Heart failure proteomics: an epidemiology study

National Heart, Lung, And Blood Institute

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Abstract

We continued our investigations into the prognostic value of proteomic signatures associated with death in a heart failure (HF) community cohort and quantified 7,335 plasma proteins using an aptamer-based technology. During the past fiscal year this was primarily accomplished through two main studies: Molecular Phenogroups of Heart Failure: The main objective of this study was exploring the use and clinical utility of proteomic-based phenomapping in HF. To accomplish this, we used k-means clustering approaches to identify distinct phenogroups based on 7000 plasma proteins measured in a HF community cohort and compared their clinical characteristics and all-cause mortality. We identified three proteomics-defined phenogroups, with substantial differences in survival, independent of clinical characteristics. Phenogroups also exhibited differences in several measures suggesting poorer health, including NT-proBNP (N-terminal pro-B-type natriuretic peptide), kidney function, and Meta-Analysis Global Group in Chronic Heart Failure scores, but did not differ by ejection fraction or New York Heart Association class. Our results demonstrated that molecular phenomapping can stratify patients with HF into distinct subgroups that go beyond predefined clinical classifications. Proteomic Profile of Ischemic Heart Disease in Heart Failure: The main goal of this study was to examine the clinical characteristics, outcomes, and proteomic profiles of prevalent ischemic heart disease (IHD) in HF. Within our HF community cohort, we classified IHD by prior myocardial infarction, angiographic coronary disease, or revascularization. We used cause-specific hazards modelling to examine the association between IHD status and cardiovascular mortality. 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 cardiovascular risk factors. We found ejection fraction significantly influenced the association between IHD status and mortality. Ischemic heart disease was associated with excess 5-year cardiovascular mortality in the reduced ejection fraction group but not in the preserved ejection fraction group. 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. Collectively, these results suggest that unique proteomic profiles reveal biologic signatures of IHD in HF, emphasizing the importance of molecular data in classifying HF phenotypes.