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.
Department of Clinical Epidemiology, and Center of Evidence Based Medicine, The First Affiliated Hospital, China Medical University, Shenyang, China.
Bing
B
Ma
School of Public Health, China Medical University, Shenyang, Liaoning, China.
Guangcong
G
Liu
Department of Clinical Epidemiology, and Center of Evidence Based Medicine, The First Affiliated Hospital, China Medical University, Shenyang, China.
Xin
X
Chen
Department of Clinical Epidemiology, and Center of Evidence Based Medicine, The First Affiliated Hospital, China Medical University, Shenyang, China.
Jianming
J
Zhang
Department of Medical Center, The First Affiliated Hospital, China Medical University, Shenyang, China.
Yiting
Y
Liu
Department of Clinical Epidemiology, and Center of Evidence Based Medicine, The First Affiliated Hospital, China Medical University, Shenyang, China. Electronic address: jingpu56@163.com.
Jingpu
J
Shi
D017548:Echocardiography, Transesophageal; D054092:Foramen Ovale, Patent / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D064887:Observational Studies as Topic; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D013997:Time Factors
PFO; Stroke; meta-analysis; observational studies