Jia Dean

Chronic kidney disease and the risk of stent thrombosis after percutaneous coronary intervention with drug-eluting stents†

Chronic kidney disease (CKD) has been demonstrated to be associated with adverse clinical outcomes for patients with coronary artery disease (CAD). However, data on relation of CKD and stent thrombosis (ST) after drug‐eluting stent (DES) implantation are limited.

Prolonged Dual Antiplatelet Therapy Improves Clinical Outcomes in High-risk Patients Implanted with Sirolimus-eluting Stents

Although a science advisory recommending 12 months of dual antiplatelet therapy after drug‐eluting stents implantation was published recently, the optimal duration of dual antiplatelet therapy has not yet been precisely determined.

The effect of exogenous creatine phosphate on myocardial injury after percutaneous coronary intervention.

Objective: To evaluate the effect of exogenous creatine phosphate (CP) on myocardial injury after percutaneous coronary intervention (PCI). Method: Four hundred patients were divided to receive conventional therapy (control group) or 3-day intravenous infusion of CP after PCI (CP group). Levels of creatine kinase MB (CK-MB) and troponin I (TnI) were measured before and on postprocedural day 3. Results: Postprocedural CK-MB and TnI in the CP group were significantly increased compared to the control group. In the CP group, 8.0% and 5.0% of patients had an increase in CK-MB 1 to 3 times and >3 times, respectively, which were significantly lower than that of the control group (19.0% and 9.0%, respectively); 12.0% and 10.0% of patients had an increase in TnI 1 to 3 times and >3 times, respectively, which were significantly lower than that of the control group (21.0% and 18.0%, respectively). Conclusion: Exogenous CP was helpful to reduce myocardial injury after PCI.

Safety and efficacy of the XIENCE V everolimus-eluting stent compared to the resolute zotarolimus-eluting stent in small vessels

Background The second generation drug-eluting stents have been shown to improve angiographic and clinical outcomes after percutaneous myocardial revascularisation, but its performance in small coronary arteries has not been investigated. Objectives To evaluate the safety and efficacy of the XIENCE V everolimus-eluting stent (EES) compared to the Resolute zotarolimus-eluting stent (ZES) in small vessels. Methods In this study, we studied a cohort of 412 patients with small coronary vessels (reference diameter <2.75 mm). EES (54.1% of pts) and ZES (45.9% of pts) were used in our study. Results Mean angiographic in-stent and in-segment late loss was non-significantly less in the EES group compared with the ZES group, (0.16±0.51 vs 0.18±0.44 mm; p=0.209 for in-stent; 0.12±0.36 mm vs 0.13±0.28 mm; p=0.387 for in-segment). EES resulted in a non-significant reduction in composite major adverse cardiac events at 1 year (6.4% vs 8.2%; p=0.130). At 1 year, the rate of non-Q-wave myocardial infarction was also the same in both groups (p=0.055). Conclusions In patients with small vessel coronary arteries, the XIENCE V EES was not superior to the Resolute ZES.

Influence of abnormal fasting plasma glucose on left ventricular function in older patients with acute myocardial infarction

Objective We assessed whether the admission fasting plasma glucose (FPG) levels were associated with all-cause mortality and left ventricular (LV) function in older patients with acute myocardial (AMI). Methods A total of 1854 consecutive patients were categorised into four groups: hypoglycaemia, euglycemia, mild hyperglycemias and severe hyperglycemias. The primary outcomes were in-hospital/3-year mortality and LV function. Results There was a near-linear relationship between FPG and Killip class. However, no significant correlation was found between FPG levels and LV ejection fraction. Both FPG levels and Killip classes were all independent significant predictors for mortality. Compared with the euglycemia group, both the hypo- and hyperglycemias were associated with higher in-hospital and 3-year mortality. Conclusions In older patients with AMI, FPG values had differential influences on LV function and mortality. There was a U-shaped relationship between FPG and in-hospital/3-year mortality, and a near-linear relationship between increased admission glucose levels and higher Killip classification.

Matched case-control study on mechanism of radial artery spasm

Objects The aim of this study is to discuss preliminarily the relationship between vaso-active substances and radial artery spasm (RAS), and provide theoretical evidence for the prevention of RAS. Methods This is a prospective, matched case-control study. The patients who suffered from RAS during coronary angiography were enrolled, and the patients without RAS were matched 1:2 according to same gender, similar age (within 2 years). The diagnostic criteria are clinical definition of RAS based on a questionnaire which was documented by angiography. Blood samples were obtained before the procedure, and were tested for nitric oxide, endothelin-1, prostacyclin, thromboxane A2 and norepinephrine. Logistic regression was made to find out the risk factors of RAS. Results Sixty patients suffered form RAS and 120 patients without RAS were enrolled. The concentration of nitric oxide (63.5875±21.2763 vs 55.6425±18.1542, p=0.351) and thromboxane A2 (0.9768±0.1953 vs 0.7824±0.2051, p=0.284) was of no difference between the RAS group and the control group. The concentration of endothelin-1 (298.5839±65.3291 vs 81.4391±20.4283, p<0.001) and norepinephrine (202.3721±38.3829 vs 56.4828±15.6025, p=0.005) was higher, prostacyclin (8.8294±2.5322 vs 15.5430±4. 8267, p=0.038) was lower in RAS group. Multiple regression showed that endothelin-1 (OR 2.954, 95% CI 1.569 to 5.354, p=0.005) and norepinephrine (OR 4.642, 95% CI 2.619 to 8.332, p=0.018) were the risk factors of RAS during the procedure. Conclusions Multiple regression showed that endothelin-1 and norepinephrine were the risk factors of RAS during the procedure.

e0520 Statin effects in stent thrombosis induced by rapamycin releasing from drug-eluting stents through KrÜppel-Like Factor 2 overexpression

Objects As we studied before, rapamycin released from drug-eluting stents (DESs) affected the antithrombogenic function of endothelial cells through Krüppel-Like Factor 2 (KLF2) decrease. However, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are known to modulate endothelial function by inducing KLF2. Here we report that statin-induced expression of KLF2 can reverse stent thrombosis. Methods We observed the effect of rapamycin on expression of KLF2, endothelial NO synthase (eNOS), tissue-plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1) and tissue factor (TF) in Human Umbilical Vein Endothelial Cells (HUVECs). And then KLF2 mRNA was induced by treatment with multiple statins in a concentration-dependent manner. The mRNA and protein were mensurated by RT-PCR and Western Blot Analysis. Furthermore, activation of KLF2 was evaluated by Electrophoretic Mobility Shift Assay (EMSA). Results Rapamycin made the expression and activation of KLF2 strongly reduce by 75.6% and 78.2% so as to induce long-term coronary endothelial dysfunction. In HUVECs, rapamycin made basal eNOS and t-PA decrease by 80% and 87.8%, while making basal PAI-1 and TF increase by 2.5 and 1.5-fold. After treatment by statins (especially lovastatin), the expression of KLF2 was increased by 3.8-fold nearly reversing to normal state. Conclusions Taken together, these observations indicate that statin-dependent induction of KLF2 provides a new treatment for stent thrombosis induced by rapamycin releasing from drug-eluting stents.

e0519 Rapamycin suppress KrÜppel-Like Factor 2 expression: mechanism of endothelial dysfunction associated with drug-eluting stents

Objects Although rapamycin released from drug-eluting stents (DESs) affect the antithrombogenic function of endothelial cells, the exactly mechanisms underlying these effects are incompletely understood. We hypothesised that Krüppel-Like Factor 2 (KLF2), a novel and potent regulator of endothelial gene expression, might play an important role in stent thrombosis. Methods We observed the effect of rapamycin on expression of KLF2, endothelial NO synthase (eNOS), tissue-plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1) and tissue factor (TF) in Human Umbilical Vein Endothelial Cells (HUVECs). Then, with overexpression of KLF2, we mensurated the above mentioned mRNA and protein, respectively. The mRNA and protein were mensurated by RT-PCR and Western Blot Analysis. Furthermore, activation of KLF2 was evaluated by Electrophoretic Mobility Shift Assay (EMSA). Results Rapamycin made the expression and activation of KLF2 strongly reduce by 75.6% and 78.2% so as to induce long-term coronary endothelial dysfunction. In HUVECs, rapamycin made basal eNOS and t-PA decrease by 80% and 87.8%, while making basal PAI-1 and TF increase by 2.5 and 1.5-fold. Overexpression of KLF2 strongly induced eNOS and t-PA expression and reduced PAI-1 and TF expression, reversing protein above-mentioned near to normal state. Conclusions The data indicated that rapamycin strongly inhibited the expression of KLF2, meanwhile, reduced anticoagulants (eNOS and t-PA) and induced procoagulants (PAI-1 and TF). KLF2 played an important role in stent thrombosis owing to rapamycin-induced endothelial dysfunction, which might be a part of mechanism of stent thrombosis associated with DESs.

e0511 Impact of smoking on platelet inhibition of clopidogrel in patients undergoing percutaneous coronary intervention

Objective The study aimed to evaluate the impact of smoking on platelet inhibition of clopidogrel. Methods The clopidogrel-native patients were enrolled. Cigarette smoking status was recorded and stratified into never smoking (NS) and current smoking (CS). All the patients were given loading dose of 300 mg and maintenance dose of 75 mg clopidogrel. Platelet aggregation was measured before and 24 h after loading by conventional light transmittance aggregometry after stimulation with 5 mmol/L ADP. Results 722 patients (60.7±9.0 years) were enrolled, including 568 men (78.7%). Among the patients, 322 patients (44.6%) were CS and 400 (55.4%) were NS. At baseline, the maximal platelet aggregation (MPA) was not significantly different between CS and NS (57.2±10.4% and 56.6±12.8%, p=0.487). After clopidogrel loading, the MPA decreased significantly among CS compared with NS. The mean decreased MPA was 23.8±10.5% and 19.2±12.8% (p<0.001) for CS and NS, respectively. Conclusion Cigarette smoking might enhance the inhibition effect of clopidogrel on platelet.

e0446 Differential influence of abnormal fasting plasma glucose on mortality and left ventricular function in older patients with acute myocardial infarction results from the BEAMIS study

Objective The aim of this study was to assess whether the admission FPG levels were associated with all-cause mortality and left ventricular (LV) function in older patients with acute myocardial (AMI) by analysing data from the Beijing Elderly Acute Myocardial Infarction Study (BEAMIS). Methods From April 2004 to October 2006, 1854 older (age ≥65 years) AMI patients were consecutively enrolled in BEAMIS Patients were categorised into 4 groups: hypoglycemia group (N=443, 23.9%), FPG≤5 mmol/l; euglycemia group (N=812, 43.8%), 5.1 mmol/L≤FPG≤7 mmol/l (5–7 mmol/l); mild hyperglycemia group (N=308, 16.6%), 7.1 mmol/L≤FPG≤9 mmol/l (7–9 mmol/l); and severe hyperglycemia group (N=291, 15.7%), FPG≥9.1 mmol/l. The primary outcomes were in-hospital and 3-year mortality and LV function during admission. Results There was a near-linear relationship between FPG levels and Killip class, with Killip classes I/II and III/IV being more frequent among patients with hypoglycemia and hyperglycemia, respectively (p=0.011). However, no significant correlation was found between admission FPG levels and LVEF, LV end-diastolic or end-systolic diameter (p=0.837, 0.073, 0.165, respectively). Both admission FPG levels (p=0.002) and Killip classes (p<0.001) were all independent significant predictors for in-hospital/3-year mortality. Compared with the euglycemia group, both the hypo- and hyperglycemia groups were associated with higher in-hospital and 3-year all-cause mortality. Patients in the FPG 5–7 mmol/l group had the best outcome. In-hospital mortality of patients with hypoglycemia and Killip class IV was the highest in the overall cohort, followed by that of patients with severe hyperglycemia and Killip class IV (60% vs 50.0%, p=0.015). In contrast, 3-year mortality of patients with severe hyperglycemia and Killip class IV was highest followed by that of patients with hypoglycemia and Killip class IV (70% vs 60.0%, p=0.001). Conclusions In older patients with AMI, abnormal FPG values had differential influences on LV function and mortality. Not only increased but also decreased admission FPG levels could predict in-hospital and 3-year mortality. There was a U-shaped relationship between admission FPG levels and short- or long-term mortality, and a near-linear relationship between increased admission glucose levels and higher Killip classification.