Journal Article
Research Support, Non-U.S. Gov't
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Population-based assessment of familial inheritance and neurologic comorbidities among patients with an isolated atrial septal defect.

BACKGROUND: Interatrial shunts, caused by either atrial septal defect (ASD) or patent foramen ovale, have been reported to have a familial association. We sought to examine the familial risk of isolated interatrial shunt and explore associated comorbidities of stroke, transient ischemic attack (TIA), and migraine using a population database.

METHODS: The Utah Population Database is linked to inpatient and outpatient records from the University of Utah Health Science Center. Patients with an interatrial shunt were identified, and those with any other form of congenital heart disease or an inheritable syndrome associated with ASD were excluded. Of the 9452 individuals diagnosed with isolated interatrial shunt, 6179 (65%) had sufficient familial and follow-up data for analysis. Five age/gender matched controls were randomly selected per case. Cases and their relatives were compared with controls to assess the relative risk for each comorbid condition.

RESULTS: Relatives of interatrial shunt cases had an increased risk for interatrial shunt: siblings relative risk (RR) 6.98 (95% confidence interval [CI] 5.75-8.48; P < 1.0 x 10(-16)), first-degree RR 5.64 (95% CI 4.76-6.68; P < 1.0 x 10(-16)), and second-degree RR 1.75 (95% CI 1.32-2.32; P= 0.0001). Patients with interatrial shunt were more likely to have a comorbid condition compared with controls (RR 21.3, 95% CI 17.1-26.5; P < 1.0 x 10(-16)). First-degree relatives of cases had an increased risk of TIA (RR 1.70, 95% CI 1.18-2.45; P= 0.0045), but no increase risk of stroke or migraine compared with controls.

CONCLUSIONS: There is a strong familial inheritance pattern for isolated interatrial shunt, with significantly higher risk of interatrial shunt among affected patients' siblings, first-, and second-degree relatives. Relatives of affected individuals also had a higher risk of TIA, a trend toward an increased risk for stroke, but no increased risk of migraine headache.

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