@article{TuetuencueOlmaKunzeetal.2022, author = {T{\"u}t{\"u}nc{\"u}, Serdar and Olma, Manuel C. and Kunze, Claudia and Kr{\"a}mer, Michael and Dietzel, Joanna and Schurig, Johannes and Filser, Paula and Pfeilschifter, Waltraud and Hamann, Gerhard F. and B{\"u}ttner, Thomas and Heuschmann, Peter U. and Kirchhof, Paulus and Laufs, Ulrich and Nabavi, Darius G. and R{\"o}ther, Joachim and Thomalla, G{\"o}tz and Veltkamp, Roland and Eckardt, Kai-Uwe and Haeusler, Karl Georg and Endres, Matthias}, title = {Levels and dynamics of estimated glomerular filtration rate and recurrent vascular events and death in patients with minor stroke or transient ischemic attack}, series = {European Journal of Neurology}, volume = {29}, journal = {European Journal of Neurology}, number = {9}, doi = {10.1111/ene.15431}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287271}, pages = {2716 -- 2724}, year = {2022}, abstract = {Background and purpose Impaired kidney function is associated with an increased risk of vascular events in acute stroke patients, when assessed by single measurements of estimated glomerular filtration rate (eGFR). It is unknown whether repeated measurements provide additional information for risk prediction. Methods The MonDAFIS (Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke) study randomly assigned 3465 acute ischemic stroke patients to either standard procedures or an additive Holter electrocardiogram. Baseline eGFR (CKD-EPI formula) were dichotomized into values of < versus ≥60 ml/min/1.73 m\(^{2}\). eGFR dynamics were classified based on two in-hospital values as "stable normal" (≥60 ml/min/1.73 m\(^{2}\)), "increasing" (by at least 15\% from baseline, second value ≥ 60 ml/min/1.73 m\(^{2}\)), "decreasing" (by at least 15\% from baseline of ≥60 ml/min/1.73 m\(^{2}\)), and "stable decreased" (<60 ml/min/1.73 m\(^{2}\)). The composite endpoint (stroke, major bleeding, myocardial infarction, all-cause death) was assessed after 24 months. We estimated hazard ratios in confounder-adjusted models. Results Estimated glomerular filtration rate at baseline was available in 2947 and a second value in 1623 patients. After adjusting for age, stroke severity, cardiovascular risk factors, and randomization, eGFR < 60 ml/min/1.73 m\(^{2}\) at baseline (hazard ratio [HR] = 2.2, 95\% confidence interval [CI] = 1.40-3.54) as well as decreasing (HR = 1.79, 95\% CI = 1.07-2.99) and stable decreased eGFR (HR = 1.64, 95\% CI = 1.20-2.24) were independently associated with the composite endpoint. In addition, eGFR < 60 ml/min/1.732 at baseline (HR = 3.02, 95\% CI = 1.51-6.10) and decreasing eGFR were associated with all-cause death (HR = 3.12, 95\% CI = 1.63-5.98). Conclusions In addition to patients with low eGFR levels at baseline, also those with decreasing eGFR have increased risk for vascular events and death; hence, repeated estimates of eGFR might add relevant information to risk prediction.}, language = {en} } @article{SchnabelCamenKnebeletal.2021, author = {Schnabel, Renate B. and Camen, Stephan and Knebel, Fabian and Hagendorff, Andreas and Bavendiek, Udo and B{\"o}hm, Michael and Doehner, Wolfram and Endres, Matthias and Gr{\"o}schel, Klaus and Goette, Andreas and Huttner, Hagen B. and Jensen, Christoph and Kirchhof, Paulus and Korosoglou, Grigorius and Laufs, Ulrich and Liman, Jan and Morbach, Caroline and Navabi, Darius G{\"u}nther and Neumann-Haefelin, Tobias and Pfeilschifter, Waltraut and Poli, Sven and Rizos, Timolaos and Rolf, Andreas and R{\"o}ther, Joachim and Sch{\"a}bitz, Wolf R{\"u}diger and Steiner, Thorsten and Thomalla, G{\"o}tz and Wachter, Rolf and Haeusler, Karl Georg}, title = {Expert opinion paper on cardiac imaging after ischemic stroke}, series = {Clinical Research in Cardiology}, volume = {110}, journal = {Clinical Research in Cardiology}, number = {7}, issn = {1861-0692}, doi = {10.1007/s00392-021-01834-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266662}, pages = {938-958}, year = {2021}, abstract = {This expert opinion paper on cardiac imaging after acute ischemic stroke or transient ischemic attack (TIA) includes a statement of the "Heart and Brain" consortium of the German Cardiac Society and the German Stroke Society. The Stroke Unit-Commission of the German Stroke Society and the German Atrial Fibrillation NETwork (AFNET) endorsed this paper. Cardiac imaging is a key component of etiological work-up after stroke. Enhanced echocardiographic tools, constantly improving cardiac computer tomography (CT) as well as cardiac magnetic resonance imaging (MRI) offer comprehensive non- or less-invasive cardiac evaluation at the expense of increased costs and/or radiation exposure. Certain imaging findings usually lead to a change in medical secondary stroke prevention or may influence medical treatment. However, there is no proof from a randomized controlled trial (RCT) that the choice of the imaging method influences the prognosis of stroke patients. Summarizing present knowledge, the German Heart and Brain consortium proposes an interdisciplinary, staged standard diagnostic scheme for the detection of risk factors of cardio-embolic stroke. This expert opinion paper aims to give practical advice to physicians who are involved in stroke care. In line with the nature of an expert opinion paper, labeling of classes of recommendations is not provided, since many statements are based on expert opinion, reported case series, and clinical experience.}, language = {en} } @article{ScheitzLimBroersenetal.2021, author = {Scheitz, Jan F. and Lim, Jess and Broersen, Leonie H. A. and Ganeshan, Ramanan and Huo, Shufan and Sperber, Pia S. and Piper, Sophie K. and Heuschmann, Peter U. and Audebert, Heinrich J. and Nolte, Christian H. and Siegerink, Bob and Endres, Matthias and Liman, Thomas G.}, title = {High-Sensitivity Cardiac Troponin T and Recurrent Vascular Events After First Ischemic Stroke}, series = {Journal of the American Heart Association}, volume = {10}, journal = {Journal of the American Heart Association}, number = {10}, doi = {10.1161/JAHA.120.018326}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239039}, year = {2021}, abstract = {Background Recent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with recurrent vascular events and death in patients with first-ever, mild to moderate ischemic stroke. Methods and Results We used data from the PROSCIS-B (Prospective Cohort With Incident Stroke Berlin) study. We computed Cox proportional hazards regression analyses to assess the association between hs-cTnT levels upon study entry (Roche Elecsys, upper reference limit, 14 ng/L) and the primary outcome (composite of recurrent stroke, myocardial infarction, and all-cause death). A total of 562 patients were analyzed (mean age, 67 years [SD 13]; 38.6\% women; median National Institutes of Health Stroke Scale=2; hs-cTnT above upper reference limit, 39.2\%). During a mean follow-up of 3 years, the primary outcome occurred in 89 patients (15.8\%), including 40 (7.1\%) recurrent strokes, 4 (0.7\%) myocardial infarctions, and 51 (9.1\%) events of all-cause death. The primary outcome occurred more often in patients with hs-cTnT above the upper reference limit (27.3\% versus 10.2\%; adjusted hazard ratio, 2.0; 95\% CI, 1.3-3.3), with a dose-response relationship when the highest and lowest hs-cTnT quartiles were compared (15.2 versus 1.8 events per 100 person-years; adjusted hazard ratio, 4.8; 95\% CI, 1.9-11.8). This association remained consistent in sensitivity analyses, which included age matching and stratification for sex. Conclusions Hs-cTnT is dose-dependently associated with an increased risk of recurrent vascular events and death within 3 years after first-ever, mild to moderate ischemic stroke. These findings support further studies of the utility of hs-cTnT for individualized risk stratification after stroke.}, language = {en} } @article{RohmannHuoSperberetal.2020, author = {Rohmann, Jessica L. and Huo, Shufan and Sperber, Pia S. and Piper, Sophie K. and Rosendaal, Frits R. and Heuschmann, Peter U. and Endres, Matthias and Liman, Thomas G. and Siegerink, Bob}, title = {Coagulation factor XII, XI, and VIII activity levels and secondary events after first ischemic stroke}, series = {Journal of Thrombosis and Haemostasis}, volume = {18}, journal = {Journal of Thrombosis and Haemostasis}, number = {12}, doi = {10.1111/jth.15092}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217877}, pages = {3316 -- 3324}, year = {2020}, abstract = {Background Though risk for recurrent vascular events is high following ischemic stroke, little knowledge about risk factors for secondary events post-stroke exists. Objectives Coagulation factors XII, XI, and VIII (FXII, FXI, and FVIII) have been implicated in first thrombotic events, and our aim was to estimate their effects on vascular outcomes within 3 years after first stroke. Patients/Methods In the Prospective Cohort with Incident Stroke Berlin (PROSCIS-B) study, we followed participants aged 18 and older for 3 years after first mild to moderate ischemic stroke event or until occurrence of recurrent stroke, myocardial infarction, or all-cause mortality. We compared high coagulation factor activity levels to normal and low levels and also analyzed activities as continuous variables. We used Cox proportional hazards models adjusted for age, sex, and cardiovascular risk factors to estimate hazard ratios (HRs) for the combined endpoint. Results In total, 94 events occurred in 576 included participants, resulting in an absolute rate of 6.6 events per 100 person-years. After confounding adjustment, high FVIII activity showed the strongest relationship with the combined endpoint (HR = 2.05, 95\% confidence interval [CI] 1.28-3.29). High FXI activity was also associated with a higher hazard (HR = 1.80, 95\% CI 1.09-2.98), though high FXII activity was not (HR = 0.86, 95\% CI 0.49-1.51). Continuous analyses yielded similar results. Conclusions In our study of mild to moderate ischemic stroke patients, high activity levels of FXI and FVIII but not FXII were associated with worse vascular outcomes in the 3-year period after first ischemic stroke.}, language = {en} } @article{MalschLimanWiedmannetal.2018, author = {Malsch, Carolin and Liman, Thomas and Wiedmann, Silke and Siegerink, Bob and Georgakis, Marios K. and Tiedt, Steffen and Endres, Matthias and Heuschmann, Peter U.}, title = {Outcome after stroke attributable to baseline factors—the PROSpective Cohort with Incident Stroke (PROSCIS)}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {9}, doi = {10.1371/journal.pone.0204285}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177342}, pages = {e0204285}, year = {2018}, abstract = {Background The impact of risk factors on poor outcome after ischemic stroke is well known, but estimating the amount of poor outcome attributable to single factors is challenging in presence of multimorbidity. We aim to compare population attributable risk estimates obtained from different statistical approaches regarding their consistency. We use a real-life data set from the PROSCIS study to identify predictors for mortality and functional impairment one year after first-ever ischemic stroke and quantify their contribution to poor outcome using population attributable risks. Methods The PROSpective Cohort with Incident Stroke (PROSCIS) is a prospective observational hospital-based cohort study of patients after first-ever stroke conducted independently in Berlin (PROSCIS-B) and Munich (PROSCIS-M). The association of baseline factors with poor outcome one year after stroke in PROSCIS-B was analysed using multiple logistic regression analysis and population attributable risks were calculated, which were estimated using sequential population attributable risk based on a multiple generalized additive regression model, doubly robust estimation, as well as using average sequential population attributable risk. Findings were reproduced in an independent validation sample from PROSCIS-M. Results Out of 507 patients with available outcome information after 12 months in PROSCIS-B, 20.5\% suffered from poor outcome. Factors associated with poor outcome were age, pre-stroke physical disability, stroke severity (NIHSS), education, and diabetes mellitus. The order of risk factors ranked by magnitudes of population attributable risk was almost similar for all methods, but population attributable risk estimates varied markedly between the methods. In PROSCIS-M, incidence of poor outcome and distribution of baseline parameters were comparable. The multiple logistic regression model could be reproduced for all predictors, except pre-stroke physical disability. Similar to PROSCIS-B, the order of risk factors ranked by magnitudes of population attributable risk was almost similar for all methods, but magnitudes of population attributable risk differed markedly between the methods. Conclusions Ranking of risk factors by population impact is not affected by the different statistical approaches. Thus, for a rational decision on which risk factor to target in disease interventions, population attributable risk is a supportive tool. However, population attributable risk estimates are difficult to interpret and are not comparable when they origin from studies applying different methodology. The predictors for poor outcome identified in PROSCIS-B have a relevant impact on mortality and functional impairment one year after first-ever ischemic stroke.}, language = {en} } @article{KolominskyRabasWiedmannWeingaertneretal.2015, author = {Kolominsky-Rabas, Peter L. and Wiedmann, Silke and Weing{\"a}rtner, Michael and Liman, Thomas G. and Endres, Matthias and Schwab, Stefan and Buchfelder, Michael and Heuschmann, Peter U.}, title = {Time Trends in Incidence of Pathological and Etiological Stroke Subtypes during 16 Years: The Erlangen Stroke Project}, series = {Neuroepidemiology}, volume = {44}, journal = {Neuroepidemiology}, number = {1}, issn = {0251-5350}, doi = {10.1159/000371353}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196503}, pages = {24-29}, year = {2015}, abstract = {Background: Population-based data, which continuously monitors time trends in stroke epidemiology are limited. We investigated the incidence of pathological and etiological stroke subtypes over a 16 year time period. Methods: Data were collected within the Erlangen Stroke Project (ESPro), a prospective, population-based stroke register in Germany covering a total study population of 105,164 inhabitants (2010). Etiology of ischemic stroke was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results: Between January 1995 and December 2010, 3,243 patients with first-ever stroke were documented. The median age was 75 and 55\% were females. The total stroke incidence decreased over the 16 year study period in men (Incidence Rate Ratio 1995-1996 vs. 2009-2010 (IRR) 0.78; 95\% CI 0.58-0.90) but not in women. Among stroke subtypes, a decrease in ischemic stroke incidence (IRR 0.73; 95\% CI 0.57-0.93) and of large artery atherosclerotic stroke (IRR 0.27; 95\% CI 0.12-0.59) was found in men and an increase of stroke due to small artery occlusion in women (IRR 2.33; 95\% CI 1.39-3.90). Conclusions: Variations in time trends of pathological and etiological stroke subtypes were found between men and women that might be linked to gender differences in the development of major vascular risk factors in the study population.}, language = {en} } @article{HaeuslerHermKunzeetal.2012, author = {Haeusler, Karl Georg and Herm, Juliane and Kunze, Claudia and Kr{\"u}ll, Matthias and Brechtel, Lars and Lock, J{\"u}rgen and Hohenhaus, Marc and Heuschmann, Peter U. and Fiebach, Jochen B. and Haverkamp, Wilhelm and Endres, Matthias and Jungehulsing, Gerhard Jan}, title = {Rate of cardiac arrhythmias and silent brain lesions in experienced marathon runners: rationale, design and baseline data of the Berlin Beat of Running study}, series = {BMC Cardiovascular Disorders}, volume = {12}, journal = {BMC Cardiovascular Disorders}, number = {69}, doi = {10.1186/1471-2261-12-69}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133677}, year = {2012}, abstract = {Background: Regular exercise is beneficial for cardiovascular health but a recent meta-analysis indicated a relationship between extensive endurance sport and a higher risk of atrial fibrillation, an independent risk factor for stroke. However, data on the frequency of cardiac arrhythmias or (clinically silent) brain lesions during and after marathon running are missing. Methods/Design: In the prospective observational "Berlin Beat of Running" study experienced endurance athletes underwent clinical examination (CE), 3 Tesla brain magnetic resonance imaging (MRI), carotid ultrasound imaging (CUI) and serial blood sampling (BS) within 2-3 days prior (CE, MRI, CUI, BS), directly after (CE, BS) and within 2 days after (CE, MRI, BS) the 38\(^{th}\) BMW BERLIN-MARATHON 2011. All participants wore a portable electrocardiogram (ECG)-recorder throughout the 4 to 5 days baseline study period. Participants with pathological MRI findings after the marathon, troponin elevations or detected cardiac arrhythmias will be asked to undergo cardiac MRI to rule out structural abnormalities. A follow-up is scheduled after one year. Results: Here we report the baseline data of the enrolled 110 athletes aged 36-61 years. Their mean age was 48.8 \(\pm\) 6.0 years, 24.5\% were female, 8.2\% had hypertension and 2.7\% had hyperlipidaemia. Participants have attended a mean of 7.5 \(\pm\) 6.6 marathon races within the last 5 years and a mean of 16 \(\pm\) 36 marathon races in total. Their weekly running distance prior to the 38\(^{th}\) BMW BERLIN-MARATHON was 65 \(\pm\) 17 km. Finally, 108 (98.2\%) Berlin Beat-Study participants successfully completed the 38\(^{th}\) BMW BERLIN-MARATHON 2011. Discussion: Findings from the "Berlin Beats of Running" study will help to balance the benefits and risks of extensive endurance sport. ECG-recording during the marathon might contribute to identify athletes at risk for cardiovascular events. MRI results will give new insights into the link between physical stress and brain damage.}, language = {en} } @article{DenglerMaldanerGlaeskeretal.2016, author = {Dengler, Julius and Maldaner, Nicolai and Gl{\"a}sker, Sven and Endres, Matthias and Wagner, Martin and Malzahn, Uwe and Heuschmann, Peter U. and Vajkoczy, Peter}, title = {Outcome of Surgical or Endovascular Treatment of Giant Intracranial Aneurysms, with Emphasis on Age, Aneurysm Location, and Unruptured Aneuryms - A Systematic Review and Meta-Analysis}, series = {Cerebrovascular Diseases}, volume = {41}, journal = {Cerebrovascular Diseases}, number = {3-4}, organization = {Giant Intracranial Aneurysm Study Group}, issn = {1015-9770}, doi = {10.1159/000443485}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196792}, pages = {187-198}, year = {2016}, abstract = {Background: Designing treatment strategies for unruptured giant intracranial aneurysms (GIA) is difficult as evidence of large clinical trials is lacking. We examined the outcome following surgical or endovascular GIA treatment focusing on patient age, GIA location and unruptured GIA. Methods: Medline and Embase were searched for studies reporting on GIA treatment outcome published after January 2000. We calculated the proportion of good outcome (PGO) for all included GIA and for unruptured GIA by meta-analysis using a random effects model. Results: We included 54 studies containing 64 study populations with 1,269 GIA at a median follow-up time (FU-T) of 26.4 months (95\% CI 10.8-42.0). PGO was 80.9\% (77.4-84.4) in the analysis of all GIA compared to 81.2\% (75.3-86.1) in the separate analysis of unruptured GIA. For each year added to patient age, PGO decreased by 0.8\%, both for all GIA and unruptured GIA. For all GIA, surgical treatment resulted in a PGO of 80.3\% (95\% CI 76.0-84.6) compared to 84.2\% (78.5-89.8, p = 0.27) after endovascular treatment. In unruptured GIA, PGO was 79.7\% (95\% CI 71.5-87.8) after surgical treatment and 84.9\% (79.1-90.7, p = 0.54) after endovascular treatment. PGO was lower in high quality studies and in studies presenting aggregate instead of individual patient data. In unruptured GIA, the OR for good treatment outcome was 5.2 (95\% CI 2.0-13.0) at the internal carotid artery compared to 0.1 (0.1-0.3, p < 0.1) in the posterior circulation. Patient sex, FU-T and prevalence of ruptured GIA were not associated with PGO. Conclusions: We found that the chances of good outcome after surgical or endovascular GIA treatment mainly depend on patient age and aneurysm location rather than on the type of treatment conducted. Our analysis may inform future research on GIA.}, language = {en} }