Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty

Fabiani, Iacopo; Santoni, Tatiana; Angelillis, Marco; Petricciuolo, Serena; Colli, Andrea; Pellegrini, Giovanni; Mazzei, Deborah; Pugliese, Nicola Riccardo; Petronio, Anna Sonia; Caterina, Raffaele De

doi:10.3390/jcm9092998

Cited by 13 publications

(14 citation statements)

References 47 publications

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“…Only for BNP (r: 0.367; p < 0.001) and IGF-BP2 (r: 0.324; p = 0.003) a moderate correlation and for GDF-15 (r: 0.204; p = 0.014) a weak correlation was found, whereas for other biomarkers a correlation was almost non-existent. Regarding the correlation of GDF-15 and sPAP, the working group around Fabiani et al [38] also showed only slightly higher values with an r: 0.36; p = 0.001. However, in contrast to our study, the same working group could detect a positive correlation between sST2 and sPAP (r: 0.36; p = 0.04) in another publication [39].…”

Section: Discussionmentioning

confidence: 94%

Systolic Pulmonary Artery Pressure and Cardiovascular Biomarkers—New Non-Invasive Ways to Detect Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing TAVR?

Boxhammer¹,

Köller²,

Paar³

et al. 2022

Rev. Cardiovasc. Med.

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Background: Patients with severe aortic valve stenosis (AS) frequently present with pulmonary hypertension (PH). The gold standard for detection of pulmonary hypertension is right heart catheterization, which is not routinely performed as a preoperative standard in cardiology centers today, neither before surgical valve replacement nor before transcatheter aortic valve replacement (TAVR) procedure. Echocardiographic determination of systolic pulmonary artery pressure (sPAP) provides an opportunity to assess the presence or absence of PH. The aim of the present study was to investigate the extent to which plasma levels of common cardiovascular biomarkers behave in patients with severe AS and an sPAP <40 mmHg in comparison to patients with an sPAP ≥40 mmHg. Methods: 179 patients with echocardiographic evidence of severe AS before TAVR procedure were divided into 2 groups based on sPAP. An sPAP of 40 mmHg was considered the cut-off value, with absence of PH defined by an sPAP <40 mmHg (n = 82) and presence of PH defined by an sPAP ≥40 mmHg (n = 97). Directly before TAVR, a blood sample was drawn from each patient, and plasma concentrations of the cardiovascular biomarkers Soluble Suppression of Tumorigenicity-2 (sST2), Growth/Differentiation of Factor-15 (GDF-15), Heart-Type Fatty-Acid Binding Protein (H-FABP), Insulin Like Growth Factor Binding Protein 2 (IGF-BP2), Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR), Brain Natriuretic Peptide (BNP) and Cardiac Troponin I (cTnI) were determined. Results: Patients with an sPAP ≥40 mmHg had significantly higher sST2 (p = 0.010), GDF-15 (p = 0.005), IGF-BP2 (p = 0.029), suPAR (p = 0.018), BNP (p < 0.001) and cTnI (p = 0.039) plasma levels. Only for H-FABP (p = 0.069), no significant differences were discernible between the two groups. In addition, cut-off values were calculated to predict an sPAP ≥40 mmHg. Significant results were shown with 16045.84 pg/mL for sST2 (p = 0.010), with 1117.54 pg/mL for GDF-15 (p = 0.005), with 107028.43 pg/mL for IGF-BP2 (p = 0.029), with 3782.84 pg/mL for suPAR (p = 0.018), with 2248.00 pg/mL for BNP (p < 0.001) and with 20.50 pg/mL for cTnI (p = 0.002). Conclusions: sPAP as an echocardiographic parameter in combination with supplementary use of cardiovascular biomarkers presented here have the potential to provide more detailed information about the presence or absence of PH in a non-invasive way.

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Section: Discussionmentioning

confidence: 94%

Systolic Pulmonary Artery Pressure and Cardiovascular Biomarkers—New Non-Invasive Ways to Detect Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing TAVR?

Boxhammer¹,

Köller²,

Paar³

et al. 2022

Rev. Cardiovasc. Med.

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“…ROC analysis of the study growth factors showed that GDF-15 might serve as a specific and sensitive biomarker for AS stenosis (fair level), and is especially seen in patients with severe AS, but Ang-2 is not significant. The clinical diagnostic significance of circulating GDF-15 in AS patients could be predicted from studies on its role in several cardiovascular diseases and mortality after transcatheter aortic valve replacement [ 1 , 2 , 3 , 4 , 17 ]. Stress conditions affect GDF-15 levels, and this, in turn, affects the regulation of myocyte hypertrophy and is therefore associated with the severity of hypertrophic cardiomyopathy [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…Several studies confirm the clinical and diagnostic role of circulating GDF-15 in AS patients [29,30]. The angiogenic markers VEGF-A and FGF-2 are involved in matrix remodeling, and proliferation plays a significant pathophysiological role in the development of AS [31].…”

Section: Discussionmentioning

confidence: 70%

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

et al. 2021

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Aortic valve stenosis (AS) develops not only with a pronounced local inflammatory response, but also oxidative stress is involved. The aim of this study was to evaluate the plasma levels of thioredoxin-1 (TRX1), myeloperoxidase (MPO), chemerin, 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), and metalloproteinase (MMP)-1, -3, and -9 in acquired AS patients as well as to clarify the correlations of TXR1 and the plasma inflammatory biomarkers regarding AS severity. 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 were selected as a control group. AS patients had significantly higher plasma levels of TRX1 compared to controls, but the highest difference was found in mild AS patients compared to the controls. We conclude that AS is associated with significantly increased plasma TRX1 levels, and TRX1 might serve as a specific and sensitive biomarker of AS. TRX1 and also chemerin, GDF-15, VEGF-A, FGF-2 and FGF-21 significantly correlate with AS severity degrees. TRX1 also showed positive association with FGF-2, VEGF-A, and MMP-3 in all AS patients.

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Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty

Cited by 13 publications

References 47 publications

Systolic Pulmonary Artery Pressure and Cardiovascular Biomarkers—New Non-Invasive Ways to Detect Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing TAVR?

Systolic Pulmonary Artery Pressure and Cardiovascular Biomarkers—New Non-Invasive Ways to Detect Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing TAVR?

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

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

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