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Background and Aims: Acute ischemic stroke (AIS) outcome prognostication remains challenging despite available prognostic models. We investigated whether a biomarker panel improves the predictive performance of established prognostic scores., Methods: We investigated the improvement in discrimination, calibration, and overall performance by adding five biomarkers (procalcitonin, copeptin, cortisol, mid-regional pro-atrial natriuretic peptide (MR-proANP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)) to the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) and age/NIHSS scores using data from two prospective cohort studies (SICFAIL, PREDICT) and one clinical trial (STRAWINSKI). Poor outcome was defined as mRS > 2 at 12 (SICFAIL, derivation dataset) or 3 months (PREDICT/STRAWINSKI, pooled external validation dataset)., Results: Among 412 SICFAIL participants (median age 70 years, quartiles 59-78; 63% male; median NIHSS score 3, quartiles 1-5), 29% had a poor outcome. Area under the curve of the ASTRAL and age/NIHSS were 0.76 (95% CI 0.71-0.81) and 0.77 (95% CI 0.73-0.82), respectively. Copeptin (0.79, 95% CI 0.74-0.84), NT-proBNP (0.80, 95% CI 0.76-0.84), and MR-proANP (0.79, 95% CI 0.75-0.84) significantly improved ASTRAL score's discrimination, calibration, and overall performance. Copeptin improved age/NIHSS model's discrimination, copeptin, MR-proANP, and NT-proBNP improved its calibration and overall performance. In the validation dataset (450 patients, median age 73 years, quartiles 66-81; 54% men; median NIHSS score 8, quartiles 3-14), copeptin was independently associated with various definitions of poor outcome and also mortality. Copeptin did not increase model's discrimination but it did improve calibration and overall model performance., Discussion: Copeptin, NT-proBNP, and MR-proANP improved modest but consistently the predictive performance of established prognostic scores in patients with mild AIS. Copeptin was most consistently associated with poor outcome in patients with moderate to severe AIS, although its added prognostic value was less obvious., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: F.A.M., V.R., K.U, A.P., D.M., B.H., M.G., W.N.W, C.K., A.M., and J.M. have nothing to disclose. S.W. reports grants from the German Ministry of Research and Education and Deutsche Herzstiftung e.V. C.M. is supported by the IZKF, University Hospital Würzburg (advanced clinician-scientist program, ADVCSP-3) and the German Research Foundation (Comprehensive Research Center 1525 “Cardio-immune interfaces,” #453989101, project C5). CM reports research cooperation with the University of Würzburg and Tomtec Imaging Systems funded by the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany; travel grants, advisory and speakers honoraria from Amgen, Tomtec, Orion Pharma, Alnylam, AKCEA, Sobi, Alexion, Janssen, Pfizer, and EBR Systems; principal investigator in trials sponsored by Alnylam, AstraZeneca, and Bayer. St.St. reports grants, personal fees, non-financial support, and/or other from Boehringer, Bayer, Thermo Fisher, and Pfizer; AstraZeneca, Sanofi, Servier, Alnylam, Ionis, Akcea; and Novartis, outside the submitted work. S.F. reports grants from the German Ministry of Research and Education during the conduct of the study. KGH reports speaker’s honoraria, consulting fees, lecture honoraria, and/or study grants from Abbott, Amarin, AstraZeneca, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Novartis, Pfizer, Portola, Premier Research, Sanofi, SUN Pharma, W.L. Gore and Associates. P.U.H. reports grants from German Ministry of Research and Education, during the conduct of the study; grants from German Ministry of Research and Education, European Union, Charité-Universitätsmedizin Berlin, German Parkinson Society, University Hospital Würzburg, Robert Koch Institute, German Heart Foundation, Federal Joint Committee (G-BA) within the Innovationfond, German Research Foundation, Bavarian State, German Cancer Aid, Charité-Universitätsmedizin Berlin (within Mondafis; supported by an unrestricted research grant to the Charité from Bayer), University Göttingen (within FIND-AF randomized; supported by an unrestricted research grant to the University Göttingen from Boehringer-Ingelheim), University Hospital Heidelberg (within RASUNOA-prime; supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo), outside the submitted work.

Background: Troponin elevation is common in ischemic stroke (IS) patients. The pathomechanisms involved are incompletely understood and comprise coronary and non-coronary causes, e.g. autonomic dysfunction. We investigated determinants of troponin elevation in acute IS patients including markers of autonomic dysfunction, assessed by heart rate variability (HRV) time domain variables., Methods: Data were collected within the Stroke Induced Cardiac FAILure (SICFAIL) cohort study. IS patients admitted to the Department of Neurology, Würzburg University Hospital, underwent baseline investigation including cardiac history, physical examination, echocardiography, and blood sampling. Four HRV time domain variables were calculated in patients undergoing electrocardiographic Holter monitoring. Multivariable logistic regression with corresponding odds ratios (OR) and 95% confidence intervals (CI) was used to investigate the determinants of high-sensitive troponin T (hs-TnT) levels ≥14 ng/L., Results: We report results from 543 IS patients recruited between 01/2014-02/2017. Of those, 203 (37%) had hs-TnT ≥14 ng/L, which was independently associated with older age (OR per year 1.05; 95% CI 1.02-1.08), male sex (OR 2.65; 95% CI 1.54-4.58), decreasing estimated glomerular filtration rate (OR per 10 mL/min/1.73 m 2 0.71; 95% CI 0.61-0.84), systolic dysfunction (OR 2.79; 95% CI 1.22-6.37), diastolic dysfunction (OR 2.29; 95% CI 1.29-4.02), atrial fibrillation (OR 2.30; 95% CI 1.25-4.23), and increasing levels of C-reactive protein (OR 1.48 per log unit; 95% CI 1.22-1.79). We did not identify an independent association of troponin elevation with the investigated HRV variables., Conclusion: Cardiac dysfunction and elevated C-reactive protein, but not a reduced HRV as surrogate of autonomic dysfunction, were associated with increased hs-TnT levels in IS patients independent of established cardiovascular risk factors. Registration-URL: https://www.drks.de/drks_web/; Unique identifier: DRKS00011615., (© 2022. The Author(s).)

Patients with ischemic stroke (IS) are at increased risk of mortality and recurrent cerebro- or cardiovascular events. Determining prognosis after IS remains challenging but blood-based biomarkers might provide additional prognostic information. As platelets are crucially involved in the pathophysiology of vascular diseases, platelet surface proteins (PSP) are promising candidates as prognostic markers in the hyperacute stage. In this pilot study, feasibility of PSP analysis by flow cytometry (HMGB1, CD84, CXCR4, CXCR7, CD62p with and without ADP-stimulation, CD41, CD61, CD40, GPVI) was investigated in 99 (median 66 years, 67.5% male) acute IS patients admitted to Stroke Unit within a substudy of the Stroke-Induced Cardiac FAILure in mice and men (SICFAIL) cohort study. Association between PSP expression and unfavorable one-year outcome (cerebro- or cardiovascular event, all-cause mortality and care dependency defined as Barthel Index <60) was explored. PSP measurements were feasible. Several process- (e.g. temperatures, processing times) and patient-related factors (e.g. prestroke ischemic events, surgery, blood pressure, antiplatelet therapy) were identified to be potentially associated with PSP expression. Elevated CD40 levels above study population's median were associated with unfavorable outcome. Standardized conditions during blood draw and processing within the hyperacute stroke unit setting are required and patient-related characteristics must be considered for valid measurements of PSP. Trial registration : German Clinical Trials Register (DRKS00011615).