The incidence of young-onset ischemic stroke is rising due to cryptogenic strokes that lack identifiable risk factors. This rise may also reflect an increasing prevalence of vascular risk factors. The hypothesis is supported by simultaneous declines in myocardial infarction and sudden cardiac death rates in young adults. These trends suggest a link between traditional risk factors and rising cryptogenic ischemic strokes (CIS).
Evaluating young stroke patients requires considering the presence of a patent foramen ovale (PFO). Previous studies on young-onset strokes struggled to consistently classify PFO-related cases accurately. Recent research highlights that atrial septal aneurysm and large shunt size are crucial in assessing PFO’s causal role and classification. This was well explained in a recent study published in the Stroke journal.
Researchers evaluated traditional, nontraditional, and female-specific risk factors for young-onset CIS in an international case-control study, including PFO presence, sex, and age group. Participants included patients aged 18-49 with recent CIS and matched stroke-free controls from 19 European sites. Physical inactivity was evaluated through the short International Physical Activity Questionnaire, with <1500 metabolic equivalents/week classified as inactive.
Logistic regression evaluated the association of risk factors, stratified by PFO, including traditional and specific factors. Analyses categorized by sex, age (18-39 and 40-49), and population-attributable risk were calculated. PFO was diagnosed via color Doppler imaging to detect right-to-left shunt, confirmed by a bubble study with microbubbles in the left atrium during transesophageal echocardiography.
There are nine nontraditional risk factors that were counted as none, 1, or ≥2, while female-specific factors were evaluated as binary variables. Researchers evaluated population-attributable risks for risk factors using the Bruzzi method and logistic regression adjustments.
Initially, 23 patients were excluded because of their poor visualization or technical difficulties observed in echocardiography. Therefore, 523 patients with CIS, 523 age- (±5 years), and sex-matched stroke-free controls (median age of 41 years; 47.2% female) were included in the study. Female patients were significantly younger than male patients, with a median age of 40 years vs 42 years, P < 0.001. A total of 196 patients had a PFO (37.5%), with no difference in sex or age.
In patients with CIS without PFO, logistic regression revealed an association for traditional (odds ratio, 1.4 [95% CI, 1.3 to 1.6]) and nontraditional (odds ratio, 1.7 [95% CI, 1.3 to 2.2]) risk factors consistent across sext and age groups.
The top three individual risks for CIS without PFO were migraine with aura (22.7%), current smoking (21.9%), and abdominal obesity (21.1%). Hypertension was linked to PFO absence in both age groups, while migraine with aura was linked to the younger group only. In a case-control study, traditional and nontraditional risk factors related to CIS varied with PFO.
In conclusion, these findings support comprehensive risk profiling for targeted prevention, considering female-specific and lifestyle factors in young adults. Comprehensive risk assessment and tailored prevention strategies are crucial.
Behavioural factors associated with migraine with aura underscore the importance of personalized risk assessment and prevention strategies for young adults. Further research is important for understanding mechanisms and improving prevention strategies for diverse populations related to migraines.
Reference: Putaala J, Martinez-Majander N, Leppert M, et al. Burden of modifiable risk factors in young-onset cryptogenic ischemic stroke by high-risk patent foramen ovale. Stroke. 2025. doi:10.1161/STROKEAHA.124.049855
