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

In patients with coronary artery disease (CAD), azithromycin therapy is ass ociated with decreased cytokine levels and overall reduction of inflammatio n. Chlamydia pneumoniae (C.Pn) is a common pathogen that may be an importan t factor in the development and progression of atherosclerosis. Cell-adhesi on molecules have an important role in recruitment of inflammatory cells du ring plaque development and are expressed by endothelial cells on activatio n. We sought to define the effect of treatment with azithromycin on circula ting levels of soluble vascular cell-adhesion molecule (VCAM-1), intercellu lar 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 patie nts with documented CAD and a positive (greater than or equal to 1:16) immu noglobulin G (IgG) titer against C.Pn, 20 subjects with normal coronary art eries, and 14 healthy volunteers. Patients were assigned randomly to receiv e either 500 mg/wk of azithromycin or placebo for 3 months. Serum samples w ere 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 no t ICAM-1 (321 +/- 65 ng/ml) concentrations as compared with the patients wi th 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-I, and E-sel ectin. Soluble markers of endothelial activation are markedly increased in patients with documented CAD as compared with those with normal coronary ar teries and healthy controls. Despite substantial heterogeneity in plasma E- selectin, ICAM-1, and VCAM-1 levels, long-term azithromycin treatment did n ot affect plasma levels of these adhesion molecules, indicative of endothel ial activation, over a period of 6 months.