Edoxaban for stroke prevention in atrial fibrillation and factors associated with dosing: patient characteristics from the prospective observational ETNA-AF-China registry.

Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

Icosapent ethyl therapy for very high triglyceride levels: a 12-week, multi-center, placebo-controlled, randomized, double-blinded, phase III clinical trial in China.

OBJECTIVES: Eicosapentaenoic acid in its ethyl ester form is the single active component of icosapent ethyl (IPE). This study was a phase III, multi-center trial assessing the safety and efficiency of IPE for treating very high triglyceride (TG) in a Chinese cohort. METHODS: Patients having TG levels (5.6-22.6 mmol/L) were enrolled and randomly assigned to receive a treatment of oral intake of 4 g or 2 g/day of IPE, or placebo. Before and after 12 weeks of treatment, TG levels were assessed and the median was calculated to determine the change between the baseline and week 12. In addition to examining TG levels, the impact of such treatments on other lipid changes was also investigated. The official Drug Clinical Trial Information Management Platform has registered this study (CTR20170362). RESULTS: Random assignments were performed on 373 patients (mean age 48.9 years; 75.1% male). IPE (4 g/day) lowered TG levels by an average of 28.4% from baseline and by an average of 19.9% after correction for placebo (95% CI: 29.8%-10.0%, P < 0.001). In addition, plasma concentration of non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein (VLDL) cholesterol, and VLDL-TG remarkedly reduced after IPE (4 g/day) treatment by a median of 14.6%, 27.9%, and 25.2%, respectively compared with participants in placebo group. Compared to the placebo, neither 4 nor 2 g of IPE daily elevated LDL-C levels with statistical significance. IPE was well tolerated by all the treatment groups. CONCLUSIONS: IPE at 4 g/day dramatically lowered other atherogenic lipids without a noticeable increase in LDL-C, thereby decreasing TG levels in an exceptionally high-TG Chinese population.

Circ_0093887 regulated ox-LDL induced human aortic endothelial cells viability, apoptosis, and inflammation through modulating miR-758-3p/BAMBI axis in atherosclerosis.

BACKGROUND: Compelling evidence demonstrated that circular RNAs (circRNAs) were involved in the progression of atherosclerosis (AS). However, the role of circ_0093887 in the progression of AS is unclear. The purpose of this study was to explore the role and mechanism of circ_0093887 in oxidized-low density lipoprotein (ox-LDL)-induced human aortic endothelial cells (HAECs). METHODS: HAECs were stimulated by ox-LDL to simulate AS-like injury in vitro. Circ_0093887, microRNA-758-3p (miR-758-3p), and BMP And Activin Membrane-Bound Inhibitor (BAMBI) levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). PCNA, Bax, Bcl-2, and BAMBI protein levels were detected by western blot. Cell viability and apoptosis were examined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Tube formation assay was used to assess tube formation. The levels of inflammatory factors TNF-α and IL-1ß were detected by corresponding ELISA kits. The relationship between miR-758-3p and circ_0093887 or BAMBI was tested via dual-luciferase reporter analysis and RNA immunoprecipitation. Oxidative stress related indexes (ROS and MDA) were detected by corresponding kits. RESULTS: The expression levels of circ_0093887 and BAMBI were prominently downregulated in ox-LDL-induced HAECs compared with control, whereas the expression of miR-758-3p was upregulated. Overexpression of circ_0093887 promoted HAECs viability and tube formation, and restrained cell apoptosis in ox-LDL-induced HAECs compared with untreated HAECs. Mechanistically, circ_0093887 regulated the expression of BAMBI through miR-758-3p. Further experiments showed that upregulation of miR-758-3p reversed changes in cell function induced by circ_0093887. In addition, reduced BAMBI salvaged miR-758-3p knockdown mediated effects on cell function. CONCLUSION: Circ_0093887 demonstrated its diagnostic and therapeutic value in AS by promoting the role of the miR-758-3p/BAMBI axis in the ox-LDL-induced endothelial injury of HAECs.

The value of Sonoclot detection technology to guide the clinical medication of the perioperative anticoagulation and antiplatelet therapy in patients with acute myocardial infarction undergoing emergent PCI.

The value of Sonoclot detection technology to guide the clinical medication of the perioperative anticoagulation and antiplatelet therapy in patients with acute myocardial infarction (AMI) undergoing emergent percutaneous coronary intervention (PCI) was estimated. One hundred and twenty-eight patients were randomly divided into control group and observation group with 64 cases in each group. Control group adopted routine blood coagulation indexes, including prothrombin time, activated partial thromboplastin time, fibrinogen and plasma thrombin time, platelet count and platelet aggregation turbidity analysis; observation group adopted Sonoclot detection technology, including activated clotting time, coagulation rate and platelet function. Anticoagulant therapy selected was of low molecular weight heparin calcium perioperatively, intraoperative unfractionated heparin, and clopidogrel (75 mg) combined with aspirin enteric-coated tablets (100 mg) as antiplatelet drugs. The therapy was administered in accordance with blood coagulation results. The blood coagulation time, postoperative creatine kinase isoenzyme MB, cardiac troponin I and B-type natriuretic peptide levels in the observation group are significantly lower than those in the control group (P<0.05) though the operating time and specifications of the stenting did not show any significant difference (P>0.05). The incidence of recurrent myocardial infarction, microembolism, acute and subacute thrombosis and bleeding events in the observation group are significantly lower than those in the control group (P<0.05). In the control group, there is no difference in the coagulation indexes of the patients with thrombosis events or bleeding events or no event (P>0.05). Whereas, in the observation group, there is significant difference in coagulation indexes of the patients with thrombosis events or bleeding events or no event (P<0.05). In conclusion, Sonoclot detection technology instructs emergent PCI treatment in AMI patients to shorten the detection time of blood coagulation, reduce the degree of myocardial injury, reduce the incidence of perioperative thrombosis and bleeding events. Furthermore, it has great value in guiding the clinical medication of anticoagulation and antiplatelet therapy.

Relationships of Inflammatory Factors and Risk Factors with Different Target Organ Damage in Essential Hypertension Patients.

BACKGROUND: Atherosclerosis (AS) is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory factors and risk factors with different target organ damages (TOD) in essential hypertension (EH) patients and to explore its clinical significance. METHODS: A total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein-associated phospholipase A2 (Lp-PLA2) in each group were detected, and the related risk factors were also statistically analyzed. RESULTS: Fibrinogen (Fbg) was the most significant independent risk factor in acute coronary syndrome (ACS) group (odds ratio [OR]: 22.242, 95% confidence interval [CI]: 6.458-76.609, P< 0.001) with the largest absolute value of the standardized partial regression coefficient B' (b': 1.079). Lp-PLA2 was the most significant independent risk factor in stroke group (OR: 13.699, 95% CI: 5.236-35.837, P< 0.001) with b' = 0.708. Uric acid (UA) was the most significant independent risk factor in renal damage group (OR: 15.307, 95% CI: 4.022-58.250, P< 0.001) with b' = 1.026. CONCLUSIONS: Fbg, Lp-PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence of ACS, ischemic stroke, and renal damage in EH patients, respectively.

[Influences of percutaneous coronary intervention on myocardial activity in myocardial infarction patients with different viable myocardium].

OBJECTIVE: To evaluate the effect of percutaneous coronary intervention (PCI) on left ventricular function in patients with different types of myocardial infarction and to explore the correlation factors for the left ventricular function. METHODS: A total of 43 patients diagnosed as acute myocardial infarction were enrolled in this study. The perfusion and delayed enhancement magnetic resonance imaging (DE-MRI) was applied to observe the following parameters before the PCI and at month 6 after the procedure: infarct mass, left ventricular ejection fraction (LVEF) and abnormal wall motion score. The subjects were divided into the following three groups by the transmural extent of myocardial infarction manifested in the DE-MRI: the transmural enhancement group, the nontransmural group and the mixed group. Laboratory test was done to detect the level of endothelin (ET), matrix metal enzyme 9 (MMP-9) and high sensitive C reactive protein (hsCRP) before PCI and at month 6 after the procedure. The t test was used to compare the differences among the groups and the multiple regression analysis was taken to explore the correlation factors for the left ventricular function. RESULTS: Compared with the parameters before PCI, the infarct mass after PCI significantly decreased in the nontransmural group and the mixed group [(4.0 ± 2.9) g/cm(3) vs (9.8 ± 5.6) g/cm(3) and (6.0 ± 3.5) g/cm(3) vs (11.8 ± 6.2)g/cm(3), all P < 0.05], while LVEF was significantly improved after PCI in both groups [(52.6 ± 15.4)% vs (41.9 ± 16.3)%,(45.6 ± 15.4)% vs (38.9 ± 16.3)%, all P < 0.05]. The infarct mass was an independent correlation factor for LVEF before PCI (RR = 0.318, P < 0.05) and LVEF after PCI (RR = 0.293, P < 0.05) . LVEF before PCI was independently correlated with the level of hsCRP (RR = 0.318, P < 0.05). CONCLUSION: The effect of PCI on the improvement of left ventricular function differs in patients with different extent of myocardial infarction, which is correlated with the amount of survival myocardium and the inflammatory factors.

Relationship between coronary atherosclerosis plaque characteristics and high sensitivity C-reactive proteins, interleukin-6.

BACKGROUND: The relationship between inflammatory markers and the characteristics of coronary atherosclerosis plaques is uncertain. The aim of the present study was to evaluate the relationship between the characteristics of coronary atherosclerosis plaques and inflammatory markers such as high sensitivity C-reactive proteins (Hs-CRP) and interleukin-6 (IL-6). METHODS: All patients suspected of having coronary heart disease (CHD) underwent Siemens 64-slice CT angiography (64-SCTA) to distinguish the quality of plaque of coronary artery lesions. Blood samples were taken to measure levels of serum Hs-CRP and IL-6 in different plaque groups and the control group and compared with the value of 64-SCTA for detection of coronary artery plaque. RESULTS: The sensitivity of detecting coronary artery plaque by 64-SCTA was 87.4%, the specificity was 87.1%, the positive predictive value was 82.2%, and the negative predictive value was 91.0%. Comparing the levels of serum Hs-CRP and IL-6 among plaque groups, the mean levels of serum Hs-CRP and IL-6 in three plaque groups were significantly higher than those in the control group (P < 0.01). The mean levels of serum Hs-CRP and IL-6 in the soft plaque group and mixed plaque group were significantly higher than those in hard plaque group (P < 0.01). Plaque burden in the soft plaque group and mixed plaque group was significantly higher than in the hard plaque group (P < 0.01), but there was no statistical difference between the soft plaque group and mixed plaque group (P = 0.246). There was a negative correlation between the CT scale and Hs-CRP and IL-6 levels in the soft plaque group (r = -0.621, P < 0.01, and r = -0.593, P < 0.01 respectively). There was a positive correlation between the plaque burden and Hs-CRP and IL-6 levels in the soft plaque group (r = 0.579, P < 0.05 and r = 0.429, P < 0.05 respectively). CONCLUSIONS: 64-SCTA is an effective way to distinguish the different quality of coronary atherosclerosis plaque. Serum Hs-CRP and IL-6 levels can be considered as the indexes to judge the degree of CHD and may reflect the activity of plaque in CHD patients. Thus it is important for clinical diagnosis and risk evaluation of acute coronary syndrome (ACS) patients.

[Plasma endothelin level in hypertensive patients receiving standard anti-hypertensive therapy with or without statins].

OBJECTIVE: To observe the association between plasma endothelin (ET) concentration and blood pressure level in essential hypertensive (EH) patients with or without complications and possible impact of statins on ET concentration. METHODS: From Sep 2007 to Mar 2009, 149 patients with EH were analyzed [44 EH, 40 EH complicated by left ventricular hypertrophy (EH-LVH), 36 EH complicated by atrial fibrillation (EH-AF), and 29 EH complicated by lacunar infarction (EH-LI)], 30 healthy persons were selected as controls. EH patients were randomly divided into routine treatment group (calcium antagonists, ACEI, diuretics, beta-receptor blocker for 8 weeks) and simvastatin intervention group (routine treatment + simvastatin 40 mg/d for 8 weeks), plasma ET concentrations before and after drug intervention were measured. RESULTS: (1) ET concentration was higher in EH group than that in control group [(71.42 +/- 6.62) pg/ml vs. (45.52 +/- 8.28) pg/ml, P < 0.01]. ET concentration was higher in EH-LVH group, EH-AF group and EH-LI group than that in EH group [(97.67 +/- 10.53) pg/ml, (102.15 +/- 12.96) pg/ml, (103.49 +/- 9.91) pg/ml vs. (71.42 +/- 6.62) pg/ml, P <0.01]. The degrees of elevated blood pressure was positively correlated with ET concentrations(all P < 0.001). (2) The left atrial diameters of EH-AF group were positively correlated with ET concentration (r = 0.684, P < 0.001). The left ventricular mass index of EH-LVH group were positively correlated with ET concentration (r = 0.545, P < 0.001). (3) The percentages of class 3 hypertension in EH-LVH group, EH-AF group and EH-LI group were higher than that in EH group (57.5%, 50.0%, 62.1% vs. 25.0%, all P < 0.05). (4) Blood pressure in class 3 hypertension patient treated with simvastatin decreased more significantly than that in routine treatment group (P < 0.05). (5) ET concentration of class 2 hypertension patient treated with simvastatin decreased significantly than that in routine treatment group (P < 0.05). ET concentrations of class 3 hypertension patient treated with simvastatin and routine treatment patient decreased significantly after treatment (P < 0.05), and the former was lower (P < 0.05). CONCLUSION: The level of ET were positively correlated with the severity of EH. Simvastatin could decrease the ET levels of patients with EH and blood pressure levels of patients with class 3 hypertension. It suggested that therapeutic alliance of antihypertensive drugs and statins could be benefit to patients with EH.