Patent foramen ovale is associated with white matter hyperintensities in young adults: a case-control study

To investigate the association between patent foramen ovale (PFO) and white matter hyperintensities (WMH) in young adults and to assess whether PFO may be associated with WMH in this population.

A multicenter retrospective case-control study was conducted. 120 young adult PFO patients aged 18-55 years diagnosed between October 2025 and March 2026 at two tertiary general hospitals in Chongqing, China, formed the case group. 121 age- and sex-matched controls were selected from the same period. The control group consisted of individuals who underwent cranial MRI and PFO-related examinations during the same period for similar clinical indications (e.g., headache, dizziness, or cryptogenic stroke/TIA workup) but were confirmed to have no PFO by transesophageal echocardiography. These participants were not necessarily "healthy" in the community sense but served as a clinical control group without the exposure of interest (PFO). Clinical data were collected for both groups. Transesophageal echocardiography (TEE) and cranial magnetic resonance imaging (MRI) were performed to measure PFO diameter and assess right-to-left shunt (RLS) severity. WMH severity was graded using the Fazekas scale. The chi-square test and Mann-Whitney U test were used to compare WMH grading differences between groups. A partial correlation analysis examined the relationship between PFO indicators and WMH grading. A multinomial logistic regression model was constructed to evaluate the association between PFO and WMH in young adults. Exclusion criteria included hypertension, diabetes, cerebrovascular disease, head and neck arterial stenosis ≥50%, and other cardiac structural abnormalities. Clinical indications for cranial MRI and PFO-related examinations in both groups included headache/migraine, dizziness, cryptogenic stroke/TIA, and other neurological symptoms, with distributions balanced between the PFO and control groups through the matching process.

WMH grade was significantly higher in the PFO group than in the control group (p < 0.001). PFO diameter and RLS grade were positively correlated with WMH grade (p < 0.05). After adjusting for confounding factors including age and sex, PFO diameter remained significantly associated with WMH grade in young adults.

These findings suggest that PFO diameter may be associated with WMH severity in young adults. The underlying mechanisms remain to be elucidated and warrant further investigation.