A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic Strokes

Acute ischemic stroke caused by large vessel occlusions (LVOs) is a major contributor to stroke deaths and disabilities; however, identification for emergency treatment is challenging. We recruited two separate cohorts of suspected stroke patients and screened a panel of blood-derived protein biomar...

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Main Authors: Edoardo Gaude, Barbara Nogueira, Marcos Ladreda Mochales, Sheila Graham, Sarah Smith, Lisa Shaw, Sara Graziadio, Gonzalo Ladreda Mochales, Philip Sloan, Joshua D. Bernstock, Shashank Shekhar, Toby I. Gropen, Christopher I. Price
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Diagnostics
Subjects:
Online Access:https://www.mdpi.com/2075-4418/11/7/1137
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spelling doaj-54c7bb07e82f4bb7957821b25502b48b2021-07-23T13:36:56ZengMDPI AGDiagnostics2075-44182021-06-01111137113710.3390/diagnostics11071137A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic StrokesEdoardo Gaude0Barbara Nogueira1Marcos Ladreda Mochales2Sheila Graham3Sarah Smith4Lisa Shaw5Sara Graziadio6Gonzalo Ladreda Mochales7Philip Sloan8Joshua D. Bernstock9Shashank Shekhar10Toby I. Gropen11Christopher I. Price12Pockit Diagnostics Ltd., Cambridge CB4 2HY, UKPockit Diagnostics Ltd., Cambridge CB4 2HY, UKPockit Diagnostics Ltd., Cambridge CB4 2HY, UKCEPA Biobank, The Newcastle NHS Foundation Trust, Newcastle upon Tyne NE3 3HD, UKNovoPath Biobank, Newcastle MRC Node, Newcastle NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UKStroke Research Group, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UKNewcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4HH, UKPockit Diagnostics Ltd., Cambridge CB4 2HY, UKCEPA Biobank, The Newcastle NHS Foundation Trust, Newcastle upon Tyne NE3 3HD, UKBrigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USAUniversity of Mississippi Medical Center, Jackson, MS 39216, USAUniversity of Alabama at Birmingham, Birmingham, AL 35294, USAStroke Research Group, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UKAcute ischemic stroke caused by large vessel occlusions (LVOs) is a major contributor to stroke deaths and disabilities; however, identification for emergency treatment is challenging. We recruited two separate cohorts of suspected stroke patients and screened a panel of blood-derived protein biomarkers for LVO detection. Diagnostic performance was estimated by using blood biomarkers in combination with NIHSS-derived stroke severity scales. Multivariable analysis demonstrated that D-dimer (OR 16, 95% CI 5–60; <i>p</i>-value < 0.001) and GFAP (OR 0.002, 95% CI 0–0.68; <i>p</i>-value < 0.05) comprised the optimal panel for LVO detection. Combinations of D-dimer and GFAP with a number of stroke severity scales increased the number of true positives, while reducing false positives due to hemorrhage, as compared to stroke scales alone (<i>p</i>-value < 0.001). A combination of the biomarkers with FAST-ED resulted in the highest accuracy at 95% (95% CI: 87–99%), with sensitivity of 91% (95% CI: 72–99%), and specificity of 96% (95% CI: 90–99%). Diagnostic accuracy was confirmed in an independent cohort, in which accuracy was again shown to be 95% (95% CI: 87–99%), with a sensitivity of 82% (95% CI: 57–96%), and specificity of 98% (95% CI: 92–100%). Accordingly, the combination of D-dimer and GFAP with stroke scales may provide a simple and highly accurate tool for identifying LVO patients, with a potential impact on time to treatment.https://www.mdpi.com/2075-4418/11/7/1137strokebiomarkerslarge vessel occlusions
collection DOAJ
language English
format Article
sources DOAJ
author Edoardo Gaude
Barbara Nogueira
Marcos Ladreda Mochales
Sheila Graham
Sarah Smith
Lisa Shaw
Sara Graziadio
Gonzalo Ladreda Mochales
Philip Sloan
Joshua D. Bernstock
Shashank Shekhar
Toby I. Gropen
Christopher I. Price
spellingShingle Edoardo Gaude
Barbara Nogueira
Marcos Ladreda Mochales
Sheila Graham
Sarah Smith
Lisa Shaw
Sara Graziadio
Gonzalo Ladreda Mochales
Philip Sloan
Joshua D. Bernstock
Shashank Shekhar
Toby I. Gropen
Christopher I. Price
A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic Strokes
Diagnostics
stroke
biomarkers
large vessel occlusions
author_facet Edoardo Gaude
Barbara Nogueira
Marcos Ladreda Mochales
Sheila Graham
Sarah Smith
Lisa Shaw
Sara Graziadio
Gonzalo Ladreda Mochales
Philip Sloan
Joshua D. Bernstock
Shashank Shekhar
Toby I. Gropen
Christopher I. Price
author_sort Edoardo Gaude
title A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic Strokes
title_short A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic Strokes
title_full A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic Strokes
title_fullStr A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic Strokes
title_full_unstemmed A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic Strokes
title_sort novel combination of blood biomarkers and clinical stroke scales facilitates detection of large vessel occlusion ischemic strokes
publisher MDPI AG
series Diagnostics
issn 2075-4418
publishDate 2021-06-01
description Acute ischemic stroke caused by large vessel occlusions (LVOs) is a major contributor to stroke deaths and disabilities; however, identification for emergency treatment is challenging. We recruited two separate cohorts of suspected stroke patients and screened a panel of blood-derived protein biomarkers for LVO detection. Diagnostic performance was estimated by using blood biomarkers in combination with NIHSS-derived stroke severity scales. Multivariable analysis demonstrated that D-dimer (OR 16, 95% CI 5–60; <i>p</i>-value < 0.001) and GFAP (OR 0.002, 95% CI 0–0.68; <i>p</i>-value < 0.05) comprised the optimal panel for LVO detection. Combinations of D-dimer and GFAP with a number of stroke severity scales increased the number of true positives, while reducing false positives due to hemorrhage, as compared to stroke scales alone (<i>p</i>-value < 0.001). A combination of the biomarkers with FAST-ED resulted in the highest accuracy at 95% (95% CI: 87–99%), with sensitivity of 91% (95% CI: 72–99%), and specificity of 96% (95% CI: 90–99%). Diagnostic accuracy was confirmed in an independent cohort, in which accuracy was again shown to be 95% (95% CI: 87–99%), with a sensitivity of 82% (95% CI: 57–96%), and specificity of 98% (95% CI: 92–100%). Accordingly, the combination of D-dimer and GFAP with stroke scales may provide a simple and highly accurate tool for identifying LVO patients, with a potential impact on time to treatment.
topic stroke
biomarkers
large vessel occlusions
url https://www.mdpi.com/2075-4418/11/7/1137
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