Underlying Causes of TIA and Minor Ischemic Stroke and Risk of Major Vascular Events

• DOI: 10.1001/jamaneurol.2023.3344
• Publication Date: 2023-10-02T15:01:36Z
• Authors: Philippa C. Lavallée; Hugo Charles; Gregory W. Albers; Louis R. Caplan; Geoffrey A. Donnan; José M. Ferro; Michael G. Hennerici; Julien Labreuche; Carlos Molina; Peter M. Rothwell; Philippe Gabriel ...; Pierre-Jean Touboul; Shinichiro Uchiyama; Éric Vicaut; Lawrence K. S. Wong; Pierre Amarenco; ; Sebastian Ameriso; Claudia Nora Gand...; Guillermo Povedano; Javier Sagesse; Heman Pavon; Jorge Cancino; Walter Toledo; Yinin Huang; Xiping Gong; Yeato Martin; Donghu Mi; Tian Song; Yilong Wang; Yongjun Wang; Fran Chandgfend; Guo Contago; Jiao Hongyun; Heman Intao; Wu Jixing; Song Liquing; Tai Liwen; Liu Ran; Tian Shujuan; Liu Wenhong; Tak Hong Soi; Lawrence Wong; Liu Roxanna; Roman Flasar; Bedriska Ziktova; Michael Reif; Daniel Sanak Gold...; Jiri Neumann; Dagmar Svakov; Daniel Sanak; Michael Kral; David Skoloudik; Daniel Vaclavik; Martin Kuhila; Pierre Amarenco; Lucie Cabrejo; Céline Guidoux; Cristina Maria Ho...; Philippa Lavallée; Elena Meseguer; Henrich Audebert; Daniel Menger; Wofgang Heide; Saskia Lipp; Huriye Ozalp; Christine Sctzmann; Christian Weimar; Katharina Platzbe...; Peter Ringleb; Michel G Hennerici; Martin Griebe; Katrin Knoll Olaf; Olaf Willmann; Juergen Harmut Faiss; Susan Dilan; Anja Kobersteein; Katarina Krimmer; Sandra Tietz; Peter Wienecke; Gerhard Hamann; Nico Burkhardt; Martin Liebetrau; Nadine Mueller; Michaela Wagner; Dr Strivastava; Peter Kelly; Hashomer David Tanne; Milena Cavazzuti; Sabrina Anticoli; Danilo Toni; Ken Nagata; Yasushi Okada; Hiroshi Yamagami; Kazuo Minematsu; Jojo Nakagawara; Shinchiro Uchiyama; Byung Chui Lee; Byung Woo Yoon; Ji Hoe; Jong Moo Park; Halim Abboud; Salam Koussa; Adnan Awada; Kay Sin Tan; Antonio Arauz; Frnando Gongora; Adrian Infante Va...; Juan M. Esamilla; Patricia Canhao; ******- Ferro; Ana Catarina Fonseca; Manuel Correia; Assuncao Tuna; Nada Sternic; Milija Mijajlovic; Beata Dupejova; Jana Szedelyova; Renata Smirkova; Tomas Segura; Carlos Molina; Ana Rodriguez; Yolanda Silva; Javier Tejada; Francisco Purroy; Jaime Masjuan; Jose Vivancos; Ernest Palomeras; Miguel Angel Gamemro; JF Arenillas; Anna Calleja; Esther Rojo; Alastair Buchan; Peter Rothwell; Tsong Hai Lee; Ku Chou Chang; Yu-Ching Huang; Ruey-Tay Lin; Somsak Timkao
• Keywords: Male; Cohort Studies; Stroke; Ischemic Attack, Transient; Risk Factors; Stroke, Lacunar; Humans; Atherosclerosis; Aged; Ischemic Stroke

ImportanceThe coexistence of underlying causes in patients with transient ischemic attack (TIA) or minor ischemic stroke as well as their associated 5-year risks are not well known.ObjectiveTo apply the ASCOD (atherosclerosis, small vessel disease, cardiac pathology, other cause, or dissection) grading system to assess coexistence of underlying causes of TIA and minor ischemic stroke and the 5-year risk for major vascular events.Design, Setting, and ParticipantsThis international registry cohort (TIAregistry.org) study enrolled 4789 patients from June 1, 2009, to December 31, 2011, with 1- to 5-year follow-up at 61 sites in 21 countries. Eligible patients had a TIA or minor stroke (with modified Rankin Scale score of 0 or 1) within the last 7 days. Among these, 3847 patients completed the 5-year follow-up by December 31, 2016. Data were analyzed from October 1, 2022, to June 15, 2023.ExposureFive-year follow-up.Main Outcomes and MeasuresEstimated 5-year risk of the composite outcome of stroke, acute coronary syndrome, or cardiovascular death.ResultsA total of 3847 patients (mean [SD] age, 66.4 [13.2] years; 2295 men [59.7%]) in 42 sites were enrolled and participated in the 5-year follow-up cohort (median percentage of 5-year follow-up per center was 92.3% [IQR, 83.4%-97.8%]). In 998 patients with probable or possible causal atherosclerotic disease, 489 (49.0%) had some form of small vessel disease (SVD), including 110 (11.0%) in whom a lacunar stroke was also probably or possibly causal, and 504 (50.5%) had no SVD; 275 (27.6%) had some cardiac findings, including 225 (22.6%) in whom cardiac pathology was also probably or possibly causal, and 702 (70.3%) had no cardiac findings. Compared with patients with none of the 5 ASCOD categories of disease (n = 484), the 5-year rate of major vascular events was almost 5 times higher (hazard ratio [HR], 4.86 [95% CI, 3.07-7.72]; P < .001) in patients with causal atherosclerosis, 2.5 times higher (HR, 2.57 [95% CI, 1.58-4.20]; P < .001) in patients with causal lacunar stroke or lacunar syndrome, and 4 times higher (HR, 4.01 [95% CI, 2.50-6.44]; P < .001) in patients with causal cardiac pathology.Conclusion and RelevanceThe findings of this cohort study suggest that in patients with TIA and minor ischemic stroke, the coexistence of atherosclerosis, SVD, cardiac pathology, dissection, or other causes is substantial, and the 5-year risk of a major vascular event varies considerably across the 5 categories of underlying diseases. These findings further suggest the need for secondary prevention strategies based on pathophysiology rather than a one-size-fits-all approach.