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. 2025 Jul;17(7):e70127.
doi: 10.1111/1753-0407.70127.

The Role of Endothelin-1, Kidney Function and Diabetes in Patients With Coronary Artery Disease Underwent Percutaneous Coronary Intervention

Zixiang Ye  1   2   3 , Enmin Xie  1   2   3 , Yuan Du  1   2   3 , Wenjia Zhang  1   2   3   4 , Kefei Dou  1   2   3   4
Affiliations

The Role of Endothelin-1, Kidney Function and Diabetes in Patients With Coronary Artery Disease Underwent Percutaneous Coronary Intervention

Zixiang Ye et al. J Diabetes. 2025 Jul.

Abstract

Objective: This study aimed to explore the association between plasma big endothelin-1 (ET-1) and major adverse cardiovascular events (MACE) in CAD patients who underwent PCI with a focus on the influence of kidney function and diabetes status in secondary prevention.

Methods: A prospective cohort of CAD patients underwent PCI and patients with impaired kidney function and diabetes were initially screened and categorized separately, subdivided based on ET-1 levels. The primary outcome was MACE, including all-cause mortality, nonfatal myocardial infarction, unplanned revascularization, and stroke. Statistical analyses included Cox regression, competing risks analysis (competing for non-cardiovascular death), and restricted cubic spline to assess the relationships between ET-1 and MACE.

Results: This study included 1344 CAD patients with impaired kidney function and 10,577 CAD patients with DM. During a median follow-up of 3 years, 20% of renal dysfunction patients and 12.9% of DM patients experienced MACE. In CAD patients with renal dysfunction, elevated ET-1 levels were associated with increased MACE risk (adjusted HR 1.333, 95% CI 1.169-1.519, p < 0.001), with those in the highest group and DM showing a 2.134-fold (95% CI, 1.334-3.413, p < 0.001) increased MACE risk. In CAD patients with DM, patients with eGFR ≤ 60 mL/min/1.73 m2 and elevated ET-1 levels had a 2.297-fold (95% CI 1.822-2.895) increased risk of MACE.

Conclusion: ET-1 offered important prognostic value for CAD patients who underwent PCI, with especially bad prognoses observed in those with elevated ET-1 levels, renal dysfunction, and DM.

Keywords: Endothelin‐1; coronary artery disease; diabetes mellitus; impaired kidney function; major adverse cardiovascular events.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart of CAD patient underwent PCI selection. ET‐1, Endothelin‐1; CAD, coronary artery disease; eGFR, estimated glomerular filtration rate; DM, diabetes mellitus; PCI, percutaneous coronary intervention.
FIGURE 2
FIGURE 2
The MACE risks in various CAD groups. (A) Incidence rate of MACE in CAD patients with impaired kidney function; (B) Incidence rate of MACE in CAD patients with DM. E1, low ET‐1 level; E2, medium ET‐1 level; E3, high ET‐1 level; DE1, non‐DM plus low ET‐1 level; DE2, non‐DM plus medium ET‐1 level; DE3, non‐DM plus high ET‐1 level; DE4, DM plus low ET‐1 level; DE5, DM plus medium ET‐1 level; DE6, DM plus high ET‐1 level. K1, eGFR ≥ 90 mL/min/1.73 m2; K2, eGFR 60–90 mL/min/1.73 m2; K3, eGFR ≤ 60 mL/min/1.73 m2; E1, low ET‐1 level; E2, medium ET‐1 level; E3, high ET‐1 level; KE1, eGFR ≥ 90 mL/min/1.73 m2 plus low ET‐1 level; KE2, eGFR ≥ 90 mL/min/1.73 m2 plus medium ET‐1 level; KE3, eGFR ≥ 90 mL/min/1.73 m2 plus high ET‐1 level; KE4, eGFR 60–90 mL/min/1.73 m2 plus low ET‐1 level; KE5, eGFR 0–90 mL/min/1.73 m2 plus medium ET‐1 level; KE6, eGFR 60–90 mL/min/1.73 m2 plus high ET‐1 level; KE7, eGFR ≤ 60 mL/min/1.73 m2 plus low ET‐1 level; KE8, eGFR ≤ 60 mL/min/1.73 m2 plus medium ET‐1 level; KE9, eGFR ≤ 60 mL/min/1.73 m2 plus high ET‐1 level. ET‐1, Endothelin‐1; MACE, major adverse cardiovascular events; DM, diabetes mellitus.
FIGURE 3
FIGURE 3
The Kaplan–Meier analysis for MACE in combined status of both DM and ET‐1 levels in CAD patients with impaired kidney function (A) and combined status of both kidney function and ET‐1 levels in CAD patients with DM. DE1, non‐DM plus low ET‐1 level; DE2, non‐DM plus medium ET‐1 level; DE3, non‐DM plus high ET‐1 level; DE4, DM plus low ET‐1 level; DE5, DM plus medium ET‐1 level; DE6, DM plus high ET‐1 level. KE1, eGFR ≥ 90 mL/min/1.73 m2 plus low ET‐1 level; KE2, eGFR ≥ 90 mL/min/1.73 m2 plus medium ET‐1 level; KE3, eGFR ≥ 90 mL/min/1.73 m2 plus high ET‐1 level; KE4, eGFR 60–90 mL/min/1.73 m2 plus low ET‐1 level; KE5, eGFR 0–90 mL/min/1.73 m2 plus medium ET‐1 level; KE6, eGFR 60–90 mL/min/1.73 m2 plus high ET‐1 level; KE7, eGFR ≤ 60 mL/min/1.73 m2 plus low ET‐1 level; KE8, eGFR ≤ 60 mL/min/1.73 m2 plus medium ET‐1 level; KE9, eGFR ≤ 60 mL/min/1.73 m2 plus high ET‐1 level. ET‐1, Endothelin‐1; MACE, major adverse cardiovascular events; DM, diabetes mellitus.
FIGURE 4
FIGURE 4
The restricted cubic spline analysis showed the relationships between ET‐1 and the risk of MACE in CAD patients with impaired kidney function. (A) MACE risk of CAD patients with impaired kidney function; (B) MACE risk of CAD patients with impaired kidney function in DM and non‐DM; (C) CV death risk of CAD patients with impaired kidney function in DM and non‐DM; (D) nonfatal MI risk of CAD patients with impaired kidney function in DM and non‐DM. ET‐1, Endothelin‐1; MACE, major adverse cardiovascular events; DM, diabetes mellitus; CV, cardiovascular; MI, myocardial infarction.
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