Abstract 15829: A Multi-locus Genetic Risk Score for Abdominal Aortic Aneurysm is Associated With Rapid Aneurysm Expansion
Background: Rapid abdominal aortic aneurysm (AAA) expansion increases the risk of aneurysm rupture that can be prevented by AAA surveillance and elective repair. Whether genetic susceptibility to AAA affects trajectory of AAA expansion is unknown. We assessed the association of a multi-locus genetic risk score (GRS) for AAA with rapid expansion trajectory.
Methods: Patients were identified from the Mayo clinic vascular disease biorepository who had AAA and with ≥ 2 measures of pre-repair AAA size assessed at least 3 months apart (all by abdominal computed tomography, n = 427, 84% men). Linear mixed-effects model was used to estimate AAA expansion trajectory. NHGRI-EBI GWAS Catalog and PubMed were used to search genetic susceptibility variants for AAA at p < 10 x 10^-5. A weighted GRS using effect sizes from the catalog or largest meta-analysis was constructed comprising of genetic variants associated with rapid AAA expansion trajectory - individual AAA expansion over time > upper limit of 95% confidence interval (CI) of mean AAA expansion rate of the cohort (4 of 28 loci identified by stepwise elimination approach).
Results: The mean baseline AAA size of the cohort was 4.0 ± 0.85 cm with a mean follow up of 4.1 ± 3.3 years. After adjustment for baseline size, mean AAA expansion was 0.21 (95% CI: 0.19 - 0.23) cm / year; 156 patients had rapid AAA expansion trajectory [mean (SE) AAA expansion 0.3 (0.01) cm / year]. Age, sex, prevalence of cardiovascular risk factors and atherosclerotic vascular diseases were similar in high- (> median) and low-GRS groups; none were associated with rapid expansion trajectory (all P > 0.05). High-GRS group was more likely to have rapid expansion and aneurysm repair than low-GRS group; rapid expansion trajectory and high-GRS group were each associated with increased risk of aneurysm repair at younger age (Figure).
Conclusions: A multi-locus GRS for AAA can identify patients at risk of having rapid AAA expansion trajectory that may need early intervention.
Author Disclosures: Z. Ye: None. E. Austin: None. I.J. Kullo: None.
- © 2016 by American Heart Association, Inc.