# Emerging biomarkers for vascular remodeling in volume and pressure overload in a cardiology cohort

**Authors:** Dora Csengeri, Daniel Engler, Patricia Schlieker, Amelie H. Ohlrogge, Niklas Schofer, Daniel Kalbacher, Larissa Fabritz, André Ziegler, Stefan Blankenberg, Paulus Kirchhof, Tanja Zeller, Renate B. Schnabel

PMC · DOI: 10.1016/j.ijcha.2025.101768 · 2025-08-07

## TL;DR

This study identifies new blood markers that are linked to heart and blood vessel changes caused by volume or pressure overload, and shows they predict worse outcomes in heart patients.

## Contribution

The study introduces four novel circulating biomarkers associated with vascular remodeling and mortality in patients with volume overload.

## Key findings

- ANGPT2, BMP10, FGF23, and IGFBP7 are significantly elevated in patients with volume overload compared to those with mild valve disease.
- FGF23 and NT-proBNP are significantly associated with pressure overload.
- Higher concentrations of these biomarkers predict all-cause mortality in patients with volume overload.

## Abstract

Emerging evidence indicates that the circulating biomarker angiopoietin-2 (ANGPT2), bone morphogenetic protein2 10 (BMP10), fibroblast growth factor 23 (FGF23), and insulin-like growth factor-binding protein7 (IGFBP7) reflect distinct pathophysiological vascular and cardiac processes contributing to adverse cardiac remodeling in the context of volume or pressure overload. This study aims to investigate the association between these circulating biomarkers, and the presence of hemodynamically significant pressure or volume overload and adverse clinical outcomes.

In an observational cohort of outpatient cardiology patients (N = 1506) the relationship between the four emerging biomarkers and pressure/volume overload using multivariable-adjusted regression models was examined.

Elevated levels of the four biomarkers were positively associated with the presence of significant volume overload compared to none/mild valve disease. (ANGPT2: Odds ratio (OR) 1.26 (95 % confidence interval (CI): 1.17–1.35), p < 0.001; BMP10: OR = 2.57 (95 %-CI: 1.89–3.48), p < 0.001; FGF23: OR = 1.51 (95 %-CI: 1.14–1.20), p = 0.004; IGFBP7: OR = 1.39 (95 %-CI: 1.14–1.69), p = 0.001, NT-proBNP: OR = 1.69 (95 %-CI: 1.47–1.95), p < 0.001).

FGF23 and NT-proBNP demonstrated statistically significant associations with pressure overload compared to none/mild burden.

Higher concentrations of all biomarkers were predictive of all-cause mortality in patients with volume overload.

This study highlights that circulating biomarkers associated with distinct pathophysiological vascular pathways, including inflammation, fibrosis, and calcification, are elevated in patients with hemodynamically significant volume overload. Given their association with mortality, these biomarkers merit further investigation of their underlying pathways, particularly in conjugation with the established biomarker NT-proBNP, to clarify their potential for more targeted clinical applications.

## Linked entities

- **Genes:** ANGPT2 (angiopoietin 2) [NCBI Gene 285], BMP10 (bone morphogenetic protein 10) [NCBI Gene 27302], FGF23 (fibroblast growth factor 23) [NCBI Gene 8074], IGFBP7 (insulin like growth factor binding protein 7) [NCBI Gene 3490]

## Full-text entities

- **Genes:** IGFBP7 (insulin like growth factor binding protein 7) [NCBI Gene 3490] {aka AGM, FSTL2, IBP-7, IGFBP-7, IGFBP-7v, IGFBPRP1}, ANGPT2 (angiopoietin 2) [NCBI Gene 285] {aka AGPT2, ANG2, LMPHM10}, BMP10 (bone morphogenetic protein 10) [NCBI Gene 27302], FGF23 (fibroblast growth factor 23) [NCBI Gene 8074] {aka ADHR, FGFN, HFTC2, HPDR2, HYPF, PHPTC}
- **Diseases:** fibrosis (MESH:D005355), pressure overload (MESH:D019190), valve disease (MESH:D006349), cardiac remodeling (MESH:D020257), calcification (MESH:D002114), inflammation (MESH:D007249)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12354793/full.md

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Source: https://tomesphere.com/paper/PMC12354793