• Víctor Llombart, Albert Antolin-Fontes, Alejandro Bustamante, Dolors Giralt, Natalia S Rost, Karen Furie, Kensaku Shibazaki, Murat Biteker, José Castillo, Manuel Rodríguez-Yáñez, Ana Catarina Fonseca, Tetsu Watanabe, Francisco Purroy, Wu Zhixin, Thorleif Etgen, Naohisa Hosomi, Scott Reza Jafarian Kerman, Jagdish C Sharma, Carolin Knauer, Estevo Santamarina, George Giannakoulas, Teresa García-Berrocoso, and Joan Montaner.
• From the Neurovascular Research Laboratory, Institut de Recerca Vall d'Hebron, Neurovascular Unit, Department of Neurology, Universitat Autònoma de Barcelona, Barcelona, Spain (V.L., A.A.-F., A.B., D.G., T.G.-B., J.M.); Acute Stroke Services, Massachusetts General Hospital, J. Philip Kistler Stroke Research Center, Boston (N.S.R.); Department of Neurology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence (K.F.); Department of Stroke Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan (K.S.); Department of Cardiology, Haydarpaşa Numune Education and Research Hospital, Istanbul, Turkey (M.B.); Department of Neurology, Clinical University, Hospital University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain (J.C., M.R.-Y.); Department of Neurosciences (Neurology), Hospital de Santa Maria, University of Lisbon, Lisbon, Portugal (A.C.F.); Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, Yamagata, Japan (T.W.); Department of Neurology, Stroke Unit, Hospital Universitari Arnau de Vilanova, Grup Neurociències Clíniques IRBLleida, Lleida, Spain (F.P.); Department of Emergency Medicine, Foshan Hospital of Traditional Chinese Medicine, Foshan, Guangdong, China (W.Z.); Department of Neurology, Kliniken Südostbayern-Klinikum Traunstein, Traunstein, Germany; Department of Psychiatry and Psychotherapy, Technische Universität München, München, Germany (T.E.); Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan (N.H.); Tehran University of Medical Sciences and Health Services, Tehran, Iran (S.R.J.K.); Stroke and Parkinson's Disease Services, Lincoln County Hospital, University of Nottingham, Nottingham, United Kingdom (J.C.S.); Department of Neurology, University of Ulm, Ulm, Germany (C.K.); Stroke Unit, Department of Neurology, Hospital
• Stroke. 2015 May 1; 46 (5): 1187-95.

Background And PurposeDetermining the underlying cause of stroke is important to optimize secondary prevention treatment. Increased blood levels of natriuretic peptides (B-type natriuretic peptide/N-terminal pro-BNP [BNP/NT-proBNP]) have been repeatedly associated with cardioembolic stroke. Here, we evaluate their clinical value as pathogenic biomarkers for stroke through a literature systematic review and individual participants' data meta-analysis.MethodsWe searched publications in PubMed database until November 2013 that compared BNP and NT-proBNP circulating levels among stroke causes. Standardized individual participants' data were collected to estimate predictive values of BNP/NT-proBNP for cardioembolic stroke. Dichotomized BNP/NT-proBNP levels were included in logistic regression models together with clinical variables to assess the sensitivity and specificity to identify cardioembolic strokes and the additional value of biomarkers using area under the curve and integrated discrimination improvement index.ResultsFrom 23 selected articles, we collected information of 2834 patients with a defined cause. BNP/NT-proBNP levels were significantly elevated in cardioembolic stroke until 72 hours from symptoms onset. Predictive models showed a sensitivity >90% and specificity >80% when BNP/NT-proBNP were added considering the lowest and the highest quartile, respectively. Both peptides also increased significantly the area under the curve and integrated discrimination improvement index compared with clinical models. Sensitivity, specificity, and precision of the models were validated in 197 patients with initially undetermined stroke with final pathogenic diagnosis after ancillary follow-up.ConclusionsNatriuretic peptides are strongly increased in cardioembolic strokes. Future multicentre prospective studies comparing BNP and NT-proBNP might aid in finding the optimal biomarker, the best time point, and the optimal cutoff points for cardioembolic stroke identification.© 2015 American Heart Association, Inc.

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