ABCA1 rs4149313 polymorphism and susceptibility to coronary heart disease: a meta-analysis.

Many existing studies have demonstrated that common polymorphisms in the ABCA1 gene may play important roles in the development and progression of coronary heart disease (CHD), but individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the relationship between the ABCA1 rs4149313 polymorphism and CHD risk. We searched the CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception through 1 September 2013. Meta-analysis was performed using the STATA 12.0 software. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated. Eleven case-control studies were included with a total of 5416 CHD patients and 20,897 healthy controls. Our meta-analysis results revealed that the ABCA1 rs4149313 polymorphism may be associated with an increased risk of CHD. Subgroup analysis by ethnicity suggested that there were significant associations between the ABCA1 rs4149313 polymorphism and an increased risk of CHD in Asian populations, but not in Caucasian populations (all P > 0.05). Meta-regression analyses showed that ethnicity may be a main source of heterogeneity. The present meta-analysis suggests that the ABCA1 rs4149313 polymorphism may contribute to the risk of CHD, especially in Asian populations.

[The prospective register study of domestic tirofiban for clinical application in acute coronary syndrome].

OBJECTIVE: To evaluate the current clinical application of domestic tirofiban in patients with acute coronary syndrome (ACS) and to explore its safety profile focused on the common causes and correlation factors for the hemorrhagic events. METHODS: The patients diagnosed as ST-elevation myocardial infarction (STEMI) and medium to high risk non-ST-elevation myocardial infarction (NSTEMI)/unstable angina(UA) in 15 hospitals from September 2009 to December 2011 and given domestic tirofiban, were enrolled in this study. The following data were carefully collected: demographic data, comorbidities, concomitant medications, laboratory data, interventional treatment, application of tirofiban, hemorrhagic events and major adverse cardiac events(MACE) in hospital and at day 30 after discharge. RESULTS: (1) A total of 927 patients were enrolled in the study. The domestic tirofiban was given to 241 subjects (26.0%) before the intervention, 567 subjects (61.2%) during the intervention and 89 subjects (9.6%) after the intervention. The standardized application was performed in 737 subjects (79.5%) with the loading dose of 10 µg/kg and the maintenance dose of 0.15 µg·kg(-1)·min(-1). In all the subjects, the average maintenance time was (30.4 ± 14.2) hours with the average dose of (339.3 ± 182.9)ml. (2)During hospitalization, major bleeding happened in 4 cases (0.4%) and major adverse cardiac events (MACE) in 37 cases (4.0%). (3)At day 30 after discharge, 1 cases (0.1%) was reported with major bleeding and 9 cases (1.0%) with MACE. (3)The least MACE was showed in the preoperative tirofiban group (2.5%) and followed by the intraoperative group (4.1%) and the postoperative group (9.0%). Compared with the non-standardized application group, MACE was significantly decreased in the standardized application group (2.44% vs 10.00%, P < 0.05). CONCLUSIONS: The standardized application of the domestic tirofiban could decrease the incidence of MACE. Taken into account the combination therapy of clopidogrel and aspirin in the vast majority of patients, the domestic tirofiban exhibits a good safety profile with a relatively lower incidence of bleeding than the similar clinical studies.

[Effects of smoke on clinical prognosis of patients with acute ST-segment elevation myocardial infarction].

OBJECTIVE: To explore the effects of smoke on the clinical prognosis of patients with acute ST-segment elevation myocardial infarction (ASTEMI). METHODS: A total of 1213 consecutive ASTEMI patients were admitted into 20 hospitals in Liaoning province between May 2009 and May 2010. They were stratified into smoke (n = 588) and non-smoke (n = 625) groups. Basic demographic profiles, treatment data and clinical outcomes were compared between two groups. The primary endpoint was cardiac death and the secondary endpoints included non-fatal myocardial infarction, stroke and revascularization. Cox proportional hazard analyses were performed. RESULTS: The proportion of percutaneous coronary intervention (PCI) in the smoke group was significantly higher than that in the non-smoke group (40.8% vs 22.1%, P < 0.001). During the follow-up period, the medication rate was significantly higher in the smoke group than that in the non-smoke group (aspirin: 75.3% vs 62.2%, P < 0.001; clopidogrel: 40.5% vs 32.2%, P = 0.003; ß receptor blockade: 45.4% vs 36.0%, P = 0.001; angiotensin-converting-enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB): 38.3% vs 32.2%, P = 0.026; statins: 57.3% vs 44.2%, P < 0.001). During the follow-up period, the rate of cardiac death was lower in the smoke group than that in the non-smoke group (10.2% vs 24.2%, P < 0.001). No significant differences existed between two groups. During the follow-up period, the rate of cardiac death was significantly correlated with smoke (HR 2.777, 95%CI 1.113 - 6.928, P = 0.029), PCI (HR 0.208, 95%CI 0.062 - 0.700, P = 0.011), age (HR 1.049, 95%CI 1.005 - 1.095, P = 0.028), aspirin (HR 0.165, 95%CI 0.061 - 0.446, P < 0.001) and statins (HR 0.382, 95%CI 0.317 - 0.462, P < 0.001). CONCLUSION: Among the ASTEMI patients, the rate of cardiac death is significantly lower in the smoke group than that in the non-smoke group. And it is significantly correlated with such independent risk factors as smoke, PCI, age, aspirin and statins.

[Value of coronary CT angiography in assessment of bifurcation lesions].

OBJECTIVE: To evaluate the value of coronary CT angiography in assessment of bifurcation lesions. METHODS: The original image of 79 established and suspected coronary artery disease patients who underwent both coronary CT angiography and conventional artery angiography (CAG) sequentially were included in this analysis. Bifurcation lesions were assessed on primary and secondary vessels with diameter ≥ 2.0 mm, bifurcation lesions were graded according to Chen's classification. CAG was used as golden standard. The sensitivity, specificity, positive predictive value and negative predictive value were calculated. Spearman's test and Kappa test were used to evaluate the correlation and classification identity of the two methods. RESULTS: CAG evidenced 177 bifurcation lesions out of 445 bifurcation vessels and coronary CT detected 168 bifurcation lesions out of 404 bifurcation vessels with satisfactory imaging quality and 390 bifurcation vessels could be analyzed by both CAG and coronary CT. Sensitivity, specificity, positive predictive value and negative predictive value of coronary CT angiography were 94.2%, 94.6%, 90.7%, 96.1%, respectively. The results for the lesions at LM-LAD/LCX + LAD/Mid, LAD/Diag, RCA/PDA were more satisfactory and the sensitivity and specificity were as high as: 97.1% and 94.2%, 95.7% and 89.5%, 92.3% and 98.7%, respectively. There were significant correlations for evaluating the narrow degree of the opening of the bifurcation branch with these two methods (r = 0.799 58, P < 0.01) and for identifying I, II, III type bifurcation lesions (Kappa coefficient = 0.7959, P < 0.01) as well as for identifying the subtype bifurcation lesions (Kappa coefficient = 0.6328, P < 0.01) using the two methods. CONCLUSION: Coronary CT angiography is efficient in identifying the bifurcation lesions and offers a reasonable indication for bifurcation lesion classification.

Sacubitril Valsartan Enhances Cardiac Function and Alleviates Myocardial Infarction in Rats through a SUV39H1/SPP1 Axis.

Sacubitril valsartan (lcz696) has been demonstrated as a substitute for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for the treatment of heart failure. This research is aimed at examining the effects of lcz696 and its target molecules on myocardial infarction (MI). A rat model of MI was induced by left anterior descending artery ligation and treated with lcz696. Lcz696 treatment significantly reduced cardiac injury and heart failure, restored the left ventricular fractional shortening and ejection fraction, and reduced oxidative stress and inflammatory responses in rat myocardium. By analyzing the heart failure-related GSE47495 dataset and performing gene ontology (GO) functional enrichment analysis, we obtained histone lysine methyltransferase SUV39H1 and secreted phosphoprotein 1 (SPP1) as two molecules implicated in the oxidative stress and inflammation processes. An elevation of SUV39H1 whereas a decline of SPP1 were detected in cardiac tissues after lcz696 treatment. Enrichments of SUV39H1 and H3K9me3 at the SPP1 promoter were identified by chromatin immunoprecipitation assay. SUV39H1 catalyzed H3K9me3 modification to suppress the expression of SPP1. Preconditioning of SUV39H1 silencing blocked the protective roles of lcz696, but SPP1 silencing alleviated the myocardial injury. In conclusion, this study demonstrates that lcz696 enhances cardiac function and alleviates MI in rats through a SUV39H1/SPP1 axis.

[Onset timing of acute ST segment elevation myocardial infarction in middle-aged and old patients].

OBJECTIVE: To compare the differences on onset timing of acute ST segment elevation myocardial infarction (STEMI) in young and aged patients. METHODS: The exact onset time of symptoms was obtained from 1024 consecutive patients with STEMI admitted to our hospital between January 2000 and May 2010. Patients were classified as the middle-aged group [< 65 years old, mean (52.2 ± 8.0) years, n = 536] and old group [≥ 65 years old, (72.2 ± 5.5) years, n = 488], the difference of the onset months, weeks, weekdays and hours between two groups was compared. RESULTS: The high onset timing of STEMI in middle-aged group was October and February, Friday, Saturday and Wednesday, at 10 A.m. and 10 P.m. The high onset timing of STEMI in old group was October, January and March, Friday, Sunday and Monday, at 6 A.m. and 2 A.m. The incidences of STEMI in the old group were significant higher than in the middle-aged group in March (11.89%), on Sunday (15.97%) and Monday (17.42%), at 6 A.m. (6.35%) and 2 A.m. (5.74%) (all P < 0.05) while the onset rate was significant higher in February (9.89%), On Saturday (16.98%), At 8 P.m. (4.86%) and 10 P.m. (5.78%) in the middle-aged group than old group (all P < 0.05). CONCLUSION: The onset timing of STEMI in old patients was significant different from the middle-aged patients suggesting the onset timing of STEMI changes with aging.

Circular RNA Foxo3 Relieves Myocardial Ischemia/Reperfusion Injury by Suppressing Autophagy via Inhibiting HMGB1 by Repressing KAT7 in Myocardial Infarction.

INTRODUCTION: Myocardial infarction is coronary artery-related heart disease, and the leading cause of mortality globally. Circular RNAs (circRNAs) are a new type of regulatory RNAs and participate in multiple pathological cardiac progression. METHODS: However, the function of circFoxo3 in MI-induced myocardial injury remains obscure. RESULTS: Significantly, we identified that circFoxo3 was downregulated in the MI rat model and the overexpression of circFoxo3 ameliorated MI-induced cardiac dysfunction and attenuated MI-induced autophagy in rat model. Meanwhile, the overexpression of circFoxo3 repressed oxygen-glucose deprivation (OGD)-induced autophagy, apoptosis, inflammation, and injury of cardiomyocyte in vitro. Mechanically, we identified that the expression of KAT7 was reduced by circFoxo3 overexpression in cardiomyocytes. Meanwhile, the expression of HMGB1 was repressed by the depletion of KAT7 in cardiomyocytes. The enrichment of histone H3 lysine 14 acetylation (H3K14ac) and RNA polymerase II (RNA pol II) on HMGB1 promoter was inhibited by the knockdown of KAT7. Moreover, the overexpression of circFoxo3 suppressed HMGB1 expression and KAT7 overexpression rescued the expression of HMGB1 in cardiomyocytes. The enrichment of KAT7, H3K14ac, and RNA poly II on HMGB1 promoter was decreased by circFoxo3 overexpression, while the overexpression of KAT7 could reverse the effect. The overexpression of KAT7 or HMGB1 could reverse circFoxo3-attenuated cardiomyocyte injury and autophagy in vitro. Thus, we conclude that circular RNA circFoxo3 relieved myocardial ischemia/reperfusion injury by suppressing autophagy via inhibiting HMGB1 by repressing KAT7 in MI. DISCUSSION: Our finding provides new insight into the mechanism by which circFoxo3 regulates MI-related cardiac dysfunction by targeting KAT7/HMGB1 axis.

[Protective effects of hypoxia-inducible factor-1 alpha on myocardial ischemia/reperfusion injury in rat and the role of protein kinase C in signal pathway].

OBJECTIVE: To study the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in a rat model of myocardial ischemia/reperfusion injury (IRI) and the role of protein kinase C (PKC) in signal pathway. METHODS: A rat model of myocardial IRI was reproduced by 30 minutes of left anterior descending coronary artery (LCA) occlusion followed by 180 minutes of reperfusion. Thirty-two healthy male Wistar rats were randomly divided into four groups. The first group was ischemic preconditioning (IPC) group; the second group was simple IRI group; the third group was IPC plus PKC inhibitor group (IPC+I group); the fourth group was the sham-operation group without ligation of LCA. Eight rats were used in each group. The heart was harvested 180 minutes post-reperfusion, the mRNA and protein expression of HIF-1 alpha and heme oxygenase-1 (HO-1) were assessed. Meanwhile, the protein expression of caspase-3 was assayed. Blood samples were obtained from heart to determine the levels of interleukin-8 (IL-8) and myeloperoxidase (MPO). RESULTS: The mRNA and protein expression of HIF-1 alpha and HO-1 increased significantly in the IRI group compared with the sham-operation group, while the protein expression of caspase-3 increased significantly in the IRI group (HIF-1 alpha mRNA: 0.849+/-0.032 vs. 0.356+/-0.022, HIF-1 alpha protein: 0.762+/-0.042 vs. 0.324+/-0.016, HO-1 mRNA: 0.862+/-0.045 vs. 0.332+/-0.012, HO-1 protein: 0.792+/-0.044 vs. 0.335+/-0.031, caspase-3 protein: 0.371+/-0.015 vs. 0.061+/-0.012, respectively, all P<0.01). The levels of IL-8 and MPO increased significantly in the IRI group [IL-8: (812+/-26) ng/L vs. (72+/-13) ng/L, MPO: (78.7+/-2.9) kU/L vs. (13.3+/-1.5) kU/L, both P<0.01]. The protein and mRNA expression of HIF-1 alpha and HO-1 increased significantly in the IPC group compared with IRI group (HIF-1 alpha mRNA: 1.412+/-0.039, HIF-1 alpha protein: 1.362+/-0.045, HO-1 mRNA: 1.523+/-0.038, HO-1 protein: 1.420+/-0.041, respectively), meanwhile the protein expression of caspase-3 (0.129+/-0.019) decreased significantly in the IPC group (all P<0.01). The levels of IL-8 [(432+/-59) ng/L] and MPO [(43.2+/-5.9) kU/L] decreased significantly in the IPC group compared with IRI group (both P<0.01). All above parameters showed no significant change between IPC+I group and IRI group. CONCLUSION: HIF-1 alpha plays a protective role in myocardial IRI, PKC is an important signal pathway of HIF-1 alpha gene expression in IRI.

[Efficacy and safety of intravenous levosimendan compared with dobutamine in decompensated heart failure].

OBJECTIVE: To compare the efficacy and safety of intravenous levosimendan and dobutamine in patients with decompensated heart failure refractory to conventional medications. METHODS: Patients were recruited into this multicentre, randomised, positive-controlled and parallel-group study to receive either levosimendan or dobutamine therapy. In the levosimendan group, an initial loading dose of levosimendan of 12 microg x kg was infused over 10 min, followed by a continuous infusion of 0.1 microg x kg(-1) x min(-1) for 1 h and then 0.2 microg x kg(-1) x min(-1) for 23 h. In the control group, dobutamine was infused for 1 h at an initial dose of 2 microg x kg(-1) x min(-1) without a loading dose, followed by a continuous infusion of 4 microg x kg(-1) x min(-1) for 23 h. Hemodynamic responses at 24 h were evaluated by echocardiography (in both groups) and Swan-Gans catheter (in the levosimendan group). Clinical assessment was performed to evaluate efficacy and safety of the medications. RESULTS: A total of 225 patients from 12 medical centers were evaluated; 119 assigned to levosimendan and 106 assigned to dobutamine group. The effectiveness rate was 31.9% (38 patients) in the levosimendan group and 17.9% (19 patients) in the dobutamine group (P < 0.01). At 24 h, left ventricular ejection fraction (LVEF) was improved by 6. 4% in the levosimendan group, compared with 4.6% in the dobutamine group (P > 0.05). Stroke volume (SV) was increased by 11.1 ml in the levosimendan group and 2.8 ml in the dobutamine group respectively (P < 0.05). Dyspnea and clinical manifestations improvements were more significant in levosimendan therapy group compared to dobutamine group. There were less adverse effects including hypokalemia, hypotension and ventricular premature beats in the levosimendan group than in the dobutamine group (P < 0.05). CONCLUSION: Levosimendan was well tolerated and superior to dobutamine for patients with decompensated heart failure refractory to conventional medications.

Chemical hypoxia-induced glucose transporter-4 translocation in neonatal rat cardiomyocytes.

BACKGROUND: AMP-activated protein kinase (AMPK) activation plays an essential role in glucose metabolism of the heart. This study aimed at investigating whether AMPK was involved in glucose transporter-4 (GLUT-4) translocation induced by azide-induced chemical hypoxia in primary cultured neonatal rat cardiomyocytes. METHODS: With or without adenine 9-beta-D-arabinofuranoside (ara A, AMPK inhibitor) preincubation, primary cultured rat cardiomyocytes were randomized to several groups as incubated with azide (the respiratory chain inhibitor), insulin, or 5-aminoimidazole-4-carboxyamide-1-beta-D-ribofuranoside (AICAR, an AMPK activator). Glucose uptake was measured through gamma-scintillation and GLUT-4 protein was detected by Western blot for each group. RESULTS: Azide-induced chemical hypoxia and AICAR both increased glucose uptake and GLUT-4 translocation in cardiomyocytes, and AICAR had an additive effect on insulin action. Ara A decreased AICAR- and azide-induced glucose uptake and GLUT-4 translocation but did not affect basal or insulin-stimulated glucose uptake. CONCLUSIONS: Azide-induced chemical hypoxia increased glucose uptake and GLUT-4 translocation in neonatal rat cardiomyocytes through a mechanism that at least was partially mediated by AMPK activation.

Multi-link Vision and MiniVision stent registry in Asian patients with coronary artery disease: a prospective, multi-center study.

BACKGROUND: Recent studies have showed that the fine mesh stents are associated with a significant reduction in both clinical and angiographic re-stenosis of the coronary arteries. To maintain a very satisfactory radio-opacity using the stents, Guidant of the USA has designed a new type of bare metal stents (BMS)-Multi-link (ML) Vision/ML MiniVision stents. The clinical outcomes of Asian patients with coronary artery disease (CAD) after implanting the Multi-link Vision or MiniVision stent were investigated in this study. METHODS: An observational, prospective, multi-center, non-randomized post marketing registry was conducted to demonstrate the efficacy of the BMS-ML Vision/ML MiniVision stents. The primary end point of the registry was clinical target lesion revascularization (TLR) at a 6-month follow-up. The major secondary end points included the rate of major adverse cardiac events (MACE) and serious adverse events (SAE) in hospital and at 6 months; and the rate of clinical TLR as a function of the type of angina. A total of 429 Asian people with 449 lesions from 14 centers were selected for this study. The average reference diameter of the lesions was (3.0 +/- 0.5) mm, and the mean length was (15.7 +/- 5.0) mm. RESULTS: The successful rate of the procedure was 99.3%. Twenty-five percent of the lesions were treated by direct stenting without pre-dilation. Eighty-six percent of the lesions were implanted with ML Vision stent. After the 6-month follow-up, the rate of clinical TLR was 1.4%. The MACE, SAE and target vessel revascularization (TVR) were 6.8%, 3.5% and 1.4% respectively. CONCLUSION: The current registry showed the excellent 6-month clinical outcomes of ML Vision/ML MiniVision stents in Asian patients with CAD.

Prediction of marker genes associated with hypertension by bioinformatics analyses.

This study aimed to explore the underlying marker genes associated with hypertension by bioinformatics analyses. A gene expression profile (GSE54015) was downloaded. The differentially expressed genes (DEGs) between the normotensive female (NF) and hypertensive female (HF), and between the normotensive male (NM) and hypertensive male (HM) groups were analyzed. Gene Ontology (GO) and pathway enrichment analyses were performed, followed by protein-protein interaction (PPI) network construction. The transcription factors (TFs), and the common DEGs between the HF and HM groups were then analyzed. In total, 411 DEGs were identified between the HF and NF groups, and 418 DEGs were identified between the HM and NM groups. The upregulated DEGs in the HF and HM groups were enriched in 9 GO terms, including oxidation reduction, such as cytochrome P450, family 4, subfamily b, polypeptide 1 (Cyp4b1) and cytochrome P450, family 4, subfamily a, polypeptide 31 Cyp4a31). The downregulated DEGs were mainly enriched in GO terms related to hormone metabolic processes. In the PPI network, cytochrome P450, family 2, subfamily e, polypeptide 1 (Cyp2e1) had the highest degree in all 3 analysis methods in the HF group. Additionally, 4 TFs were indentified from the 2 groups of data, including sterol regulatory element binding transcription factor 1 (Srebf1), estrogen receptor 1 (Esr1), retinoid X receptor gamma (Rxrg) and peroxisome proliferator-activated receptor gamma (Pparg). The intersection genes were mainly enriched in GO terms related to the extracellular region. On the whole, our data indicate that the DEGs, Cyp4b1, Cyp4a31 and Loxl2, and the TFs, Esr1, Pparg and Rxrg, are associated with the progression of hypertension, and may thus serve as potential therapeutic targets in this disease.

Current Trends for ST-segment Elevation Myocardial Infarction during the Past 5 Years in Rural Areas of China's Liaoning Province: A Multicenter Study.

BACKGROUND: Since 2010, two versions of National Guidelines aimed at promoting the management of ST-segment elevation myocardial infarction (STEMI) have been formulated by the Chinese Society of Cardiology. However, little is known about the changes in clinical characteristics, management, and in-hospital outcomes in rural areas. METHODS: In the present multicenter, cross-sectional study, participants were enrolled from rural hospitals located in Liaoning province in Northeast China, during two different periods (from June 2009 to June 2010 and from January 2015 to December 2015). Data collection was conducted using a standardized questionnaire. In total, 607 and 637 STEMI patients were recruited in the 2010 and 2015 cohorts, respectively. RESULTS: STEMI patients in rural hospitals were older in the second group (63 years vs. 65 years, P = 0.039). We found increases in the prevalence of hypertension, prior percutaneous coronary intervention (PCI), and prior stroke. Over the past 5 years, the cost during hospitalization almost doubled. The proportion of STEMI patients who underwent emergency reperfusion had significantly increased from 42.34% to 54.47% (P < 0.0001). Concurrently, the proportion of primary PCI increased from 3.62% to 10.52% (P < 0.0001). The past 5 years have also seen marked increases in the use of guideline-recommended drugs and clinical examinations. However, in-hospital mortality and major adverse cardiac events did not significantly change over time (13.01% vs. 10.20%, P = 0.121; 13.34% vs. 13.66%, P = 0.872). CONCLUSIONS: Despite the great progress that has been made in guideline-recommended therapies, in-hospital outcomes among rural STEMI patients have not significantly improved. Therefore, there is still substantial room for improvement in the quality of care.

Statin-ezetimibe versus statin lipid-lowering therapy in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

BACKGROUND: Studies comparing the clinical efficacy and safety of intensive statin therapy with ezetimibe-statin combination therapy are still rare at present, especially in Asian population. METHODS: We enrolled 202 patients who suffered acute coronary syndrome (ACS) and underwent percutaneous coronary intervention (PCI) between May and July in 2016. Patients were allocated into three groups based on the lipid lowering strategy: moderate-intensity statin group (n=118), ezetimibe combined with moderate-intensity statin group (ezetimibe-statin combination, n=55) and intensive statin group (n=29). The lipid profiles and side effects were analyzed and compared among the patients in three groups at admission, 1 month and 3 months after PCI. The clinical outcomes of the patients were observed through 6-month follow-up. RESULTS: One month after PCI, the level of non-high density lipoprotein-cholesterol (non-HDL-C) was decreased by 41.9%, 21.6% and 29.8% by ezetimibe-statin combination therapy, moderate-intensity statin therapy and intensive statin therapy, respectively (P<0.05). The reduction percentages of TC and LDL-C were significantly higher in ezetimibe-statin combination group than in moderate-intensity statin group (P<0.001). The proportion of patients reaching LDL-C goal was higher in ezetimibe-statin combination group (69.1%, P=0.007) and intensive statin group (67.9%, P=0.047) compared with moderate-intensity statin group (46.9%) at 1 month after PCI. There was no significant difference among the three groups with respect to hepatic enzymes level, creatine kinase (CK) level and incidence of muscle symptoms. CONCLUSIONS: The reduction percentage of non-HDL-C was larger in ezetimibe-statin combination group than intensive statin group. This finding suggested that statin/ezetimibe combination therapy could be an alternative to intensive statin therapy in Chinese patients with atherosclerotic cardiovascular disease.

Efficacy and safety of ticagrelor versus clopidogrel with different dosage in high-risk patients with acute coronary syndrome.

BACKGROUND: Dual antiplatelet therapy is recommended as a standard antiplatelet strategy in acute coronary syndrome. For those with reduced pharmacologic response to clopidogrel, strengthening antiplatelet therapy (clopidogrel 150mg daily) may reduce adverse clinical events. Ticagrelor is a direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and offset than clopidogrel. METHODS: In this retrospective study, we compared ticagrelor (180mg loading dose 90mg twice daily thereafter), clopidogrel (300mg loading dose, 75mg or 150mg daily thereafter) for the prevention of cardiovascular events in 273 high-risk patients admitted to coronary care unit with acute coronary syndrome. RESULTS: The rate of IST in hospital was significantly reduced in patients of ticagrelor group comparing with those receiving clopidogrel 75mg (0.69% vs 8.2%, p=0.009). Moreover, the TVR rate was less in the ticagrelor group than clopidogrel 75mg group (2.7% vs 13.1%, p=0.007) 6months follow-up. The incidence of MACCE has no difference between the two clopidogrel groups. Kaplan-Meier analysis of MACCE-free indicated that there was no difference between the three groups. Ticagrelor significantly increased the rate of minor bleeding compared with clopidogrel 75mg daily during hospital (45.5% vs 26.2%,p=0.012) and 6-month follow-up (66.9% vs 45.9%,p=0.004).Bleeding-free prognosis was significantly better in the clopidogrel 75mg daily group. CONCLUSIONS: In patients with acute coronary syndrome undergoing PCI, the rate of in-stent thrombosis and TVR were significantly reduced treated with ticagrelor compared with clopidogrel 75mg daily, without an increase of overall major bleeding, but with an increase of minor bleeding.

[Effects of different catheter ablation strategies in treatment of typical atrial flutter complicated with paroxysmal atrial fibrillation].

OBJECTIVE: To evaluate the clinical effects of different catheter ablation strategies in the treatment of typical atrial flutter complicated with paroxysmal atrial fibrillation (PAF). [CTIA, pulmonary vein segmental isolation (PVSI), CTIA + PVI] to the patients coexisted with typical atrial flutter and PAF. METHODS: 66 patients with typical atrial flutter complicated with PAF were divided into 3 groups: Group A (n = 30), undergoing cavotricuspid isthmus ablation, (CTIA), Group B (n = 17), undergoing pulmonary vein segmental isolation, (PVSI), and Group C (n = 19), undergoing CTIA + PVSI. Follow-up was conducted for 30.5 weeks +/- 10.4 weeks. The clinical curative effects, operation safety, and complication were evaluated. RESULTS: The recurrence rate of typical atrial flutter within 12 weeks after operation of Groups A and C were 13.3% and 10.5% respectively, both significantly lower than that of Group B (52.9%, both P < 0.05) without no significant difference between Group A and Group C (P > 0.05). The recurrence rate of typical atrial flutter within 36 weeks after operation of the Groups A, B, and C were 10%, 11.8%, and 10.5% respectively, without significant differences among these 3 groups (all P > 0.05). The recurrence rates of PAF within 12 weeks and 30 weeks after operation of Groups B and C were 29.4% and 31.6%, and 23.5% and 26.3% respectively, all significantly lower than those of Group A (46.7% and 73.3% respectively, all P < 0.05) without significant o differences between Groups B and C. CONCLUSION: In patients with both typical atrial flutter and PAF, pure CTIA has a good effect on typical atrial flutter, whereas the PAF recurrence rate is higher; Pure PVSI has a good control of typical atrial flutter while curing PAF; PVSI + CTIA only reduces the early recurrence of typical atrial flutter, however, has no advantage in long-term follow up.

[Pitavastatin enhances angiogenesis and perfusion in a murine mode of limb ischemia].

OBJECTIVE: We investigated the effects of pitavastatin on angiogenesis and perfusion in C3H/He mice with unilateral hind limb ischemia. METHODS: C3H/He mice treated with saline (n = 15) or pitavastatin (1 mg.kg(-1).d(-1), n = 15) per gavage for 1 week underwent unilateral hind limb ischemia surgery and were treated for another 5 weeks. Hind-limb blood flow was measured by Laser Doppler perfusion imager (LDPI, ischemic/nonischemic limb, %) at baseline, immediately after ischemia and weekly thereafter for 5 weeks. Endpoints included local vessel counts by immunofluorescence, phospho-Akt positive cell counts by immunoenzyme histochemical technique, vascular endothelial growth factors (VEGFs) expression in ischemic limbs by Western blot and serum nitric oxide metabolite (NOx) by chrome dioxide Griess method. RESULTS: Lower extremity perfusion was significantly improved in pitavastatin treated mice vs. controls as measured by LDPI% at 1 week post ischemia and thereafter (P < 0.05). Pitavastatin treatment was associated with significantly increased capillary count [(47 +/- 11) vs. (26 +/- 14)/per high-power field (x 200), P < 0.05] and greater percentage of phospho-Akt positive cells [(6 +/- 1) vs. (2 +/- 0)/per high-power field (x 200), P < 0.05] in ischemic limbs. Serum NOx [(77.3 +/- 21.8) vs. (52.1 +/- 11.2) mol/L, P < 0.05) and VEGF protein expression in ischemic limbs were also significantly increased in pitavastatin group than those in control group. CONCLUSIONS: Pitavastatin enhances angiogenesis and perfusion in CsH/He mice with limb ischemia.

The efficacy of N-acetylcysteine plus sodium bicarbonate in the prevention of contrast-induced nephropathy after cardiac catheterization and percutaneous coronary intervention: A meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of combining use of N-acetylcysteine (NAC) and sodium bicarbonate (SOB) in the prevention of contrast-induced nephropathy (CIN) after cardiac catheterization and percutaneous coronary intervention (PCI) is unclear. METHODS: All relevant studies that compared the effect of combining the use of NAC and SOB with individual use on CIN in patients undergoing cardiac catheterization and PCI were identified by searching the databases including Pubmed, Embase, Cochrane Library, and Web of Science without time and language limitation. Only randomized controlled trials (RCTs) with full-text published were considered. RESULTS: Sixteen RCTs involving 4432 cases were included into this meta-analysis. The results showed there were no additional benefit in reduction of CIN in COM group (COM versus NAC: RR 0.85, 95% CI 0.70-1.03, P=0.103; COM versus SOB: RR 0.91, 95% CI 0.71-1.16, P=0.449), even in patients with diabetes mellitus (COM versus NAC: RR 1.11, 95% CI 0.71-1.75, P=0.646; COM versus SOB: RR 1.06, 95% CI 0.45-2.47, P=0.893), undergoing PCI procedure (COM versus NAC: RR0.76, 95% CI 0.39-1.47, P=0.411; COM versus SOB: RR0.96, 95% CI 0.65-1.40, P=0.814), or with baseline renal dysfunction (COM versus NAC: RR 0.89, 95% CI 0.70-1.14, P=0.366; COM versus SOB: RR 0.95, 95% CI 0.67-1.36, P=0.788). CONCLUSIONS: The present study demonstrated combining use of NAC and SOB was not significantly superior to individual use method in the prevention of CIN after cardiac catheterization and PCI.

Bioinformatics Analyses of Differentially Expressed Genes Associated with Acute Myocardial Infarction.

BACKGROUND: We aimed to predict key genes associated with acute myocardial infarction (AMI) by bioinformatics analysis. METHODS: The microarray data of GSE48060, including peripheral blood samples from 31 first-time AMI patients within 48-h post-MI and 21 normal controls, were obtained from Gene Expression Omnibus database. The differentially expressed genes (DEGs) in AMI samples compared with normal controls were identified. Functional enrichment analysis was then performed, followed by analysis of protein-protein interaction (PPI) network and transcription regulatory network (TRN). RESULTS: A total of 385 up- and 504 down-regulated DEGs were identified. They were mainly enriched in five pathways, such as natural killer (NK) cell-mediated cytotoxicity and chemokine signaling pathway. Chemokine (C-C motif) ligand 5 (CCL5) was hub protein in PPI network. Besides, four transcription factors (TFs), including nuclear receptor subfamily 2, group C, member 2 (NR2C2), MYC-associated factor X (MAX), general transcription factor IIIC, polypeptide 2, beta 110 kDa (GTF3C2), and B-cell CLL/lymphoma 3 (BCL3), were identified. Notably, nuclear receptor coactivator 7 (NCOA7) interacted with GTF3C2 and MAX directly. CONCLUSIONS: CCL5, BCL3, NR2C2, MAX, GTF3C2, and NCOA7 might play important roles in AMI development.

Effect of Pioglitazone in Preventing In-Stent Restenosis after Percutaneous Coronary Intervention in Patients with Type 2 Diabetes: A Meta-Analysis.

BACKGROUND: The benefits of pioglitazone in patients with type 2 diabetes mellitus (T2DM) after percutaneous coronary intervention (PCI) is unclear. OBJECTIVES: To evaluate the effect of pioglitazone on prevention of in-stent restenosis (ISR) in patients with T2DM after PCI. METHODS: All full-text published relevant studies compared the effect of pioglitazone with control group (placebo or no pioglitazone treatment) on ISR in patients with T2DM after PCI were identified by searching the databases including PubMed, EMBASE, Cochrane Library and ISI Web of Science through October 2015. The endpoints were defined as the rate of ISR, late lumen loss, in-stent neointimal volume, target lesion revascularization (TLR) and major adverse cardiac events (MACE). RESULTS: Six studies (5 RCTs and 1 retrospective study), comprising 503 patients, were included into this meta-analysis. In the pioglitazone group, as compared with the control group, the risk ratio for ISR was 0.48 (I2 = 14.5%, P = 0.322; 95%CI 0.35 to 0.68, P<0.001), the risk ratio for TLR was 0.58 (I2 = 6.0%, P = 0.363; 95%CI 0.38 to 0.87, P = 0.009). The result showed there was no association between the use of pioglitazone and the events of MACE (I2 = 36.7%, P = 0.209; RR 0.56, 95%CI 0.30 to 1.05, P = 0.071). For the considerable heterogeneity, further analysis was not suitable for the endpoints of late lumen loss (I2 = 81.9%, P<0.001) and neointimal volume (I2 = 75.9%, P = 0.016). CONCLUSIONS: The treatment of pioglitazone was associated with a reduction in ISR and TLR in T2DM patients suffering from PCI, except the incidence of MACE.