Author + information
- Kaleigh L. Evansa,b,
- Heidi Wirtza,b,
- Jia Lia,b,
- Ruicong Shea,b,
- Juan Mayaa,b,
- Christophe Deprea,b,
- Andrew Hamera,b and
- David Lanfeara,b
Background: Elevated heart rate (HR) is a risk factor and therapeutic target in patients with heart failure and reduced ejection fraction (HFrEF). The goal of this study was to assess race and genetic influences on HR in HFrEF.
Methods: Patients who met Framingham criteria for HF, had EF<50%, and self-identified as African American (AA) or white were prospectively enrolled (2007-2015, n=1059). Subjects underwent genome-wide genotyping with which we estimated heritability of resting HR, and then performed genome-wide association study (GWAS) adjusted for race using EMMAX. Heritability p<0.05 was considered significant. GWAS significance was considered at p<5x10-8.
Results: Resting HR was 2 bpm lower in AA vs white patients (70 vs 72.4 bpm, p=0.004). Heritability of HR was high among AA patients (h2 =1, p=0.00048) but not statistically significant among white patients (h2 =0.05, p=0.48). The GWAS results are shown in the figure; one SNP on chromosome (chr) 22 (rs535263906) met genome-wide significance (p=3.3 × 10-8), while two others on chr 6 (rs149447933) and chr 5 (rs541284506) were borderline (p=7.5 × 10-8 and p=9.5 × 10-8, respectively). The chr 22 SNP lies in the gene CELSR1, which is a cadherin and appears to be expressed in cardiac and smooth muscle.
Conclusions: Our data suggest that Race and genetics impact HR in HFrEF patients, and identify a novel genetic locus influencing HR in CELSR1. Additional study is needed to better understand the relationship of race and genetics on HR as a treatment target in HFrEF.
Moderated Poster Contributions
Heart Failure and Cardiomyopathies Moderated Poster Theater, Poster Hall, Hall C
Saturday, March 18, 2017, 12:30 p.m.-12:40 p.m.
Session Title: Put Your Codon! Genetic Insights Into Heart Failure
Abstract Category: 12. Heart Failure and Cardiomyopathies: Basic
Presentation Number: 1226M-03
- 2017 American College of Cardiology Foundation