Prognostic Factors Associated with Long-Term Risk of Stroke After Transient Ischemic Attack or Minor Stroke: A Systematic Review and Meta-Analysis

BACKGROUND: Patients with a transient ischemic attack (TIA) or minor stroke have an increased risk of subsequent stroke that persists for at least 10 years. We aimed to identify prognostic factors associated with long-term risk of stroke in this patient group, and estimate their population attribution fraction (PAF). METHODS: A systematic review was performed of MEDLINE, Embase, and Web of Science for cohort studies including patients with TIA or minor stroke that evaluated factors for subsequent stroke over a follow-up period of ≥1 year. We pooled hazard ratios adjusted for relevant confounders using random-effect meta-analysis and determined the PAF of factors based on their pooled prevalence and adjusted hazard ratio (aHR). We assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The study is registered in PROSPERO (CRD42023476551). RESULTS: From 14 732 identified citations, we included 28 cohort studies comprising 86 810 patients with TIA or minor stroke (median age, 69 years [IQR, 65-71]; 52-60% male patients). Factors that had high certainty evidence of association with increased long-term risk of stroke included older age (aHR 1.04 per year increase, 95% CI 1.02-1.05), male sex (1.25, 1.15-1.36; PAF 13.0%, 95% CI 7.8-18.7), atrial fibrillation (1.34, 1.18-1.52; 3.8%, 95% CI 0.3-9.9), diabetes mellitus (1.52, 1.32-1.75; 7.7%, 3.1-14.1), hypertension (1.60, 1.31-1.94; 19.3%, 8.4-31.6), ischemic heart disease (1.67, 1.28-2.18; 10.7%, 2.8-22.9), history of stroke or TIA before the index event (1.70, 1.43-2.02; 12.0%, 5.2-21.4), smoking (1.29, 1.05-1.60; 11.2%, 1.0-30.7), ABCD2 score of ≥4 (1.59, 1.31-1.94; 18.0%, 2.9-39.9), presence of acute infarct on neuroimaging (1.97, 1.41-2.74; 19.0%, 5.2-38.9) including diffusion-weighted imaging positive lesions (1.86, 1.02-3.37; 14.0%, 7.0-25.0), minor stroke as index event (1.75, 1.35-2.27 vs TIA; 28.0%, 10.2-47.6), presentation with aphasia or dysarthria (1.45, 1.24-1.69; 19.2%, 0.2-53.1), presentation with paresis (1.45, 1.15-1.84; 22.0%, 3.8-43.4), and etiologic stroke subtypes including cardioembolism (2.16, 1.53-3.05; 14.6%, 3.1-33.5), large artery atherosclerosis (2.19, 1.68-2.86; 13.2%, 5.1-25.5), and small vessel disease (1.69, 1.14-2.49; 16.8%, 5.0-34.3). CONCLUSIONS: These findings can help identify patients with a particularly enduring risk of stroke who are most likely to benefit from ongoing monitoring and treatment, and facilitate the development and implementation of targeted stroke prevention strategies.