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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.