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Abstract Background The stress hyperglycemia ratio (SHR) has been established as a predictor of unfavorable outcomes across various diseases. However, its relationship with prognosis in patients with cardiogenic shock (CS) remains unclear. This study aims to investigate the association between SHR and outcomes in CS patients. Methods A total of 904 CS patients with their first ICU admission were included in this study, utilizing data from the American Medical Information Mart for Intensive Care (MIMIC-IV) database. The primary endpoints were all-cause mortality at 30 days and 360 days. Patients were stratified into three groups based on the tertiles of the SHR. Results The mean age of the cohort was 67.62 years, with 67.3% of participants being men. During the follow-up period, 221 patients (24.4%) died within 30 days, and 360 patients (39.8%) died within 360 days. The 30-day all-cause mortality rates were 16.9%, 22.3%, and 34.2% in the T1, T2, and T3 groups, respectively (p

Abstract Aims Left ventricular assist device (LVAD) implantation, a therapy for end‐stage heart failure, is associated with platelet (PLT) activation. This study aims to evaluate the prognostic impact of PLT count in patients with LVAD implantation. Methods and Results Data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry were investigated, and patients were divided into three groups according to tertiles. The dynamic change of PLT counts and its associations with long‐term outcomes were analysed. The primary outcome was long‐term mortality. A total of 19 517 patients who received the first continuous‐flow LVAD were identified from the INTERMACS registry. The PLT count underwent a dynamic change towards normalization after LVAD implantation. Compared with intermediate, both high (hazard ratio [HR], 1.09, 95% confidence interval [CI]: 1.01 to 1.17, P = 0.033) and low (HR, 1.18, 95% CI: 1.10 to 1.27, P

Abstract Background China has undergone a significant socioeconomic transformation over the past few decades due to the implementation of family planning policies. These societal changes have resulted in an increased susceptibility among females to developing cardiometabolic diseases (CMD). Unfortunately, studies investigating the correlation between family planning policies in China and the incidence of CMD remain scarce. Methods Data from 1,226 females, aged 30 years or older with ≥ 1 live birth, undergoing routine physical examinations between January 2018 and December 2021 were collected, and they were grouped by number of live births 1, 2, and ≥ 3. A binary logistic regression model was employed to examine the association between the number of live births with CMD. Furthermore, the subgroup analysis was performed to elucidate the impact of the implementation of family planning policies with CMD. Results Women with live births ≥ 3 tended to be older, had higher gravidities, a greater proportion of central obesity, general obesity, hypertension, and dyslipidemia (all P

Stimulator of interferon genes (STING) has recently been found to play a crucial role in cardiac sterile inflammation and dysfunction. The role of stimulator of interferon genes (STING) in cardiac sterile inflammation and dysfunction has been recently discovered. This study aims to examine the involvement of STING in pathological cardiac remodeling and the mechanisms that govern the activation of the STING pathway. To investigate this, transverse aortic constriction (TAC) was performed on STING knockout mice to induce pressure overload-induced cardiac remodeling. Subsequently, cardiac function, remodeling, and inflammation levels were evaluated. The STING pathway was found to be activated in the pressure overload-stressed heart and angiotensin II (Ang II)-stimulated cardiac fibroblasts. Loss of STING expression led to a significant reduction in inflammatory responses, mitochondrial fragmentation, and oxidative stress in the heart, resulting in attenuated cardiac remodeling and dysfunction. Furthermore, the exacerbation of pressure overload-induced STING-mediated inflammation and pathological cardiac remodeling was observed when mitophagy was suppressed through the silencing of Parkin, an E3 ubiquitin ligase. Taken together, these findings indicate that STING represents a newly identified and significant molecule implicated in the process of pathological cardiac remodeling and that mitophagy is an upstream mechanism that regulates STING activation. Targeting STING may therefore provide a novel therapeutic strategy for pathological cardiac remodeling and heart failure.

Abstract Background We have reported a positive correlation between S100 calcium-binding protein (S100) A8/S100A9 and sepsis-induced lung damage before. However, limited knowledge exists concerning the biological role of S100A8/A9 in pulmonary vascular endothelial barrier dysfunction, as well as the diagnostic value of S100A8/A9 in sepsis. Methods Sepsis was induced in C57BL/6J mice and S100A9-knockout (KO) mice through the cecal ligation and puncture (CLP). Pulmonary vascular leakage was determined by measuring extravasated Evans blue (EB). Reverse transcription polymerase chain reaction and the histological score were used to evaluate inflammation and lung injury, respectively. Recombinant S100A8/A9 (rhS100A8/A9) was used to identify the effects of S100A8/A9 on endothelial barrier dysfunction in human umbilical vein endothelial cells (HUVECs). Additionally, the diagnostic value of S100A8/A9 in sepsis was assessed using receiver operating characteristic. Results S100A8/A9 expression was up-regulated in the lungs of CLP-operated mice. S100A9 KO significantly reversed CLP-induced hypothermia and hypotension, resulting in an improved survival rate. S100A9 KO also decreased the inflammatory response, EB leakage, and histological scores in the lungs of CLP-operated mice. Occludin and VE-cadherin expressions were decreased in the lungs of CLP-operated mice; However, S100A9 KO attenuated this decrease. Moreover, CLP-induced signal transducer and activator of transcription 3 (STAT3) and p38/extracellular signal-regulated kinase (ERK) signalling activation and apoptosis were mitigated by S100A9 KO in lungs. In addition, rhS100A8/A9 administration significantly decreased occludin and VE-cadherin expressions, increased the phosphorylated (p)-ERK/ERK, p-p38/p38, and B-cell leukaemia/lymphoma 2 protein (Bcl-2)-associated X protein/Bcl-2 ratios in HUVECs. Conclusion The present study demonstrated S100A8/A9 aggravated sepsis-induced pulmonary inflammation, vascular permeability, and lung injury. This was achieved, at least partially, by activating the P38/STAT3/ERK signalling pathways. Moreover, S100A8/A9 showed the potential as a biomarker for sepsis diagnosis.

Dapagliflozin (DAPA) has been demonstrated to reduce cardiovascular mortality and heart failure hospitalization rates in diabetic patients. However, the mechanism underlying its cardio-protective effect in non-diabetic patients remains unclear. Our study aimed to explore the cardio-protective impact of DAPA on myocardial infarction in non-diabetic mice. We induced myocardial infarction in C57BL/6 mice by ligating the descending branch of the left coronary artery. After surgery, the animals were randomly treated with either saline or DAPA. We employed echocardiography, Western blot analysis, and tissue staining to assess post-infarction myocardial injury. Additionally, we investigated the mechanism of action through cell experiments. Compared to the myocardial infarction group, DAPA treatment significantly attenuated ventricular remodeling and improved cardiac function. By mitigating myocardial oxidative stress and apoptosis, DAPA may activate the AMPKα signaling pathway, thereby exerting a protective effect. These findings suggest that DAPA could serve as a novel therapeutic approach for patients with cardiac infarction.

Key Clinical Message Patients with transthyretin cardiac amyloidosis (ATTR‐CM) commonly present with dyspnea, fatigue, and edema. In our case, the main presentation was exertional angina, which was atypical in patients with ATTR‐CM and should be paid more attention to. Abstract A 54‐year‐old woman was admitted with a complaint of exertional chest pain, and she had a history of hypertension. The results of the electrocardiogram and echocardiography revealed the clues of cardiac amyloidosis, and the patient was finally diagnosed with transthyretin cardiac amyloidosis, then she received tafamidis, and the symptoms improved significantly.

Background: Acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) carries a high mortality risk. Inflammation and nutrition are involved in the pathogenesis and prognosis of both AMI and CS. The advanced lung cancer inflammation index ratio (ALI) combines the inflammatory and nutritional status. Our present study aimed to explore the prognostic value of ALI in patients with CS following AMI. Methods: In total, 217 consecutive patients with AMI complicated by CS were divided into two groups based on the ALI admissions cut-off: ≤12.69 and >12.69. The primary endpoint of this study was 30-day all-cause mortality. The secondary endpoints were gastrointestinal hemorrhage and major adverse cardiovascular events (MACEs), including 30-day all-cause mortality, atrioventricular block, ventricular tachycardia/ventricular fibrillation, and nonfatal stroke. The association of ALI with the study endpoints was analyzed by Cox regression analysis. Results: During the 30-day follow-up period after admission, 104 (47.9%) patients died and 150 (69.1%) suffered MACEs. The Kaplan–Meier analysis revealed significantly higher cumulative mortality and lower MACE rates in the low-ALI group compared to the high-ALI group (both log-rank p < 0.001). The 30-day mortality rate was significantly higher in patients with ALI ≤12.69 compared to ALI >12.69 (72.1% vs. 22.6%; p < 0.001). Furthermore, the incidence of MACEs was higher in patients with ALI ≤12.69 (85.6% vs. 51.9%; p < 0.001). The receiver operating curve showed that ALI had a modest predictive value (area under the curve [AUC]: 0.789, 95% confidence interval [CI]: 0.729, 0.850). After multivariable adjustment, ALI ≤12.69 was an independent predictor for both 30-day all-cause mortality (hazard ratio [HR]: 3.327; 95% CI: 2.053, 5.389; p < 0.001) and 30-day MACEs (HR: 2.250; 95% CI 1.553, 3.260; p < 0.001). Furthermore, the addition of ALI to a base model containing clinical and laboratory data statistically improved the predictive value. Conclusions: Assessing ALI levels upon admission can provide important information for the short-term prognostic assessment of patients with AMI complicated by CS. A lower ALI may serve as an independent predictor of increased 30-day all-cause mortality and MACEs.

Inflammatory macrophages play a crucial role in atherosclerosis development. The long non-coding RNA growth arrest-specific 5 (GAS5) regulates THP-1 macrophage inflammation by sponging microRNAs. The purpose of this study was to investigate the regulatory mechanism of GAS5 in atherosclerosis development. GSE40231, GSE21545, and GSE28829 datasets from the Gene Expression Omnibus database were integrated after adjusting for batch effect. Differential analysis was performed on the integrated dataset and validated using the Genotype-Tissue Expression and GSE57691 datasets. Potential biological functions of GAS5 and annexin A2 (ANXA2) were identified using gene set enrichment analysis (GSEA). ssGSEA, CIBERSORTx, and ImmuCellAI algorithms were used to identify immune infiltration in plaque samples. GAS5 and ANXA2 expression levels in RAW264.7 cells treated with oxidized low-density lipoprotein (ox-LDL) were measured by qRT-PCR and Western blot. Small interfering and short hairpin RNA were used to silence GAS5 expression. Plasmids of ANXA2 were used to establish ANXA2 overexpression. Apoptosis and inflammatory markers in macrophages were detected by Western blot. Aortic samples from APOE−/− mice were collected to validate the expression of GAS5 and ANXA2. GAS5 expression was significantly increased during atherosclerosis. GAS5 expression was positively correlated with macrophage activation and ANXA2 expression in plaques. Furthermore, ANXA2 upregulation was also related to the activation of macrophage. GSEA indicated similar biological functions for GAS5 and ANXA2 in plaques. Moreover, in vitro experiments showed that both GAS5 and ANXA2 contributed to macrophage apoptosis and inflammation. Rescue assays revealed that the inflammatory effects of GAS5 on macrophages were ANXA2-dependent. In vivo experiments confirmed the highly expression of Gas5 and Anxa2 in the plaque group. We identified the atherogenic roles of GAS5 and ANXA2 in the inflammatory response of macrophages. The inflammatory response in ox-LDL-treated macrophages was found to be mediated by GAS5-ANXA2 regulation, opening new avenues for atherosclerosis therapy.

BackgroundSick Sinus Syndrome (SSS) is generally regarded as a degenerative disease with aging; however, genetic mutations have been confirmed to be associated with SSS. Among them, mutations in SCN5A are common in patients with SSS. We report three young SSS patients with SCN5A mutations at different sites that have not been previously reported in Asian patients.Case presentationThe three patients were all young females who presented with symptoms of severe bradycardia and paroxysmal atrial flutter, for which two patients received ablation therapy. However, after ablation, Holter monitoring indicated a significant long cardiac arrest; therefore, the patients received pacemaker implantation. The three patients had familial SSS, and genetic testing was performed. Mutations were found in SCN5A at different sites in the three families. All three patients received pacemaker implantation, resulting in the symptoms of severe bradycardia disappearing.ConclusionSCN5A heterozygous mutations are common among patients clinically affected by SSS. Their causative role is confirmed by our data and by the co-occurrence of genetic arrhythmias among our patients. Genetic testing for SSS cannot be performed as a single gene panel because of feasible literature results, but in presence of familial and personal history of SSS in association with arrhythmias can provide clinically useful information.

An increasing body of studies has demonstrated the significance of long non-coding RNA (lncRNA) growth arrest specific 5 (GAS5) in inflammation and myocardial injury in septic shock. This research aims to determine whether GAS5 contributes to the pathological development of sepsis-induced cardiac damage and NLRP3 inflammasome-mediated myocardial cell pyroptosis. Cecal ligation and puncture (CLP) surgery was used to cause septic shock in C57BL/6 wild-type mice. After CLP, inflammatory, pyroptosis parameters of myocardial tissue, survival rate, and Murine Sepsis Score (MSS) were assessed to evaluate the involvement of GAS5 in the mouse myocardial depression. To investigate GAS5's function in lipopolysaccharide (LPS) induced myocardial cell pyroptosis, gain- and loss-of-function experiments were conducted in vitro on HL-1 cells. Our findings indicated that CLP dramatically reduced survival rates, MSS, SIRT3 and p-AMPK expression, and activated the Nuclear factor-κB (NF-κB) pathway and NLRP3 inflammasome-mediated pyroptosis. The NF-κB and pyroptosis pathways were greatly elevated while SIRT3/p-AMPKα was dramatically decreased as a result of GAS5 being downregulated. Meanwhile, the regulatory effect could be suppressed by SIRT3 and AMPKα activator. Our observations supported the idea that GAS5 has a crucial protective impact against myocardial inflammation and pyroptosis in sepsis.

Abstract Background Elevated resting heart rate (HR) predicts poor outcomes in patients with coronary artery disease. Ivabradine has been recommended as a second-line anti-anginal agent in chronic coronary syndrome, while there are no clear indications for acute ST-elevation myocardial infarction (STEMI). Results We systematically searched PubMed, Medline, EMBASE, Clinical Trials.gov, and the Cochrane Central Register of Controlled Trials with search terms Ivabradine and Acute myocardial infarction. There are two study outcomes from this study: therapeutic and safety effects. Therapeutic effects include the efficacy of Ivabradine on HR, all-cause mortality, heart failure incidence, left ventricular function and remodeling. Safety effects include troponin levels and ischemic events (recurrent angina pectoris). A total of 6 RCTs was included and showed that Ivabradine was associated with greater resting HR reduction [MD − 5.40; 95%CI − 8.60, − 2.20], improvement of left ventricular ejection fraction [MD 2.98; 95%CI 0.44, 5.51], and left ventricular end systolic volume [MD − 3.81; 95%CI − 6.88, − 0.75]. However, Ivabradine had no impact on all-cause mortality [OR 0.76; 95%CI 0.35, 1.67], heart failure incidence [OR 0.61; 95%CI 0.21, 1.80], and recurrent angina pectoris [OR 0.71; 95%CI 0.50, 1.00]. Conclusions Ivabradine is safe and effective for resting HR reduction in patients with STEMI; however, it has no significant influence on mortality. These results suggest that an elevated HR is only a marker of risk but not a modifiable determinant of outcomes in patients who have suffered an acute myocardial infarction.

Introduction: Despite the high morbidity and mortality of heart failure with preserved fraction (HFpEF), there are currently no effective therapies for this condition. Moreover, the pathophysiological basis of HFpEF remains poorly understood. Objective: The aim of the present study was to investigate the role of inducible nitric oxide synthase (iNOS) and its underlying mechanism in a high-fat diet and Nω-nitro-L-arginine methyl ester-induced HFpEF mouse model. Methods: The selective iNOS inhibitor L-NIL was used to examine the effects of short-term iNOS inhibition, whereas the long-term effects of iNOS deficiency were evaluated using iNOS-null mice. Cardiac and mitochondrial function, oxidative stress and Akt S-nitrosylation were then measured. Results: The results demonstrated that both pharmacological inhibition and iNOS knockout mitigated mitochondrial dysfunction, oxidative stress and Akt S-nitrosylation, leading to an ameliorated HFpEF phenotype in mice. In vitro, iNOS directly induced Akt S-nitrosylation at cysteine 224 residues , leading to oxidative stress, while inhibiting insulin-mediated glucose uptake in myocytes. Conclusion: Altogether, the present findings suggested an important role for iNOS in the pathophysiological development of HFpEF, indicating that iNOS inhibition may represent a potential therapeutic strategy for HFpEF.

Abstract Background Addison’s disease which is due to dysfunction of the adrenal gland, with abnormal secretion of glucocorticoids and mineralocorticoids, is rare. By inducing inflammation and disorders of water and electrolyte metabolism, Addison’s disease may accelerate progression of co-existed cardiovascular diseases. Addison’s disease combined with cardiovascular disease is infrequent, only 10 cases in the literature. Case presentation We reported a 51-year-old male patient with unstable angina pectoris and hypotension. Changes on coronary angiography within 2 years suggested rapid progression of coronary artery disease in a patient with low cardiovascular risk. An additional clue of skin hyperpigmentation, fatigue and further examination confirmed the diagnosis of Addison’s disease caused by adrenal tuberculosis. After hormone replacement treatment, the frequency and severity of the angina pectoris were alleviated significantly, as were hypotension, hyperpigmentation and fatigue. Conclusions The combination of Addison’s disease and coronary artery disease in one patient is rare. Addison’s disease can induce inflammation and disorders of water and electrolyte metabolism, which may further accelerate the course of coronary artery disease. Meanwhile, the hypotension in Addison’s disease may affect the coronary blood flow, which may result in an increased susceptibility to unstable angina in the presence of coronary stenosis. So, we should analyze comprehensively if the coronary artery disease progress rapidly.

Characterisation of macrophages from human carotid artery plaques and in vitro assays reveal that macrophages regulate vascular smooth muscle cell function during atherosclerosis progression through the IL-1β/STAT3 axis.

Abstract Aim Endoplasmic reticulum (ER) stress is common in different human pathologies, including cardiac diseases. Sphingosine kinase‐1 (SPHK1) represents an important player in cardiac growth and function. Nevertheless, its function in cardiomyocyte ER stress remains vague. This study sought to evaluate the mechanism through which SPHK1 might influence ER stress during myocardial infarction (MI). Methods MI‐related GEO data sets were queried to screen differentially expressed genes. Murine HL‐1 cells exposed to oxygen‐glucose deprivation (OGD) and mice with MI were induced, followed by gene expression manipulation using short hairpin RNAs and overexpression vectors. The activating transcription factor 3 (ATF3) and SPHK1 expression was examined in cells and tissues. Cell counting kit‐8, TUNEL, DHE, HE, and Masson's staining were conducted in vitro and in vivo. The inflammatory factor concentrations in mouse serum were measured using ELISA. Finally, the transcriptional regulation of SPHK1 by ATF3 was validated. Results ATF3 and SPHK1 were upregulated in vivo and in vitro. ATF3 downregulation reduced the SPHK1 transcription. ATF3 and SPHK1 downregulation increased the viability of OGD‐treated HL‐1 cells and decreased apoptosis, oxidative stress, and ER stress. ATF3 and SPHK1 downregulation narrowed the infarction area and attenuated myocardial fibrosis in mice, along with reduced inflammation in the serum and ER stress in the myocardium. In contrast, SPHK1 reduced the protective effect of ATF3 downregulation in vitro and in vivo. Conclusions ATF3 downregulation reduced SPHK1 expression to attenuate cardiomyocyte injury in MI.

Introduction: Chronic fluid accumulation or congestion is considered an important pathophysiologic mechanism in heart failure, leading to cardinal symptoms such as dyspnea, pulmonary congestion, and pitting edema. Edema index (EI) recently emerged as a surrogate for extracellular volume status and has been proven to be able to reflect one’s congestion status. In this study, we aimed to evaluate the prognostic value of EI in patients with chronic heart failure (CHF). Methods: A total of 401 consecutive patients with CHF between August 2019 and October 2021 were prospectively enrolled. EI was obtained by InBody S10. The primary endpoint was long-term all-cause and cardiovascular mortality. Results: Patients with high EI (>0.397) tended to be older, presented with atrial fibrillation, have higher N-terminal brain natriuretic peptide, and have higher creatinine (all p < 0.05). During a median follow-up of 1200 days, the all-cause and cardiovascular mortality rate was significantly higher in the high EI group compared to the low EI group (all-cause mortality rate 43.8% vs. 30.3%, p < 0.001, and cardiovascular mortality rate 17.5% vs. 13.0%, p < 0.001, respectively). In the multivariate Cox proportional hazard analysis, EI > 0.397 was an independent predictor for both all-cause mortality (HR 1.959; 95% CI 1.304, 2.944; p = 0.001) and cardiovascular mortality (HR 2.051; 95% CI 1.276, 3.296; p = 0.003). Conclusions: Admission EI could be used as a marker for predicting long-term mortality in patients with CHF, and higher EI was associated with an increased risk of all-cause and cardiovascular mortality. Furthermore, EI-guided management could be a promising therapy in patients with CHF.

Backgrounds: Ventricular functional mitral regurgitation (FMR) is a common morbidity in patients with heart failure (HF). In addition to guideline-directed medical therapy, mitral valve (MV) repair or replacement has become an option for such patients. However, the impact of different treatments on cardiac remodeling, function, and clinical outcomes remains unclear. Methods: We systematically searched PubMed, EMBASE, Medline, Clinical Trials.gov, and the Cochrane Central Register of Controlled Trials with search terms related to mitral regurgitation, mitral valve repair, surgical mitral valve replacement, mitral annuloplasty device, and MitraClip. The outcomes were left ventricular ejection fraction (LVEF), left ventricular (LV) remodeling, all-cause mortality, cardiovascular death, and HF hospitalization. Sensitivity analysis was performed by removing high-bias risk studies. The analysis was done by Review Manager 5.4 Analyzer and MedCalc Statistical Software version 19.2.6. Results: This meta-analysis included 10 studies with a total of 2533 patients (567 with transcatheter MitraClip, 823 with surgical MV repair, 651 with surgical MV replacement, and 492 with medical therapy). Our meta-analysis revealed that surgical MV repair had significant improvement in LVEF compared to the surgical MV replacement (mean differences (MD) 2.32, [95% CI 0.39, 4.25]), while transcatheter MitraClip treatment was associated with LVEF reduction (MD –4.82, [95% CI –7.29, –2.34]). In terms of LV remodeling, transcatheter MitraClip treatment was associated with improvement in left ventricular end-diastolic volume (MD –10.36, [95% CI –18.74, –1.99]). Furthermore, compared to surgical MV replacement, surgical MV repair was not associated with a reduction of all-cause mortality (risk ratio (RR) 0.83, [95% CI 0.61, 1.13]) and cardiovascular death (RR 0.95, [95% CI 0.56, 1.62]), while transcatheter MitraClip was associated with reduced risk of all-cause mortality (RR 0.87, [95% CI 0.78, 0.98]). Conclusions: Surgical MV repair was associated with significant improvement in LVEF but had no significant effect on all-cause mortality compared to surgical MV replacement. Transcatheter MitraClip was associated with better long-term survival than the non-MitraClip group, thus, transcatheter MitraClip could be considered an alternative treatment in patients with HF-complicated ventricular FMR.

Abstract A woman that suffered burns previously presented with leg swelling and was diagnosed with venous thromboembolism. Heparin was given until she suddenly developed myocardial infarction. Ventricular septal rupture was detected and managed by transcatheter closure. She developed massive bleeding and extensive thrombosis that made treatment paradoxical and eventually died.

Summary: To determine the effect of aerobic exercise in different intensities on renal injury and epithelial-mesenchymal transformation (EMT) in the kidney of spontaneously hypertensive rats (SHR) and explore possible mechanisms, we subjected SHR to different levels of 14-week aerobic treadmill training. We tested the effects of aerobic exercise on irisin level, renal function, and EMT modulators in the kidney. We also treated angiotensin II-induced HK-2 cells with irisin and tested the changes in EMT levels. The data showed low and moderate aerobic exercise improved renal function and inhibited EMT through promoting irisin expression in SHR. However, high-intensity exercise training had no effect on renal injury and EMT in SHR but did significantly activate STAT3 phosphorylation in the kidney. These results clarify the mechanisms of exercise in improving hypertension-related renal injury and suggest that irisin might be a therapeutic target for patients with kidney injury.

BackgroundShock is associated with the activation of the coagulation and fibrinolytic system, and D-dimer is the degradation product of cross-linked fibrin. However, the prognostic value of D-dimer in patients with cardiogenic shock (CS) after acute myocardial infarction (AMI) remains unclear.MethodsWe retrospectively analyzed the data of consecutive patients with CS complicating AMI. The primary endpoint was 30-day mortality and the secondary endpoint was the major adverse cardiovascular events (MACEs) including 30-day all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal hemorrhage, and non-fatal stroke. Restricted cubic spline (RCS) analyses were performed to assess the association between admission D-dimer and outcomes. A multivariable Cox regression model was performed to identify independent risk factors. The risk predictive potency with D-dimer added to the traditional risk scores was evaluated by C-statistics and the net reclassification index.ResultsAmong 218 patients with CS complicating AMI, those who died during the 30-day follow-up presented with worse baseline characteristics and laboratory test results, including a higher level of D-dimer. According to the X-tile program result, the continuous plasma D-dimer level was divided into three gradients. The 30-day all-cause mortality in patients with low, medium, and high levels of D-dimer were 22.4, 53.3, and 86.2%, respectively (p < 0.001 for all). The 30-day incidence of MACEs was 46.3, 77.0, and 89.7%, respectively (p < 0.001). In the multivariable Cox regression model, the trilogy of D-dimer level was an independent risk predictor for 30-day mortality (median D-dimer cohort: HR 1.768, 95% CI 0.982–3.183, p = 0.057; high D-dimer cohort: HR 2.602, 95% CI 1.310–5.168, p = 0.006), a similar result was observed in secondary endpoint events (median D-dimer cohort: HR 2.012, 95% CI 1.329–3.044, p = 0.001; high D-dimer cohort: HR 2.543, 95% CI 1.452–4.453, p = 0.001). The RCS analyses suggested non-linear associations of D-dimer with 30-day mortality. The enrollment of D-dimer improved risk discrimination for all-cause death when combined with the traditional CardShock score (C-index: 0.741 vs. 0.756, pdifference = 0.004) and the IABP-SHOCK II score (C-index: 0.732 vs. 0.754, pdifference = 0.006), and the GRACE score (C-index: 0.679 vs. 0.715, pdifference < 0.001). Similar results were acquired after logarithmic transformed D-dimer was included in the risk score. The improvements in reclassification which were calculated as additional net reclassification index were 7.5, 8.6, and 12.8%, respectively.ConclusionAdmission D-dimer level was independently associated with the short-term outcome in patients with CS complicating AMI and addition of D-dimer brought incremental risk prediction value to traditional risk prediction scores.

Abstract “De Winter” electrocardiogram pattern is considered an equivalent risk to ST‐elevation myocardial infarction and usually indicates occlusion of the left anterior descending artery, which needs emergent revascularization treatment. However, some conditions can mimic “de Winter” electrocardiogram pattern and may cause misdiagnosis. Here, we reported a case of hyperkalemia presented with “de Winter‐like” electrocardiogram pattern. This study aimed to increase physicians' awareness about the impact of electrolyte disorder on electrocardiographic changes.

PurposeThe advanced lung cancer inflammation index (ALI) is a novel inflammatory and nutritional index that exerts prognostic value in various types of cancer. A previous study demonstrated that ALI at discharge could predict the prognosis in patients with acute decompensated heart failure (ADHF). However, the long-term prognostic value of ALI on admission in elderly heart failure (HF) inpatients remains unclear.Materials and methodsWe retrospectively collected HF inpatients over 65-year-old who were hospitalized in our cardiology center during the whole year of 2015. ALI was calculated as body mass index (BMI) × serum albumin (Alb)/neutrophil-to-lymphocyte ratio (NLR). Patients were divided into two groups by the optimal cutoff value of ALI for predicting all-cause mortality using time-dependent receiver operating characteristic (ROC) curves. The Spearman rank correlation coefficient was computed to evaluate the correlation between ALI and the geriatric nutritional risk index (GNRI). Kaplan–Meier curves, Cox survival analyses, time-dependent ROC analyses, and net reclassification improvement (NRI) analyses were used to assess the prognostic effect of ALI on all-cause mortality and cardiovascular mortality.ResultsOver a 28-month median follow-up, all-cause and cardiovascular mortality occurred in 192 (35.4%) and 132 (24.3%) out of 543 patients, respectively. The optimal cutoff value of ALI for predicting all-cause mortality at 2 years was 25.8. Spearman’s correlation coefficient showed a moderate positive linear correlation between ALI and GNRI (r = 0.44, p < 0.001). The Kaplan–Meier analysis revealed that the cumulative incidences of both all-cause and cardiovascular mortalities were significantly higher in patients with lower ALI (log-rank test, all-cause mortality: p < 0.0001; cardiovascular mortality: p < 0.0001). The multivariate Cox proportional hazard analyses indicated that ALI was an independent predictor for both all-cause mortality (HR 0.550, 95% CI 0.349–0.867, p = 0.01) and cardiovascular mortality (HR 0.536, 95% CI 0.302–0.953, p = 0.034). Time-dependent ROC analyses showed that ALI was comparable to GNRI in predicting long-term all-cause mortality (AUC: ALI 0.625, GNRI 0.641, p = 0.976) and cardiovascular mortality (AUC: ALI 0.632, GNRI 0.626, p = 0.999) at 2 years. However, the estimated NRI indicated that the addition of ALI could not significantly improve risk stratification of base models for all-cause mortality (categorical NRI 4.9%, p = 0.433, continuous NRI 25%, p = 0.022) or cardiovascular mortality (categorical NRI 6.5%, p = 0.223, continuous NRI 27.5%, p = 0.029).ConclusionHigher ALI was significantly associated with lower all-cause and cardiovascular mortalities in elderly HF patients. ALI on admission could be a competent nutrition-inflammation marker with independent predictive value for evaluating the long-term mortality of HF in elder population.

BackgroundAcute coronary syndrome (ACS) is the most time-sensitive acute cardiac event that requires rapid dispatching and response. The medical priority dispatch system (MPDS), one of the most extensively used types of emergency dispatch systems, is hypothesized to provide better-quality prehospital emergency treatment. However, few studies have revealed the impact of MPDS use on the process of ACS care. ObjectiveThis study aimed to investigate whether the use of MPDS was associated with higher prehospital diagnosis accuracy and shorter prehospital delay for patients with ACS transferred by an emergency medical service (EMS), using a national database in China. MethodsThis retrospective analysis was based on an integrated database of China’s MPDS and hospital registry. From January 1, 2016, to December 31, 2020, EMS-treated ACS cases were divided into before MPDS and after MPDS groups in accordance with the MPDS launch time at each EMS center. The primary outcomes included diagnosis consistency between hospital admission and discharge, and prehospital delay. Multivariable logistic regression and propensity score–matching analysis were performed to compare outcomes between the 2 groups for total ACS and subtypes. ResultsA total of 9806 ACS cases (3561 before MPDS and 6245 after MPDS) treated by 43 EMS centers were included. The overall diagnosis consistency of the after MPDS group (Cohen κ=0.918, P

ObjectiveThis study aimed to analyze the characteristics of patients with pericardial effusion requiring pericardiocentesis and to evaluate the safety of pericardiocentesis without discontinuation of anticoagulant or antiplatelet drugs.MethodsWe performed a retrospective study of patients undergoing pericardiocentesis in our hospital between 2012 and 2022. Patients were categorized into the Antithrombotic Group if they had used any antiplatelet or anticoagulant drugs on the day of pericardiocentesis; otherwise they were categorized into the Non-antithrombotic Group. All procedures were performed by experienced cardiologists with echocardiographic guidance. Bleeding events were defined using the National Institutes of Health scale of adverse events.ResultsA total of 501 consecutive patients were identified and 70 cases were under antithrombotic drugs (Antithrombotic Group). Patients in Antithrombotic Group were older, had more comorbidities, presented with lower platelet counts and prolonged activated partial thromboplastin time (all p < 0.05). Malignancy was the most common etiology for pericardial effusion in both groups (28.6% in Antithrombotic Group and 54.7% in Non-antithrombotic Group) and tuberculosis was the second etiology in the Non-antithrombotic Group (21.9%), while procedure-related effusion (17.1%) accounted for the second cause in the Antithrombotic Group. Two patients in the Antithrombotic Group had mild oozing at the puncture site that resolved without interventions (2.9 vs. 0%, p = 0.019), and no bleeding events higher than Grade 1 occurred in either group.ConclusionAlthough antiplatelet or anticoagulant drugs may put patients undergoing pericardiocentesis at theoretically higher risk of bleeding, our study demonstrated that they are not associated with increased major bleeding complications.

Abstract O-GlcNAcylation, an energy-sensitive posttranslational modification, can regulate the activity of endothelial nitric oxide synthase (eNOS). Previous studies found that Thr866 is the key site for low-glucose-mediated regulation of eNOS O-GlcNAc. However, it is not known whether this activity functions through the Thr866 site concomitant with other physical and chemical factors. Therefore, we first explored the effects of physical and chemical factors on eNOS O-GlcNAc and its Thr866 site. In this study, hypertonic stress, hyperthermia and hydrogen peroxide all increased the expression levels of eNOS O-GlcNAc, whereas hypoxia and high levels of alcohol had no effect. on the expression levels of eNOS O-GlcNAc; by contrast, low pH led to a decrease in eNOS O-GlcNAc levels. Notably, eNOS O-GlcNAc protein levels were unchanged after Thr866 site mutation only under hypertonic conditions, suggesting that hypertonic stress may act through the Thr866 site. Upon exploring the mechanism of hypertonic stress on eNOS O-GlcNAc activity and function, we found that hypertonic stress can upregulate the expression of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which is dependent on AMPK. When AMPK was knocked out, the upregulation of OGT expression and increased O-GlcNAc modifications induced by hypertonic stress were reversed.

Abstract Background Numerous studies have revealed the relationship between lipid expression and increased cardiovascular risk in ST-segment elevation myocardial infarction (STEMI) patients. Nevertheless, few investigations have focused on the risk stratification of STEMI patients using machine learning algorithms. Methods A total of 1355 STEMI patients who underwent percutaneous coronary intervention were enrolled in this study during 2015–2018. Unsupervised machine learning (consensus clustering) was applied to the present cohort to classify patients into different lipid expression phenogroups, without the guidance of clinical outcomes. Kaplan-Meier curves were implemented to show prognosis during a 904-day median follow-up (interquartile range: 587–1316). In the adjusted Cox model, the association of cluster membership with all adverse events including all-cause mortality, all-cause rehospitalization, and cardiac rehospitalization was evaluated. Results All patients were classified into three phenogroups, 1, 2, and 3. Patients in phenogroup 1 with the highest Lp(a) and the lowest HDL-C and apoA1 were recognized as the statin-modified cardiovascular risk group. Patients in phenogroup 2 had the highest HDL-C and apoA1 and the lowest TG, TC, LDL-C and apoB. Conversely, patients in phenogroup 3 had the highest TG, TC, LDL-C and apoB and the lowest Lp(a). Additionally, phenogroup 1 had the worst prognosis. Furthermore, a multivariate Cox analysis revealed that patients in phenogroup 1 were at significantly higher risk for all adverse outcomes. Conclusion Machine learning-based cluster analysis indicated that STEMI patients with increased concentrations of Lp(a) and decreased concentrations of HDL-C and apoA1 are likely to have adverse clinical outcomes due to statin-modified cardiovascular risks. Trial registration ChiCTR1900028516 ( http://www.chictr.org.cn/index.aspx ).

We aimed to examine the effects of aerobic exercise training on renal function in spontaneously hypertensive rats (SHR) and elucidate their possible mechanisms. Adult male SHR and age-matched Wistar-Kyoto rats (WKY) were divided into four groups: WKY sedentary group, SHR sedentary group, low-intensity training group, and medium-intensity training group. Using molecular and biochemical approaches, we investigated the effects of 14-week training on renalase (RNLS) protein levels, renal function, and apoptosis and oxidative stress modulators in kidney tissues. In vitro, angiotensin II (Ang II)-induced human kidney proximal epithelial cells (HK-2) were treated with RNLS, and changes in apoptosis and oxidative stress levels were observed. Our results show that moderate training improved renal function decline in SHR. In addition, aerobic exercise therapy significantly increased levels of RNLS in the renal medulla of SHR. We observed in vitro that RNLS significantly inhibited the increase of Ang II-inducedapoptosis and oxidative stress levels in HK-2. In conclusion, aerobic exercise training effectively improved renal function in SHR by promoting RNLS expression in the renal medulla. These results explain the possible mechanism in which exercise improves renal injury in hypertensive patients and suggest RNLS as a novel therapy for kidney injury patients.

Abstract Background Ketogenic diet (KD) has been proposed to be an effective lifestyle intervention in metabolic syndrome. However, the effects of KD on cardiac remodeling have not been investigated. Our aim was to investigate the effects and the underling mechanisms of KD on cardiac remodeling in spontaneously hypertensive rats (SHRs). Methods 10-week-old spontaneously hypertensive rats were subjected to normal diet or ketogenic diet for 4 weeks. Then, their blood pressure and cardiac remodeling were assessed. Cardiac fibroblasts were isolated from 1- to 3-day-old neonatal pups. The cells were then cultured with ketone body with or without TGF-β to investigate the mechanism in vitro. Results 4 weeks of KD feeding aggravated interstitial fibrosis and cardiac remodeling in SHRs. More interestingly, ketogenic diet feeding increased the activity of mammalian target of rapamyoin (mTOR) complex 2 pathway in the heart of SHRs. In addition, β-hydroxybutyrate strengthened the progression of TGF-β-induced fibrosis in isolated cardiac fibroblasts. mTOR inhibition reversed this effect, indicating that ketone body contributes to cardiac fibroblasts via mTOR pathway. Conclusions These data suggest that ketogenic diet may lead to adverse effects on the remodeling in the hypertensive heart, and they underscore the necessity to fully evaluate its reliability before clinical use.

Background: Although the past decade has witnessed substantial scientific progress with the advent of cardioprotective pharmacological agents, most have failed to protect against myocardial ischemia/reperfusion (I/R) injury in diabetic hearts. This study was aimed at investigating the role of stimulator of interferon genes (STING) in I/R injury in diabetic mice and further exploring the underlying mechanisms. Methods: Type 2 diabetic mice were subjected to I/R or sham operation to investigate the role of STING. STING knockout mice were subjected to 30 minutes of ischemia followed by reperfusion for 24 hours. Finally, myocardial injury, cardiac function, and inflammation levels were assessed. Results: STING pathway activation was observed in diabetic I/R hearts, as evidenced by increased p-TBK and p-IRF3 expression. STING knockout significantly decreased the ischemic area and improved cardiac function after I/R in diabetic mice. STING knockout also elicited cardio-protective effects by decreasing serum cardiac troponin T and lactate dehydrogenase levels, thus diminishing the inflammatory response in the heart after I/R in diabetic mice. In vitro , STING inhibition decreased the expression of hypoxia-re-oxygenation-induced inflammatory cytokines. Conclusions: Targeting STING inhibits inflammation and prevents I/R injury in diabetic mice. Thus, STING may be a potential novel therapeutic target against myocardial I/R injury in diabetes.

Abstract Background Hypertension is a highly prevalent disease and the leading cause of chronic kidney disease (CKD). Metabolic syndrome could also be the risk factor for CKD. We sought to study the association between metabolic syndrome components and the prevalence of CKD in patients with hypertension. Methods We carried out a multi-center cross-sectional study from Apr. 2017- Apr. 2018 in 15 cities in China. Results A total of 2484 patients with hypertension were enrolled. Among them, 56% were male and the average age was 65.12 ± 12.71 years. The systolic BP/diastolic BP was 142 ± 18/83 ± 12 mmHg. Metabolic syndrome components turned out to be highly prevalent in patients with hypertension, ranging from 40 to 58%. The prevalence of chronic kidney disease reached 22.0%. Multi-variate logistic analysis revealed that elevated triglyceride (TG) (OR = 1.81, 95% CI 1.28–2.57, p

Background: The present study was to evaluate the value of CHADS2 and CHA2DS2VASC scores on predicting left atrial (LA) or left atrial appendage (LAA) thrombus in atrial fibrillation (AF) patients prior to ablation in the real world of China. Methods and results: A total of 397 patients with non-valvular AF were analyzed to determine the relationship between CHADS2 and CHA2DS2VASC scores and LA/LAA thrombus identified on transesophageal echocardiography prior to radiofrequency ablation(RFA). LA/LAA thrombus was present in 38 patients (9.6%). There was a strong association between higher CHADS2 score or CHA2DS2VASC score and LA/LAA thrombus. No thrombus was identified in patients with CHA2DS2VASC score of 0 regardless of anticoagulation status. However, LA/LAA thrombus was detected in 2.9% patients with CHADS2 score of 0 without adequate anticoagulation, while no thrombus was present in the patients with CHADS2 score of 0 with adequate anticoagulation. Univariate analysis showed that heart failure (LVEF＜50%), LA≥40 mm, diabetes mellitus, previous stroke or TIA, CAD, hypertension, inadequate anticoagulation therapy, CHADS2 score of ≥2 and CHA2DS2VASC score of ≥2 were significantly associated with LA/LAA thrombus. Multivariable Cox regression analysis demonstrated that CHA2DS2VASC score of ≥2 (p = 0.02) and previous stroke or TIA (p = 0.04) were independently associated with LA/LAA thrombus regardless of anticoagulation status. ROC curve analysis showed that higher CHADS2 score and CHA2DS2VASC score could be similarly used to predict the presence of LA thrombus. Conclusions: Both higher CHA2DS2VASC and CHADS2 scores were associated with LA/LAA thrombus in non-valvular AF patients prior to ablation. Although CHA2DS2VASC score and CHADS2 score had similar value to predict LA/LAA thrombus, CHA2DS2VASc score was better to identify low-risk patients for LA/LAA thrombus than CHADS2 score without anticoagulation. There will be a possibility of performing AF ablation or cardioversion in patients with a CHA2DS2VASC of 0 without TEE or anticoagulation therapy. The safety need to be verified by more multicentre randomized controlled clinical trails. Keywords: Atrial fibrillation, Left atrial or left atrial appendage thrombus, Transesophageal echocardiography, CHADS2 score, CHA2DS2VASC score

Background: Imbalance of testosterone/estradiol ratio are frequently reported to be associated with the risk of cardiometabolic diseases; however, studies have yet to report the testosterone/estradiol ratio and its relationship to cardiometabolic diseases in women at menopause transition. This study aimed to explore the association between testosterone/estradiol ratio with cardiometabolic diseases in women during their menopausal transition age. Methods: 551 women aged from 45 to 55 years old were involved in this study. Their baseline information, disease comorbidity, blood biochemical tests, echocardiography and serum sex hormones were collected. Women were categorized by tertile distribution of testosterone/estradiol ratio. We used binary logistic regression model (for odds ratio) and poissoon loglinear model (for prevalence ratio) to evaluate the association between testosterone/estradiol ratio with cardiometabolic diseases. Results: The mean age of the study population was 48.6 ± 3.5 years old. Taking testosterone/estradiol ratio

Background: The coronary atherosclerotic burden in patients with ST-segment elevation myocardial infarction (STEMI) has been identified as the main predictor of prognosis. However, the association of lipoprotein(a) [Lp(a)], a well-established proatherogenic factor, with atherosclerotic burden in patients with STEMI is unclear.Methods: In total, 1,359 patients who underwent percutaneous coronary intervention (PCI) for STEMI were included in analyses. Three prespecified models with adjustment for demographic parameters and risk factors were evaluated. Generalized additive models and restricted cubic spline analyses were used to assess the relationships of Lp(a) with Gensini scores and the no-reflow phenomenon. Kaplan–Meier curves were generated to explore the predictive value of Lp(a) for long-term all-cause mortality. Furthermore, mRNA expression levels of LPA in different groups were compared using the GEO database.Results: Patients in the highest tertile according to Lp(a) levels had an increased incidence of heart failure during hospitalization. Furthermore, patients with high levels of Lp(a) (>19.1 mg/dL) had sharply increased risks for a higher Gensini score (Pfor trend = 0.03) and no-reflow (Pfor trend = 0.002) after adjustment for demographic parameters and risk factors. During a median follow-up of 930 days, 132 deaths (9.95%) were registered. Patients with high levels of Lp(a) (>19.1 mg/dL) had the worst long-term prognosis (Pfor trend < 0.0001). In a subgroup analysis, patients with higher Lp(a) still had the highest all-cause mortality. Additionally, the mRNA expression levels of LPA in patients with STEMI with lower cardiac function were higher than those in other groups (P = 0.003). A higher coronary atherosclerotic burden was correlated with higher LPA expression (P = 0.01).Conclusion: This study provides the first evidence that Lp(a) (at both the protein and mRNA levels) is independently associated with coronary atherosclerotic lesions and prognosis in patients with STEMI treated with PCI.Clinical Trial Registration:http://www.chictr.org.cn/index.aspx, identifier: ChiCTR1900028516.

Increasing evidence has indicated that modulation of epigenetic mechanisms, especially methylation and long-non-coding RNA (lncRNA) regulation, plays a pivotal role in the process of atherosclerosis; however, few studies focused on revealing the epigenetic-related subgroups during atherosclerotic progression using unsupervised clustering analysis. Hence, we aimed to identify the epigenetics-related differentially expressed genes associated with atherosclerosis subtypes and characterize their clinical utility in atherosclerosis. Eighty samples with expression data (GSE40231) and 49 samples with methylation data (GSE46394) from a large artery plaque were downloaded from the GEO database, and aberrantly methylated–differentially expressed (AMDE) genes were identified based on the relationship between methylation and expression. Furthermore, we conducted weighted correlation network analysis (WGCNA) and co-expression analysis to identify the core AMDE genes strongly involved in atherosclerosis. K-means clustering was used to characterize two subtypes of atherosclerosis in GSE40231, and then 29 samples were recognized as validation dataset (GSE28829). In a blood sample cohort (GSE90074), chi-square test and logistic analysis were performed to explore the clinical implication of the K-means clusters. Furthermore, significance analysis of microarrays and prediction analysis of microarrays (PAM) were applied to identify the signature AMDE genes. Moreover, the classification performance of signature AMDE gene-based classifier from PAM was validated in another blood sample cohort (GSE34822). A total of 1,569 AMDE mRNAs and eight AMDE long non-coding RNAs (lncRNAs) were identified by differential analysis. Through the WGCNA and co-expression analysis, 32 AMDE mRNAs and seven AMDE lncRNAs were identified as the core genes involved in atherosclerosis development. Functional analysis revealed that AMDE genes were strongly related to inflammation and axon guidance. In the clinical analysis, the atherosclerotic subtypes were associated with the severity of coronary artery disease and risk of adverse events. Eight genes, including PARP15, SERGEF, PDGFD, MRPL45, UBR1, STAU1, WIZ, and LSM4, were selected as the signature AMDE genes that most significantly differentiated between atherosclerotic subtypes. Ultimately, the area under the curve of signature AMDE gene-based classifier for atherosclerotic subtypes was 0.858 and 0.812 in GSE90074 and GSE34822, respectively. This study identified the AMDE genes (lncRNAs and mRNAs) that could be implemented in clinical clustering to recognize high-risk atherosclerotic patients.

A previous meta-analysis of randomized controlled studies that were not designed to investigate cancer as a primary outcome suggested that ARB-based therapy is associated with increased risk of cancer; however, results of recent observational studies considering the association have been contradictory. This study sought to evaluate the association between angiotensin receptor blocker (ARB)-based therapy and risk of cancer by conducting a meta-analysis of observational studies.Relevant articles published before February 2014 were identified by searching PubMed and the Cochrane Library. Pooled relative risks (RRs) were determined using a random effects model and were used to assess the strength of association between use of ARB-based therapy and risk of cancer.Six retrospective cohort studies involving a total of 3,827,109 participants and four case-control studies involving a total of 193,029 cases were included. The present study found that ARB-based therapy was not significantly associated with an increased risk of cancer (RR = 0.87, 95%CI: [0.75, 1.01]). However, an analysis including only cohort studies suggested a significantly decreased risk of cancer among individuals with any history of ARB use as compared to those with no history of ARB use (RR = 0.80, 95%CI: [0.55, 0.95]); no significant association was found between ARB use and risk of cancer when the case-control studies were separately considered (RR = 1.03, 95%CI: [0.93, 1.13]). Subgroup analyses showed that use of ARB-based therapy was associated with decreased risk of lung cancer (RR = 0.81, 95%CI: [0.69, 0.94]); however, no significant associations were found with the other cancer sites investigated. Furthermore, no association was observed upon adjustment by type of ARB drug. No publication bias was detected.Overall, ARB-based therapy was not associated with increased risk of cancer. However, its use may be related to decreased incidence of lung cancer; this finding should be considered carefully and confirmed with further studies.

The present study is to investigate whether inflammatory cytokines inhibit ABCA1/ABCG1-mediated cholesterol efflux by regulating miR-33a-5P in THP-1 macrophages. We used interleukin-6 and tumor necrosis factor-alpha in the presence or absence of native low density lipoprotein (LDL) to stimulate THP-1 macrophages. THP-1 macrophages were infected by either control lentivirus vectors or lentivirus encoding miR-33a-5P or antisense miR-33a-5P. The effects of inflammatory cytokines, miR-33a-5P and antisense miR-33a-5P on intracellular lipids accumulation and intracellular cholesterol contents were assessed by oil red O staining and quantitative intracellular cholesterol assay. ApoA-I-mediated cholesterol efflux was examined using the fluorescent sterol (BODIPY-cholesterol). The gene and protein expressions of the molecules involved in cholesterol trafficking were examined using quantitative real-time polymerase chain reaction and Western blotting. Inflammatory cytokines or miR-33a-5P increased intracellular lipid accumulation and decreased apoA-I-mediated cholesterol efflux via decreasing the expression of ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. However, antisense miR-33a-5P reversed the effects of inflammatory cytokines on intracellular lipid accumulation, cholesterol efflux, and the expression of miR-33a-5P, ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. This study indicated that inflammatory cytokines inhibited ABCA1/ABCG1-mediated cholesterol efflux by up-regulating miR-33a-5P in THP-1 macrophages.

Backgrounds: Ventricular functional mitral regurgitation (FMR) is a common morbidity in patients with heart failure (HF). In addition to guideline-directed medical therapy, mitral valve (MV) repair or replacement has become an option for such patients. However, the impact of different treatments on cardiac remodeling, function, and clinical outcomes remains unclear. Methods: We systematically searched PubMed, EMBASE, Medline, Clinical Trials.gov, and the Cochrane Central Register of Controlled Trials with search terms related to mitral regurgitation, mitral valve repair, surgical mitral valve replacement, mitral annuloplasty device, and MitraClip. The outcomes were left ventricular ejection fraction (LVEF), left ventricular (LV) remodeling, all-cause mortality, cardiovascular death, and HF hospitalization. Sensitivity analysis was performed by removing high-bias risk studies. The analysis was done by Review Manager 5.4 Analyzer and MedCalc Statistical Software version 19.2.6. Results: This meta-analysis included 10 studies with a total of 2533 patients (567 with transcatheter MitraClip, 823 with surgical MV repair, 651 with surgical MV replacement, and 492 with medical therapy). Our meta-analysis revealed that surgical MV repair had significant improvement in LVEF compared to the surgical MV replacement (mean differences (MD) 2.32, [95% CI 0.39, 4.25]), while transcatheter MitraClip treatment was associated with LVEF reduction (MD -4.82, [95% CI -7.29, -2.34]). In terms of LV remodeling, transcatheter MitraClip treatment was associated with improvement in left ventricular end-diastolic volume (MD -10.36, [95% CI -18.74, -1.99]). Furthermore, compared to surgical MV replacement, surgical MV repair was not associated with a reduction of all-cause mortality (risk ratio (RR) 0.83, [95% CI 0.61, 1.13]) and cardiovascular death (RR 0.95, [95% CI 0.56, 1.62]), while transcatheter MitraClip was associated with reduced risk of all-cause mortality (RR 0.87, [95% CI 0.78, 0.98]). Conclusions: Surgical MV repair was associated with significant improvement in LVEF but had no significant effect on all-cause mortality compared to surgical MV replacement. Transcatheter MitraClip was associated with better long-term survival than the non-MitraClip group, thus, transcatheter MitraClip could be considered an alternative treatment in patients with HF-complicated ventricular FMR. [ABSTRACT FROM AUTHOR]