Acceptance of COVID-19 boosters among hypertensive patients in China: A multicenter cross-sectional study.

Hypertension, a prevalent chronic disease, has been associated with increased COVID-19 severity. To promote the COVID-19 booster vaccination of hypertensive patients, this study investigated the willingness to receive boosters and the related influencing factors based on the health belief model (HBM model). Between June and October 2022, 453 valid questionnaires were collected across three Chinese cities. The willingness to receive a booster vaccination was 72.2%. The main factors that influenced the willingness of patients with hypertension to receive a booster shot were male (χ2 = 7.008, p = .008), residence in rural (χ2 = 4.778, p = .029), being in employment (χ2 = 7.232, p = .007), taking no or less antihypertensive medication (χ2 = 9.372, p = .025), with less hypertension-related comorbidities (χ2 = 35.888, p < .0001), and did not have any other chronic diseases (χ2 = 28.476, p < .0001). Amid the evolving COVID-19 landscape, the willingness to receive annual booster vaccination was 59.4%, and employment status (χ2 = 10.058, p = .002), and presence of other chronic diseases (χ2 = 14.256, p < .0001) are associated with the willingness of annual booster vaccination. Respondents with higher perceived severity, perceived benefits, perceived self-efficacy, and lower perceived barriers were more willing to receive booster shots. The mean and median value of willingness to pay (WTP) for a dose of booster were 53.17 CNY and 28.31 CNY. Concerns regarding booster safety and the need for professional advice were prevalent. Our findings highlight the importance of promoting booster safety knowledge and health-related management among hypertensive individuals through professional organizations and medical specialists.

Suppression of the gut microbiota-bile acid-FGF19 axis in patients with atrial fibrillation.

This study aimed to investigate the role of the gut microbiota (GM)-bile acid (BA)-fibroblast growth factor (FGF) 19 axis in patients with atrial fibrillation (AF). Gut bacterial metabolisms of BAs were determined in an AF metagenomic dataset. The composition of faecal BAs pools was characterized by targeted metabolomics in an independent AF cross-sectional cohort. Circulating levels of FGF19 were measured by ELISA. In vitro cell experiments were conducted to validate the regulatory role of FGF19 in atrial cardiomyocytes stimulated with palmitic acid. First, metagenomic profiling revealed that gut microbial biotransformation from primary to secondary BAs was dysregulated in AF patients. Second, the proportion of secondary BAs decreased in the faeces of patients with AF. Also, eight BAs were identified as AF-associated BAs, including seven AF-enriched BAs (ursodeoxycholic acid, chenodeoxycholic acid, etc.), and AF-decreased dehydrolithocholic acid. Third, reduced levels of circulating FGF19 were observed in patients with AF. Subsequently, FGF19 was found to protect against palmitic acid-induced lipid accumulation and dysregulated signalling in atrial cardiomyocytes, including attenuated phosphorylation of YAP and Ca2+ /calmodulin-dependent protein kinases II and secretion of interleukin-1ß, mediated via peroxisome proliferator-activated receptor α. Our data found decreased levels of secondary BAs and circulating FGF19, resulting in the impaired protective function of FGF19 against lipid accumulation in atrial cardiomyocytes.

Circulating plasma galectin-3 predicts new-onset atrial fibrillation in patients after acute myocardial infarction during hospitalization.

BACKGROUND: New-onset atrial fibrillation (NOAF) is a common complication in patients with acute myocardial infarction (AMI) during hospitalization. Galectin-3 (Gal-3) is a novel inflammation marker that is significantly associated with AF. The association between post-AMI NOAF and Gal-3 during hospitalization is yet unclear. OBJECTIVE: The present study aimed to investigate the predictive value of plasma Gal-3 for post-AMI NOAF. METHODS: A total of 217 consecutive patients admitted with AMI were included in this retrospective study. Peripheral venous blood samples were obtained within 24 h after admission and plasma Gal-3 concentrations were measured. RESULTS: Post-AMI NOAF occurred in 18 patients in this study. Patients with NOAF were older (p < 0.001) than those without. A higher level of the peak brain natriuretic peptide (BNP) (p < 0.001) and Gal-3 (p < 0.001) and a lower low-density lipoprotein cholesterol level (LDL-C) (p = 0.030), and an estimated glomerular filtration rate (e-GFR) (p = 0.030) were recorded in patients with post-AMI NOAF. Echocardiographic information revealed that patients with NOAF had a significantly decreased left ventricular eject fraction (LVEF) (p < 0.001) and an increased left atrial diameter (LAD) (p = 0.004) than those without NOAF. The receiver operating characteristic (ROC) curve analysis revealed a significantly higher value of plasma Gal-3 in the diagnosis of NOAF for patients with AMI during hospitalization (area under the curve (p < 0.001), with a sensitivity of 72.22% and a specificity of 72.22%, respectively. Multivariate logistic regression model analysis indicated that age (p = 0.045), plasma Gal-3 (p = 0.018), and LAD (p = 0.014) were independent predictors of post-MI NOAF. CONCLUSIONS: Plasma Gal-3 concentration is an independent predictor of post-MI NOAF.

Predictive value of CTRP3 for the disease recurrence of atrial fibrillation patients after radiofrequency ablation.

OBJECTIVE: To explore the expression of plasma CTRP3 in patients with non-valvular paroxysmal atrial fibrillation after radiofrequency ablation and its predictive value for disease recurrence. METHODS: In this retrospective study, the patients in the Heart Center of Beijing Chaoyang Hospital from June 2016 to November 2017 were collected. According to the guidelines for diagnosis and treatment of atrial fibrillation 2016, patients diagnosed with paroxysmal atrial fibrillation were selected as the study subjects. All patients with successful radiofrequency ablation of atrial fibrillation were followed up by telephone or outpatient service at 1, 3, 6 and 12 months after radiofrequency ablation, respectively. Recurrence of atrial fibrillation was defined as a duration of rapid atrial arrhythmia ≥30 seconds confirmed by electrocardiogram or 24-hour ambulatory electrocardiogram 3 months after radiofrequency ablation. According to the follow-up results, the patients were divided into a recurrent group and non-recurrent group. The level of CTRP3 was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Analysis of clinical baseline data showed significant differences between the recurrent group and the non-recurrent group in age, systolic blood pressure, diastolic blood pressure, EGFR, thyroid stimulating hormone level, platelet count, high-sensitivity C-reactive protein, NT proBNP, left atrial anterior posterior diameter, left atrial upper and lower diameter and CTRP3 (P < 0.05). The univariate logistic regression showed that older age (or = 1.08, P < 0.001), increased diastolic blood pressure (OR = 1.051, P = 0.002), cardiac dysfunction (OR = 2.594, P = 0.01), high-sensitivity C-reactive protein (OR = 1.134, P = 0.008) and NT proBNP (OR = 1.000, P = 0.005), increased anterior posterior diameter of left atrium (OR = 1.158, P < 0.001), increased upper and lower diameter of left atrium (OR = 1.133, P < 0.001), thrombocytopenia (OR = -0.008, P < 0.027) and CTRP3 (OR = 1.007, P = 0.006) were the risk factors for the recurrence of atrial fibrillation after radiofrequency ablation. Moreover, the multivariate logistic regression analysis demonstrated that CTRP3 (or = 1.032, P = 0.005) was an independent predictor of recurrence. CONCLUSION: The plasma concentration of CTRP3 increased significantly in patients with recurrent atrial fibrillation after radiofrequency ablation. Moreover, CTRP3 was a predictor of recurrence after radiofrequency ablation in patients with atrial fibrillation.

Adeno-associated virus-mediated in vivo suppression of expression of EPHX2 gene modulates the activity of paraventricular nucleus neurons in spontaneously hypertensive rats.

BACKGROUND: Hypertension can be attributed to increased sympathetic activities. Presympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus are capable of modulating sympathetic outflow, thus contributing to the pathogenesis of neurogenic hypertension. Epoxyeicosatrienoic acids (EETs) were reported to have anti-hypertensive effects, which could be degraded by soluble epoxide hydrolase (sEH), encoded by EPHX2. However, the potential effect of EETs on PVN neuron activity and the underlying molecular mechanism are largely unknown. METHODS: Knockdown of EPHX2 in spontaneously hypertensive rats (SHRs) was achieved by tail-intravenous injection of AAV plasmid containing shRNA targeting EPHX2. Whole-cell patch clamp was used to record action potentials of PVN neurons. An LC-MS/MS System was employed to determine 14,15-EET levels in rat cerebrospinal fluid. qPCR and western blotting were applied to examine the expression level of EPHX2 in various tissues. ELISA and immunofluorescence staining were applied to examine the levels of ATP, D-serine and glial fibrillary acidic protein (GFAP) in isolated astrocytes. RESULTS: The expression level of EPHX2 was higher, while the level of 14,15-EET was lower in SHRs than normotensive Wistar-Kyoto rats (WKY) rats. The spike firing frequency of PNV neurons in SHRs was higher than in WKY rats at a given stimulus current, which could be reduced by either EPHX2 downregulation or 14,15-EET administration. In isolated hypothalamic astrocytes, the elevated intracellular ATP or D-serine induced by Angiotensin II (Ang II) treatment could be rescued by 14,15-EET addition or 14,15-EET combing serine racemase (SR) downregulation by siRNA, respectively. Furthermore, 14,15-EET treatment reduced the Ang II-induced elevation of GFAP immunofluorescence. CONCLUSIONS: The elevation of EET levels by EPHX2 downregulation reduced presympathetic neuronal activity in the PVN of SHRs, leading to a reduced sympathetic outflow in hypertension rats. The ATP/SR/D-serine pathway of astrocytes is involved in EET-mediated neuroprotection.

Distal Transradial Access: a Safe and Feasible Approach for Coronary Catheterization in Cases of Total Radial Artery Occlusion.

Radial artery occlusion (RAO) is still a major complication of coronary catheterization (CC) via transradial access (TRA). Recently, coronary angiography (CAG) and percutaneous coronary intervention (PCI) through distal transradial access (dTRA) have been proven to be safe and feasible, but RAO recanalization and complete CC via dTRA have been rarely reported. Twenty-nine consecutive patients with RAO were enrolled in the present study. RAO was first confirmed by ultrasonography and after puncture of the distal radial artery (RA) in the anatomical snuffbox; cannula angiography was conducted to confirm total RAO. With the exception of two patients, we successfully recanalized the occluded RA in 27 patients. After RAO recanalization, subsequent CAG and PCI were successful, and no complications occurred. RAO recanalization and complete coronary catheterization via dTRA are safe and feasible.

Phytate Coordination-Enhanced Electrocatalytic Activity of Copper for Nitroarene Hydrogenation through Concerted Proton-Coupled Electron Transfer.

Coupling acid-electrolyte proton exchange membrane fuel cells for electricity generation and cathodic hydrogenation for valuable chemical production shows great potential in energy and chemical industry. The key for this promising approach is the identification of cathode electrocatalysts with acid resistance, high activity, and low fabrication cost for practical applications. Among various promising cathodic candidates for this integrative approach, the easily available and cheap Cu suffers from low acidic hydrogenation activity due to kinetically arduous proton adsorption/activation. Inspired by the kinetic advantages of the concerted proton-coupled electron transfer (CPET) over the sequential proton-electron transfer process, herein, we use phytate coordination on Cu surface to overcome the kinetic bottleneck for proton adsorption/activation through the CPET pathway in an acidic half-cell setup; this leads to 1 order of magnitude activity enhancement (36.94-fold) for nitrobenzene hydrogenation. Mechanistic analysis confirms that phytate, as proton acceptor, induces the CPET process and overcomes the above kinetic limitations by tuning the d-band center and concentrating protons on the Cu surface. Consequently, the CPET process facilitates the formation of active hydrogen intermediates for efficient cathodic hydrogenation. This work provides a promising approach to integrate electricity generation and chemical production.

The common characteristics and mutual effects of heart failure and atrial fibrillation: initiation, progression, and outcome of the two aging-related heart diseases.

Atrial fibrillation (AF) and heart failure (HF) are common chronic diseases noted in humans. AF and HF share several risk factors, such as age, hypertension, obesity, diabetes, and dyslipidemia. They can interact with each other, while both their morbidity and mortality have been considerably increased. And AF and HF often occur together, suggesting a strong association between the two. However, the underlying mechanism behind this association is not well understood. Among them, aging is the most significant common risk factor, which represents an aging heart and is characterized by fibrosis and decreased number of cardiomyocytes, known as senescence-related cardiac remodeling for both atria and ventricles. Finally, it is proposed that cardiac remodeling is the key link between AF and HF.

Effect of ApoE ε4 gene polymorphism on the correlation between serum uric acid and left ventricular hypertrophy remodeling in patients with coronary heart disease.

Background: Hyperuricemia and dyslipidemia are associated with left ventricular hypertrophy (LVH), while the effect of ApoE gene polymorphism on the correlation between serum uric acid (UA) level and severity of LVH in patients with coronary heart disease (CHD) has not been clarified. Methods: This was a retrospective observational study of patients with CHD. Patients were divided into groups of ε4 carriers and non-ε4 carriers based on sanger sequencing. The association of ApoE ε4 gene polymorphism, serum UA level, and LVH, determined by cardiac color Doppler ultrasound, was evaluated by multivariate analysis. Results: A total of 989 CHD patients who underwent ApoE genotyping were enrolled and analyzed. Among them, the frequency of the ApoE ε4 genotype was 17.9% (15.7% for E3/4, 1.1% for E4/4, and 1.1% for E2/4). There were 159 patients with LVH, 262 with end-diastolic LV internal diameter (LVEDD) enlargement, 160 with left ventricular ejection fraction (LVEF) reduction, and 154 with heart failure. Multivariate analysis showed that for every increase of 10 µmol/L in serum UA level, the risk of LVH decreased in ε4 carriers (odds ratio (OR) = 0.94, 95% confidence interval (CI): 0.890-0.992, P = 0.025) and increased in non-ε4 carriers (OR = 1.03, 95% CI: 1.005-1.049, P = 0.016). The risk of LVEDD enlargement tended to decrease in ε4 carriers (OR = 0.98, 95% CI: 0.943-1.023, P = 0.391) and increased in non-ε4 carriers (OR = 1.03, 95% CI: 1.009-1.048, P = 0.003). The risk of LVEF reduction was reduced in ε4 carriers (OR = 0.996, 95% CI: 0.949-1.046, P = 0.872) and increased in non-ε4 carriers (OR = 1.02, 95% CI: 0.994-1.037, P = 0.17). The risk of LVEDD enlargement decreased in ε4 carriers (OR = 0.98, 95% CI: 0.931-1.036, P = 0.508) and increased in non-ε4 carriers (OR = 1.02, 95% CI: 0.998-1.042, P = 0.07). Conclusion: High serum UA levels decreased the risk of LVH in ApoE ε4 carriers with CHD, while increased the risk of LVH in non-ε4 carriers.

Association of atrial arrhythmias with thrombospondin-1 in patients with acute myocardial infarction.

OBJECTIVES: Atrial remodeling is the main developmental cause of atrial arrhythmias (AA), which may induce atrial fibrillation, atrial flutter, atrial tachycardia, and frequent premature atrial beats in acute myocardial infarction (AMI) patients. Thrombospondin-1 (TSP-1) has been shown to play an important role in inflammatory and fibrotic processes, but its role in atrial arrhythmias is not well described. The purpose of this study was to investigate the role of TSP-1 in AMI patients with atrial arrhythmias. METHODS: A total of 219 patients with AMI who underwent percutaneous coronary intervention and with no previous arrhythmias were included. TSP-1 were analyzed in plasma samples. Patients were classified into 2 groups, namely, with and without AA during the acute phase of MI. Continuous electrocardiographic monitoring was used for AA diagnosis in hospital. RESULTS: Twenty-four patients developed AA. Patients with AA had higher TSP-1 levels (29.01 ± 25.87 µg/mL vs 18.36 ± 10.89 µg/mL, p < 0.001) than those without AA. AA patients also tended to be elderly (65.25 ± 9.98 years vs 57.47 ± 10.78 years, p < 0.001), had higher Hs-CRP (39.74 ± 43.50 mg/L vs 12.22 ± 19.25 mg/L, p < 0.001) and worse heart function. TSP-1 (OR 1.033; 95% CI 1.003-1.065, p = 0.034), Hs-CRP (OR 1.023; 95% CI 1.006-1.041, p = 0.008), age (OR 1.067; 95% CI 1.004-1.135, p = 0.038) and LVDd (OR 1.142; 95% CI 1.018-1.282, p = 0.024) emerged as independent risk factors for AA in AMI patients. CONCLUSION: TSP-1 is a potential novel indicator of atrial arrhythmias during AMI.

The efficacy and safety of radiofrequency ablation on the platelet activation and the inflammatory response in elderly atrial fibrillation patients.

BACKGROUND: Atrial fibrillation (AF) is the most common type of arrhythmia. AF is more common in the elderly population than in the young population. Radiofrequency ablation (RA) is the treatment option for drug-naïve AF; however, previous studies have focused on the young population. Therefore, it would be clinically valuable to compare the efficacy and safety of RA in both elderly and young patients with AF. OBJECTIVE: This study intended to compare the efficacy and safety of RA in elderly and young patients with AF. METHODS: Forty patients with drug-naïve AF who underwent RA at our hospital were retrospectively evaluated, of whom 20 were < 65 years old (group 1) and 20 were ≥ 65 years old (group 2). The treatment efficacy was evaluated by comparing the durations of the surgical procedures, the postoperative platelet activation, and the inflammatory factor levels. RESULTS: The total operation times for RA (160.64 ± 7.25 vs. 160.64 ± 7.25 min, P = 0.341) and the fluoroscopy times (40.82 ± 5.93 vs. 39.89 ± 6.35 min, P = 0.636) did not differ between the elderly (74.1 ± 6.7 years) and the young (54.6 ± 7.9 years) groups. The postoperative platelet activation levels (6.90% ± 0.64% vs. 6.90% ± 0.70%, P = 0.991), the P-selectin expression levels (4.5 ± 1.3 vs. 4.9 ± 1.3, P = 0.333) and the activated glycoprotein IIb/IIIa (0.5 ± 1.0 vs. 0.4 ± 1.1, P = 0.649), and the inflammatory factor levels (C-reactive protein: 26.45 ± 6.66 vs. 25.72 ± 7.78 mg/L, P = 0.750) were elevated in both groups but did not differ between the two groups. CONCLUSION: RA is a safe and effective procedure in elderly and young patients with medically refractory AF.

Shortened leukocyte telomere length as a potential biomarker for predicting the progression of atrial fibrillation from paroxysm to persistence in the short-term.

ABSTRACT: This study aimed to assess the role of leukocyte telomere length (LTL) in the development of atrial fibrillation (AF) among Chinese patients.This is a cross-sectional study. A total of 350 patients from June 2016 to December 2017 were retrospectively analyzed. These included 219 AF patients and 131 with sinus rhythm in the control group. Quantitative real-time PCR was used to measure relative LTL.The relative LTLs of all subjects (n = 350) ranged from 0.4 to 2.41 (0.98 ±â€Š0.29), showing a significant negative correlation (P < .001) with age. The AF-group had significantly shorter LTLs (0.93 ±â€Š0.26 vs 1.07 ±â€Š0.33, P < .001) and were older (61.50 ±â€Š6.49 vs 59.95 ±â€Š6.17, P = .028) than controls. LTLs among patients with persistent AF (PsAF), paroxysmal AF (PAF), and controls were significantly different (P < .001), with LTLs of PsAF patients being the shortest and controls being the longest. After adjusting for possible confounding factors, the PsAF group still showed significantly shorter LTLs than the PAF and control groups (P = .013 and P = .001, respectively). After an 18-month follow-up, 20 out of 119 PAF patients had progressed into PsAF and a relative LTL of ≤0.73 was an independent predictor for progression of PAF into PsAF.LTL was found to be shorter in patients with AF than in age-matched individuals with sinus rhythm and positively correlated with severity of AF. LTL shortening could be an independent risk factor for progression from paroxysmal AF to persistent AF in the short term.

Plasma Galectin-3 is associated with progression from paroxysmal to persistent atrial fibrillation.

BACKGROUND: Galectin-3 (Gal-3) is currently recognized as a promising biomarker for myocardial fibrosis. This study aimed to explore the potential association between plasma Gal-3 concentrations and atrial fibrillation (AF) progression in paroxysmal AF (PAF) patients METHODS: A total of 213 PAF patients were included for analysis in this study. All peripheral blood samples were prospectively collected and stored at -80℃ for subsequent Gal-3 quantification. The AF progression was defined as transformation from PAF to persistent AF (PsAF). RESULTS: A total of 51 PAF patients progressed to PsAF during a mean follow-up period of 674.44 ± 19.48 days. Patients with AF progression had significantly higher baseline plasma Gal-3 concentrations than those stayed in PAF status (13.52 ± 0.94 vs. 7.93 ± 0.37, p < 0.001). All PAF patients were divided into two subgroups based on the median value of plasma Gal-3 concentrations. Kaplan-Meier curve analysis showed a significantly higher AF progression rate in the higher plasma Gal-3 concentration group (log-rank test p < 0.001). In the Cox regression analysis, plasma Gal-3 concentration and left atrial diameter (LAD) were showed significantly associated with AF progression, even after adjustment of other potential confounding risk factors. Discrimination for AF progression with a simple model which consists of plasma Gal-3 concentration and LAD was modest with a C-statistic 0.72 (95%CI 0.64-0.80). Plasma Gal-3 concentration significantly improved the predictability by appropriately reclassifying several patients with progression (NRI = 28.3%, p = 0.003). CONCLUSION: Elevated plasma Gal-3 concentration is significantly associated with AF progression from PAF to PsAF. Plasma Gal-3 concentration could be used for PAF progression risk stratification and guiding management for PAF patients.

Predictive value of CHA2DS2-VASc score combined with hs-CRP for new-onset atrial fibrillation in elderly patients with acute myocardial infarction.

BACKGROUND: New-onset atrial fibrillation (NOAF) is common during acute myocardial infarction (AMI) and independently associated with worse prognosis. We aimed to validate the discrimination performance of CHA2DS2-VASc score combined with hs-CRP in the prediction of NOAF after AMI in elderly Chinese population. METHODS: 311 consecutive elderly patients (age ≥ 65 years old) with AMI from 1 January 2018 to 1 January 2019 without atrial fibrillation history were enrolled in our study. Univariable and multivariable logistic regression analyses were used to identify risk factors of NOAF. The discrimination performance of different score models were evaluated using ROC curve analysis and AUCs were compared using the Z test. RESULTS: 30 (9.65%) patients developed NOAF during hospitalization. The NOAF group were older and had higher hs-CRP, initial Killip class, BNP, LAD, CHADS2 score, CHA2DS2-VASc score, in-hospital mortality and lower LVEF and ACEI/ARB use (P < 0.05 vs group without NOAF for all measures). In multivariate regression analyses, age (OR = 1.127, 95% CI 1.063-1.196, P < 0.001) and hs-CRP (OR = 1.034, 95% CI 1.018-1.05, P < 0.001) were independent predictors of NOAF. In ROC curve analyses, both CHADS2 score (AUC = 0.624, 95% CI 0.516-0.733, P = 0.026) and CHA2DS2-VASc score (AUC = 0.687, 95% CI 0.584-0.79, P = 0.001) had acceptable but unsatisfactory discrimination performance in predicting NOAF after AMI. The combined model with CHA2DS2-VASc score and hs-CRP showed a significant better predictive value (AUC = 0.791, 95% CI 0.692-0.891, P < 0.001) compared to that of the CHA2DS2-VASc score alone (Z test, P = 0.008). CONCLUSION: The combined model with CHA2DS2-VASc score and hs-CRP had high accuracy in predicting post-AMI NOAF.

MiR-339 is a potential biomarker of coronary heart disease to aggravate oxidative stress through Nrf2/FOXO3 targeting Sirt2.

BACKGROUND: MicroRNA (miRNA) is a class of small-molecule RNA that can regulate gene expression at post-transcription level. It is involved in the genesis and development of multiple diseases. The aim of this paper was to explore the mechanisms of miR-339 in coronary heart disease (CHD). METHODS: In this study, we enrolled patients with CHD from Beijing Chaoyang Hospital and performed animal experiments on CHD rats. In vitro experiments, such as histopathologic assay, quantitative real-time PCR assay, luciferase reporter assay, western blotting assay, and immunofluorescence assay were carried out to characterize the contents and associations of miR-339, Nrf2, FOXO3, and Sirt2 in CHD samples and cells. In vivo model was also established on rats. RESULTS: In CHD rat, miR-339 was up-regulated compared with control group. The expression of miR-339 up-regulation increased oxidative stress in vitro model via suppression of Sirt2/Nrf2/FOXO3. However, down-regulation of miR-339 expression inhibited oxidative stress in vitro model via activation of Sirt2/Nrf2/FOXO3. The Sirt2 or Nrf2 inhibitor reduced the protective effect of miR-339 down-regulation on oxidative stress in vitro model. CONCLUSIONS: Down-regulation miR-339 may be the new targets to treat CHD through Nrf2/FOXO3 targeting Sirt2, and miR-339 may be a potential biomarker of CHD.

The potential regulatory role of hsa_circ_0004104 in the persistency of atrial fibrillation by promoting cardiac fibrosis via TGF-ß pathway.

INTRODUCTION: The progression of paroxysmal AF (PAF) to persistent AF (PsAF) worsens the prognosis of AF, but its underlying mechanisms remain elusive. Recently, circular RNAs (circRNAs) were reported to be associated with cardiac fibrosis. In case of the vital role of cardiac fibrosis in AF persistency, we hypothesis that circRNAs may be potential regulators in the process of AF progression. MATERIALS AND METHODS: 6 persistent and 6 paroxysmal AF patients were enrolled as derivation cohort. Plasma circRNAs expressions were determined by microarray and validated by RT-PCR. Fibrosis level, manifested by serum TGF-ß, was determined by ELISA. Pathways and related non-coding RNAs involving in the progression of AF regulated were predicted by in silico analysis. RESULTS: PsAF patients showed a distinct circRNAs expression profile with 92 circRNAs significantly dysregulated (fold change ≥ 2, p < 0.05), compared with PAF patients. The validity of the expression patterns was subsequently validated by RT-PCR in another 60 AF patients (30 PsAF and PAF, respectively). In addition, all the 5 up and down regulated circRNAs were clustered in MAPK and TGF-beta signaling pathway by KEGG pathway analysis. Among the 5 circRNAs, hsa_circ_0004104 was consistently downregulated in PsAF group (0.6 ± 0.33 vs 1.46 ± 0.41, p < 0.001) and predicted to target several AF and/or cardiac fibrosis related miRNAs reported by previous studies. In addition, TGF-ß1 level was significantly higher in the PsAF group (5560.23 ± 1833.64 vs 2236.66 ± 914.89, p < 0.001), and hsa_circ_0004104 showed a significant negative correlation with TGF-ß1 level (r = - 0.797, p < 0.001). CONCLUSION: CircRNAs dysregulation plays vital roles in AF persistency. hsa_circ_0004104 could be a potential regulator and biomarker in AF persistency by promoting cardiac fibrosis via targeting MAPK and TGF-beta pathways.

Leukocyte Telomere Length Predicts Progression From Paroxysmal to Persistent Atrial Fibrillation in the Long Term After Catheter Ablation.

BACKGROUND: Aging is significantly associated with the incidence and progression of atrial fibrillation (AF) incidence. This study aimed to evaluate the potential predictive value of leukocyte telomere length (LTL) for progression from paroxysmal AF (PAF) to persistent AF (PsAF) after catheter ablation. METHODS AND RESULTS: A total of 269 patients with AF (154 patients with PAF and 115 patients with PsAF, respectively) were prospectively enrolled, and all patients with PAF at baseline were regularly followed up to determine whether and when they should progress to PsAF after catheter ablation therapy. Baseline relative LTL was measured by quantitative real-time PCR (rt-PCT). There was a significant negative association between LTL and age (r = -0.23, p < 0.001). Patients with PsAF had significantly shorter LTL than those with PAF. After a mean follow-up of 854.9 ± 18.7 d, progression events occurred in 35 out of the 154 patients with PAF. Those progressed patients with PAF were older (70.9 ± 8.0 vs. 62.3 ± 10.3, p < 0.001) and had shorter LTL (1.2 ± 0.3 vs. 1.5 ± 0.3, p < 0.001) than those who did not. The receiver operating characteristic (ROC) curve analysis showed a significant value of LTL in distinguishing patients with PAF from patients with PsAF, with an area under the ROC curve (AUC) of 0.63 (95% CI 0.56-0.70, p < 0.001), and the optimal cut-off value of LTL was 1.175, with a sensitivity and specificity of 56.03 and 82.04%, respectively. All patients with PAF were divided into two subgroups according to the optimal cut-off point of LTL calculated by the ROC curve analysis: high LTL group (≥1.175) and low LTL group (<1.175). Kaplan-Meier curve analysis showed that PAF patients with shorter LTL had a significantly higher rate of progression after catheter ablation (40.5% vs. 18.8%, log-rank test p < 0.001). Multivariate Cox proportional-hazards model indicated that LTL [hazard ratio (HR): 2.71, 95% CI 1.36-5.42, p = 0.005] was an independent predictor for progression from PAF to PsAF after catheter ablation therapy, but HATCH score was not (HR: 1.02, 95% CI: 0.68-1.52, p = 0.923). CONCLUSION: Leukocyte telomere length was significantly associated with AF types. LTL was independently associated with progression from PAF to PsAF after catheter ablation therapy.Chinese Clinical Trial Registry, Registration Number: ChiCTR1900021341.

A risk score model to predict in-hospital mortality of patients with end-stage renal disease and acute myocardial infarction.

Chronic kidney disease (CKD) significantly increases the rate of adverse cardiovascular events in patients with coronary artery disease. In this study, we aimed to establish a risk score (RS) model to predict in-hospital mortality risk in patients with end-stage renal disease (ESRD) and acute myocardial infarction (AMI). A total of 113 consecutive patients with ESRD and AMI were retrospectively enrolled between January 1, 2015 and December 31, 2019. All patients received regular hemodialysis and were divided into two groups according to the prognosis during hospitalization. Univariable and multivariable logistic regression analyses were used to identify the risk factors of in-hospital mortality. A RS model was developed based on multiple regression analysis and was internally validated using 1000 bootstrap analysis. The receiver operating characteristic (ROC) curve was performed, and the area under curve (AUC) was analyzed to evaluate the performance of the RS model. AUCs were compared using the Z test. Thirty-three patients died during hospitalization, resulting in in-hospital mortality rate of 29.2%. After multivariate logistic regression, an RS model (0-8) was established based on five independent factors that were assigned with different points according to relative coefficients (coefficient of the index risk factor divided by the lowest coefficient among these five risk factors; rounded to closest integer): 1 for C-reactive protein (CRP) ≥ 14.2 mg/L and left ventricular ejection fraction (LVEF) ≤ V3%; 2 for age ≥ 65 years old, heart rate (HR) at admission ≥ 86 beats per minute (bpm) and D-dimer ≥ 2.4 mg/L FEU. The present RS model had a sensitivity of 85.7%, the specificity of 84%, and an accuracy of 78.1%. In ROC curve analysis, the model demonstrated a good discriminate power in predicting in-hospital mortality (AUC = 0.895, 95% CI 0.814-0.96; P < 0.001), which was significantly better than the predictive power of the Global Registry of Acute Coronary Events risk score (GRACE RS) (AUC = 0.754, 95% CI 0.641-0.868; P < 0.001 after Z test). A novel RS model, which was established to help predict in-hospital mortality of patients with ESRD and AMI, was easy to use and had higher accuracy than the GRACE RS.

p38/JNK Is Required for the Proliferation and Phenotype Changes of Vascular Smooth Muscle Cells Induced by L3MBTL4 in Essential Hypertension.

AIM: Hypertension is a complicated disorder with multifactorial etiology and high heritability. Our previous work has identified L3MBTL4 as a novel susceptibility gene for the development of essential hypertension, accompanied with activation of p38/JNK. Yet, little evidence has been reported whether p38/JNK contributed directly to L3MBTL4-induced vascular remodeling and exploring the potential mechanism of L3MBTL4 in vascular smooth muscle cells (VSMCs). METHODS: We evaluated the contribution of L3MBTL4 on proliferation, migration, and phenotype changes of VSMCs and further explored the critical role of p38 and JNK signaling pathway underlying. RESULTS: In L3MBTL4 transgenic rats, we found that the elevated blood pressure, increased left ventricular hypertrophy, and thickened vascular media layer were significantly relieved by both p38 and JNK inhibitors. Meanwhile, increased cell proliferation, advanced cell cycle progression, greater migratory capability, and synthetic phenotype were observed in L3MBTL4 overexpressed VSMCs, which could be blocked by either p38 or JNK inhibitor. CONCLUSIONS: Our findings pinpointed that p38 and JNK were required for the proliferation and phenotype changes of VSMCs induced by L3MBTL4 in hypertension. These novel findings yield new insights into the genetic and biological basis of hypertension and are fundamental for further studies to explore the intervention strategies targeting L3MBTL4 and p38/JNK to counteract the progression of hypertension.

Blood group A: a risk factor for heart rupture after acute myocardial infarction.

INTRODUCTION: Studies have been performed to identify the association between ABO blood groups and coronary artery disease. However, data is scarce about the impact of ABO blood groups on heart rupture (HR) after acute myocardial infarction (AMI). METHODS: We conducted a retrospective case-control study that included 61 consecutive patients with HR after AMI during a period from 1 January 2012 to 1 December 2019. The controls included 600 patients who were selected randomly from 8143 AMI patients without HR in a ratio of 1:10. Univariate and multivariate logistic regression analysis were used to identify the association between ABO blood groups and HR. RESULTS: Patients with blood group A had a greater risk of HR after AMI than those with non-A blood groups (12.35% vs 7.42%, P < 0.001). After adjusting for age, gender, heart rate at admission, body mass index (BMI), and systolic blood pressure (SBP), blood group A was independently related to the increased risk of HR after AMI (OR = 2.781, 95% CI 1.174-7.198, P = 0.035), and remained as an independent risk factor of HR after AMI in different multivariate regression models. CONCLUSION: Blood group A is significantly associated with increased HR risk after AMI.