What does this research mean for the field?

Elevated plasma endothelin-1 levels increase the risk of major adverse cardiovascular events by 62.7% in coronary artery disease patients with impaired kidney function, and by 119.2% in those with diabetes. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

February 8, 2026

Validation of endothelin-1 as a predictor of adverse prognosis in coronary artery disease patients with impaired kidney function with or without diabetes

Key Result

In CAD patients with impaired kidney function, elevated endothelin-1 increased MACE risk (adjusted SHR 1.627), especially with diabetes (adjusted SHR 2.192).

Key Points

This research investigates the link between endothelin-1 levels and major adverse cardiovascular events in coronary artery disease patients with impaired kidney function, focusing on diabetes effects.
Conducted a prospective cohort study with 1,344 CAD patients having impaired kidney function.
Evaluated primary outcome, major adverse cardiovascular events (MACE), including mortality and revascularization.
Applied Cox regression and restricted cubic spline analysis to analyze the relationship between ET-1 levels and MACE.
Elevated ET-1 levels were significantly associated with a higher risk of MACE (adjusted SHR 1.627).
Diabetes patients exhibited a notably higher risk of MACE with high ET-1 levels (adjusted SHR 2.192).
Non-linear relationships between ET-1 and MACE were confirmed through subgroup analyses.

Structured PICO

Does elevated endothelin-1 predict major adverse cardiovascular events in coronary artery disease patients with impaired kidney function?

Population

1,344 coronary artery disease (CAD) patients with impaired kidney function

Intervention

Elevated plasma endothelin-1 (ET-1) levels

Comparator

Reference/lower endothelin-1 (ET-1) levels

Outcome

Major adverse cardiovascular events (MACE), including cardiovascular mortality, nonfatal myocardial infarction, unplanned revascularization, and strokecomposite

Elevated plasma endothelin-1 is a significant predictor of major adverse cardiovascular events in patients with coronary artery disease and impaired kidney function, particularly those with concurrent diabetes.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract Objective This study aimed to explore the association between endothelin-1 (ET-1) and major adverse cardiovascular events (MACE) in CAD patients with impaired kidney function with a focus on the influence of diabetes status. Methods A prospective cohort involved 1,344 CAD patients with impaired kidney function. The primary outcome was MACE, including cardiovascular 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 analysis to assess the relationships between ET-1 and MACE. Results ET-1 levels were substantially correlated with a higher risk of MACE (adjusted subdistribution hazard ratios SHR 1.627, 95% confidence interval CI 1.119-2.365). Notably, the risk of MACE was significantly higher in patients with diabetes and high ET-1 compared to reference (adjusted SHR 2.192; 95% CI 1.262-3.804). Non-linear relationships between ET-1 levels and MACE were observed, and subgroup analyses confirmed the robustness of the findings in acute coronary syndrome patients. Conclusion In CAD patients with impaired kidney function, elevated plasma ET-1 levels are related to a higher risk of MACE, particularly in those with diabetes. ET-1 might be a useful biomarker for therapeutic targeting and risk assessment in this high-risk group.

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