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Elevated plasma WIF-1 levels are associated with worse prognosis in heart failure with pulmonary hypertension

Kania, Kriss LU orcid ; Ahmed, Abdulla LU orcid ; Ahmed, Salaheldin LU orcid and Rådegran, Göran LU (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.

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author
; ; and
organization
publishing date
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
  • scopus:85137497664
  • pmid:36082780
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
2024-07-12 00:22:06
@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 &lt; 0.01), which decreased towards the controls' levels after HT (P &lt; 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 &lt; 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 &lt; 0.01), stroke volume index (r<sub>s</sub> = 0.41; P &lt; 0.01), cardiac index (r<sub>s</sub> = −0.42; P &lt; 0.01), left ventricular stroke work index (r<sub>s</sub> = −0.41; P &lt; 0.01), and NT-proBNP (r<sub>s</sub> = 0.63; P &lt; 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}},
}