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

Front Cardiovasc Med. 2022 May 26:9:854107. doi: 10.3389/fcvm.2022.854107. eCollection 2022.


Background: Patients with diabetes are a high-risk group for coronary in-stent restenosis (ISR), so it would be valuable to identify biomarkers to predict their prognosis. The plasma big endothelin-1 (big ET-1) level is closely related to cardiovascular adverse events; however, for patients with ISR and diabetes who undergo percutaneous coronary intervention (PCI), whether big ET-1 is independently correlated with prognosis is still uncertain.

Methods: Patients with drug-eluting stent (DES) restenosis who underwent successful re-PCI from January 2017 to December 2018 at the Chinese Academy of Medical Sciences Fuwai Hospital were enrolled and followed up for 3 years. The patients were divided into the tertiles of baseline big ET-1. The primary end points were major adverse cardiovascular events (MACEs): cardiac death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), and stroke. A Cox multivariate proportional hazard model and the C-statistic were used to evaluate the potential predictive value of big ET-1 beyond traditional and angiographic risk factors.

Results: A total of 1,574 patients with ISR were included in this study, of whom 795 were diabetic. In patients with ISR and diabetes, after an average follow-up of 2.96 ± 0.56 years, with the first tertile of big ET-1 as a reference, the hazard ratio [HR] (95% CI) of MACEs after adjustment for traditional and angiographic risk factors was 1.24 (0.51-3.05) for the second tertile and 2.60 (1.16-5.81) for the third. Big ET-1 improved the predictive value for MACEs over traditional risk factors (C-statistic: 0.64 vs. 0.60, p = 0.03). Big ET-1 was not significantly associated with the risk of MACEs in patients without diabetes.

Conclusion: Increased plasma big ET-1 was associated with a higher risk of adverse cardiovascular prognosis independent of traditional and angiographic risk factors, and therefore, it might be used as a predictive biomarker, in patients with ISR and diabetes.

Keywords: big endothelin-1 (big ET-1); cardiovascular prognosis; coronay artery disease; diabetes mellitus; in-stent restenosis.