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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Identify prognostic proteins in PAH that complement NT-proBNP and clinical risk scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2009=\u2009357) and the French EFORT (Evaluation of Prognostic Factors and Therapeutic Targets in PAH) study (n\u2009=\u200979). Prognostic proteins were identified in discovery\u2013replication 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>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\u20130.85) and follow-up in EFORT (AUC, 0.84; 95% CI, 0.75\u20130.94; P\u2009=\u20099.96\u2009\u00d7\u200910\u22126). 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\u20130.821) to 0.818 (0.767\u20130.869) by receiver operating characteristic analysis (P\u2009=\u20090.00426 for difference in AUC) in the UK replication and French samples combined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The plasma proteome informs prognosis beyond established factors in PAH and may provide a more sensitive measure of therapeutic response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202105-1118oc","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T13:49:26Z","timestamp":1643204966000},"page":"1102-1111","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":81,"title":["Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4962-3204","authenticated-orcid":false,"given":"Christopher J.","family":"Rhodes","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8110-2575","authenticated-orcid":false,"given":"John","family":"Wharton","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia M.","family":"Swietlik","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9422-6195","authenticated-orcid":false,"given":"Lars","family":"Harbaum","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Girerd","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2013Saclay, AP-HP, INSERM UMR_S 999, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Centre, H\u00f4pital de Bic\u00eatre, Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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