Risk of Stroke in Patients with Patent Foramen Ovale: An Updated Meta-analysis of Observational Studies

Background: Although patent foramen ovale (PFO) is considered to be associated with cryptogenic stroke (CS), there remains an ongoing disputation on this issue because of unstable results from randomized controlled trials. The aim of this study was to reassess the PFO effect on stroke through observational data. Methods: An electronic search of PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) were finished. Only case-control studies and cohort studies in Chinese or English were included in the analysis. Then random-effected meta-analysis models were performed to assess the association between PFO and stroke. Results: Twelve case-control studies and 6 cohort studies were eligible. Case-control studies showed strong association between PFO and CS (odds ratio [OR]: 2.94, 95% confidence interval [CI]: 2.06, 4.20; P < .001), but cohort studies failed to demonstrate a significant association (hazard ratio [HR]: 1.28, 95% CI:.91, 1.80; P = .155). Subgroup analysis revealed that the pooled OR decreased significantly when the region was limited to the United States (OR: 1.52, 95% CI: 1.00, 2.32; P = .083). OR of studies that adjusted major confounders was 1.74 (95% CI: 1.22, 2.47; P = .119) and high-quality studies was 1.68 (95% CI: 1.14, 2.47; P = .072). For cohort studies, a weak statistical association was observed in using transesophageal echocardiography (TEE) studies (HR: 1.45, 95% CI: 1.06, 2.01; P = .138) and follow-up years less than 4 years' studies (HR: 1.45, 95% CI: 1.00, 2.09; P = .064). Conclusions: Although case-control studies still show a positive effect of PFO on stroke, the results of cohort challenged the credibility. Further trial data are needed to confirm the effect of PFO on stroke.