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Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension

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Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension. / Rhodes, Christopher J; Wharton, John; Swietlik, Emilia M; Harbaum, Lars; Girerd, Barbara; Coghlan, J Gerry; Lordan, James; Church, Colin; Pepke-Zaba, Joanna; Toshner, Mark; Wort, Stephen J; Kiely, David G; Condliffe, Robin; Lawrie, Allan; Gräf, Stefan; Montani, David; Boucly, Athénaïs; Sitbon, Olivier; Humbert, Marc; Howard, Luke S; Morrell, Nicholas W; Wilkins, Martin R; UK National PAH Cohort Study Consortium.

In: AM J RESP CRIT CARE, Vol. 205, No. 9, 01.05.2022, p. 1102-1111.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Rhodes, CJ, Wharton, J, Swietlik, EM, Harbaum, L, Girerd, B, Coghlan, JG, Lordan, J, Church, C, Pepke-Zaba, J, Toshner, M, Wort, SJ, Kiely, DG, Condliffe, R, Lawrie, A, Gräf, S, Montani, D, Boucly, A, Sitbon, O, Humbert, M, Howard, LS, Morrell, NW, Wilkins, MR & UK National PAH Cohort Study Consortium 2022, 'Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension', AM J RESP CRIT CARE, vol. 205, no. 9, pp. 1102-1111. https://doi.org/10.1164/rccm.202105-1118OC

APA

Rhodes, C. J., Wharton, J., Swietlik, E. M., Harbaum, L., Girerd, B., Coghlan, J. G., Lordan, J., Church, C., Pepke-Zaba, J., Toshner, M., Wort, S. J., Kiely, D. G., Condliffe, R., Lawrie, A., Gräf, S., Montani, D., Boucly, A., Sitbon, O., Humbert, M., ... UK National PAH Cohort Study Consortium (2022). Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension. AM J RESP CRIT CARE, 205(9), 1102-1111. https://doi.org/10.1164/rccm.202105-1118OC

Vancouver

Rhodes CJ, Wharton J, Swietlik EM, Harbaum L, Girerd B, Coghlan JG et al. Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension. AM J RESP CRIT CARE. 2022 May 1;205(9):1102-1111. https://doi.org/10.1164/rccm.202105-1118OC

Bibtex

@article{73eed96925bc416ebcc801ace05fdd0f,
title = "Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension",
abstract = "Rationale: NT-proBNP (N-terminal pro-brain natriuretic peptide), 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 that complement NT-proBNP and clinical risk scores. Methods: An aptamer-based assay (SomaScan version 4) 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 (Evaluation of Prognostic Factors and Therapeutic Targets in PAH) study (n = 79). Prognostic proteins were identified in discovery-replication analyses of UK samples. Proteins independent of 6-minute-walk distance and NT-proBNP entered least absolute shrinkage and selection operator modeling, 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-minute-walk distance in the UK cohort. A weighted combination score of six proteins was validated at baseline (5-yr mortality; area under the curve [AUC], 0.73; 95% confidence interval [CI], 0.63-0.85) and follow-up in EFORT (AUC, 0.84; 95% CI, 0.75-0.94; P = 9.96 × 10-6). The protein score risk stratified patients independent of established clinical targets and risk equations. The addition of the six-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 receiver operating characteristic 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.",
author = "Rhodes, {Christopher J} and John Wharton and Swietlik, {Emilia M} and Lars Harbaum and Barbara Girerd and Coghlan, {J Gerry} and James Lordan and Colin Church and Joanna Pepke-Zaba and Mark Toshner and Wort, {Stephen J} and Kiely, {David G} and Robin Condliffe and Allan Lawrie and Stefan Gr{\"a}f and David Montani and Ath{\'e}na{\"i}s Boucly and Olivier Sitbon and Marc Humbert and Howard, {Luke S} and Morrell, {Nicholas W} and Wilkins, {Martin R} and {UK National PAH Cohort Study Consortium}",
year = "2022",
month = may,
day = "1",
doi = "10.1164/rccm.202105-1118OC",
language = "English",
volume = "205",
pages = "1102--1111",
journal = "AM J RESP CRIT CARE",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "9",

}

RIS

TY - JOUR

T1 - Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension

AU - Rhodes, Christopher J

AU - Wharton, John

AU - Swietlik, Emilia M

AU - Harbaum, Lars

AU - Girerd, Barbara

AU - Coghlan, J Gerry

AU - Lordan, James

AU - Church, Colin

AU - Pepke-Zaba, Joanna

AU - Toshner, Mark

AU - Wort, Stephen J

AU - Kiely, David G

AU - Condliffe, Robin

AU - Lawrie, Allan

AU - Gräf, Stefan

AU - Montani, David

AU - Boucly, Athénaïs

AU - Sitbon, Olivier

AU - Humbert, Marc

AU - Howard, Luke S

AU - Morrell, Nicholas W

AU - Wilkins, Martin R

AU - UK National PAH Cohort Study Consortium

PY - 2022/5/1

Y1 - 2022/5/1

N2 - Rationale: NT-proBNP (N-terminal pro-brain natriuretic peptide), 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 that complement NT-proBNP and clinical risk scores. Methods: An aptamer-based assay (SomaScan version 4) 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 (Evaluation of Prognostic Factors and Therapeutic Targets in PAH) study (n = 79). Prognostic proteins were identified in discovery-replication analyses of UK samples. Proteins independent of 6-minute-walk distance and NT-proBNP entered least absolute shrinkage and selection operator modeling, 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-minute-walk distance in the UK cohort. A weighted combination score of six proteins was validated at baseline (5-yr mortality; area under the curve [AUC], 0.73; 95% confidence interval [CI], 0.63-0.85) and follow-up in EFORT (AUC, 0.84; 95% CI, 0.75-0.94; P = 9.96 × 10-6). The protein score risk stratified patients independent of established clinical targets and risk equations. The addition of the six-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 receiver operating characteristic 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.

AB - Rationale: NT-proBNP (N-terminal pro-brain natriuretic peptide), 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 that complement NT-proBNP and clinical risk scores. Methods: An aptamer-based assay (SomaScan version 4) 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 (Evaluation of Prognostic Factors and Therapeutic Targets in PAH) study (n = 79). Prognostic proteins were identified in discovery-replication analyses of UK samples. Proteins independent of 6-minute-walk distance and NT-proBNP entered least absolute shrinkage and selection operator modeling, 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-minute-walk distance in the UK cohort. A weighted combination score of six proteins was validated at baseline (5-yr mortality; area under the curve [AUC], 0.73; 95% confidence interval [CI], 0.63-0.85) and follow-up in EFORT (AUC, 0.84; 95% CI, 0.75-0.94; P = 9.96 × 10-6). The protein score risk stratified patients independent of established clinical targets and risk equations. The addition of the six-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 receiver operating characteristic 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.

U2 - 10.1164/rccm.202105-1118OC

DO - 10.1164/rccm.202105-1118OC

M3 - SCORING: Journal article

C2 - 35081018

VL - 205

SP - 1102

EP - 1111

JO - AM J RESP CRIT CARE

JF - AM J RESP CRIT CARE

SN - 1073-449X

IS - 9

ER -