrer
Subjects: atherosclerosis, intracerebral hemorrhage, ischemic stroke, oral anticoagulants, small vessel disease, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Data on the relative contribution of clinical and neuroimaging risk factors to acute ischemic stroke (AIS) versus intracerebral hemorrhage (ICH) occurring on oral anticoagulant treatment are scarce. Methods and Results Cross‐sectional study was done on consecutive oral anticoagulant–treated patients presenting with AIS, transient ischemic attack (TIA), or ICH from the prospective observational NOACISP (Novel‐Oral‐Anticoagulants‐In‐Stroke‐Patients)‐Acute registry. We compared clinical and neuroimaging characteristics (small vessel disease markers and atherosclerosis) in ICH versus AIS/TIA (reference) using logistic regression. Among 734 patients presenting with stroke on oral anticoagulant treatment (404 [55%] direct oral anticoagulants, 330 [45%] vitamin K antagonists), 605 patients (82%) had AIS/TIA and 129 (18%) had ICH. Prior AIS/TIA, coronary artery disease, dyslipidemia, and worse renal function were associated with AIS/TIA (adjusted odds ratio [aOR] [95% CI] 0.51 [0.32–0.82], 0.48 [0.26–0.86], 0.55 [0.34–0.89], and 0.82 [0.75–0.90] per 10 mL/min). Prior ICH, older age, higher admission blood pressure, and statin treatment were associated with ICH (aOR [95% CI] 6.33 [2.87–14.04], 1.37 [1.04–1.81] per 10 years, 1.19 [1.10–1.29] per 10 mm Hg, and 1.81 [1.09–3.03]). Cerebral microbleeds and moderate‐to‐severe white matter hyperintensities contributed more to ICH (aOR [95% CI] 2.77 [1.34–6.18], and 2.62 [1.28–5.63]). Aortic arch, common and internal carotid artery atherosclerosis, and internal carotid artery stenosis ≥50% contributed more to AIS/TIA (aOR [95% CI] 0.54 [0.31–0.90], 0.29 [0.05–0.97], 0.48 [0.30–0.76], and 0.32 [0.13–0.67]). Conclusions In patients presenting with stroke on oral anticoagulant, AIS/TIA was 5 times more common than ICH. A high atherosclerotic burden (indicated by cardiovascular comorbidities and extracranial atherosclerosis) and prior AIS/TIA contributed more to AIS/TIA, while small vessel disease markers and prior ICH were stronger determinants for ICH. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02353585.
Published: 2022
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11. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author: Mark K. Bakker, Jos P. Kanning, Gad Abraham, Amy E. Martinsen, Bendik S. Winsvold, John-Anker Zwart, Romain Bourcier, Tomonobu Sawada, Masaru Koido, Yoichiro Kamatani, Sandrine Morel, Philippe Amouyel, Stéphanie Debette, Philippe Bijlenga, Takiy Berrandou, Santhi K. Ganesh, Nabila Bouatia-Naji, Gregory Jones, Matthew Bown, Gabriel J.E. Rinkel, Jan H. Veldink, Ynte M. Ruigrok, Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian’an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex SF Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David CM Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth JF Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O’Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda WJH Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna MM Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin NA Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M. Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Lynn Cherkas, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Christian Kubisch, Michel D Ferrari, Andrea C Belin, Maija Wessman, Arn M J M van den Maagdenberg, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Dale R Nyholt, Masato Akiyama, Varinder S. Alg, Joseph P. Broderick, Ben M. Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M. Friedrich, Emília I. Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C. Hostettler, Henry Houlden, Juha E. Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y. Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A. Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W. M. Monique Verschuren, Robin G. Walters, David J. Werring, Cristen J. Willer, Daniel Woo, Bradford B. Worrall, Sirui Zhou, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Systems Ecology, Sociology and Social Gerontology, Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J. E., Veldink, Jan H., Ruigrok, Ynte M., Girotto, G., All-In Stroke, Hunt, Group, Cadisp, Consortium for Blood Pressure, International, Headache Genetics Consortium, International, Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, International, Utrecht University [Utrecht], Baker Heart and Diabetes Institute (AUSTRALIA), University of Melbourne, University of Oslo (UiO), Norwegian University of Science and Technology (NTNU), Oslo University Hospital [Oslo], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Tokyo (UTokyo), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Université de Genève = University of Geneva (UNIGE), Excellence Laboratory LabEx DISTALZ, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Otago [Dunedin, Nouvelle-Zélande], University of Leicester, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group: Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian'an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex Sf Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David Cm Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth Jf Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O'Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda Wjh Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna Mm Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin Na Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie, Masato Akiyama, Varinder S Alg, Sigrid Børte, Joseph P Broderick, Ben M Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M Friedrich, Emília I Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C Hostettler, Henry Houlden, Kristian Hveem, Juha E Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W M Monique Verschuren, Robin G Walters, David J Werring, Cristen J Willer, Daniel Woo, Bradford B Worrall, Sirui Zhou, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Admin, Oskar
Subjects: Advanced and Specialized Nursing, Incidence, risk assessment, Smoking/epidemiology, intracranial aneurysm, genetic heterogeneity, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Risk Factors, Intracranial Aneurysm/epidemiology, Humans, Subarachnoid Hemorrhage/epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, genetics, Neurology (clinical), aneurysmal subarachnoid hemorrhage, genetic, Cardiology and Cardiovascular Medicine
Abstract: Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.
Published: 2023

12. Sex Differences in Outcomes of Intravenous Thrombolysis in Acute Ischemic Stroke Patients with Preadmission Use of Antiplatelets

Author: Roberta Noseda, Federico Rea, Alberto Pagnamenta, Pamela Agazzi, Giovanni Bianco, Shairin Sihabdeen, David Seiffge, Patrik Michel, Krassen Nedeltchev, Leo Bonati, Georg Kägi, Julien Niederhauser, Thomas Nyffeler, Andreas Luft, Susanne Wegener, Ludwig Schelosky, Friedrich Medlin, Biljana Rodic, Nils Peters, Susanne Renaud, Marie-Luise Mono, Emmanuel Carrera, Urs Fischer, Alessandro Ceschi, Carlo Walter Cereda, Noseda, R, Rea, F, Pagnamenta, A, Agazzi, P, Bianco, G, Sihabdeen, S, Seiffge, D, Michel, P, Nedeltchev, K, Bonati, L, Kägi, G, Niederhauser, J, Nyffeler, T, Luft, A, Wegener, S, Schelosky, L, Medlin, F, Rodic, B, Peters, N, Renaud, S, Mono, M, Carrera, E, Fischer, U, Ceschi, A, and Cereda, C
Subjects: Psychiatry and Mental health, ischemic stroke, sex, intravenous thrombolysis, Pharmacology (medical), Neurology (clinical), antiplatelet
Abstract: Aim: To compare safety and functional outcomes of intravenous thrombolysis (IVT) between females and males with acute ischaemic stroke (AIS) in relation to preadmission use of antiplatelets. Methods: Multicentre cohort study of patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry, presenting with AIS and receiving IVT. Primary safety outcome was in-hospital symptomatic intracerebral haemorrhage (sICH). Primary functional outcome was functional independence at 3 months after discharge. Multivariable logistic regression models were fitted to assess the association between sex and each outcome according to preadmission use of antiplatelets. Results: The study included 4996 patients (42.51 % females, older than males, median age 79 vs 71 years, p < 0.0001). Comparable proportions of females (39.92 %) and males (40.39 %) used antiplatelets before admission (p = 0.74). In total, 3.06 % females and 2.47 % males developed in-hospital sICH (p = 0.19), with similar odds (adjusted odds ratio, [AOR] 0.93, 95 % confidence interval, [CI] 0.63–1.39). No interaction was found between sex and preadmission use of either single or dual antiplatelets in relation to in-hospital sICH (p = 0.94 and p = 0.23). Males had higher odds of functional independence at 3 months (AOR 1.34, 95 % CI 1.09–1.65), regardless of preadmission use of antiplatelets (interaction between sex and preadmission use of either single or dual antiplatelets p = 0.41 and p = 0.58). Conclusion: No sex differences were observed in the safety of IVT regarding preadmission use of antiplatelets. Males showed more favourable 3-month functional independence than females; however, this sex difference was apparently not explained by a sex-specific mechanism related to preadmission use of antiplatelets.
Published: 2023

13. Nonverbal memory tests revisited: Neuroanatomical correlates and differential influence of biasing cognitive functions

Author: Nadia Mock, Christian Balzer, Klemens Gutbrod, Lutz Jäncke, Jasmin Wandel, Leo Bonati, and Wiebke Trost
Subjects: Neuropsychology and Physiological Psychology, Cognitive Neuroscience, Experimental and Cognitive Psychology, 610 Medicine & health, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Abstract: The detection of right temporal lobe dysfunction with nonverbal memory tests has remained difficult in the past. Reasons for this might be the potential influence of other biasing cognitive functions such as executive functions or the verbalisability of nonverbal material. The aim of this study was to investigate three classic nonverbal memory tests by identifying their neuroanatomical correlates with lesion-symptom mapping (LSM) and by probing their independence from verbal encoding abilities and executive functions. In a cohort of 119 patients with first-time cerebrovascular accident, memory performance was assessed in the Nonverbal Learning and Memory Test for Routes (NLMTR), the Rey Complex Figure Test (RCFT), and the Visual Design Learning Test (VDLT). Calculating multivariate LSM, we identified crucial brain structures for these three nonverbal memory tests. Behavioural analyses were performed to assess the impact of executive functions and verbal encoding abilities with regression analyses and likelihood-ratio tests. LSM revealed for the RCFT mainly right-hemispheric frontal, insular, subcortical, and white matter structures and for the NLMTR right-hemispheric temporal (hippocampus), insular, subcortical, and white matter structures. The VDLT did not reach significance in LSM analyses. Behavioural results showed that amongst the three nonverbal memory tests the impact of executive functions was most pronounced for RCFT, and the impact of verbal encoding abilities was most important in VDLT. Likelihood-ratio tests confirmed that only for NLMTR did the goodness of fit not significantly improve by adding executive functions or verbal encoding abilities. These results suggest that amongst the three nonverbal memory tests the NLMTR, as a spatial navigation test, could serve as the most suitable marker of right-hemispheric temporal lobe functioning, with the right hippocampus being involved only in this test. In addition, the behavioural results propose that only NLMTR seems mostly unaffected by executive functions and verbal encoding abilities.
Published: 2023

14. Abstract TP150: Outcome Of Patients With Lacunar Strokes In The Era Of Thrombectomy

Author: Yael van der Geest, Giulio Disanto, Giovanni Bianco, Shairin Sihabdeen, Marco Pileggi, Davide Strambo, Patrik Michel, Timo Kahles, Krassen Nedeltchev, Urs Fischer, Leo Bonati, Georg Kaegi, Jose Bernardo Escribano, Emmanuel Carrera, Thomas Nyffeler, Manuel Bolognese, Susanne Wegener, Andreas Luft, Friedrich Medlin, Susanne Renaud, Marie-Luise Mono, Luca Remonda, Paolo Machi, Marios Psychogios, Johannes Kaesmacher, Joanna M Wardlaw, and Carlo W Cereda
Subjects: Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract: Introduction: Endovascular treatment (EVT), in particular mechanical thrombectomy, has dramatically improved the clinical outcome of patients with large vessels occlusion (LVO) of the anterior circulation. In contrast, the benefits of EVT cannot be applied to lacunar strokes (LS). The absence of a LVO in LS has been historically associated with a more favorable outcome, but in the new era of EVT, this assumption may not be correct anymore. We aimed to test the general assumption that LS have a better prognosis than other stroke subtypes, and analyze the outcome of LS treated with IVT as compared to strokes with LVO treated with IVT and/or mechanical thrombectomy in the multicentric Swiss Stroke Registry. Methods: retrospective propensity score matching analysis of patients from the Swiss stroke registry (SSR) with lacunar stroke treated with thrombolysis versus LVO of the medial cerebral artery treated with EVT (with or without thrombolysis). Primary endpoint was a shift analysis of mRs at 90 days after stroke. Secondary outcomes were favorable functional outcome (mRS 0-1), independence (mRS 0-2), survival with high disability (mRS 3-5) and mortality (mRS 6) at 90 days. Results: From 13'227 patients, the propensity score method matched (sex, age, NIHSS, time to treatment, prior anticoagulation, pre-stroke modified Rankin Score, mRs) 538 patients (269 in each group. There was no difference between groups in mRs shift analysis at 90 days after stroke (OR=0.99, 95%CI=0.73-1.35, p=0.952). There was also no significant difference in mRS 0-1 (59.9% vs 55.8% respectively; OR=0.79, 95%CI=0.55-1.16, p=0.75). LS+IVT patients showed a non-significant trend towards mRS 3-5 (OR=1.23, 95%CI=0.78-1.94, p=0.38), while patients treated with EVT had a slightly, non-significant, higher mortality (6.3% vs 1.9%, p=0.38). Conclusions: Lacunar strokes - which cannot directly benefit from thrombectomy therapy - when treated with IVT and matched on key prognostic variables, seem to have similar outcomes as LVO strokes treated with EVT. This observation confirms that lacunar stroke is not a benign entity and therefore suggests that reperfusion therapy should be addressed with the same intensity as LVO stroke.
Published: 2023

15. Ischaemic stroke despite antiplatelet therapy: Causes and outcomes

Author: Norbert Silimon, Boudewijn Drop, Leander Clénin, Krassen Nedeltchev, Timo Kahles, Alexander A Tarnutzer, Mira Katan, Leo Bonati, Stephan Salmen, Sylvan Albert, Alexander Salerno, Emmanuel Carrera, Christian Berger, Nils Peters, Friedrich Medlin, Carlo Cereda, Manuel Bolognese, Georg Kägi, Susanne Renaud, Julien Niederhauser, Christophe Bonvin, Michael Schärer, Marie-Luise Mono, Andreas Luft, Biljana Rodic-Tatic, Urs Fischer, Simon Jung, Marcel Arnold, Thomas Meinel, and David Seiffge
Subjects: Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract: Background: Ischaemic stroke may occur despite antiplatelet therapy (APT). We aimed to investigate frequency, potential causes and outcomes in patients with ischaemic stroke despite APT. Methods: In this cohort study, we enrolled patients with imaging-confirmed ischaemic stroke from the Swiss Stroke Registry (01/2014-07/2022). We determined the frequency of prior APT, assessed stroke aetiology (modified TOAST classification) and determined the association of prior APT with unfavourable functional outcome (modified Rankin Scale score 3–6) and recurrent ischaemic stroke at 3 months using regression models. Results: Among 53,352 patients, 27,484 (51.5%) had no prior antithrombotic treatment, 17,760 (33.3%) were on APT, 7039 (13.2%) on anticoagulation and 1069 (2.0%) were on APT + anticoagulation. In patients with a history of ischaemic stroke/TIA ( n = 11,948; 22.4%), 2401 (20.1%) had no prior antithrombotic therapy, 6594 (55.2%) were on APT, 2489 (20.8%) on anticoagulation and 464 (3.9%) on APT + anticoagulation. Amongst patients with ischaemic stroke despite APT, aetiology was large artery atherosclerosis in 19.8% ( n = 3416), cardiac embolism in 23.6% ( n = 4059), small vessel disease in 11.7% ( n = 2011), other causes in 7.4% ( n = 1267), more than one cause in 6.3% ( n = 1078) and unknown cause in 31.3% ( n = 5388). Prior APT was not independently associated with unfavourable outcome (aOR = 1.06; 95% CI: 0.98–1.14; p = 0.135) or death (aOR = 1.10; 95% CI: 0.99–1.21; p = 0.059) at 3-months but with increased odds of recurrent stroke (6.0% vs 4.3%; aOR 1.26; 95% CI: 1.11–1.44; p Conclusions: One-third of ischaemic strokes occurred despite APT and 20% of patients with a history of ischaemic stroke had no antithrombotic therapy when having stroke recurrence. Aetiology of breakthrough strokes despite APT is heterogeneous and these patients are at increased risk of recurrent stroke.
Published: 2023

16. Sex differences of vascular brain lesions in patients with atrial fibrillation

Author: Selinda, Ceylan, Stefanie, Aeschbacher, Anna, Altermatt, Tim, Sinnecker, Nicolas, Rodondi, Manuel, Blum, Michael, Coslovsky, Simone, Evers-Dörpfeld, Sacha, Niederberger, David, Conen, Stefan, Osswald, Michael, Kühne, Marco, Düring, Jens, Wuerfel, Leo, Bonati, and Ramun, Schmid
Subjects: Male, Sex Characteristics, Cross-Sectional Studies, Infarction, Atrial Fibrillation, Brain, Humans, Female
Abstract: To examine sex differences in prevalence, volume and distribution of vascular brain lesions on MRI among patients with atrial fibrillation (AF).In this cross-sectional analysis, we included 1743 patients with AF (27% women) from the multicentre Swiss Atrial Fibrillation study (SWISS-AF) with available baseline brain MRI. We compared presence and total volume of large non-cortical or cortical infarcts (LNCCIs), small non-cortical infarcts, microbleeds (MB) and white matter hyperintensities (WMH, Fazekas score ≥2 for moderate or severe degree) between men and women with multivariable logistic regression. We generated voxel-based probability maps to assess the anatomical distribution of lesions.We found no strong evidence for an association of female sex with the prevalence of all ischaemic infarcts (LNCCI and SNCI combined; adjusted OR 0.86, 95% CI 0.67 to 1.09, p=0.22), MB (adjusted OR 0.91, 95% CI 0.68 to 1.21, p=0.52) and moderate or severe WMH (adjusted OR 1.15, 95% CI 0.90 to 1.48, p=0.27). However, total WMH volume was 17% larger among women than men (multivariable adjusted multiplicative effect 1.17, 95% CI 1.01 to 1.35; p=0.04). Lesion probability maps showed a right hemispheric preponderance of ischaemic infarcts in both men and women, while WMH were distributed symmetrically.Women had higher white matter disease burden than men, while volume and prevalence of other lesions did not differ. Our findings highlight the importance of controlling risk factors for cerebral small vessel disease in patients with AF, especially among women.
Published: 2022

17. Abstract WP75: Sex Differences In The Outcomes Of Intravenous Thrombolysis In Acute Ischemic Stroke Patients With Preadmission Use Of Antiplatelet Agents: A Population-based Study In The Swiss Stroke Registry

Author: Roberta Noseda, Federico Rea, Alberto Pagnamenta, Giovanni Bianco, Shairin Sihabdeen, pamela agazzi, David Seiffge, Patrik Michel, Krassen Nedeltchev, Leo Bonati, Georg Kägi, Julien Niederhauser, Thomas Nyffeler, Andreas Luft, Ludwig Schelosky, Friedrich Medlin, Biljana Rodic, Nils Peters, Susanne Renaud, Marie-Luise Mono, Emmanuel Carrera, Urs Fischer, Professor Alessandro Ceschi, and Carlo W Cereda
Subjects: Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract: Introduction: This study aimed to evaluate whether patient sex modifies the association between preadmission use of antiplatelet agents (APAs) and safety and efficacy outcomes of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS). Methods: Cohort study from the Swiss Stroke Registry of consecutive patients with AIS treated with IVT stratified according to sex and assessed for preadmission use of APAs in multivariate logistic regression models. The primary safety outcome was in-hospital symptomatic intracerebral haemorrhage (sICH). The primary efficacy outcome was functional independence (FI) at 3 months after discharge. Secondary efficacy outcomes included favourable functional outcome (FFO), modified Rankin Scale score shift analysis, survival with high disability or death at 3 months. Results: Study cohort included 4996 patients, 2124 women (43%) and 2872 men (57%). Women were older than men (79 vs 71 years, P P =0.74). Preadmission use of dual APAs was associated with higher odds of in-hospital sICH (adjOR 2.89, 95%CI 1.15-7.29), with a statistically significant trend from single to dual APAs ( P =0.02). No interaction was found between preadmission use of either single or dual APAs and patient sex ( P =0.89 and P =0.21, respectively). Men had significantly higher chances of 3-month FI (adjOR 1.34, 95%CI 1.09-1.65), better outcomes across all levels of disability and mortality (adjOR 0.86, 95%CI 0.75-0.99). We found no sex differences in FFO and severe disability or death at 3 months after discharge (adjOR 1.15, 95%CI 0.96-1.36 and adjOR 1.11, 95%CI 0.79-1.55, respectively). We found no interaction between patient sex and preadmission use of either single or dual APAs for any of the secondary efficacy outcomes. Conclusions: Female sex was associated with more unfavourable 3-month efficacy outcomes than male sex after IVT. Even though preadmission use of dual APAs was associated with increased odds of in-hospital sICH, sex-gender differences in 3-month efficacy outcomes apparently were not explained by a sex-specific mechanism related to preadmission use of APAs.
Published: 2022

18. [Stroke Unit- / Stroke Center Care]

Author: Joachim, Fladt, Stefan, Engelter, Gian Marco, De Marchis, Marios, Psychogios, Philippe, Lyrer, Leo, Bonati, and Henrik, Gensicke
Subjects: Stroke, Humans, Switzerland
Abstract: Stroke Unit- / Stroke Center Care
Published: 2021

19. Sex and Carotid Disease

Author: Leo Bonati
Subjects: Carotid Artery Diseases, Advanced and Specialized Nursing, Brain Ischemia, Clinical and Population Sciences, lipid, Go Red for Women, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Humans, carotid stenosis, magnetic resonance imaging, Neurology (clinical), atherosclerosis, hemorrhage, sex characteristics, Cardiology and Cardiovascular Medicine, computed tomography angiography
Abstract: Supplemental Digital Content is available in the text., Background and Purpose: Incidence of ischemic stroke differs between men and women, with substantially higher rates in men. The underlying mechanism of this difference remains poorly understood but may be because of differences in carotid atherosclerosis. Using an in-depth imaging-based approach, we investigated differences between carotid plaque composition and morphology in male and female patients with stroke, taking into account differences in total plaque burden. Additionally, we investigated all possible within-artery combinations of plaque characteristics to explore differences between various plaque phenotypes. Methods: We included 156 men and 68 women from the PARISK (Plaque At Risk) study, a prospective cohort study of patients with recent ischemic cerebrovascular symptoms and
Published: 2022

20. Clinical images: Granulomatosis with polyangiitis and transthyretin‐related amyloidosis

Author: Justas Grimalauskas‐Suchina, Frank Behrendt, Corina Schuster‐Amft, Katrin Parmar, Leo Bonati, and Hans U. Gerth
Subjects: Rheumatology, Immunology, Granulomatosis with Polyangiitis, Humans, Prealbumin, Immunology and Allergy, Amyloidosis, Churg-Strauss Syndrome
Published: 2022

21. Response to ‘Re. Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials’

Author: Urs Fisch and Leo Bonati
Subjects: Stroke, Endarterectomy, Carotid, Humans, Carotid Stenosis, Stents, Surgery, Cardiology and Cardiovascular Medicine, Vascular Surgical Procedures
Published: 2021

22. Insulin-like growth factor-binding protein 7 and risk of congestive heart failure hospitalization in patients with atrial fibrillation

Author: Steffen Blum, Stefanie Aeschbacher, Pascal Meyre, Michael Kühne, Nicolas Rodondi, Jürg H. Beer, Peter Ammann, Giorgio Moschovitis, Leo H. Bonati, Manuel R. Blum, Peter Kastner, Fiona Baguley, Christian Sticherling, Stefan Osswald, David Conen, Chloé Auberson, Leo Bonati, Selinda Ceylan, Simone Doerpfeld, Ceylan Eken, Marc Girod, Peter Hämmerle, Philipp Krisai, Christine Meyer-Zürn, Andreas U. Monsch, Christian Müller, Anne Springer, Thomas Szucs, Gian Voellmin, Leon Zwimpfer, Drahomir Aujesky, Urs Fischer, Juerg Fuhrer, Laurent Roten, Simon Jung, Heinrich Mattle, Luise Adam, Carole Elodie Aubert, Martin Feller, Axel Loewe, Elisavet Moutzouri, Claudio Schneider, Tanja Flückiger, Cindy Groen, Lukas Ehrsam, Sven Hellrigl, Alexandra Nuoffer, Damiana Rakovic, Nathalie Schwab, Rylana Wenger, Christopher Beynon, Roger Dillier, Michèle Deubelbeiss, Franz Eberli, Christine Franzini, Isabel Juchli, Claudia Liedtke, Jacqueline Nadler, Thayze Obst, Jasmin Roth, Fiona Schlomowitsch, Xiaoye Schneider, Katrin Studerus, Noreen Tynan, Dominik Weishaupt, Andreas Müller, Simone Fontana, Silke Kuest, Karin Scheuch, Denise Hischier, Nicole Bonetti, Alexandra Grau, Jonas Villinger, Eva Laube, Philipp Baumgartner, Mark Filipovic, Marcel Frick, Giulia Montrasio, Stefanie Leuenberger, Franziska Rutz, Jürg-Hans Beer, Angelo Auricchio, Adriana Anesini, Cristina Camporini, Giulio Conte, Maria Luce Caputo, Francois Regoli, Tiziano Moccetti, Roman Brenner, David Altmann, Michaela Gemperle, Mathieu Firmann, Sandrine Foucras, Martine Rime, Daniel Hayoz, Benjamin Berte, Virgina Justi, Frauke Kellner-Weldon, Brigitta Mehmann, Sonja Meier, Myriam Roth, Andrea Ruckli-Kaeppeli, Ian Russi, Kai Schmidt, Mabelle Young, Melanie Zbinden, Richard Kobza, Jane Frangi-Kultalahti, Anica Pin, Luisa Vicari, Georg Ehret, Hervé Gallet, Elise Guillermet, Francois Lazeyras, Karl-Olof Lovblad, Patrick Perret, Philippe Tavel, Cheryl Teres, Dipen Shah, Nathalie Lauriers, Marie Méan, Sandrine Salzmann, Jürg Schläpfer, Andrea Grêt, Jan Novak, Sandra Vitelli, Frank-Peter Stephan, Augusto Gallino, Marcello Di Valentino, Fabienne Witassek, Matthias Schwenkglenks, Jens Würfel, Anna Altermatt, Michael Amann, Petra Huber, Esther Ruberte, Tim Sinnecker, Vanessa Zuber, Michael Coslovsky, Pascal Benkert, Gilles Dutilh, Milica Markovic, Patrick Simon, Ramun Schmid, Clinical sciences, Auberson, Chloé, Bonati, Leo, Ceylan, Selinda, Doerpfeld, Simone, Eken, Ceylan, Girod, Marc, Hämmerle, Peter, Krisai, Philipp, Meyer-Zürn, Christine, Monsch, Andreas U., Müller, Christian, Springer, Anne, Szucs, Thomas, Voellmin, Gian, Zwimpfer, Leon, Aujesky, Drahomir, Fischer, Urs, Fuhrer, Juerg, Roten, Laurent, Jung, Simon, Mattle, Heinrich, Adam, Luise, Aubert, Carole Elodie, Feller, Martin, Loewe, Axel, Moutzouri, Elisavet, Schneider, Claudio, Flückiger, Tanja, Groen, Cindy, Ehrsam, Lukas, Hellrigl, Sven, Nuoffer, Alexandra, Rakovic, Damiana, Schwab, Nathalie, Wenger, Rylana, Beynon, Christopher, Dillier, Roger, Deubelbeiss, Michèle, Eberli, Franz, Franzini, Christine, Juchli, Isabel, Liedtke, Claudia, Nadler, Jacqueline, Obst, Thayze, Roth, Jasmin, Schlomowitsch, Fiona, Schneider, Xiaoye, Studerus, Katrin, Tynan, Noreen, Weishaupt, Dominik, Müller, Andreas, Fontana, Simone, Kuest, Silke, Scheuch, Karin, Hischier, Denise, Bonetti, Nicole, Grau, Alexandra, Villinger, Jonas, Laube, Eva, Baumgartner, Philipp, Filipovic, Mark, Frick, Marcel, Montrasio, Giulia, Leuenberger, Stefanie, Rutz, Franziska, Auricchio, Angelo, Anesini, Adriana, Camporini, Cristina, Conte, Giulio, Caputo, Maria Luce, Regoli, Francois, Moccetti, Tiziano, Brenner, Roman, Altmann, David, Gemperle, Michaela, Firmann, Mathieu, Foucras, Sandrine, Rime, Martine, Hayoz, Daniel, Berte, Benjamin, Justi, Virgina, Kellner-Weldon, Frauke, Mehmann, Brigitta, Meier, Sonja, Roth, Myriam, Ruckli-Kaeppeli, Andrea, Russi, Ian, Schmidt, Kai, Young, Mabelle, Zbinden, Melanie, Kobza, Richard, Frangi-Kultalahti, Jane, Pin, Anica, Vicari, Luisa, Ehret, Georg Benedikt, Gallet, Hervé, Guillermet, Elise, Lazeyras, François, Lövblad, Karl-Olof, Perret, Patrick, Tavel, Philippe, Teres Castillo, Cheryl, Shah, Dipen, Lauriers, Nathalie, Méan, Marie, Salzmann, Sandrine, Schläpfer, Jürg, Grêt, Andrea, Novak, Jan, Vitelli, Sandra, Stephan, Frank-Peter, Gallino, Augusto, Di Valentino, Marcello, Witassek, Fabienne, Schwenkglenks, Matthias, Würfel, Jens, Altermatt, Anna, Amann, Michael, Huber, Petra, Ruberte, Esther, Sinnecker, Tim, Zuber, Vanessa, Coslovsky, Michael, Benkert, Pascal, Dutilh, Gilles, Markovic, Milica, Simon, Patrick, and Schmid, Ramun
Subjects: Male, medicine.medical_specialty, medicine.drug_class, Epidemiology, Heart failure, 030204 cardiovascular system & hematology, ddc:616.0757, 03 medical and health sciences, 0302 clinical medicine, Insulin-Like Growth Factor Binding Proteins/blood, Physiology (medical), Internal medicine, Atrial Fibrillation, Clinical endpoint, Natriuretic peptide, medicine, Heart Failure/blood, Humans, 030212 general & internal medicine, cardiovascular diseases, Hospitalization/statistics & numerical data, Aged, Retrospective Studies, ddc:616, Heart Failure, Proportional hazards model, business.industry, Insulin-like growth factor-binding protein 7, Hazard ratio, Atrial fibrillation, Middle Aged, medicine.disease, Prognosis, Confidence interval, Hospitalization, Insulin-Like Growth Factor Binding Proteins, Atrial Fibrillation/blood, Cardiology, Disease Progression, Female, business, Cardiology and Cardiovascular Medicine, Biomarkers/blood, Biomarkers, Cohort study, Follow-Up Studies
Abstract: BACKGROUND: The occurrence of congestive heart failure (CHF) hospitalization among patients with atrial fibrillation (AF) is a poor prognostic marker. OBJECTIVE: The purpose of this study was to assess whether insulin-like growth factor-binding protein 7 (IGFBP-7), a marker of myocardial damage, identifies AF patients at high risk for this complication. METHODS: We analyzed 2 prospective multicenter observational cohort studies that included 3691 AF patients. Levels of IGFBP-7 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured from frozen plasma samples at baseline. The primary endpoint was hospitalization for CHF. Multivariable adjusted Cox regression analyses were constructed. RESULTS: Mean patient age was 69 ± 12 years, 1028 (28%) were female, and 879 (24%) had a history of CHF. The incidence per 1000 patient-years across increasing IGFBP-7 quartiles was 7, 10, 32, and 85. The corresponding multivariable adjusted hazard ratios (aHRs) (95% confidence interval [CI]) were 1.0, 1.05 (0.63-1.77), 2.38 (1.50-3.79), and 4.37 (2.72-7.04) (P for trend
Published: 2020

23. Focused Workshop

Author: Leo Bonati and Krzysztof Selmaj
Subjects: Neurology, Neurology (clinical)
Published: 2017

24. 3 - OUTCOME OF ENDOVASCULAR THERAPY IN STROKE PATIENTS WITH LARGE VESSEL OCCLUSION AND MILD SYMPTOMS

Author: Michel Patrik, Leo Bonati, PD Dr. Georg Kägi, Alessandro Cianfoni, Claudio Staedler, Krassen Nedeltchev, andreas.luft andreas.luft, XXX XXX, Urs Fischer, Emmanuel Carrera, Henrik Gensicke, Sebastian Thilemann, Mandy Muller, Johannes Kaesmacher, Marcel Arnold, Simon Jung, Mirjam R Heldner, Stefania Nannoni, Carlo Cereda, Giovanni Bianco, Giulio Disanto, and Concetta Manno
Published: 2019

25. EARLY MIDREGIONAL PRO-ATRIAL NATRIURETIC PEPTIDE PREDICTS THE OCCURRENCE OF ATRIAL FIBRILLATION IN STROKE PATIENTS: DATA FROM THE BIOSIGNAL STUDY

Author: Mira Katan, Arnold von Eckardstein, Christian Foerch, George Ntaios, Joan Montaner, Alejandro Bustamante, Michel Patrik, PD Dr. Georg Kägi, Carlo Cereda, Krassen Nedeltchev, XXX XXX, Gian Marco De Marchis, Leo Bonati, Urs Fischer, Marcel Arnold, Katharina Spanaus, and Juliane Schweizer
Published: 2019

26. SERUM LIGHT-CHAIN NEUROFILAMENT, A BRAIN LESION MARKER, IS ASSOCIATED WITH THE CHA2DS2-VASC SCORE AMONG PATIENTS WITH ATRIAL FIBRILLATION: A CROSS-SECTIONAL STUDY

Author: Leo Bonati
Published: 2018

27. Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke

Author: Marta Bilik, Steve Vucic, Waldemar Brola, Monica Badve, Joseph Kwan, David Werring, Graeme Hankey, David Doig, Christian Lueck, Maurizio BALESTRINO, Richard Lindley, Geoffrey Cloud, Francesco Corea, Cathie Sudlow, Joana Damásio, Rui Felgueiras, Andrea Zini, William Whiteley, Stefan Engelter, Malcolm Robert Macleod, Manuel Correia, Joanna Wardlaw, Tomasz Litwin, Bartosz Karaszewski, Robert Simister, Grant Mair, Hedley Emsley, Jan Aaseth, Leo Bonati, Marta Leńska-Mieciek, Marc Randall, UCL - SSS/IONS/NEUR - Clinical Neuroscience, and UCL - (SLuc) Service de neurologie
Subjects: Male, OCCLUSION, 1702 Cognitive Sciences, 030204 cardiovascular system & hematology, Tissue plasminogen activator, law.invention, Brain Ischemia, Brain ischemia, 0302 clinical medicine, CT hyperdense artery sign, Randomized controlled trial, law, PROGNOSTIC-SIGNIFICANCE, 80 and over, IST-3 Collaborative Group, Tomography, Stroke, Aged, 80 and over, trials, ASSOCIATION, Arteries, RANDOMIZED CONTROLLED-TRIAL, X-Ray Computed, medicine.anatomical_structure, Treatment Outcome, Tissue Plasminogen Activator, outcome, Cardiology, Third International Stroke Trial, Female, INTRAVENOUS THROMBOLYSIS, SENSITIVITY, Life Sciences & Biomedicine, IST-3, Artery, medicine.drug, medicine.medical_specialty, IV alteplase, Clinical Neurology, HAS, ischemic stroke, Article, 03 medical and health sciences, Fibrinolytic Agents, Internal medicine, Ophthalmology, medicine, Humans, Thrombus, TISSUE-PLASMINOGEN ACTIVATOR, Aged, Science & Technology, Neurology & Neurosurgery, business.industry, 1103 Clinical Sciences, Odds ratio, medicine.disease, Follow-Up Studies, Tomography, X-Ray Computed, Neurology (clinical), Neurosciences & Neurology, business, 1109 Neurosciences, 030217 neurology & neurosurgery, Fibrinolytic agent, SCAN
Abstract: Objective: To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3). Methods: All prerandomization and follow-up (24–48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518). Results: HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167). Conclusions: IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS. Classification of evidence: This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.
Published: 2016

28. Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial

Author: Paul Sidhu, Jan Blankensteijn, Jonas Malmstedt, Martin M Brown, Angel Chamorro, Jeroen Hendriks, Karl-olof Lovblad, David Doig, Barry Beiles, Tim McGahan, Gerard Stansby, Lorenz Hirt, Stefan Engelter, Christophe Bonvin, Sami Curtze, Dick Zeilstra, Juan Miguel Macho Fernandez, Geert Vanhooren, Gary A Ford, Carl Magnus Wahlgren, Leo Bonati, Petra Ijäs, Jonathan Tibballs, Bonvin, Christophe, Kalangos, Afksendiyos, Lövblad, Karl-Olof, Sztajzel, Roman, Halliday, A, ACS - Amsterdam Cardiovascular Sciences, Surgery, Neurology, Radiology and Nuclear Medicine, and ANS - Amsterdam Neuroscience
Subjects: PROTOCOL, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, ddc:616.0757, Modified Rankin Scale, Angioplasty, medicine, media_common.cataloged_instance, Humans, Carotid Stenosis, Functional ability, cardiovascular diseases, European union, ANGIOPLASTY, Stroke/etiology/mortality/prevention & control, Stroke, media_common, Endarterectomy, Aged, Endarterectomy, Carotid, Intention-to-treat analysis, ddc:617, business.industry, ARTERY STENOSIS, Articles, General Medicine, Recovery of Function, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], medicine.disease, equipment and supplies, 3. Good health, Surgery, ddc:616.8, surgical procedures, operative, Treatment Outcome, cardiovascular system, Female, Stents, Carotid stenting, business, STROKE, Carotid Stenosis/complications/mortality/therapy, Follow-Up Studies
Abstract: Background Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments. Methods Patients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centres worldwide. Randomisation was computer generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent endpoint committee unaware of treatment assignment. The primary endpoint was fatal or disabling stroke in any territory after randomisation to the end of follow-up. Analysis was by intention to treat ([ITT] all patients) and per protocol from 31 days after treatment (all patients in whom assigned treatment was completed). Functional ability was rated with the modified Rankin scale. This study is registered, number ISRCTN25337470. Findings 1713 patients were assigned to stenting (n=855) or endarterectomy (n=858) and followed up for a median of 4·2 years (IQR 3·0–5·2, maximum 10·0). Three patients withdrew immediately and, therefore, the ITT population comprised 1710 patients. The number of fatal or disabling strokes (52 vs 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups (6·4% vs 6·5%; hazard ratio [HR] 1·06, 95% CI 0·72–1·57, p=0·77). Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs 72 events; ITT population, 5-year cumulative risk 15·2% vs 9·4%, HR 1·71, 95% CI 1·28–2·30, p Interpretation Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis. Funding Medical Research Council, Stroke Association, Sanofi-Synthélabo, European Union.
Published: 2015

29. Erratum to: Risk factors, aetiology and outcome of ischaemic stroke in young adults: the Swiss Young Stroke Study (SYSS)

Author: Barbara Goeggel Simonetti, Marie-Luise Mono, Uyen Huynh-Do, Patrik Michel, Celine Odier, Roman Sztajzel, Philippe Lyrer, Stefan T. Engelter, Leo Bonati, Henrik Gensicke, Christopher Traenka, Barbara Tettenborn, Bruno Weder, Urs Fischer, Aekaterini Galimanis, Simon Jung, Rudolf Luedi, Gian Marco De Marchis, Anja Weck, Carlo W. Cereda, Ralf Baumgartner, Claudio L. Bassetti, Heinrich P. Mattle, Krassen Nedeltchev, and Marcel Arnold
Subjects: Neurology, 610 Medicine & health, Neurology (clinical)
Published: 2015

30. Characteristics and Outcomes of Patients With Multiple Cervical Artery Dissection

Author: Yannick, Béjot, Corine, Aboa-Eboulé, Stéphanie, Debette, Alessandro, Pezzini, Turgut, Tatlisumak, Stefan, Engelter, Caspar, Grond-Ginsbach, Emmanuel, Touzé, Maria, Sessa, Tiina, Metso, Antti, Metso, Manja, Kloss, Valeria, Caso, Jean, Dallongeville, Philippe, Lyrer, Didier, Leys, Maurice, Giroud, Massimo, Pandolfo, Shérine, Abboud, and Leo, Bonati
Subjects: Adult, Male, Manipulation, Spinal, medicine.medical_specialty, Cervical Artery, Vertebral artery dissection, Fibromuscular dysplasia, Carotid Artery, Internal, Dissection, Brain Ischemia, Pseudoaneurysm, Disability Evaluation, Risk Factors, Odds Ratio, Medicine, Humans, Prospective Studies, Registries, Prospective cohort study, Stroke, Aged, Cerebral Hemorrhage, Retrospective Studies, Advanced and Specialized Nursing, Aged, 80 and over, Vertebral Artery Dissection, Neck pain, Neck Pain, business.industry, Age Factors, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Surgery, Treatment Outcome, Data Interpretation, Statistical, Multivariate Analysis, Female, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, Neck
Abstract: Background and Purpose— Little is known about factors contributing to multiple rather than single cervical artery dissections (CeAD) and their associated prognosis. Methods— We compared the baseline characteristics and short-term outcome of patients with multiple to single CeAD included in the multicenter Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study. Results— Among the 983 patients with CeAD, 149 (15.2%) presented with multiple CeAD. Multiple CeADs were more often associated with cervical pain at admission (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.10–2.30), a remote history of head or neck surgery (OR, 1.87; 95% CI, 1.16–3.00), a recent infection (OR, 1.71; 95% CI, 1.12–2.61), and cervical manipulation (OR, 2.23; 95% CI, 1.26–3.95). On imaging, cervical fibromuscular dysplasia (OR, 3.97; 95% CI, 2.04–7.74) and the presence of a pseudoaneurysm (OR, 2.91; 95% CI, 1.86–4.57) were more often seen in patients with multiple CeAD. The presence of multiple rather than single CeAD had no effect on functional 3-month outcome (modified Rankin Scale score, ≥3; 12% in multiple CeAD versus 11.9% in single CeAD; OR, 1.20; 95% CI, 0.60–2.41). Conclusions— In the largest published series of patients with CeAD, we highlighted significant differences between multiple and single artery involvement. Features suggestive of an underlying vasculopathy (fibromuscular dysplasia) and environmental triggers (recent infection, cervical manipulation, and a remote history of head or neck surgery) were preferentially associated with multiple CeAD.
Published: 2014

31. Carotid stenosis

Author: Martin M Brown, James Grotta, Kosmas I. Paraskevas, Leo Bonati, and J. David Spence
Subjects: Stroke, Humans, Carotid Stenosis, Female, General Medicine
Published: 2013

32. Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial

Author: Jan Blankensteijn, Jonas Malmstedt, Kirsten Krohg-Sørensen, Hans Rolf Jäger, Martin M Brown, Jeroen Hendriks, Peter Gillgren, Karl-olof Lovblad, Lorenz Hirt, Stefan Engelter, Christophe Bonvin, Geert Vanhooren, Markku Kaste, Carl Magnus Wahlgren, Leo Bonati, Petra Ijäs, Amsterdam Cardiovascular Sciences, Surgery, Neurology, Radiology and Nuclear Medicine, Amsterdam Neuroscience, Cras, Patrick, Hendriks, Jeroen, van Schil, Paul, and ICSS Investigators
Subjects: Male, Risk, medicine.medical_specialty, medicine.medical_treatment, Clinical Neurology, Cerebral Revascularization, Carotid endarterectomy, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Leukoencephalopathies, Internal medicine, Angioplasty, medicine, media_common.cataloged_instance, Humans, Carotid Stenosis, Single-Blind Method, cardiovascular diseases, European union, Stroke, Endarterectomy, media_common, Cardiovascular diseases [DCN MP - Plasticity and memory NCEBP 14], Aged, Aged, 80 and over, Endarterectomy, Carotid, business.industry, Cardiovascular diseases Tissue engineering and pathology [NCEBP 14], Articles, Middle Aged, medicine.disease, 3. Good health, Surgery, Stenosis, Treatment Outcome, Cardiology, Female, Stents, Human medicine, Neurology (clinical), Carotid stenting, business, Cardiovascular diseases Aetiology, screening and detection [NCEBP 14], 030217 neurology & neurosurgery
Abstract: Item does not contain fulltext BACKGROUND: Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy. METHODS: Patients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com, number ISRCTN 25337470. FINDINGS: 1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2.76, 95% CI 1.17-6.51; p=0.021; HR for non-disabling stroke 3.00, 1.10-8.36; p=0.031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1.18, 0.40-3.55; p=0.76; HR for disabling or fatal stroke 1.41, 0.38-5.26; p=0.607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2.98, 1.29-6.93; p=0.011; HR for non-disabling stroke 6.34, 1.45-27.71; p=0.014), but there was no risk difference in patients with an ARWMC score of less than 7. INTERPRETATION: The presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthelabo, the European Union Research Framework Programme 5.
Published: 2013

33. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial

Author: Steff Lewis, Rustam Al-Shahi Salman, William Strain, Marta Bilik, Steve Vucic, Waldemar Brola, Gordon Murray, Monica Badve, Richard Gray, Joseph Kwan, David Werring, Salim Yusuf, Erik Lundström, Anna Czlonkowska, Paul Bentley, Philip Bath, Graeme Hankey, Philip White, Alastair Buchan, David Doig, Chris Armit, Christian Lueck, Maurizio BALESTRINO, Urszula Fiszer, Richard Lindley, Geoffrey Cloud, Francesco Corea, Karl Matz, Cathie Sudlow, Joana Damásio, Rui Felgueiras, Andrea Zini, William Whiteley, Stefan Engelter, Malcolm Robert Macleod, Luana Benedetti, Joanna Wardlaw, Peter Sandercock, Michael Hill, Bartosz Karaszewski, Hedley Emsley, Jan Aaseth, Leo Bonati, Marta Leńska-Mieciek, Mark Wardle, Marc Randall, Pippa Tyrrell, and Antonio Arauz
Subjects: Male, Pediatrics, medicine.medical_treatment, 030204 cardiovascular system & hematology, Severity of Illness Index, law.invention, Brain Ischemia, 0302 clinical medicine, Randomized controlled trial, law, Case fatality rate, Secondary Prevention, intravenous thrombolysis, Thrombolytic Therapy, Young adult, Infusions, Intravenous, Stroke, acute ischaemic stroke, Aged, 80 and over, third international stroke trial, General Medicine, Thrombolysis, Middle Aged, Recombinant Proteins, 3. Good health, Treatment Outcome, Tissue Plasminogen Activator, recombinant tissue plasminogen activator, Female, IST-3, Adult, medicine.medical_specialty, Adolescent, early treatment, Drug Administration Schedule, 03 medical and health sciences, Young Adult, Age Distribution, Double-Blind Method, Fibrinolytic Agents, Severity of illness, medicine, Humans, Aged, business.industry, Odds ratio, medicine.disease, business, 030217 neurology & neurosurgery, Fibrinolytic agent
Abstract: BACKGROUND: Thrombolysis is of net benefit in patients with acute ischaemic stroke, who are younger than 80 years of age and are treated within 4·5 h of onset. The third International Stroke Trial (IST-3) sought to determine whether a wider range of patients might benefit up to 6 h from stroke onset. METHODS: In this international, multicentre, randomised, open-treatment trial, patients were allocated to 0·9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) or to control. The primary analysis was of the proportion of patients alive and independent, as defined by an Oxford Handicap Score (OHS) of 0-2 at 6 months. The study is registered, ISRCTN25765518. FINDINGS: 3035 patients were enrolled by 156 hospitals in 12 countries. All of these patients were included in the analyses (1515 in the rt-PA group vs 1520 in the control group), of whom 1617 (53%) were older than 80 years of age. At 6 months, 554 (37%) patients in the rt-PA group versus 534 (35%) in the control group were alive and independent (OHS 0-2; adjusted odds ratio [OR] 1·13, 95% CI 0·95-1·35, p=0·181; a non-significant absolute increase of 14/1000, 95% CI -20 to 48). An ordinal analysis showed a significant shift in OHS scores; common OR 1·27 (95% CI 1·10-1·47, p=0·001). Fatal or non-fatal symptomatic intracranial haemorrhage within 7 days occurred in 104 (7%) patients in the rt-PA group versus 16 (1%) in the control group (adjusted OR 6·94, 95% CI 4·07-11·8; absolute excess 58/1000, 95% CI 44-72). More deaths occurred within 7 days in the rt-PA group (163 [11%]) than in the control group (107 [7%], adjusted OR 1·60, 95% CI 1·22-2·08, p=0·001; absolute increase 37/1000, 95% CI 17-57), but between 7 days and 6 months there were fewer deaths in the rt-PA group than in the control group, so that by 6 months, similar numbers, in total, had died (408 [27%] in the rt-PA group vs 407 [27%] in the control group). INTERPRETATION: For the types of patient recruited in IST-3, despite the early hazards, thrombolysis within 6 h improved functional outcome. Benefit did not seem to be diminished in elderly patients. FUNDING: UK Medical Research Council, Health Foundation UK, Stroke Association UK, Research Council of Norway, Arbetsmarknadens Partners Forsakringsbolag (AFA) Insurances Sweden, Swedish Heart Lung Fund, The Foundation of Marianne and Marcus Wallenberg, Polish Ministry of Science and Education, the Australian Heart Foundation, Australian National Health and Medical Research Council (NHMRC), Swiss National Research Foundation, Swiss Heart Foundation, Assessorato alla Sanita, Regione dell'Umbria, Italy, and Danube University.
Published: 2012

34. SS27. The Risk of Carotid Artery Stenting Compared with Carotid Endarterectomy Is Greatest in Patients Treated within Seven Days of Symptoms

Author: Barbara Rantner, Georg Goebel, Leo Bonati, and Gustav Fraedrich
Subjects: Surgery, Cardiology and Cardiovascular Medicine
Published: 2012
Full Text: View/download PDF

35. Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited

Author: Marta Bilik, Steve Vucic, Waldemar Brola, Monica Badve, Grzegorz Kozera, Joseph Kwan, David Werring, Erik Lundström, Anna Czlonkowska, Paul Bentley, Graeme Hankey, Alastair Buchan, David Doig, Christian Lueck, Maurizio BALESTRINO, Urszula Fiszer, Richard Lindley, Geoffrey Cloud, Francesco Corea, Karl Matz, Cathie Sudlow, Joana Damásio, Rui Felgueiras, Andrea Zini, William Whiteley, Stefan Engelter, Malcolm Robert Macleod, Luana Benedetti, Joanna Wardlaw, Peter Sandercock, Bartosz Karaszewski, Hedley Emsley, Jan Aaseth, Leo Bonati, Marta Leńska-Mieciek, Mark Wardle, Marc Randall, Antonio Arauz, UCL - SSS/IONS/NEUR - Clinical Neuroscience, and UCL - (SLuc) Service de neurologie
Subjects: Neurology, medicine.medical_treatment, Medicine (miscellaneous), Research & Experimental Medicine, Tissue plasminogen activator, law.invention, Brain Ischemia, 0302 clinical medicine, Randomized controlled trial, law, Brain Ischemia drug therapy, Data monitoring committee, Pharmacology (medical), Thrombolytic Therapy, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Stroke, 1102 Cardiorespiratory Medicine and Haematology, lcsh:R5-920, Thrombolysis, 3. Good health, Medicine, Research & Experimental, Tissue Plasminogen Activator, Acute Disease, lcsh:Medicine (General), Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Double-Blind Method, Fibrinolytic Agents, Humans, Sample Size, Stroke drug therapy, Update, 03 medical and health sciences, ALTEPLASE, Double-Blind Method, Fibrinolytic Agents, IST-3 collaborative group, General & Internal Medicine, medicine, Science & Technology, business.industry, 1103 Clinical Sciences, medicine.disease, Cardiovascular System & Hematology, Emergency medicine, Physical therapy, business, 030217 neurology & neurosurgery, Fibrinolytic agent
Abstract: Background Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit. Design International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics. Results The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials. Conclusion The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials. Trial registration ISRCTN25765518
Published: 2011

36. Workshop for Studies in Development Novel oral anticoagulants in stroke patients (NOACISP) - A prospective registry

Author: Seiffge, D., Hert, L., Traenka, C., Marchis, G. M., Gensicke, H., Peters, N., Leo Bonati, Lyrer, P., and Engelter, S.

37. Diagnostic and prognostic value of plasma light-chain neurofilaments in acute cerebrovascular events - a prospective cohort study

Author: Marchis, G. M., Katan, M., Barro, C., Buhl, D., Traenka, C., Seiffge, D. J., Hert, L., Gensicke, H., Disanto, G., Sutter, R., Peters, N., Sarikaya, H., Goeggel-Simonetti, B., El-Koussy, M., Engelter, S. T., Lyrer, P. A., Christ-Crain, M., Arnold, M., Kuhle, J., and Leo Bonati

38. Early start of NOAC after an acute cerebrovascular event: risk of intracranial hemorrhage and recurrent events

Author: Seiffge, D., Traenka, C., Polymeris, A., Hert, L., Sutter, R., Peters, N., Lyrer, P., Leo Bonati, Engelter, S., and Marchis, G. M.

39. Acute ischemic stroke as trigger of non-convulsive status epilepticus: A case series

Author: Traenka, C., Marchis, G. M., Hert, L., Seiffge, D., Peters, N., Leo Bonati, Engelter, S. T., Lyrer, P., Rueegg, S., and Sutter, R.

40. Treatment of intracerebral hemorrhage in patients on direct oral anticoagulants with tranexamic acid - TICH-DOAC

Author: Seiffge, D., Peters, N., Sprigg, N., Guzman, R., Hert, L., Marchis, G. M., Hessling, A., Tsakiris, D., Nickel, C., Traenka, C. H., Leo Bonati, Lyrer, P., and Engelter, S.

41. The omega-3 fatty acid eicosapentaenoic acid (EPA) is inversely associated with ischemic brain infarcts in elderly patients with atrial fibrillation

Author: Reiner, M. F., Baumgartner, P., Wiencierz, A., Aeschbacher, S., Rodondi, N., Baretella, O., Kuehne, M., Moschovitis, G., Leo Bonati, Schacky, C., Luescher, T. F., Camici, G. G., Osswald, S., Conen, D., and Beer, J. H.

42. Neurofilament light chain serum levels in cervical artery dissection patients - An exploratory analysis

Author: Traenka, C., Gensicke, H., Seiffge, D., Peters, N., Kloss, M., Disanto, G., Marchis, G. M., Leo Bonati, Kuhle, J., and Engelter, S. T.

43. Determinants of adherence to oral anticoagulants in patients with atrial fibrillation and stroke

Author: Polymeris, A., Traenka, C., Hert, L., Seiffge, D. J., Peters, N., Marchis, G. M., Leo Bonati, Lyrer, P. A., and Engelter, S. T.

44. Early Start of NOAC After an Acute Ischemic Stroke or TIA: Risk of Intracranial Hemorrhage and Recurrent Events

Author: Seiffge, D. J., Traenka, C., Polymeris, A., Hert, L., Peters, N., Lyrer, P., Engelter, S., Leo Bonati, and Marchis, G. M.

45. Reasons for Prehospital Delay in Acute Ischemic Stroke: Hints on Increasing the Rate of Recanalization Therapies - a Prospective Cohort Study

Author: Fladt, J., Seiffge, D. J., Traenka, C., Polymeris, A., Thilemann, S., Sutter, R., Peters, N., Leo Bonati, Engelter, S., Lyrer, P., and Marchis, G. M.

46. Risk Of Stroke Or Death Occurring On The Day Of Procedure Versus Day 1-30 After Procedure In Endarterectomy Or Stenting For Symptomatic Carotid Stenosis

Author: Muller, M. D., Felten, S., Algra, A., Becquemin, J. P., Brown, M., Bulbulia, R., Calvet, D., Eckstein, H. H., Fraedrich, G., Halliday, A., Hendrikse, J., Howard, G., Jansen, O., Roubin, G. S., Mas, J. L., Brott, T. G., Ringleb, P. A., and Leo Bonati

47. Controversies and Updates in Vascular Surgery

Author: Thompson, M., Canaud, L., Kolbel, T., Resch, T., Cao, P., Brunkwall, J., Mastracci, T., Alsac, J. M., Gibbs, R., Ducasse, E., Mcwilliams, R., Haulon, S., Bicknell, C., Liapis, C., Sambeek, M., Blankensteijn, J., Powell, J., Desgranges, P., Kakkos, S., Leo Bonati, Cronenwett, J., Bosiers, M., Zeller, T., Goueffic, Y., Mendes, L., Baumgartner, I., Castier, Y., Schneider, P., Deloose, K., Mussa, F., Pengloan, J., Canaud, B., Shoenfeld, R., Gibbons, C., Bonforte, G., Lazarides, M., Landenheim, E., Boura, B., Veroux, P., Raynaud, A., Bourquelet, P., Kobeiter, H., Cochennec, F., Maleti, O., Nelzen, O., Guex, J. J., Camerota, A., Bresson, A. Bisdorff, Desnos, C. Hamel, Frullini, A., Den Bos, R., Rasmussen, L., Mansilha, A., Kabnick, L., Gohel, M., Gloviczki, P., Davies, A., Bouayed, M., and Pichot, O.

48. Fast-track versus open-end hospitalizations for patients with non-disabling, acute ischemic stroke requiring hospitalization

Author: Hoffmann, L., Fladt, J., Polymeris, A., Seiffge, D. J., Imhof, A., Traenka, C., Hert, L., Simon, P., Peters, N., Leo Bonati, Engelter, S. T., Lyrer, A., and Marchis, G. M.

49. Recognizing calcifications of the carotid artery on panoramic radiographs to prevent strokes

Author: Leo Bonati

50. Untangling Prehospital Delay in Acute Ischemic Stroke: Hints on Increasing the Thrombolysis Rate - a Prospective Cohort Study

Author: Marchis, Gian Marco, Fladt, Joachim, Seiffge, David J., Traenka, Christopher, Polymeris, Alexandros, Sutter, Raoul, Leo Bonati, Engelter, Stefan, and Lyrer, Philippe

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