Harnessing the Plasma Proteome to Predict Mortality in Heart Failure Subpopulations.

IF 7.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Circulation: Heart Failure Pub Date : 2025-03-07 DOI:10.1161/CIRCHEARTFAILURE.123.011208

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 Loupey, Alena Orlenko, Rachel Ostroff, Laura Sampson, Sama Shrestha, Nancy K Sweitzer, Stephen A Williams, Lei Zhao, Isabella Kardys, David E Lanfear

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引用次数: 0

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.

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利用血浆蛋白质组预测心力衰竭亚群的死亡率。

背景：我们推导并验证了心力衰竭（HF）预后的蛋白质组学风险评分（PRSs），该评分提供了1年内全因死亡率的绝对风险估计。方法：取HF伴射血分数降低(HFrEF；结果：在验证中，HFpEF PRS在预测死亡率方面具有显著性优势（P≤0.1）(c指数，0.79；AUC, 0.82)优于MAGGIC (C-index, 0.71；AUC, 0.74)和NT-proBNP （PRS c指数0.76，AUC为0.81，NT-proBNP c指数0.72，AUC为0.76）。HFrEF PRS的表现与MAGGIC相当（PRS c指数，0.76和AUC， 0.83比MAGGIC c指数，0.75和AUC， 0.84），但c指数（P=0.026）明显优于NT-proBNP （PRS c指数，0.75和AUC， 0.78比NT-proBNP c指数，0.73和AUC， 0.77）。PRS包括已知的HF病理生理生物标志物（93%）和新蛋白（7%）。纵向评估显示，在随访期间经历致命事件的个体中，HFrEF和HFpEF PRSs更高，并且随着时间的推移增加更多。结论：prs可以为心衰患者提供有效、准确和动态的预后评估。这种方法有可能改善患者的纵向监测和促进个性化护理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Circulation: Heart Failure 医学-心血管系统

CiteScore

12.90

自引率

3.10%

发文量

271

审稿时长

6-12 weeks

期刊介绍： Circulation: Heart Failure focuses on content related to heart failure, mechanical circulatory support, and heart transplant science and medicine. It considers studies conducted in humans or analyses of human data, as well as preclinical studies with direct clinical correlation or relevance. While primarily a clinical journal, it may publish novel basic and preclinical studies that significantly advance the field of heart failure.