Blood biomarkers for the diagnosis and differentiation of stroke: A systematic review and meta-analysis

Abstract

Background Correct diagnosis of stroke and its subtypes is pivotal in early stages for optimum treatment. Aims The aim of this systematic review and meta-analysis is to summarize the published evidence on the potential of blood biomarkers in the diagnosis and differentiation of stroke subtypes. Methods A literature search was conducted for papers published until 20 April 2020 in PubMed, EMBASE, Cochrane Library, TRIP, and Google Scholar databases to search for eligible studies investigating the role of blood biomarkers in diagnosing stroke. Quality assessment was done using modified Quality Assessment of Diagnostic Accuracy Studies questionnaire. Pooled standardized mean difference and 95% confidence intervals were calculated. Presence of heterogeneity among the included studies was investigated using the Cochran's Q statistic and I2 metric tests. If I2 was < 50% then a fixed-effect model was applied else a random-effect model was applied. Risk of bias was assessed using funnel plots and between-study heterogeneity was assessed using meta-regression and sensitivity analyses. Entire statistical analysis was conducted in STATA version 13.0. Results A total of 40 studies including patients with 5001 ischemic strokes, 756 intracerebral hemorrhage, 554 stroke mimics, and 1774 healthy control subjects analyzing 25 biomarkers (within 24 h after symptoms onset/after the event) were included in our meta-analysis; 67.5% of studies had moderate evidence of quality. Brain natriuretic peptide, matrix metalloproteinase-9, and D-dimer significantly differentiated ischemic stroke from intracerebral hemorrhage, stroke mimics, and health control subjects ( p < 0.05). Glial fibrillary acidic protein successfully differentiated ischemic stroke from intracerebral hemorrhage (standardized mean difference −1.04; 95% confidence interval −1.46 to −0.63) within 6 h. No studies were found to conduct a meta-analysis of blood biomarkers differentiating transient ischemic attack from healthy controls and stroke mimics. Conclusion This meta-analysis highlights the potential of brain natriuretic peptide, matrix metalloproteinase-9, D-dimer, and glial fibrillary acidic protein as diagnostic biomarkers for stroke within 24 h. Results of our meta-analysis might serve as a platform for conducting further targeted proteomics studies and phase-III clinical trials. PROSPERO Registration ID: CRD42019139659.

Proteomics-Based Approach to Identify Novel Blood Biomarker Candidates for Differentiating Intracerebral Hemorrhage From Ischemic Stroke—A Pilot Study

“…Its potential use has been demonstrated in an Indian trial, too (16)(17)(18)(19)(20)(21). On the other side, comparable markers of IS have not been identified so far (22)(23)(24).…”

Scalable Bio Marker Combinations for Early Stroke Diagnosis: A Systematic Review

“…Note that glial fibrillary acidic protein (GFAP) was the most promising biomarker in the study of separate ischemic stroke (IS), intracerebral hemorrhage (ICH), and healthy controls. The same study mentions D-dimer, matrix metalloproteinase 9 (MMP-9), brain natriuretic peptide (BNP), and protein S100-β (S100β) derived from the meta-regression analysis as significant markers to be evaluated within 6 and 24 h of symptom onset (22).…”

Association of Plasma Thrombin-Antithrombin Complex and Ischemic Stroke: A Systematic Review and Meta-analysis

“…The PRISMA ow diagram for study inclusion in our meta-analysis was depicted in Fig 1 . 1651 articles remaining after deduplication, and then the letters, reviews, cases reported, animal studies, and literature not related to the topic were excluded by browsing the titles and abstracts, totaling 759 publications. A full-text of 538 potentially eligible articles was retrieved, studies were excluded again for no relation with TAT (379), study topic is not a stroke (138), and without full text (9). Finally, 12 studies were included in our meta-analysis.…”

“…Research on some easily available blood markers in ischemic stroke has been reported in a previous review for the diagnosis and differentiation of stroke, including matrix metalloproteinase-9, brain natriuretic peptide, and D-dimer [9]. Situ thrombosis and thromboembolism are the main causes of blood circulation blockage in ischemic stroke, which involve disorders of the coagulation system.…”