Serum biomarkers in patients suspected of transient ischaemic attack in primary care: a diagnostic accuracy study

Objective The diagnosis of transient ischaemic attack (TIA) based on symptoms and signs can be challenging and would greatly benefit from a rapid serum biomarker of brain ischaemia. We aimed to quantify the added diagnostic value of serum biomarkers in patients suspected of TIA beyond symptoms and s...

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Main Authors: Arno W Hoes, Paul J Nederkoorn, Ewoud J Van Dijk, Jaap Kappelle, Louis Servaas Dolmans, Frans Rutten, Marie-Louise E L Bartelink, LS Dolmans, MEL Bartelink, FH Rutten, AW Hoes, LJ Kappelle, EJ van Dijk, PJ Nederkoorn, S van Delft, GJ Seppenwoolde
Format: Article
Language:English
Published: BMJ Publishing Group 2019-10-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/9/10/e031774.full
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author Arno W Hoes
Paul J Nederkoorn
Ewoud J Van Dijk
Jaap Kappelle
Louis Servaas Dolmans
Frans Rutten
Marie-Louise E L Bartelink
LS Dolmans
MEL Bartelink
FH Rutten
AW Hoes
LJ Kappelle
EJ van Dijk
PJ Nederkoorn
S van Delft
GJ Seppenwoolde
author_facet Arno W Hoes
Paul J Nederkoorn
Ewoud J Van Dijk
Jaap Kappelle
Louis Servaas Dolmans
Frans Rutten
Marie-Louise E L Bartelink
LS Dolmans
MEL Bartelink
FH Rutten
AW Hoes
LJ Kappelle
EJ van Dijk
PJ Nederkoorn
S van Delft
GJ Seppenwoolde
author_sort Arno W Hoes
collection DOAJ
description Objective The diagnosis of transient ischaemic attack (TIA) based on symptoms and signs can be challenging and would greatly benefit from a rapid serum biomarker of brain ischaemia. We aimed to quantify the added diagnostic value of serum biomarkers in patients suspected of TIA beyond symptoms and signs.Methods This is a cross-sectional diagnostic accuracy study with a 6-month follow-up period. Participants were patients suspected of TIA by the general practitioner (GP) in whom a blood sample could be collected within 72 hours from symptom onset. A research nurse visited the participant for the blood sample and a standardised interview. The GP referred participants to the regional TIA service. An expert panel of three neurologists classified cases as TIA, minor stroke or any other diagnosis, based on all available diagnostic information including the GP’s and neurologist’s correspondence and the follow-up period. We used multivariable logistic regression analyses to quantify the diagnostic accuracy of clinical predictors and the improvement of accuracy by seven biomarkers (NR2, NR2 antibodies, PARK7, NDKA, UFD1, B-FABP and H-FABP).Results 206 patients suspected of TIA participated, of whom 126 (61.2%) were diagnosed with TIA (n=104) or minor stroke (n=22) by the expert panel. The median time from symptom onset to the blood sample collection was 48.0 (IQR 28.3–56.8) hours. None of the seven biomarkers had discriminative value in the diagnosis of TIA, with C-statistics ranging from 0.45 to 0.58. The final multivariable model (C-statistic 0.83 (0.78–0.89)) consisted of eight clinical predictors of TIA/minor stroke: increasing age, a history of coronary artery disease, sudden onset of symptoms, occurrence of symptoms in full intensity, dysarthria, no history of migraine, absence of loss of consciousness and absence of headache. Addition of the individual biomarkers did not further increase the C-statistics.Conclusions Currently available blood biomarkers have no added diagnostic value in suspected TIA.Trial registration number NCT01954329
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spelling doaj-art-20885cdabd5647c8a89d57f35a6a99052025-08-20T02:38:38ZengBMJ Publishing GroupBMJ Open2044-60552019-10-0191010.1136/bmjopen-2019-031774Serum biomarkers in patients suspected of transient ischaemic attack in primary care: a diagnostic accuracy studyArno W Hoes0Paul J Nederkoorn1Ewoud J Van Dijk2Jaap Kappelle3Louis Servaas Dolmans4Frans Rutten5Marie-Louise E L Bartelink6LS DolmansMEL BartelinkFH RuttenAW HoesLJ KappelleEJ van DijkPJ NederkoornS van DelftGJ SeppenwooldeDepartment of General Practice, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands7 Neurology, Amsterdam UMC, Amsterdam, NetherlandsDeparment of Neurology, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Neurology, University Medical Center Utrecht Brain Center, Utrecht, The Netherlands1 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands1 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands1 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The NetherlandsObjective The diagnosis of transient ischaemic attack (TIA) based on symptoms and signs can be challenging and would greatly benefit from a rapid serum biomarker of brain ischaemia. We aimed to quantify the added diagnostic value of serum biomarkers in patients suspected of TIA beyond symptoms and signs.Methods This is a cross-sectional diagnostic accuracy study with a 6-month follow-up period. Participants were patients suspected of TIA by the general practitioner (GP) in whom a blood sample could be collected within 72 hours from symptom onset. A research nurse visited the participant for the blood sample and a standardised interview. The GP referred participants to the regional TIA service. An expert panel of three neurologists classified cases as TIA, minor stroke or any other diagnosis, based on all available diagnostic information including the GP’s and neurologist’s correspondence and the follow-up period. We used multivariable logistic regression analyses to quantify the diagnostic accuracy of clinical predictors and the improvement of accuracy by seven biomarkers (NR2, NR2 antibodies, PARK7, NDKA, UFD1, B-FABP and H-FABP).Results 206 patients suspected of TIA participated, of whom 126 (61.2%) were diagnosed with TIA (n=104) or minor stroke (n=22) by the expert panel. The median time from symptom onset to the blood sample collection was 48.0 (IQR 28.3–56.8) hours. None of the seven biomarkers had discriminative value in the diagnosis of TIA, with C-statistics ranging from 0.45 to 0.58. The final multivariable model (C-statistic 0.83 (0.78–0.89)) consisted of eight clinical predictors of TIA/minor stroke: increasing age, a history of coronary artery disease, sudden onset of symptoms, occurrence of symptoms in full intensity, dysarthria, no history of migraine, absence of loss of consciousness and absence of headache. Addition of the individual biomarkers did not further increase the C-statistics.Conclusions Currently available blood biomarkers have no added diagnostic value in suspected TIA.Trial registration number NCT01954329https://bmjopen.bmj.com/content/9/10/e031774.full
spellingShingle Arno W Hoes
Paul J Nederkoorn
Ewoud J Van Dijk
Jaap Kappelle
Louis Servaas Dolmans
Frans Rutten
Marie-Louise E L Bartelink
LS Dolmans
MEL Bartelink
FH Rutten
AW Hoes
LJ Kappelle
EJ van Dijk
PJ Nederkoorn
S van Delft
GJ Seppenwoolde
Serum biomarkers in patients suspected of transient ischaemic attack in primary care: a diagnostic accuracy study
BMJ Open
title Serum biomarkers in patients suspected of transient ischaemic attack in primary care: a diagnostic accuracy study
title_full Serum biomarkers in patients suspected of transient ischaemic attack in primary care: a diagnostic accuracy study
title_fullStr Serum biomarkers in patients suspected of transient ischaemic attack in primary care: a diagnostic accuracy study
title_full_unstemmed Serum biomarkers in patients suspected of transient ischaemic attack in primary care: a diagnostic accuracy study
title_short Serum biomarkers in patients suspected of transient ischaemic attack in primary care: a diagnostic accuracy study
title_sort serum biomarkers in patients suspected of transient ischaemic attack in primary care a diagnostic accuracy study
url https://bmjopen.bmj.com/content/9/10/e031774.full
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