The significance of circulating endothelin-1 as a predictor of coronary artery disease status and clinical outcomes following coronary artery catheterization

Abstract

Background/objectives: Coronary artery disease (CAD) is responsible for significant morbidity and mortality. Inflammatory, pro-thrombotic and structural factors contribute to the etiology of CAD. This study sought to determine the relationship of plasma endothelin-1 (pET-1), a potent vasoconstrictor, mitogen and modulator of cardiac inflammation, to clinical characteristics and outcomes of CAD patients.

Methods: Blood samples were collected from 336 patients with underlying chest pain or recent myocardial infarction (MI), prior to coronary catheterization. pET-1 was correlated with clinical characteristics and outcomes following catheterization and at 30-day follow-up.

Results: pET-1 was higher in recent MI patients than in patients with CAD (coronary occlusion≥50%) or without CAD (<50%) (Mean±sem (pg/ml): 2.12±0.13, 1.51±0.10, 1.21±0.06; 95% confidence interval (1.85-2.38, 1.31-1.72, 1.07-1.32; respectively, P<.0001). Patients with ST elevation MI (STEMI) had higher pET-1 than non-STEMI (P=.008). pET-1 was associated with heart failure (HF) and low left ventricular ejection fraction (LVEF) and was highest in MI patients presented with acute HF. At 30-day follow up, pET-1 was not associated with the change in LVEF. In multivariate analysis, pET-1 was positively associated with age, smoking, HF, CAD status, and need for revascularization by coronary artery bypass surgery (CABG). pET-1 was negatively correlated with LVEF and preoperative statin use.

Conclusions: pET-1 is associated with recent MI, HF, age, smoking, CABG, and low LVEF. Preoperative statin use was associated with lower pET-1. pET-1 may serve as a risk marker and a potential therapeutic target in CAD patients.

Keywords: Coronary artery disease; Endothelin-1; Myocardial infarction.

Figure 1

Plasma ET-1 among patients with coronary artery disease. a) Plasma levels of ET-1 in patients with CAD<50%, CAD≥50%, and recent MI. * P<.01 CAD≥50% vs. CAD<50%, ***P<.0001 MI vs. CAD≥&<50%, Kruskal Wallis/Dunns post-test). b) Plasma ET-1 among patients with no heart failure (HF), chronic HF, and acute HF, **P<.001 chronic HF vs. no HF, ***P<.0001 acute HF vs. no HF (Kruskil Wallis/Dunns post-test). c) Plasma ET-1 among MI patients with/without acute HF. d) Plasma ET-1 in patients with STEMI and non-STEMI.