Abstract 15520: The Association of a Genetic Risk Score With Presence of Polyvascular Disease
Background: Atherosclerotic cardiovascular disease (ASCVD) often affects > 1 arterial location (polyvascular disease, PVD). The risk of adverse outcomes increases with the number of arterial territories involved. The genetic susceptibility to PVD is unknown.
Hypothesis: We hypothesized that a genetic risk score representing cumulative effects of susceptibility variants to ASCVD is associated with presence of PVD.
Methods: We searched genome-wide association study (GWAS) catalog to identify genetic variants associated with coronary heart disease (CHD), ischemic stroke, peripheral arterial disease (PAD) or abdominal aortic aneurysm (AAA). No variants were reported to be associated with PVD in ≥ 3 arterial territories at GWAS significance. 10 loci were associated with PVD in 2 arterial territories. We calculated a multi-locus GRS using 10 lead single nuclear polymorphisms (SNP) from these distinct loci (1 per each loci) in 7486 participants in Mayo Vascular Disease Biorepository (age 68±10 years, 61% men, 31% with CHD; 27% carotid artery stenosis; 39% PAD; 14% AAA; 38% without any of these vascular diseases).
Results: Of all participants 34% had PVD (2%, 10% and 22% with exact 4, 3 and 2 arterial territories involved respectively). A higher GRS was associated with greater number of arterial territories involved (P for trend of ANOVA <0.001). Patients with PVD in ≥ 3 arterial locations had higher GRS compared to those with 2 arterial locations involved after adjustment for age, sex and cardiovascular risk factors (P =0.008). One unit increase in GRS was associated with 9% higher likelihood for each additional arterial territory involved after adjustment for all covariates (odds ratio from ordinal regression model= 1.09, P <0.001). The result remained significant after further adjustment for combinations of AAA, CHD, carotid arterial stenosis and PAD (all P ≤ 0.01). 5 Of the 10 SNPs were each associated with presence of PVD after adjustment for all covariates (all P <0.01). None of them remained significant after further adjustment for combinations of PVD in different arterial territories (all P ≥ 0.4).
Conclusions: A GRS derived from 10 SNPs of ASCVD is associated with PVD,suggesting genetic contribution to the dimension of PVD that may lead to adverse outcome.
Author Disclosures: Z. Ye: None. E. Austin: None. A.M. Arruda-Olson: None. I.J. Kullo: None.
- © 2015 by American Heart Association, Inc.