Patent Forman Ovale Status Linked to Cryptogenic Ischemic Stroke Risk Profile for Younger Adults

Because the incidence of young-onset ischemic stroke is on the rise in patients without vascular risk factors, researchers examined the traditional, nontraditional, and female-sex-specific risk factors with cryptogenic ischemic stroke (CIS). The researchers focused on relevant patent foramen ovale (PFO), which can disclose high-risk features of atrial septal aneurysm or large right-to-left shunt, based on the presence or absence of PFO. The researchers also considered how nontraditional risk factors may have a greater effect on the increased incidence of stroke based on sex.

Results were published in Stroke.

Patients aged 18-49 with CIS from the SECRETO study (n=523) and an equal number of matched stroke-free controls were included. The median age was 41, 47.3% of the patients were women, and 196 (37.5%) had PFO.

Compared to stroke-free individuals, patients with CIS without PFO were more likely to have lower education levels and a higher prevalence of traditional risk factors, including cardiovascular disease, hypertension, smoking, abdominal obesity, physical inactivity, poor diet, heavy alcohol consumption, psychosocial stress, and depression.

Patients with CIS and PFO showed significantly higher rates of current smoking and abdominal obesity than controls. Regarding nontraditional risk factors, venous thrombosis and migraine with aura were more common in CIS patients without PFO compared to controls. However, migraine with aura was also more frequent in CIS patients with PFO compared to controls.

Within the CIS group, those without PFO were more likely than those with PFO to have low education, obstructive sleep apnea, hypertension, unhealthy diet, smoking habits, and heavy alcohol use. Among nontraditional factors, migraine with aura was notably more common in CIS patients with PFO. “Furthermore, each additional female sex–specific risk factor increased the odds of CIS with PFO by 1.9 (95% CI, 1.2-3.0),” the researchers noted.

For CIS without PFO, traditional, nontraditional, and female-specific risk factors accounted for 64.7%, 26.5%, and 18.9% of the population-attributable risk, respectively. In CIS with PFO, these values were 33.8%, 49.4%, and 21.8%. Migraine with aura emerged as the leading contributor, responsible for 45.8% of CIS with PFO and 22.7% of CIS without PFO, with a particularly strong effect in women.

“Our study highlights the multifaceted nature of young-onset CIS, revealing that both traditional and nontraditional risk factors significantly influence its development, with variations based on clinically relevant PFO status. The prominent role of behavioral factors and the strong association with migraine with aura underscore the necessity for a thorough and tailored approach to risk factor assessment and prevention strategies in young adults,” the researchers concluded.

Reference

Putaala J, et al. Stroke. Published online April 17, 2025. doi:10.1161/STROKEAHA.124.049855