Subclinical atherosclerosis burden and patent foramen ovale in young and middle-aged patients with stroke of undetermined etiology: A real-life retrospective cohort study

OBJECTIVES: To characterize the subclinical atherosclerosis in a group of young and middle-aged patients with stroke of undetermined etiology, in relation to the stroke causal likelihood of patent foramen ovale (PFO). METHODS: We conducted a retrospective review of prospectively collected medical records of consecutive patients aged 18–60 years with a diagnosis of acute ischemic stroke of undetermined origin between January 2016 and June 2022. Patients were grouped by the PFO presence and the stroke-causal likelihood of PFO according to the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system. RESULTS: We included 157 patients with stroke of undetermined etiology (mean age 48.2 ± 8.7 years; 43.3% female). Of these, 75 patients presented PFO. After adjusting for age and sex, the PFO+ group presented a lower mean carotid intima-media thickness (cIMT; P = 0.046), carotid stenosis inside ( P = 0.016), and outside ( P = 0.003) the stroke territory. Plaques of any grade were associated with negative findings at the PFO investigation (odds ratios 0.271 [95% confidence interval: 0.134–0.547]). Risk of Paradoxical Embolism scores were inversely correlated to mean cIMT ( P = 0.028; Spearman’s rho = −0.257). cIMT was progressively lower in patients without PFO compared to those with low- and high-risk PFO ( P = 0.003) and across PASCAL categories ( P = 0.010). Among PFO+ patients, the presence of stenosis ipsilateral to stroke ( P = 0.001) and any plaque ( P = 0.001) was differently distributed across PASCAL categories. CONCLUSIONS: The burden of subclinical atherosclerosis is progressively lower in patients with unlikely, possible, and probable stroke-causative PFO. These results support the idea that atherosclerosis may play a significant causal role in some patients with stroke of undetermined origin with or without PFO.