High prevalence of aspirin resistance in elderly patients with cardiovascular disease and metabolic syndrome

Background Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential determinants of aspirin resistance in patients with cardiovascular disease （CVD）. Methods A total of 469 elderly patients with CVD were recruited. One hundred and seventy-two patients with metabolic syndrome and 297 without metabolic syndrome （control group） received daily aspirin therapy （〉 75 mg） over one month. Platelet aggregation was measured by light transmission aggregometry （LTA）. Aspirin resistance was defined as 〉 20% arachidonic acid （AA）- and 〉 70% adenosine diphosphate （ADP）-induced aggregation according to LTA. Aspirin semi-responders were defined as meeting one （but not both） of these criteria. Results By LTA, 38 of 469 （8.1%） patients were aspirin resistant. The prevalence of aspirin resistance was higher in the metabolic syndrome group compared with the control group [11.6 % vs. 6.6%, odds ratio （OR） = 2.039; 95% confidence interval （CI）： 1.047-3.973]. In the multivariate logistic regression analysis, metabolic syndrome （OR = 4.951, 95% CI： 1.440-17.019, P = 0.011） was a significant risk factor for aspirin resistance. Conclusions A significant number of patients with CVD and metabolic syndrome are resistant to aspirin therapy. This might further increase the risk of cardiovascular morbidity and mortality in these patients.

Establishing a predictive model for aspirin resistance in elderly Chinese patients with chronic cardiovascular disease

Background Resistance to anti-platelet therapy is detrimental to patients. Our aim was to establish a predictive model for aspirin resistance to identify high-risk patients and to propose appropriate intervention. Methods Elderly patients （n = 1130） with stable chronic coronary heart disease who were taking aspirin （75 mg） for 〉 2 months were included. Details of their basic characteristics, laboratory test results, and medications were collected. Logistic regression analysis was performed to establish a predictive model for aspirin resistance. Risk score was finally established according to coefficient B and type of variables in logistic regression. The Hosmer-Lemeshow （HL） test and receiver operating characteristic curves were performed to respectively test the calibration and discrimination of the model. Results Seven risk factors were included in our risk score. They were serum creatinine （〉 110 μmol/L, score of 1）; fasting blood glucose （〉 7.0 mmol/L, score of 1）; hyperlipidemia （score of 1）; number of coronary arteries （2 branches, score of 2; 〉 3 branches, score of 4）; body mass index （20-25 kg/m2, score of 2; 〉 25 kg/m2, score of 4）; percutaneous coronary intervention （score of 2）; and smoking （score of 3）. The HL test showed P ≥ 0.05 and area under the receiver operating characteristic curve ≥ 0.70. Conclusions We explored and quantified the risk factors for aspirin resistance. Our predictive model showed good calibration and discriminative power and therefore a good foundation for the further study of patients undergoing anti-platelet therapy.

Association of the Platelet Membrane Glycoprotein Ⅰa C807T Gene Polymorphism with Aspirin Resistance

To explore the correlation between the C807T polymorphism of platelet membrane glycoprotein Ⅰa （GP Ⅰa） gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin （100 mg/d） for 7 days. Platelet aggregation function was detected using adenosine diphosphate （ADP） and arachidonic acid （AA） before and after the administration of aspirin. Then the subjects were divided into three groups according to the results of platelet aggregation function： an aspirin resistant （AR） group, an aspirin semi-responder （ASR） group and an aspirin-sensitive （AS） group. Platelet GP Ⅰa gene 807CT polymorphism was examined by means of polymerase chain reaction-sequence specific primers （PCR-SSP）. The results showed that T allelic frequency in AR group and ASR group were higher that of AS group （P〈0.005）, and the prevalence of genotypes （TT＋TC） of these two groups was significantly higher than that in AS group （P〈0.05）. Platelet GP Ⅰa T allele was significantly associated with aspirin resistance as revealed by multiple logistic regression （OR=3.76, 95% CI： 2.87-9.58）. The results suggest that inherited platelet GP Ⅰa variations may have an important impact on aspirin resistance and the presence of GP Ⅰa T allele may be a marker of genetic susceptibility to aspirin resistance.

Study on Related Factors of Aspirin Resistance in Acute Ischemic Stroke

Objective:To study the related factors of aspirin resistance(AR)in acute ischemic stroke.Methods:A total of 138 patients with acute ischemic stroke treated in hospital affiliated to Xuzhou medical university from August 2016 to August 2018 were the study subjects,examine his medical data from the past.They were divided into the AR group(40 cases)and the non-AR group(98 cases)according to whether AR appears.Gender,disease history,biochemical indicators and etc.were compared between the two groups.The independent risk factors of AR were investigated using univariate analysis and logistic regression analysis.Results:40 cases of AR occurred in 138 patients,with an incidence rate of 28.99%.Diabetes,platelet count(PLT),microRNA-19a(m iR-19a)expression,smoking,high-sensitivity C-reactive protein(hs-CRP),Low-density lipoprotein cholesterol(LDL-C),fibrinogen(FIB)and age difference between the AR group and non-AR group was statistically significant(P<0.05).Gender,hypertension,uric acid(UA),high-density lipoprotein cholesterol(HDL-C),triglycerides(TG),homocysteine(Hcy),total cholesterol(TC),and alanine aminotransferase(ALT)between the two groups were not significantly different(P>0.05).Logistic regression analysis showed that the independent risk factors for AR in acute ischemic stroke were diabetes(OR=2.773,95%CI:1.102~5.065,P=0.025),miR-19a(OR=3.021,95%CI:1.322~6.545,P=0.021),hs-CRP(OR=2.719,95%CI:1.301~5.022,P=0.028)and smoking(OR=1.983,95%CI:1.114~3.887,P=0.040).Conclusion:The incidence of AR is higher in acute ischemic stroke.Risk factors include diabetes,miR-19a expression,hs-CRP,smoking,etc.Clinical intervention measures can be taken to reduce the risk of AR and improve acute ischemic stroke prognosis.

Clopidogrel improves aspirin response after off-pump coronary artery bypass surgery

We sought to assess the incidence of aspirin resistance after off-pump coronary artery bypass （OPCAB） surgery, and investigate whether clopidogrel can improve aspirin response and be safely applied early after OPCAB surgery. Sixty patients who underwent standard OPCAB surgery were randomized into two groups. One group （30 patients） received mono-antiplatelet treatment （MAPT） with aspirin 100 mg daily and the other group received dual anfiplatelet treatment （DAPT） with aspirin 100 mg daily plus clopidogrel 75 mg daily. Platelet aggregations in response to arachi- donic acid （PLAA） and adenosine diphosphate （ADP） （PLADP） were measured preoperatively and on days 1 to 6, 8 and 10 after the antiplatelet agents were administered. A PLAA level above 20% was defined as aspirin resistance. Postoperative bleeding and other perioperative variables were also recorded. There were no significant differences between the two groups in baseline characteristics, average number of distal anastomosis, operation time, postoperative bleeding, ventilation time and postoperative hospital stay. However, the incidence of aspirin resistance was significantly lower in the DAPT group than that in the MAPT group on the first and second day after antiplatelet agents were given （62.1% vs, 32.1%, 34.5% vs. 10.7%, respectively, both P 〈 0.05）. There was no significant difference in postoperative complication between the two groups. DAPT with aspirin and clopidogrel can be safely applied to OPCAB patients early after the procedure. Moreover, clopidogrel reduces the incidence of OPCAB-related aspirin resistance.

Earlier application of loading doses of aspirin and clopidogrel decreases rate of recurrent cardiovascular ischemic events for patients undergoing percutaneous coronary intervention

Background Aspirin and clopidogrel resistance plays a significant role in the development of cardiovascular ischemic events for ninety patients undergoing percutaneous coronary intervention.Recent studies have indicated that increasing the dose of antiplatelet drugs maybe a potent method to improve the inhibition of platelet aggregation.Methods Thrombelastograph （TEG） determinations were used to evaluate the effect of antiplatelet therapy.According to the results,90 patients were divided into three groups and given different doses of aspirin and clopidogrel.Thirty patients with both an inhibition rate of aspirin 〉50% and an inhibition rate of clopidogrel 〉50% were defined as the control group.Sixty patients with an inhibition rate for aspirin 〈50% and an inhibition rate for clopidogrel 〈50% were defined as the resistance group.Patients in resistance group were randomly assigned to be given a routine dose （100 mg aspirin plus 75 mg clopidogrel per day,which we called a resistance plus routine dose group,R＋R） and a loading dose （200 mg aspirin and 150 mg clopidogrel per day,which we called resistance plus loading dose group,R＋L） of antiplatelet therapy.A 12-month follow-up was observed to examine the change of inhibition rate of antiplatelet therapy and to estimate the relationship between inhibition rate and the occurrence of cardiovascular ischemic events.Results After 6 months of antiplatelet therapy,the inhibition rate of aspirin in the R＋L group increased from （31.4±3.7）% to （68.6±7.1）%,which was significantly higher than that in R＋R group,（51.9±8.2）% （P 〈0.01）.The inhibition rate of clopidogrel in the R＋L group increased from （22.1±3.8）% to （60.2±7.4）%,which was significantly higher than in the R＋R group,（45.9±4.3）% （P 〈0.01）.The occurrence rates of cardiovascular ischemic events,stent thrombosis,recurrent unstable angina and myocardial infarction in the R＋R group were 20%,36% and 17%,respectively.Occurrence was significantly increased compared with that in the control group,3%,10% and 1%,respectively （P 〈0.01）.In contrast,the occurrence rates in the R＋L group （10%,23% and 6%,respectively） were attenuated compared with those in the R＋R group （P 〈0.01 ）,although still higher than in the control group （P 〈0.01）.Conclusions Almost all of the cardiovascular ischemic events occurred in the first six months after percutaneous coronary intervention.According to the result of TEG determinations,earlier application of a loading dose of aspirin and clopidogrel can decrease the rate of recurrent cardiovascular ischemic events.