Harnessing the Plasma Proteome to Predict Mortality in Heart Failure Subpopulations
Year: 2025
Type: article
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.
Source: Circulation Heart Failure
Authors: Jessica Chadwick, Michael A. Hinterberg, Folkert W. Asselbergs, Hannah Biegel, Eric Boersma, Thomas P. Cappola, Julio A. Chirinos, Joseph Coresh, Peter Ganz, David A. Gordon, Natasha Kureshi, Kelsey M. Loupy, Alena Orlenko, Rachel Ostroff, Laura Sampson, Sama Shrestha, Nancy K. Sweitzer, Stephen A. Williams, Lei Zhao, Isabella Kardys, David E. Lanfear
Institutions: SomaLogic (United States), Health Data Research UK, Amsterdam University Medical Centers, University College London, University of Amsterdam, Erasmus MC, Hospital of the University of Pennsylvania, University of Pennsylvania, Johns Hopkins University, San Francisco General Hospital, University of California, San Francisco, Bristol-Myers Squibb (United States), Cedars-Sinai Medical Center, University of Arizona, Henry Ford Hospital
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: European Federation of Pharmaceutical Industries and Associations, National Institute for Health and Care Research, European Commission, Jaap Schouten Foundation, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Proteomics of Cardiovascular Risk: The Multiethnic Study of Atherosclerosis, G1114307781, G1805328512, Identifying Proteomics Risk Markers for Abdominal Aortic Aneurysm, GWA for Gene-Environment Interaction Effects Influencing CHD, G3874773046, G3973572274, G471361583, G4747441672, G4790942633, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, Epidemiology of Venous Thrombosis and Pulmonary Embolism, G5770678025, G5901998020, G5928944960, G6634173328, G6837735701, G7155745631, G7535686976, G8738262636, From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, G931818222, Proteomic signatures to identify pathways underlying the progression to heart failure
OpenAlex ID: W4408236150