TY - JOUR T1 - A Systematic Review with Meta-analysis of Biomarkers for detection of Pulmonary Arterial Hypertension JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00009-2022 SP - 00009-2022 AU - A. Josien Smits AU - Liza Botros AU - Marijke A.E. Mol AU - Kirsten A. Ziesemer AU - Martin R. Wilkins AU - Anton Vonk Noordegraaf AU - Harm Jan Bogaard AU - Jurjan Aman Y1 - 2022/01/01 UR - http://openres.ersjournals.com/content/early/2022/03/10/23120541.00009-2022.abstract N2 - Rationale The blood is a rich source of potential biomarkers for the diagnosis of idiopathic and hereditary pulmonary arterial hypertension (iPAH and hPAH, referred to as “PAH”). While a lot of biomarkers have been identified for PAH, the clinical utility of these biomarkers often remains unclear. Here, we used unbiased meta-analysis of published biomarkers to identify biomarkers with the highest performance in the detection of PAH.Methods A literature search (in PubMed, Embase.com, Clarivate Analytics/Web of Science Core Collection and Wiley/Cochrane Library) was performed up to January 28, 2021. Primary end points were blood biomarker levels in PAH versus asymptomatic controls or patients suspected of pulmonary hypertension (PH) with proven normal haemodynamic profiles.Results 149 articles were identified by the literature search. Meta-analysis of 26 biomarkers yielded 17 biomarkers that were differentially expressed in PAH and non-PH control subjects. Red cell distribution width, LDL-c, d-dimer, NT-proBNP, IL-6 and uric acid were biomarkers with the largest observed differences, largest sample sizes and a low risk of publication bias. Receiver operating characteristic curves and sensitivity/specificity analyses demonstrated that NT-proBNP had a high sensitivity, but low specificity for PAH. For the other biomarkers, insufficient data on diagnostic accuracy with receiver operating characteristic curves were available for meta-analysis.Conclusion This meta-analysis validates NT-proBNP as a biomarker with high sensitivity for PAH, albeit with low specificity. The majority of biomarkers evaluated in this meta-analysis lacked either external validation or data on diagnostic accuracy. Further validation studies are required, and studies that test combinations of biomarkers to improve specificity.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Harm Jan Bogaard reports receiving grants or contracts from Janssen, MSD, and Ferrer, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, received from Janssen, and MSD, outside the submitted work.Martin Wilkins reports received consulting fees from Actelion, MorphogenIX, and Novartis, outside the submitted work. Patents planned, issued or pending; Prognostic biomarker panel derived from discovery science. Leadership or fiduciary role in other board, society, committee or advocacy group for Pulmonary Vascular Research Institute, unpaid.The remaining authors have nothing to disclose. ER -