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Endothelin-1 Is a Prognostic Marker in Patients Undergoing Coronary Angiography

Key findings

  • Among patients undergoing diagnostic coronary angiography, higher concentrations of endothelin-1 (ET-1) were associated with worse left ventricular function and comorbidities that have been linked to CVD risk
  • Increased ET-1 concentrations did predict heart failure and all-cause mortality, even when adjusted for other prognostic biomarkers
  • ET-1 concentration did not predict the presence or extent of coronary atherosclerosis
  • Elevated ET-1 was accompanied by higher concentrations of several other prognostic biomarkers

Endothelin-1 (ET-1), a vasoconstrictor produced by vascular endothelial cells, is thought to have a central role in the pathogenesis of cardiovascular (CV) disease. Circulating ET-1 has been shown to be a prognostic marker in patients with heart failure (HF) or acute myocardial infarction (MI), and in a population-based study of African Americans, ET-1 concentrations predicted the risk of HF, pulmonary hypertension and death.

James L. Januzzi, Jr., MD, Hutter Professor of Medicine, Nasrien Ibrahim, MD, associate director of Resynchronization and Advanced Cardiac Therapeutics, and colleagues wondered about the prognostic value of ET-1 in a population typical of clinical practice: patients undergoing coronary angiography for various acute and non-acute cardiovascular indications. In Clinical Chemistry, they report that elevated ET-1 in such patients predicted HF and all-cause mortality and was associated with greater near-term risk of CV events.

Using data from the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) study conducted at Massachusetts General Hospital, which examined the value of various cardiac and renal biomarkers for predicting CV events, the researchers analyzed 1,084 patients who underwent diagnostic coronary angiography after having their ET-1 measured through a blood sample.

Follow-up was complete for all patients, with a maximum of six years. The median follow-up period was four years.

Patients with an ET-1 concentration above the median of 2.57 ng/L were significantly more likely than those with lower ET-1 concentrations to have a history of smoking, atrial fibrillation/flutter, hypertension, HF, peripheral artery disease, chronic obstructive pulmonary disease, diabetes or chronic kidney disease. They also had significantly worse left ventricular ejection fractions and significantly lower estimated glomerular filtration rates. In addition, four biomarkers of cardiac and renal function (high-sensitivity cardiac troponin T, N-terminal pro–B-type natriuretic peptide, cystatin C and ST2) were significantly elevated in patients with above-median ET-1.

After excluding 90 patients who had acute MI, the research team found that ET-1 concentration was not associated with the presence or severity of coronary artery disease. The team attributes this finding to the use of an assay that measures biologically active concentrations of ET-1, which tend to rise and fall substantially based on disease acuity.

The researchers then performed a regression analysis that adjusted for clinical variables and for prognostic biomarkers besides ET-1. The results showed that ET-1 concentration predicted new-onset HF and all-cause mortality, although not MI or CV mortality.

In cumulative hazard analyses, ET-1 at or above the median was associated with shorter time to a new diagnosis of HF, the first episode of MI, cardiovascular mortality, all-cause mortality and the composite of new-onset HF, first MI or cardiovascular mortality.

The researchers comment that future studies should examine whether patients with increased concentrations of ET-1 and other biomarkers may benefit from targeted interventions aimed at reducing their risk of CV events.

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