ArticleCirculation2017
Plasma Metabolomics Implicates Modified Transfer RNAs and Altered Bioenergetics in the Outcomes of Pulmonary Arterial Hypertension.
Open access · greenAbstract read
In one paragraph
Article in Circulation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed, 1 pooled it
10.5field-weighted citation impact, top 1% of its field
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.
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.
Who cites it
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 209 citations in OpenAlex.
- Metabolomics in Pulmonary Hypertension-A Useful Tool to Provide Insights into the Dark Side of a Tricky Pathology.International journal of molecular sciences · 2023Pooled it
- Novel Metabolites Associated With Blood Pressure After Dietary Interventions.Hypertension (Dallas, Tex. : 1979) · 2024Trial
- Mechanistic Phase II Clinical Trial of Metformin in Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2020Trial
- Artificial Intelligence and Multi-Omics Approaches in the Precision Management of Pulmonary Hypertension: From Early Diagnosis to Therapeutic Stratification.International journal of molecular sciences · 2026Review
- Article
- A metabolomic clock of population ageing: cross-cohort validation and associations with frailty and cognitive function.GeroScience · 2026Article
- Metabolic Markers as Potential Risk Factors in Pulmonary Hypertension.Pulmonary circulation · 2026Article
- Metabolomic Network Analysis Reveals Reorganization of Lipid and Steroid Programs Linked to Right Ventricular-Pulmonary Vascular Function in Pulmonary Hypertension.bioRxiv : the preprint server for biology · 2026Article
- The bile acid-oxysterol axis in pulmonary arterial hypertension: from sterol trafficking to precision phenotyping and therapeutic opportunities.Molecular biology reports · 2026Review
- Hemodynamic and metabolomic responses to infusion of GLP-1 agonist exenatide in pulmonary arterial hypertension.JCI insight · 2026Article
- A Metabolomics Roadmap to Right Ventricular Function in Pulmonary Hypertension.Circulation research · 2026Article
- Metabolomics of Right Ventricular Function in Pulmonary Hypertension.Circulation research · 2026Article
- Multi-Omics Identification of Biomarkers for High-Altitude Pulmonary Hypertension.Journal of cardiovascular development and disease · 2026Article
- A circulating MicroRNA signature for the diagnosis of pulmonary arterial hypertension and functional characterization of candidate miR-3168.Scientific reports · 2026Article
- Metabolomic and lipidomic signatures associated with clinical improvement after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.Chinese medical journal pulmonary and critical care medicine · 2026Article
- Associations Between Right Ventricular Remodeling, Exercise and Circulating Metabolites in Volume and Pressure Overload States.JACC. Asia · 2026Article
- Review
- Sex differences in pulmonary (arterial) hypertension: does it matter?Current opinion in pulmonary medicine · 2025Review
- c-Myc promotes metabolic reprogramming in pulmonary hypertension via the stimulation of glutaminolysis and the reductive tricarboxylic acid cycle.Redox biology · 2025Article
- Metabolomic Evidence of Biological Overlap with Heart Failure with Preserved Ejection Fraction in a Subset of Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2025Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 1 institution in 1 country.
Christopher J RhodesFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Pavandeep GhataorheFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
John WhartonFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Kevin C Rue-AlbrechtFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Charaka HadinnapolaFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Geoffrey WatsonFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Marta BledaFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Matthias HaimelFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Gerry CoghlanFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Paul A CorrisFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Luke S HowardFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
David G KielyFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Andrew J PeacockFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Joanna Pepke-ZabaFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Mark R ToshnerFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
S John WortFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
J Simon R GibbsFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Allan LawrieFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Stefan GräfFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Nicholas W MorrellFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.).
Martin R WilkinsFrom the Department of Medicine, Imperial College London, Hammersmith Campus, United Kingdom (C.J.R., P.G., J.W., K.C.R.-A., G.W., M.R.W.); Department of Medicine, University of Cambridge School of Clinical Medicine, United Kingdom (C.H., M.B., M.H., M.R.T., S.G., N.W.M.); Cardiology Department, Royal Free Hospital, London, United Kingdom (G.C.); Institute of Cellular Medicine, Newcastle University and the Newcastle Upon Tyne Hospitals NHS Foundation Trust, United Kingdom (P.A.C.); National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom (L.S.H., J.S.R.G.); National Heart and Lung Institute, Imperial College London, Hammersmith Campus, United Kingdom (L.S.H., J.S.R.G.); Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, United Kingdom (D.G.K.); Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, United Kingdom (D.G.K., A.L.); Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom (A.J.P.); Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom (J.P.Z., M.R.T.); Pulmonary Hypertension Service, Royal Brompton Hospital, London, United Kingdom (S.J.W.); and Department of Haematology, University of Cambridge, United Kingdom (S.G.). m.wilkins@imperial.ac.uk.
Hammersmith Hospital · GB
Funding
British Heart Foundation FS/13/48/30453British Heart Foundation FS/15/59/31839British Heart Foundation PG/11/116/29288British Heart Foundation RG/10/16/28575British Heart Foundation SP/12/12/29836Department of Health IMPCRF-2012-1Medical Research Council G0800318Medical Research Council MR/K020919/1
Abstract
backgroundPulmonary arterial hypertension (PAH) is a heterogeneous disorder with high mortality.
methodsWe conducted a comprehensive study of plasma metabolites using ultraperformance liquid chromatography mass spectrometry to identify patients at high risk of early death, to identify patients who respond well to treatment, and to provide novel molecular insights into disease pathogenesis.
resultsFifty-three circulating metabolites distinguished well-phenotyped patients with idiopathic or heritable PAH (n=365) from healthy control subjects (n=121) after correction for multiple testing (P<7.3e-5) and confounding factors, including drug therapy, and renal and hepatic impairment. A subset of 20 of 53 metabolites also discriminated patients with PAH from disease control subjects (symptomatic patients without pulmonary hypertension, n=139). Sixty-two metabolites were prognostic in PAH, with 36 of 62 independent of established prognostic markers. Increased levels of tRNA-specific modified nucleosides (N2,N2-dimethylguanosine, N1-methylinosine), tricarboxylic acid cycle intermediates (malate, fumarate), glutamate, fatty acid acylcarnitines, tryptophan, and polyamine metabolites and decreased levels of steroids, sphingomyelins, and phosphatidylcholines distinguished patients from control subjects. The largest differences correlated with increased risk of death, and correction of several metabolites over time was associated with a better outcome. Patients who responded to calcium channel blocker therapy had metabolic profiles similar to those of healthy control subjects.
conclusionsMetabolic profiles in PAH are strongly related to survival and should be considered part of the deep phenotypic characterization of this disease. Our results support the investigation of targeted therapeutic strategies that seek to address the alterations in translational regulation and energy metabolism that characterize these patients.
Indexed as
AdultAgedEnergy MetabolismFemaleHumansHypertension, PulmonaryMaleMetabolomicsMiddle AgedPrognosisRNA, TransferTreatment OutcomeYoung AdultRNA, Transferhypertension, pulmonarymetabolismmetabolomemetabolomicspulmonary circulation
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.