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Stroke risk following traumatic brain injury: Systematic review and meta-analysis

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McMullan, C 
Aiyegbusi, OL 
Bem, D 
Marshall, T 


Background Traumatic brain injury (TBI) is a global health problem; worldwide, >60 million people experience a TBI each year and incidence is rising. TBI has been proposed as an independent risk factor for stroke.

Aims To investigate the association between TBI and stroke risk.

Summary of review We undertook a systematic review of MEDLINE, EMBASE, CINAHL, and The Cochrane Library from inception to 4th December 2020. We used random-effects meta-analysis to pool hazard ratios (HR) for studies which reported stroke risk post-TBI compared to controls. Searches identified 10,501 records; 58 full texts were assessed for eligibility and 18 met the inclusion criteria. The review included a large sample size of 2,606,379 participants from four countries. Six studies included a non-TBI control group, all found TBI patients had significantly increased risk of stroke compared to controls (pooled HR 1.86; 95% CI 1.46-2.37). Findings suggest stroke risk may be highest in the first four months post-TBI, but remains significant up to five years post-TBI. TBI appears to be associated with increased stroke risk regardless of severity or subtype of TBI. There was some evidence to suggest an association between reduced stroke risk post-TBI and Vitamin K antagonists and statins, but increased stroke risk with certain classes of antidepressants.

Conclusion TBI is an independent risk factor for stroke, regardless of TBI severity or type. Post-TBI review and management of risk factors for stroke may be warranted.



Traumatic brain injury, traumatic brain injury, stroke, risk, meta-analysis, systematic review

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International Journal of Stroke

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This research was funded by the National Institute for Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre (SRMRC). GMT is funded by the NIHR Postdoctoral Fellowship programme (PDF-2017-10-047) and NIHR SRMRC. MC receives funding from the NIHR Birmingham Biomedical Research Centre, NIHR SRMRC at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Health Data Research UK, Innovate UK, part of UK Research and Innovation, and Macmillan Cancer Support. OLA receives funding from the Health Foundation an independent charity working to improve the quality of healthcare in the UK. He also receives funding from the NIHR Birmingham Biomedical Research Centre. TM is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) West Midlands. The views expressed are those of the authors are not necessarily those of the NHS, the NIHR, the Health Foundation or the Department of Health and Social Care. The funders had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.