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

F Faizan Khan (Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada (F.K., R.L., A.G., P.A.B., S.B.C., M.D.H.).) V Vignan Yogendrakumar (Department of Neurology, University of Melbourne, Melbourne, VIC, Australia (V.Y.).) R Ronda Lun (Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada (F.K., R.L., A.G., P.A.B., S.B.C., M.D.H.).) C Caterina E. Marx (The Ottawa Hospital and Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada (V.Y., C.E.M., A.T.).) B Bram Rochwerg A Alexandre Tran (The Ottawa Hospital and Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada (V.Y., C.E.M., A.T.).) S Shannon M. Fernando (Department of Critical Care, Lakeridge Health, Oshawa, ON, Canada (S.M.F.).) A Aravind Ganesh (Department of Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, AB, Canada) P Philip A. Barber J Joachim Ögren A Angel Ois (Hospital del Mar Medical Research Institute, Barcelona, Spain (A.O., E.G.-S.).) E Eva Giralt-Steinhauer (Hospital del Mar Medical Research Institute, Barcelona, Spain (A.O., E.G.-S.).) A Andrej Netland Khanevski (Department of Neurology, Haukeland University Hospital, Bergen, Norway (A.N.K.).) X Xinyi Leng X Xuan Tian T Thomas W. Leung (Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong) E Esmee Verburgt (Department of Neurology, Research Institute for Medical Research and Innovation, Radboud University Medical Centre, Nijmegen and Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands (E.V., J.V., F.-E.d.L.).) J Jamie Verhoeven (Department of Neurology, Research Institute for Medical Research and Innovation, Radboud University Medical Centre, Nijmegen and Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands (E.V., J.V., F.-E.d.L.).) F Frank-Erik de Leeuw F Fredrik Ildstad (St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway (F.I.).) S Simon Fandler-Höfler (Department of Neurology, Medical University of Graz, Graz, Austria (S.F.-H.).) K Karoliina Aarnio (Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland (K.A.).) B Bettina von Sarnowski (University Medicine Greifswald, Greifswald, Germany (B.v.S.).) D Diane L. Lorenzetti (Department of Community Health Sciences, Cumming School of Medicine and Health Sciences Library (D.L.L.), University of Calgary, Calgary, AB, Canada.) S Shelagh B. Coutts (Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada (F.K., R.L., A.G., P.A.B., S.B.C., M.D.H.).) P Pierre Amarenco (Department of Neurology, Bichat Hospital and University of Paris Cité, Paris) G Graeme J. Hankey M Michael D. Hill (Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary and Foothills Medical Centre, Calgary, AB, Canada)

Abstract

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 attributable 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. 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 [interquartile range, 65–71]; 52%–60% male patients). Factors that had high certainty evidence of association with increased long-term risk of stroke included older age (adjusted hazard ratio, 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 (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); ABCD 2 (age, blood pressure, clinical features, duration of TIA, and presence of diabetes) 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 versus 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.

Article Details

Journal Circulation
Volume / Issue Vol. 153, Issue 17
Published April 28, 2026
Pages 1281-1295
ISSN 0009-7322
Publisher Lippincott Williams & Wilkins

Journal Info

Circulation

Lippincott Williams & Wilkins

ISSN: 0009-7322 Health Sciences

Authors (28)

F

Faizan Khan

Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada (F.K., R.L., A.G., P.A.B., S.B.C., M.D.H.).

V

Vignan Yogendrakumar

Department of Neurology, University of Melbourne, Melbourne, VIC, Australia (V.Y.).

R

Ronda Lun

Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada (F.K., R.L., A.G., P.A.B., S.B.C., M.D.H.).

C

Caterina E. Marx

The Ottawa Hospital and Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada (V.Y., C.E.M., A.T.).

B

Bram Rochwerg

A

Alexandre Tran

The Ottawa Hospital and Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada (V.Y., C.E.M., A.T.).

S

Shannon M. Fernando

Department of Critical Care, Lakeridge Health, Oshawa, ON, Canada (S.M.F.).

A

Aravind Ganesh

Department of Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, AB, Canada

P

Philip A. Barber

J

Joachim Ögren

A

Angel Ois

Hospital del Mar Medical Research Institute, Barcelona, Spain (A.O., E.G.-S.).

E

Eva Giralt-Steinhauer

Hospital del Mar Medical Research Institute, Barcelona, Spain (A.O., E.G.-S.).

A

Andrej Netland Khanevski

Department of Neurology, Haukeland University Hospital, Bergen, Norway (A.N.K.).

X

Xinyi Leng

X

Xuan Tian

T

Thomas W. Leung

Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong

E

Esmee Verburgt

Department of Neurology, Research Institute for Medical Research and Innovation, Radboud University Medical Centre, Nijmegen and Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands (E.V., J.V., F.-E.d.L.).

J

Jamie Verhoeven

Department of Neurology, Research Institute for Medical Research and Innovation, Radboud University Medical Centre, Nijmegen and Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands (E.V., J.V., F.-E.d.L.).

F

Frank-Erik de Leeuw

F

Fredrik Ildstad

St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway (F.I.).

S

Simon Fandler-Höfler

Department of Neurology, Medical University of Graz, Graz, Austria (S.F.-H.).

K

Karoliina Aarnio

Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland (K.A.).

B

Bettina von Sarnowski

University Medicine Greifswald, Greifswald, Germany (B.v.S.).

D

Diane L. Lorenzetti

Department of Community Health Sciences, Cumming School of Medicine and Health Sciences Library (D.L.L.), University of Calgary, Calgary, AB, Canada.

S

Shelagh B. Coutts

Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada (F.K., R.L., A.G., P.A.B., S.B.C., M.D.H.).

P

Pierre Amarenco

Department of Neurology, Bichat Hospital and University of Paris Cité, Paris

G

Graeme J. Hankey

M

Michael D. Hill

Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary and Foothills Medical Centre, Calgary, AB, Canada