Jan Emmerich , Aditya Chanpura , Tyler Lu , Alison Baird , Frank Barone , Deborah Gustafson , Timo Siepmann , Hagen Huttner , Kristian Barlinn
{"title":"基于血液的MMP-9对急性缺血性卒中早期鉴别的系统回顾和荟萃分析","authors":"Jan Emmerich , Aditya Chanpura , Tyler Lu , Alison Baird , Frank Barone , Deborah Gustafson , Timo Siepmann , Hagen Huttner , Kristian Barlinn","doi":"10.1016/j.jstrokecerebrovasdis.2025.108454","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Early differentiation between acute ischemic stroke (AIS) and stroke mimics remains challenging in emergency setting. Molecular biomarkers such as matrix metalloproteinase-9 (MMP-9) may aid in improving diagnostic accuracy.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted according to PRISMA guidelines across PubMed, EMBASE, Cochrane Library, and Web of Science. Studies assessing MMP-9 concentrations within 24 hours of symptom onset in AIS patients versus stroke mimics or healthy/matched controls ≥18 years were included. Random-effects meta-analyses were used to estimate pooled mean differences (MD) in MMP-9 levels between groups. Heterogeneity was assessed using I² and Cochran’s Q.</div></div><div><h3>Results</h3><div>Twenty-seven studies were included, with 16 (2,661 AIS patients, 1,283 all controls) meeting criteria for meta-analysis. Mean MMP-9 concentrations were significantly higher in AIS patients compared to all controls combined (MD: 93.9 ng/mL; 95%CI: 25.0-162.8; p=0.01, I²=96%, Cochran's Q: p<0.001). Subgroup analyses confirmed elevated levels in AIS patients versus healthy/matched controls (MD: 110.6 ng/mL; 95%CI:13.8-207.4; p=0.029) and versus stroke mimics (MD: 66.61 ng/mL; 95%CI: -6.2-139.4; p=0.01). Heterogeneity remained consistently high across comparisons (I² ≥ 95%; p<0.05).</div></div><div><h3>Conclusion</h3><div>MMP-9 levels appear significantly elevated in AIS patients compared to both stroke mimics and healthy controls/matched controls, supporting its potential as a diagnostic biomarker in the acute setting. However, substantial inter-study heterogeneity limits generalizability, and standardized studies are needed to validate their clinical applicability. (PROSPERO: CRD42024611953)</div></div><div><h3>Funding</h3><div>We acknowledge support from the German Research Foundation, the Medical Faculty Carl Gustav Carus, and the SLUB, as well as the Open Access Publication Funds of the TU Dresden. The funding bodies had no impact on any aspect of the study or the content of the manuscript.</div></div>","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"34 11","pages":"Article 108454"},"PeriodicalIF":1.8000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Blood-based MMP-9 for the early differentiation of acute ischemic stroke: a systematic review and meta-analysis\",\"authors\":\"Jan Emmerich , Aditya Chanpura , Tyler Lu , Alison Baird , Frank Barone , Deborah Gustafson , Timo Siepmann , Hagen Huttner , Kristian Barlinn\",\"doi\":\"10.1016/j.jstrokecerebrovasdis.2025.108454\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Early differentiation between acute ischemic stroke (AIS) and stroke mimics remains challenging in emergency setting. Molecular biomarkers such as matrix metalloproteinase-9 (MMP-9) may aid in improving diagnostic accuracy.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted according to PRISMA guidelines across PubMed, EMBASE, Cochrane Library, and Web of Science. Studies assessing MMP-9 concentrations within 24 hours of symptom onset in AIS patients versus stroke mimics or healthy/matched controls ≥18 years were included. Random-effects meta-analyses were used to estimate pooled mean differences (MD) in MMP-9 levels between groups. Heterogeneity was assessed using I² and Cochran’s Q.</div></div><div><h3>Results</h3><div>Twenty-seven studies were included, with 16 (2,661 AIS patients, 1,283 all controls) meeting criteria for meta-analysis. Mean MMP-9 concentrations were significantly higher in AIS patients compared to all controls combined (MD: 93.9 ng/mL; 95%CI: 25.0-162.8; p=0.01, I²=96%, Cochran's Q: p<0.001). Subgroup analyses confirmed elevated levels in AIS patients versus healthy/matched controls (MD: 110.6 ng/mL; 95%CI:13.8-207.4; p=0.029) and versus stroke mimics (MD: 66.61 ng/mL; 95%CI: -6.2-139.4; p=0.01). Heterogeneity remained consistently high across comparisons (I² ≥ 95%; p<0.05).</div></div><div><h3>Conclusion</h3><div>MMP-9 levels appear significantly elevated in AIS patients compared to both stroke mimics and healthy controls/matched controls, supporting its potential as a diagnostic biomarker in the acute setting. However, substantial inter-study heterogeneity limits generalizability, and standardized studies are needed to validate their clinical applicability. (PROSPERO: CRD42024611953)</div></div><div><h3>Funding</h3><div>We acknowledge support from the German Research Foundation, the Medical Faculty Carl Gustav Carus, and the SLUB, as well as the Open Access Publication Funds of the TU Dresden. The funding bodies had no impact on any aspect of the study or the content of the manuscript.</div></div>\",\"PeriodicalId\":54368,\"journal\":{\"name\":\"Journal of Stroke & Cerebrovascular Diseases\",\"volume\":\"34 11\",\"pages\":\"Article 108454\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2025-09-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Stroke & Cerebrovascular Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1052305725002319\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Stroke & Cerebrovascular Diseases","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1052305725002319","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Blood-based MMP-9 for the early differentiation of acute ischemic stroke: a systematic review and meta-analysis
Background
Early differentiation between acute ischemic stroke (AIS) and stroke mimics remains challenging in emergency setting. Molecular biomarkers such as matrix metalloproteinase-9 (MMP-9) may aid in improving diagnostic accuracy.
Methods
A systematic literature search was conducted according to PRISMA guidelines across PubMed, EMBASE, Cochrane Library, and Web of Science. Studies assessing MMP-9 concentrations within 24 hours of symptom onset in AIS patients versus stroke mimics or healthy/matched controls ≥18 years were included. Random-effects meta-analyses were used to estimate pooled mean differences (MD) in MMP-9 levels between groups. Heterogeneity was assessed using I² and Cochran’s Q.
Results
Twenty-seven studies were included, with 16 (2,661 AIS patients, 1,283 all controls) meeting criteria for meta-analysis. Mean MMP-9 concentrations were significantly higher in AIS patients compared to all controls combined (MD: 93.9 ng/mL; 95%CI: 25.0-162.8; p=0.01, I²=96%, Cochran's Q: p<0.001). Subgroup analyses confirmed elevated levels in AIS patients versus healthy/matched controls (MD: 110.6 ng/mL; 95%CI:13.8-207.4; p=0.029) and versus stroke mimics (MD: 66.61 ng/mL; 95%CI: -6.2-139.4; p=0.01). Heterogeneity remained consistently high across comparisons (I² ≥ 95%; p<0.05).
Conclusion
MMP-9 levels appear significantly elevated in AIS patients compared to both stroke mimics and healthy controls/matched controls, supporting its potential as a diagnostic biomarker in the acute setting. However, substantial inter-study heterogeneity limits generalizability, and standardized studies are needed to validate their clinical applicability. (PROSPERO: CRD42024611953)
Funding
We acknowledge support from the German Research Foundation, the Medical Faculty Carl Gustav Carus, and the SLUB, as well as the Open Access Publication Funds of the TU Dresden. The funding bodies had no impact on any aspect of the study or the content of the manuscript.
期刊介绍:
The Journal of Stroke & Cerebrovascular Diseases publishes original papers on basic and clinical science related to the fields of stroke and cerebrovascular diseases. The Journal also features review articles, controversies, methods and technical notes, selected case reports and other original articles of special nature. Its editorial mission is to focus on prevention and repair of cerebrovascular disease. Clinical papers emphasize medical and surgical aspects of stroke, clinical trials and design, epidemiology, stroke care delivery systems and outcomes, imaging sciences and rehabilitation of stroke. The Journal will be of special interest to specialists involved in caring for patients with cerebrovascular disease, including neurologists, neurosurgeons and cardiologists.