The effect of chronic azithromycin therapy on soluble endothelium-derived adhesion molecules in patients with coronary artery disease

Abstract

In patients with coronary artery disease (CAD), azithromycin therapy is associated with decreased cytokine levels and overall reduction of inflammation. Chlamydia pneumoniae (C.Pn) is a common pathogen that may be an important factor in the development and progression of atherosclerosis. Cell-adhesion molecules have an important role in recruitment of inflammatory cells during plaque development and are expressed by endothelial cells on activation. We sought to define the effect of treatment with azithromycin on circulating levels of soluble vascular cell-adhesion molecule (VCAM-I), intercellular adhesion molecule (ICAM-1), and E-selectin in patients with CAD. Plasma concentrations of VCAM-1, ICAM-1, and E-selectin were measured in 40 patients with documented CAD and a positive (> or = 1:16) immunoglobulin G (IgG) titer against C.Pn, 20 subjects with normal coronary arteries, and 14 healthy volunteers. Patients were assigned randomly to receive either 500 mg/wk of azithromycin or placebo for 3 months. Serum samples were obtained at baseline, at 3 months, and during the follow-up visit at 6 months. Patients with documented CAD exhibited elevation of VCAM-1 (535 +/- 227 ng/ ml; p = 0.0001) and E-selectin (69 +/- 29 ng/ml; p = 0.006), but not ICAM-1 (321 +/- 65 ng/ml) concentrations as compared with the patients with angiographically proven normal coronary arteries (252 +/- 80; 50 +/- 22; and 311 +/- 40 ng/ml) and healthy controls (110 +/- 18; 29 +/- 2; and 238 +/- 47 ng/ml, respectively). Prolonged treatment with azithromycin did not significantly affect the plasma levels of soluble VCAM-1, ICAM-1, and E-selectin. Soluble markers of endothelial activation are markedly increased in patients with documented CAD as compared with those with normal coronary arteries and healthy controls. Despite substantial heterogeneity in plasma E-selectin, ICAM-1, and VCAM-1 levels, long-term azithromycin treatment did not affect plasma levels of these adhesion molecules, indicative of endothelial activation, over a period of 6 months.