ABSTRACT
Background
We sought to determine whether circulating modifiers of endothelial function are associated
with cardiac structure and clinical outcomes in patients with heart failure with reduced
ejection fraction (HFrEF).
Methods
We measured 25 proteins related to endothelial function in 99 patients from the GUIDE-IT
study. Protein levels were evaluated for association with echocardiographic parameters
and the incidence of all-cause death and hospitalization for heart failure (HHF).
Results
Higher concentrations of angiopoietin 2 (ANGPT2), vascular endothelial growth factor
receptor 1 (VEGFR1) and hepatocyte growth factor (HGF) were significantly associated
with worse function and larger ventricular volumes. Over time, decreases in ANGPT2
and, to a lesser extent, VEGFR1 and HGF, were associated with improvements in cardiac
size and function. Individuals with higher concentrations of ANGPT2, VEGFR1 or HGF
had increased risks for a composite of death and HHF in the following year (HR 2.76
(95% CI 1.73–4.40) per 2-fold change in ANGPT2; HR 1.76 (95% CI 1.11–2.79) for VEGFR1;
and HR 4.04 (95% CI 2.19–7.44) for HGF).
Conclusions
Proteins related to endothelial function associate with cardiac size, cardiac function
and clinical outcomes in patients with HFrEF. These results support the concept that
endothelial function may be an important contributor to the progression to and the
recovery from HFrEF.
Graphical Abstract
Graphical Abstract
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Article info
Publication history
Published online: January 08, 2023
Accepted:
December 12,
2022
Received in revised form:
December 8,
2022
Received:
April 26,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
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- Angiogenesis markers and reverse remodeling in patients with HFrEFJournal of Cardiac Failure
- PreviewCardiac remodeling is a compensatory process, triggered by cardiac stress, preceding the onset of heart failure (HF). It involves a group of alterations on the molecular, cellular and interstitial levels that manifest clinically as changes in cardiac structure and function. Remodeling affects all cardiac tissue constituents, including cardiomyocytes, fibroblasts, endothelial cells, and immune cells.1 Cardiac remodeling is a dynamic process with either a worsening progress, that may lead to HF, called adverse remodeling and leading to a poor outcome or, conversely, a recovery in response to HF treatment termed reverse remodeling associated with a better outcome.
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