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EXPEDITED REVIEW

Patent Foramen Ovale: Innocent or Guilty?

Evidence From a Prospective Population-Based Study

Irene Meissner, MD^_*,||,_*, Bijoy K. Khandheria, MD, John A. Heit, MD^_*, George W. Petty, MD^_*, Sheldon G. Sheps, MD, Gary L. Schwartz, MD, Jack P. Whisnant, MD, David O. Wiebers, MD^_*,||, Jody L. Covalt^¶, Tanya M. Petterson^||, Teresa J.H. Christianson^|| and Yoram Agmon, MD^_*

^_* Department of Neurology
Division of Cardiovascular Diseases
Division of Nephrology and Hypertension
Department of Health Sciences Research
^|| Division of Epidemiology
^¶ Stroke Research Center
^|| Division of Biostatistics, Mayo Clinic, Rochester, Minnesota

Manuscript received July 28, 2005; revised manuscript received September 26, 2005, accepted October 3, 2005.

^_* Reprint requests and correspondence: Dr. Irene Meissner, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905 (Email: meissner.irene{at}mayo.edu).

OBJECTIVES: We sought to determine the association between patent foramen ovale (PFO), atrial septal aneurysm (ASA), and stroke prospectively in a unselected population sample.

BACKGROUND: The disputed relationship between PFO and stroke reflects methodologic weaknesses in studies using invalid controls, unblinded transesophageal echocardiography examinations, and data that are unadjusted for age or comorbidity.

METHODS: The use of transesophageal echocardiography to identify PFO was performed by a single echocardiographer using standardized definitions in 585 randomly sampled, Olmsted County (Minnesota) subjects age 45 years or older participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study.

RESULTS: A PFO was identified in 140 (24.3%) subjects and ASA in 11 (1.9%) subjects. Of the 140 subjects with PFO, 6 (4.3%) had an ASA; of the 437 subjects without PFO, 5 had an ASA (1.1%, two-sided Fisher exact test, p = 0.028). During a median follow-up of 5.1 years, cerebrovascular events (cerebrovascular disease-related death, ischemic stroke, transient ischemic attack) occurred in 41 subjects. After adjustment for age and comorbidity, PFO was not a significant independent predictor of stroke (hazard ratio 1.46, 95% confidence interval 0.74 to 2.88, p = 0.28). The risk of a cerebrovascular event among subjects with ASA was nearly four times higher than that in those without ASA (hazard ratio 3.72, 95% confidence interval 0.88 to 15.71, p = 0.074).

CONCLUSIONS: These prospective population-based data suggest that, after correction for age and comorbidity, PFO is not an independent risk factor for future cerebrovascular events in the general population. A larger study is required to test the putative stroke risk associated with ASA.

Abbreviations and Acronyms   ASA = atrial septal aneurysm   CVD = cerebrovascular events   IAS = interatrial septum   PFO = patent foramen ovale   SPARC = Stroke Prevention: Assessment of Risk in a Community study   TEE = transesophageal echocardiography   VTE = venous thromboembolism

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