M. Zak1, H. Hanson1, C. Selzman2, J. Glotzbach2 1University Of Utah,Division Of General Surgery,Salt Lake City, UT, USA 2University Of Utah,Division Of Cardiothoracic Surgery,Salt Lake City, UT, USA
Introduction: Thoracic aortic aneurysm and dissection (TAAD) are significant causes of morbidity and mortality. Dissections have a very poor prognosis, with 40% of patients dying before reaching the hospital and up to 20% unable to survive the perioperative period. In contrast to syndromic TAAD (e.g. Marfan’s syndrome), the natural history remains largely unknown in non-syndromic thoracic aortic aneurysm and dissection (ns-TAAD) and extent of heritability and familial association has not been fully elucidated. Eighty percent of ns-TAAD cases have no identifiable pathogenic genetic variant. Studies have found varying phenotypic expression between relatives with the same genetic mutation. Given the extent of genetic heterogeneity, screening and management guidelines are still developing. Our goal was to stratify familial risk of TAAD to gain further understanding of heritability patterns and guide individualized screening and treatment algorithms.
Methods: We performed a retrospective case cohort study using a large multi-institutional population database. We queried the database using ICD codes to identify patients diagnosed with thoracic aortic dissection (TAD) or thoracic aortic aneurysm (TAA). First degree relatives (FDR), second degree relatives (SDR), and first cousins (FC) were identified for each case diagnosed with thoracic disease as well as for age- and sex-matched control patients (10 controls for each case). A Cox Regression model was used to generate hazard ratios to determine the risk for relatives of patients with each diagnosis compared to non-affected control patients and relatives.
Results: We identified 3107 patients with TAD and 2011 patients with TAA. FDRs of TAD patients had a hazard ratio of 4.8 (95% CI 3.92, 5.94; p<0.001), SDRs of TAD patients had a hazard ratio of 1.7 (95% CI 1.34, 2.03; p<0.001), and FCs of TAD patients had a hazard ratio of 1.2 (95% CI 1.04, 1.45; p=0.015) (Figure 1). In the TAA group (Figure 2), FDRs had a hazard ratio of 6.4 (95% CI 4.61, 8.93; p<0.001), SDRs had a hazard ratio of 1.7 (95% CI 1.30, 2.29; p<0.001), and FCs had a hazard ratio of 1.1 (95% CI 0.77, 1.41; p>0.05).
Conclusion: This extensive dataset provides novel evidence of the heritability of TAAD and establishes a quantitative assessment of familial risk in this population. Relatives of patients affected with TAD or TAA are more likely to develop the respective diagnosis with closer degrees of kinship associated with higher risk.
