ArticleNEJM evidence2022
Endotrophin, a Collagen VI Formation-Derived Peptide, in Heart Failure.
Article in NEJM evidence, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Epidemiology of heart failure in diabetes: a disease in disguise.Diabetologia · 2024Pooled it
- Trial
- Urinary Proteomics and Outcomes in Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2024Trial
- An update on the landscape of collagen bioactive fragments.The FEBS journal · 2026Review
- Circulating Endotrophin Predicts Myocardial Fibrosis Burden and Is Sensitive to Antifibrotic Therapy.JACC. Advances · 2026Article
- Circulating type I collagen pro-α1 chain is inversely associated with the presence of coronary atherosclerosis in a Swedish middle-aged population.Scientific reports · 2026Article
- Characterization of a novel assay for full-length endotrophin in heart failure with preserved ejection fraction.Scientific reports · 2026Article
- Targeting COL6A3-C5 with nigericin suppresses endotrophin formation and enhances insulin sensitivity in obesity.Experimental & molecular medicine · 2026Article
- Preventing hypocontractility-induced fibroblast expansion alleviates dilated cardiomyopathy.Science (New York, N.Y.) · 2025Article
- ETP-specific-knockout mice reveal endotrophin as a key regulator of kidney fibrosis in ischemia-reperfusion injury models.Experimental & molecular medicine · 2025Article
- Serum endotrophin relates to blood pressure in young South Asian women but not White women: evidence of ethnic variation in its early vascular implications.BMC cardiovascular disorders · 2025Article
- ECM formation and degradation during fibrosis, repair, and regeneration.npj metabolic health and disease · 2025Review
- Circulating collagen type I fragments as specific biomarkers of cardiovascular outcome risk: Where are the opportunities?Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.Nature genetics · 2025Article
- Plasma proteome-wide Mendelian randomization reveals the association of extracellular matrix proteins with abdominal aortic aneurysm.JVS-vascular science · 2025Article
- Proteomic Correlates and Prognostic Significance of Kidney Injury in Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2024Article
- Article
- Endotrophin, a Key Marker and Driver for Fibroinflammatory Disease.Endocrine reviews · 2024Review
- Cardiac and Renal Fibrosis, the Silent Killer in the Cardiovascular Continuum: An Up-to-Date.Journal of cardiovascular development and disease · 2024Review
- Macrophage profiling in atherosclerosis: understanding the unstable plaque.Basic research in cardiology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 10 institutions in 5 countries.
Funding
Abstract
backgroundEndotrophin, a collagen type VI-derived peptide, mediates metabolic dysregulation, inflammation, and fibrosis in animal models, but has not been studied in human heart failure (HF).
methodsWe examined the association between circulating endotrophin and outcomes in participants suffering from HF with preserved ejection fraction (HFpEF) enrolled in the TOPCAT trial (n=205). Associations were validated in a participant-level meta-analysis (n=810) that included participants with HFpEF from the PHFS study (United States; n=174), PEOPLE cohort (New Zealand; n=168), a randomized trial of vasodilator therapy (United States; n=45), a cohort from Donostia University Hospital and University of Navarra (Spain; n=171), and the TRAINING-HF trial (Spain; n=47). We also assessed associations in HF with reduced ejection fraction in PHFS (n=1,642).
resultsPlasma endotrophin levels at baseline were associated with risk of future death (standardized hazard ratio [HR] = 1.74; 95% confidence interval [CI]=1.36-2.24; P<0.001) and death or HF-related hospital admission (DHFA; standardized HR=2.11; 95% CI= 1.67-2.67; P<0.001) in TOPCAT. Endotrophin improved reclassification and discrimination for these outcomes beyond the MAGGIC risk score and NT-proBNP (N-terminal pro b-type natriuretic peptide). Findings were confirmed in the participant-level meta-analysis. In participants with HF with reduced ejection fraction in PHFS, endotrophin levels were associated with death (standardized HR=1.82; 95% CI=1.66-2.00; P<0.001) and DHFA (standardized HR=1.40; 95% CI=1.31-1.50; P<0.001), but the strength of the latter association was substantially lower than for the MAGGIC risk score (standardized HR=1.93; 95% CI=1.76-2.12) and BNP (standardized HR=1.78; 95% CI=1.66-1.92).
conclusionsCirculating endotrophin levels are independently associated with future poor outcomes in patients with HF, particularly in HFpEF. (Funded by Bristol Myers Squibb; Instituto de Salud Carlos III [Spain] and European Regional Development Fund; European Commission CRUCIAL project; and the U.S. National Institutes of Health National Heart, Lung, and Blood Institute.).
Identifiers
What Socratic 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 Socratic graph.