Familial Associations of Prevalence and Cause-Specific Mortality for Thoracic Aortic Disease and Bicuspid Aortic Valve in a Large-Population Database

Journal Article · Thu Jun 15 00:00:00 EDT 2023 · Circulation

DOI:https://doi.org/10.1161/circulationaha.122.060439· OSTI ID:1995714

Glotzbach, Jason P. ^[1]; Hanson, Heidi A. ^[2]; Tonna, Joseph E. ^[1]; Horns, Joshua J. ^[1]; McCarty Allen, Chelsea ^[1]; Presson, Angela P. ^[1]; Griffin, Claire L. ^[1]; Zak, Megan ^[1]; Sharma, Vikas ^[1]; Tristani-Firouzi, Martin ^[1]; Selzman, Craig H. ^[1]

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1. Univ. of Utah, Salt Lake City, UT (United States). School of Medicine
2. Univ. of Utah, Salt Lake City, UT (United States). School of Medicine; Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Thoracic aortic disease and bicuspid aortic valve (BAV) likely have a heritable component, but large population-based studies are lacking. This study characterizes familial associations of thoracic aortic disease and BAV, as well as cardiovascular and aortic-specific mortality, among relatives of these individuals in a large-population database. In this observational case-control study of the Utah Population Database, we identified probands with a diagnosis of BAV, thoracic aortic aneurysm, or thoracic aortic dissection. Age- and sex-matched controls (10:1 ratio) were identified for each proband. First-degree relatives, second-degree relatives, and first cousins of probands and controls were identified through linked genealogical information. Cox proportional hazard models were used to quantify the familial associations for each diagnosis. We used a competing-risk model to determine the risk of cardiovascular-specific and aortic-specific mortality for relatives of probands. The study population included 3,812,588 unique individuals. Familial hazard risk of a concordant diagnosis was elevated in the following populations compared with controls: first-degree relatives of patients with BAV (hazard ratio [HR], 6.88 [95% CI, 5.62–8.43]); first-degree relatives of patients with thoracic aortic aneurysm (HR, 5.09 [95% CI, 3.80–6.82]); and first-degree relatives of patients with thoracic aortic dissection (HR, 4.15 [95% CI, 3.25–5.31]). In addition, the risk of aortic dissection was higher in first-degree relatives of patients with BAV (HR, 3.63 [95% CI, 2.68–4.91]) and in first-degree relatives of patients with thoracic aneurysm (HR, 3.89 [95% CI, 2.93–5.18]) compared with controls. Dissection risk was highest in first-degree relatives of patients who carried a diagnosis of both BAV and aneurysm (HR, 6.13 [95% CI, 2.82–13.33]). First-degree relatives of patients with BAV, thoracic aneurysm, or aortic dissection had a higher risk of aortic-specific mortality (HR, 2.83 [95% CI, 2.44–3.29]) compared with controls. Our results indicate that BAV and thoracic aortic disease carry a significant familial association for concordant disease and aortic dissection. The pattern of familiality is consistent with a genetic cause of disease. Furthermore, we observed higher risk of aortic-specific mortality in relatives of individuals with these diagnoses. In conclusion, this study provides supportive evidence for screening in relatives of patients with BAV, thoracic aneurysm, or dissection.

• Research Organization: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
• Sponsoring Organization: National Cancer Institute (NCI); National Institute of Health (NIH); USDOE
• Grant/Contract Number: AC05-00OR22725
• OSTI ID: 1995714
• Journal Information: Circulation, Journal Name: Circulation Journal Issue: 8 Vol. 148; ISSN 0009-7322
• Publisher: American Heart Association, Inc.
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
aortic dissection
bicuspid aortic valve disease
risk assessment
thoracic aortic aneurysm