Soluble adhesion molecules and unstable coronary artery disease

Leukocyte adhesion and transendothelial migration, prerequisites in the development of atherosclerosis, are largely mediated by adhesion molecules. In addition, unstable coronary syndromes usually involve platelet activation and thrombus formation at the site of atherosclerotic plaque. Therefore, we compared plasma levels of soluble P-selectin, a measurement of platelet activation, as well as E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with atherosclerosis undergoing coronary angiography (n=76). Soluble P-selectin levels, as measured by ELISA, were significantly elevated in patients with unstable (n=44) vs stable (n=32) atherosclerotic disease (73.0 +/- 2.5 ng/ml vs 52.3 +/- 3.0 ng/ml, respectively, P<0.01). By logistic regression analysis, plasma level of soluble P-selectin was an independent predictor of an unstable coronary syndrome (OR 4.2, CI 1.4-12.9, P<0.01). Soluble E-selectin level, a marker of endothelial activation, was associated with extent of atherosclerosis but did not correlate with disease stability. Interestingly, soluble P-selectin was inversely correlated with plasma levels of the antioxidant alpha-tocopherol (R=-0.443, P<0.001), a known inhibitor of platelet function. In summary, amongst the soluble adhesion molecules, only P-selectin is significantly increased in patients with unstable coronary syndromes. This study suggests that platelet activation persists in patients with unstable coronary syndromes despite concurrent aspirin therapy. In addition, the beneficial effects of alpha-tocopherol in patients with cardiovascular disease may be related to inhibition of platelet function.