Strategies on biosynthesis and production of bioactive compounds in medicinal plants / 中草药·英文版

Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy. Compared with chemical synthesis and extraction, the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants, and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants. Here, we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants. The strategies and methods mainly include genetic engineering, plant cell culture engineering, metabolic engineering, and synthetic biology based on multiple "OMICS" technologies, with paradigms for the biosynthesis of terpenoids and alkaloids. We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products, exemplifying compounds such as vindoline (alkaloid), artemisinin and paclitaxel (terpenoids), to illustrate the power of biotechnology in medicinal plants.

Analysis of dyslipidemia management status in atrial fibrillation patients with very high and high risk of atherosclerotic cardiovascular disease / 中华心血管病杂志

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.

Current use of oral anticoagulation therapy and influencing factors among coronary artery disease patients with nonvalvular atrial fibrillation in China / 中华心血管病杂志

Objective: To investigate current use of oral anticoagulant (OAC) therapy and influencing factors among coronary artery disease (CAD) patients with nonvalvular atrial fibrillation (NVAF) in China. Methods: Results of this study derived from "China Atrial Fibrillation Registry Study", the study prospectively enrolled atrial fibrillation (AF) patients from 31 hospitals, and patients with valvular AF or treated with catheter ablation were excluded. Baseline data such as age, sex and type of atrial fibrillation were collected, and drug history, history of concomitant diseases, laboratory results and echocardiography results were recorded. CHA2DS2-VASc score and HAS-BLED score were calculated. The patients were followed up at the 3rd and 6th months after enrollment and every 6 months thereafter. Patients were divided according to whether they had coronary artery disease and whether they took OAC. Results: 11 067 NVAF patients fulfilling guideline criteria for OAC treatment were included in this study, including 1 837 patients with CAD. 95.4% of NVAF patients with CAD had CHA2DS2-VASc score≥2, and 59.7% of patients had HAS-BLED≥3, which was significantly higher than NVAF patients without CAD (P<0.001). Only 34.6% of NVAF patients with CAD were treated with OAC at enrollment. The proportion of HAS-BLED≥3 in the OAC group was significantly lower than in the no-OAC group (36.7% vs. 71.8%, P<0.001). After adjustment with multivariable logistic regression analysis, thromboembolism(OR=2.48,95%CI 1.50-4.10,P<0.001), left atrial diameter≥40 mm(OR=1.89,95%CI 1.23-2.91,P=0.004), stain use (OR=1.83,95%CI 1.01-3.03, P=0.020) and β blocker use (OR=1.74,95%CI 1.13-2.68,P=0.012)were influence factors of OAC treatment. However, the influence factors of no-OAC use were female(OR=0.54,95%CI 0.34-0.86,P=0.001), HAS-BLED≥3 (OR=0.33,95%CI 0.19-0.57,P<0.001), and antiplatelet drug(OR=0.04,95%CI 0.03-0.07,P<0.001). Conclusion: The rate of OAC treatment in NVAF patients with CAD is still low and needs to be further improved. The training and assessment of medical personnel should be strengthened to improve the utilization rate of OAC in these patients.

Catheter ablation versus medical therapy for atrial fibrillation with prior stroke history: a prospective propensity score-matched cohort study / 老年心脏病学杂志（英文版）

BACKGROUND@#Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients.@*METHODS@#AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE.@*RESULTS@#During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants.@*CONCLUSIONS@#In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

ABC-AF-Stroke score predicts thromboembolism in non-anticoagulated patients following successful atrial fibrillation ablation: a report from the Chinese Atrial Fibrillation Registry / 中华医学杂志(英文版)

BACKGROUND@#The age, biomarkers, and clinical history (ABC)-atrial fibrillation (AF)-Stroke score have been proposed to refine stroke risk stratification, beyond what clinical risk scores such as the CHA2DS2-VASc score can offer. This study aimed to identify risk factors associated with thromboembolism and evaluate the performance of the ABC-AF-Stroke score in predicting thromboembolism in non-anticoagulated AF patients following successful ablations.@*METHODS@#A total of 2692 patients who underwent successful ablations with discontinued anticoagulation after a 3-month blanking period in the Chinese Atrial Fibrillation Registry (CAFR) between 2013 and 2019 were included. Cox regression analysis was conducted to present the association of risk factors with thromboembolism risk. The ABC-AF-Stroke score was evaluated in terms of discrimination, including concordance index (C-index), net reclassification improvement (NRI) and integrated discrimination improvement (IDI), clinical utilization by decision curve analysis (DCA), and calibration by comparing the predicted risk with the observed annualized event rate.@*RESULTS@#After a median follow-up of 3.5 years, 64 patients experienced thromboembolism events. Age, prior history of stroke/transient ischemic attack (TIA), high-sensitivity cardiac troponin T (cTnT-hs), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were independently associated with thromboembolism risk. The ABC-AF-Stroke score performed statistically significantly better than the CHA2DS2-VASc score in terms of C-index (0.67, 95% confidence interval [CI]: 0.59-0.74 vs. 0.60, 95% CI: 0.52-0.67, P = 0.030) and reclassification capacity. The DCA implied that the ABC-AF-Stroke score could identify more thromboembolism events without increasing the false positive rate compared to the CHA2DS2-VASc score. The calibration curve showed that the ABC-AF-Stroke score was well calibrated in this population.@*CONCLUSIONS@#In this real-world study enrolling non-anticoagulated AF patients following successful ablations, age, prior history of stroke/TIA, level of NT-proBNP, and cTnT-hs were independently associated with an increased risk of thromboembolism. The ABC-AF-Stroke score was well-calibrated and statistically significantly outperformed the CHA2DS2-VASc score in predicting thromboembolism risk.

Exploration of the relationship between the storage time of leukodepleted red blood cell and transfusion adverse reactions / 中国输血杂志

【Objective】 To explore the relationship between the storage time of leukodepleted red blood cells and transfusion adverse reactions by analyzing the occurrence of transfusion adverse reactions of patients after leukodepleted red blood cells transfusion from four hospitals. 【Methods】 By using the electronic medical record management system, the collection and transfusion dates of leukodepleted red blood cells from four hospitals in Enshi Prefecture from 2018 to 2022, as well as the information on transfusion adverse reactions, were retrieved. 【Results】 From 2018 to 2022, a total of 697 61 bags of leukodepleted red blood cells were transfused in four hospitals, resulting in 166 cases of transfusion adverse reactions, among which 93 were allergic reactions, 63 were non hemolytic febrile reactions, and 10 were others, with a total incidence rate of transfusion adverse reactions at 0.24%. The average storage time of leukodepleted red blood cells with and without transfusion adverse reactions was (20.25±6.31) and (19.88±5.50) days, respectively. With a storage time of 7 days as the threshold, the incidence of transfusion adverse reactions was the lowest for a storage time of 15~21 days. The incidence of transfusion adverse reactions of leukodepleted red blood cells in two groups (with storage days ≤21 days and >21 days) was not statistically significant(P>0.05). 【Conclusion】 Allergic reactions were the main type of transfusion adverse reaction caused by leukodepleted red blood cells, and the incidence of transfusion adverse reactions decreased and then increased with the prolongation of the storage time of leukodepleted red blood cells. There was no significant difference in the incidence of transfusion adverse reactions with leukodepleted red blood cells stored for ≤ 21 days and >21 days.

Compliance of oral anticoagulant medication and influencing factors among nonvalvular atrial fibrillation patients with new-onset acute ischemic stroke / 中华全科医师杂志

Objective:To investigate the compliance of oral anticoagulant(OAC) medication and influencing factors among nonvalvular atrial fibrillation(NVAF) patients with new-onset acute ischemic stroke (AIS).Methods:A total of 396 NVAF patients, who initiated OAC therapy after a new-onset AIS from August 2011 to December 2020 were enrolled from China Atrial Fibrillation Registry (China-AF). The demographic characteristics, medical history, comorbid diseases and medication of patients were collected before and after the index stroke, and the influencing factors of compliance of OAC medication were analyzed.Results:Patients were followed up for a mean of 26.9 months. Among 396 patients, 228 (57.6%) had continuous anticoagulant medication (persistent OAC group);while 168 (42.4%) discontinued OAC therapy within 2 years after the index stroke (non-persistent OAC group). Patients on persistence OAC had a higher proportion of atrial fibrillation episodes than patients on non-persistent OAC [83.3% (190/228) vs. 73.8% (126/168); χ 2=5.34, P=0.021], while lower proportion of radiofrequency ablation(RFA)[18.9% (43/228) vs. 32.1% (43/228); χ 2=9.22, P=0.002]. Multivariate Cox regression modelshowed that history of RFA ( HR=1.77, 95% CI: 1.25-2.50; P=0.001) was positively associated with non-persistence of OAC. Conclusion:The study indicates that quite large proportion of NVAD patients with a new-onset of AIS discontinued OAC therapy during 2 years of follow up, and a history of RFA procedure might be an independent factor associated with discontinuing of anticoagulant therapy.

Mechanism of Hedysarum Polysaccharide in Diabetic Nephropathy in db/db Mice Based on Wnt/β-catenin Signal Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Hedysarum polysaccharides （HPS） on the Wnt/β-catenin signal pathway in db/db mice with diabetic nephropathy. MethodFifty db/db mice were randomly divided into model group， irbesartan group， and high， middle， and low-dose HPS experimental groups according to their body mass， with 10 mice in each group， and another 10 C57BL/6 mice were selected as a normal group. The normal group and the model group were given 5 mL·kg-1·d-1 distilled water， the irbesartan group was given 22.75 mg·kg-1·d-1 irbesartan suspension， and the high， middle， and low-dose HPS experimental groups were given 200， 100， and 50 mg·kg-1·d-1 HPS suspensions， respectively. The mice in the 6 groups were given intragastric administration once a day for 12 weeks. The general state， blood glucose （GLU）， 24 h urine protein （UTP）， blood creatinine （SCr）， and urea nitrogen （BUN） of mice in each group were determined. The pathological changes in the kidney tissue were observed by hematoxylin-eosin staining （HE）. The protein and mRNA expression levels of Wnt1， β-catenin， glycogen synthesis kinase-3β （GSK-3β）， and phosphorylated GSK-3β （p-GSK-3β） in the kidney were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultAfter treatment for 12 weeks， as compared with the normal group， the general state of mice in the model group was worse and the pathological ultrastructural lesions of kidney tissues were obvious. The levels of GLU， 24 h UTP， SCr， and BUN in the model group increased （P<0.01）. As compared with the model group， the general state and renal pathological ultrastructure of mice in the high and middle-dose HPS groups were improved to some extent， and the levels of SCr， BUN， and 24 h UTP in the high and middle-dose HPS groups decreased （P<0.05，P<0.01）. As compared with the normal group， the expression levels of Wnt1， β-catenin， GSK-3β， and p-GSK-3β protein and mRNA in the model group were higher （P<0.01）， while the expression levels of Wnt1， β-catenin， GSK-3β， and p-GSK-3β protein and mRNA in the high and middle-dose HPS groups were lower than those in the model group （P<0.05，P<0.01）. ConclusionHPS can alleviate the renal injury of diabetic nephropathy to some extent， and its mechanism may be related to the inhibition of the activation of the Wnt/β-catenin signal pathway.

The relationship between fasting blood glucose level and thromboembolism events in patients with non-valvular atrial fibrillation / 中华心血管病杂志

Objective: To explore the relationship between fasting blood glucose level and thromboembolism events in patients with non-valvular atrial fibrillation (NVAF). Methods: This was an observational study based on data from a multicenter, prospective Chinese atrial fibrillation registry cohort, which included 18 703 consecutive patients with atrial fibrillation (AF) in 31 hospitals in Beijing from August 2011 to December 2018. Patients were divided into 5 groups according to status of comorbid diabetes and fasting glucose levels at admission: normal blood glucose (normal glucose group), pre-diabetes group, strict glycemic control group, average glycemic control group and poor glycemic control group. Patients were followed up by telephone or outpatient service every 6 months. The primary follow-up endpoint was thromboembolic events, including ischemic stroke and systemic embolism. The secondary endpoint was the composite endpoint of cardiovascular death and thromboembolic events. Kaplan-Meier survival analysis and multifactorial Cox regression were used to analyze the correlation between fasting glucose levels and endpoint events. Results: The age of 18 703 patients with NVAF was (63.8±12.0) years, and there were 11 503 (61.5%) male patients. There were 11 877 patients (63.5%) in normal blood glucose group, 2 023 patients (10.8%)in pre-diabetes group, 1 131 patients (6.0%) in strict glycemic control group, 811 patients in average glycemic control group and 2 861 patients(4.3%) in poor glycemic control group. Of the 4 803 diabetic patients, 1 131 patients (23.5%) achieved strict glycemic control, of whom 328 (29.0%) were hypoglycemic (fasting blood glucose level<4.4 mmol/L at admission). During a mean follow-up of (51±23) months (up to 82 months), thromboembolic events were reported in 984 patients (5.3%). The survival curve analysis of Kaplan Meier showed that the incidence rates of thromboembolic events in normal glucose group, pre-diabetes group, strict glycemic control group, average glycemic control group and poor glycemic control group were 1.10/100, 1.41/100, 2.09/100, 1.46/100 and 1.71/100 person-years, respectively (χ²=53.0, log-rank P<0.001). The incidence rates of composite endpoint events were 1.86/100, 2.17/100, 4.08/100, 2.58/100, 3.16/100 person-years (χ²=72.3, log-rank P<0.001). The incidence of thromboembolic events and composite endpoint events in the other four groups were higher than that in the normal blood glucose group (P<0.001). Multivariate Cox regression analysis showed that compared with normal glucose group, the risk of thromboembolism increased in pre-diabetes group(HR=1.23, 95%CI 1.00-1.51, P=0.049), strict glycemic control group(HR=1.32, 95%CI 1.06-1.65, P=0.013) and poor glycemic control group(HR=1.26, 95%CI 1.01-1.58, P=0.044). Conclusion: Both high or low fasting glucose may be an independent risk factor for thromboembolic events in patients with NVAF.

Efficacy and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and hypertrophic cardiomyopathy / 中华心血管病杂志

Objective: To evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOAC) in patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM). Methods: This study was a prospective cohort study. The data of this study were based on the Chinese Atrial Fibrillation Registry (CAFR) Study, which was a prospective, multicenter registry study. The CAFR Study enrolled inpatients and outpatients with AF from 31 hospitals. Patients with AF and HCM were selected from August 2011 to December 2018. The patients were divided into NOAC-treated group and warfarin-treated group. General clinical data, echocardiographic results and treatment options were collected and compared between the two groups. Patients were followed up every 6 months; outcome events included effective endpoint events(thromboembolism)and safety endpoint events(major bleeding). The incidence of endpoint events in both groups was calculated and compared. Cox proportional hazards regression models and Kaplan-Meier survival analysis were performed to determine the association between NOAC use and endpoint events. Results: A total of 393 patients were included (average age: (60.5±11.8) years, 252 men (64.1%)). There were 133 (34.0%) patients in the NOAC-treated group and 260 (66.0%) patients in the warfarin-treated group. Compared with the warfarin-treated group, the patients in the NOAC-treated group had a higher proportion of paroxysmal AF, catheter ablation of AF, a lower proportion of hypertension, ischemic stroke/transient ischemic attack (TIA), lower heart rate, lower usage rate of angiotensin-converting enzyme inhibitors(ACEI)/angiotensin receptor blockers(ARB), β-blockers, non-dihydropyridine calcium channel blockers(NDH-CCB)(P<0.05). There were no significant differences on the echocardiographic results, including interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic diameter, left atrial diameter, left ventricular ejection fraction(P>0.05). After a follow-up of 42 (24, 60)months, the incidence rates of thromboembolism were 1.63 and 2.10 events per 100 person-years for NOAC-and warfarin-treated group, and those of major bleeding were 0.66 and 1.03 events per 100 person-years. Kaplan-Meier survival analysis showed survival rates free from endpoint events were similar between NOAC-treated group and warfarin-treated group(thromboembolism-free survival comparison, P=0.476; major bleeding-free survival comparison, P=0.855). Cox multivariate regression analysis revealed that there was no significant difference on risk of thromboembolism(HR=1.21, 95%CI: 0.42-3.50, P=0.720) and major bleeding(HR=1.50, 95%CI: 0.27-8.41, P=0.642) between NOAC-treated and warfarin-treated group. Conclusion: Patients with AF and HCM can be safely and effectively treated with NOAC.

Effect of Hedysarum Polysaccharides on Bcl-2/Caspase-3 Signaling Pathway of Schwann Cells Cultured in High Glucose / 中国实验方剂学杂志

ObjectiveTo observe the effects of Hedysarum polysaccharides（HPS）on the signaling pathways of B-cell lymphoma 2 （Bcl-2）， cysteinyl aspartate-specific protease 3 （Caspase-3）， and Bcl-2-associated X protein （Bax） in Schwann cells（SCs）cultured in high glucose，and explore the possible mechanism of HPS against diabetic peripheral neuropathy（DPN）. MethodFour SD suckling mice aged 5-7 days were randomly divided into a normal group，a high-glucose group，an HPS + high-glucose group，and an α-lipoic acid（α-LA）+ high-glucose group. SCs were extracted from the sciatic nerve and cultured in a 37 ℃，5% CO2 incubator. After the cells reached 80% confluence，Cell Counting Kit-8（CCK-8）was used to screen the experimental concentrations suitable for high glucose，HPS， and α-LA interventions. Western blot and Real-time polymerase chain reaction （Real-time PCR）were used to detect the protein and mRNA expression of Bcl-2，Bax，and Caspase-3. The apoptosis rate of SCs was detected by flow cytometry using Annexin V-fluorescein isothiocyanate （FITC）/propidium iodide （PI）. ResultAs revealed by Western blot and real-time PCR，compared with the normal group，the high-glucose group showed reduced protein and mRNA expression of Bcl-2 and increased protein and mRNA expression of Bax and Caspase-3（P<0.01）. Compared with the high-glucose group，the HPS + high-glucose group and the α-LA + high-glucose group showed increased protein and mRNA expression of Bcl-2 and decreased protein and mRNA expression of Bax and Caspase-3（P<0.01）. As displayed by the results of flow cytometry using Annexin V/PI， compared with the normal group，the high-glucose group showed increased apoptosis rate；compared with the high-glucose group，the HPS + high-glucose group and the α-LA + high-glucose group showed reduced apoptosis rate（P<0.01）. ConclusionHPS can alleviate the apoptotic response of SCs，and its mechanism may be related to the inhibition of the activation of the Bcl-2/Caspase-3 signaling pathway.

The impact of digoxin on the long-term outcomes in patients with coronary artery disease and atrial fibrillation / 中华内科杂志

Objective:To investigate the long-term safety of digoxin in patients with coronary artery disease (CAD) and atrial fibrillation (AF).Methods:This was a prospective study, in which 25 512 AF patients were enrolled from China Atrial Fibrillation Registry Study. After exclusion of patients receiving ablation therapy at the enrollment, 1 810 CAD patients [age: (71.5±9.3)years] with AF were included. The subjects were grouped into the digoxin group and non-digoxin group, and were followed up for a period of 80 months. Long-term outcomes were compared between the groups and an adjusted Cox regression analysis was applied to evaluate the risk of digoxin on the long-term outcomes. The primary endpoint was all-cause mortality.Results:The patients were followed up for a median period of 3.05 years. After multivariable adjustment, the Cox regression analysis showed that digoxin significantly increased the risk of all-cause mortality ( HR=1.28, 95% CI 1.01-1.61, P=0.038), cardiovascular mortality ( HR=1.48,95% CI 1.10-2.00, P=0.010), cardiovascular hospitalization ( HR=1.67,95% CI 1.35-2.07, P=0.008) and the composite endpoints ( HR=2.02,95% CI 1.71-2.38, P<0.001). In the subgroup of patients with heart failure (HF), digoxin was not associated with the risk of all-cause mortality, but was still associated with the increased risk of cardiovascular mortality ( HR=1.44,95% CI 1.05-1.98, P=0.025), cardiovascular hospitalization ( HR=1.44,95% CI 1.09-1.90, P=0.010) and the composite endpoints ( HR=1.37, 95% CI 1.01-1.70, P=0.004). However, in the subgroup of patients without HF, digoxin was only associated with all-cause mortality ( HR=2.56,95% CI 1.44-4.54, P=0.001). Conclusion:Digoxin significantly increased the risk of all-cause mortality in CAD patients with AF, especially in patients without HF.

Feasibility and safety of intracardiac ultrasound-assisted atrial septal puncture during radiofrequency ablation for atrial fibrillation / 中华心血管病杂志

Objective: To explore the feasibility and safety of intracardiac ultrasound-assisted atrial septal puncture (ASP) during radiofrequency ablation for atrial fibrillation. Methods: We enrolled 241 consecutive patients scheduled to radiofrequency ablation for atrial fibrillation in Beijing Anzhen Hospital from July to September 2020. Inclusion criteria: patients aged over 18 years with a clear electrocardiogram record of atrial fibrillation. Patients were divided into 2 groups: ASP with ultrasound-assisted X-ray (ultrasound group, n=123), ASP under X-ray alone (X-ray group, n=118). Clinical features of patients including age, sex, percent of paroxysmal atrial fibrillation, and repeat ablation, CHA2DS2-VASc score and past history (hypertension, diabetes mellitus, coronary artery disease, stroke/transient ischemic attack (TIA), valve diseases) and echocardiographic parameters (left atrial dimension, left ventricular ejection fraction, left ventricular end-diastolic dimension) were obtained and compared. The first-pass rate, radiation exposure time, duration of ASP, and complications of ASP were also compared between the two groups. Results: The age of patients in this cohort was (62.5±8.0) years, and the proportion of males was 57.0% (n=138). Among them, the proportion of paroxysmal atrial fibrillation was 56.0% (n=135), and the ratio of repeat ablation was 17.8% (n=43). Age, sex, percent of paroxysmal atrial fibrillation, history of hypertension, diabetes mellitus were similar between the two groups. The first-pass rate was significantly higher in the ultrasound group than in the X-ray group (94.3% (116/123) vs. 79.7% (94/118), P=0.001); the exposure time of X-ray was significantly shorter in the ultrasound group than in the X-ray group ((31.3±7.9) s vs. (124.8±35.7) s, P<0.001), while the duration of ASP was longer in the ultrasound group ((10.1±1.8) minutes vs. (8.2±1.3) minutes, P<0.001). In terms of complications, the incidence of puncture into the pericardium was lower in the ultrasound group (0 vs.3.4% (4/118), P=0.039); the rate of transient ST-segment elevation post ASP was similar between the ultrasound group and X-ray group (2.4% (3/123) vs. 1.7% (2/118), P=0.999). Conclusion: Intracardiac ultrasound-assisted atrial septal puncture can effectively improve the accuracy of atrial septal puncture, shorten the radiation exposure time, and reduce the complications related to atrial septal puncture.

Causes of death and influencing factors of atrial fibrillation patients undergoing anticoagulation therapy / 中华心血管病杂志

Objective: To investigate the causes of death and predictors in patients with nonvalvular atrial fibrillation (AF) undergoing anticoagulation therapy. Methods: Consecutive anticoagulated nonvalvular AF patients were recruited from the China Atrial Fibrillation Registry (China-AF) Study from August 2011 to December 2018. After exclusion of patients with hypertrophic cardiomyopathy, dilated cardiomyopathy, or loss of follow-up within 1 year, 2 248 patients were included in this analysis. Enrolled patients were followed up were followed up for 3 and 6 months, and then every 6 months. The primary endpoint was death, including cardiovascular death, non-cardiovascular death and undetermined death. The patients were divided into survival group and death group according to the survival status after follow-up. Clinical information such as age and sex was collected. Cox proportional hazards regression was performed to identify associated risk factors for all-cause mortality, and Fine-Gray competing risk model was used to identify associated risk factors for cardiovascular mortality. Results: A total of 2 248 patients with atrial fibrillation receiving anticoagulant therapy died over a mean follow-up of (42±24) months, mean age was (67±10) years old and 41.1% (923/2 248) patients were female. The mortality rate was 2.8 deaths per 100 patient-years. The most common cause of death was cardiovascular deaths, accounted for 55.0% (120/218). Worsening heart failure was the most common cause of cardiovascular deaths (18.3% (40/218)), followed by bleeding events (12.9% (28/218)) and ischemic stroke (8.7% (19/218)). Multivariate Cox regression analysis showed that age (HR = 1.05, 95%CI 1.04-1.07, P<0.001), anemia (HR = 1.81, 95%CI 1.02-3.18, P = 0.041), heart failure (HR=2.40, 95%CI 1.75-3.30, P<0.001), ischemic stroke/transient ischemic attack (TIA)(HR = 1.59, 95%CI 1.21-2.13, P = 0.001) and myocardial infarction (HR = 2.93, 95%CI 1.79-4.81, P<0.001) were independently associated with all-cause death. Fine-Gray competing risk model showed that age (HR=1.05, 95%CI 1.02-1.08, P<0.001), heart failure (HR=2.81, 95%CI 1.79-4.39, P<0.001), ischemic stroke/TIA (HR=1.50, 95%CI 1.02-2.22, P=0.041) and myocardial infarction (HR=3.31, 95%CI 1.72-6.37, P<0.001) were independently associated with cardiovascular death. Conclusions: In anticoagulated nonvalvular AF patients, ischemic stroke represents only a small subset of deaths, whereas worsening heart failure is the most common cause of cardiovascular deaths. Heart failure, ischemic stroke/TIA, and myocardial infarction are associated with increased mortality.

The thromboembolism risk of low-risk atrial fibrillation patients with different clinical characteristics / 中华心血管病杂志

Objective: This study explored the thromboembolism risk of low-risk atrial fibrillation (AF) patients (CHA2DS2-VASc score of 0 or 1 for male and 1 or 2 for female) with different clinical characteristics to provide the basis for anticoagulation decision-making in these patients. Methods: We prospectively enrolled consecutive 2 862 nonvalvular low-risk AF patients between August 2011 to December 2018 in China-AF (China Atrial Fibrillation Registry) Study, their CHA2DS2-VASc score was 0 or 1 for male and 1 or 2 for female. According to their age, sex, presence or absence of hypertension, diabetes mellitus, congestive heart failure, and vascular disease at the time of enrolling, patients were divided into CHA2DS2-VASc score 0 score group, 1 score group, and 2 score group. Patients were followed up every 6 months by outpatient clinic visit or telephone interview. The outcome was a thromboembolic event, including ischemic stroke and systemic embolism. Univariate Cox regression analysis was used to compare the thromboembolism risk between the patients with different risk factors and CHA2DS2-VASc score 0 group. Results: A total of 2 862 low-risk atrial fibrillation patients were enrolled in this study. 915 patients (32.0%) were female, and age was (55.0±10.7) years old. There were 933 patients (32.6%) in CHA2DS2-VASc score 0 group, 1 401 patients (49.0%) in score 1 group and 528 patients (18.5%) in score 2 group. During follow-up (median 1.5 years, 5 811.82 person-years), 33 cases of thromboembolic events were recorded, the annual rate of thromboembolism was 0.57% (95%CI 0.40%~0.80%). The number of thromboembolic events in patients with CHA2DS2-VASc score 0, 1 and 2 were 8, 11 and 14, respectively, and the annual thromboembolism event rates were 0.40% (95%CI 0.20%-0.81%), 0.39% (95%CI 0.22%-0.71%) and 1.34% (95%CI 0.80%-2.27%), respectively. The risk of thromboembolism of CHA2DS2-VASc score 2 group (HR=3.53, 95%CI 1.48-8.44; P=0.005), especially female patients aged 65-74 years in CHA2DS2-VASc score 2 group (HR=2.67, 95%CI 1.63-4.38; P<0.000) was significantly higher than that in patients of CHA2DS2-VASc score 0 group. Conclusion: Low-Risk Atrial Fibrillation patients with CHA2DS2-VASc score 2, especially female patients aged 65-74 years old with CHA2DS2-VASc score 2 are at higher risk of thromboembolism in low-risk AF patients. For such patients, intensified oral anticoagulant therapy might be helpful to reduce the risk of thrombolism.

Impact of history of hypertension and blood pressure levels on the risk of thromboembolism in nonvalvular atrial fibrillation patients / 中华心血管病杂志

Objective: To investigate the impact of history of hypertension and blood pressure levels on the thromboembolism risk in the setting of nonvalvular atrial fibrillation (NVAF). Methods: China Atrial Fibrillation Registry Study prospectively enrolled 25 512 atrial fibrillation (AF) patients between August 2011 and December 2018. After exclusion of patients with valvular AF, hypertrophic cardiomyopathy, receiving anticoagulation or ablation therapy at the enrollment, 7 757 patients were included in analysis. The primary endpoint was the time to the first occurrence of ischemic stroke or systemic embolism. Cox proportional hazards models were performed to evaluate whether a history of hypertension or blood pressure levels were independently associated with thromboembolism. Results: During a mean follow up of (35±25) months, 455 （5.9%）thromboembolic events occurred. The crude incidence rate of thromboembolism in patients with a history of hypertension was higher than that in patients without hypertension (2.38 vs. 1.35 per 100 patient-years, χ²=16.8，Log-rank P<0.001). Patients were further divided into 4 groups according to systolic blood pressure (SBP) levels at baseline, the crude incidence rate of thromboembolism significantly increased in proportion to the elevation of SBP levels (χ²=17.9，Log-rank P<0.001). However, there was no significant difference in thromboembolism risk among 4 groups stratified by diastolic blood pressure (DBP) levels (χ²=0.6，Log-rank P=0.907). Multivariable regression analysis showed that history of hypertension was independently associated with a 27% higher risk of thromboembolism (HR=1.27, 95%CI 1.01-1.61, P=0.045). Patients with SBP≥140 mmHg (1 mmHg=0.133 kPa) was associated with 36% higher risk of thromboembolism than patients with SBP<120 mmHg (HR=1.36, 95%CI 1.02-1.82, P=0.036). However, patients with SBP 120-129 mmHg or 130-139 mmHg were not at a higher risk of thromboembolism as compared to the patients with SBP<120 mmHg (SBP 120-129 mmHg: HR=1.23, 95%CI 0.90-1.67, P=0.193; SBP 130-139 mmHg: HR=1.30, 95%CI 0.95-1.77, P=0.098). In addition, DBP levels were not independently associated with the increased thromboembolism risk. Conclusion: A history of hypertension and SBP≥140 mmHg are independent predictors of thromboembolism risk in patients with NVAF. These results indicate that intensive efforts to lower SBP below 140 mmHg might be an important strategy to reduce the risk of stroke in patients with NVAF.

Risk factors for recurrent hospitalizations of patients with atrial fibrillation / 中华心血管病杂志

Objective: To determine the predictors of recurrent hospitalizations among atrial fibrillation (AF) patients. Methods: We analyzed data from the Chinese Atrial Fibrillation Registry (CAFR), a prospective cohort study involving non-valvular atrial fibrillation (NVAF) patients from Augest 2011 to December 2017. A total of 5 349 NVAF patients with a minimum of 48 months follow-up were included for analysis. Data including patient demographics, complications, medical and ablation history were collected. The maximum number of all-cause hospitalizations within one-year for each patient served as the primary endpoint. Patients hospitalized less than twice within one-year were defined as non-recurrent hospitalizations group, those hospitalized at least twice within one-year were definned as recurrent hospitalizations group. Logistic regression model was used to identify associated risk factors for recurrent hospitalizations. Results: Of 5 349 NVAF patients, those hospitalized for 0, 1, 2, 3, 4 and at least 5 times within one-year was 2 703 (50.5%), 1 776 (33.2%), 642 (12.0%), 161(3.0), 52 (1.0%), 15 (0.3%), respectively. Eight hundred and seventy (16.3%) patients were included in recurrent hospitalizations group, 4 479 (83.7%) patients were included in non-recurrent hospitalizations group. Compare with non-recurrent hospitalizations group, patients in recurrent hospitalizations group was more likely to be older and female, more frequently had a history of hypertension, heart failure, coronary heart disesase, ischaemic stroke/transient ischaemic attack, diabetes mellitus, peptic ulcer, a AF duration for more than 1 year, medication including drugs for ventricular rate control, statin, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blocker (ARB) and higher CHA(2)DS(2)-VASc scores (P<0.05), but less frequently had higher education, a history of drinking, smoking and ablation (P<0.05). Multivariable analysis showed that age 50-64 (OR=1.47, 95%CI 1.20-1.80), age≥65 (OR=1.89, 95%CI 1.50-2.38), female (OR=1.21, 95%CI 1.01-1.46), hypertension history (OR=1.42, 95%CI 1.16-1.74), heart failure history (OR=1.73, 95%CI 1.37-2.18), coronary heart disease history (OR=1.63, 95%CI 1.31-2.03), peptic ulcer history (OR=2.00, 95%CI 1.18-3.39) were independent risk factors for recurrent hospitalizations, while higher education (college or above) (OR=0.82, 95%CI 0.69-0.99) was the protective factor for recurrent hospitalizations. Conclusions: Nearly 1 in 6 of AF patients were admitted to hospital more than once within one year in this NVAF cohort. Age≥50, female, hypertension history, heart failure history, coronary heart disease history, peptic ulcer history are associated with an increased risk of recurrent hospitalizations.

Association between use of amiodarone for non-valvular atrial fibrillation and patient survival: from the prospective China Atrial Fibrillation Registry / 中华医学杂志(英文版)

BACKGROUND@#Post hoc analysis of the landmark atrial fibrillation follow-up investigation of rhythm management trial revealed that amiodarone was associated with higher risks of mortality, intensive care unit admission, and non-cardiovascular death. We aim to evaluate the association between amiodarone use and patient survival under updated medical mode and level using data from the China Atrial Fibrillation (China-AF) Registry study.@*METHODS@#Clinical data of 8161 non-valvular atrial fibrillation (NVAF) patients who were antiarrhythmic drug (AAD)-naive before enrollment into the China-AF Registry, recruited between August 2011 and February 2017, were collected. The primary outcome was all-cause mortality. A Cox proportional hazard regression model was used to evaluate the association between amiodarone use and the outcome. We also calculated the rate of sinus rhythm maintenance at the penultimate follow-up.@*RESULTS@#Compared with 6167 patients of non-AAD group, 689 patients of the amiodarone group were younger (mean age 65.6 vs. 68.6 years), more frequently completed high school education, had fewer comorbidities such as chronic heart failure, prior bleeding, and stroke, and were more likely to be treated in tertiary hospitals while less hospitalization. The proportion of persistent AF was much lower among users of amiodarone, who were also less likely to be taking oral anticoagulants. The patients in the amiodarone group had a statistically insignificant lower incidence of all-cause mortality (2.44 vs. 3.91 per 100 person-years) over a mean follow-up duration of 300.6 ± 77.5 days. After adjusting for potential confounders, amiodarone use was not significantly associated with a lower risk of all-cause mortality (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42-1.49). Sub-group analysis revealed the consistent results. The rate of sinus rhythm maintenance at the penultimate follow-up in the amiodarone group was significantly higher than in the non-AAD group.@*CONCLUSIONS@#Our study indicated that amiodarone use was not significantly associated with a lower risk of 1-year all-cause mortality compared with a non-AAD strategy in "real-world" patients with NVAF.

Effectiveness of different screening strategies for primary prevention of cardiovascular diseases in a rural northern Chinese population / 北京大学学报(医学版)

OBJECTIVE@#To estimate the potential health benefit of screening strategies for cardiovascular diseases primary prevention in a rural northern Chinese population.@*METHODS@#A total of 6 221 adults aged 40-74 years old, from rural Beijing, China and free from cardiovascular diseases at baseline were included. The following screening strategies were compared: Strategy 1, the strategy based on numbers of risk factors recommended by the Chinese Guideline for Prevention of Cardiovascular Diseases in people aged 40-74; Strategy 2, screening people aged 40-74 based on the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) risk prediction model; Strategy 3, screening people aged 50-74 using the China-PAR risk prediction model. Participates who were classified into medium- or high-risk by the corresponding strategies would be introduced to lifestyle intervention, while high risk population would take medication in addition. Markov model was used to compare the potential health benefits within 10 years in each scenario, which applied the parameters from this rural northern Chinese cohort, published literatures, meta-analyses and systematic reviews, clinical trials and other cohort studies of Chinese population. Quality-adjusted life year (QALY) gained, cardiovascular diseases (CVD) events/deaths could be prevented and number needed to be screened (NNS) per QALY gained/per CVD event prevented/per CVD death prevented were calculated to compare the effectiveness. One-way sensitivity analysis concerning uncertainty of cardiovascular disease incidence rate and probabilistic sensitivity analysis about the uncertainty of hazard ratios were conducted.@*RESULTS@#Compared with non-screening strategy, the potential health benefits of each strategy were: Strategy 1 would gain QALY of 498 (95%CI: 103-894) and prevent 298 (95%CI: 155-441) CVD events; Strategy 2 would gain QALY of 691 (95%CI: 233-1 149) and prevent CVD events of 374 (95%CI: 181-567); Strategy 3 would gain QALY of 654 (95%CI: 199-1 108) and prevent CVD events of 346 (95%CI: 154-538). Screening strategy based on ChinaPAR risk prediction model (strategy 2 or 3) would be generally better in terms of QALY gained, CVD events/deaths prevented and NNS than the strategy based on numbers of CVD risk factors (all P<0.05 except NNS per QALY gained and NNS per CVD event prevented in 40-74 years). Similar benefits were obtained for the strategy 2 and 3. The results were consistent in the sensitivity analyses on the parameters of incidence rates and hazard ratios.@*CONCLUSION@#Screening people to target increased risks of cardiovascular diseases in this rural northern Chinese population is necessary. Screening strategy based on China-PAR risk prediction model could gain more health benefits than that based on numbers of CVD risk factors.

Statin adherence and influencing factors in hyperlipidemia patients treated in community health centers in Beijing / 中华健康管理学杂志

Objective@#To investigate statin adherence and influencing factors in hyperlipidemia patients treated in community health centers.@*Method@#This study enrolled hyperlipidemia patients for whom statins were newly prescribed by doctors at 7 community health centers. Baseline and follow-up information was collected by well-trained investigators by telephone. Adherence to statins was evaluated after 3 months of follow-up.@*Results@#We included 104 hyperlipidemia patients for whom statins were newly prescribed between July and December 2017; of these, 48.1% knew about the complications of hyperlipidemia and 84.6% thought it was necessary to take lipid-lowering drugs; however, 63.5% were concerned about the side effects of these drugs. After 3 months of follow-up, 40.4% of patients had stopped taking statins, and 60.5% were nonadherent to the statin prescriptions. The analysis of influencing factors showed that hyperlipidemia history less than 6 months (OR=9.644, 95%CI: 3.214-28.943, P<0.001) and having to take more than 2 pills per day (OR=3.536, 95%CI: 1.254-9.972, P=0.017) were positively associated with cessation of statin use, while thinking it necessary to take lipid-lowering drugs (OR=0.126, 95%CI: 0.018-0.883, P=0.037) was negatively associated with cessation of statin use. Meanwhile, hyperlipidemia history for less than 6 months (OR=3.368, 95%CI: 1.283-8.847, P=0.014) was positively associated with poor statin adherence.@*Conclusion@#Poor statin adherence was observed in patients treated in community health centers. Health knowledge awareness, attitude toward chronic disease treatment, i.e., lipid-lowering treatment, and pill burden might influence statin adherence.