Prognostic Utility of Circulating Growth Factors in Aortic Valve Stenosis: A Pilot Study

• Published in: Medicina (Kaunas, Lithuania) Vol. 57; no. 1; p. 78
• Main Authors: Hofmanis, Juris, Tretjakovs, Peteris, Svirskis, Simons, Gersone, Gita, Hofmane, Dace, Rozenberga, Ulla, Blumfelds, Leons, Bahs, Guntis, Lejnieks, Aivars, Mackevics, Vitolds
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 18.01.2021; MDPI AG
• Subjects: angiopoietin-2; aortic valve stenosis; Aortic Valve Stenosis - diagnosis; Biomarkers; fibroblast growth factor 2; fibroblast growth factor-21; growth differentiation factor 15; Humans; Pilot Projects; Prognosis; ROC Curve; Vascular Endothelial Growth Factor A; angiopoietin-2; aortic valve stenosis; fibroblast growth factor-21; growth differentiation factor 15; vascular endothelial growth factor A; fibroblast growth factor 2
• ISSN: 1648-9144; 1010-660X; 1648-9144
• DOI: 10.3390/medicina57010078

Background and Objectives: 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), and fibroblast growth factor 21 (FGF-21) could be proposed as clinically relevant biomarkers to improve risk stratification in AS patients. Materials and Methods: 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 FGF-21 were measured in plasma by the ELISA method. Results: GDF-15 levels differed significantly not only when comparing AS patients with control groups (p < 0.0001), but also a statistically significant difference was achieved when comparing AS patients at a mild degree stage with control individuals. We found a 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 the 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 (AUC = 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. Conclusions: AS is associated with significantly increased GDF-15, VEGF-A, FGF-2, and FGF-21 levels in plasma, but only GDF-15 shows a pronounced relationship regarding AS severity degree, and GDF-15 might serve as a specific and sensitive biomarker of AS stenosis.