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

Abstract

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.

Thioredoxin-1 and Correlations of the Plasma Cytokines Regarding Aortic Valve Stenosis Severity

“…In another previous study, we also found that plasma concentrations of several growth factors are increased in AS patients [28]. Our results in this study show that not only TRX1, but also proinflammatory biomarkers, namely chemerin, GDF-15, VEGF-A, and FGF-2, and the anti-inflammation biomarker FGF-21 have significant correlations regarding AS severity degrees.…”

“…Our studies, which included testing a broad spectrum of cytokines, growth factors, and oxidative stress-related biomarkers, suggest that GDF-15 and chemerin most effectively reflect the early stage of AS [21,28], and TRX1 joined this study.…”

“…To increase the diagnostic plausibility, we also recommend the measurement of plasma GDF-15 and chemerin levels in patients with suspected AS [21,28].…”

Angiopoietin-like 2 is essential to aortic valve development in mice

“…Inflammation and tissue remodeling involving numerous growth factors contribute to AVS pathogenesis, and circulating growth factors have been recently proposed as potential biomarkers for AVS 11 . Angiopoietin like-2 (ANGPTL2) is a circulating proinflammatory and pro-angiogenic protein 12 , a member of the large family of angiopoietin-like glycoproteins (Angptls), a family of eight (angptl1-8) members that play key roles in various biological and pathological processes.…”

Severe Aortic Valve Stenosis and Pulmonary Hypertension: A Systematic Review of Non-Invasive Ways of Risk Stratification, Especially in Patients Undergoing Transcatheter Aortic Valve Replacement

“…Previously, predictive ability for cardiovascular events, all-cause mortality and cardiovascular mortality was demonstrated in HF patients [138]. GDF-15 levels were found to be sufficiently elevated in patients with mild to severe AS compared to patients without this disease [139]. Moreover, a strong association of GDF-15 levels with the degree of aortic stenosis was found [140].…”