Search

Abstract Background The neutrophil-to-lymphocyte ratio (NLR) has emerged as a novel inflammatory marker related to disease prognosis, this study aimed to evaluate the association between NLR and mortality in metabolic syndrome (MetS) patients. Methods This study used data from 13,156 participants with MetS, derived from the National Health and Nutrition Examination Survey from 1999 to 2020. The NLR was calculated, and its associations with cardiovascular disease (CVD) mortality and all-cause mortality were assessed by multivariate Cox regression, restricted cubic spline and Kaplan-Meier curves. The study performed subgroup analyses to validate the robustness of the findings in different populations. The predictive ability of NLR was evaluated using time-dependent receiver operating characteristic curve. The indirect impact of eGFR was explored by mediation analysis. Results As NLR values increased, there was an obvious rise in the risk of mortality in MetS. The fully adjusted continuous model revealed a 16.0%, 14.4% elevated risk of CVD mortality (HR = 1.160; 95% CI: 1. 090-1.234, p

Abstract Cardiovascular disease (CVD) is a significant health concern, particularly among patients with diabetes. The weight-adjusted waist circumference index (WWI), a novel metric that accounts for central obesity, has shown potential in predicting obesity-related health risks. This study aimed to evaluate the association of WWI with CVD and mortality in patients with diabetes. Utilizing data from the National Health and Nutrition Examination Survey from 1999 to 2020, WWI was calculated by dividing waist circumference (WC) by the square root of body weight. Multivariate logistic regression, multivariate Cox regression and restricted cubic spline curves were used to assess the association between WWI and the prevalence of CVD and mortality in patients with diabetes, subgroup and sensitivity analyses were carried out to delve into the stability of the findings. The predictive performance of WWI was evaluated using the area under the receiver operating characteristic curve (ROC). This study included 8,005 individuals with diabetes. With the increase in WWI values, the risk of developing CVD and the likelihood of mortality progressively rise. The fully adjusted continuous model indicated a 28% higher chance of developing CVD and a 25% higher risk of all-cause mortality for each one-unit increase in WWI. When using the lowest quartile of WWI as the reference category, the highest quartile was linked to an increased risk of CVD (OR 1.66; 95% CI 1.10–2.50, p = 0.015) and all-cause mortality (HR 1.53, 95% CI 1.27–1.83, p

Abstract Metabolic syndrome (MetS) is prevalent and significantly impacts global public health, with obesity being a major risk factor for cardiovascular diseases (CVD) and mortality. Traditional metrics like body mass index (BMI) have limitations in assessing obesity-related risks. The weight-adjusted waist circumference index (WWI) has emerged as a novel obesity metric, this study aimed to evaluate the association of WWI with CVD and mortality in MetS patients. This study used data from 12,641 participants with MetS, derived from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2020. The WWI was calculated, and its association with CVD and mortality was assessed using multivariate logistic and Cox regression models. The study controlled for potential confounders and performed subgroup and sensitivity analyses to validate the robustness of the findings. The predictive performance of WWI was evaluated using the area under the receiver operating characteristic curve (ROC). Kaplan–Meier (KM) curves further were used to evaluate the associations between WWI and mortality of the MetS population. As WWI values escalated, there was a proportional rise in the risk of CVD and mortality in MetS. The fully adjusted continuous model revealed a 32.0% elevated likelihood of CVD development, a 69.5% increased probability of heart failure (HF), a 51.1% heightened risk for CVD mortality, and a 22.8% augmented risk for all-cause mortality with each one-unit increment in WWI. Comparing the highest to the lowest quartile of WWI, the top quartile exhibited a significantly increased risk of CVD (odds ratio [OR] = 1.883; 95% confidence interval [CI]: 1.276–2.633, p-value = 0.001), HF (OR = 2.909; 95% CI: 1.490–5.677, p-value = 0.002), CVD mortality (hazard ratio [HR] = 2.088; 95% CI: 1.279–3.409, p-value = 0.003), and all-cause mortality (HR = 1.394; 95% CI: 1.070–1.816, p-value = 0.014) among individuals with MetS. Sensitivity and subgroup analyses substantiated the consistency and stability of these associations across various demographic groups. The ROC analysis demonstrated that WWI outperforms BMI in predicting adverse outcomes in MetS. The KM curves validated that higher WWI values was correlated with diminished survival rates in MetS population. The WWI served as a significant indicator for assessing the risk of CVD and mortality in the MetS population. This study recommended the regular assessment of WWI in MetS individuals for evaluating their risk of CVD and mortality, potentially enhancing preventive and treatment strategies for this patient population.

Abstract Background The study aimed to explore the association between manganese concentration and all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality in the general population of the United States. Methods We integrated the data from the National Health and Nutrition Examination Survey from 2011 to 2018. A total of 9,207 subjects were selected based on the inclusion and exclusion criteria. The relationship between manganese concentration and all-cause, CVD-related, and cancer-related mortality was analyzed by constructing a Cox proportional hazard regression model and a restricted cubic spline (RCS) plot. Additionally, subgroup analyses stratified by age, sex, race/ethnicity, hypertension, diabetes mellitus (DM), chronic heart disease, chronic heart failure, angina pectoris, heart attack, stroke, and BMI were further performed. Results In the full adjusted model, compared with the lowest quartile, the adjusted hazard ratios with 95% confidence intervals (CIs) for all-cause, CVD-related, and cancer-related mortality across manganese quartiles were (1.11 (0.87,1.41), 0.96 (0.74, 1.23), and 1.23 (0.96, 1.59); P-value for trend =0.041), (0.86 (0.54, 1.37), 0.87 (0.55, 1.40), and 1.07 (0.67, 1.72); P-value for trend =0.906), and (1.45 (0.92, 2.29), 1.14 (0.70, 1.88), and 1.26 (0.75, 2.11); P-value for trend =0.526), respectively. The RCS curve shown a U-shaped association between manganese concentration and all-cause mortality and CVD-related mortality (P-value for nonlinear

Background: Heart failure (HF) is a severe disease threatening people's health. The aim of this study is to find a significant biomarker inducive to predicting the prognosis of HF. Methods: GSE135055 and GSE161472 datasets were reanalyzed for exploring key genes related to HF. This single-center, prospective, observational cohort study enrolled 298 patients with or without HF from the Cardiology Department of Zhongda Hospital. Levels of ADAM8 were measured using ELISA kits. Major adverse cardiovascular events (MACEs) were defined as the composite end points of the first occurrence of rehospitalization because of HF or cardiac-related death during one-year follow-up. Results: (1) Bioinformatics analysis showed that ADAM8 was a key gene in HF via mainly regulating the mechanisms of extracellular matrix (ECM) organization. (2) Levels of ADAM8 were significantly increased in the HF group, compared to the non-failing (NF) group (p

Patients who suffer from severe tricuspid regurgitation (TR) and who are at high surgical risk have no standard care therapy. Therefore, minimally invasive and safer methods are sought. K-clip™, the first ultrasound-positioned interventional tricuspid annuloplasty instrument intended for percutaneous transcatheter repair. We report a patient with severe functional TR and high surgical risk who underwent K-clip™ tricuspid annuloplasty under echocardiography and fluoroscopy guidance.

Abstract 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

Summary: Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. Findings: The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. Interpretation: The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

Abstract Early and prompt reperfusion therapy has markedly improved the survival rates among patients enduring myocardial infarction (MI). Nonetheless, the resulting adverse remodeling and the subsequent onset of heart failure remain formidable clinical management challenges and represent a primary cause of disability in MI patients worldwide. Macrophages play a crucial role in immune system regulation and wield a profound influence over the inflammatory repair process following MI, thereby dictating the degree of myocardial injury and the subsequent pathological remodeling. Despite numerous previous biological studies that established the classical polarization model for macrophages, classifying them as either M1 pro-inflammatory or M2 pro-reparative macrophages, this simplistic categorization falls short of meeting the precision medicine standards, hindering the translational advancement of clinical research. Recently, advances in single-cell sequencing technology have facilitated a more profound exploration of macrophage heterogeneity and plasticity, opening avenues for the development of targeted interventions to address macrophage-related factors in the aftermath of MI. In this review, we provide a summary of macrophage origins, tissue distribution, classification, and surface markers. Furthermore, we delve into the multifaceted roles of macrophages in maintaining cardiac homeostasis and regulating inflammation during the post-MI period.

Abstract Aims Heart failure (HF) remains a major public health problem with increasing prevalence in China. This study evaluated the clinical performance and quality measures for HF management to identify gaps in the standardization of care for patients hospitalized for HF in China. Methods and results Following the results of China‐HF stage I (2012–2015), the second stage of the China‐HF was launched in 2017. Among 113 hospitals with ≥100 cases, the China‐HF Stage II assessed the quality of care measures for HF and compared results with previous data in China and the US‐based Get with The Guidelines‐Heart Failure (GWTG‐HF) registries. In total, 34 938 patients hospitalized with HF were enrolled from January 2017 to October 2020. Echocardiographic left ventricular function and natriuretic peptide test were performed in 93.7% and 93.0% of the cases, respectively. Adherence to standardized guidelines in China‐HF stage II was higher than that in the China‐HF stage I, but generally lower than GWTG‐HF registry with 78.2% of eligible patients was prescribed oral diuretics, 78.7% renin‐angiotensin‐system inhibitors, and 82.2% beta‐blockers. Implantable cardioverter‐defibrillators and cardiac resynchronization devices were implanted in 3.9% and 14.6%, respectively. In contrast, the proportion of eligible patients discharged with spironolactone (87.8%) was higher than GWTG‐HF. The median length of hospitalization was 9 (6, 12) days, and 938 (2.8%) patients died or withdrew from treatment during hospitalization. Conclusions Despite significant improvements in the use of guideline‐recommended testing and therapy, there remain major gaps in quality of care for patients hospitalized for HF in China that are generally larger than gaps observed in the United States.

Background Although the Japanese chronic total occlusion (J-CTO) score is widely used to assess the complexity of revascularization for CTO lesions, ambiguous and conflicting results are reported in validation studies. Therefore, we aimed to quantitatively evaluate the effectiveness of the J-CTO score and explore the heterogeneity of its comparison with other CTO scores.Methods PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov databases were systematically searched from January 1st, 2011 to December 23rd, 2021. Studies that examined the accuracy of the J-CTO score were eligible. Where feasible, estimates of discrimination and calibration were pooled with a random-effects model. The Prediction model Risk Of Bias ASsessment Tool (PROBAST) was used for risk-of-bias assessment. This study was reported according to PRISMA guidelines and prospectively registered with PROSPERO (CRD42019126161).Results Of 28 included studies (N = 34,944 lesions), 24 were eligible for meta-analysis. The J-CTO score demonstrated significant discrimination for 30-min wire crossing (summary C-statistic 0.76; 95% CI 0.68–0.84) and technical success (0.68; 95% CI 0.61–0.74) despite significant heterogeneity. Only 19 (33%) of the 58 pairwise comparisons with 14 competing scores that were based on discrimination reported a statistical result. The J-CTO score performed worse (relative difference of C-statistics >5%) in eight out of 33 independent comparisons but better in another 13. Methodological shortcomings resulted from only one study evaluating model calibration appropriately.Conclusion The discrimination power of the J-CTO score was useful for time-efficient wire crossing and moderate for angiographic success. Head-to-head comparisons of CTO scores would benefit from standardized reporting and appropriate statistical methods.Key messagesThe J-CTO score has useful discrimination in predicting 30-min wire crossing while performing moderately for technical success.After excluding optimism bias, there is insufficient independent evidence supporting the superiority of newly introduced models over the J-CTO score.Standardized methodology and assessment are needed to achieve a better understanding of CTO scores, especially for their calibration.

ABSTRACTThe potential future burden of COVID-19 is determined by the level of susceptibility of the population to infection. The protective effect provided by those previously infected diminishes over several months, while individuals with mixed immunity have the highest degree and persistence of protection. This study aimed to clarify the vaccination status of COVID-19 patients with hypertension and to analyze the characteristics and risk factors of non-vaccinated patients to protect this vulnerable population in the future. The study ultimately enrolled 4576 hypertensive patients with Omicron infection from April 6, 2022, to May 15, 2022. Among them, 3556 patients (77.7%) had received at least one dose of vaccine, and 2058 patients (45.0%) received a booster dose. In the multivariate logistic analysis, male (OR 1.328, 95% CI 1.138–1.550, p

Mechanical stress and strain conditions are closely related to atherosclerotic plaque progression and rupture and have been under intensive investigations in recent years. It is well known that arteries have a three-layer structure: intima, media and adventitia. However, in vivo image-based multilayer plaque models are not available in the current literature due to lack of multilayer image segmentation data. A multilayer segmentation and repairing technique was introduced to segment coronary plaque optical coherence tomography (OCT) image to obtain its three-layer vessel structure. A total of 200 OCT slices from 20 patients (13 male; 7 female) were used to construct multilayer and single-layer 3D thin-slice models to calculate plaque stress and strain and compare model differences. Our results indicated that the average maximum plaque stress values of 20 patients from multilayer and single-layer models were 385.13 ± 110.09 kPa and 270.91 ± 95.86 kPa, respectively. The relative difference was 42.2%, with single-layer stress serving as the base value. The average mean plaque stress values from multilayer and single-layer models were 129.59 ± 32.77 kPa and 93.27 ± 18.20 kPa, respectively, with a relative difference of 38.9%. The maximum and mean plaque strain values obtained from the multilayer models were 11.6% and 19.0% higher than those from the single-layer models. Similarly, the maximum and mean cap strains showed increases of 9.6% and 12.9% over those from the single-layer models. These findings suggest that use of multilayer models could improve plaque stress and strain calculation accuracy and may have large impact on plaque progression and vulnerability investigation and potential clinical applications. Further large-scale studies are needed to validate our findings.

Background The Murray law‐based quantitative flow ratio (μQFR) is a novel technique that simulates fractional flow reserve (FFR) from a single angiographic view. However, the impact of sex differences on the diagnostic performance of μQFR has not been investigated. Methods and Results In this study, FFR and μQFR were assessed in 497 intermediate stenoses (30%–70% by visual estimation) from 460 patients (34.3% female). Physiological significance was defined as FFR ≤0.80 or μQFR ≤0.80. After adjusting for potential confounders, female sex was independently associated with higher FFR (P=0.048 and 0.026, respectively) and μQFR (P=0.001 for both) in both fully adjusted and stepwise backward models. μQFR provided superior diagnostic accuracy compared with angiography alone for detecting FFR ≤0.80 in both women (area under the curve, 0.93 [95% CI, 0.88–0.97] versus 0.80 [95% CI, 0.73–0.86]; P=0.001) and men (area under the curve, 0.88 [95% CI, 0.84–0.92] versus 0.73 [95% CI, 0.68–0.78]; P

Abstract Background Hypertension-induced cardiac hypertrophy is one of the most common pre-conditions that accompanies heart failure. This study aimed to identify the key pathogenic genes in the disease process. Methods GSE18224 was re-analyzed and differentially expressed genes (DEGs) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. Networks of transcription factor (TF)-mRNA, microRNA (miRNA)-mRNA and Protein-Protein interaction (PPI) were constructed, and a key module was further screened out from PPI network. GSE36074 dataset and our transverse aortic constriction (TAC) mouse model were used to validate gene expression in the module. Finally, the correlation between the genes and biomarkers of cardiac hypertrophy were evaluated. Results Totally, there were 348 DEGs in GSE18224, which were mainly enriched in biological processes including collagen fibril organization, cellular response to transforming growth factor-beta stimulus and were involved in ECM-receptor interaction and Oxytocin signaling pathway. There were 387 miRNAs targeted by 257 DEGs, while 177 TFs targeted 71 DEGs. The PPI network contained 222 nodes and 770 edges, with 18 genes screened out into the module. After validation, 8 genes, which were also significantly upregulated in the GSE36074 dataset, were selected from the 18 DEGs. 2 of the 8 DEGs, including Eln and Tgfb3 were significantly upregulated in our mouse model of myocardial hypertrophy. Finally, the expression of Eln and Tgfb3 were found to be positively correlated with the level of the disease biomarkers. Conclusions Upregulated key genes Eln and Tgfb3 were positively correlated with the severity of cardiac hypertrophy, which may provide potential therapeutic targets for the disease.

Abstract Background METTL3 is the core catalytic enzyme in m6A and is involved in a variety of cardiovascular diseases. However, whether and how METTL3 plays a role during angiotensin II (Ang-II)-induced myocardial hypertrophy is still unknown. Methods Neonatal rat cardiomyocytes (NRCMs) and C57BL/6J mice were treated with Ang-II to induce myocardial hypertrophy. qRT-PCR and western blots were used to detect the expression of RNAs and proteins. Gene function was verified by knockdown and/or overexpression, respectively. Luciferase and RNA immunoprecipitation (RIP) assays were used to verify interactions among multiple genes. Wheat germ agglutinin (WGA), hematoxylin and eosin (H&E), and immunofluorescence were used to examine myocardial size. m6A methylation was detected by a colorimetric kit. Results METTL3 and miR-221/222 expression and m6A levels were significantly increased in response to Ang-II stimulation. Knockdown of METTL3 or miR-221/222 could completely abolish the ability of NRCMs to undergo hypertrophy. The expression of miR-221/222 was positively regulated by METTL3, and the levels of pri-miR-221/222 that bind to DGCR8 or form m6A methylation were promoted by METTL3 in NRCMs. The effect of METTL3 knockdown on hypertrophy was antagonized by miR-221/222 overexpression. Mechanically, Wnt/β-catenin signaling was activated during hypertrophy and restrained by METTL3 or miR-221/222 inhibition. The Wnt/β-catenin antagonist DKK2 was directly targeted by miR-221/222, and the effect of miR-221/222 inhibitor on Wnt/β-catenin was abolished after inhibition of DKK2. Finally, AAV9-mediated cardiac METTL3 knockdown was able to attenuate Ang-II-induced cardiac hypertrophy in mouse model. Conclusions Our findings suggest that METTL3 positively modulates the pri-miR221/222 maturation process in an m6A-dependent manner and subsequently activates Wnt/β-catenin signaling by inhibiting DKK2, thus promoting Ang-II-induced cardiac hypertrophy. AAV9-mediated cardiac METTL3 knockdown could be a therapeutic for pathological myocardial hypertrophy.

Abstract Background Spontaneous coronary artery dissection (SCAD) is now recognized as an important cause of acute coronary syndrome (ACS), which is thought to be more prevalent in women. However, the male patients, on the other hand, cannot be easily ignored. Case presentation A 26-year-old male suffered from SCAD that occurred in the left main coronary artery (LMCA) and a secondary acute myocardial infraction (AMI). Coronary CT angiography and coronary angiography (CAG) revealed aneurysms in the LMCA and right coronary artery (RCA), as well as a total occlusion in the proximal branch of the left anterior descending artery (LAD). Along with drug therapy, coronary artery bypass graft (CABG) surgery was recommended, and the patient has been symptom-free for one year. Conclusion We report a case of spontaneous left main coronary artery dissection that occurred in a young male. The necessity of identifying typical imaging features and following up patients with SCAD for life to reduce the risk of fatal cardiac complications cannot be overstated.

BackgroundDespite anthocyanidins have anti-inflammatory and antioxidant properties, no studies have researched association between dietary intake of anthocyanidins and heart failure.MethodsWe enrolled 15,869 participants from the National Health and Nutrition Examination Survey (NHANES) (2007–2010 and 2017–2018) in this cross-sectional study. We examined baseline data and prevalence of heart failure in different quartile groups of anthocyanin intake (Q1-4). Three models were established through logistic regression to evaluate the protective effect of Q4 (highest anthocyanidins intake) on heart failure. The protective effect of high anthocyanidins intake on heart failure was further evaluated in different subgroups.ResultsParticipants with the highest anthocyanidins intake (Q4) had the lowest prevalence of heart failure (Q1:2.54%, Q2:2.33%, Q3:2.43%, Q4:1.57%, p = 0.02). After adjusting for possible confounding factors, compared with the Q1 group, the highest anthocyanidins intake (Q4) was independently related to lower presence of heart failure (Q4: OR 0.469, 95%CI [0.289, 0.732], p = 0.003). And this association was still stable in subgroups of female, ≥45 years, smoker, non-Hispanic White or without diabetes, stroke and renal failure.ConclusionDietary intake of anthocyanidins had negative association with the presence of heart failure.

Abstract In‐stent restenosis is a common complication after percutaneous coronary intervention (PCI) for coronary heart disease requiring revascularization. We performed a retrospective analysis to assess the value of inflammatory biomarker albumin to globulin ratio (AGR) in clinical prognosis of PCI. In total, 992 patients with coronary heart disease who underwent the first drug‐eluting stent implantation and re‐examination angiography in our hospital were enrolled in this study. The AGR was measured. At mean follow‐up of 11.2 ± 4 months, the in‐stent restenosis (ISR) and revascularization events (including target lesion revascularization, target vessel revascularization, and revascularization of de novo lesions) occurred in 127 and 284 patients, respectively. Compared with the non‐ISR or non‐event group, AGR was significantly lower in the ISR group and the events group. Beyond that, albumin was significantly lower, whereas urea nitrogen, glucose, and Gensini score, as well as the proportions of a history of diabetes and peripheral vascular diseases were significantly higher in the ISR group and the events group. Age, heart rate, white blood cell, neutrophils, lymphocyte, monocyte, and incidence of ischemic stroke were significantly higher in the events group. Multivariate Cox regression analysis showed that AGR was independently associated with ISR (p = 0.032) and events (p = 0.024). Besides, Kaplan‐Meier analysis indicated that the higher quartile of AGR had a lower rate of ISR (p = 0.038) and events (p ≤ 0.001). Finally, the receiver operating characteristic curve for AGR in diagnosing ISR and events indicated that the area under the curve were 0.56 and 0.57, respectively. Therefore, AGR is one of the most important factors that independently associate with the ISR and revascularization events after PCI.

Quantitative flow ratio (QFR) is a new method for the assessment of the extent of coronary artery stenosis. But it may be obscured by the cardiac remodeling and abnormal blood flow of the coronary artery when encountering atrial fibrillation (AF). The present study aimed to examine the impact of these changed structures and blood flow of coronary arteries on QFR results in AF patients. Methods and Results. We evaluated QFR in 223 patients (112 patients with AF; 111 non-AF patients served as controls) who had undergone percutaneous coronary intervention (PCI) due to severe stenoses in coronary arteries. QFR of the target coronary was determined according to the flow rate of the contrast agent. Results showed that AF patients had significantly higher QFR values than control (0.792 ± 0.118 vs. 0.685 ± 0.167, p

SARS-CoV-2 Omicron variant is significantly different from all the previous variants and has rapidly replaced other variants as the dominant variant across the globe. An easily obtained, inexpensive, and rapid marker is needed to predict the negative conversion time (NCT) of nucleic acid in nonsevere COVID-19 patients infected by the Omicron variant. This retrospective study enrolled 226 patients infected by the Omicron variant between April 23, 2022, and May 16, 2022. The median age of the patients was 61 (interquartile range (IQR), 48–70) years, and 56.2% were male. 84 patients (37.2%) had at least one comorbidity, and 49 patients (21.7%) were classified into the moderate illness group. 145 patients (64.2%) received at least one dose of vaccine, in which 67 patients (29.6%) received a booster dose of vaccine. The median duration of NCT was 8 (IQR, 7–11) days. Univariate Cox analyses found that high NLR (>2.22), aged ≥65 years, vaccination, and moderate illness were significantly related to the NCT of nucleic acid. Multivariate Cox regression analysis showed that high NLR (NLR > 2.22, hazard ratio (HR):0.718, 95% CI: 0.534–0.964, p = 0.028) and vaccination (vaccinated ≥1 dose, HR: 1.536, 95% CI: 1.147–2.058, p = 0.004) were independently associated with NCT of nucleic acid. NLR is a rapid, simple, and useful prognostic factor for predicting NCT of nucleic acid in nonsevere COVID-19 patients with the Omicron variant. In addition, vaccination may also play a valuable role in predicting the NCT of nucleic acid.

Doxorubicin is one of the most common antitumor drugs. However, cardiotoxicity’s side effect limits its clinical applicability. In the present study, Gene Expression Omnibus (GEO) datasets were applied to reanalyze differentially expressed genes (DEGs) and construct weighted correlation network analysis (WGCNA) modules of doxorubicin-induced cardiotoxicity in wild-type mice. Several other bioinformatics analyses were performed to pick out the hub gene, and then the correlation between the hub gene and immune infiltration was evaluated. In total, 120 DEGs were discovered in a mouse model of doxorubicin-induced cardiotoxicity, and PF-04217903, propranolol, azithromycin, etc. were found to be potential drugs against this pathological condition. Among all the DEGs, 14 were further screened out by WGCNA modules, of which Limd1 was upregulated and finally regarded as the hub gene after being validated in other GEO datasets. Limd1 was upregulated in the peripheral blood mononuclear cell (PBMC) of the rat model, and the area under curve (AUC) of the receiver operating characteristic curve (ROC) in diagnosing cardiotoxicity was 0.847. The GSEA and PPI networks revealed a potential immunocyte regulatory role of Limd1 in cardiotoxicity. The proportion of “dendritic cells activated” in the heart was significantly elevated, while “macrophage M1” and “monocytes” declined after in vivo doxorubicin application. Finally, Limd1 expression was significantly positively correlated with “dendritic cells activation’ and negatively correlated with “monocytes” and “macrophages M1’. In summary, our results suggested that limd1 is a valuable biomarker and a potential inflammation regulator in doxorubicin-induced cardiotoxicity.

Background The triglycerides-glucose index (TyG) and the triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) are simple indicators for assessing insulin resistance in epidemiological studies. We aimed to clarify the relationship between indicators of insulin resistance and prognosis in non-diabetic acute myocardial infarction (AMI) patients. Methods A total of 1,648 AMI patients without diabetes were enrolled from the Department of Cardiology, Zhongda Hospital, between 2012.03 and 2018.12. The medical history, laboratory and imaging data of patients were collected through the medical record system, and all-cause death events were recorded. Pearson analysis was used to study the correlation among different variables. Logistic regression analysis was used to analyze the predictive effect of TyG and TG/HDL-C in in-hospital death of AMI patients. Results 1. In AMI group, the TyG index was significantly increased in death groups compared to no-death groups (P = 0.025). TG/HDL-C was not significantly increased in the death group of AMI patients (P = 0.588). The patients were respectively divided into Q1-Q4 groups and T1-T4 groups according to the quartiles of TyG and TG/HDL-C. The trends of in-hospital mortality in the Q4 group of TyG and T4 group of TG/HDL-C were higher than in other groups, although these differences were not significant. 2. Pearson correlation analysis showed that TyG was positively correlated with lipid-related markers, including ApoB (r = 0.248, P

Summary: The role of tripartite motif (TRIM) 38, a ubiquitin E3 ligase regulating various pathophysiological processes, in cardiac fibrosis remains unclear. Here, a model of angiotensin II and myocardial infarction (MI)-induced fibrosis was established to explore its role in cardiac fibrosis and its underlying mechanisms. Cardiac fibrosis in the mouse MI model was mitigated by TRIM38 overexpression, but aggravated by its depletion. Consistently, in vitro overexpression or knockdown of TRIM38 ameliorated or aggravated the proliferation and secretion of cardiac fibroblasts (CFs) exposed to fibrotic stimulation, respectively. Mechanistically, TRIM38 suppressed cardiac fibrosis progression by attenuating TAK1/MAPK signaling. Inhibiting TAK1/MAPK signaling with a pharmacological inhibitor greatly reversed the effects of TRIM38 knockdown on CF secretion. Specifically, TRIM38 interacted with and “targeted” TAB2 and TAB3 for degradation, subsequently inhibiting TAK1 phosphorylation and negatively regulating MAPK signaling. These findings can help develop therapeutic strategies to treat and prevent cardiac fibrosis.

Tripartite motif (TRIM) 38 is a ubiquitin E3 protein ligase that is involved in various intracellular physiological processes. However, the role of TRIM38 in myocardial ischaemia/reperfusion (I/R) injury remains to be elucidated. We aimed to establish an in vitro cellular hypoxia/reperfusion (H/R) model to explore the role and potential mechanisms of TRIM38 in H9c2, a rat cardiomyoblast cell line. Recombinant adenoviruses for silencing or overexpressing TRIM38 were constructed and transfected into H9c2 cells. Western blotanalysisshowed that TRIM38 expression was significantly decreased after H/R injury. Functionally, TRIM38 expression relieved inflammatory responses and oxidative stress, and inhibited H/R-induced apoptosis in H9c2 cells. Mechanistically, TRIM38 overexpression inhibited H/R-induced transforming growth factor beta-activated kinase 1 (TAK1)/nuclear factor-kappa B (NF-κB) pathway activity in H9c2 cells. The opposite results were observed after TRIM38 knockdown. Furthermore, H/R-induced injury aggravated by TRIM38 deficiency in H9c2 cells was reversed upon treatment with 5Z-7-oxozeaenol, a TAK1 inhibitor. Therefore, TRIM38 reduction attenuated the anti-apoptotic capacity and anti-inflammatory potential of H/R-stimulated H9c2 cells by activating the TAK1/NF-κB signalling pathway. Specifically, TRIM38 alleviated H/R-induced H9c2 cell injury by promoting TNF receptor-associated factor 6 degradation, which led to the inactivation of the TAK1/NF-κB signalling pathway. Thus, our study provides new insights into the molecular mechanisms underlying H/R-induced myocardial injuries.

Safe and non-invasive on-demand relief is a crucial and effective treatment for postoperative pain because it considers variable timing and intensity of anesthetics. Ultrasound modulation is a promising technique for this treatment because it allows convenient timed and non-invasive controlled drug release. Here, we created an ultrasound-triggered lidocaine (Lido) release platform using an amino acid hydrogel functioning as three-dimensional (3D) scaffold material (Lido-PPIX@ER hydrogel). It allows control of the timing, intensity and duration of lidocaine (Lido) to relieve postoperative pain. The hydrogel releases Lido due to the elevated reactive oxygen species (ROS) levels generated by PPIX under ultrasound triggering. The Lido-PPIX@ER hydrogel under individualized ultrasound triggering released lidocaine and provided effective analgesia for more than 72 h. The withdrawal threshold was higher than that in the control group at all time points measured. The hydrogel showed repeatable and adjustable ultrasound-triggered nerve blocks in vivo, the duration of which depended on the extent and intensity of insonation. On histopathology, no systemic effect or tissue reaction was observed in the ultrasound-triggered Lido-PPIX@ER hydrogel-treated group. The Lido-PPIX@ER hydrogel with individualized (highly variable) ultrasound triggering is a convenient and effective method that offers timed and spatiotemporally controlled Lido release to manage postoperative pain. This article presents the delivery system for a new effective strategy to reduce pain, remotely control pain, and offer timed and spatiotemporally controlled release of Lido to manage postoperative pain.

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007.

Abstract Background GATA4 is an early cardiac-specific transcription factor, and endogenous GATA4-positive cells play a critical role in cardioprotection after myocardial injury. As functional paracrine units of therapeutic cells, exosomes can partially reproduce the reparative properties of their parental cells. Here, we investigated the cardioprotective capabilities of exosomes derived from cardiac colony-forming unit fibroblasts (cCFU-Fs) overexpressing GATA4 (cCFU-FsGATA4) and the underlying mechanism through which these exosomes use microRNA (miRNA) delivery to regulate target proteins in myocardial infarction (MI). Methods Exosomes were harvested from cCFU-Fs by ultracentrifugation. miRNA arrays were performed to determine differential miRNA expression between exosomes derived from cCFU-FsGATA4 (GATA4-Exo) and control cCFU-Fs (NC-Exo). A dual-luciferase reporter assay confirmed that miR221 directly targets the 3′ untranslated region (UTR) of the phosphatase and tensin homolog on chromosome ten (PTEN) gene. Cardiac function and myocardial infarct size were evaluated by echocardiography and Masson trichrome staining, respectively. Results Compared with NC-Exo, GATA4-Exo increased the survival and reduced the apoptosis of H9c2 cells. Direct intramyocardial transplantation of GATA4-Exo at the border of the ischemic region following ligation of the left anterior descending (LAD) coronary artery significantly restored cardiac contractile function and reduced infarct size. Microarray analysis revealed significantly increased miR221 expression in GATA4-Exo. qPCR confirmed higher miR221 levels in H9c2 cells treated with GATA4-Exo than in those treated with NC-Exo. miR221 mimic-transfected H9c2 cells demonstrated a significantly higher survival rate following exposure to hypoxic conditions than those transfected with miR221 inhibitor. A dual-luciferase reporter gene assay confirmed the PTEN gene as a target of miR221. Western blot analysis showed that H9c2 cells treated with GATA4-Exo exhibited lower PTEN protein expression and higher p-Akt expression. Conclusion GATA4 overexpression enhances the protective effect of cCFU-F-derived exosomes on myocardial ischemic injury. In terms of the mechanism, it is at least partly due to the miR221 transferred by GATA4-Exo, which inhibits PTEN expression, activates the phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway, and subsequently alleviates apoptosis of myocardial cells (CMs).

Aims. To evaluate the regression of coronary atherosclerosis with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in acute coronary syndrome (ACS) patients following primary percutaneous coronary intervention (PPCI). Methods and Result. We examined 40 nontarget lesions in 17 ACS patients who underwent PPCI and were treated with PCSK9 inhibitors. At 1 year, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and atherogenic index (AI) decreased significantly by 2.5 mmol/L, 2.01 mmol/L, and 1.86, respectively. On quantitative coronary angiography, treatment with PCSK9 inhibitors reduced significantly the atherosclerotic area stenosis in nontarget lesions (61.18 ± 14.55 at baseline vs. 52.85 ± 15.51 at 1 year, P

Acute myocardial infarction (AMI) is a leading cause of death and disability worldwide. Early diagnosis of AMI and interventional treatment can significantly reduce myocardial damage. However, owing to limitations in sensitivity and specificity, existing myocardial markers are not efficient for early identification of AMI. Transcriptome-wide association studies (TWASs) have shown excellent performance in identifying significant gene–trait associations and several cardiovascular diseases (CVDs). Furthermore, ferroptosis is a major driver of ischaemic injury in the heart. However, its specific regulatory mechanisms remain unclear. In this study, we screened three Gene Expression Omnibus (GEO) datasets of peripheral blood samples to assess the efficiency of ferroptosis-related genes (FRGs) for early diagnosis of AMI. To the best of our knowledge, for the first time, TWAS and mRNA expression data were integrated in this study to identify 11 FRGs specifically expressed in the peripheral blood of patients with AMI. Subsequently, using multiple machine learning algorithms, an optimal prediction model for AMI was constructed, which demonstrated satisfactory diagnostic efficiency in the training cohort (area under the curve (AUC) = 0.794) and two external validation cohorts (AUC = 0.745 and 0.711). Our study suggests that FRGs are involved in the progression of AMI, thus providing a new direction for early diagnosis, and offers potential molecular targets for optimal treatment of AMI.

Background. Acute coronary artery occlusion (CAO) during transcatheter aortic valve replacement (TAVR) is a rare but life-threatening complication during the procedure; there were a few case reports about an anomalous LCX during perioperative period. We report a case of successful coronary protection using the chimney stenting technique in a patient with a severely calcified aortic valve and an anomalous LCX. Case Summary. A 75-year-old man was found an anomalous left circumflex coronary artery (LCX) originating from the right coronary cusp with severely calcified aortic valve stenosis requiring TAVR. When a self-expanding aortic valve was deployed, we found flow compromise in the right coronary system and circumflex to TIMI-0 flow. By using the chimney stenting technique, we rapidly planted 2 stents from the proximal CX branch to the sinotubular junction and the coronary flow was maintained. Conclusion. Chimney stenting protection as a bailout technique is safe and feasible and should be considered in patients deemed to be at high risk of coronary flow compromise, especially with an anomalous LCX.

Background: Warfarin, along with aspirin and clopidogrel, has long been recommended for patients with atrial fibrillation (AF) who are undergoing percutaneous coronary intervention with a drug-eluting stent (PCI-DES). However, this triple therapy has been known to increase the risk of bleeding complications. Meanwhile, there is no evidence from prospective trials on the use of ticagrelor in a dual therapy. We here aimed to compare the antiplatelet drug ticagrelor as a dual antithrombotic agent to aspirin and clopidogrel in bleeding events.Methods: In this multicenter, active-controlled, open-label, randomized trial, patients with AF taking warfarin who had undergone PCI-DES were randomly assigned to the ticagrelor therapy group (Dual group) or the clopidogrel plus aspirin therapy group (Triple group). The primary and secondary endpoints were overall bleeding events and major bleeding events, respectively, according to the Thrombolysis in Myocardial Infarction (TIMI) criteria at 6 months. Cardiovascular events [re-PCI, surgical bypass, myocardial infarction (MI), heart failure, rehospitalization due to angina pectoris, stent thrombosis and death due to cardiovascular causes] at 6 months were also recorded.Results: A total of 296 patients from 12 medical centers in China were randomized after PCI-DES to either the Dual therapy group (n = 148) or the Triple group (n = 146) for 6 months. The overall incidence of bleeding events at 6 months was 36.49% in the Dual therapy group and 35.62% in the Triple group [hazard ratio, 0.930; 95% confidence interval (CI), 0.635 to 1.361; P = 0.7088]. The incidence of the secondary endpoint over 6 months was 4.73% in the Dual therapy group and 1.37% in the Triple group (hazard ratio, 0.273; 95% CI, 0.057 to 1.315; P = 0.1056). Cardiovascular event occurrence was also comparable in both groups at 6 months (18.24 vs. 16.44%; hazard ratio, 0.845; 95% CI, 0.488 to 1.465; P = 0.5484).Conclusions: The incidence of total bleeding events in AF patients treated with ticagrelor was comparable to that in patients treated with clopidogrel plus aspirin at 6 month; Meanwhile, the incidence of cardiovascular events were also comparable between the groups.Clinical Trial Registration: MANJUSRI, ClinicalTrials.gov# NCT02206815, 2014, August 1st

Introduction: Mechanical forces are closely associated with plaque progression and rupture. Precise quantifications of biomechanical conditions using in vivo image-based computational models depend heavily on the accurate estimation of patient-specific plaque mechanical properties. Currently, mechanical experiments are commonly performed on ex vivo cardiovascular tissues to determine plaque material properties. Patient-specific in vivo coronary material properties are scarce in the existing literature.Methods:In vivo Cine intravascular ultrasound and virtual histology intravascular ultrasound (IVUS) slices were acquired at 20 plaque sites from 13 patients. A three-dimensional thin-slice structure-only model was constructed for each slice to obtain patient-specific in vivo material parameter values following an iterative scheme. Effective Young's modulus (YM) was calculated to indicate plaque stiffness for easy comparison purposes. IVUS-based 3D thin-slice models using in vivo and ex vivo material properties were constructed to investigate their impacts on plaque wall stress/strain (PWS/PWSn) calculations.Results: The average YM values in the axial and circumferential directions for the 20 plaque slices were 599.5 and 1,042.8 kPa, respectively, 36.1% lower than those from published ex vivo data. The YM values in the circumferential direction of the softest and stiffest plaques were 103.4 and 2,317.3 kPa, respectively. The relative difference of mean PWSn on lumen using the in vivo and ex vivo material properties could be as high as 431%, while the relative difference of mean PWS was much lower, about 3.07% on average.Conclusion: There is a large inter-patient and intra-patient variability in the in vivo plaque material properties. In vivo material properties have a great impact on plaque stress/strain calculations. In vivo plaque material properties have a greater impact on strain calculations. Large-scale-patient studies are needed to further verify our findings.

Objective: To explore the role of neutrophil-to-lymphocyte ratio (NLR) in predicting the short-term prognosis of NSTEMI and STEMI.Methods: This study was a single-center, retrospective and observational study. 2618 patients including 1289 NSTMI and 1329 STEMI patients were enrolled from June 2013 to February 2018 in Zhongda Hospital, Southeast University. The demographic information, clinical characteristics, medical history, laboratory examination, treatment, and outcome of individuals at admission and during hospitalization were extracted from the electronic medical record system. Outcome was defined as the all-cause death during hospitalization.Results: (1) In the NSTEMI group, the ability of NLR in predicting in-hospital death (AUC = 0.746) was higher than the neutrophil-monocyte ratio (NMR) (AUC = 0.654), the platelet-lymphocyte ratio (PLR) (AUC = 0.603) and the lymphocyte-monocyte ratio (LMR) (AUC = 0.685), and also higher than AST (AUC = 0.621), CK (AUC = 0.595), LDH (AUC = 0.653) and TnI (AUC = 0.594). The AUC of NLR in the STEMI group was only 0.621. (2) The optimal cut-off value of NLR in NSTEMI group was 5.509 (Youden index = 0.447, sensitivity = 77.01%, specificity = 67.72%). After adjusting variables including age, sex, diabetes history, smoking history, LDL-C and Cr, the logistic regression showed that the patients with NLR>5.509 had higher hazard risk of death (HR4.356; 95%CI 2.552–7.435; P < 0.001) than the patients with NLR ≤ 5.509. (3) Stratification analysis showed that the in-hospital mortality of patients with NLR > 5.509 was 14.611-fold higher than those with NLR ≤ 5.509 in patients aged 71. The HR in patients with or without diabetes were 6.586 and 3.375, respectively. The HR in smoking or no smoking patients were 6.646 and 4.145, respectively. The HR in patients with LDL-C ≥ 2.06 or

Coronary vessel layer structure may have a considerable impact on plaque stress/strain calculations. Most current plaque models use single-layer vessel structures due to the lack of available multilayer segmentation techniques. In this paper, an automatic multilayer segmentation and repair method was developed to segment coronary optical coherence tomography (OCT) images to obtain multilayer vessel geometries for biomechanical model construction. Intravascular OCT data were acquired from six patients (one male; mean age: 70.0) using a protocol approved by the local institutional review board with informed consent obtained. A total of 436 OCT slices were selected in this study. Manually segmented data were used as the gold standard for method development and validation. The edge detection method and cubic spline surface fitting were applied to detect and repair the internal elastic membrane (IEM), external elastic membrane (EEM) and adventitia–periadventitia interface (ADV). The mean errors of automatic contours compared to manually segmented contours were 1.40%, 4.34% and 6.97%, respectively. The single-layer mean plaque stress value from lumen was 117.91 kPa, 10.79% lower than that from three-layer models (132.33 kPa). On the adventitia, the single-layer mean plaque stress value was 50.46 kPa, 156.28% higher than that from three-layer models (19.74 kPa). The proposed segmentation technique may have wide applications in vulnerable plaque research.

Background Acute myocardial infarction (AMI) is one of the fatal cardiac emergencies. The detection of triggering receptor expressed on myeloid cells 1 (TREM1), a cell surface immunoglobulin that amplifies pro-inflammatory responses, screened by bioinformatics was shown to be significant in diagnosing and predicting the prognosis of AMI. Methods GSE66360, GSE61144 and GSE60993 were downloaded from the Gene Expression Omnibus (GEO) database to explore the differentially expressed genes (DEGs) between AMI and control groups using R software. A total of 147 patients in total were prospectively enrolled from October 2018 to June 2019 and divided into two groups, the normal group (n = 35) and the AMI group (n = 112). Plasma was collected from each patient at admission and all patients received 6-month follow-up care. Results According to bioinformatic analysis, TREM1 was an important DEG in patients with AMI. Compared with the normal group, TREM1 expression was markedly increased in the AMI group (p < 0.001). TREM1 expression was positively correlated with fasting plasma glucose (FPG), glycosylated hemoglobin (HbAC), and the number of lesion vessels, although it had no correlation with Gensini score. TREM1 expression in the triple-vessels group was significantly higher than that of the single-vessel group (p < 0.05). Multiple linear regression showed that UA and HbAC were two factors influencing TREM1 expression. The ROC curve showed that TREM1 had a diagnostic significance in AMI (p < 0.001), especially in AMI patients without diabetes. Cox regression showed increased TREM1 expression was closely associated with 6-month major adverse cardiac events (MACEs) (p < 0.001). Conclusions TREM1 is a potentially significant biomarker for the diagnosis of AMI and may be closely associated with the severity of coronary lesions and diabetes. TREM1 may also be helpful in predicting the 6-month MACEs after AMI.

Background: This study aimed to examine whether quantitative flow ratio (QFR), an angiography-based computation of fractional flow reserve, was associated with intravascular imaging-defined vulnerable plaque features, such as thin cap fibroatheroma (TCFA) in patients with stable angina, and non-ST-segment elevation acute coronary syndrome.Methods: Patients undergoing optical coherence tomography (OCT) or intravascular ultrasound (IVUS) examinations were identified from two prospective studies and their interrogated vessels were assessed with QFR. Lesions in the OCT cohort were classified into tertiles: QFR-T1 (QFR ≤ 0.85), QFR-T2 (0.85 < QFR ≤ 0.93), and QFR-T3 (QFR > 0.93). Lesions in the IVUS cohort were classified dichotomously as low or high QFR groups.Results: This post-hoc analysis included 132 lesions (83 for OCT and 49 for IVUS) from 126 patients. The prevalence of OCT-TCFA was significantly higher in QFR-T1 (50%) than in QFR-T2 (14%) and QFR-T3 (19%) (p = 0.003 and 0.018, respectively). Overall significant differences were also observed among tertiles in maximum lipid arc, thinnest fibrous cap thickness, and minimal lumen area (p = 0.017, 0.040, and

Background. Circulating endothelial progenitor cells (EPCs) play important roles in vascular repair. However, the mechanisms of high-glucose- (HG-) induced cord blood EPC senescence and the role of B2 receptor (B2R) remain unknown. Methods. Cord blood samples from 26 patients with gestational diabetes mellitus (GDM) and samples from 26 healthy controls were collected. B2R expression on circulating CD34+ cells of cord blood mononuclear cells (CBMCs) was detected using flow cytometry. The plasma concentrations of 8-isoprostaglandin F2α (8-iso-PGF2α) and nitric oxide (NO) were measured. EPCs were treated with HG (40 mM) alone or with bradykinin (BK) (1 nM). The B2R and eNOS small interfering RNAs (siRNAs) and the PI3K antagonist LY294002 were added to block B2R, eNOS, and PI3K separately. To determine the number of senescent cells, senescence-associated β-galactosidase (SA-β-gal) staining was performed. The level of mitochondrial reactive oxygen species (ROS) in EPCs was assessed by Mito-Sox staining. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assays. Mitochondrial DNA (mtDNA) copy number and the relative length of telomeres were detected by real time-PCR. The distribution of human telomerase reverse transcriptase (hTERT) in the nucleus, cytosol, and mitochondria of EPCs was detected by immunofluorescence. The expression of B2R, p16, p21, p53, P-Ser473AKT, T-AKT, eNOS, and hTERT was demonstrated by Western blot. Results. B2R expression on circulating CD34+ cells of CBMCs was significantly reduced in patients with GDM compared to healthy controls. Furthermore, B2R expression on circulating CD34+ cells of CBMCs was inversely correlated with plasma 8-iso-PGF2α concentrations and positively correlated with plasma NO levels. BK treatment decreased EPC senescence and ROS generation. Furthermore, BK treatment of HG-exposed cells led to elevated P-Ser473AKT and eNOS protein expression compared with HG treatment alone. BK reduced hTERT translocation in HG-induced senescent EPCs. B2R siRNA, eNOS siRNA, and antagonist of the PI3K signalling pathway blocked the protective effects of BK. Conclusion. BK, acting through PI3K-AKT-eNOS signalling pathways, reduced hTERT translocation, increased the relative length of telomeres while reducing mtDNA copy number, and finally protected against EPC senescence induced by HG.

Objective Coronary tortuosity may affect epicardial coronary arterial blood flow. This study aimed to investigate the effect of coronary tortuosity on coronary flow reserve and the coronary microcirculation in patients without apparent coronary atherosclerosis. Methods Prospective patients (n = 8, 3 men, mean age: 58 ± 6.0 years) with coronary tortuosity and without apparent coronary atherosclerosis were enrolled. Coronary tortuosity was defined by the finding of ≥three bends (defined as a ≥45° change in vessel direction) along the main trunk of the left anterior descending artery or left circumflex artery. Coronary flow reserve and the index of microcirculatory resistance were measured by the thermodilution technique. Results A total of eight coronary arteries with coronary tortuosity were analyzed. The mean fractional flow reserve was 0.98 ± 0.007. The mean coronary flow reserve was 1.5 ± 0.3, which is much lower than that in the normal coronary artery as reported in the literature. The mean index of microcirculatory resistance was 26.7 ± 2.3, which is much higher than that in the normal coronary artery. Conclusions Coronary tortuosity is associated with decreased coronary flow reserve and an increased index of microcirculatory resistance. Trial registration: This study is registered at the Chinese Clinical Trial Registry, NCT No: ChiCTR2000033671

Introduction. Randomized clinical trials have not shown an additional clinical benefit of sitagliptin treatment over conventional treatment alone. However, studies of sitagliptin treatment have not examined the relationship between anemia and treatment group outcomes. Methods. The PROLOGUE study is a prospective clinical trial of 442 participants with type 2 diabetes mellitus (T2DM) randomized to sitagliptin treatment or conventional treatment which showed no treatment differences [Estimated mean (± standard error) common carotid intima-media thickness (CIMT) was 0.827±0.007 mm and 0.837±0.007 mm, respectively, with a mean difference of -0.009 mm (97.2% CI −0.028 to 0.011, p=0.309) at 24 mo of follow-up]. This is a post hoc subanalysis using data obtained from the PROLOGUE study; the study population was divided into anemic groups (n=94) and nonanemic group (n=343) based on hemoglobin level. And we analyzed for the changes in each CIMT parameter from baseline to 24 months in subgroups. Results. The treatment group difference in baseline-adjusted mean common carotid artery- (CCA-) IMT at 24 months was −0.003 mm (95% CI −0.022 to 0.015, p=0.718) in the nonanemic subgroup and −0.007 mm (95% CI −0.043 to 0.030, p=0.724) in the anemic subgroup. Although there were no significant differences in the other CIMT parameters between the treatment groups in the anemic subgroup, the changes in mean and max ICA-IMT at 24 months in the nonanemic subgroup were significantly lower in the sitagliptin group than the conventional group [−0.104 mm (95% CI −0.182 to −0.026), p=0.009 and −0.142 mm (−0.252 to −0.033), p=0.011, respectively]. Conclusion. These data suggest that nonanemia may indicate a potentially large subgroup of those with T2DM patients that sitagliptin therapy has a better antiatherosclerotic effect than conventional therapy. Further research is needed to confirm these preliminary observations.

Background. Ly6Chigh monocytes are inflammatory cells that accumulate in an infarcted myocardium, and Ly6Clow monocytes are believed to be reparative and curb myocardial remodeling. NR4A1 is a novel target for modulating the inflammatory phenotype of monocytes during atherogenesis. Objectives. We aimed to investigate whether MSCs can contribute to the heterogeneity of Ly6Chigh monocytes differentiated into Ly6Clow monocytes and whether this regulation is related to nuclear receptor NR4A1. Methods. Ly6Chigh/low monocytes were first cocultured with MSCs. C57BL/6CX3CR1-/- mice and C57BL/6 wild-type mice were then used to construct AMI models, and survival functions in the two groups were further compared. Ly6Chigh/low monocytes in circulation and in MI tissue of C57BL/6CX3CR1-/- AMI mice with or without MSC transplantation were determined by flow cytometry at day 1 and day 3. NR4A1 expression was further determined by Western blot. Apoptosis of cardiac myocytes in the infarct border zone at day 3 and day 7 was identified by TUNEL kits. Angiogenesis in the AMI heart at day 7 and day 21 was determined through immunohistochemistry by CD31. Results. We first demonstrated that the percentage of Ly6Clow monocytes increased greatly after 3 days of coculture with MSCs (12.8%±3.77% vs. 3.69%±0.74%, p

Background/Aims: C-kit-positive cardiac stem cells (CSCs) may have potential as a treatment for cardiovascular disease. However, the low survival rates of c-kit-positive CSCs present a major challenge during the transplantation process. Methods: The hierarchical structure of the 3D cell scaffold was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and N2 adsorption-desorption isotherms. Analyses of the proliferation and migration performances of the IGF-1 scaffold on c-kit-positive CSCs were conducted by experiments including QuantiT PicoGreen dsDNA and transwell assays. Results: In this study, we synthesized for the first time a novel hierarchical macro-mesoporous silica material (denoted MS15-c) in a one-pot procedure for the release of insulin-like growth factor-1 (IGF-1) and a three-dimensional (3D) cell scaffold. Both macropores and mesopores were visible in MS15-c and enabled the sustained release of IGF-1, extending its half-life and enhancing CSC proliferation and migration. Proliferation and migration were detected by QuantiT PicoGreen dsDNA and transwell assays, respectively. Moreover, an in vivo experiment was conducted to detect heart function with the addition of MS15-c. The new strategy proposed in this paper may extend the bio-applications of 3D cell scaffolds, thus permitting the sustained release of growth factors and efficient promotion of cell proliferation. Conclusion: This work successfully demonstrated an effective strategy for the construction of MS15-c cell scaffolds with hierarchical macro-mesoporous structures. The macro-mesoporous structures gave cell scaffolds the ability to release a growth factor to facilitate cell growth, while the scaffold structure promoted cell proliferation.

Abstract Background C-kit-positive cardiac stem cells (CSCs) have been shown to be a promising candidate treatment for myocardial infarction and heart failure. Insulin-like growth factor (IGF)-1 is an anabolic growth hormone that regulates cellular proliferation, differentiation, senescence, and death in various tissues. Although IGF-1 promotes the migration and proliferation of c-kit-positive mouse CSCs, the underlying mechanism remains unclear. Methods Cells were isolated from adult mouse hearts, and c-kit-positive CSCs were separated using magnetic beads. The cells were cultured with or without IGF-1, and c-kit expression was measured by Western blotting. IGF-1 induced CSC proliferation and migration, as measured through Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. The miR-193a expression was measured by quantitative real-time PCR (qPCR) assays. Results IGF-1 enhanced c-kit expression in c-kit-positive CSCs. The activities of the phosphoinositol 3-kinase (PI3K)/AKT signaling pathway and DNA methyltransferases (DNMTs) were enhanced, and their respective inhibitors LY294002 and 5-azacytidine (5-AZA) blunted c-kit expression. Based on the results of quantitative real-time PCR (qPCR) assays, the expression of miR-193a, which is embedded in a CpG island, was down-regulated in the IGF-1-stimulated group and negatively correlated with c-kit expression, whereas c-kit-positive CSCs infected with lentivirus carrying micro-RNA193a displayed reduced c-kit expression, migration and proliferation. Conclusions IGF-1 upregulated c-kit expression in c-kit-positive CSCs resulting in enhanced CSC proliferation and migration by activating the PI3K/AKT/DNMT signaling pathway to epigenetically silence miR-193a, which negatively modifies the c-kit expression level.

Abstract Background Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in angiogenesis and maintenance of endothelial integrity. Whether circulating BDNF levels are associated with von Willebrand factor (vWF) levels, which are indicators of endothelial dysfunction is not known. This study investigated the association between plasma BNDF and vWF levels and whether these biomarkers could predict cardiovascular events at a 12-month follow-up in patients with stable coronary artery disease (CAD). Methods We recruited 234 patients with suspected angina pectoris. Subjects were divided into CAD (n = 143) and control (n = 91) groups based on coronary angiography. Plasma BDNF and vWF levels were measured using ELISA. Patients were followed-up for one year, and information on adverse cardiac events was collected. Results CAD patients exhibited significantly lower plasma BDNF and higher vWF levels than those of control patients. High vWF levels were associated with low BDNF levels even after adjustment for age, gender, low-density lipoprotein (LDL) levels, and the presence of diabetes mellitus. A receiver operating characteristic curve was used to determine whether low BDNF and high vWF levels could predict adverse cardiovascular events. The area under the curve for vWF and the inverse of BDNF were 0.774 and 0.804, respectively. Conclusions These findings suggest that endothelial dysfunction is an important determinant of the impaired circulating BDNF levels, and they further reflected cardiovascular prognosis in stable CAD patients.

Aim. The aim of present study was to determine the safety and efficacy of a new renal artery denervation system for treatment of hypertensive patients. Methods. Hypertensive patients with mean office systolic blood pressure ≥150mmHg and ≤180mmHg or an average of 24-hour ambulatory systolic blood pressure ≥145mmHg and ≤170mmHg after stopping hypertensive medications for 2 weeks or more were enrolled to undergo renal denervation (RDN) using a new RDN system. Changes in office blood pressure and mean 24-hour ambulatory blood pressure and safety were assessed after 6 months. Results. Fifteen patients underwent RDN and followed up for 6 months. At the 6-month follow-up, office systolic blood pressure decreased 11.5±9.9mmHg (P0.05) compared to baseline values. There were no serious RDN-related adverse events during follow-up. Conclusion. Our results demonstrate that the new RDN system is safe and could significantly reduce blood pressure in hypertensive patients in the absence of antihypertensive medications. This trial is registered with ChiCTR1800017815.

Increasing evidence shows that statins increase the risk of new-onset diabetes mellitus, but the exact mechanism is not clearly known. Free fatty acid receptor 1 (FFA1) has been recognized to mediate insulin secretion, and pioglitazone has direct effects on glucose-stimulated insulin secretion in addition to the reversion of insulin resistance. In this study, we found that atorvastatin decreased potassium-stimulated insulin secretion and inhibited the expression of FFA1, PDX-1, and BETA2/NeuroD in INS-1 cells. Further study demonstrated that pioglitazone prevented the impairment of insulin secretion induced by atorvastatin and enhanced the expression of FFA1, PDX-1, and BETA2/NeuroD reduced by atorvastatin in INS-1 cells. In addition, the preventive effect of pioglitazone on atorvastatin-induced impairment of insulin secretion and the enhancement of the expression of PDX-1 and BETA2/NeuroD was abolished by knockdown of FFA1 using siRNA or the PLC inhibitor, U-73122, respectively. Ultimately, FFA1 may mediate the atorvastatin-induced pancreatic β-cell dysfunction and pioglitazone may ameliorate this deleterious effect through the upregulation of FFA1 expression.

Objective The impact of coronary tortuosity on coronary atherosclerosis remains unclear. This study was performed to determine to the relationship between coronary tortuosity and the presence of coronary atherosclerosis. Methods Tortuosity and the presence of coronary atherosclerosis in the main coronary arteries were evaluated. The coronary artery was divided into non-tortuous and tortuous segments. The incidence of coronary atherosclerosis between the two segments was compared. Results The prevalence of coronary atherosclerotic stenosis was significantly lower in the tortuous than non-tortuous segment. Conclusion The prevalence of coronary atherosclerotic stenosis is lower in the coronary tortuous than non-tortuous segment, indicating that coronary tortuosity might be considered a protective factor for atherosclerosis.

Background Kallistatin exerts beneficial effects on organ injury by inhibiting oxidative stress and inflammation. However, the role of kallistatin in atherosclerosis is largely unknown. Here, we investigated the role and mechanisms of kallistatin in patients with coronary artery disease (CAD), atherosclerotic plaques of apoE−/− mice, and endothelial activation. Methods and Results Plasma kallistatin levels were analyzed in 453 patients at different stages of CAD. Kallistatin levels were significantly lower in patients with CAD and negatively associated with CAD severity and oxidative stress. Human kallistatin cDNA in an adenoviral vector was injected intravenously into apoE−/− mice after partial carotid ligation, with or without nitric oxide synthase inhibitor (Nω‐nitro‐L‐arginine methyl ester) or sirtuin 1 inhibitor (nicotinamide). Kallistatin gene delivery significantly reduced macrophage deposition, oxidative stress, and plaque volume in the carotid artery, compared with control adenoviral injection. Kallistatin administration increased endothelial nitrous oxide synthase, sirtuin 1, interleukin‐10, superoxide dismutase 2, and catalase expression in carotid plaques. The beneficial effects of kallistatin in mice were mitigated by Nω‐nitro‐L‐arginine methyl ester or nicotinamide. Furthermore, human kallistatin protein suppressed tumor necrosis factor‐α–induced NADPH oxidase activity and increased endothelial nitrous oxide synthase and sirtuin 1 expression in cultured human endothelial cells. These effects were also abolished by Nω‐nitro‐L‐arginine methyl ester or nicotinamide. Conclusions This was the first study to demonstrate that reduced plasma kallistatin levels in patients are associated with CAD severity and oxidative stress. Kallistatin treatment prevents carotid atherosclerotic plaque formation in mice by stimulating the sirtuin 1/endothelial nitrous oxide synthase pathway. These findings indicate the potential protective effects of kallistatin on atherosclerosis in human subjects and mouse models.

Objective The clinical implication of coronary tortuosity is unclear. The present study was conducted to determine the relationships between coronary tortuosity and the high-sensitivity C-reactive protein (hs-CRP) concentration and between coronary tortuosity and cerebrovascular accident in hypertensive patients without coronary artery disease. Methods In total, 236 patients with normal coronary angiography findings were categorized into 3 different groups: control participants (n = 58), who had neither hypertension nor coronary tortuosity; patients with hypertension but no coronary tortuosity (H-NCT group, n = 93); and patients with both hypertension and coronary tortuosity (H-CT group, n = 85). The hs-CRP concentration was measured in every patient, and 168 hypertensive patients were followed up for at least 2 years to check for the development of cerebrovascular accident. Results The hs-CRP concentration was significantly higher in the H-CT group than in the control and H-NCT groups (4.33 ± 3.15 vs. 1.52 ± 1.31 and 2.31 ± 2.09 mg/L, respectively). The incidence of lacunar infarction was higher in the H-CT than H-NCT group during the follow-up. Conclusions Hypertensive patients with coronary tortuosity have a higher serum hs-CRP level concentration and have a higher incidence of lacunar infarction than hypertensive patients without coronary tortuosity.

Inflammatory mechanisms are involved in the process of atherosclerotic plaque formation and rupture. Accumulating evidence suggests that protease-activated receptor (PAR)-2 contributes to the pathophysiology of chronic inflammation on the vasculature. To directly examine the role of PAR-2 in atherosclerosis, we generated apolipoprotein E/PAR-2 double-deficient mice. Mice were fed with high-fat diet for 12 weeks starting at ages of 6 weeks. PAR-2 deficiency attenuated atherosclerotic lesion progression with reduced total lesion area, reduced percentage of stenosis and reduced total necrotic core area. PAR-2 deficiency increased fibrous cap thickness and collagen content of plaque. Moreover, PAR-2 deficiency decreased smooth muscle cell content, macrophage accumulation, matrix metallopeptidase-9 expression and neovascularization in plaque. Relative quantitative PCR assay using thoracic aorta revealed that PAR-2 deficiency reduced mRNA expression of inflammatory molecules, such as vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. In vitro experiment, we found that PAR-2 deficiency reduced mRNA expression of interferon-γ, interleukin-6, TNF-α and MCP-1 in macrophage under unstimulated and lipopolysaccharide-stimulated conditions. These results suggest that PAR-2 deficiency attenuates the progression and instability of atherosclerotic plaque.