Harnessing the Plasma Proteome to Predict Mortality in Heart Failure Subpopulations
Recommended Citation
Chadwick J, Hinterberg MA, Asselbergs FW, Biegel H, Boersma E, Cappola TP, Chirinos JA, Coresh J, Ganz P, Gordon DA, Kureshi N, Loupey KM, Orlenko A, Ostroff R, Sampson L, Shrestha S, Sweitzer NK, Williams SA, Zhao L, Kardys I, and Lanfear DE. Harnessing the Plasma Proteome to Predict Mortality in Heart Failure Subpopulations. Circ Heart Fail 2025;18(4):011208.
Document Type
Article
Publication Date
4-1-2025
Publication Title
Circ Heart Fail
Abstract
BACKGROUND: We derived and validated proteomic risk scores (PRSs) for heart failure (HF) prognosis that provide absolute risk estimates for all-cause mortality within 1 year.
METHODS: Plasma samples from individuals with HF with reduced ejection fraction (HFrEF; ejection fraction < 40%; training/validation n=1247/762) and preserved ejection fraction (HFpEF; ejection fraction ≥ 50%; training/validation n=725/785) from 3 independent studies were run on the SomaScan Assay measuring ≈5000 proteins. Machine learning techniques resulted in unique 17- and 14-protein models for HFrEF and HFpEF that predict 1-year mortality. Discrimination was assessed via C-index and 1-year area under the curve (AUC), and survival curves were visualized. PRSs were also compared with Meta-Analysis Global Group in Chronic HF (MAGGIC) score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurements and further assessed for sensitivity to disease progression in longitudinal samples (HFrEF: n=396; 1107 samples; HFpEF: n=175; 350 samples).
RESULTS: In validation, the HFpEF PRS performed significantly better (P≤0.1) for mortality prediction (C-index, 0.79; AUC, 0.82) than MAGGIC (C-index, 0.71; AUC, 0.74) and NT-proBNP (PRS C-index, 0.76 and AUC, 0.81 versus NT-proBNP C-index, 0.72 and AUC, 0.76). The HFrEF PRS performed comparably to MAGGIC (PRS C-index, 0.76 and AUC, 0.83 versus MAGGIC C-index, 0.75 and AUC, 0.84) but had a significantly better C-Index (P=0.026) than NT-proBNP (PRS C-index, 0.75 and AUC, 0.78 versus NT-proBNP C-index, 0.73 and AUC, 0.77). PRS included known HF pathophysiology biomarkers (93%) and novel proteins (7%). Longitudinal assessment revealed that HFrEF and HFpEF PRSs were higher and increased more over time in individuals who experienced a fatal event during follow-up.
CONCLUSIONS: PRSs can provide valid, accurate, and dynamic prognostic estimates for patients with HF. This approach has the potential to improve longitudinal monitoring of patients and facilitate personalized care.
Medical Subject Headings
Humans; Heart Failure; Male; Female; Aged; Stroke Volume; Middle Aged; Risk Assessment; Biomarkers; Prognosis; Proteome; Proteomics; Natriuretic Peptide, Brain; Predictive Value of Tests; Peptide Fragments; Risk Factors; Disease Progression
PubMed ID
40052265
ePublication
ePub ahead of print
Volume
18
Issue
4
First Page
011208
Last Page
011208
