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Observational Study
. 2024 Feb 5;7(2):e240054.
doi: 10.1001/jamanetworkopen.2024.0054.

Short-Term and Long-Term Risk of Recurrent Vascular Event by Cause After Ischemic Stroke in Young Adults

Esmée Verburgt  1 , Nina A Hilkens  1 , Merel S Ekker  1 , Mijntje M I Schellekens  1 , Esther M Boot  1 , Maikel H M Immens  1 , Mayte E van Alebeek  2 , Paul J A M Brouwers  3 , Renate M Arntz  3 , Gert W van Dijk  4 , Rob A R Gons  5 , Inge W M van Uden  5 , Tom den Heijer  6 , Julia H van Tuijl  7 , Karlijn F de Laat  8 , Anouk G W van Norden  9 , Sarah E Vermeer  10 , Marian S G van Zagten  11 , Robert J van Oostenbrugge  12 , Marieke J H Wermer  13   14 , Paul J Nederkoorn  15 , Henk Kerkhoff  16 , Fergus A Rooyer  17 , Frank G van Rooij  18 , Ido R van den Wijngaard  19 , Tim J F Ten Cate  20 , Anil M Tuladhar  1 , Frank-Erik de Leeuw  1 , Jamie I Verhoeven  1
Affiliations
Observational Study

Short-Term and Long-Term Risk of Recurrent Vascular Event by Cause After Ischemic Stroke in Young Adults

Esmée Verburgt et al. JAMA Netw Open. .

Abstract

Importance: Cause of ischemic stroke in young people is highly variable; however, the risk of recurrence is often presented with all subtypes of stroke grouped together in classification systems such as the Trial of ORG (danaparoid sodium [Orgaran]) 10172 in Acute Stroke Treatment (TOAST) criteria, which limits the ability to individually inform young patients with stroke about their risk of recurrence.

Objective: To determine the short-term and long-term risk of recurrent vascular events after ischemic stroke at a young age by stroke cause and to identify factors associated with recurrence.

Design, setting, and participants: This cohort study used data from the Observational Dutch Young Symptomatic Stroke Study, a prospective, multicenter, hospital-based cohort study, conducted at 17 hospitals in the Netherlands between 2013 and 2021. Eligible participants included 30-day survivors of an initial, neuroimaging-proven ischemic stroke (aged 18-49 years). Data analysis was conducted from June to July 2023.

Exposure: Diagnosis of a first-ever, ischemic stroke via neuroimaging.

Main outcome and measures: The primary outcome was short-term (within 6 months) and long-term (within 5 years) recurrence risk of any vascular event, defined as fatal or nonfatal recurrent ischemic stroke, transient ischemic attack, myocardial infarction, and revascularization procedure. Predefined characteristics were chosen to identify factors associated with risk of recurrence (cause of stroke, age, sex, stroke severity, and cardiovascular health factors).

Results: A total of 1216 patients (median [IQR] age, 44.2 [38.4-47.7] years; 632 male [52.0%]; 584 female [48.0%]) were included, with a median (IQR) follow-up of 4.3 (2.6-6.0) years. The 6-month risk of any recurrent ischemic event was 6.7% (95% CI, 5.3%-8.1%), and the 5-year risk was 12.2% (95% CI, 10.2%-14.2%)The short-term risk was highest for patients with cervical artery dissections (13.2%; 95% CI, 7.6%-18.7%). Other factors associated with a recurrent short-term event were atherothrombotic stroke, rare causes of stroke, and hypertension. The long-term cumulative risk was highest for patients with atherothrombotic stroke (22.7%; 95% CI, 10.6%-34.7%) and lowest for patients with cryptogenic stroke (5.8%; 95% CI, 3.0%-8.5%). Cardioembolic stroke was associated with a recurrent long-term event, as were diabetes and alcohol abuse.

Conclusions and relevance: The findings of this cohort study of 1216 patients with an ischemic stroke at a young age suggest that the risk of recurrent vascular events was high and varied by cause of stroke both for short-term and long-term follow-up, including causes that remained concealed when combined into 1 category in the routinely used TOAST criteria. This knowledge will allow for more personalized counseling of young patients with stroke.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr van den Wijngaard reported receiving personal fees from Philips and Medtronic outside the submitted work. Dr de Leeuw reported serving as an assistant editor for the International Journal of Stroke outside the submitted work. Dr Verhoeven reported being a member of the editorial board of the European Stroke Journal outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Patient Inclusion
aOther reasons for loss to follow-up were patients with aphasia, not speaking the Dutch language, or patients being too affected by the stroke to participate during follow-up.
Figure 2.
Figure 2.. Five-Year Cumulative Incidence and Incidence Rate Per 100 Person-Years by Type of Recurrent Event
The cumulative incidence was calculated through cumulative incidence functions. The incidence rate per 100 person-years was calculated by dividing the number of events by the total person-years at risk per 6-month intervals. The middle of those intervals was chosen as the point estimator in the graph. Shaded regions indicate 95% CIs. TIA indicates transient ischemic attack.
Figure 3.
Figure 3.. Cumulative Incidence and Incidence Rate Per 100 Person-Years Per Cause of Stroke
Cumulative incidence is shown for (A) short-term recurrence (<6 months) and (B) long-term recurrence (5 years). Recurrence was calculated through cumulative incidence functions. The incidence rate per 100 person-years (C) was calculated by dividing the number of events by the total person-years at risk in the first 6 months, 6 months to 2 years, and 2 to 5 years. The middle of those intervals was chosen as the point estimator in the graph. Shaded region indicates the short-term period. TOAST indicates Trial of ORG (danaparoid sodium [Orgaran]) 10172 in Acute Stroke Treatment.
See this image and copyright information in PMC

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