Circulating growth factors as clinical biomarkers in aortic valve stenosis

Aortic valve stenosis (AS) develops with a pronounced local inflammatory response, where a variety of growth factors are involved in the process, and may have a pro-inflammatory and anti-inflammatory effect. The aim of our study was to elucidate whether circulating growth factors: growth differentiation factor 15 (GDF-15), angiopoietin-2 (Ang-2), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), fibroblast growth factor 21 (FGF-21) could be proposed as clinically relevant biomarkers to improve risk stratification in AS patients AS patients were classified into three groups: 16 patients with mild AS stenosis; 19 with moderate and 11 with severe AS, and 30 subjects without AS (echocardiographically approved) were selected as a control group. GDF-15, Ang-2, VEGF-A, FGF-2 and TGF-21 were measured in plasma by ELISA method. GDF-15 levels differ significantly not only when comparing AS patients with control groups (p <0.0001), but also a statistically significant difference was achieved when comparing mild degree AS patients at mild stage with control individuals. We found strong relationship of GDF-15 levels regarding AS severity degree (p <0.0001). VEGF-A, FGF-2 and FGF-21 levels were significantly higher in AS patients than in controls, but relationships regarding AS severity degree were weaker (p <0.02). ROC analysis of the study growth factors showed that GDF-15 might serve as a specific and sensitive biomarker of AS stenosis (AUV = 0.75, p = 0.0002). FGF-21 correlated with GDF-15, Ang-2, and FGF-2, but it did not reach the level to serve as a clinically relevant biomarker of AS stenosis. AV stenosis is associated with significantly increased GDF-15, VEGF-A, FGF-2 and FGF-21 levels in plasma, but only GDF-15 shows pronounced relationship regarding AS severity degree, and GDF-15 may serve as a specific and sensitive biomarker of AS stenosis.