Anxiety Disorders, Obsessive-Compulsive Disorder and Post-Traumatic Stress Disorder and Risk of First-Ever Stroke: A Systematic Review and Meta-Analysis of 11.2 Million Participants

Background Anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder are characterised by chronic stress-related physiological dysregulation that may increase vascular risk. However, the association of anxiety and related disorders with stroke has not been systematically evaluated. Prior studies often pooled clinical diagnoses with symptom-based measures, risking exposure misclassification. We aimed to quantify the association between these disorders and risk of first-ever stroke. Methods We conducted a systematic review and meta-analysis of cohort studies examining anxiety and related disorders in relation to first-ever stroke. Eligible studies defined psychiatric exposure dichotomously using either clinically confirmed Diagnostic and Statistical Manual of Mental Disorders (DSM)/International Classification of Diseases (ICD) diagnoses or validated symptom-based cut-off thresholds. Studies using DSM/ICD diagnoses and symptom-based measures were pooled separately. Hazard ratios (HR) were combined using random-effects models. Subgroup analyses examined risks by psychiatric disorder type, stroke subtype, geographical region, follow-up duration, excluding early stroke events to minimise reverse causality, and additional adjustment for depression. Results Across 23 cohort studies (11 181 338 participants) anxiety and related disorders were associated with higher stroke risk (HR 1.38; 95% CI: 1.28–1.50). Post-traumatic stress disorder showed the strongest association (HR 1.50; 95% CI: 1.31–1.72), while anxiety disorders showed a modest risk (HR 1.29, 95% CI 1.14–1.46). Obsessive-compulsive disorder was described narratively due to a single eligible study, which reported a similarly increased risk (HR 1.25; 95% CI: 1.18–1.32). Risk was significant for ischaemic stroke (HR 1.34; 95% CI: 1.13–1.58) but not haemorrhagic stroke. Estimates were higher in Asian populations (HR 1.53) than Western populations. Associations persisted in sensitivity analyses excluding early strokes and after adjustment for depression. Conclusions Anxiety and related disorders are associated with increased risk of first-ever ischaemic stroke, with post-traumatic stress disorder showing the strongest association, supporting their recognition as non-traditional stroke risk factors.