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Published on: December 23, 2022
Burden of Modifiable Risk Factors in Young-Onset Cryptogenic Ischemic Stroke by High-Risk Patent Foramen Ovale
Jukka Putaala1, Nicolas Martinez-Majander1, Michelle Leppert2
1Department of Neurology (J. Putaala, N.M.-M., L.T.), Helsinki University Hospital and University of Helsinki, Finland.
Insights
Young-onset cryptogenic ischemic stroke (CIS) risk is linked to traditional and nontraditional factors, especially in patients with patent foramen ovale (PFO). Migraine with aura is a key risk factor, particularly for women.
Area of Science:
- Neurology
- Cardiology
- Epidemiology
Background:
- Rising incidence of young-onset ischemic stroke (CIS).
- Focus on modifiable risk factors in CIS.
- Stratification by patent foramen ovale (PFO) status.
Purpose of the Study:
- Examine risk factors for young-onset CIS.
- Assess traditional, nontraditional, and sex-specific factors.
- Evaluate risk factor associations stratified by PFO.
Main Methods:
- Included 523 CIS patients and 523 controls (ages 18-49).
- Used logistic regression to assess risk factor counts and individual factors.
- Stratified analyses by PFO, sex, and age group.
Main Results:
- Traditional, nontraditional, and female sex-specific factors increased CIS risk without PFO.
- Nontraditional factors were most significant for CIS with PFO.
- Migraine with aura was a major contributor, especially in women.
Conclusions:
- Traditional factors contribute to CIS without PFO; nontraditional factors are critical for CIS with PFO.
- Migraine with aura significantly impacts young-onset CIS, particularly in women.
- Understanding these factors can inform prevention strategies.
Background:
The incidence of young-onset ischemic stroke is rising, driven by cryptogenic ischemic stroke (CIS) and patients without vascular risk factors. This study examines the burden and associations of modifiable traditional, nontraditional, and female sex-specific risk factors with young-onset CIS, stratified by clinically relevant patent foramen ovale (PFO), defined by high-risk features of atrial septal aneurysm or large right-to-left shunt.
Methods:
We enrolled consecutive patients aged 18 to 49 years with recent CIS and frequency-matched stroke-free controls of the same age and sex from 19 European sites. Logistic regression assessed the association of risk factor counts (12 traditional, 10 nontraditional, 5 female sex-specific) and individual risk factors, stratified by PFO. Analyses were stratified by sex and age (18-39 and 40-49 years), with computation of population-attributable risk.
Results:
We included 523 patients (median age, 41 years; 47.3% women; 196 [37.5%] with PFO) and 523 controls. In patients with CIS without PFO, each additional traditional (odds ratio, 1.417 [95% CI, 1.282-1.568]), nontraditional (odds ratio, 1.702 [95% CI, 1.338-2.164]), and female sex-specific risk factor (odds ratio, 1.700 [95% CI, 1.107.1-2.611]) increased CIS risk. For patients with CIS with PFO, each traditional risk factor increased the risk (odds ratio, 1.185 [1.057-1.328]), but only nontraditional risk factors remained significant when fully adjusted (odds ratio, 2.656 [2.036-3.464]). Population-attributable risks for CIS without PFO were 64.7%, 26.5%, and 18.9% for traditional, nontraditional, and female sex-specific risk factors. For CIS with PFO, population-attributable risks were 33.8%, 49.4%, and 21.8%, respectively. Migraine with aura was the most significant contributor, with population-attributable risks of 45.8% for CIS with PFO and 22.7% for CIS without PFO, showing a stronger impact in women.
Conclusions:
Despite the initial cryptogenic label of these strokes, traditional risk factors significantly contribute to CIS without PFO, while nontraditional factors seem more critical for CIS with PFO. Migraine with aura plays a prominent role in young-onset CIS development, particularly in women.
Registration:
URL: https://www.clinicaltrials.gov; Unique identifier: NCT01934725.
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