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

BMJ Open. 2019 Oct 17;9(10):e031774. doi: 10.1136/bmjopen-2019-031774.


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.

Keywords: TIA; biomarker; diagnostic accuracy; minor stroke; panel.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Cross-Sectional Studies
  • Female
  • Humans
  • Ischemic Attack, Transient / blood
  • Ischemic Attack, Transient / diagnosis*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Netherlands
  • Primary Health Care
  • Referral and Consultation
  • Stroke / blood
  • Stroke / diagnosis*


  • Biomarkers

Associated data