Back to Search Start Over

Endotrophin, a Collagen VI Formation-Derived Peptide, in Heart Failure.

Authors :
Chirinos, Julio A.
Zhao, Lei
Reese-Petersen, Alexander L.
Cohen, Jordana B.
Genovese, Federica
Richards, A. Mark
Doughty, Robert N.
Díez, Javier
González, Arantxa
Querejeta, Ramón
Zamani, Payman
Nuñez, Julio
Zhaoqing Wang
Ebert, Christina
Kammerhoff, Karl
Maranville, Joseph
Basso, Michael
Qian, Chenao
Rasmussen, Daniel G.K.
Schafer, Peter H.
Source :
NEJM Evidence; Oct2022, Vol. 1 Issue 10, p1-1, 1p
Publication Year :
2022

Abstract

Background: Endotrophin, 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). Methods: We 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). Results: Plasma 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). Conclusions: Circulating 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.) [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
27665526
Volume :
1
Issue :
10
Database :
Supplemental Index
Journal :
NEJM Evidence
Publication Type :
Academic Journal
Accession number :
162525885
Full Text :
https://doi.org/10.1056/EVIDoa2200091