Towards the identification of blood biomarkers for acute stroke in humans: a comprehensive systematic review.
OBJECTIVE
Identification of biomarkers for stroke will aid our understanding of its aetiology, provide diagnostic and prognostic indicators for patient selection and stratification, and play a significant role in developing personalized medicine. We undertook the largest systematic review conducted to date in an attempt to characterize diagnostic and prognostic biomarkers in acute ischaemic and haemorrhagic stroke and those likely to predict complications following thrombolysis.


METHODS
A comprehensive literature search was carried out to identify diagnostic and prognostic stroke blood biomarkers. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated for each biomarker.


RESULTS
We identified a total of 141 relevant studies, interrogating 136 different biomarkers. Three biomarkers (C-reactive protein, P-selectin and homocysteine) significantly differentiated between ischaemic stroke and healthy control subjects. Furthermore, glial fibrillary acidic protein levels were significantly different between haemorrhagic stroke and ischaemic stroke patients (MD 224.58 ng l⁻¹; 95% CI 25.84, 423.32; P= 0.03), high levels of admission glucose were a strong predictor of poor prognosis after ischaemic stroke and symptomatic intracerebral haemorrhage post-thrombolysis, glutamate was found to be an indicator of progressive (unstable) stroke (MD 172.65 µmol l⁻¹, 95% CI 130.54, 214.75; P= 0.00001), D-dimer predicted in-hospital death (MD 0.67 µg ml⁻¹, 95% CI 0.35, 1.00; P= 0.0001), and high fibrinogen levels were associated with poor outcome at 3 months (MD 47.90 mg l⁻¹, 95% CI 14.88, 80.93; P= 0.004) following ischaemic stroke.


CONCLUSIONS
Few biomarkers currently investigated have meaningful clinical value. Admission glucose may be a strong marker of poor prognosis following acute thrombolytic treatment. However, molecules released in the bloodstream before, during or after stroke may have potential to be translated into sensitive blood-based tests.
Imperial College Cerebrovascular Research Unit-ICCRU, Division of Experimental Medicine, Imperial College, London, UK.
Nazeeha
N
Hasan
Peter
P
McColgan
Paul
P
Bentley
Robert J
RJ
Edwards
Pankaj
P
Sharma
D015415:Biomarkers / Q000097:blood*; D006801:Humans; D018579:Patient Selection; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000628:therapy
D015415:Biomarkers