Differential hormonal profiles of adrenomedullin and proadrenomedullin N-terminal 20 peptide in patients with heart failure and effect of treatment on their plasma levels

Background:Adrenomedullin (AM) is a potent vasodilatory peptide discovered in human pheochromocytoma tissue. Proadrenomedullin N-terminal 20 peptide ( PAMP) processed from an AM precursor is also a novel hypotensive peptide wh ich inhibits catecholamine secretion from sympathetic nerve endings. Hypothesis: The present study sought to examine the relationships between t he two peptides and other clinical parameters by measuring the plasma AM an d PAMP concentrations in 98 patients with heart failure. Methods: In all, 98 patients [65 men and 33 women, aged 58.2 +/- 11.0 years , mean +/- standard deviation (SD)] with heart failure and 26 healthy volun teers (12 men and 14 women, aged 54.1 +/- 8.6 years) were examined in this study. Heart failure was secondary to previous myocardial infarction in 58 patients, valvular disease in 28, cardiomyopathy in 9, and congenital heart disease in 3. All patients were classified into two groups of class I or I I (Group 1) and class III or IV (Group 2) according to the New York Heart A ssociation (NYHA) functional classification. Results: Both plasma AM and PAMP concentrations in the patients were signif icantly higher than those in healthy volunteers. In addition, plasma AM and PAMP concentrations in patients in class III or IV of New York Heart Assoc iation (NYHA) classification were significantly higher than those in NYHA c lass I or II. The elevated plasma concentrations of these peptides in patie nts in NYHA class III or IV significantly decreased in response to the trea tment for 7 days. There was a significant correlation between plasma AM and PAMP, though the plasma concentration of PAMP was one-fifth to one-seventh of that of AM in patients and controls. The plasma AM concentration correl ated significantly with the plasma concentrations of atrial and brain natri uretic peptides, epinephrine, and right atrial pressure, whereas such a rel ationship was not noted for the plasma PAMP concentration. Conclusions: Judging from the difference in not only the biological actions but also the hormonal profiles between AM and PAMP, they may differentiall y modulate the cardiovascular system in patients with heart failure, althou gh they are processed from the same precursor.