Big Endothelin-1 associated with all-cause death in diabetes patients with CAD

High big ET-1 levels are associated with risk of all–cause death in diabetes patients with CAD

Big Endothelin-1 associated with all-cause death in diabetes patients with CAD

A clinical study in 8550 patients investigated the association between the cardio-vascular marker big endothelin-1 (big ET-1) and long-term all-cause death in patients with coronary artery disease (CAD) and impaired glucose metabolism.

Patients were categorized into both glucose status (diabetes mellitus, pre-diabetes mellitus, normalglycemia) and big ET-1 level groups. Primary endpoint was all-cause death. The data indicate that baseline big ET-1 levels were independently associated with the long-term mortality in diabetes patients with CAD.

Read more Big Endothelin-1 associated with all-cause death in diabetes patients with CAD.

What is Big Endothelin-1 (Big ET-1) ?

Big ET-1 is a 38 amino acid peptide and is the precursor of Endothelin-1 (ET-1). ET-1 is a potent vasoconstrictor secreted by endothelial cells. It acts as the counterpart of the vasodilator nitric oxide (NO).

• ET-1 is cleaved from Big ET-1 by the ET converting enzyme -1 (ECE-1).

• Both the precursor Big ET-1 and the shorter 21 aminoacid vasoactive form Endothelin-1 circulate in blood.

• ET-1, the biologically active form, is rapidly cleared and has a short half-life.

• ET-1 and big ET-1 are found in equimolar concentrations in the plasma.

• Thus, the longer half-life of big ET-1, its slower clearance and the findings that increased plasma levels of ET-1 in patients with heart failure are mainly due to an increase in big ET-1 concentrations, offers an analytical window for the measurement of Big ET-1 .

How can you measure Big ET-1?

Big ET-1 can easily be measured using  in serum and plasma with only 50µl sample volume.

Biomedica’s Big ET-1 ELISA cat. no. BI-20082H

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Related publications – Citations Big ET-1 ELISA – Biomedica

The Biomedica Big Endothelin-1 (Big ET-1) ELISA kit was utilized in the following studies:

Big Endothelin-1 and long-term all-cause death in patients with coronary artery disease and prediabetes or diabetes after percutaneous coronary intervention

Xu N, Zhu P, Yao Y, Jiang L, Jia S, Yuan D, Xu J, Wang H, Song Y, Gao L, Gao Z, Song L, Zhao X, Chen J, Yang Y, Xu B, Gao R, Yuan J. Nutr Metab Cardiovasc Dis. 2022 Sep;32(9):2147-2156. doi: 10.1016/j.numecd.2022.06.002. Epub 2022 Jun 11. PMID: 35843800.

Abstract

Background and aims: The present study aimed to examine the association between big endothelin-1 (big ET-1) and long-term all-cause death in patients with coronary artery disease (CAD) and different glucose metabolism status.

Methods and results: We consecutively enrolled 8550 patients from January 2013 to December 2013. Patients were categorized according to both status of glucose metabolism status [Diabetes Mellitus (DM), Pre-Diabetes (Pre-DM), Normoglycemia (NG)] and big ET-1 levels. Primary endpoint was all-cause death. During a median of 5.1-year follow-up periods, 301 all-cause deaths occurred. Elevated big ET-1 was significantly associated with long-term all-cause death (adjusted HR: 2.230, 95%CI 1.629-3.051; p < 0.001). Similarly, patients with DM, but not Pre-DM, had increased risk of all-cause death compared with NG group (p < 0.05). When patients were categorized by both status of glucose metabolism and big ET-1 levels, high big ET-1 were associated with significantly higher risk of all-cause death in Pre-DM (adjusted HR: 2.442, 95% CI 1.039-5.740; p = 0.041) and DM (adjusted HR: 3.162, 95% CI 1.376-7.269; p = 0.007). The Kaplan-Meier curve indicated that DM patients with the highest big ET-1 levels were associated with the greatest risk of all-cause death (p < 0.05).

Conclusions: The present data indicate that baseline big ET-1 levels were independently associated with the long-term all-cause death in DM and Pre-DM patients with CAD undergoing PCI, suggesting that big ET-1 may be a valuable marker in patients with impaired glucose metabolism.

Predictive Value of Plasma Big Endothelin-1 in Adverse Events of Patients With Coronary Artery Restenosis and Diabetes Mellitus: Beyond Traditional and Angiographic Risk Factors. Ma Y, Tian T, Wang T, Wang J, Guan H, Yuan J, Song L, Yang W, Qiao S. Front Cardiovasc Med. 2022 May 26;9:854107. doi: 10.3389/fcvm.2022.854107. PMID: 35694656; PMCID: PMC9177997.

Big Endothelin-1 and long-term all-cause death in patients with coronary artery disease and prediabetes or diabetes after percutaneous coronary intervention . Xu N, Zhu P, Yao Y, Jiang L, Jia S, Yuan D, Xu J, Wang H, Song Y, Gao L, Gao Z, Song L, Zhao X, Chen J, Yang Y, Xu B, Gao R, Yuan J. Nutr Metab Cardiovasc Dis. 2022 Sep;32(9):2147-2156. doi: 10.1016/j.numecd.2022.06.002. Epub 2022 Jun 11. PMID: 35843800.

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.

Plasma big endothelin-1 concentrations in congestive heart failure patients with or without systemic hypertension. Pacher R, Bergler-Klein J, Globits S, Teufelsbauer H, Schuller M, Krauter A, Ogris E, Rödler S, Wutte M, Hartter E. Am J Cardiol. 1993 Jun 1;71(15):1293-9. doi: 10.1016/0002-9149(93)90543-l. PMID: 8498369.

Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: A cohort study in patients with stable coronary artery disease. Zhou BY, Guo YL, Wu NQ, Zhu CG, Gao Y, Qing P, Li XL, Wang Y, Dong Q, Liu G, Xu RX, Cui CJ, Sun J, Li JJ. Int J Cardiol. 2017 Mar 1;230:76-79. doi: 10.1016/j.ijcard.2016.12.082. Epub 2016 Dec 21. PMID: 28038820.

Background: Big endothelin-1 (ET-1) has been proposed as a novel prognostic indicator of acute coronary syndrome, while its predicting role of cardiovascular outcomes in patients with stable coronary artery disease (CAD) is unclear.

Methods and results: A total of 3154 consecutive patients with stable CAD were enrolled and followed up for 24months. The outcomes included all-cause death, non-fatal myocardial infarction, stroke and unplanned revascularization (percutaneous coronary intervention and coronary artery bypass grafting). Baseline big ET-1 was measured using sandwich enzyme immunoassay method. Cox proportional hazard regression analysis and Kaplan-Meier analysis were used to evaluate the prognostic value of big ET-1 on cardiovascular outcomes. One hundred and eighty-nine (5.99%) events occurred during follow-up. Patients were divided into two groups: events group (n=189) and non-events group (n=2965). The results indicated that the events group had higher levels of big ET-1 compared to non-events group. Multivariable Cox proportional hazard regression analysis showed that big ET-1 was positively and statistically correlated with clinical outcomes (Hazard Ratio: 1.656, 95% confidence interval: 1.099-2.496, p=0.016). Additionally, the Kaplan-Meier analysis revealed that patients with higher big ET-1 presented lower event-free survival (p=0.016).

Conclusions: The present study firstly suggests that big ET-1 is an independent risk marker of cardiovascular outcomes in patients with stable CAD. And more studies are needed to confirm our findings.

Superiority of big endothelin-1 and endothelin-1 over natriuretic peptides in predicting survival in severe congestive heart failure: a 7-year follow-up study. Van Beneden R, Gurné O, Selvais PL, Ahn SA, Robert AR, Ketelslegers JM, Pouleur HG, Rousseau MF. J Card Fail. 2004 Dec;10(6):490-5. doi: 10.1016/j.cardfail.2004.04.001. PMID: 15599839.