Observational studyCirculation2020
Proteomic Evaluation of the Comorbidity-Inflammation Paradigm in Heart Failure With Preserved Ejection Fraction: Results From the PROMIS-HFpEF Study.
Observational study in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06247774 (Reducing Heart Failure Risk in Late-Life With Physical Activity), which is not on this map. Cited by 172 papers, 3 of them syntheses that pooled 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.
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.
Reducing Heart Failure Risk in Late-Life With Physical Activity: Impact on Cardiac Structure and Function and Proteomic Signatures
Who cites it
172 citing papers in PubMed, 3 syntheses or guidelines pooled it, 256 citations in OpenAlex.
- Comorbidities and incidence of heart failure with preserved ejection fraction: a systematic review and meta-analysis of cohort studies.BMJ open · 2025Pooled it
- Development and Validation of a Protein Risk Score for Mortality in Heart Failure : A Community Cohort Study.Annals of internal medicine · 2024Pooled it
- Protein biomarkers of cardiac remodeling and inflammation associated with HFpEF and incident events.Scientific reports · 2022Pooled it
- Myeloperoxidase inhibition with mitiperstat in heart failure with preserved or mildly reduced ejection fraction: a randomized phase 2b trial.Nature medicine · 2026Trial
- Proteomic pathways across the ejection fraction spectrum in patients with heart failure and diabetes mellitus: an EXSCEL trial substudy.Scientific reports · 2025Trial
- Cardiometabolic Co-morbidity Burden and Circulating Biomarkers in Patients With Chronic Coronary Disease in the ISCHEMIA Trials.The American journal of cardiology · 2024Trial
- Aptamer Proteomics for Biomarker Discovery in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Proteomic Substudy.Journal of the American Heart Association · 2024Trial
- Urinary Proteomics and Outcomes in Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2024Trial
- Inflammatory cytokines and immune signalling in heart failure: mechanisms, models, and emerging therapies.Cardiovascular research · 2026Review
- Molecular Mechanisms Governing Vascular Function in Heart Failure.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Myeloid Cell Expansion Propels Right Ventricular Dysfunction in HFpEF Through Sterile Inflammation.Circulation · 2026Article
- The plasma protein profile of left ventricular diastolic function.Scientific reports · 2026Article
- Candidate Residual Inflammatory Risk in HFpEF: A Multiorgan Framework for Longitudinal Phenotyping, Trial Enrichment, and Therapeutic Evidence Appraisal.Cardiovascular drugs and therapy · 2026Review
- Interleukin-6 in acute heart failure: A marker of phenotype-specific biology or multimorbidity?Heart and vessels · 2026Article
- Echocardiographic Phenomapping in HFpEF: From Imaging Biomarkers to Precision Cardiovascular Medicine.Echocardiography (Mount Kisco, N.Y.) · 2026Review
- Association of testosterone-to-estradiol ratio with inflammation and clinical outcomes among postmenopausal HFpEF.Endocrine connections · 2026Article
- Review
- Single-Cell Analysis of Human Heart Failure With Preserved Ejection Fraction.Circulation research · 2026Article
- Relative Contributions of Functional Capacity and Inflammatory Activity to Quality of Life in Heart Failure with Preserved Ejection Fraction.Biomedicines · 2026Article
- Inflammation, metabolism, and aging in heart failure with preserved ejection fraction: Mechanisms and treatment perspectives.Journal of translational internal medicine · 2026Article
112 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
15 authors at 7 institutions in 5 countries.
Funding
Abstract
backgroundA systemic proinflammatory state has been hypothesized to mediate the association between comorbidities and abnormal cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). We conducted a proteomic analysis to investigate this paradigm.
methodsIn 228 patients with HFpEF from the multicenter PROMIS-HFpEF study (Prevalence of Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction), 248 unique circulating proteins were quantified by a multiplex immunoassay (Olink) and used to recapitulate systemic inflammation. In a deductive approach, we performed principal component analysis to summarize 47 proteins known a priori to be involved in inflammation. In an inductive approach, we performed unbiased weighted coexpression network analyses of all 248 proteins to identify clusters of proteins that overrepresented inflammatory pathways. We defined comorbidity burden as the sum of 8 common HFpEF comorbidities. We used multivariable linear regression and statistical mediation analyses to determine whether and to what extent inflammation mediates the association of comorbidity burden with abnormal cardiac structure/function in HFpEF. We also externally validated our findings in an independent cohort of 117 HFpEF cases and 30 comorbidity controls without heart failure.
resultsComorbidity burden was associated with abnormal cardiac structure/function and with principal components/clusters of inflammation proteins. Systemic inflammation was also associated with increased mitral E velocity, E/e' ratio, and tricuspid regurgitation velocity; and worse right ventricular function (tricuspid annular plane systolic excursion and right ventricular free wall strain). Inflammation mediated the association between comorbidity burden and mitral E velocity (proportion mediated 19%-35%), E/e' ratio (18%-29%), tricuspid regurgitation velocity (27%-41%), and tricuspid annular plane systolic excursion (13%) (
conclusionsProteins involved in inflammation form a conserved network in HFpEF across 2 independent cohorts and may mediate the association between comorbidity burden and echocardiographic indicators of worse hemodynamics and right ventricular dysfunction. These findings support the comorbidity-inflammation paradigm in HFpEF.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.