Proteomic pathways across the ejection fraction spectrum in patients with heart failure and diabetes mellitus: an EXSCEL trial substudy

作者：Anthony E. Peters, Maggie Nguyen, Jennifer B. Green, Ewan R. Pearson, John B. Buse, Harald Sourij, Adrian F. Hernandez, Naveed Sattar, Rury R. Holman, Robert J. Mentz, Svati H. Shah · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-025-14414-0 · 被引用次数：4 · 研究领域：Cardiovascular Function and Risk Factors、Heart Failure Treatment and Management、Diabetes Treatment and Management

Ejection fraction (EF) is a key component of heart failure (HF) classification. However, the biologic basis of HF with mildly reduced EF (HFmrEF) as a distinct biologic entity distinct from HF with preserved EF (HFpEF) and reduced EF (HFrEF) has not been well characterized. The EXSCEL trial randomized participants with type 2 diabetes (T2DM) to a once-weekly glucagon-like peptide receptor agonist (GLP-1 RA) exenatide (EQW) vs. placebo. For this study, profiling of ~ 5000 proteins using the SomaLogic SomaScan platform was performed in baseline and 12-month serum samples from N = 1199 participants with prevalent HF at baseline. Unsupervised principal component analysis (PCA) and ANOVA (FDR p < 0.1) were used to identify proteins that were significantly between three EF groups (EF > 55% [HFpEF], EF 40-55% [HFmrEF], EF < 40% [HFrEF], categories as previously curated in the parent trial). Cox proportional hazards was used to assess association between baseline levels of proteins significantly different between groups, and changes in protein level between baseline and 12-month, with time-to-HF hospitalization. Mixed models were used to assess whether significant proteins changed differentially with exenatide vs. placebo therapy. Of N = 1199 EXSCEL participants with prevalent HF, 284 (24%), 704 (59%) and 211 (18%) had HFpEF, HFmrEF and HFrEF, respectively. Eight principal components analysis (PCA) protein factors differed significantly across the three EF groups, of which 270 indivi...