The potential role of the triglyceride-glucose index in left ventricular systolic function and in-hospital outcomes for patients with acute myocardial infarction.

BACKGROUND: A limited number of small-sample cohort studies have investigated the association between the triglyceride-glucose index and in-hospital prognosis. Moreover, the translational potential role of left ventricular systolic function - measured by left ventricular ejection fraction - combined with the triglyceride-glucose index in prioritizing patients with acute myocardial infarction at high risk of in-hospital major adverse cardiovascular events remains unknown. AIM: To explore the potential role of the triglyceride-glucose index in left ventricular systolic function and in-hospital major adverse cardiovascular events in patients with acute myocardial infarction. METHODS: The Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project (CCC-ACS) was analysed for this study. RESULTS: We included 43,796 patients with acute myocardial infarction. Patients with a higher triglyceride-glucose index showed an increased risk of major adverse cardiovascular events (adjusted odds ratio 1.46, 95% confidence interval 1.31-1.63). Interaction analyses revealed that left ventricular ejection fraction modified the relationship between the triglyceride-glucose index and major adverse cardiovascular events. Furthermore, patients with acute myocardial infarction were categorized by the triglyceride-glucose index and left ventricular ejection fraction; the low left ventricular ejection fraction/high triglyceride-glucose index group showed the highest risk of major adverse cardiovascular events (adjusted odds ratio 2.14, 95% confidence interval 1.58-2.89). CONCLUSIONS: In a comprehensive nationwide acute myocardial infarction registry conducted in China, a higher triglyceride-glucose index was found to be associated with in-hospital major adverse cardiovascular events, and this was particularly evident among patients with a lower left ventricular ejection fraction. Moreover, the triglyceride-glucose index combined with left ventricular ejection fraction was helpful for risk stratification of patients with acute myocardial infarction.

Efficacy and safety of olmesartan medoxomil­amlodipine besylate tablets (Sevikar®) in older patients with essential hypertension: Subgroup analysis from the Sevikar study.

Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablets in older Chinese patients with essential hypertension has not been performed. Therefore, the present study aimed to evaluate the efficacy and safety of OM-AML tablets in these patients. A total of 463 older Chinese patients with essential hypertension treated with OM-AML (20/5 mg) tablets (Sevikar®) were analyzed in a prospective, single-arm, multi-center, real-world study. Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, and at week (W)4 and W8 after OM-AML tablet administration were measured. The mean ± standard error change of SeSBP/SeDBP was -10.3±0.8/-4.6±0.5 and -12.5±0.8/-5.6±0.5 mmHg at W4 and W8, respectively. At W4, 74.1 and 26.8% of patients achieved BP target according to the China and American Heart Association (AHA) criteria, while at W8, 78.0 and 38.7% of patients reached these BP targets accordingly. Finally, 76.5 and 80.5% of patients achieved BP response at W4 and W8, respectively. Furthermore, home-measured SeSBP and SeDBP were significantly decreased from W1 to W8 (both P<0.001). Additionally, the satisfaction of both patients and physicians was elevated at W8 compared with at W0 (both P<0.001). The medication possession rate from baseline to W4 and W8 was 95.5 and 92.5%. The most common drug-associated adverse events by system organ classes were nervous system disorder (4.5%), vascular disorder (2.8%), and general disorder and administration site conditions (2.6%), which were generally mild. In conclusion, OM-AML tablets may be considered effective and safe in lowering BP, enabling the achievement of guideline-recommended BP targets in older Chinese patients with essential hypertension.

Recurrent cardiac arrest and complete atrioventricular block due to idiopathic coronary vasospasm: A case report.

Recurrent complete atrioventricular block induced by coronary spasm is rare. We present a case of a 47-year-old woman who suffered from two episodes of out-of-hospital cardiac arrest within one year due to complete atrioventricular block caused by coronary vasospasm. No implantable cardioverter defibrillator was implanted after her first episode. As for the second episode, permanent brain injury was left behind despite successful cardiopulmonary resuscitation. She underwent a challenging rehabilitation process and an implantable cardioverter defibrillator was implanted before discharge. We captured the dynamic changes of the electrocardiogram during the episode with high temporal resolution. This case illustrates the importance of recognizing coronary spasm as a potential cause of complete atrioventricular block and highlights the need for implantable cardioverter defibrillator in such patients to improve survival and quality of life.

Prognostic value of red blood cell distribution width combined with chloride in predicting short- and long-term mortality in critically ill patients with congestive heart failure: Findings from the MIMIC-IV database.

Background: Hypochloremia and red blood cell distribution width (RDW) play important roles in congestive heart failure (CHF) pathophysiology, and they were associated with the prognosis of CHF. However, the prognostic value of chloride combined with RDW in patients with CHF remains unknown. Methods: We retrospectively analyzed critically ill patients with CHF. The database was derived from the Medical Information Mart for Intensive Care IV v2.0 (MIMIC-IV-v2.0) database. Results: In the final analysis, 5376 critically ill patients with CHF were included, and 2428 patients (45.2 %) experienced 5-year mortality. The restricted cubic spline model revealed a positive correlation between RDW and 5-year mortality, whereas chloride showed a U-shaped correlation with 5-year mortality. The median values of RDW and chloride were used to classify patients into four groups: high chloride/low RDW, low chloride/low RDW, high chloride/high RDW, and low chloride/high RDW. We observed the prognostic value of RDW combined with chloride in the Cox proportional hazard model, in predicting 5-year mortality, in-hospital mortality and 1-year mortality. Furthermore, we discovered that patients with chronic kidney disease (CKD) had a higher 5-year mortality risk than patients without CKD. Conclusion: We found the translational potential role of chloride combined with RDW in prioritizing patients at high risk for short- and long-term mortality in a cohort of critically ill patients with CHF. Prospective multicenter investigations are warranted to validate our results.

Efficacy and safety of olmesartan medoxomil-amlodipine besylate tablet in Chinese patients with essential hypertension: A prospective, single-arm, multi-center, real-world study.

There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

Prognostic Impact of Early Administration of ß-Blockers in Critically Ill Patients with Acute Myocardial Infarction.

In critically ill patients with acute myocardial infarction (AMI), the relationship between the early administration of ß-blockers and the risks of in-hospital and long-term mortality remains controversial. Furthermore, there are conflicting evidences for the efficacy of the early administration of intravenous followed by oral ß-blockers in AMI. We conducted a retrospective analysis of critically ill patients with AMI who received the early administration of ß-blockers within 24 hours of admission. The data were extracted from the Medical Information Mart for Intensive Care IV database. We enrolled 2467 critically ill patients with AMI in the study, with 1355 patients who received the early administration of ß-blockers and 1112 patients who were non-users. Kaplan-Meier survival analysis and Cox proportional hazards models showed that the early administration of ß-blockers was associated with a lower risk of in-hospital mortality (adjusted hazard ratio [aHR] 0.52; 95% confidence interval [95%CI] 0.42-0.64), 1-year mortality (aHR 0.54, 95%CI 0.47-0.63), and 5-year mortality (aHR 0.60, 95%CI 0.52-0.69). Furthermore, the early administration of both oral ß-blockers and intravenous ß-blockers followed by oral ß-blockers may reduce the mortality risk, compared with non-users. The risks of in-hospital and long-term mortality were significantly decreased in patients who underwent revascularization with the early administration of ß-blockers. We found that the early administration of ß-blockers could lower the risks of in-hospital and long-term mortality. Furthermore, the early administration of both oral ß-blockers and intravenous ß-blockers followed by oral ß-blockers may reduce the mortality risk, compared with non-users. Notably, patients who underwent revascularization with the early administration of ß-blockers showed the lowest risks of in-hospital and long-term mortality.

Effect of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on In-Hospital Outcomes Based on Renal Function Among Critically Ill Patients: Findings From the Medical Information Mart for Intensive Care IV Database.

Renal dysfunction is associated with increased mortality and length of hospital stay in critically ill patients. However, it remains unclear whether the early administration of an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) for intensive care unit patients with renal dysfunction is associated with reduced in-hospital mortality. We conducted a retrospective analysis of critically ill patients who received early administration of an ACEI/ARB within 72 hours after being hospitalized. Patients were selected from the Medical Information Mart for Intensive Care IV database. We included 18,986 critically ill patients in our analysis. After propensity score matching, our final study cohort of 4974 patients consisted of patients who received early administration of an ACEI/ARB (n = 2487) and nonusers (n = 2487). Results of logistic regression showed that early administration of an ACEI/ARB was associated with reduced risk of in-hospital mortality (odds ratio, 0.64; 95% confidence interval, 0.53-0.77; P < .001) and intensive care unit death (odds ratio, 0.56; 95% confidence interval, 0.45-0.70; P < .001) when compared to nonusers. There was no meaningful interaction for early administration of an ACEI/ARB versus nonusers across estimated glomerular filtration rate in outcomes. Sensitivity analysis showed there was no difference in the outcomes between early administration of ACEI and that of ARB. In this study, we found that early administration of an ACEI/ARB was associated with a reduced risk of in-hospital adverse outcomes based on renal function among critically ill patients. There was no interaction between early administration of an ACEI/ARB and in-hospital adverse outcomes across estimated glomerular filtration rate.

Relationship between stress hyperglycemia ratio and allcause mortality in critically ill patients: Results from the MIMIC-IV database.

Background: Stress hyperglycemia ratio (SHR) was developed to reduce the impact of long-term chronic glycemic factors on stress hyperglycemia levels, which have been linked to clinical adverse events. However, the relationship between SHR and the short- and long-term prognoses of intensive care unit (ICU) patients remains unclear. Methods: We retrospectively analyzed 3,887 ICU patients (cohort 1) whose initial fasting blood glucose and hemoglobin A1c data within 24 hours of admission were available and 3,636 ICU patients (cohort 2) who were followed-up for 1-year using the Medical Information Mart for Intensive Care IV v2.0 database. Patients were divided into two groups based on the optimal cutoff value of SHR, which was determined using the receiver operating characteristic (ROC) curve. Results: There were 176 ICU deaths in cohort 1 and 378 patients experienced all-cause mortality during 1 year of follow-up in cohort 2. The results of logistic regression revealed that SHR was associated with ICU death (odds ratio 2.92 [95% confidence interval 2.14-3.97] P < 0.001), and non-diabetic patients rather than diabetic patients showed an increased risk of ICU death. As per the Cox proportional hazards model, the high SHR group experienced a higher incidence of 1-year all-cause mortality (hazard ratio 1.55 [95% confidence interval 1.26-1.90] P < 0.001). Moreover, SHR had an incremental effect on various illness scores in predicting ICU all-cause mortality. Conclusion: SHR is linked to ICU death and 1-year all-cause mortality in critically ill patients, and it has an incremental predictive value in different illness scores. Moreover, we found that non-diabetic patients, rather than diabetic patients, showed an increased risk of all-cause mortality.

A five-parameter score for predicting saphenous vein graft degenerative and/or occlusive disease in recurring ischemic symptoms after one year post coronary artery bypass grafting.

BACKGROUND: The recurrence rate of ischemic symptoms after coronary artery bypass grafting (CABG) is increasing in recent years. How to prevent and treat saphenous vein graft disease (SVGD [symptomatic ⩾50% stenosis in at least one Saphenous vein graft]) has been a clinical challenge to date. Different pathogenesis may exist in SVGD of different periods. There are currently few available scores for estimating the risk of SVGD after one year post CABG. OBJECTIVE: We sought to develop and validate a simple predictive clinical risk score for SVGD with recurring ischemia after one year post CABG. METHODS AND RESULTS: This was a cross-sectional study and the results were validated using bootstrap resampling on a separate cohort. A nomogram and risk scoring system were developed based on retrospective data from a training cohort of 606 consecutive patients with recurring ischemia >1 year after CABG. Logistic regression model was used to find the predictive factors and to build a nomogram. To assess the generalization, models were validated using bootstrap resampling and an external cross-sectional study of 187 consecutive patients in four other hospitals. In multivariable analysis of the primary cohort, native lesion vessel number, SVG age, recurring ischemia type, very low-density lipoprotein level, and left ventricular end-diastolic diameter were independent predictors. A summary risk score was derived from nomogram, with a cut-off value of 15. In internal and external validation, the C-index was 0.86 and 0.82, indicating good discrimination. The calibration curve for probability of SVGD showed optimal agreement between actual observations and risk score prediction. CONCLUSION: A simple-to-use risk scoring system based on five easily variables was developed and validated to predict the risk of SVGD among patients who recurring ischemia after one year post CABG. This score may be useful for providing patients with individualized estimates of SVGD risk.

Knockdown of TRIM27 alleviated sepsis-induced inflammation, apoptosis, and oxidative stress via suppressing ubiquitination of PPARγ and reducing NOX4 expression.

BACKGROUND: Sepsis is a global fatal disease and leads to severe lung injury due to dysfunction of inflammation response. TRIM27 is closely related to the diseased with dysfunction of inflammation response. The aim of this study was to clarify the role and mechanism of TRIM27 in sepsis-induced lung injury. METHODS: The lipopolysaccharide (LPS)-induced septic mouse model was successfully established. The lung injury was evaluated by lung wet/dry (W/D) ratio and hematoxylin-eosin (H&E) staining. The cell apoptosis was evaluated by TUNEL assay. The inflammatory cytokines were measured by quantitative real time-PCR (qRT-PCR) assay and commercial enzyme-linked immunosorbent assay (ELISA). The oxidative stress was assessed by the contents of superoxide dismutase (SOD) and malondialdehyde (MDA), and the expression of dihydroethidium (DHE). RESULTS: In this study, we demonstrated that TRIM27 was up-regulated in LPS-induced septic mice. In loss-of-function experiments, knockdown of TRIM27 alleviated sepsis-induced lung injury, inflammation, apoptosis, and oxidative stress. More importantly, knockdown of TRIM27 was observed to reduce p-p65/NOX4 expression via suppressing ubiquitination of PPARγ. In rescue experiments, overexpression of NOX4 abolished the effect of sh-TRIM27 on alleviating sepsis-induced inflammation, apoptosis, and oxidative stress. CONCLUSION: These findings highlighted that knockdown of TRIM27 alleviated sepsis-induced inflammation, oxidative stress and apoptosis via suppressing ubiquitination of PPARγ and reducing NOX4 expression, which supports the potential utility of TRIM27 as a therapeutic target in septic lung injury.

Human Plasma Transcriptome Implicates Dysregulated S100A12 Expression: A Strong, Early-Stage Prognostic Factor in ST-Segment Elevated Myocardial Infarction: Bioinformatics Analysis and Experimental Verification.

The ability of blood transcriptome analysis to identify dysregulated pathways and outcome-related genes following myocardial infarction remains unknown. Two gene expression datasets (GSE60993 and GSE61144) were downloaded from Gene Expression Omnibus (GEO) Datasets to identify altered plasma transcriptomes in patients with ST-segment elevated myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. GEO2R, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes annotations, protein-protein interaction analysis, etc., were adopted to determine functional roles and regulatory networks of differentially expressed genes (DEGs). Dysregulated expressomes were verified at transcriptional and translational levels by analyzing the GSE49925 dataset and our own samples, respectively. A total of 91 DEGs were identified in the discovery phase, consisting of 15 downregulated genes and 76 upregulated genes. Two hub modules consisting of 12 hub genes were identified. In the verification phase, six of the 12 hub genes exhibited the same variation patterns at the transcriptional level in the GSE49925 dataset. Among them, S100A12 was shown to have the best discriminative performance for predicting in-hospital mortality and to be the only independent predictor of death during follow-up. Validation of 223 samples from our center showed that S100A12 protein level in plasma was significantly lower among patients who survived to discharge, but it was not an independent predictor of survival to discharge or recurrent major adverse cardiovascular events after discharge. In conclusion, the dysregulated expression of plasma S100A12 at the transcriptional level is a robust early prognostic factor in patients with STEMI, while the discrimination power of the protein level in plasma needs to be further verified by large-scale, prospective, international, multicenter studies.

Human Plasma Metabolomics Identify 9-cis-retinoic Acid and Dehydrophytosphingosine Levels as Novel biomarkers for Early Ventricular Fibrillation after ST-elevated Myocardial Infarction.

The relevant metabolite biomarkers for risk prediction of early onset of ventricular fibrillation (VF) after ST-segment elevation myocardial infarction (STEMI) remain unstudied. Here, we aimed to identify these imetabolites and the important metabolic pathways involved, and explore whether these metabolites could be used as predictors for the phenotype. Plasma samples were obtained retrospectively from a propensity-score matched cohort including 42 STEMI patients (21 consecutive VF and 21 non-VF). Ultra-performance liquid chromatography and mass spectrometry in combination with a comprehensive analysis of metabolomic data using Metaboanalyst 5.0 version were performed. As a result, the retinal metabolism pathway proved to be the most discriminative for the VF phenotype. Furthermore, 9-cis-Retinoic acid (9cRA) and dehydrophytosphingosine proved to be the most discriminative biomarkers. Biomarker analysis through receiver operating characteristic (ROC) curve showed the 2-metabolite biomarker panel yielding an area under the curve (AUC) of 0.836. The model based on Monte Carlo cross-validation found that 9cRA had the greatest probability of appearing in the predictive panel of biomarkers in the model. Validation of model efficiency based on an ROC curve showed that the combination model constructed by 9cRA and dehydrophytosphingosine had a good predictive value for early-onset VF after STEMI, and the AUC was 0.884 (95% CI 0.714-1). Conclusively, the retinol metabolism pathway was the most powerful pathway for differentiating the post-STEMI VF phenotype. 9cRA was the most important predictive biomarker of VF, and a plasma biomarker panel made up of two metabolites, may help to build a potent predictive model for VF.

Effects of percutaneous balloon mitral valvuloplasty in patients with mitral stenosis and atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVE: The study aimed to systematically review the existing literature and assess the effects of percutaneous balloon mitral valvuloplasty (PBMV) in patients with mitral stenosis and atrial fibrillation (AF) as opposed to sinus rhythm (SR). METHODS: Eligible studies were identified from six electronic databases before June 2021. The primary outcome was mitral valve area (MVA), and secondary outcomes were hemodynamic measurements, in-hospital complications, and long-term outcomes. Relative risks (RRs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were used as effect sizes. RESULTS: Fifteen studies were included involving 6351 patients. For the primary outcome, the AF group obtained less favourable changes in MVA (WMD: -0.10, 95%CI: -0.14, -0.06) and a significantly smaller postoperative and long-term MVA (WMD: -0.13, 95%CI: -0.18, -0.08 and WMD: -0.10, 95%CI: -0.17, -0.03, respectively) compared to the SR group. For secondary outcome, the AF group was associated with suboptimal outcomes as following (WMD/RR, [95%CI]): higher LAP (1.37, [0.86, 1.87]), more embolism (2.85, [1.44, 5.63]), lower event-free survival (0.89, [0.80, 1.00]), higher incidences of mitral valve replacement (2.20, [1.40, 3.46]), re-PBMV (2.28, [1.63, 3.19]), and mortality (3.28, [2.42, 4.44]). No significant differences were found in other outcomes. CONCLUSIONS: The currently available evidence suggests that PBMV may be less effective in patients with AF than in those with SR. However, early treatment and appropriate management of AF patients undergoing PBMV may benefit the immediate and long-term outcomes.

Comparative genomic analysis of different sexes and diet-specific amino acid mutation identification in Ancherythroculter nigrocauda.

Determining the sex and controlling the sex ratio are essential aspects of fish genetics that can assist in developing successful fish breeding programs. High quality genome assembly and annotations are prerequisites to determine sex-specific genes and their expression. In addition, analysis of resequencing data can identify genomic difference between male and female fishes. In this study, we performed chromosome-level genome assembly in female Ancherythroculter nigrocauda fish having low heterozygosity using PacBio reads. High-throughput chromatin conformation capture (HiC) yielded a genome of size 1054.05 Mb, with a contig N50 length of 3.40 Mb and a scaffold N50 length of 42.68 Mb. In addition, we sequenced 5 female and 5 male A. nigrocauda samples and identified sex-specific regions on LG20 Furthermore, diet-specific amino acid mutation were found on 582 genes between herbivorous and carnivorous fishes, with 26 of them exhibiting significantly different expression patterns in the liver tissue of these two types of fishes. The chromosome-level genome assembly of A. nigrocauda provides valuable resources for conducting in-depth comparative genomic studies with immense applications in fish genetic breeding and farming. Similarly, the diet-specific amino acid mutations are useful in the breeding of new strains of carnivorous fishes with an herbivorous diet.

Identification of atrial fibrillation-associated lncRNAs and exploration of their functions based on WGCNA and ceRNA network analyses.

Atrial fibrillation (AF) is a common cardiac arrhythmia that induces serious complications. However, pharmacological treatments of AF remain challenging. This study aimed to screen crucial long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNA (mRNAs) for AF using the microarray datasets (lncRNAs and mRNAs: GSE79768, GSE115574; miRNAs: GSE68475) collected from the Gene Expression Omnibus database. Weighted correlation network analysis of GSE79768 and GSE115574 datasets identified five modules were highly related to AF status. Among 118 module-related differentially expressed mRNAs, FBXW7, EGFR, CXCR2, ROCK1 and UBE2D1 were considered as hub genes according to the gene significance, module membership and the topological characteristics for the nodes in the protein-protein interaction network. lncRNA MIR100HG and LINC01105 may function by co-expressing with (MIR100HG-ROCK1/FBXW7/UBE2D1, LINC01105-EGFR) mRNAs or sponging miRNAs to regulate mRNAs (LINC01105-miR-125a-3p-EGFR, MIR100HG-miR-200b-3p- FBXW7, MIR100HG-miR-561-3p-CXCR2, MIR100HG-miR-548z-UBE2D1). Connectivity Map and Comparative Toxicogenomics Database searches predicted dexamethasone may treat AF by reversing the expression of MIR100HG; artemisinin may reverse the expression of hub DEGs. In conclusion, our results may provide novel molecular mechanisms and potential therapeutic targets and drugs for AF.

Efficacy and safety of Shexiang Baoxin pill (MUSKARDIA) in patients with stable coronary artery disease: a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial.

BACKGROUND: The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD. METHODS: A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency. RESULTS: In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45-1.07; P  = 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785). CONCLUSIONS: As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD. TRIAL REGISTRATION: chictr.org.cn, No. ChiCTR-TRC-12003513.

Optimization of GRACE Risk Stratification by N-Terminal Pro-B-type Natriuretic Peptide Combined With D-Dimer in Patients With Non-ST-Elevation Myocardial Infarction.

We aimed to explore the utility of multiple biomarkers with GRACE risk stratification for non-ST-elevation myocardial infarction (NSTEMI). A total of 1,357 patients diagnosed with NSTEMI were enrolled in this study at multiple medical centers in Tianjin, China. The outcomes were 1-year all-cause death and major adverse cardiac events (MACE: all-cause death, hospital admission for unstable angina, hospital admission for heart failure, nonfatal recurrent myocardial infarction, and stroke). C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to verify that the biomarkers improve the predictive accuracy of the GRACE score. A total of 57 participants died, while 211 participants experienced 231 MACEs during follow-up (mean: 339 days). For all-cause death, the combination of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and D-dimer improved the predictive accuracy of GRACE the most, with C-index, IDI, and NRI values of 0.88, 0.085, and 1.223, respectively. For MACE, trigeminal combination of NT-proBNP, fibrinogen, and D-dimer resulted in C-index, IDI, and NRI values of 0.80, 0.079, and 0.647, respectively. As a result, NT-proBNP, D-dimer, fibrinogen, and GRACE comprise a new scoring system for assessing 1-year clinical events. Kaplan-Meier analysis revealed a significant increase in 1-year mortality (score ≥3.85 vs <3.85, p < 0.0001) and 1-year MACE (score ≥1.72 vs <1.72, p < 0.0001) between different score groups. In conclusion, the combination of NT-proBNP and D-dimer added prognostic value to GRACE for all-cause death. Combining NT-proBNP, fibrinogen, and D-dimer increased the prognostic value of GRACE for MACE. This newly developed scoring system is strongly correlated with all-cause mortality and MACE, and can be easily utilized in clinical practice.

A comparison of the clinical effects and safety between the distal radial artery and the classic radial artery approaches in percutaneous coronary intervention.

BACKGROUND: Compared with a classic wrist puncture for radial artery catheterization, a distal radial artery puncture has the advantage of reducing the incidence of radial artery occlusion in anatomic and physiological procedures. This study aimed to explore the difference in clinical effects between the distal radial artery and classic radial artery approaches in percutaneous coronary intervention. METHODS: A total of 620 patients who underwent coronary angiography and/or percutaneous coronary intervention in our hospital from December 2017 to December 2018 were enrolled in this study. These patients were divided into two groups based on the puncture site: a distal radial artery group and a classic radial artery group. There were 312 patients in the radial artery group and 308 patients in the classic radial artery group. The puncture time, puncture success rate, surgery time, implanted stents, puncture site hemorrhage, hematoma, aneurysm, and iliac artery occlusion rate were observed. RESULTS: There was no significant difference in puncture time, puncture success rate, surgery time, implanted stent, puncture site hemorrhage, hematoma and aneurysm (P>0.05), while the radial artery occlusion rate was lower in the distal radial artery group, and the difference was statistically significant (P<0.05). CONCLUSIONS: The results of this study showed that the distal radial artery approach had a lower rate of brachial artery occlusion, indicating that it could be used as an alternative to the classic radial artery approach.

Suppression of circular RNA circDHCR24 alleviates aortic smooth muscle cell proliferation and migration by targeting miR-149-5p/MMP9 axis.

Circular RNAs (circRNAs) are involved in many courses of atherosclerosis and coronary artery disease (CHD). However, the role and effect of circRNAs in vascular restenosis after PCI remains unclear. Human aortic vascular smooth muscle cell (HA-VSMC) was cultured and stimulated with PDGF-BB. The expression profile of circRNAs in HA-VSMCs was screened using microarray analysis. A total 257 aberrantly expressed circRNAs were screened with 2 fold change. Has_circ_0113656 (also called circDHCR24) was validated by qRT-PCR to be significantly up-regulated in PDGF-BB induced HA-VSMCs. CircDHCR24 silencing obviously inhibited the proliferation, migration and phenotypic switch. Moreover, bioinformatics analysis predicted that miR-149-5p had complementary binding sites in 3'-UTR of circDHCR24. Luciferase reporter assay and RIP assay further verified the circDHCR24 acts as a spong for miR-149-5p in HA-VSMCs. Besides, bioinformatics analysis, luciferase reporter assay and RIP assay proved MMP9 was a directly target of miR-149-5p. Finally, cells were transfected with si-circDHCR24 with or without miR-149 inhibitor, and the results showed that co-transfection si-circDHCR24 and miR-149 inhibitor reversed the effect of si-circDHCR24 on cell proliferation, migration and phenotypic switch. Taken together, our study suggested for the first time that the knockdown of circDHCR24 alleviates HA-VSMCs proliferation, migration and phenotypic switching, thereby preventing vascular restenosis.