Evidence map›Paper›PMID 37335853›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2023

Metabolomic Differences in Connective Tissue Disease-Associated Versus Idiopathic Pulmonary Arterial Hypertension in the PVDOMICS Cohort.

Catherine E Simpson, Anna R Hemnes, Megan Griffiths, Gabriele Grunig, W H Wilson Tang, Joe G N Garcia, John Barnard, Suzy A Comhair, Rachel L Damico, Stephen C Mathai and 2 more

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04071327 (Pulmonary Hypertension Association Registry), which is not on this map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 6% 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.

NCT04071327 recruitingnot on this map

Pulmonary Hypertension Association Registry

Typeobservational_patient_registrySponsorPulmonary Hypertension Association, Inc.Ran2015 to 2025Enrolled3,000ConditionsPulmonary Arterial Hypertension, Chronic Thromboembolic Pulmonary Hypertension, Pulmonary Hypertension
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Observational
  8. Application of Metabolomics across the Spectrum of Pulmonary and Critical Care Medicine.American journal of respiratory cell and molecular biology · 2024
    Review
  9. Observational
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

12 authors at 7 institutions in 1 country.

Catherine E SimpsonJohns Hopkins University, Baltimore, Maryland.ORCID 0000-0002-2388-5660
Anna R HemnesVanderbilt University Medical Center, Nashville, Tennessee.
Megan GriffithsUniversity of Texas Southwestern Medical Center, Dallas.
Gabriele GrunigNew York University Grossman School of Medicine, New York.
W H Wilson TangCleveland Clinic, Cleveland, Ohio.
Joe G N GarciaUniversity of Arizona College of Medicine, Tucson.
John BarnardCleveland Clinic Lerner Research Institute, Cleveland, Ohio.
Suzy A ComhairCleveland Clinic Lerner Research Institute, Cleveland, Ohio.
Rachel L DamicoJohns Hopkins University, Baltimore, Maryland.
Stephen C MathaiJohns Hopkins University, Baltimore, Maryland.ORCID 0000-0003-3188-7209
Paul M HassounJohns Hopkins University, Baltimore, Maryland.
PVDOMICS Study Group
Johns Hopkins University · USCleveland Clinic Lerner College of Medicine · USCleveland Clinic · USNew York University · USThe University of Texas Southwestern Medical Center · USUniversity of Arizona · USVanderbilt University Medical Center · US

Funding

Novel Involvement of NAMPT and TLR4 in PAH Vascular RemodelingR01HL141387 · NHLBI · UNIVERSITY OF FLORIDA · 2022 to 2025
$1.3M
NHLBI NIH HHS K23 HL153781NHLBI NIH HHS K23HL153781NHLBI NIH HHS R01 HL132153NHLBI NIH HHS R01HL132153NHLBI NIH HHS R01 HL141387NHLBI NIH HHS U01 HL125175NHLBI NIH HHS U01HL125175NHLBI NIH HHS U01 HL125177NHLBI NIH HHS U01HL125177NHLBI NIH HHS U01 HL125205NHLBI NIH HHS U01HL125205NHLBI NIH HHS U01 HL125208NHLBI NIH HHS U01HL125208NHLBI NIH HHS U01 HL125212NHLBI NIH HHS U01HL125212NHLBI NIH HHS U01 HL125215NHLBI NIH HHS U01HL125215NHLBI NIH HHS U01 HL125218NHLBI NIH HHS U01HL125218
6 · The paper itself

Abstract

objectivePatients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) experience worse survival and derive less benefit from pulmonary vasodilator therapies than patients with idiopathic PAH (IPAH). We sought to identify differential metabolism in patients with CTD-PAH versus patients with IPAH that might underlie these observed clinical differences.

methodsAdult participants with CTD-PAH (n = 141) and IPAH (n = 165) from the Pulmonary Vascular Disease Phenomics (PVDOMICS) study were included. Detailed clinical phenotyping was performed at cohort enrollment, including broad-based global metabolomic profiling of plasma samples. Participants were followed prospectively for ascertainment of outcomes. Supervised and unsupervised machine learning algorithms and regression models were used to compare CTD-PAH versus IPAH metabolomic profiles and to measure metabolite-phenotype associations and interactions. Gradients across the pulmonary circulation were assessed using paired mixed venous and wedged samples in a subset of 115 participants.

resultsMetabolomic profiles distinguished CTD-PAH from IPAH, with patients with CTD-PAH demonstrating aberrant lipid metabolism with lower circulating levels of sex steroid hormones and higher free fatty acids (FAs) and FA intermediates. Acylcholines were taken up by the right ventricular-pulmonary vascular (RV-PV) circulation, particularly in CTD-PAH, while free FAs and acylcarnitines were released. In both PAH subtypes, dysregulated lipid metabolites, among others, were associated with hemodynamic and RV measurements and with transplant-free survival.

conclusionsCTD-PAH is characterized by aberrant lipid metabolism that may signal shifted metabolic substrate utilization. Abnormalities in RV-PV FA metabolism may imply a reduced capacity for mitochondrial beta oxidation within the diseased pulmonary circulation.

Indexed as

Connective Tissue DiseasesHypertension, PulmonaryPulmonary Arterial HypertensionAdultFamilial Primary Pulmonary HypertensionHumansPhenomicsVasodilator AgentsVasodilator Agents

Identifiers

PMID37335853
PMCPMC10728345
OpenAlexW4381189268

What Socratic holds

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Registered trials

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 Socratic graph.