Prognostic value of Big Endothelin-1 in heart failure

Big Endothelin-1 (Big ET-1) is the precursor to the most potent vasoconstrictor peptide Endothelin-1 (ET-1), which is mainly produced by endothelial cells (1). Interestingly, there is evidence of stimulated ET-1 release from various immune cells, including macrophages and dendritic cells, indicating that these cells can also synthesize ET-1 (2).

While ET-1 is essential in regulating vascular tone and blood pressure, Big ET-1 itself is biologically inactive and mainly functions as a reservoir for ET-1. Big ET-1 has a longer half-life compared to ET-1 and circulates in equal molar amounts, making it a more stable and reliable biomarker (3). Elevated levels of Big ET-1 can signal vascular dysfunction and are linked to cardiovascular conditions such as hypertension and heart failure (4).

Prognostic value of Big Endothelin-1 in heart failure

A study recently explored the prognostic value of Big ET-1 in 4,368 patients hospitalized with heart failure with a median follow-up of 875 days (5).

Key findings:

• Elevated Big ET-1 was independently associated with cardiovascular death in patients with HF.
• Big ET-1 is a promising indicator of HF prognosis.

 

Big Endothelin-1 and NT-proBNP were measured with the following ELISA assay kits:

Big Endothelin-1 ELISA | BI-20082H

• Direct measurement – 50µl serum/plasma per well.
• High Quality – fully validated according to international quality guidelines
• Trusted – cited in over 90 publications
• Protocol booklet click here

 

NT-proBNP ELISA | SK-1204

• Convenient – ready -to-use reagents
• Flexible – can be run in every lab
• Two controls included
• High quality – fully validated according to international quality guidelines
• Trusted- cited in over 140 publications
• Protocol booklet click here

 

 

Literature

1. Endothelin-1 in Health and Disease. Banecki KMRM, Dora KA. Int J Mol Sci. 2023 Jul 10;24(14):11295. doi: 10.3390/ijms241411295. PMID: 37511055; PMCID: PMC10379484.
2. Endothelin-1 in Health and Disease. Banecki KMRM, Dora KA. Int J Mol Sci. 2023 Jul 10;24(14):11295. doi: 10.3390/ijms241411295. PMID: 37511055; PMCID: PMC10379484.
3. Biomarkers in aortic dissection. Wen D, Zhou XL, Li JJ, Hui RT. Clin Chim Acta. 2011 Apr 11;412(9-10):688-95. doi: 10.1016/j.cca.2010.12.039. Epub 2011 Jan 13. PMID: 21237193.
4. Plasma concentration of big endothelin-1 and its relation with plasma NT-proBNP and ventricular function in heart failure patients. Rivera M, Cortés R, Portolés M, Valero R, Sancho-Tello MJ, Martínez-Dolz L, Sevilla B, Taléns-Visconti R, Jordán A, Miró V, Pérez-Boscá JL, Marín F, Climent V, García de Burgos F, Payá R, Sogorb F, Bertomeu V, Salvador A. Rev Esp Cardiol. 2005 Mar;58(3):278-84. Spanish. PMID: 15766450.
5. Prognostic Value of Plasma Big Endothelin-1 in Patients Hospitalized for Heart Failure. Wang J, Feng J, Tse G, Zhai M, Huang Y, Zhou Q, Zhuang X, Liu H, Zhang Y, Zhang J. Korean Circ J. 2025 Aug;55(8):705-717. doi: 10.4070/kcj.2024.0354. Epub 2025 Apr 11. PMID: 40345830; PMCID: PMC12314060.  

 

 

Prognostic Value of Plasma Big Endothelin-1 in Patients Hospitalized for Heart Failure.

Abstract:

Background and objectives: Endothelin-1 (ET-1) is a potent vasoconstrictor and multifunctional neuroendocrine hormone that is closely associated with the pathophysiology of heart failure (HF). Currently, the evidence about the predictive value of big ET-1 in HF remains insufficient. This study aims to investigate the prognostic importance of big ET-1 in HF.

Methods: We examined the incidence of cardiovascular death in a single-center retrospective cohort of HF (de novo, worsening, or chronic included).

Results: The 4,368 hospitalized HF patients were enrolled. During the median follow-up of 875 (365-1,400) days, 851 (19.5%) patients had primary outcome events. Big ET-1 was independently associated with cardiovascular death as a continuous variable (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21; p<0.001) and by tertiles (HR, 1.35; 95% CI, 1.06-1.72; p=0.017 for tertile 2 and HR, 1.70; 95% CI, 1.32-2.19; p<0.001 for tertile 3). This pattern of risk was maintained after further adjustment for NT-proBNP (HR, 1.11; 95% CI, 1.03-1.19; p=0.006 for continuous variable, HR, 1.30; 95% CI, 1.02-1.67; p=0.035 for tertile 2, and HR, 1.69; 95% CI, 1.23-2.05; p=0.034 for tertile 3). Net reclassification index (NRI) and integrated discrimination improvement (IDI) analysis showed that big ET-1 provided additional predictive power in combination with NT-proBNP (NRI, 0.11; 95% CI, 0.04-0.17; p=0.012 and IDI, 0.012; 95% CI, 0.003-0.017; p<0.001).

Conclusions: Elevated big ET-1 was independently associated with cardiovascular death in patients with HF. Big ET-1 may be a promising indicator of HF prognosis. In combination with NT-proBNP, big ET-1 may provide incremental predictive information.