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December 03, 2013; 81 (23) Article

B-type natriuretic peptides and mortality after stroke

A systematic review and meta-analysis

Teresa García-Berrocoso, Dolors Giralt, Alejandro Bustamante, Thorleif Etgen, Jesper K. Jensen, Jagdish C. Sharma, Kensaku Shibazaki, Ayhan Saritas, Xingyong Chen, William N. Whiteley, Joan Montaner
First published November 1, 2013, DOI: https://doi.org/10.1212/01.wnl.0000436937.32410.32
Teresa García-Berrocoso
From the Neurovascular Research Laboratory (T.G.-B., D.G., A.B., J.M.), Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain; Department of Neurology (T.E.), Kliniken Südostbayern-Klinikum Traunstein, Germany; Department of Psychiatry and Psychotherapy (T.E.), Technische Universität München, Germany; Department of Cardiology (J.K.J.), Odense University, Denmark; Stroke Medicine (J.C.S.), Lincoln County Hospital, University of Nottingham, UK; Department of Stroke Medicine (K.S.), Kawasaki Medical School, Kurashiki City, Okayama, Japan; Department of Emergency Medicine (A.S.), School of Medicine, Duzce University, Turkey; Department of Neurology (X.C.), Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China; and Centre for Clinical Brain Sciences (W.N.W.), University of Edinburgh, UK.
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Dolors Giralt
From the Neurovascular Research Laboratory (T.G.-B., D.G., A.B., J.M.), Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain; Department of Neurology (T.E.), Kliniken Südostbayern-Klinikum Traunstein, Germany; Department of Psychiatry and Psychotherapy (T.E.), Technische Universität München, Germany; Department of Cardiology (J.K.J.), Odense University, Denmark; Stroke Medicine (J.C.S.), Lincoln County Hospital, University of Nottingham, UK; Department of Stroke Medicine (K.S.), Kawasaki Medical School, Kurashiki City, Okayama, Japan; Department of Emergency Medicine (A.S.), School of Medicine, Duzce University, Turkey; Department of Neurology (X.C.), Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China; and Centre for Clinical Brain Sciences (W.N.W.), University of Edinburgh, UK.
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Alejandro Bustamante
From the Neurovascular Research Laboratory (T.G.-B., D.G., A.B., J.M.), Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain; Department of Neurology (T.E.), Kliniken Südostbayern-Klinikum Traunstein, Germany; Department of Psychiatry and Psychotherapy (T.E.), Technische Universität München, Germany; Department of Cardiology (J.K.J.), Odense University, Denmark; Stroke Medicine (J.C.S.), Lincoln County Hospital, University of Nottingham, UK; Department of Stroke Medicine (K.S.), Kawasaki Medical School, Kurashiki City, Okayama, Japan; Department of Emergency Medicine (A.S.), School of Medicine, Duzce University, Turkey; Department of Neurology (X.C.), Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China; and Centre for Clinical Brain Sciences (W.N.W.), University of Edinburgh, UK.
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Thorleif Etgen
From the Neurovascular Research Laboratory (T.G.-B., D.G., A.B., J.M.), Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain; Department of Neurology (T.E.), Kliniken Südostbayern-Klinikum Traunstein, Germany; Department of Psychiatry and Psychotherapy (T.E.), Technische Universität München, Germany; Department of Cardiology (J.K.J.), Odense University, Denmark; Stroke Medicine (J.C.S.), Lincoln County Hospital, University of Nottingham, UK; Department of Stroke Medicine (K.S.), Kawasaki Medical School, Kurashiki City, Okayama, Japan; Department of Emergency Medicine (A.S.), School of Medicine, Duzce University, Turkey; Department of Neurology (X.C.), Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China; and Centre for Clinical Brain Sciences (W.N.W.), University of Edinburgh, UK.
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Jesper K. Jensen
From the Neurovascular Research Laboratory (T.G.-B., D.G., A.B., J.M.), Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain; Department of Neurology (T.E.), Kliniken Südostbayern-Klinikum Traunstein, Germany; Department of Psychiatry and Psychotherapy (T.E.), Technische Universität München, Germany; Department of Cardiology (J.K.J.), Odense University, Denmark; Stroke Medicine (J.C.S.), Lincoln County Hospital, University of Nottingham, UK; Department of Stroke Medicine (K.S.), Kawasaki Medical School, Kurashiki City, Okayama, Japan; Department of Emergency Medicine (A.S.), School of Medicine, Duzce University, Turkey; Department of Neurology (X.C.), Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China; and Centre for Clinical Brain Sciences (W.N.W.), University of Edinburgh, UK.
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Jagdish C. Sharma
From the Neurovascular Research Laboratory (T.G.-B., D.G., A.B., J.M.), Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain; Department of Neurology (T.E.), Kliniken Südostbayern-Klinikum Traunstein, Germany; Department of Psychiatry and Psychotherapy (T.E.), Technische Universität München, Germany; Department of Cardiology (J.K.J.), Odense University, Denmark; Stroke Medicine (J.C.S.), Lincoln County Hospital, University of Nottingham, UK; Department of Stroke Medicine (K.S.), Kawasaki Medical School, Kurashiki City, Okayama, Japan; Department of Emergency Medicine (A.S.), School of Medicine, Duzce University, Turkey; Department of Neurology (X.C.), Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China; and Centre for Clinical Brain Sciences (W.N.W.), University of Edinburgh, UK.
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Kensaku Shibazaki
From the Neurovascular Research Laboratory (T.G.-B., D.G., A.B., J.M.), Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain; Department of Neurology (T.E.), Kliniken Südostbayern-Klinikum Traunstein, Germany; Department of Psychiatry and Psychotherapy (T.E.), Technische Universität München, Germany; Department of Cardiology (J.K.J.), Odense University, Denmark; Stroke Medicine (J.C.S.), Lincoln County Hospital, University of Nottingham, UK; Department of Stroke Medicine (K.S.), Kawasaki Medical School, Kurashiki City, Okayama, Japan; Department of Emergency Medicine (A.S.), School of Medicine, Duzce University, Turkey; Department of Neurology (X.C.), Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China; and Centre for Clinical Brain Sciences (W.N.W.), University of Edinburgh, UK.
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Ayhan Saritas
From the Neurovascular Research Laboratory (T.G.-B., D.G., A.B., J.M.), Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain; Department of Neurology (T.E.), Kliniken Südostbayern-Klinikum Traunstein, Germany; Department of Psychiatry and Psychotherapy (T.E.), Technische Universität München, Germany; Department of Cardiology (J.K.J.), Odense University, Denmark; Stroke Medicine (J.C.S.), Lincoln County Hospital, University of Nottingham, UK; Department of Stroke Medicine (K.S.), Kawasaki Medical School, Kurashiki City, Okayama, Japan; Department of Emergency Medicine (A.S.), School of Medicine, Duzce University, Turkey; Department of Neurology (X.C.), Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China; and Centre for Clinical Brain Sciences (W.N.W.), University of Edinburgh, UK.
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Xingyong Chen
From the Neurovascular Research Laboratory (T.G.-B., D.G., A.B., J.M.), Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain; Department of Neurology (T.E.), Kliniken Südostbayern-Klinikum Traunstein, Germany; Department of Psychiatry and Psychotherapy (T.E.), Technische Universität München, Germany; Department of Cardiology (J.K.J.), Odense University, Denmark; Stroke Medicine (J.C.S.), Lincoln County Hospital, University of Nottingham, UK; Department of Stroke Medicine (K.S.), Kawasaki Medical School, Kurashiki City, Okayama, Japan; Department of Emergency Medicine (A.S.), School of Medicine, Duzce University, Turkey; Department of Neurology (X.C.), Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China; and Centre for Clinical Brain Sciences (W.N.W.), University of Edinburgh, UK.
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William N. Whiteley
From the Neurovascular Research Laboratory (T.G.-B., D.G., A.B., J.M.), Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain; Department of Neurology (T.E.), Kliniken Südostbayern-Klinikum Traunstein, Germany; Department of Psychiatry and Psychotherapy (T.E.), Technische Universität München, Germany; Department of Cardiology (J.K.J.), Odense University, Denmark; Stroke Medicine (J.C.S.), Lincoln County Hospital, University of Nottingham, UK; Department of Stroke Medicine (K.S.), Kawasaki Medical School, Kurashiki City, Okayama, Japan; Department of Emergency Medicine (A.S.), School of Medicine, Duzce University, Turkey; Department of Neurology (X.C.), Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China; and Centre for Clinical Brain Sciences (W.N.W.), University of Edinburgh, UK.
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Joan Montaner
From the Neurovascular Research Laboratory (T.G.-B., D.G., A.B., J.M.), Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain; Department of Neurology (T.E.), Kliniken Südostbayern-Klinikum Traunstein, Germany; Department of Psychiatry and Psychotherapy (T.E.), Technische Universität München, Germany; Department of Cardiology (J.K.J.), Odense University, Denmark; Stroke Medicine (J.C.S.), Lincoln County Hospital, University of Nottingham, UK; Department of Stroke Medicine (K.S.), Kawasaki Medical School, Kurashiki City, Okayama, Japan; Department of Emergency Medicine (A.S.), School of Medicine, Duzce University, Turkey; Department of Neurology (X.C.), Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China; and Centre for Clinical Brain Sciences (W.N.W.), University of Edinburgh, UK.
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Citation
B-type natriuretic peptides and mortality after stroke
A systematic review and meta-analysis
Teresa García-Berrocoso, Dolors Giralt, Alejandro Bustamante, Thorleif Etgen, Jesper K. Jensen, Jagdish C. Sharma, Kensaku Shibazaki, Ayhan Saritas, Xingyong Chen, William N. Whiteley, Joan Montaner
Neurology Dec 2013, 81 (23) 1976-1985; DOI: 10.1212/01.wnl.0000436937.32410.32

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Abstract

Objective: To measure the association of B-type natriuretic peptide (BNP) and N-terminal fragment of BNP (NT-proBNP) with all-cause mortality after stroke, and to evaluate the additional predictive value of BNP/NT-proBNP over clinical information.

Methods: Suitable studies for meta-analysis were found by searching MEDLINE and EMBASE databases until October 26, 2012. Weighted mean differences measured effect size; meta-regression and publication bias were assessed. Individual participant data were used to estimate effects by logistic regression and to evaluate BNP/NT-proBNP additional predictive value by area under the receiver operating characteristic curves, and integrated discrimination improvement and categorical net reclassification improvement indexes.

Results: Literature-based meta-analysis included 3,498 stroke patients from 16 studies and revealed that BNP/NT-proBNP levels were 255.78 pg/mL (95% confidence interval [CI] 105.10–406.47, p = 0.001) higher in patients who died; publication bias entailed the loss of this association. Individual participant data analysis comprised 2,258 stroke patients. After normalization of the data, patients in the highest quartile had double the risk of death after adjustment for clinical variables (NIH Stroke Scale score, age, sex) (odds ratio 2.30, 95% CI 1.32–4.01 for BNP; and odds ratio 2.63, 95% CI 1.75–3.94 for NT-proBNP). Only NT-proBNP showed a slight added value to clinical prognostic variables, increasing discrimination by 0.028 points (integrated discrimination improvement index; p < 0.001) and reclassifying 8.1% of patients into correct risk mortality categories (net reclassification improvement index; p = 0.003). Neither etiology nor time from onset to death affected the association of BNP/NT-proBNP with mortality.

Conclusion: BNPs are associated with poststroke mortality independent of NIH Stroke Scale score, age, and sex. However, their translation to clinical practice seems difficult because BNP/NT-proBNP add only minor predictive value to clinical information.

GLOSSARY

AUC=
area under the receiver operating characteristic curve;
BNP=
B-type natriuretic peptide;
CI=
confidence interval;
IDI=
integrated discrimination improvement;
IPD=
individual participant data;
IQR=
interquartile range;
NIHSS=
NIH Stroke Scale;
NRI=
net reclassification improvement;
NT-proBNP=
N-terminal fragment of B-type natriuretic peptide;
OR=
odds ratio;
WMD=
weighted mean difference

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 1970

  • Supplemental data at www.neurology.org

  • Received March 21, 2013.
  • Accepted in final form July 29, 2013.
  • © 2013 American Academy of Neurology
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Letters: Rapid online correspondence

  • Response to Brain Natriuretic Peptide and Mortality Following Subarachnoid Hemorrhage
    • Joan Montaner, Neurologist and Principal investigator, Vall d'Hebron Institute of Research31862jmv@comb.es
    • Teresa Garcia-Berrocoso, Barcelona, Spain; Joan Montaner, Barcelona, Spain
    Submitted January 13, 2014
  • Brain Natriuretic Peptide and Mortality Following Subarachnoid Hemorrhage
    • Katherine M. Duello, Mayo Clinic Floridaduello.katherine@mayo.edu
    • Jay P. Nagel, Jacksonville, FL; Joseph L. Blackshear, Jacksonville, FL; William D. Freeman, Jacksonville, FL; Joseph L. Blackshear, Jacksonville, FL; William D. Freeman, Jacksonville, FL
    Submitted January 10, 2014
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