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.

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.

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.

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.

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.

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.

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.

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.

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.

Gender disparity in early death after ST-elevation myocardial infarction.

BACKGROUND: Females with acute myocardial infarction (AMI) have a higher risk of adverse outcomes because of receiving less evidence-based medical care. Our aim was to investigate the gender disparity in early death after ST-elevation myocardial infarction (STEMI) in the current era. METHODS: A total of 1429 consecutive patients with STEMI in the Liaoning district were analyzed. We compared hospital care and cardiac event data by sex for in-patients with acute STEMI within 24 hours of symptom onset. RESULTS: In the emergency reperfusion group (n = 754), in-hospital mortality occurred in 4.2% of the males and 11.2% of the females (P = 0.001). In the non-emergency reperfusion group (n = 675), in-hospital mortality occurred in 13.0% of the males and 22.9% of the females (P = 0.001). Multivariate Logistic regression analysis revealed female sex as an independent risk factor of death for STEMI patients during hospitalization (OR = 1.691, P = 0.007). After controlling for patients who died within 24 hr after admission, female sex was no longer an independent risk factor (OR = 1.409, P = 0.259). CONCLUSION: Female sex was an independent risk factor for in-hospital mortality of STEMI patients, which is explained by an excess of very early deaths.

Relationship between low-density lipoprotein levels on admission and 1-year outcome in patients with acute ST-segment-elevation myocardial infarction.

This study assessed the relationship between low-density lipoprotein cholesterol (LDL-C) levels on admission and the incidence of major adverse cardiovascular events (MACE) in patients with acute ST-segment-elevation myocardial infarction (ASTEMI). Patients with ASTEMI who had a lipid profile tested within 24 hours of symptom onset were enrolled. They were stratified into high and low LDL-C groups according to whether their LDL-C was above (n = 501) or below (n = 575) the median level, respectively. The incidence of MACE, cardiovascular death, non-fatal MI, revascularization, and stroke was compared between the groups at 1 month, 6 months, and 1 year. Survival analysis and Cox proportional hazard analysis were performed. In-hospital use of beta blockers was better in the high than in the low LDL-C group (76.6% vs. 69.7%, p = 0.01). Statin use was significantly higher in the high than in the low LDL-C group during follow-up (86.8% vs. 80.0%, p = 0.003 at1 month; 71.6% vs. 62.4%, p = 0.002 at 6 months; 67.8% vs. 61.2%, p = 0.03 at 1 year). The incidence of MACE on follow-up at 1 month was higher in the low than in the high LDL-C group (12.0% vs. 8.1%, p = 0.04). At 1 year, survival was not significantly different between the groups. Cox proportional hazards analysis indicated that the incidence of MACE was significantly associated with hypertension, current smoking, high-density lipoprotein cholesterol (HDL-C), in-hospital use of beta blockers, and statin use on follow-up (p < 0.01). LDL-C levels on admission in patients with ASTEMI had no significant effect on the 6-month and 1-year incidence of MACE, but the incidence of MACE was significantly higher in the low LDL-C group at 1 month. It would be relevant to further investigate the HDL-C level on admission, in-hospital use of beta blockers, and statin use during follow-up in relation to MACE.

[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.

[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.

[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.

Effect of high-dose rosuvastatin loading before percutaneous coronary intervention in female patients with non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Early loading statin therapy before percutaneous coronary intervention (PCI) is associated with reduced mortality and periprocedural myocardial injury. The aim of this study was to study the effect of rosuvastatin loading therapy before PCI in female patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). METHODS: Consecutive 117 female patients with NSTEACS were randomly assigned to either the group of rosuvastatin loading before PCI (20 mg 12 hours before angioplasty procedure, with a further 10 mg dose 2 hours before procedure, the loading dose group, n = 59) or the no rosuvastatin treatment group before PCI (control group, n = 58). Periprocedural myocardial injury, periprocedural changes of high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-a in serum and the incidence of major adverse cardiac events (MACE) 3 months and 6 months later were assessed. RESULTS: The incidence of periprocedural myocardial injury was higher in control group than loading dose group (CKMB: 10.17% vs. 25.86%, P = 0.027; Troponin I: 11.86% vs. 29.31%, P = 0.019). MACE occurred in 1.69% of patients in loading dose group and 12.07% of those in control group 3 months after procedure (P = 0.026), 3.39% vs. 17.24% at 6 months (P = 0.014). The levels of hs-CRP, IL-1, IL-6, and TNF-a in serum were not significantly different between the two groups before PCI, but after PCI they were significantly higher in control group. CONCLUSIONS: High-dose rosuvastatin loading before PCI significantly reduced periprocedural myocardial injury and periprocedural inflammation cytokines release and improved 3-month and 6-month clinical outcomes in female patients with NSTEACS who underwent PCI.

Prospective multi-center study of female patients with ST-elevation myocardial infarction in Liaoning province, China.

BACKGROUND: In cardiology, it is controversial whether gender influences prognosis after acute myocardial infarction (MI). We examined the 30-day and 1-year prognosis for female patients with ST-elevation myocardial infarction (STEMI) in Liaoning province, and we analyzed factors that influenced these outcomes. METHODS: This was a prospective, multicenter, observational study in which patient data were collected by questionnaire at the time of diagnosis and at approximately 30 days and 1 year later by telephone inquiries. Patients were diagnosed with STEMI between June 1, 2009 and June 1, 2010 at any of the 20 hospitals that gave treatment representative of current STEMI treatment in Liaoning Province. Unified follow-up questionnaire was used to visit the STEMI patients. RESULTS: We analyzed data from a total of 1429 consecutive patients with STEMI in Liaoning province. Female patients were older (70.0 vs. 60.3, P < 0.001) and were less likely to receive emergency reperfusion therapy than male ones (39.2% vs. 58.0%, P < 0.001). Female gender was associated with higher unadjusted 30-day mortality rates (HR = 2.118, 95%CI: 1.572 - 2.854, P < 0.001) and higher unadjusted 1-year mortality rates (HR = 2.174, 95%CI: 1.659 - 2.848, P < 0.001). Multivariate Cox regression analysis showed that female gender was not an independent predictor of 30-day mortality rates (HR = 1.273, 95%CI: 0.929 - 1.745, P = 0.133) nor of 1-year mortality rates (HR = 1.112, 95%CI: 0.831 - 1.487, P = 0.475). CONCLUSIONS: Women with STEMI appear to be at increased risk of 30-day and 1-year mortality compared with male STEMI patients, but this difference may be explained by older age and less frequent receipt of reperfusion therapy among the women.

[Impact of high-density lipoprotein levels at hospital admission on the outcome of patients with acute ST-segment elevation myocardial infarction].

OBJECTIVE: To analyze the impact of high-density lipoprotein cholesterol (HDL-C) levels at hospital admission on the incidence of major adverse cardiovascular events (MACCE) in patients with acute ST segment elevation myocardial infarction (ASTEMI). METHODS: 1067 patients with ASTEMI who were admitted to the 20 hospitals in Liaoning region and with lipid profile tested within the 24 hours of admission from May 2009 until May 2010, were enrolled. Data on basic demographic, clinical, status on admission and method of treatment were collected. Rate on various medical use and MACCE (cardiovascular death, non-fatal myocardial infarction, revascularization and stoke) were compared between the two groups through follow-up observation. Cox proportional hazard analysis was estimation. RESULTS: The median HDL-C level was 1.27 mmol/L, with 587 patients having HDL-C below and 489 patients HDL-C above the median level. The incidence rates of non-fatal myocardial infarction and MACCE at one-year follow-up period, was higher in low HDL-C group (4.8% vs. 0.9%, P<0.001; 23.7% vs. 18.1%, P=0.03, respectively). At one month follow-up, the incidence rate of non-fatal myocardial infarction was higher in low HDL-C group (1.4% vs. 0.0%, P=0.01). At six month follow-up, the incidence rates of non-fatal myocardial infarction and MACCE on one-year follow-up was higher in low HDL-C group (2.8% vs. 0.4%, P=0.003; 18.3% vs. 13.7%, P=0.04, respectively). RESULTS: from Cox proportional hazards analysis indicated that age (HR=1.02, 95%CI: 1.006-1.035, P=0.005), diabetes (HR=1.05, 95%CI: 1.053-2.171, P=0.03), HDL-C level (HR=0.56, 95%CI: 0.340-0.921, P=0.02) were significantly related to the incidence of MACCE. CONCLUSION: The incidence rates of one year and six month MACCE (mainly non-fatal myocardial infarction) and one month non-fatal myocardial infarction were significant higher in patients with low than high HDL-C levels at admission while kept on the ascending along with time. Age, diabetes, HDL-C level were independent risk factors related to the incidence of MACCE.

[The role of gender difference on the prognosis of ST-segment elevation myocardial infarction (STEMI) in patients treated with primary percutaneous coronary intervention].

OBJECTIVE: To investigate and analyze the impact of gender difference on outcome and prognosis of ST-segment elevation myocardial infarction (STEMI) in patients treated with primary percutaneous coronary intervention (PCI). METHODS: This was a prospective and multicentered observation study. All the patients with acute STEMI admitted to the hospitals from June 1(st) 2009 to June 1(st) 2010 were continuously recruited. In this study, a unified questionnaire was applied and the 382 patients satisfied the criteria. A unified follow-up questionnaire was used on patients who were discharged from the hospital. RESULTS: On average, the female patients were 8 years older than the males. The median "symptom-to-balloon time" was 312.5 minutes in females and 270.0 minutes in males, and it was significantly different (P = 0.007). During hospitalization, a higher proportion of female patients developed heart failure, angina and bleeding. No gender differences were found on the in-hospital mortality rates and medical therapy recommended by the guideline. The female patients were more prone to multi-vessel disease than males (P = 0.002). Success rates of primary PCI did not show any gender differences. One-month mortality and other cardiovascular events also did not show gender difference when the patients were followed for one month after being discharged. The rates of heart failure and re-hospitalization due to cardiac incidents among female patients were obviously higher than the males, three months after being discharged (P = 0.007, respectively). However, the three-month and long-term cardiac mortality did not show differences related to gender. Female patients were associated with higher all-cause mortality than that in males, but there was no statistically significant difference (female 4.2% vs. male 1.6%; P = 0.056). Data from multi-factor regression analysis showed that being female was not an independent predictor related to in-hospital mortality or during the follow-up period. CONCLUSION: Being female was not an independent predictor of in-hospital mortality or during follow-up period among patients who were treated with primary PCI. Worse long-term outcome seen in female patients was likely to be explained by older age or longer pre-hospital delayed time.

Increased poly(ADP-ribosyl)ation in peripheral leukocytes and the reperfused myocardium tissue of rats with ischemia/reperfusion injury: prevention by 3-aminobenzamide treatment.

The overactivation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is considered a final common effector in ischemia/reperfusion (I/R) injury. The aim of the current study was to examine the precise time course of the activation of PARP in peripheral leukocytes and the reperfused myocardium tissue on myocardial I/R injury from the same rat and to identify the relationship between myocardial infarct size and the degree of PARP activation in circulating leukocytes. Another aim of the study was to test the effect of 3-aminobenzamide (a well-known and widely used PARP inhibitor) on the activation of PARP in the reperfused myocardium and peripheral leukocytes. Poly(ADP-ribose) polymerase activation was measured by Western blotting for its product, poly(ADP-ribose) (PAR). The localization of PARP activation was determined by PAR immunohistochemistry. The results showed that poly(ADP-ribosyl)ation was detected 15 min, peaked 2 to 6 h, and remained markedly detectable 24 h in the reperfused heart after I/R model. Similarly, PAR content of the leukocytes increased in cells isolated just after reperfusion from the same rat. Immunohistochemical studies localized the staining of PAR primarily to the cardiac myocytes and vascular endothelial cells. At 6 h, there was a significant linear correlation between infarct size and PARP activity, whereas at 2 and 24 h, no relationship was found. The PARP inhibitor 3-aminobenzamide (3-AB, 20 mg kg⁻¹ i.v. injection 15 min before reperfusion, and every 2 h thereafter for 6 h) markedly reduced infarct size through depressing the activation of the enzyme in myocytes and peripheral leukocytes even when the treatment is initiated at 2 h after reperfusion.