Clinical Study On Aspirin Resistance In Patients With Coronary Heart Disease During The Early Reatment Of Low-dose Aspirin

Background and objectives:Coronary heart disease (CHD) is caused by coronary atherosclerosis inducing vascular stenosis or obstruction, because they change the coronary artery function leading to myocardial hypoxia and ischemia or myocardial infarction. Although the incidence of CHD in our country is less than that in Europe and the United States, we can find a growing trend in that the proportion of CHD increased among hospitalized patients with heart disease in recent years. It has been demonstrated that the activation and aggregation of platelets may play an important role in the occurrence and development of coronary atherosclerosis and thrombosis.Currently, aspirin is the most widely prescribed drug to anti-platelet aggregation effectively. It may inactive cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) respectively mainly through the irreversible inactivation of platelet cyclooxygenase (COX) and further acetylation modification of the active site of serine residues (Ser529, Ser516) irreversible, which can inhibit the generation of thromboxane A2(TXA2), antagonize platelet aggregation, prevent the thrombosis, and reduce the cardiovascular events. However, there are still some thromboembolic events in patients undergoing aspirin treatment, this phenomenon was known as the "aspirin resistance" (AR), which including, (1) occurrence of vascular thrombotic complications, (2)failure to prolong bleeding time, (3)platelet function did not reach the expected effect in vivo tests. Aspirin resistance is judged by laboratary standard abroad:the rates of platelet aggregation (PAG) induced by 10 Pmol/L adenosine diphosphate (ADP)≥70% and PAG induced by 0.5 mmol/L arachidonic acid (AA)≥20%. If meeting both of the above criteria,it is identified as "aspirin resistance" (AR), while meeting only one of them, it is identified as "aspirin semi-resistance" (ASR).About aspirin resistance (AR) in CHD, domestic and foreign scholars mainly focus on the study of incidence of AR with different doses of aspirin and the related factors of AR. There has been studied on AR for over 10 years abroad, but its internal generating mechanism has not been clarified completely.It is extremely rare to have the related study on detection index for early recognition AR in CHD patients during the treatment of aspirin.This study was designed to explore the correlation between aspirin resistance (AR) in patients with CHD and thromboxane B2 (TXB2), platelet membrane glycoprotein GPⅡb/Ⅲa and CD62p, which can provide baseline information for patients with CHD undergoing aspirin treatment to discover aspirin resistance (AR) early, and to guide the adjustment of anti-platelet therapy.Methods: Before and after 2 weeks'aspirin treatment, flow cytometry (FCM) and enzyme-linked immunosorbent assay (ELISA) were used respectively to detecte the expressions of platelet membrane glycoprotein CD62p and GP II b/IIIa as well as the levels of plasma TXB2 in healthy persons (NC group, n=20) and CHD inpatients (CHD group, n=92) being treated with low-dose aspirin (100mg, qd) in cardiovascular department. Inpatients were diagnosed as stable angina pectoris according to the results of coronary angiography. PAG induced by ADP or AA was determinated by turbidimetry. We judged "aspirin resistance"(AR) in general standard:PAG induced by 10μmol/L ADP≥70% and PAG induced by 0.5 mmol/L AA＞20%. Data was analysed by using SPSS 10.0 software.Results:1. The levels of plasma TXB2 in CHD patients (n=92) treated with aspirin for 2 weeks were significantly lower than those in the same group before treatment (P＜0.01), but still higher than those in the normal controls (n=20) (P＜0.01). Aspirin-resistant patients were found in 8 (8.7%) patients among 92 patients with CHD and 84 (91.3%) patients were aspirin-sensitive. The levels of plasma TXB2 in aspirin-resistant subgroup were higher than those in the aspirin-sensitive subgroup (P＜0.01).2. The platelet numbers of CD62p-positive or GP II b/IIIa-positive expression in patients with CHD (n=92) before treatment were significantly higher than those in normal controls (n=20) (P＜0.01). After 2 weeks'aspirin treatment, the platelet numbers of CD62p-positive or GPⅡb/Ⅲa-positive expression in patients with CHD were significantly lower than those in the same group before treatment (P＜0.01), but still higher than those in the normal controls (P＜0.01). The platelet numbers of GPⅡb/Ⅲa-positive expression in aspirin-resistant subgroup were higher than those in aspirin-sensitive subgroup (P＜0.01).Conclusions:1. The activation and aggregation of platelet may play an important role in the pathogenesis of coronary heart disease (CHD) while aspirin can inhibit the activation and aggregation of platelet in patients with coronary heart disease (CHD) to a certain extent.2. The incidence of aspirin resistance (AR) is 8.7% in patients with coronary heart disease (CHD) after 2 weeks'treatment of low-dose aspirin (100 mg/d).3. The levels of plasma TXB2 or the platelet numbers of GPⅡb/Ⅲa-positive expression in patients may be used as a predicator for early identification of aspirin resistance (AR) in patients with coronary heart disease (CHD) during the treatment of low-dose aspirin (100 mg/d).