Key result
Adding a six-protein score to NT-proBNP improves 5-year mortality prediction in PAH.
Why the study?
NT-proBNP, a cardiac biomarker used for risk stratifying PAH patients, has limitations including poor sensitivity to early vascular pathology, necessitating identification of additional prognostic proteins.
Does a six-protein plasma score improve 5-year mortality prediction compared to NT-proBNP alone in patients with pulmonary arterial hypertension?
Cohort (n=436)
Yes
Does a six-protein plasma score improve 5-year mortality prediction compared to NT-proBNP alone in patients with pulmonary arterial hypertension?
Effect estimate: AUC 0.818 (95% CI 0.767-0.869)
Absolute Event Rate: 0.818% vs 0.762%
p-value: p=0.00426
A novel six-protein plasma score significantly improves the prediction of 5-year mortality in PAH patients when added to established biomarkers like NT-proBNP.
May refine PAH risk stratification; hypothesis-generating and requires prospective validation before practice change.
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.
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A 2022 study conducted a cohort in Pulmonary Arterial Hypertension (n=436). Six-protein model score vs. NT-proBNP alone was evaluated on Prediction of 5-year outcomes (AUC 0.818, 95% CI 0.767-0.869, p=0.00426). The addition of a six-protein model score to NT-proBNP improved the prediction of 5-year outcomes in patients with pulmonary arterial hypertension (AUC 0.818 vs 0.762; P=0.00426).
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