Relationship between endothelial dysfunction, oxidant stress and aspirin resistance in patients with stable coronary heart disease

Abstract

Interindividual variability of platelet inhibition after aspirin administration has been described. Additionally, aspirin resistance occurs in some individuals, but the mechanism for aspirin resistance is still unknown. The aim of the present study was to examine the role of endothelial dysfunction in aspirin resistance. The antiplatelet effect of aspirin was studied prospectively in 54 consecutive patients with stable coronary heart disease. Platelet aggregation rate was measured and aspirin resistance was defined by a relative inhibition of adenosine diphosphate (5 micromol/L)-induced platelet aggregation of >or=70%. Thrombomodulin (TM) and free tissue factor pathway inhibitor (TFPI) were measured as endothelial dysfunction markers. Erythrocyte superoxide dismutase activity, plasma level of vitamin C, vitamin E and lipoperoxide were measured to estimate the oxidative stress. Platelet aggregation was positively correlated with TM (r = 0.277, P < 0.05) and TFPI (r = 0.288, P < 0.05) respectively. The TFPI level in aspirin-resistant patients (119.5 +/- 13.5 ng/mL) was significantly higher than that in aspirin-sensitive patients (107.8 +/- 18.9 ng/mL; P < 0.05). There were no statistically significant differences on any indicator of oxidative stress between two groups. Endothelial dysfunction is one of the mechanisms for aspirin resistance, whereas oxidative stress may not involve in the process of aspirin resistance.