Common Variants on Increase Hazard of Mortality or Rehospitalization in Patients With Heart Failure From the ASCEND-HF Trial
AUTHORS
- PMID: 37725680 [PubMed].
ABSTRACT
BACKGROUND: Heart failure remains a global health burden, and patients hospitalized are particularly at risk, but genetic associates for subsequent death or rehospitalization are still lacking.
METHODS: The genetic substudy of the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) was used to perform genome-wide association study and transethnic meta-analysis. The overall trial included the patients of self-reported European ancestry (n=2173) and African ancestry (n=507). The end point was death or heart failure rehospitalization within 180 days. Cox models adjusted for 11 a priori predictors of rehospitalization and 5 genetic principal components were used to test the association between single-nucleotide polymorphisms and outcome. Summary statistics from the 2 populations were combined via meta-analysis with the significance threshold considered <5×10.
RESULTS: Common variants (rs2342882 and rs35850039 in complete linkage disequilibrium) located in were significantly associated with the primary outcome in both ancestry groups (European Americans: hazard ratio [HR], 1.38; =2.42×10; African ancestry: HR, 1.51; =4.43×10; HR in meta-analysis, 1.41; =4.25×10). encodes a regulator of VEGF (vascular endothelial growth factor)-mediated angiogenesis, and in silico investigation revealed several previous genome-wide association study hits in this gene, among which rs748431 was associated with our outcome (HR, 1.20; meta <0.01). Sensitivity analysis proved common variants survival association did not appear to operate via coronary artery disease or nesiritide treatment (>0.05); and the signal was still significant when changing the censoring time from 180 to 30 days (HR, 1.39; =1.59×10).
CONCLUSIONS: In this multiethnic genome-wide association study of ASCEND-HF, single-nucleotide polymorphisms in were associated with increased risk of death or rehospitalization. Additional investigation is required to examine biological mechanisms and whether could be a therapeutic target.
REGISTRATION: URL: https://www.
CLINICALTRIALS: gov; Unique identifier: NCT00475852.
Tags: 2023 Alumni Publications