Circulating biomarkers and proteomic profile changes in elderly patients with heart failure with improved ejection fraction: a real-life study
M R Scarcelli, V Cassano, C Gabriele, G Armentaro, G Severini, D Martire, C A Pastura, S Miceli, M L Hribal, G M C Rosano, M Gaspari, A SciacquaAbstract
Background
Heart failure (HF) is a complex clinical syndrome. Its pathophysiology involves multiple interconnected pathways, generating numerous circulating molecules that can serve as biomarkers. Circulating biomarkers in HF have emerged as powerful tools for risk stratification, diagnostic confirmation, prognostic assessment, and monitoring of treatment efficacy.
Purpose
The aim of the present study was to evaluate circulating levels of biomarkers in elderly patients with HFimpEF, previously with LVEF < 40%, after 6 months of drug therapy optimisation.
Methods
We enrolled 100 HFimpEF elderly outpatients (mean age 66.7±11.8years). All patients underwent an accurate medical history and complete physical examination, at the baseline and after 6 months of follow-up. The serum values of circulating biomarkers were assessed with an ELISA test. Proteomic analysis was performed on serum samples collected from a subset of 13 patients at baseline and after 6 months of follow-up.
Results
No significant differences were observed in the comparison between males and females, for clinical parameters. After 6 months of follow-up, we observed significant improvements in glycometabolic, renal and inflammatory profile and significant reductions in pro-inflammatory cytokine levels were observed (p<0.001). A comprehensive proteomic analysis, performed in a subgroup of 13 patients with HFimpEF, revealed selective changes in key cardiovascular (CV)-related proteins. Insulin-like growth factor-binding protein 4 (IBP4) showed a significant decrease (p=0.012), suggesting alterations in growth factor signalling pathways. Thrombospondin-4 (TSP4), an extracellular matrix protein involved in vascular remodelling, decreased (p=0.028). Intercellular adhesion molecule 1 (ICAM1), a marker of endothelial activation, showed a modest but statistically significant increase (p=0.030). Syndecan-4 (SDC4), involved in cell adhesion and signalling, decreased significantly (p=0.005).
Conclusions
This study demonstrates significant improvements across multiple CV biomarkers, after 6 months of therapy optimization, in HFimpEF patients, providing evidence for comprehensive therapeutic effects targeting inflammation, oxidative stress, neurohormonal activation, and thrombotic risk. However, these are preliminary data, obtained from a relatively small sample, especially regards to proteomic investigation, in which the associations do not prove causality. Further investigations are therefore needed on this matter, in a larger cohort of patients.