Imperial College London
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DrChristopherRhodes

Faculty of Medicine, National Heart & Lung Institute

Reader in Pulmonary Vascular Disease
 
 
 
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Contact

 

+44 (0)20 7594 7638c.rhodes07

 
 
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Location

 

535ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Rhodes:2022,
author = {Rhodes, C and Wharton, J and Swietlik, E and Harbaum, L and Girerd, B and Coghlan, G and Lordan, J and Church, C and Pepke-Zaba, J and Toshner, M and Wort, SJ and Kiely, D and Condliffe, R and Lawrie, A and Graf, S and Montani, D and Boucly, A and Sitbon, O and Humbert, M and Howard, LS and Morrell, NW and Wilkins, MR},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {1102--1111},
title = {Using the plasma proteome for risk stratifying patients with pulmonary arterial hypertension},
url = {https://www.atsjournals.org/doi/10.1164/rccm.202105-1118OC},
volume = {205},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Rationale: N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of cardiac origin, is used to risk stratify patients with pulmonary arterial hypertension (PAH). Its limitations include poor sensitivity to early vascular pathology. Other biomarkers of vascular or systemic origin may also be useful in the management of PAH.Objectives: Identify prognostic proteins in PAH which complement NT-proBNP and clinical risk scores.Methods: An aptamer-based assay (SomaScan-V4) targeting 4,152 proteins was used to measure plasma proteins in patients with idiopathic, heritable or drug-induced-PAH from the UK National Cohort of PAH (n=357) and the French EFORT study (n=79). Prognostic proteins were identified in discovery-replication analyses of UK samples. Proteins independent of 6-minute walk distance (6-MWD) and NT-proBNP entered LASSO modelling and the best combination in a single score was evaluated against clinical targets in EFORT.Measurements and Main Results: Thirty-one proteins robustly informed prognosis independent of NT-proBNP and 6-MWD in the UK Cohort. A weighted combination score of 6 proteins was validated at baseline (5-year mortality, AUC:0.73, 95%CI:0.63-0.85) and follow-up in EFORT (AUC:0.84, 95%CI:0.75-0.94, p=9.96x10-6). The protein score risk-stratified patients independent of established clinical targets and risk equations. The addition of the 6-protein model score to NT-proBNP improved prediction of 5-year outcomes from AUC:0.762 (0.702-0.821) to 0.818 (0.767-0.869) by ROC analysis (p=0.00426 for difference in AUC) in the UK replication and French samples combined.  Conclusions: The plasma proteome informs prognosis beyond established factors in PAH and may provide a more sensitive measure of therapeutic response.
AU  - Rhodes,C
AU  - Wharton,J
AU  - Swietlik,E
AU  - Harbaum,L
AU  - Girerd,B
AU  - Coghlan,G
AU  - Lordan,J
AU  - Church,C
AU  - Pepke-Zaba,J
AU  - Toshner,M
AU  - Wort,SJ
AU  - Kiely,D
AU  - Condliffe,R
AU  - Lawrie,A
AU  - Graf,S
AU  - Montani,D
AU  - Boucly,A
AU  - Sitbon,O
AU  - Humbert,M
AU  - Howard,LS
AU  - Morrell,NW
AU  - Wilkins,MR
EP  - 1111
PY  - 2022///
SN  - 1073-449X
SP  - 1102
TI  - Using the plasma proteome for risk stratifying patients with pulmonary arterial hypertension
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - https://www.atsjournals.org/doi/10.1164/rccm.202105-1118OC
UR  - http://hdl.handle.net/10044/1/93254
VL  - 205
ER  -
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