Evidence map›Paper›PMID 28624389›Full record

Observational studyThe Lancet. Respiratory medicine2017

Plasma proteome analysis in patients with pulmonary arterial hypertension: an observational cohort study.

Christopher J Rhodes, John Wharton, Pavandeep Ghataorhe, Geoffrey Watson, Barbara Girerd, Luke S Howard, J Simon R Gibbs, Robin Condliffe, Charles A Elliot, David G Kiely and 9 more

Abstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The Lancet. Respiratory medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

96 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  13. A Peek into Pulmonary Hypertension through the Plasma Proteome.American journal of respiratory and critical care medicine · 2025
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36 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Christopher J RhodesDepartment of Medicine, Imperial College London, Hammersmith Campus, London, UK.
John WhartonDepartment of Medicine, Imperial College London, Hammersmith Campus, London, UK.
Pavandeep GhataorheDepartment of Medicine, Imperial College London, Hammersmith Campus, London, UK.
Geoffrey WatsonDepartment of Medicine, Imperial College London, Hammersmith Campus, London, UK.
Barbara GirerdUniversity Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France; AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, Paris, France; Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis-Robinson, Paris, France.
Luke S HowardNational Heart and Lung Institute, Imperial College London, Hammersmith Campus, London, UK; National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK.
J Simon R GibbsNational Heart and Lung Institute, Imperial College London, Hammersmith Campus, London, UK; National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK.
Robin CondliffeSheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.
Charles A ElliotSheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.
David G KielySheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK.
Gerald SimonneauUniversity Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France; AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, Paris, France; Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis-Robinson, Paris, France.
David MontaniUniversity Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France; AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, Paris, France; Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis-Robinson, Paris, France.
Olivier SitbonUniversity Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France; AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, Paris, France; Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis-Robinson, Paris, France.
Henning GallUniversity of Giessen and Marburg Lung Center, Member of the German Center for Lung Research (DZL), Giessen, Germany.
Ralph T SchermulyUniversity of Giessen and Marburg Lung Center, Member of the German Center for Lung Research (DZL), Giessen, Germany.
H Ardeschir GhofraniUniversity of Giessen and Marburg Lung Center, Member of the German Center for Lung Research (DZL), Giessen, Germany.
Allan LawrieDepartment of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
Marc HumbertUniversity Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France; AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, Paris, France; Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis-Robinson, Paris, France.
Martin R WilkinsDepartment of Medicine, Imperial College London, Hammersmith Campus, London, UK. Electronic address: m.wilkins@imperial.ac.uk.

Funding

British Heart Foundation FS/13/48/30453British Heart Foundation FS/15/59/31839British Heart Foundation PG/11/116/29288British Heart Foundation RG/10/16/28575Medical Research Council MC_PC_14100Wellcome Trust
6 · The paper itself

Abstract

backgroundIdiopathic and heritable pulmonary arterial hypertension form a rare but molecularly heterogeneous disease group. We aimed to measure and validate differences in plasma concentrations of proteins that are associated with survival in patients with idiopathic or heritable pulmonary arterial hypertension to improve risk stratification.

methodsIn this observational cohort study, we enrolled patients with idiopathic or heritable pulmonary arterial hypertension from London (UK; cohorts 1 and 2), Giessen (Germany; cohort 3), and Paris (France; cohort 4). Blood samples were collected at routine clinical appointment visits, clinical data were collected within 30 days of blood sampling, and biochemical data were collected within 7 days of blood sampling. We used an aptamer-based assay of 1129 plasma proteins, and patient clinical details were concealed to the technicians. We identified a panel of prognostic proteins, confirmed with alternative targeted assays, which we evaluated against the established prognostic risk equation for pulmonary arterial hypertension derived from the REVEAL registry. All-cause mortality was the primary endpoint.

findings20 proteins differentiated survivors and non-survivors in 143 consecutive patients with idiopathic or heritable pulmonary arterial hypertension with 2 years' follow-up (cohort 1) and in a further 75 patients with 2·5 years' follow-up (cohort 2). Nine proteins were both prognostic independent of plasma NT-proBNP concentrations and confirmed by targeted assays. The functions of these proteins relate to myocardial stress, inflammation, pulmonary vascular cellular dysfunction and structural dysregulation, iron status, and coagulation. A cutoff-based score using the panel of nine proteins provided prognostic information independent of the REVEAL equation, improving the C statistic from area under the curve 0·83 (for REVEAL risk score, 95% CI 0·77-0·89; p<0·0001) to 0·91 (for panel and REVEAL 0·87-0·96; p<0·0001) and improving reclassification indices without detriment to calibration. Poor survival was preceded by an adverse change in panel score in paired samples from 43 incident patients with pulmonary arterial hypertension in cohort 3 (p=0·0133). The protein panel was validated in 93 patients with idiopathic or heritable pulmonary arterial hypertension in cohort 4, with 4·4 years' follow-up and improved risk estimates, providing complementary information to the clinical risk equation.

interpretationA combination of nine circulating proteins identifies patients with pulmonary arterial hypertension with a high risk of mortality, independent of existing clinical assessments, and might have a use in clinical management and the evaluation of new therapies.

fundingNational Institute for Health Research, Wellcome Trust, British Heart Foundation, Assistance Publique-Hôpitaux de Paris, Inserm, Université Paris-Sud, and Agence Nationale de la Recherche.

Indexed as

AdultAgedArterial PressureBiomarkersBlood ProteinsCohort StudiesFamilial Primary Pulmonary HypertensionFemaleHumansHypertensionMaleMiddle AgedProteomeRisk AssessmentRisk FactorsBiomarkersBlood ProteinsProteome

Identifiers

PMID28624389
PMCPMC5573768

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.