Clinical Characteristics, Treatment Patterns, and Effectiveness in Chinese Patients with Angina Pectoris Using Electronic Patient-Reported Outcomes: Protocol for a Multicenter, Prospective, Cohort Study (GREAT).

BACKGROUND: Angina pectoris (AP) is the initial and the most common manifestation of coronary artery disease (CAD). Therefore, management and control of AP can help prevent further complications associated with CAD. However, there is under-reporting of angina symptoms in clinical practice, resulting in under-treatment and reduced quality of life (QoL). Prospective and standardized monitoring is needed to support timely and appropriate treatment. OBJECTIVES: To establish a large cohort of Chinese patients with AP and compare the effectiveness of different anti-angina regimens with the help of electronic patient-reported outcomes (e-PROs), using the Seattle Angina Questionnaire (SAQ) to assess health status. METHODS: The registry study (GREAT) is a multicenter, prospective, observational, cohort study. Patients diagnosed with AP will be enrolled from 10 hospitals and assessed based on the different anti-anginal regimens. Patients will be followed up every 3 months from baseline to 12 months to observe the difference in the therapeutic effectiveness of the drugs. Data will be collected in the form of e-PROs combined with on-site visit records. PLANNED OUTCOMES: The change in SAQ summary score (SAQ SS) at Month 12 from baseline will be the primary outcome. The secondary measures will include changes in SAQ SS at Months 3, 6, and 9 from baseline, changes in retest results of vascular stenosis imaging at Month 12 from baseline, and medication adherence based on the proportion of days covered. Safety data will be evaluated based on the incidence of adverse events (AEs). CONCLUSION: This study will evaluate the effectiveness of anti-anginal regimens using ePROs in real-world settings in China. The results from this study may provide a new perspective on treatment patterns and the effectiveness of different anti-anginal regimens for patients with AP. STUDY REGISTRATION NUMBER: NCT05050773.

Trimetazidine ameliorates myocardial ischemia-reperfusion injury.

Aim of this study was to investigate the effects of trimetazidine attenuating the myocardial ischemia-reperfusion injury to myocardium in rats and the underlying mechanisms. A model of myocardial ischemia reperfusion was established via ligating the left anterior descending coronary artery in 30 rats, and then they were randomly assigned to model group (n=10), low dose group (n=10) and high dose group (n=10). Moreover, additional 10 rats were collected and allocated to sham operation group, which was served as control group. Then, rats in the low dose group and high dose group were given trimetazidine with the dose of 10mg/kg and 30mg/kg respectively by intragastric administration, while rats in the control group and model group were given the equivalent volume saline. The dose was given once a day for consecutive 4 weeks in all rats. Echocardiography was applied to evaluate cardiac function, including left ventricular end-systolic dimension (LVESD), left ventricular end diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF). Next, myocardial tissue was collected, and Bax and Bcl-2 mRNA and the protein levels in the four groups were detected by RT-PCR and Western blot respectively. The level of malonaldehyde (MDA) and super oxide dismutase (SOD) activity in rat myocaridum in each group were detected by colorimetric methods, while the variables of apoptosis were measured by TUNEL methods. In comparison with the control group, LVEDD, LVEDS of rats increased significantly, LVEF decreased obviously, as well as Bax level, MDA level and the apoptotic variables in myocardial tissue increased (P<0.05), but Bcl-2 level and SOD activity decreased significantly in low dose, high dose and model group (P<0.05). Compared with model group, LVEDD, LVEDS of rats decreased obviously, LVEF increased significantly, as well as Bax level, MDA level and the apoptotic variables in myocardial tissue decreased (P<0.05), but Bcl-2 level and SOD activity increased significantly in low dose group, high dose group (P<0.05). The regulatory role of trimetazidine on above indicators of rats was in a dose-dependent manner. Trimetazidine can ameliorate rat myocardium following ischemia-reperfusion injury by effectively attenuating the injury from myocardial cell apoptosis; meanwhile, it can resist cell apoptosis through regulating Bax and bcl-2 expression, which exhibits guiding significance for the treatment of myocardial ischemia and reperfusion.

FGF21 protects myocardial ischemia-reperfusion injury through reduction of miR-145-mediated autophagy.

AIMS: Fibroblast growth factor 21 (FGF21) plays a critical role in protecting against myocardial ischemia/reperfusion (I/R) injury. However, the molecular mechanism is not completely understood. Here, we aimed to examine whether miRNA-145 (miR-145) is involved in FGF21 protection against myocardial I/R injury through angiopoietin-2 (Angpt2) and autophagy. METHODS: We established a rat myocardial I/R model and H9c2 hypoxia/reoxygenation (H/R) model. After administration of FGF21 in the rat I/R model, the infarct size, morphological changes and apoptosis in myocardium were determined by 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin and eosin (HE), and Masson's trichrome staining, and TUNEL assay, respectively. The expression levels of miR-145 and Angpt2 were evaluated by quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemical (IHC) staining. The activity of lactate dehydrogenase (LDH), TNF-α and IL-6 were assayed. Using a dual-luciferase reporter system, the targeted role of miR-145 on Angpt2 was studied. After transfection with miR-145 inhibitor, H9c2 cells were subjected to stimulated H/R with or without FGF21 treatment. The expression of Angpt2 was assessed while cell apoptosis and cell migration assays were performed. RESULTS: FGF21 significantly decreased infarction after I/R, ameliorated I/R-induced cell apoptosis, and inhibited I/R-induced LDH, TNF-α and IL-6 in serum. FGF21 inhibited I/R-induced decrease in miR-145 level, increase in Angpt2 expression and decrease in autophagy; FGF21 also upregulated LC3-B and Beclin1 levels. miR-145 directly targeted Angpt2. The roles of FGF21 in expression of miR-145 and Angpt2 and activation of autophagy after H/R were reversed by miR-145 inhibitor. In addition, the FGF21-inhibited cell apoptosis and FGF21-promoted migration after H/R were restored by miR-145 inhibitor. CONCLUSION: FGF21 protects myocardial cells against I/R injury by promoting an increase in miR-145 levels and autophagy while inhibiting Angpt2 expression, suggesting a novel therapeutic strategy for protecting against myocardial I/R injury.

Evaluation of Short- and Long-Term Efficacy of Combined Intracoronary Administration of High-Dose Adenosine and Tirofiban during Primary Percutaneous Coronary Intervention.

BACKGROUND: To assess the influence of combined intracoronary application of high-dose adenosine and tirofiban in primary percutaneous coronary intervention (PCI) on clinical events and cardiac function. METHODS: Our study evaluated consecutive patients with acute ST-segment elevation myocardial infarction undergoing primary PCI, who were randomly divided into adenosine group (n = 130) and control group (n = 128). Combined with thrombus aspiration and then intracoronary tirofiban, the adenosine group received intracoronary adenosine (2 mg) through the aspiration catheter 2 times. After thrombus aspiration and stenting of the infarct- related artery, the control group received placebo. The primary endpoint of our investigation was major adverse cardiac events (MACE) at the 1-year and 3-year marks. The secondary endpoint comprised left ventricular remodeling (LVR) at 6 months, myocardial blush grade (MBG), thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) after PCI. RESULTS: Our study found that TIMI flow grade post-PCI did not differ significantly between the 2 groups, while CTFC favored the adenosine-treated patients (21.6 ± 6.5 vs. 25.1 ± 7.8, p = 0.001). Although the adenosine group achieved a higher rate of MBG 3 (45.1% vs. 32.0%, p = 0.035) and MBG 2-3 (76.2% vs. 62.3%, p = 0.018) than the control group, the incidences of MACE at 1 year (20.0% vs. 25.0%, p = 0.373) and 3 years (26.9% vs. 32.0%, p = 0.413) were comparable. LVR occurred in 23.1% (27/117) of adenosine-treated patients and in 29.8% (43/114) of the controls (p = 0.296). CONCLUSIONS: Intracoronary administration of high-dose adenosine combined with intracoronary tirofiban and thrombus aspiration may further improve myocardial perfusion after primary PCI.

Downregulation of the miR-30 family microRNAs contributes to endoplasmic reticulum stress in cardiac muscle and vascular smooth muscle cells.

BACKGROUND: Endoplasmic reticulum (ER) stress is a common subcellular response to stresses and central to ER stress is increased expression of glucose-regulated protein 78 (GRP78). However, the mechanisms for GRP78 upregulation remained poorly understood. Our study goal was to shed light on this issue. METHODS: H2O2 was used to create cellular models of ER stress in neonatal rat ventricular cells (NRVCs) and rat aorta vascular smooth muscle cells (RAVSMCs). Molecular Biology techniques were used to quantify protein and mRNA levels. Luciferase reporter gene assay was employed to investigate miRNA targeting. MTT assay and ELISA were used to detect cell death. RESULTS: MiRNAs belonging to the miR-30 family including miR-30a, b, c, d and e were all downregulated in ER stress induced by H2O2 in cardiovascular cells NRVCs and RAVSMCs, along with the upregulation of GRP78, cleaved ATF6, CHOP, and cleaved caspase-12. GRP78 was confirmed to be a target gene for miR-30. Artificial knockdown of miR-30 by antimiR-30 triggered the phenotypic ER stress with significant GRP78/ATF6/CHOP/caspase-12 upregulations and cell death, while miR-30 replacement mitigated ER stress. Knockdown of CHOP by siRNA regulated all members of the miR-30 family whereas sequestration of C/EBP transcription factor by its decoy downregulated miR-30 miRNAs. CONCLUSIONS: Collectively, downregulation of the miR-30 family miRNAs contributes to the ER stress and the associated upregulation of GRP78 in the cardiovascular system. The participation of miR-30 creates a positive feedback loop in the ER stress signaling pathway. MiR-30 replacement may be a viable approach for alleviating disorders associated with ER stress.

Association between interleukin 6 and interleukin 16 gene polymorphisms and coronary heart disease risk in a Chinese population.

OBJECTIVE: To investigate the role of interleukin 6 (IL6) and IL16 single nucleotide polymorphisms (SNPs) in coronary artery disease (CAD) risk in a Chinese population. METHODS: Patients with CAD and healthy control subjects were recruited. IL6 (rs1800795 and rs1800796) and IL16 (rs8034928, rs3848180, rs4577037, rs1131445, rs4778889 and rs11556218) genotyping was performed on the MassARRAY® platform (Sequenom®, San Diego, CA, USA). RESULTS: Frequencies of rs8034928 variant C allele and rs11556218 variant T allele were higher in patients with CAD (n = 326) than controls (n = 341). The rs8034928 C/C genotype (odds ratio [OR] 2.03; 95% confidence intervals [CI] 1.16, 3.62) and C allele (OR 1.97; 95%CI 1.15, 3.45) were associated with increased risk of CAD compared with wild type. Similarly, the rs11556218 T/T genotype (OR 2.44; 95%CI 1.15, 5.44) and T allele (OR 2.37; 95%CI 1.13, 5.24) were associated with increased CAD risk compared with wild type. CONCLUSION: The SNPs rs8034928 and rs11556218 are associated with CAD risk in the Chinese population, and may be useful predictive markers for CAD susceptibility.

Efficacy and safety of a biodegradable polymer sirolimus-eluting stent in primary percutaneous coronary intervention: a randomized controlled trial.

INTRODUCTION: With long-term follow-up, whether biodegradable polymer drug-eluting stents (DES) is efficient and safe in primary percutaneous coronary intervention (PCI) remains a controversial issue. This study aims to assess the long-term efficacy and safety of DES in PCI for ST-segment elevation myocardial infarction (STEMI). MATERIAL AND METHODS: A prospective, randomized single-blind study with 3-year follow-up was performed to compare biodegradable polymer DES with durable polymer DES in 332 STEMI patients treated with primary PCI. The primary end point was major adverse cardiac events (MACE) at 3 years after the procedure, defined as the composite of cardiac death, recurrent infarction, and target vessel revascularization. The secondary end points included in-segment late luminal loss (LLL) and binary restenosis at 9 months and cumulative stent thrombosis (ST) event rates up to 3 years. RESULTS: The rate of the primary end points and the secondary end points including major adverse cardiac events, in-segment late luminal loss, binary restenosis, and cumulative thrombotic event rates were comparable between biodegradable polymer DES and durable polymer DES in these 332 STEMI patients treated with primary PCI at 3 years. CONCLUSIONS: Biodegradable polymer DES has similar efficacy and safety profiles at 3 years compared with durable polymer DES in STEMI patients treated with primary PCI.

[Efficacy comparison of combined intracoronary administration of high-dose adenosine and tirofiban versus intracoronary tirofiban during primary percutaneous coronary intervention in patients with acute myocardial infarction].

OBJECTIVE: To compare the efficacy of intracoronary administration of combined high-dose adenosine and tirofiban versus intracoronary tirofiban during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction. METHODS: Consecutive 258 patients with acute ST-segment elevation myocardial infarction (STEMI) underwent primary PCI, treated with thrombus aspiration and then intracoronary tirofiban, were randomly divided into adenosine group (n = 130) and control group (n = 128). Adenosine group received 2 times intracoronary adenosine (2 mg) after thrombus aspiration and after stenting of the infarct-related artery through the aspiration catheter. Control group received placebo. The primary end point was myocardial blush grade (MBG) after PCI. Secondary end points were thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) after PCI, ST-segment elevation resolution (STR), and major adverse cardiac events (MACE) at 30 days and 12 months. RESULTS: TIMI flow grade post PCI did not differ between the 2 groups, while CTFC favored the adenosine-treated patients [(21.6 ± 6.5) frames] compared with the placebo-treated patients [(25.1 ± 7.8) frames, P = 0.001]. MBG 3 was more frequently observed in the adenosine compared to the control group [45.1% (55/122) vs.32.0% (39/122), P = 0.035]. Patients in the adenosine group had a trend of higher rate of compete STR after the procedure compared patients in the control group [53.6% (67/125) vs. 41.9% (52/124), P = 0.065]. The incidence of MACE was comparable between patients randomized to adenosine and placebo at 30 days [12.3% (16/130) vs. 17.2% (22/128), P = 0.295] and at 12 months [12.3% (16/130) vs. 18.0% (23/128), P = 0.227]. CONCLUSION: Intracoronary administration of high-dose adenosine combined with tirofiban provides further improvement on myocardial perfusion after primary PCI but does not affect the clinical outcomes in patients with STEMI.

[Primary percutaneous coronary intervention in patients with acute myocardial infarction induced by left main artery occlusion or severe stenosis].

OBJECTIVE: The effects of primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) induced by left main (LM) artery occlusion were analyzed retrospectively in this study. METHODS: A total of 1343 consecutive AMI patients who underwent primary PCI between January 1995 and December 2004 were retrospectively studied. RESULTS: LM occlusion or severe stenosis were found in 11 patients [all male, mean age (56.4 +/- 9.2) years (range 43-70 years)], cardiogenic shock was overt in 6 patients. Primary PCI were performed under the assistance of intra-aortic balloon pump (IABP) in these patients [8 stent implantation, 3 balloon dilation and 2 necessitating emergency CABG after balloon dilation]. In-hospital mortality was 45.5% (5/11). Three-month follow-up were made in all survivals (6/11). Analysis showed good collateral circulation flow from right coronary artery to left coronary artery was existed in all survival cases before PCI. CONCLUSION: Prognosis of AMI patients with LM artery obstruction or severe stenosis was poor. Patients with pre-existed collateral circulation before primary PCI and IABP had a better clinical outcomes.