Felipe A Montellano, Viktoria Rücker, Kathrin Ungethüm, Anna Penalba, Benjamin Hotter, Marina Giralt, Silke Wiedmann, Daniel Mackenrodt, Caroline Morbach, Stefan Frantz, Stefan Störk, William N Whiteley, Christoph Kleinschnitz, Andreas Meisel, Joan Montaner, Karl Georg Haeusler, Peter U Heuschmann
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We investigated whether a biomarker panel improves the predictive performance of established prognostic scores.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>Copeptin, NT-proBNP, and MR-proANP improved modest but consistently the predictive performance of established prognostic scores in patients with mild AIS. 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引用次数: 0
摘要
背景和目的：尽管已有预后模型，但急性缺血性卒中（AIS）的预后仍然具有挑战性。我们研究了生物标记物面板是否能提高既有预后评分的预测性能：我们研究了添加五种生物标记物（降钙素原、 copeptin、皮质醇、中区域前心房钠尿肽（MR-proANP）、和 N 端前 B 型利钠肽 (NT-proBNP)）以及年龄/NIHSS 评分，并利用两项前瞻性队列研究（SICFAIL、PREDICT）和一项临床试验（STRAWINSKI）的数据。不良预后定义为 12 个月时 mRS > 2（SICFAIL，衍生数据集）或 3 个月时（PREDICT/STRAWINSKI，汇总外部验证数据集）：在 412 名 SICFAIL 参与者（中位年龄 70 岁，四分位数 59-78；63% 为男性；中位 NIHSS 评分 3 分，四分位数 1-5）中，29% 的患者预后不佳。ASTRAL 和年龄/NIHSS 的曲线下面积分别为 0.76（95% CI 0.71-0.81）和 0.77（95% CI 0.73-0.82）。Copeptin（0.79，95% CI 0.74-0.84）、NT-proBNP（0.80，95% CI 0.76-0.84）和 MR-proANP（0.79，95% CI 0.75-0.84）显著提高了 ASTRAL 评分的区分度、校准和整体性能。Copeptin 提高了年龄/NIHSS 模型的辨别能力，copeptin、MR-proANP 和 NT-proBNP 则提高了其校准能力和整体性能。在验证数据集（450 名患者，中位年龄 73 岁，四分位数 66-81；54% 为男性；中位 NIHSS 评分 8 分，四分位数 3-14）中，谷丙肽与各种不良预后定义以及死亡率均有独立关联。谷丙转氨酶并未提高模型的区分度，但却改善了校准和模型的整体性能：讨论：谷丙转氨酶、NT-proBNP 和 MR-proANP 对轻度 AIS 患者既有预后评分的预测性能改善不大，但持续改善。在中度至重度 AIS 患者中，谷丙转氨酶与不良预后的相关性最为一致，但其增加的预后价值并不明显。
Biomarkers to improve functional outcome prediction after ischemic stroke: Results from the SICFAIL, STRAWINSKI, and PREDICT studies.
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.
期刊介绍：
Launched in 2016 the European Stroke Journal (ESJ) is the official journal of the European Stroke Organisation (ESO), a professional non-profit organization with over 1,400 individual members, and affiliations to numerous related national and international societies. ESJ covers clinical stroke research from all fields, including clinical trials, epidemiology, primary and secondary prevention, diagnosis, acute and post-acute management, guidelines, translation of experimental findings into clinical practice, rehabilitation, organisation of stroke care, and societal impact. It is open to authors from all relevant medical and health professions. Article types include review articles, original research, protocols, guidelines, editorials and letters to the Editor. Through ESJ, authors and researchers have gained a new platform for the rapid and professional publication of peer reviewed scientific material of the highest standards; publication in ESJ is highly competitive. The journal and its editorial team has developed excellent cooperation with sister organisations such as the World Stroke Organisation and the International Journal of Stroke, and the American Heart Organization/American Stroke Association and the journal Stroke. ESJ is fully peer-reviewed and is a member of the Committee on Publication Ethics (COPE). Issues are published 4 times a year (March, June, September and December) and articles are published OnlineFirst prior to issue publication.
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