Patent foramen ovale (PFO) diameter and right-to-left shunt grade were positively correlated with white matter hyperintensity grade in young adults, with WMH grade significantly higher in the PFO group than in controls after adjusting for confounding factors.
Key Findings
Results
WMH grade was significantly higher in the PFO group compared to the control group.
120 young adult PFO patients aged 18-55 years formed the case group; 121 age- and sex-matched controls were selected from the same period.
The study was conducted at two tertiary general hospitals in Chongqing, China, between October 2025 and March 2026.
WMH severity was graded using the Fazekas scale.
The difference in WMH grading between groups was statistically significant (p < 0.001).
Chi-square test and Mann-Whitney U test were used to compare WMH grading differences between groups.
Results
PFO diameter was positively correlated with WMH grade in young adults.
Partial correlation analysis examined the relationship between PFO indicators and WMH grading.
The correlation between PFO diameter and WMH grade was statistically significant (p < 0.05).
After adjusting for confounding factors including age and sex, PFO diameter remained significantly associated with WMH grade.
A multinomial logistic regression model was constructed to evaluate the association between PFO and WMH.
Results
Right-to-left shunt (RLS) grade was positively correlated with WMH grade in young adults.
RLS severity was measured via transesophageal echocardiography (TEE).
The correlation between RLS grade and WMH grade was statistically significant (p < 0.05).
Both PFO diameter and RLS grade were assessed as PFO indicators in the partial correlation analysis.
Methods
The study excluded major traditional cerebrovascular risk factors to isolate the potential effect of PFO on WMH.
Exclusion criteria included hypertension, diabetes, cerebrovascular disease, head and neck arterial stenosis ≥50%, and other cardiac structural abnormalities.
Control group participants were confirmed to have no PFO by transesophageal echocardiography.
Both groups were drawn from patients presenting with similar clinical indications including headache/migraine, dizziness, cryptogenic stroke/TIA, and other neurological symptoms.
Clinical indication distributions were balanced between groups through the matching process, meaning controls were not necessarily healthy community individuals.
Discussion
The underlying mechanisms linking PFO to WMH in young adults remain unclear and require further investigation.
The authors noted that PFO diameter 'may be associated with WMH severity in young adults.'
The study design was retrospective and case-control, limiting causal inference.
The authors stated that 'the underlying mechanisms remain to be elucidated and warrant further investigation.'
What This Means
This research suggests that a common heart defect called patent foramen ovale (PFO) — a small hole between the upper chambers of the heart that fails to close after birth — is linked to white matter hyperintensities (WMH) in young adults. WMH are bright spots seen on brain MRI scans that indicate areas of subtle brain tissue damage; they are normally associated with aging or vascular risk factors like high blood pressure. In this study of 120 young adults with PFO and 121 matched controls without PFO (all aged 18–55, with conditions like high blood pressure and diabetes excluded), those with PFO had significantly more severe WMH on their brain scans. Moreover, the larger the PFO opening and the greater the blood flow passing through it from right to left, the worse the WMH severity tended to be.
These findings are notable because they suggest that even in the absence of traditional cardiovascular risk factors, PFO alone may contribute to subtle brain changes in younger people. The study controlled for age, sex, and other confounders, and the association between PFO size and WMH remained significant. This research suggests that the structural characteristics of a PFO — particularly its diameter and the degree of abnormal blood shunting — could matter for brain health beyond just the well-known risk of stroke.
However, because this was a retrospective case-control study conducted at clinical centers (not a general population sample), the findings may not apply to all people with PFO. The study also does not prove that PFO causes WMH — only that the two are associated. The authors acknowledge that the biological mechanisms behind this link are not yet understood and call for further research to clarify whether PFO treatment might reduce WMH risk in young adults.
Chen C, Gu D, Lu J, Wang C, Cai Z. (2026). Patent foramen ovale is associated with white matter hyperintensities in young adults: a case-control study.. Frontiers in neurology. https://doi.org/10.3389/fneur.2026.1906472