Towards the identification of blood biomarkers for acute stroke in humans: a comprehensive systematic review

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTStroke is the largest single cause of disability in the UK. While tests based upon biomarkers have been around for decades, interest in the applications of biomarkers has increased greatly in recent years. Biomarkers released into the bloodstream following a stroke are useful not only for understanding the pathogenesis of stroke, but also play a significant role in the development of personalised medicine. The efficacy of current clinical models and imaging techniques for the diagnosis and prognosis of acute stroke could be improved when used in conjunction with blood biomarkers. While several studies have proposed a number of biomarkers associated with acute stroke in humans, there is conflicting information about the significance of implicated markers, and their clinical relevance is unclear. WHAT THIS STUDY ADDSIn an attempt to consolidate the plethora of data in this field, we have conducted a comprehensive systematic review and meta-analysis of proteomic and metabolomic blood biomarkers associated with acute stroke. Our meta-analysis has found eight biomarkers that are significantly associated with the diagnosis and prognosis of acute stroke. Interestingly we also found that CRP, a protein commonly implicated as a strong biomarker of inflammation and stroke, may not have sufficient sensitivity and specificity to be of clinical value, Thus while the biomarkers identified through our study are likely to be biologically informative about the mechanisms of vascular disease, their clinical potential for a blood-based test warrants further investigation. AIMSIdentification 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. METHODSA 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. RESULTSWe 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 mmol l -1 , 95% CI 130.54, 214.75; P = 0.00001), D-dimer predicted in-hospi...

The Role of D-Dimer, Fibrinogen and C-Reactive Protein as Plasma Biomarkers in Acute Ischemic Stroke

“…There was highly significant difference between the patients and controls regarding CRP which agreed with Hasan et al [19] who found that CRP within 24 h of the onset of the symptoms was significantly differentiated between ischemic stroke and healthy control subjects.…”

Blood Markers of Coagulation, Fibrinolysis, Endothelial Dysfunction and Inflammation in Lacunar Stroke versus Non-Lacunar Stroke and Non-Stroke: Systematic Review and Meta-Analysis

“…Another review [3] found C-reactive protein (CRP), P-selectin and homocysteine to differ significantly between ischaemic stroke (in general) and non-stroke controls, but did not assess levels of blood markers between ischaemic stroke subtypes. …”

The Link between Early Biomarker Analysis and the Neurological Outcome in Stroke Patients

“…Hasan concluded in their report that high levels of glucose were a strong predictor for poor outcome following an ischemic stroke [28]. Another study from 2015 by Masrur found that both acute and chronic hyperglycemia were associated with worse post-stroke outcome, regardless whether diabetes was diagnosed before occurrence of the stroke or not [29].…”