| Background:Endothelial dysfunction has been recognized as an important early step in the development of atherosclerosis. Endothelial dysfunction is featured by reduced bioavailability of vasodilators as well as inflammatory activity and is considered to be an important contributory factor for developing an acute coronary syndrome (ACS). It is a systemic condition, which is highlighted by the fact that coronary artery endothelial dysfunction correlates to dysfunction in the brachial artery. Microvascular dysfunction has been shown to increase risk of future cardiovascular events. Improvement of the microcirculation could therefore be an important factor to reduce the risk of cardiovascular disease.The platelet inhibitor ticagrelor is a potent adenosine diphosphate (ADP) P2Y12 receptor antagonist. In the PLATO (Platelet Inhibition and Patient Outcomes) study, ticagrelor was superior to clopidogrel with respect to cardiovascular outcomes and total death, without increasing the risk of bleeding. More potent and reversible receptor binding are possible advantages. Adverse effects of ticagrelor include ventricular pauses and dyspnea, which might be due to increased levels of adenosine, since these are commonly seen side effects of adenosine treatment.Ticagrelor has previously been demonstrated to increase adenosine levels by inhibiting adenosine reuptake in red blood cells. Furthermore, ticagrelor can induce adenosine triphosphate (ATP) release from human red blood cell. Extracellular adenosine and ATP both stimulate vasodilation, adenosine mainly via a direct dilatory effect of the vascular smooth muscle cell and ATP by stimulating the endothelium to release vasodilatory factors such as nitric oxide, endothelial hyperpolarizing factor, and prostacyclins.Objective:To investigate the protective effect of ticagrelor on peripheral vessel endothelial function in patients with acute coronary syndrome (ACS) using Doppler ultrasound.Methods:Among 122 patients diagnosed with ACS in department of cardiovasology, Xinhui hospital affiliated to Southern Medical University, during July 2013 to September 2014,81 patients were enrolled. Patients were randomly assigned to receive either on maintenance dose of aspirin with ticagrelor (TA group, n= 41) or clopidogrel (CA group, n= 40). Doppler ultrasound technique was applied to evaluate the internal diameter and blood flow at rest, flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), as well as the change of peak flow at 1st,3rd and 6th month after medication administration. ELISA test was applied to evaluated serum endothelin (ET-1) and nitric oxide (NO) during the follow-up. Additionally, drugs-related bleeding adverse events were recorded.Results:Compared with CA group, ticagrelor significantly improved FMD% (TA group vs. CA group:8.93±1.66% vs.6.22±1.89%, P<0.05) and the change of peak flow at 6th month after treatment (TA group vs. CA group:67.43±10.66% vs. 57.90±10.03%, P< 0.05), while no more remarkable improvements of the internal diameter (TA group vs. CA group:3.86±0.68mm vs.3.80±0.64mm, P>0.05) and blood flow at rest (TA group vs. CA group:84.74±32.81 ml/min vs.82.45±30.15 ml/min, P>0.05), as well as NMD%(TA group vs. CA group:18.15±4.01% vs. 18.13±3.98%, P>0.05) were observe. Serum ET-1 in TA group was significantly decreased and NO was significantly increased than CA group at 3rd (ET-1:TA group vs. CA group:41.85±19.55 pg/ml vs.50.78±19.02 pg/ml, P<0.05; NO:TA group vs. CA group:74.61±9.67μmol/L vs.66.55±9.02μmol/L, P<0.05) and 6th month (ET-1:TA group vs. CA group:27.56±14.05 pg/ml vs.36.18±14.51 pg/ml, P<0.05; NO:TA group vs. CA group:92.54± 9.44μmol/L vs.83.08±9.68μmol/L, P<0.05) after treatment. No significance in drugs-related bleeding adverse events during the follow-up between two groups(P>0.05).Conclusion:1. Both ticagrelor and clopidogrel can improve peripheral vessel endothelial-dependent dilation function after a 6-month treatment, and the protective effect of ticagrelor is superior to clopidogrel. However, neither ticagrelor nor clopidogrel plays a positive role on peripheral vessel non-endothelial-dependent dilation function.2. Treatment with ticagrelor improves peripheral vessel endothelial-dependent dilation function, suggesting a protective effect might benefit the patients with ACS. |
