Proteomic Profile of Ischemic Heart Disease in Heart Failure: A Community Study.

Abstract

To investigate the clinical characteristics, outcomes, and proteomic profiles of prevalent ischemic heart disease (IHD) in heart failure (HF) in a clinically phenotyped cohort. We studied an HF community cohort (N=1351) enrolled between September 10, 2003, and September 18, 2012, with linked medical records and measured 7289 plasma protein targets using an aptamer-based assay. Ischemic heart disease was defined by prior myocardial infarction, angiographic coronary disease, or revascularization. Cause-specific hazards model was used to test the association between IHD status and cardiovascular (CV) mortality while considering the interaction by ejection fraction (EF) group. Linear regression adjusting for age, sex, and estimated glomerular filtration rate with multiple testing correction was used to evaluate the cross-sectional association of proteins with IHD status and with CV risk factors. There were 678 patients with IHD (median age, 78 years [interquartile range, 69 to 84 years]; 271 [40%] female). The association between IHD status and CV mortality was markedly influenced by EF (P_interaction=.002). Ischemic heart disease was associated with excess 5-year CV mortality in the reduced EF group (hazard ratio, 2.14; 95% CI, 1.42 to 3.21) but not in the preserved EF group (hazard ratio, 1.04; 95% CI, 0.80 to 1.36). Fifty-two proteins (31 up-regulated, 21 down-regulated) were associated with IHD compared with non-IHD, including 42 proteins associated with risk factors and 10 with no association with risk factors. These data suggest that unique proteomic profiles reveal biologic signatures of IHD in HF, emphasizing the importance of molecular data in classifying HF phenotypes. In addition, our findings underscore the prognostic significance of IHD in HF with reduced EF.