Advanced

Higher plasma fibroblast growth factor 23 levels are associated with a higher risk profile in pulmonary arterial hypertension

Bouzina, Habib LU ; Hesselstrand, Roger LU and Rådegran, Göran LU (2019) In Pulmonary Circulation 9(4).
Abstract

Metabolic abnormalities are proposed to contribute to pulmonary arterial as well as right ventricular remodelling in pulmonary arterial hypertension. Among the proposed abnormalities are altered glucose and lipid processing, mitochondrial malfunction, oxidative stress as well as vitamin D and iron abnormalities. In the present study, we investigated 11 metabolic plasma biomarkers, with the hypothesis that metabolic proteins may mirror disease severity in pulmonary arterial hypertension. Using proximity extension assays, plasma metabolic biomarkers were measured in 48 pulmonary arterial hypertension patients at diagnosis and, in 33 of them, at an early treatment follow-up, as well as in 16 healthy controls. Among the studied metabolic... (More)

Metabolic abnormalities are proposed to contribute to pulmonary arterial as well as right ventricular remodelling in pulmonary arterial hypertension. Among the proposed abnormalities are altered glucose and lipid processing, mitochondrial malfunction, oxidative stress as well as vitamin D and iron abnormalities. In the present study, we investigated 11 metabolic plasma biomarkers, with the hypothesis that metabolic proteins may mirror disease severity in pulmonary arterial hypertension. Using proximity extension assays, plasma metabolic biomarkers were measured in 48 pulmonary arterial hypertension patients at diagnosis and, in 33 of them, at an early treatment follow-up, as well as in 16 healthy controls. Among the studied metabolic biomarkers, plasma fibroblast growth factor-23 (p < 0.001), fibroblast growth factor-21 (p < 0.001), fatty acid binding protein 4 (p < 0.001) and lectin-like oxidised low-density lipoprotein receptor 1 (p < 0.001) were increased and paraoxonase-3 was decreased (p < 0.001) in pulmonary arterial hypertension at diagnosis versus controls. Fibroblast growth factor-23 showed the strongest correlations to studied clinical parameters and was therefore selected for further analyses. Fibroblast growth factor-23 correlated specifically to mean right atrial pressure (r = 0.67, p < 0.001), six-min walking distance (r = −0.66, p < 0.001), NT-proBNP (r = 0.64, p < 0.001), venous oxygen saturation (r = −0.61, p < 0.001), cardiac index (r = −0.39, p < 0.007) and pulmonary vascular resistance (r = 0.37, p < 0.01). Fibroblast growth factor-23 correlated moreover to ESC/ERS (r = 0.72, p < 0.001) and the REVEAL risk score (r = 0.61, p < 0.001). Comparing early treatment follow-up with baseline, fibroblast growth factor-23 decreased (p < 0.02), with changes in fibroblast growth factor-23 correlating to changes in six-min walking distance (r = −0.56, p < 0.003), venous oxygen saturation (r = −0.46, p < 0.01), pulmonary vascular resistance (r = 0.43, p < 0.02), mean right atrial pressure (r = 0.38, p < 0.04) and cardiac index (r = −0.39, p < 0.04). Elevated plasma fibroblast growth factor-23 levels at pulmonary arterial hypertension diagnosis were associated with worse haemodynamics and a higher risk profile, and were decreased after the administration of pulmonary arterial hypertension-specific treatment.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
fibroblast growth factor 23, metabolism, pulmonary arterial hypertension, risk assessment
in
Pulmonary Circulation
volume
9
issue
4
publisher
University of Chicago Press
external identifiers
  • pmid:31908768
  • scopus:85077213051
ISSN
2045-8932
DOI
10.1177/2045894019895446
language
English
LU publication?
yes
id
f541bfa7-691a-4991-a58c-421328b9d039
date added to LUP
2020-01-14 14:18:04
date last changed
2020-01-16 04:09:30
@article{f541bfa7-691a-4991-a58c-421328b9d039,
  abstract     = {<p>Metabolic abnormalities are proposed to contribute to pulmonary arterial as well as right ventricular remodelling in pulmonary arterial hypertension. Among the proposed abnormalities are altered glucose and lipid processing, mitochondrial malfunction, oxidative stress as well as vitamin D and iron abnormalities. In the present study, we investigated 11 metabolic plasma biomarkers, with the hypothesis that metabolic proteins may mirror disease severity in pulmonary arterial hypertension. Using proximity extension assays, plasma metabolic biomarkers were measured in 48 pulmonary arterial hypertension patients at diagnosis and, in 33 of them, at an early treatment follow-up, as well as in 16 healthy controls. Among the studied metabolic biomarkers, plasma fibroblast growth factor-23 (p &lt; 0.001), fibroblast growth factor-21 (p &lt; 0.001), fatty acid binding protein 4 (p &lt; 0.001) and lectin-like oxidised low-density lipoprotein receptor 1 (p &lt; 0.001) were increased and paraoxonase-3 was decreased (p &lt; 0.001) in pulmonary arterial hypertension at diagnosis versus controls. Fibroblast growth factor-23 showed the strongest correlations to studied clinical parameters and was therefore selected for further analyses. Fibroblast growth factor-23 correlated specifically to mean right atrial pressure (r = 0.67, p &lt; 0.001), six-min walking distance (r = −0.66, p &lt; 0.001), NT-proBNP (r = 0.64, p &lt; 0.001), venous oxygen saturation (r = −0.61, p &lt; 0.001), cardiac index (r = −0.39, p &lt; 0.007) and pulmonary vascular resistance (r = 0.37, p &lt; 0.01). Fibroblast growth factor-23 correlated moreover to ESC/ERS (r = 0.72, p &lt; 0.001) and the REVEAL risk score (r = 0.61, p &lt; 0.001). Comparing early treatment follow-up with baseline, fibroblast growth factor-23 decreased (p &lt; 0.02), with changes in fibroblast growth factor-23 correlating to changes in six-min walking distance (r = −0.56, p &lt; 0.003), venous oxygen saturation (r = −0.46, p &lt; 0.01), pulmonary vascular resistance (r = 0.43, p &lt; 0.02), mean right atrial pressure (r = 0.38, p &lt; 0.04) and cardiac index (r = −0.39, p &lt; 0.04). Elevated plasma fibroblast growth factor-23 levels at pulmonary arterial hypertension diagnosis were associated with worse haemodynamics and a higher risk profile, and were decreased after the administration of pulmonary arterial hypertension-specific treatment.</p>},
  author       = {Bouzina, Habib and Hesselstrand, Roger and Rådegran, Göran},
  issn         = {2045-8932},
  language     = {eng},
  number       = {4},
  publisher    = {University of Chicago Press},
  series       = {Pulmonary Circulation},
  title        = {Higher plasma fibroblast growth factor 23 levels are associated with a higher risk profile in pulmonary arterial hypertension},
  url          = {http://dx.doi.org/10.1177/2045894019895446},
  doi          = {10.1177/2045894019895446},
  volume       = {9},
  year         = {2019},
}