Abstract:Dual antiplatelet therapy is the cornerstone of antithrombotic therapy in patients with acute coronary syndrome. Aspirin and P2Y12 receptor antagonists are commonly used antiplatelet drugs in clinic. At present, new P2Y12 receptor antagonists, especially ticagrelor monotherapy, are the subject of in-depth research in the field of antiplatelet optimization therapy. Studies have found that P2Y12 receptor antagonists can reduce thromboxane A2 receptor expression and thromboxane A2 production in platelets. Ticagrelor has broad-spectrum antiplatelet mechanism. This article summarizes the relevant research on the antiplatelet mechanism of new P2Y12 receptor antagonists, especially ticagrelor, and proposes new ideas for optimizing antiplatelet therapy.

Abstract:Aim To investigate the effect of obstructive sleep apnea syndrome (OSAS) on peripheral blood C1q level in patients with unstable angina pectoris (UAP) and its correlation with platelet aggregation rate (PAR) after percutaneous coronary intervention (PCI). Methods 182 patients with UAP who underwent PCI treatment in Beijing Anzhen Hospital from July 2018 to July 2019 were continuously selected. All patients underwent polysomnography. Patients with apnea hypopnea index (AHI)≥15 were taken as the OSAS group (n＝92), and patients with AHI＜15 were taken as the control group (n＝90). Serum C1q level and adenosine diphosphate induced PAR were detected. The relationship between AHI, serum C1q and PAR was analyzed. Results The serum C1q level in OSAS group was significantly higher than that in control group (176.00 (174.8,9.26) mg/L vs 174.50 (167.5,0.76) mg/L, P＝0.030). One month after PCI, PAR in OSAS group was significantly higher than that in control group ((51.36%±19.34%) vs (42.56%±22.23%), P＝0.007). Spearman correlation analysis showed that AHI and serum C1q were positively correlated with PAR (r＝0.219, P＝0.003; r＝0.634, P＜0.001). Multivariable linear regression analysis showed that AHI and serum C1q were independent factors influencing the increase of PAR after PCI (P＝0.036; P＜0.001). Conclusions Serum C1q is significantly increased in UAP patients with OSAS. AHI and C1q are the influencing factors of high platelet reactivity in UAP patients with OSAS one month after PCI.

Abstract:Aim To investigate the efficacy and safety of bivalirudin during percutaneous coronary intervention (PCI) for patients with acute coronary syndrome and high bleeding risk. Methods 108 patients with acute coronary syndrome and high bleeding risk and receiving PCI treatment were randomly divided into test group (bivalirudin group) and control group (heparin group), 54 cases in each group. TIMI blood flow, activated coagulation time (ACT), platelet count, platelet aggregation rate, high-sensitivity C-reactive protein (hs-CRP) and interleukin-4 (IL-4), 30-days bleeding events and major adverse cardiovascular events (MACE) were compared between the test group and the control group before and after operation. Results There was no significant difference in TIMI blood flow between the test group and the control group. The ACT compliance rate, platelet count, platelet aggregation rate, hs-CRP, IL-4 and other indicators in the test group were significantly better than those in the control group, and the differences were statistically significant (P＜0.05). The incidences of hemorrhagic events and MACE in the test group were significantly lower than those in the control group, and the differences were statistically significant (P＜0.05). Conclusion The application of bivalirudin during PCI for patients with acute coronary syndrome and high bleeding risk can significantly reduce the incidences of bleeding events and MACE, and has good safety.

Abstract:Aim To evaluate the clinical efficacy and safety of ticagrelors antiplatelet therapy for patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing direct percutaneous coronary intervention (PCI).Methods A total of 164 patients diagnosed with STEMI who underwent direct PCI was randomly divided into two groups:ticagrelor group (40 cases) and clopidogrel group (124 cases). According to the results of platelet aggregation rate on the fifth day after treatment, clopidogrel group was divided into two subgroups:non-clopidogrel resistance (CPGR) group (81 cases) and CPGR group (43 cases). The patients in group CPGR were changed to oral administration of ticagrelor. The patients were followed up for 3 months. 5 days, 1 month, 3 months after medication, platelet aggregation rate, main adverse cardiovascular events (MACE) (including cardiac death, nonfatal myocardial infarction, stroke, revascularization of target vessels, stent thrombosis, recurrent angina pectoris, cardiac insufficiency) and adverse drug reactions (including haemorrhage and dyspnea) were analyzed and compared between ticagrelor group and non-CPGR group. Change of platelet aggregation rate before and after the change of medicine was analyzed in CPGR group. Results Platelet aggregation rates in ticagrelor group were significantly lower than that in non-CPGR group at 5 days, 1 month and 3 months after treatment (33.94%±14.90% vs 53.13%±14.07%, 25.26%±8.89% vs 35.51%±9.45%, 24.91%±7.55% vs 31.57%±9.53%), and differences were statistically significant (P＜0.05). In CPGR group, the platelet aggregation rate decreased significantly after 1 months change to ticagrelor (28.33%±8.11% vs 64.50%±11.38%), and difference was statistically significant (t＝18.944, P＜0.05). Followed up for 3 months, the incidences of MACE and mild to moderate dyspnea in ticagrelor group were significantly lower than those in non-CPGR group, and the differences were statistically significant (P＜0.05). There was no significant difference in mild bleeding between the two groups (P＞0.05). There were no severe bleeding and severe dyspnea in the two groups. Conclusion The antiplatelet effect of ticagrelor is superior to clopidogrel, and it is safe and effective for CPGR patients with mild adverse reactions and good safety.

Abstract:Aim To detect the plasma AnnexinⅤexpression rate in elderly patients with acute coronary syndrome (ACS), and explore the correlation between AnnexinⅤexpression rate and cardiovascuar risk factors, fibrinogen (FIB), D-dimer, platelet aggregation rate (PAR). Methods 156 patients who were successfully examined by coronary angiography were recruited in our hospital from December 2014 to May 2016. These patients were divided into ACS group (n＝88), stable angina pectoris (SAP) group (n＝36) and control group (n＝32). The AnnexinⅤexpression rate and PAR were detected by flow cytometry instrument, the levels of FIB and D-dimer were detected by immunofluorescence method determination. Detailed information were recorded in age, history of smoking, diabetes, hypertension and so on.Different groups were compared to analyse the correlation between the AnnexinⅤexpression rate and cardiovascuar risk factors, FIB, D-dimer, PAR. Results The differences of AnnexinⅤexpression rate in ACS group were statistically significant compared with SAP group and control group (P＜0.05 or P＜0.01), but there was no statistically significant difference between SAP group and control group (P＝0.487). When the area under the ROC curve (AUC) was 0.876, the cut-off point was 29.36%, the sensitivity and specificity of diagnosis of ACS were 80.1% and 79.9%. The AnnexinⅤexpression rate in ACS group had a positive correlation with plasma FIB (r＝0.468, P＝0.047), D-dimer (r＝0.451, P＝0.040), PAR (r＝0.531, P＝0.010), smoking (r＝0.510, P＝0.009), hypertension (r＝0.506, P＝0.012) and diabetes (r＝0.493, P＝0.026). Conclusion The plasma AnnexinⅤexpression rate in elderly patients with ACS were positively correlated with diabetes, hypertension, smoking, FIB, D-dimer and PAR, which may be helpful to predict the occurrence and clinical risk of ACS.

Abstract:Aim To investigate the clinical factors which influence platelet aggregation function in patients after percutaneous coronary intervention(PCI). Methods A retrospective study was conducted on 266 patients with coronary heart disease which underwent PCI. All patients were treated with clopidogrel and aspirin dual anti-platelet therapy and standard medication. Patients were divided into 0%~29%, 30%~49%, 50%~69%, 70%~100% groups according to the adenosine diphosphate(ADP)-induced platelet aggregation rate(PAR). The CYP2C19 genotypes, general clinical information, lab indexes and coronary artery lesions after PCI were compared among the four groups. Risk factors of elevated PAR were explored by logistic regression analysis. Results There were significant differences in gender ratio, age, brain natriuretic peptide(BNP), CYP2C19 genotype among four groups of PAR(P<0.05). Logistic regression analysis revealed that female(OR=2.713, P=0.027), higher BNP(OR=1.002, P=0.007), slow metabolism genotype(OR=5.159, P<0.001) were risk factors for PAR≥50%; and female(OR=5.716, P=0.008), slow metabolism genotype(OR=3.149, P=0.049) was independent risk factor for PAR ≥70%. Conclusion Majority of patients with PAR<50% were fast metabolism genotype, and patients with slow metabolism genotype usually had PAR more than 50%; CYP2C19 polymorphism had strong impact to PAR. In addition, female and higher BNP might be risk factors of elevated PAR in patients with coronary heart disease after PCI.

Abstract:Aim To access the antithrombotic effect of Ticagrelor and Clopidogrel in diabetic coronary atherosclerotic heart disease and further illustrate the role of serum advanced glycation end products(AGE) in treatment. Methods 120 patients suffered from diabetic coronary atherosclerotic heart disease hospitalized for percutaneous coronary intervention(PCI) in the department of cardiology, affiliated hospital of Jiangsu university were recruited from October 2014 to February 2017. They were randomly divided into two groups. Each group was provided with Clopidogrel and Ticagrelor, respectively. To compare the effect of anti-platelet therapy, platelet aggregation rates were measured via flow cytometry before and after double anti-platelet therapy. And platelet inhibition rate induced by arachidonic acid (AA) and adenosine diphosphate (ADP) pathway was measured by thrombus elastography. The levels of serum advanced glycation endproducts (AGE) were measured by ELISA. After treatment of 6 months, the occurrence of bleeding events and ischemic events were followed up in the two groups. Results The platelet aggregation rate of Ticagrelor group was significantly 14.09% lower than that of the Clopidogrel group ((35.92±7.57)% vs (41.81±9.56)%,P<0.05), but the platelet inhibition rate induced by ADP pathway was significantly higher than that of Clopidogrel group (1.22 fold)((65.73±11.69)% vs(53.67± 8.75)%,P<0.05). There was no significant difference in the level of serum AGE before treatment and in platelet inhibition rate induced by AA pathway between the two groups (P>0.05). After treatment the level of serum AGE in Ticagrelor group was significantly lower than that in Clopidogrel group (18.71 ± 3.14) mg/L vs (25.71 ± 4.01) mg/L, P<0.05). Pearson correlation analysis revealed that serum AGE levels were positively correlated with platelet aggregation (r=0.87, P<0.001) and negatively correlated with platelet inhibition (r=－0.95, P<0.001). There was no significant difference in bleeding events occurrence between the two groups after 6 months of treatment. However, the appearance of ischemic events in the Ticagrelor group was significantly lower than that in the Clopidogrel group (8.33% vs 18.33%, P<0.05). Conclusion Compared with Clopidogrel, Ticagrelor can significantly reduce platelet aggregation within one week after PCI and incidence of ischemic events within six months after PCI, and serum AGE may be the key node of this process.

Abstract:Aim To detect the levels of plasma oxidized low density lipoprotein (ox-LDL) and platelet aggregation in patients with acute coronary syndrome (ACS), and explore the effects of ox-LDL on the levels of platelet aggregation in patients with ACS. Methods A total of 158 patients with coronary heart disease (CHD) diagnosed by coronary angiography were enrolled in this study, including 48 patients with stable angina (SA), 59 patients with unstable angina (UA) and 51 patients with acute myocardial infarction (AMI). In addition, 60 hospital patients, chest pain without coronary artery stenosis, served as a control group. The levels of plasma ox-LDL were determined by ELISA, the levels of platelet aggregation were detected by turbidimetric aggregation monitoring device. Results Compared with control group, the levels of plasma ox-LDL and platelet aggregation were significantly increased in patients with UA and AMI, and there was no obvious change between control group and SA group, UA and AMI groups. In addition, the levels of plasma ox-LDL were positively correlated with the levels of platelet aggregation. Moreover, in vitro, ox-LDL could markedly promote ADP-induced platelet aggregation in patients with ACS. Conclusions Increased levels of plasma ox-LDL were associated with elevated levels of platelet aggregation in patients with ACS. Increased levels of plasma ox-LDL played a key factor role in the formation of atherothrombosis in patients with ACS, therefore, it was crucially important to detect the levels of ox-LDL in patients with ACS.

Abstract:Aim To investigate the relationship between the thromboxane A2 receptor(TXA2R) gene polymorphism(rs768963) and platelet aggregation in Han people in Shanghai. Methods TXA2R gene types,tested by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP),as well as platelet aggregation of 59 cerebral infarction patients and 40 health controls were detected. Results Triglyceride(TG) and blood pressure of cerebral infraction group were significantly higher when high density lipoprotein cholesterol(HDLC) was lower than that of health control(P<0.05).Mutant of TXA2R(CT and CC) improves the platelet aggregation(1) in health control group and platelet aggregation(1 and max) in cerebral infarction group,compared with wild type(TT).Studied as a whole group,mutant of TXA2R also had more significant impact on the platelet aggregation(1 and max) than wild type. Conclusion Compared with wild type,mutant of TXA2R(rs768963) improves the platelet aggregation,which may increase the incidence of thrombosis.

Abstract:Aim To study the effects of BPI-1096,a nitric oxide-releasing aspirin,on platelet aggregation. Methods Platelet-rich plasma(PRP) samples was prepared from healthy adult volunteers.The antiaggregant effects of BPI-1096 were tested by a standard nephelometric technique after incubating the drug with platelet at 37℃ for 10 min. Results The platelet aggregation induced by adenosine diphosphate(ADP),platelet activating factor(PAF),adnephrin and restocetin was inhibited by BPI-1096 at different concentration(p<0.05).BPI1096 inhibited platelet aggregation induced by arachidonic acid in every concentration but did ont show any significance(p>0.05).BPI-1096 displayed inhibitory effects similar to ASA at the same concentration.BPI-1096 did not strengthen the inhibitory effects on platelet aggregation at high concentration. Conclusions As a newly nitric oxide-releasing aspirin,BPI-1096 can significantly inhibit platelet aggregation induced by adnephrin,restocetin,ADP and PAF in vitro;the antiaggregation effects was similar to Aspirin at the same concentration.BPI-1096 did not show the correlation between concentration and efficiency.