Neurohormonal markers of clinical outcome in cardiovascular disease: is endothelin the best one?
Endothelin-1 (ET-1) is the most potent vasoconstrictor yet described. The active 21-amino-acid peptide is derived from the conversion of the inactive precursor "Big ET-1" by an enzyme called endothelin-converting enzyme. In addition to its potent action as a vasoconstrictor, endothelin promotes growth and proliferation of smooth muscle and myocardial hypertrophy. ET-1 levels are elevated in acute myocardial infarction (MI), atherosclerosis, renal failure, diabetes, pulmonary hypertension, and congestive heart failure (CHF). ET-1 levels correlate extremely well with the seriousness of the pathophysiologic condition. ET-1 levels at 72 h post MI accurately predict long-term survival. In patients with heart failure, ET-1 levels also predict long-term outcome, with the prognosis being severely compromised in patients with elevated ET-1 levels. Levels of plasma big ET-1 have been demonstrated to predict 1-year mortality and have been shown to be a better predictor of 1-year outcome than plasma atrial natriuretic peptide and norepinephrine, NYHA class, age, and echocardiographic left ventricular parameters. Although a small number of studies have reported beneficial effects of ACE inhibitors on ET-1 levels in animal models, most reports in humans have not found an effect of ACE inhibitors on ET-1 levels. Only one ACE inhibitor, fosinopril, has been shown to be effective in normalizing ET-1 levels in clinically relevant situations, such as the long-term study of patients with CHF. This observation may point to a superior role of fosinopril compared with other ACE inhibitors in CHF patients and may indicate beneficial effects of fosinopril beyond blood pressure control.
Monge
J C
JC
St. Michael's Hospital and University of Toronto, Ontario, Canada.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000097:blood* / Q000188:drug therapy; D019332:Endothelin-1 / Q000097:blood*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy; D006801:Humans; D011379:Prognosis; D017466:Receptors, Endothelin / Q000032:analysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D019332:Endothelin-1; D017466:Receptors, Endothelin