Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases

Abstract

Backgruound: Endothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in coronary artery disease (CAD) and diabetes. This study aimed to determine the prognostic value of ET-1 in the patients with stable CAD under different glucose metabolism states.

Methods: In this prospective, large-cohort study, we consecutively enrolled 7,947 participants with angiography-diagnosed stable CAD from April 2011 to April 2017. Patients were categorized by baseline glycemic status into three groups (normoglycemia, prediabetes, and diabetes) and further divided into nine groups by circulating ET-1 levels. Patients were followed for the occurrence of cardiovascular events (CVEs), including nonfatal myocardial infarction, stroke, and cardiovascular mortality.

Results: Of the 7,947 subjects, 3,352, 1,653, and 2,942 had normoglycemia, prediabetes, and diabetes, respectively. Over a median follow-up of 37.5 months, 381 (5.1%) CVEs occurred. The risk for CVEs was significantly higher in patients with elevated ET-1 levels after adjustment for potential confounders. When patients were categorized by both status of glucose metabolism and plasma ET-1 levels, the high ET-1 levels were associated with higher risk of CVEs in prediabetes (adjusted hazard ratio [HR], 2.089; 95% confidence interval [CI], 1.151 to 3.793) and diabetes (adjusted HR, 2.729; 95% CI, 1.623 to 4.588; both P<0.05).

Conclusion: The present study indicated that baseline plasma ET-1 levels were associated with the prognosis in prediabetic and diabetic patients with stable CAD, suggesting that ET-1 may be a valuable predictor in CAD patients with impaired glucose metabolism.

Keywords: Coronary artery disease; Diabetes mellitus; Endothelin-1; Prediabetic state; Prognosis.

Fig. 1.

Study flow chart. CAD, coronary artery disease; ACS, acute coronary syndrome; PCI, percutaneous coronary artery intervention; CABG, coronary artery bypass grafting.

Fig. 2.

The incident rates of cardiovascular events in different glucose metabolism status, endothelin-1 (ET-1) levels and status of both ET-1 levels and glycemic status. G1, normoglycemia; G2, prediabetes; G3, diabetes; E1, low ET-1 levels; E2, medium ET-1 levels; E3, high ET-1 levels; C1, normoglycemia+low ET-1 levels; C2, normoglycemia+medium ET-1 levels; C3, normoglycemia+ high ET-1 levels; C4, prediabetes+low ET-1 levels; C5, prediabetes+medium ET-1 levels; C6, prediabetes+high ET-1 levels; C7, diabetes+low ET-1 levels; C8, diabetes+medium ET-1 levels; C9, diabetes+high ET-1 levels.

Fig. 3.

The Kaplan-Meier analysis according to (A) glucose metabolism status, (B) endothelin-1 (ET-1) levels, and (C) status of both ET-1 levels and glycemic status.