Evidence map›Paper›PMID 36597887›Full record

ArticleCirculation research2023

Metabolomic Signatures Associated With Pulmonary Arterial Hypertension Outcomes.

Hongyang Pi, Lu Xia, David D Ralph, Samuel G Rayner, Ali Shojaie, Peter J Leary, Sina A Gharib

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
12.9field-weighted citation impact, top 1% of its field
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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Trial
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  5. Review
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  12. Multi-Omics Identification of Biomarkers for High-Altitude Pulmonary Hypertension.Journal of cardiovascular development and disease · 2026
    Article
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  17. Proteomic and metabolomic profiling nominates druggable targets and biomarkers for pulmonary arterial hypertension-associated myopathy and exercise intolerance in male monocrotaline rats.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2025
    Article
  18. Article
  19. Article
  20. Plasma non-targeted metabolomics unravels the metabolic features of normal trans-right heart.Metabolomics : Official journal of the Metabolomic Society · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 3 countries.

Hongyang Pi *Department of Medicine (H.P., D.D.R., S.G.R., P.J.L., S.A.G.), University of Washington.
Lu Xia *Department of Biostatistics (L.X., A.S.), University of Washington.
David D RalphDepartment of Medicine (H.P., D.D.R., S.G.R., P.J.L., S.A.G.), University of Washington.
Samuel G RaynerDepartment of Medicine (H.P., D.D.R., S.G.R., P.J.L., S.A.G.), University of Washington.ORCID 0000-0002-2541-4221
Ali ShojaieDepartment of Biostatistics (L.X., A.S.), University of Washington.
Peter J Leary *Department of Medicine (H.P., D.D.R., S.G.R., P.J.L., S.A.G.), University of Washington.ORCID 0000-0001-5716-248X
Sina A Gharib *Department of Medicine (H.P., D.D.R., S.G.R., P.J.L., S.A.G.), University of Washington.
University of Washington · USRafael Advanced Defense Systems (Israel) · IL

Funding

Institute of Translational Health SciencesKL2TR000421 · NCATS · UNIVERSITY OF WASHINGTON · PI DISIS, MARY L. · 2012 to 2016
$12.6M
Integrated Multi-omics of MelioidosisR01AI137111 · NIAID · UNIVERSITY OF WASHINGTON · PI GHARIB, SINA A, WEST, TIMOTHY EOIN · 2018 to 2021
$3.2M
REHAB-PH Trial: Repurposing a Histamine Antagonist to Benefit Patients with Pulmonary HypertensionR33HL142539 · NHLBI · UNIVERSITY OF WASHINGTON · PI LEARY, PETER J · 2019 to 2022
$2.7M
Machine Learning Tools for Discovery and Analysis of Active Metabolic PathwaysR01GM114029 · NIGMS · UNIVERSITY OF WASHINGTON · PI SHOJAIE, ALI · 2016 to 2020
$1.7M
Novel Statistical Inference for Biomedical Big DataR01GM133848 · NIGMS · UNIVERSITY OF WASHINGTON · PI SHOJAIE, ALI · 2020 to 2023
$1.7M
The Pulmonary Hypertension- Multi-Dimensional Omics to Characterize Right Heart Adaptation (PH-MOCHA) studyR01HL152724 · NHLBI · UNIVERSITY OF WASHINGTON · PI GHARIB, SINA A, LEARY, PETER J · 2020 to 2023
$1.6M
REVAMP-PH: REpurposing Valsartan May Protect against Pulmonary HypertensionR61HL167848 · NHLBI · UNIVERSITY OF WASHINGTON · PI LEARY, PETER J · 2023 to 2023
$762k
REHAB-PH Trial: Repurposing a Histamine Antagonist to Benefit Patients with Pulmonary HypertensionR61HL142539 · NHLBI · UNIVERSITY OF WASHINGTON · PI LEARY, PETER J · 2018 to 2018
$685k
NCATS NIH HHS KL2 TR000421NHLBI NIH HHS R01 HL152724NHLBI NIH HHS R33 HL142539NHLBI NIH HHS R61 HL142539NHLBI NIH HHS R61 HL167848NIAID NIH HHS R01 AI137111NIGMS NIH HHS R01 GM114029NIGMS NIH HHS R01 GM133848
6 · The paper itself

Abstract

backgroundPulmonary arterial hypertension (PAH) is a complex disease characterized by progressive right ventricular (RV) failure leading to significant morbidity and mortality. Investigating metabolic features and pathways associated with RV dilation, mortality, and measures of disease severity can provide insight into molecular mechanisms, identify subphenotypes, and suggest potential therapeutic targets.

methodsWe collected data from a prospective cohort of PAH participants and performed untargeted metabolomic profiling on 1045 metabolites from circulating blood. Analyses were intended to identify metabolomic differences across a range of common metrics in PAH (eg, dilated versus nondilated RV). Partial least squares discriminant analysis was first applied to assess the distinguishability of relevant outcomes. Significantly altered metabolites were then identified using linear regression, and Cox regression models (as appropriate for the specific outcome) with adjustments for age, sex, body mass index, and PAH cause. Models exploring RV maladaptation were further adjusted for pulmonary vascular resistance. Pathway enrichment analysis was performed to identify significantly dysregulated processes.

resultsA total of 117 participants with PAH were included. Partial least squares discriminant analysis showed cluster differentiation between participants with dilated versus nondilated RVs, survivors versus nonsurvivors, and across a range of NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, REVEAL 2.0 composite scores, and 6-minute-walk distances. Polyamine and histidine pathways were associated with differences in RV dilation, mortality, NT-proBNP, REVEAL score, and 6-minute walk distance. Acylcarnitine pathways were associated with NT-proBNP, REVEAL score, and 6-minute walk distance. Sphingomyelin pathways were associated with RV dilation and NT-proBNP after adjustment for pulmonary vascular resistance.

conclusionsDistinct plasma metabolomic profiles are associated with RV dilation, mortality, and measures of disease severity in PAH. Polyamine, histidine, and sphingomyelin metabolic pathways represent promising candidates for identifying patients at high risk for poor outcomes and investigation into their roles as markers or mediators of disease progression and RV adaptation.

Indexed as

Heart FailureHypertension, PulmonaryPulmonary Arterial HypertensionHistidineHumansNatriuretic Peptide, BrainPeptide FragmentsProspective StudiesSphingomyelinsHistidineNatriuretic Peptide, BrainPeptide FragmentsSphingomyelinshistidinemetabolomicsmortalitypulmonary arterial hypertensionright-sided heart failuresphingomyelinssystems biology

Identifiers

PMID36597887
PMCPMC9904878
OpenAlexW4313488708

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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.