ADAM8 deficiency in macrophages promotes cardiac repair after myocardial infarction via ANXA2-mTOR-autophagy pathway.

INTRODUCTION: A disintegrin and metalloproteinase 8 (ADAM8), a crucial regulator in macrophages, is closely associated with cardiovascular disease progression. OBJECTIVES: This study aimed to explore how ADAM8 regulates macrophage function to inhibit cardiac repair after myocardial infarction (MI). METHODS: Macrophage-specific ADAM8 knockout mice (ADAM8flox/flox, Lyz2-Cre, KO) and corresponding control mice (ADAM8flox/flox, Flox) were established using the CRISPR/Cas9 system. Bone marrow transplantation was performed, and macrophage-specific ADAM8-overexpressing adeno-associated virus (AAV6-CD68-Adam8) was produced. Finally, proteomics, RNA sequencing, and co-immunoprecipitation/mass spectrometry (COIP/MS) were used to explore the underlying mechanisms involved. RESULTS: ADAM8 was highly expressed in the plasma of patients with acute myocardial infarction (AMI) and in cardiac macrophages derived from AMI mice. ADAM8 KO mice exhibited enhanced angiogenesis, suppressed inflammation, reduced cardiac fibrosis, and improved cardiac function during AMI, which were reversed by overexpressing macrophage-specific ADAM8 and intervention with the clinical anti-angiogenic biologic bevacizumab. Bone marrow transplantation experiments produced ADAM8 KO phenotypes. RNA sequencing showed that autophagy was activated in bone marrow-derived macrophages (BMDMs) with ADAM8 KO, which was confirmed via p-mTOR Ser2448/mTOR, p62, and LC3II/I detection. Autophagy inactivation suppressed angiogenic factor release and promoted inflammation in BMDMs with ADAM8 KO. Mechanistically, ADAM8 could bind to ANXA2 and promote phosphorylation of the ANXA2 Ser26 site. ADAM8 KO impeded ANXA2 phosphorylation, inhibited mTOR Ser2448 site phosphorylation, and activated autophagy, which were demonstrated using the activation or inactivation of ANXA2 phosphorylation. CONCLUSIONS: ADAM8 was increased in cardiac macrophages after AMI. The ADAM8-ANXA2-mTOR-autophagy axis in macrophages is responsible for regulating angiogenesis and inflammation following MI. Thus, ADAM8 may be a new target in MI treatment.

Association of weight-adjusted waist index with cardiovascular disease and mortality among metabolic syndrome population.

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.

The association between weight-adjusted waist circumference index and cardiovascular disease and mortality in patients with diabetes.

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 < 0.001) among patients with diabetes. Subgroup and sensitivity analyses confirmed that these associations were consistent and stable in most different demographics. The ROC analysis indicated that WWI had a higher predictive capacity for CVD and all-cause mortality than WC, waist to hip ratio, and weight to height ratio. The WWI was significantly associated with the prevalence of CVD and all-cause mortality among patients with diabetes in the United States and may serve as a useful tool for identifying individuals at risk.

Prognostic value of a disintegrin and metalloproteinase Domain-8 in heart failure.

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 < 0.001), especially in patients with HFrEF (p < 0.05), and HFmEF (p < 0.05). The prevalence of HF in the high ADAM8 group (≧472.916 pg/mL) was significantly higher than in the low ADAM8 group (<472.916 pg/mL) (41.95 % vs 30.54 %, p < 0.01). (3) Correlation analysis revealed that ADAM8 was negatively correlated to the left ventricular ejection fraction (LVEF) (r = -0.272, p < 0.001). ROC analysis showed that the AUC of ADAM8 in predicting HF and predicting the MACE were 0.701 (p < 0.0001) and 0.683 (p < 0.0001), respectively. (4) Logistic and Cox regression both indicated that high ADAM8 expression can predict adverse prognosis of HF. Conclusions: ADAM8 may be a risk factor for HF, especially in cases of HFrEF and HFmEF. High ADAM8 expression in plasma was related to the decreased heart function, and can predict the adverse prognosis of HF.

Identification of potential crucial cuproptosis-related genes in myocardial ischemia-reperfusion injury through the bioinformatic analysis.

BACKGROUND: Cuproptosis is known to regulate diverse physiological functions in many diseases, but its role in regulating Myocardial Ischemia-Reperfusion Injury (MI/RI) remains unclear. METHODS: For this purpose, the MI/RI microarray datasets GSE61592 were downloaded from the Gene Expression Omnibus (GEO) database, and the Differently Expressed Genes (DEGs) in MI/RI were identified using R software. Moreover, the MI/RI mice model was established to confirm further the diagnostic value of Pyruvate Dehydrogenase B (Pdhb), Dihydrolipoamide S-acetyltransferase (Dlat), and Pyruvate dehydrogenase E1 subunit alpha 1 (Pdhα1). RESULTS: The analysis of microarray datasets GSE61592 revealed that 798 genes were upregulated and 768 were downregulated in the myocardial tissue of the ischemia-reperfusion injury mice. Furthermore, Dlat, Pdhb, Pdhα1, and cuproptosis-related genes belonged to the downregulated genes. The receiver operating characteristics curve analysis results indicated that the Dlat, Pdhb, and Pdhα1 levels were downregulated in MI/RI and were found to be potential biomarkers for MI/RI diagnosis and prognosis. Similarly, analysis of Dlat, Pdhb, and Pdhα1 levels in the MI/RI mice revealed Pdhb being the key diagnostic marker. CONCLUSIONS: This study demonstrated the prognostic value of cuproptosis-related genes (Dlat, Pdhb, and Pdhα1), especially Pdhb, MI/RI, providing new insight into the MI/RI treatment.

K-clip™, a Novel Transcatheter Treatment in Patients with Severely Tricuspid Regurgitation.

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.

Biolimus-coated versus paclitaxel-coated balloons for coronary in-stent restenosis (BIO ASCEND ISR): a randomised, non-inferiority trial.

BACKGROUND: The treatment of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains challenging in current clinical practice. AIMS: The study was conducted to investigate a novel biolimus-coated balloon (BCB) for the treatment of coronary DES-ISR compared with the best-investigated paclitaxel-coated balloon (PCB). METHODS: This was a prospective, multicentre, randomised, non-inferiority trial comparing a novel BCB with a clinically proven PCB for coronary DES-ISR. The primary endpoint was in-segment late lumen loss (LLL) at 9 months assessed by an independent core laboratory. Baseline and follow-up optical coherence tomography were performed in a prespecified subgroup of patients. RESULTS: A total of 280 patients at 17 centres were randomised to treatment with a BCB (n=140) versus a PCB (n=140). At 9 months, LLL in the BCB group was 0.23±0.37 mm compared to 0.25±0.35 mm in the PCB group; the mean difference between the groups was -0.02 (95% confidence interval [CI]: -0.12 to 0.07) mm; p-value for non-inferiority<0.0001. Similar clinical outcomes were also observed for both groups at 12 months. In the optical coherence tomography substudy, the neointimal area at 9 months was 2.32±1.04 mm2 in the BCB group compared to 2.37±0.93 mm2 in the PCB group; the mean difference between the groups was -0.09 (95% CI: -0.94 to 0.76) mm2; p=non-significant. CONCLUSIONS: This head-to-head comparison of a novel BCB shows similar angiographic outcomes in the treatment of coronary DES-ISR compared with a clinically proven PCB. (ClinicalTrials.gov: NCT04733443).

The burden and management competency of cardiomyopathies in China: a nationwide survey study.

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).

The relationship between serum manganese concentration with all-cause and cause-specific mortality: a retrospective and population-based cross-sectional study.

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 <0.05). However, there was an increase and then a decrease in the link between manganese concentration and cancer-related mortality (P-value for nonlinear <0.05). Manganese exposure was positively correlated with sex (correlation coefficient, r =0.19, P-value <0.001) and negatively correlated with age (correlation coefficient, r =-0.11, P-value <0.001) and serum creatinine (correlation coefficient, r =-0.12, P-value <0.001), respectively. CONCLUSIONS: Our findings suggest that elevated serum manganese concentrations are associated with all-cause and CVD-related mortality in the U.S. population and that maintenance of serum manganese between 8.67-9.23 µg/L may promote public health.

Prognostic significance of serum dynamin­related protein 1 in patients with heart failure: Findings from a prospective observational study.

Mitochondrial dysfunction plays a critical role in the development and exacerbation of heart failure (HF). Dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fission, influences cardiac energy metabolism. The present study investigated the relationship between serum Drp1 levels and the prognosis of patients with HF across a broad spectrum. Serum Drp1 concentrations were measured using ELISA. The primary outcome was the risk of composite major adverse cardiac events (MACEs), which included instances of cardiac death and HF-related readmissions. To assess the prognostic significance of serum Drp1, a receiver operating characteristic curve was constructed to predict MACE-free survival. Additionally, an optimal threshold value for Drp1 was determined and was used to stratify patients into different risk categories. A total of 256 HF patients were finally included and categorized into two groups based on their serum Drp1 levels, labeled as the low (Drp1 ≤2.66 ng/ml, n=101) and high group (Drp1 >2.66 ng/ml, n=155). Patients with low serum Drp1 concentrations showed impaired heart structure and function, as assessed by echocardiography. The 6-month follow-up results indicated that patients with reduced Drp1 concentrations faced a substantially increased risk of MACEs (21.1% vs. 2.8%; P<0.001). The present study revealed that diminished serum Drp1 concentrations could potentially act as a predictive marker for the prognosis of HF in a broad patient population.

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.

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.

Inhibition of myocardial remodeling through miR-150/TET3 axis after AMI.

BACKGROUND: Current studies have suggested that miRNA is beneficial in inhibiting myocardial remodeling after myocardial infarction (AMI), however, its underlying mechanism is unclear. OBJECTIVES: We aimed to investigate whether miR-150 can inhibit myocardial remodeling after myocardial infarction and whether this process is regulated by the miR-150/TET3 pathway. METHODS: On the first day, C57BL/6 AMI mice(n = 15) were administrated with miR-150, and another 15 AMI mice were administrated with the same volume of control Agomir. Left ventricular ejection fraction (LVEF%) and myocardial remodeling were compared after one week; TET3 (ten-eleven translocation 3) and VEGF-α (vascular endothelial growth factor-α) were also determined in the infracted heart simultaneously. The neovascularization in the infarcted area at day 21 was compared through CD31 using fluorescence microscopy; Activated monocytes stimulated with LPS were transfected with miR-150. Laser scanning confocal microscopy was used to detect the intracytoplasmic imaging of miR-150 in Ly6Chigh monocytes. Expression of the miR-150 in the monocytes was measured using Q-PCR. After 48 h, the proportion of Ly6Chigh/low monocytes was determined using flow cytometry. Expression of TET3 in Ly6Chigh/low monocytes was measured using Q-PCR and Western blot. After the downregulation of TET3 specifically, the levels of Ly6Chigh/low monocytes were further determined. RESULTS: We first observed an increased trend of mice survival rate in the miR-150 injection group, but it didn't reach a statistical difference (66.7% vs. 40.0%, p = 0.272). However, AMI mice administrated with miR-150 displayed better LVEF% (51.78%±2.90% vs. 40.28%±4.20%, p<0.001) and decreased infarct size% (25.47 ± 7.75 vs. 50.39 ± 16.91, p = 0.002). After miR-150 was transfected into monocytes, the percentage of Ly6Clow monocytes increased significantly after 48 h (48.5%±10.1% vs. 42.5%±8.3%, p < 0.001). Finally, Western blot analysis (0.56 ± 0.10/ß-actin vs. 0.99 ± 0.12/ß-actin, p < 0.001) and real-time PCR (1.09 ± 0.09/GAPDH vs. 2.53 ± 0.15/GAPDH, p < 0.001, p < 0.001) both confirmed decreased expression of TET3 in monocytes after transfection with miR-150. After the downregulation of TET3 specifically, Ly6Clow monocytes showed a significant increase (16.73%±6.45% vs. 6.94%±2.99%, p<0.001, p < 0.001). CONCLUSIONS: miR-150 alleviated myocardial remodeling after AMI. Possible mechanisms are ascribed to the regulating of TET3 and VEGF-α in inflammatory monocytes.

Insight into tricuspid transcatheter edge-to-edge repair: no longer the forgotten valve.

INTRODUCTION: Tricuspid regurgitation (TR) is one of the most prevalent types of valvular heart disease linked to poor prognosis in patients with heart failure and is usually ignored. TR has received considerable attention due to the progressive advancements in transcatheter therapies in recent years. AREAS COVERED: With relatively solid data and rapid technological advancements, tricuspid transcatheter edge-to-edge repair (T-TEER) is the most frequently employed in a series of tricuspid transcatheter interventional treatments for TR. However, the efficacy and technical benefits of T-TEER are limited because of the unique anatomical characteristics and pathological mechanisms of the tricuspid valve. The aim of this review is to summarize reported data on current status of T-TEER and to provide an expert opinion regarding the challenges it is now experiencing and future development direction and approach. EXPERT OPINION: T-TEER is a significant treatment for TR, but its effectiveness and technical promotion are limited due to the tricuspid valve unique anatomical characteristics and pathological mechanisms. The selection criteria for suitable patients, the choice of when to intervene, device innovation, the advancement of ultrasound technology, and the volume of evidence in evidence-based medicine all indicate that the disorder of TR will eventually be better treated and understood.

Factors associated with COVID-19 vaccination coverage in hypertensive patients with Omicron infection in Shanghai, China.

The 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 < .001), age (60-69 years vs.18-49 years) (OR 0.348, 95% CI 0.270-0.448, p < .001), age (≥70 years vs.18-49 years) (OR 0.130, 95% CI 0.100-0.169, p < .001), diabetes mellitus (OR 0.553, 95% CI 0.463-0.661, p < .001), chronic pulmonary diseases (OR 0.474, 95% CI 0.260-0.863, p = .015), chronic kidney disease (OR 0.177, 95% CI 0.076-0.410, p < .001), and cancer (OR 0.225, 95% CI 0.094-0.535, p = .001) were associated with vaccinated status. The vaccine coverage rate, especially the booster vaccine, was low for hypertensive patients with Omicron infection. Females, increasing age, and coexisting chronic diseases were associated with more inadequate vaccine coverage in hypertensive COVID-19 patients. Targeted interventions are required to address the under-vaccination of diverse hypertensive populations.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Vaccination for Negative Conversion Time of Nucleic Acid in Nonsevere COVID-19 Patients Infected by SARS-CoV-2 Omicron Variant.

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.

Macrophage-driven cardiac inflammation and healing: insights from homeostasis and myocardial infarction.

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.

The Differences of Quantitative Flow Ratio in Coronary Artery Stenosis with or without Atrial Fibrillation.

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 < 0.001). We further analyzed local QFR around the stenoses (0.858 ± 0.304 vs. 0.756 ± 0.146, p=0.002), residual QFR (0.958 ± 0.055 vs. 0.929 ± 0.093, p=0.005), and index QFR (0.807 ± 0.108 vs. 0.713 ± 0.152, p < 0.001) in these two groups of patients with and without AF. Further analysis revealed that QFR in AF patients was negatively correlated with coronary flow velocity (R = -0.22, p=0.02) and area of stenosis (R = -0.70, p < 0.001) but positively correlated with the minimum lumen area (MLA) (R = 0.47, p < 0.001). Conclusion. AF patients with coronary artery stenosis have higher QFR values, which are associated with decreased blood flow velocity, smaller stenosis, and larger MLA in AF patients upon cardiac remodeling.

Comparison of multilayer and single-layer coronary plaque models on stress/strain calculations based on optical coherence tomography images.

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.

Kallistatin Improves High-Fat-Induced Insulin Resistance via Epididymal Adipose Tissue-Derived Exosomes.

Objective: Studies have found that high expression of human Kallistatin (HKS) in adipose tissue can improve obesity and its associated comorbidities, but the underlying mechanism of specific regulation is unclear. Methods: An obesity model was built by injecting 8-week-old C57BL/6 mice (n = 6 mice per group) with Ad.Null and Ad.HKS adenovirus into epididymal adipose tissue and fed with a high-fat diet (HFD). Insulin resistance-related proteins, AKT and IRS1, were detected in the liver, subcutaneous fat, and skeletal muscle by western blotting after one month of HFD. Epididymal adipose tissue was isolated after 24 h for culture, and exosomes were extracted by differential centrifugation. Enzyme-linked immunosorbent assay detected the expression of HKS protein in serum and exosomes. To examine the role of exosomes in AML12 insulin resistance, we used epididymal adipose tissue-derived exosomes or transfected Ad.HKS into mature 3T3L1-derived exosomes to interfere with palmitic acid (PA)-induced mouse AML12 insulin resistance model. GW4869 was used to inhibit exosome biogenesis and release. Results: Our results showed that HFD-induced mice with high expression of HKS in epididymal adipose tissue had slower weight gain, lower serum triglycerides, reduced free fatty acids, and improved liver insulin resistance compared with the Ad.Null group. We also demonstrated that HKS was enriched in epididymal adipose tissue-derived exosomes and released through the exosome pathway. In PA-induced AML12 cells, insulin resistance was alleviated after incubation of the HKS-related exosome; this effect was reversed with GW4869. Conclusion: High expression of HKS in epididymal adipose tissue could lead to its exocrine secretion in the form of exosomes and improve liver insulin resistance by promoting the phosphorylation of AKT. Production of high HKS vesicles might be a possible way to alleviate insulin resistance associated with obesity.