Angiotensin II type 1 receptor antagonist decreases plasma levels of tumornecrosis factor alpha, interleukin-6 and soluble adhesion molecules in patients with chronic heart failure

OBJECTIVES To evaluate the effects of an angiotensin (Ang II) type 1 recept or antagonist on immune markers in patients with congestive heart failure ( CHF). BACKGROUND Ang II stimulates production of immune factors via the Ang II ty pe 1 receptor in vitro, and the long-term effects of Ang II type 1 receptor antagonists on plasma markers of immune activation are unknown in patients with CHF. METHODS Twenty-three patients with mild to moderate CHF with left ventricul ar dysfunction were randomly divided into mio groups: treatment with Ang II type 1 receptor (candesartan cilexetil) (n = 14) or placebo (n = 9). We me asured plasma levels of immune factors such as tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). We also measured plasma levels of the neurohumoral factors such as atrial natriure tic peptide (ANP) and brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP), a biological marker of ANP and BNP. RESULTS Plasma levels of TNFalpha, IL-6, sICAM-1 and sVCAM-1 were increased in the 23 CHF patients compared with normal subjects and significantly dec reased after 14 weeks of candesartan cilexetil treatment, but did not chang e in the placebo group. Plasma levels of BNP, which is a marker of ventricu lar injury, significantly decreased, and the molar ratio of plasma cGMP to cardiac natriuretic peptides (ANP + BNP) was significantly increased after candesartan cilexetil treatment, but did not change in the placebo group. CONCLUSIONS These findings suggest that 14 weeks of treatment with an Ang I I type 1 receptor antagonist (candesartan cilexetil) decreased plasma level s of the immune markers such as TNFalpha, IL-6, sICAM-1 and sVCAM-1 and tha t it improved the biological compensatory action of endogenous cardiac natr iuretic peptides in patients with mild to moderate CHF. (C) 2000 by the Ame rican College of Cardiology.