Elevated plasma WIF-1 levels are associated with worse prognosis in heart failure with pulmonary hypertension
(2022) In ESC Heart Failure 9(6). p.4139-4149- Abstract
Aims: Heart failure (HF) is a progressive condition that is becoming more prevalent in the ageing population. Pulmonary hypertension is a common complicating factor in HF and negatively impacts survival. Plasma biomarkers are a potential method for determining the prognosis of patients with left heart failure with pulmonary hypertension (LHF-PH). We aimed to analyse the prognostic capability of 33 proteins related to, among other pathways, inflammation, coagulation, and Wnt signalling in LHF-PH. Methods: Plasma levels of 33 proteins were analysed using proximity extension assay from the plasma of 20 controls and 67 LHF-PH patients, whereof 19 underwent heart transplantation (HT). Haemodynamics in the patients were assessed using right... (More)
Aims: Heart failure (HF) is a progressive condition that is becoming more prevalent in the ageing population. Pulmonary hypertension is a common complicating factor in HF and negatively impacts survival. Plasma biomarkers are a potential method for determining the prognosis of patients with left heart failure with pulmonary hypertension (LHF-PH). We aimed to analyse the prognostic capability of 33 proteins related to, among other pathways, inflammation, coagulation, and Wnt signalling in LHF-PH. Methods: Plasma levels of 33 proteins were analysed using proximity extension assay from the plasma of 20 controls and 67 LHF-PH patients, whereof 19 underwent heart transplantation (HT). Haemodynamics in the patients were assessed using right heart catheterization. Results: Eleven proteins had elevated plasma levels in LHF-PH compared with controls (P < 0.01), which decreased towards the controls' levels after HT (P < 0.01). Survival analysis of these proteins showed that elevated plasma levels of growth hormone, programmed cell death 1 ligand 2, tissue factor pathway inhibitor 2, and Wnt inhibitory factor 1 (WIF-1) were associated with worse transplantation-free survival in LHF-PH (P < 0.05). When adjusted for age, sex and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels using multivariable cox regressions, only WIF-1 remained prognostic [hazard ratio (95% confidence interval)] [1.013 (1.001–1.024)]. WIF-1 levels in LHF-PH patients also correlated with the mean right atrial pressure (rs = 0.42; P < 0.01), stroke volume index (rs = 0.41; P < 0.01), cardiac index (rs = −0.42; P < 0.01), left ventricular stroke work index (rs = −0.41; P < 0.01), and NT-proBNP (rs = 0.63; P < 0.01). Conclusions: The present study demonstrated that LHF-PH patients have higher plasma WIF-1 levels than healthy controls, suggesting that plasma WIF-1 may be a potential future prognostic biomarker in LHF-PH. Its prognostic capability could be further refined by including it in a multi-marker panel. Further studies are needed to establish the potential role of WIF-1 in LHF-PH pathophysiology in larger cohorts to determine its clinical applicability.
(Less)
- author
- Kania, Kriss LU ; Ahmed, Abdulla LU ; Ahmed, Salaheldin LU and Rådegran, Göran LU
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Biomarkers, Coagulation proteins, Haemodynamics, PD-L2, TFPI-2, WIF1
- in
- ESC Heart Failure
- volume
- 9
- issue
- 6
- pages
- 4139 - 4149
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:36082780
- scopus:85137497664
- ISSN
- 2055-5822
- DOI
- 10.1002/ehf2.14148
- project
- Plasma proteome profiling in the prognostication and differentiation of pulmonary hypertension
- language
- English
- LU publication?
- yes
- id
- 97540b1e-6715-41fb-b625-decbf1a374fa
- date added to LUP
- 2022-10-21 14:11:36
- date last changed
- 2024-09-20 07:04:52
@article{97540b1e-6715-41fb-b625-decbf1a374fa, abstract = {{<p>Aims: Heart failure (HF) is a progressive condition that is becoming more prevalent in the ageing population. Pulmonary hypertension is a common complicating factor in HF and negatively impacts survival. Plasma biomarkers are a potential method for determining the prognosis of patients with left heart failure with pulmonary hypertension (LHF-PH). We aimed to analyse the prognostic capability of 33 proteins related to, among other pathways, inflammation, coagulation, and Wnt signalling in LHF-PH. Methods: Plasma levels of 33 proteins were analysed using proximity extension assay from the plasma of 20 controls and 67 LHF-PH patients, whereof 19 underwent heart transplantation (HT). Haemodynamics in the patients were assessed using right heart catheterization. Results: Eleven proteins had elevated plasma levels in LHF-PH compared with controls (P < 0.01), which decreased towards the controls' levels after HT (P < 0.01). Survival analysis of these proteins showed that elevated plasma levels of growth hormone, programmed cell death 1 ligand 2, tissue factor pathway inhibitor 2, and Wnt inhibitory factor 1 (WIF-1) were associated with worse transplantation-free survival in LHF-PH (P < 0.05). When adjusted for age, sex and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels using multivariable cox regressions, only WIF-1 remained prognostic [hazard ratio (95% confidence interval)] [1.013 (1.001–1.024)]. WIF-1 levels in LHF-PH patients also correlated with the mean right atrial pressure (r<sub>s</sub> = 0.42; P < 0.01), stroke volume index (r<sub>s</sub> = 0.41; P < 0.01), cardiac index (r<sub>s</sub> = −0.42; P < 0.01), left ventricular stroke work index (r<sub>s</sub> = −0.41; P < 0.01), and NT-proBNP (r<sub>s</sub> = 0.63; P < 0.01). Conclusions: The present study demonstrated that LHF-PH patients have higher plasma WIF-1 levels than healthy controls, suggesting that plasma WIF-1 may be a potential future prognostic biomarker in LHF-PH. Its prognostic capability could be further refined by including it in a multi-marker panel. Further studies are needed to establish the potential role of WIF-1 in LHF-PH pathophysiology in larger cohorts to determine its clinical applicability.</p>}}, author = {{Kania, Kriss and Ahmed, Abdulla and Ahmed, Salaheldin and Rådegran, Göran}}, issn = {{2055-5822}}, keywords = {{Biomarkers; Coagulation proteins; Haemodynamics; PD-L2; TFPI-2; WIF1}}, language = {{eng}}, number = {{6}}, pages = {{4139--4149}}, publisher = {{John Wiley & Sons Inc.}}, series = {{ESC Heart Failure}}, title = {{Elevated plasma WIF-1 levels are associated with worse prognosis in heart failure with pulmonary hypertension}}, url = {{http://dx.doi.org/10.1002/ehf2.14148}}, doi = {{10.1002/ehf2.14148}}, volume = {{9}}, year = {{2022}}, }