Association Between Traumatic Brain Injury and Increased Risk of Stroke: A Systematic Review and Meta-analysis

Objective: To determine whether exposure to traumatic brain injury (TBI) is associated with increased risk of stroke in adults compared with referents not exposed to TBI, and to understand whether an association exists throughout the spectrum of injury severity, whether it differs between the acute and chronic phases after TBI, and whether the association is greater with hemorrhagic compared with ischemic stroke after TBI. Setting: A database search was conducted on January 22, 2021. Searches were run in MEDLINE (1946 to present), Embase (1988 to present), Evidence-Based Medicine Reviews (various dates), Scopus (1970 to present), and Web of Science (1975 to present). Design: Observational studies that quantified the association of stroke after TBI compared with referents without TBI were included. Three coauthors independently reviewed titles and abstracts to determine study eligibility. Study characteristics were extracted independently by 2 coauthors who followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and study quality was assessed independently by 2 coauthors who used the Newcastle-Ottawa Scale. Random-effects meta-analyses were performed. Main Measures: The primary exposure was TBI of any severity, and the primary outcome was stroke of any kind. Subgroup analysis was performed to assess heterogeneity associated with severity of TBI, type of stroke, and time from TBI to stroke. Results: A total of 64 full-text articles were reviewed, and data were extracted from 8 cohort studies (N = 619 992 individuals exposed to TBI along with nonexposed referents). A significant overall association was found with TBI and stroke (hazard ratio, 2.06; 95% CI, 1.28-3.32). Significant subgroup differences were found with a smaller risk of ischemic stroke compared with stroke of all types (P <.001, I² = 93.9%). Conclusions: TBI, regardless of injury severity, was associated with a higher risk of stroke. To improve secondary stroke prevention strategies, future studies should classify TBI severity and type of stroke more precisely and determine long-term risk.