Prospective evaluation of cardiovascular risk and mortality in patients with psoriasis: An American population-based study.

The association between psoriasis and cardiovascular disease (CVD) has long been discussed and continually refined. However, there is currently a lack of prospective studies on the cardiovascular risk attributed to psoriasis in the United States general population. Representative adult participants were selected from the National Health and Nutrition Examination Survey (NHANES). Risks of cardiovascular symptoms and diseases prevalence were evaluated between participants with and without psoriasis. The hazards for all-cause mortality and CVD mortality were stratified by psoriasis status. Mediation analysis was then conducted to identify potential mediators between psoriasis and cardiac death. Overall, 19 741 participants were included in the current study, 542 (2.7%) had psoriasis and 19 199 (97.3%) did not have psoriasis. After adjusting for known CVD risk factors, odds for hypertension (OR = 1.37, 95% CI: 1.13-1.66, p = 0.001), hypercholesterolemia (OR = 1.37, 95% CI: 1.13-1.64, p < 0.001) and angina pectoris (OR = 1.74, 95% CI: 1.11-2.60, p = 0.011) were higher in psoriasis patients. Compared with participants without psoriasis, moderate/severe but not mild patients showed significantly higher CVD mortality (HR = 2.55, 95% CI: 1.27-5.15, p = 0.009). This result was supported by subgroup analyses. Mediation analysis further suggested that the direct effect of moderate/severe psoriasis on CVD mortality accounted for 81.4% (65.8%-97.1%). Besides, the indirect effect might derive from disturbance of serum albumin, urea nitrogen and uric acid. Moderate-to-severe psoriasis is an independent risk factor for cardiovascular disease, making it necessary to regularly conduct cardiovascular disease-related examinations for patients with higher severity of psoriasis in clinical settings.

Estimated Pulse Wave Velocity Predicts All-Cause and Cardiovascular-Cause Mortality in Individuals With Hypertension　- Findings From a National Health and Nutrition Examination Study 1999-2018.

BACKGROUND: This study aimed to investigate the association between estimated pulse wave velocity (ePWV) and mortality outcomes among individuals with hypertension. METHODS AND RESULTS: Based on the National Health and Nutrition Examination Survey (NHANES) 1999-2018, a total of 14,396 eligible participants with hypertension were enrolled. The ePWV was calculated using the equation based on blood pressure and age. The mortality outcomes of included participants were directly acquired from the National Death Index database. The multivariable Cox regression analysis was used to examine the relationship between ePWV and mortality outcomes. Moreover, the restricted cubic spline (RCS) was also used to explore this relationship. Receiver operating characteristics curves (ROC) were adopted to evaluate the prognostic ability of ePWV for predicting mortality outcomes of patients with hypertension. The median follow-up duration was 10.8 years; individuals with higher an ePWV had higher risks of mortality from both all causes (HR: 2.79, 95% CI: 2.43-3.20) and cardiovascular diseases (HR: 3.41, 95% CI: 2.50-4.64). After adjusting for confounding factors, each 1 m/s increase in ePWV was associated with a 43% increase in all-cause mortality risk (HR: 1.43, 95% CI: 1.37-1.48) and a 54% increase in cardiovascular mortality risk (HR: 1.54, 95% CI: 1.43-1.66). CONCLUSIONS: This study indicates that ePWV is a novel prognostic indicator for predicting the risks of mortality among patients with hypertension.

Association between dietary inflammatory index and Stroke in the US population: evidence from NHANES 1999-2018.

BACKGROUND: There is an increasing awareness that diet-related inflammation may have an impact on the stroke. Herein, our goal was to decipher the association of dietary inflammatory index (DII) with stroke in the US general population. METHODS: We collected the cross-sectional data of 44,019 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2018. The association of DII with stroke was estimated using weighted multivariate logistic regression, with its nonlinearity being examined by restricted cubic spline (RCS) regression. The least absolute shrinkage and selection operator (LASSO) regression was applied for identifying key stroke-related dietary factors, which was then included in the establishment of a risk prediction nomogram model, with the receiver operating characteristic (ROC) curve being built to evaluate its discriminatory power for stroke. RESULTS: After confounder adjustment, the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for stroke across higher DII quartiles were 1.19 (0.94-1.54), 1.46 (1.16-1.84), and 1.87 (1.53-2.29) compared to the lowest quartile, respectively. The RCS curve showed a nonlinear and positive association between DII and stroke. The nomogram model based on key dietary factors identified by LASSO regression displayed a considerable predicative value for stroke, with an area under the curve (AUC) of 79.8% (78.2-80.1%). CONCLUSIONS: Our study determined a nonlinear and positive association between DII and stroke in the US general population. Given the intrinsic limitations of cross-sectional study design, it is necessary to conduct more research to ensure the causality of such association.

Prevalence of neutropenia in US residents: a population based analysis of NHANES 2011-2018.

AIMS: Neutrophils play a pivotal in immunity and inflammation. We aim to investigate the prevalence of neutropenia in the United States. METHODS: In this cross-sectional study, participants from the National Health and Nutrition Examination Survey (NHANES) (2011-2018) were enrolled. Demographic information, hematologic measurements, smoking status of all participants were collected for all participants. All statistical analyses were performed utilizing the NHANES survey weights. Covariate-adjusted linear regression was used to compare hematologic indices in different population grouped by age, sex, ethnicity, and smoking. We also employed multivariate-logistic regression to estimate the weighted odds ratio with a 95% confidence interval and predict the neutropenia risk among. RESULTS: 32,102 participants from NHANES survey were included, represented 286.6 million multiracial population in the United States. Black participants had lower mean leukocyte count (mean difference (MD): 0.71 × 109/L; P < 0.001) and lower neutrophil count (MD: 0.83 × 109/L; P < 0.001) compared with white participants after adjusting for age and sex. Furthermore, t a notable observation was the significant downward shift in the distribution curves of leukocyte count and neutrophil count among black participants. Smokers had a higher mean leukocyte count (MD: 1.10 × 109 cells/L; P < 0.001) and a higher mean neutrophil count (MD: 0.75 × 109 cells/L; P < 0.001) comparing with nonsmokers. The estimated prevalence of neutropenia was 1.24% (95% CI: 1.11 - 1.37%), which corresponds to approximately 35.5 million individuals in the United States. The prevalence of neutropenia in black participants was significantly higher than other races. Results of logistic regression analysis showed that black individuals, male individuals, and children younger than 5 years had a higher risk of neutropenia. CONCLUSIONS: Neutropenia is more common in the general population than we thought, especially in black individuals and children. More attention should be paid to neutropenia.

Involvement of pyroptosis pathway in epicardial adipose tissue - myocardium axis in experimental heart failure with preserved ejection fraction.

Epicardial adipose tissue (EAT) is a metabolically active organ which generates inflammatory cytokines. Thickness of EAT is associated with onset and development of heart failure with preserved ejection fraction (HFpEF). However, it is still unclear the specific mechanisms and pharmacological targets on EAT induced inflammation in HFpEF. A two-hit protocol with western diet and Nω-nitrol-arginine methyl ester (L-NAME) was used to establish HFpEF mouse model. In HFpEF mice, inflammatory biomarkers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and von willebrand factor (vWF) elevated in myocardium compared to control. Inflammatory cell infiltration in myocardium was increased. In HFpEF mice, inflammasome-mediated pyroptosis pathway was activated in the EAT. Suppression of pyroptosis-related protein gasdermin D (GSDMD) in cultured EAT could lower cardiomyocyte inflammation and autophagy. Furthermore, spironolactone and rosuvastatin, the two-hit anti-inflammatory agents, reduced NLR family pyrin domain containing 3 (NLRP3)/GSDMD pyroptosis in EAT and autophagy in myocardium of HFpEF mouse. The combination treatment also enhanced exercise tolerance and appeased inflammatory injuries in HFpEF mice. CONCLUSION: Pyroptosis signaling is involved in EAT-myocardium axis in mouse model of HFpEF. Targeting adipocyte-derived inflammation in EAT bears potential to treatment HFpEF.

Microvillar dynamic in renal tubular epithelial cells mediated by insulin/PLCγ signal pathway.

Significant cellular morphology changes in renal tubules were observed in diabetes patients and animal models. However, the interaction between insulin and tubular epithelial cells microvillar structure remains obscure. To understand microvillar dynamics, we used Scanning Ion Conductance Microscope to visualize microvillar in the living cell. Here, we found two layers of microvilli on the tubular epithelial cell surface: short compact microvilli and netlike long microvilli. Insulin treatment could increase microvilli length and density. This process was mediated by the PI3K/PLCγ signaling pathway, other than the PI3K/Arp2/3 signal pathway. In conclusion, our findings present a novel insulin signaling transduction mechanism, which contributes to understanding renal tubular epithelial cell microvilli dynamic regulation.

The long-term efficacy and safety of combining ablation and left atrial appendage closure: A systematic review and meta-analysis.

BACKGROUND: Combined ablation and left atrial appendage closure (LAAC) is an alternative for atrial fibrillation patients with a high risk of stroke. However, the long-term outcomes of this combined procedure remain elusive. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from the establishment of databases to 1 January 2021. Studies on the long-term (defined as a mean follow-up of approximately 12 months or longer) efficacy and safety outcomes of combined ablation and LAAC were included. RESULTS: A total of 16 studies comprising 1428 patients were enrolled. The pooled long-term freedom rate from atrial arrhythmia was 0.66 (95% confidence interval [CI]: 0.59-0.71), long-term successful rate sealing of LAAC was 1.00 (95% CI: 1.00-1.00), and ischemic stroke/transient ischemic attack/systemic embolism during follow-up was 0.01 (95% CI: 0.00-0.02). Meanwhile, of the periprocedural adverse events, phrenic nerve palsy, intracoronary air embolus, device embolization, and periprocedural death had a rate of 0.00 (95% CI: 0.00-0.00), procedure-related bleeding events of 0.03 (95% CI: 0.02-0.04), and pericardial effusion requiring or not requiring intervention of 0.00 (95% CI: 0.00-0.01). Moreover, for the long-term adverse events, device dislocation, intracranial bleeding, pericardial effusion requiring or not requiring intervention, and all-cause mortality had a rate of 0.00 (95% CI: 0.00-0.00), device embolization of 0.01 (95% CI: 0.00-0.01), and other bleeding events of 0.01 (95% CI: 0.00-0.03). CONCLUSION: This meta-analysis suggests that the combined atrial ablation and LAAC is an effective and safe strategy with long-term benefits.

His-Purkinje conduction system pacing: A systematic review and network meta-analysis in bradycardia and conduction disorders.

BACKGROUND: His-Purkinje conduction system pacing (HPCSP) has emerged as an effective alternative to overcome the limitations of right ventricular pacing (RVP) via physiological left ventricular activation, but there remains a paucity of comparative information for His bundle pacing (HBP) and left bundle branch pacing (LBBP). METHODS: A Bayesian random-effects network analysis was conducted to compare the relative effects of HBP, LBBP, and RVP in patients with bradycardia and conduction disorders. PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from database inception until September 21, 2021. RESULTS: Twenty-eight studies involving 4160 patients were included in this meta-analysis. LBBP significantly improved success rate, pacing threshold, pacing impedance, and R-wave amplitude compared with HBP. LBBP also demonstrated a nonsignificant trend towards superior outcomes of lead complications, heart failure hospitalization, atrial fibrillation, and all-cause death. However, HBP was associated with significantly shorter paced QRS duration relative to LBBP. Despite higher success rates, shorter procedure/fluoroscopy duration, and fewer lead complications, patients receiving RVP were more likely to experience reduced left ventricular ejection fraction, longer paced QRS duration, and higher rates of heart failure hospitalization than those receiving HPCSP. No statistical differences were observed in the remaining outcome measures. CONCLUSIONS: This network meta-analysis demonstrates the efficacy and safety of HPCSP for the treatment of bradycardia and conduction disorders, with differences in pacing parameters, electrophysiology characteristics, and clinical outcomes between HBP and LBBP. Larger-scale, long-term comparative studies are warranted for further verification.

Modulation of Actin Filament Dynamics by Inward Rectifying of Potassium Channel Kir2.1.

Apart from its ion channel properties, the Kir2.1 channel has been found in tumors and cancer cells to facilitate cancer cell motility. It is assumed that Kir2.1 might be associated with cell actin filament dynamics. With the help of structured illumination microscopy (SIM), we show that Kir2.1 overexpression promotes actin filament dynamics, cell invasion, and adhesion. Mutated Kir2.1 channels, with impaired membrane expression, present much weaker actin regulatory effects, which indicates that precise Kir2.1 membrane localization is key to its actin filament remolding effect. It is found that Kir2.1 membrane expression and anchoring are associated with PIP2 affinity, and PIP2 depletion inhibits actin filament dynamics. We also report that membrane-expressed Kir2.1 regulates redistribution and phosphorylation of FLNA (filamin A), which may be the mechanism underlying Kir2.1 and actin filament dynamics. In conclusion, Kir2.1 membrane localization regulates cell actin filaments, and not the ion channel properties. These data indicate that Kir2.1 may have additional cellular functions distinct from the regulation of excitability, which provides new insight into the study of channel proteins.

A Novel Strategy to Enhance the pH Stability of Zein Particles through Octenyl Succinic Anhydride-Modified Starch: The Role of Preparation pH.

Ensuring the stability of zein nanoparticles at different pH levels is crucial for their application as nanocarriers. In this study, octenyl succinic anhydride-modified starch (OSA-modified starch) was employed to enhance the stability of zein nanoparticles against different pH levels by forming complex nanoparticles with OSA-modified starch. The effect of preparation pH on the stability of the zein/OSA-modified starch nanoparticles was investigated. Sedimentation occurred in zein nanoparticles as the pH reached the isoelectric point. However, the stability of zein nanoparticles at various pH levels significantly improved after adding OSA-modified starch to form zein/OSA-modified starch nanoparticles regardless of whether they were prepared under acidic or alkaline pH conditions. Notably, the stability of zein/OSA-modified starch nanoparticles prepared at an acidic pH was higher than that of those prepared at an alkaline pH, thereby highlighting the critical role of the preparation pH for zein/OSA-modified starch in maintaining the stability of zein. The stable zein/OSA-modified starch nanoparticles developed in this study exhibit significant potential for use in delivery systems across various pH environments.

Association between dietary intake of niacin and stroke in the US residents: evidence from national health and nutrition examination survey (NHANES) 1999-2018.

Objective: This study aims to explore the association between niacin intake and stroke within a diverse, multi-ethnic population. Methods: A stringent set of inclusion and exclusion criteria led to the enrollment of 39,721 participants from the National Health and Nutrition Examination Survey (NHANES). Two interviews were conducted to recall dietary intake, and the USDA's Food and Nutrient Database for Dietary Studies (FNDDS) was utilized to calculate niacin intake based on dietary recall results. Weighted multivariate logistic regression was employed to examine the correlation between niacin and stroke, with a simultaneous exploration of potential nonlinear relationships using restricted cubic spline (RCS) regression. Results: A comprehensive analysis of baseline data revealed that patients with stroke history had lower niacin intake levels. Both RCS analysis and multivariate logistic regression indicated a negative nonlinear association between niacin intake and stroke. The dose-response relationship exhibited a non-linear pattern within the range of dietary niacin intake. Prior to the inflection point (21.8 mg) in the non-linear correlation between niacin intake and stroke risk, there exists a marked decline in the risk of stroke as niacin intake increases. Following the inflection point, the deceleration in the decreasing trend of stroke risk with increasing niacin intake becomes evident. The inflection points exhibit variations across diverse populations. Conclusion: This investigation establishes a negative nonlinear association between niacin intake and stroke in the broader American population.

HFpEF as systemic disease, insight from a diagnostic prediction model reminiscent of systemic inflammation and organ interaction in HFpEF patients.

Systemic inflammation and reciprocal organ interactions are associated with the pathophysiology of heart failure with preserved ejection fraction (HFpEF). However, the clinical value, especially the diagnositc prediction power of inflammation and extra-cardiac organ dysfunction for HfpEF is not explored. In this cross-sectional study, 1808 hospitalized patients from January 2014 to June 2022 in ChiHFpEF cohort were totally enrolled according to inclusion and exclusion criteria. A diagnostic model with markers from routine blood test as well as liver and renal dysfunction for HFpEF was developed using data from ChiHFpEF-cohort by logistic regression and assessed by receiver operating characteristic curve (ROC) and Brier score. Then, the model was validated by the tenfold cross-validation and presented as nomogram and a web-based online risk calculator as well. Multivariate and LASSO regression analysis revealed that age, hemoglobin, neutrophil to lymphocyte ratio, AST/ALT ratio, creatinine, uric acid, atrial fibrillation, and pulmonary hypertension were associated with HFpEF. The predictive model exhibited reasonably accurate discrimination (ROC, 0.753, 95% CI 0.732-0.772) and calibration (Brier score was 0.200). Subsequent internal validation showed good discrimination and calibration (AUC = 0.750, Brier score was 0.202). In additoin to participating in pathophysiology of HFpEF, inflammation and multi-organ interactions have diagnostic prediction value for HFpEF. Screening and optimizing biomarkers of inflammation and multi-organ interactions stand for a new field to improve noninvasive diagnostic tool for HFpEF.

Integrated genomic analysis defines molecular subgroups in dilated cardiomyopathy and identifies novel biomarkers based on machine learning methods.

Aim: As the most common cardiomyopathy, dilated cardiomyopathy (DCM) often leads to progressive heart failure and sudden cardiac death. This study was designed to investigate the molecular subgroups of DCM. Methods: Three datasets of DCM were downloaded from GEO database (GSE17800, GSE79962 and GSE3585). After log2-transformation and background correction with "limma" package in R software, the three datasets were merged into a metadata cohort. The consensus clustering was conducted by the "Consensus Cluster Plus" package to uncover the molecular subgroups of DCM. Moreover, clinical characteristics of different molecular subgroups were compared in detail. We also adopted Weighted gene co-expression network analysis (WGCNA) analysis based on subgroup-specific signatures of gene expression profiles to further explore the specific gene modules of each molecular subgroup and its biological function. Two machine learning methods of LASSO regression algorithm and SVM-RFE algorithm was used to screen out the genetic biomarkers, of which the discriminative ability of molecular subgroups was evaluated by receiver operating characteristic (ROC) curve. Results: Based on the gene expression profiles, heart tissue samples from patients with DCM were clustered into three molecular subgroups. No statistical difference was found in age, body mass index (BMI) and left ventricular internal diameter at end-diastole (LVIDD) among three molecular subgroups. However, the results of left ventricular ejection fraction (LVEF) statistics showed that patients from subgroup 2 had a worse condition than the other group. We found that some of the gene modules (pink, black and grey) in WGCNA analysis were significantly related to cardiac function, and each molecular subgroup had its specific gene modules functions in modulating occurrence and progression of DCM. LASSO regression algorithm and SVM-RFE algorithm was used to further screen out genetic biomarkers of molecular subgroup 2, including TCEAL4, ISG15, RWDD1, ALG5, MRPL20, JTB and LITAF. The results of ROC curves showed that all of the genetic biomarkers had favorable discriminative effectiveness. Conclusion: Patients from different molecular subgroups have their unique gene expression patterns and different clinical characteristics. More personalized treatment under the guidance of gene expression patterns should be realized.

Systemic Immune Inflammation Index (SII), System Inflammation Response Index (SIRI) and Risk of All-Cause Mortality and Cardiovascular Mortality: A 20-Year Follow-Up Cohort Study of 42,875 US Adults.

BACKGROUND AND AIM: Chronic low-grade inflammation is associated with various health outcomes, including cardiovascular diseases (CVDs) and cancers. Systemic immune inflammation index (SII) and system inflammation response index (SIRI) have lately been explored as novel prognostic markers for all-cause mortality and cardiovascular mortality. However, studies on prediction value in nationwide representative population are scarce, which limit their generalization. To bridge the knowledge gap, this study aims to prospectively assess the association of SII, SIRI with all-cause mortality and cardiovascular mortality in the National Health and Nutrition Examination Survey (NHANES). METHODS: From 1999 to 2018, 42,875 adults who were free of pregnancy, CVDs (stroke, acute coronary syndrome), cancers, and had follow-up records and participated in the NHANES were included in this study. SII and SIRI were quantified by calculating the composite inflammation indicators from the blood routine. To explore the characteristics of the population in different SII or SIRI levels, we divided them according to the quartile of SII or SIRI. The associations between SII, SIRI, and all-cause mortality and cardiovascular mortality events were examined using a Cox regression model. To investigate whether there was a reliable relationship between these two indices and mortalities, we performed subgroup analysis based on sex and age. RESULTS: A total of 42,875 eligible individuals were enrolled, with a mean age of 44 ± 18 years old. During the follow-up period of up to 20 years, 4250 deaths occurred, including 998 deaths from CVDs. Cox proportional hazards modeling showed that adults with SII levels of >655.56 had higher all-cause mortality (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.18-1.41) and cardiovascular mortality (HR, 1.33; 95% CI, 1.11-1.59) than those with SII levels of <335.36. Adults with SIRI levels of >1.43 had higher risk of all-cause (HR, 1.39; 95% CI, 1.26-1.52) and cardiovascular death (HR, 1.39; 95% CI, 1.14-1.68) than those with SIRI levels of <0.68. In general population older than 60 years, the elevation of SII or SIRI was associated with the risk of all-cause death. CONCLUSION: Two novel inflammatory composite indices, SII and SIRI, were closely associated with cardiovascular death and all-cause death, and more attention should be paid to systemic inflammation to provide better preventive strategies.

Association of different obesity patterns with hypertension in US male adults: a cross-sectional study.

Obesity is an important risk factor for hypertension. We aimed to investigate the association between different obesity patterns and hypertension risk in a large male population in the US. Male participants from the National Health and Nutrition Examination Survey (NHANES) (2007-2018) were enrolled in this cross-sectional study. Social demographic information, lifestyle factors, anthropometric measurements and biochemical measurements were collected. Three obesity patterns were classified according to the body mass index (BMI) and waist circumference (WC), including overweight and general obesity, abdominal obesity, and compound obesity. We adopted multivariate logistic regression to investigate the associations between hypertension and different obesity patterns after adjusting for cofounding factors. Subgroup analysis, stratified by age, smoking, drinking and estimated glomerular filtration rate (eGFR), was also conducted to explore the associations between obesity patterns and hypertension risk among different populations. Moreover, the association between WC and hypertension among male individuals was also explored using restricted cubic spline (RCS) analysis. Receiver operating characteristic (ROC) was used to evaluate the discriminatory power of WC for screening hypertension risk. 13,859 male participants from NHANES survey (2007-2018) were enrolled. Comparing with the normal-weight group, the odds ratios (ORs) [95% confidence interval (CI)] for hypertension in individuals with overweight and general obesity, abdominal obesity and compound obesity were 1.41 [1.17-1.70], 1.97 [1.53-2.54] and 3.28 [2.70-3.99], respectively. Subgroup analysis showed that the effect of different obesity patterns on hypertension risk was highly stable among individuals with different clinical conditions. In addition, WC had a positive correlation with the risk of hypertension (OR: 1.43; 95% CI 1.37-1.52; P < 0.001) in fully adjusted multivariate logistic regression model. RCS analysis showed that the association between WC and hypertension risk was in a nonlinear pattern, and WC had a good discriminatory power for hypertension in ROC analysis. Different patterns of obesity have a great impact on the risk of hypertension among male individuals. Increment of WC significantly increased the hypertension risk. More attention should be paid to the prevention of obesity, especially abdominal obesity and compound obesity in male individuals.

Disparate Clinical Characteristics and Prognosis of HFpEF versus HFrEF Phenotype of Diabetic Cardiomyopathy.

AIMS: Diabetic cardiomyopathy (DCM) is an ill-defined entity. This study aims to explore the clinical characteristics and prognosis of diabetic patients that disparately develop heart failure (HF) with preserved ejection fraction (HFpEF) other than HF with reduced ejection fraction (HFrEF). PATIENTS AND METHODS: A total of 911 patients diagnosed with diabetes mellitus were identified in the ChiHFpEF cohort (NCT05278026). DCM was defined as diabetic patients diagnosed with HF, absent from flow obstructive coronary artery disease (CAD), uncontrolled refractory hypertension and hemodynamics significant heart valvular diseases, arrhythmia and congenital heart diseases. The primary endpoint was a composite of all-cause death and rehospitalization due to HF. RESULTS: As compared to DCM-HFrEF patients, DCM-HFpEF patients had a longer duration of diabetes, were older and more noticeable in hypertension and non-obstructive CAD. After a median follow-up of 45.5 months, survival analysis showed that DCM-HFpEF patients had a better composite endpoint. Cox regression implicated that non-obstructive CAD was a negative (HR 0.101, 95% CI 0.028-0.373, p = 0.001) predictor for the composite endpoint of DCM-HFrEF patients. Age was a positive predictor for the composite endpoint of DCM-HFpEF patients (HR 1.044, 95% CI 1.007-1.082, p = 0.018). CONCLUSION: DCM-HFpEF is a disparate entity from DCM-HFrEF. Additional phenomic studies are needed to explore the molecular mechanisms and develop targeted therapies.

Estimated pulse wave velocity is associated with all-cause mortality and cardiovascular mortality among adults with diabetes.

Aims: We aim to examine the association of estimated pulse wave velocity (ePWV) with all-cause and cardiovascular mortality in patients with diabetes. Methods: All of adult participants with diabetes from the National Health and Nutrition Examination Survey (NHANES) (1999-2018) were enrolled. ePWV was calculated according to the previously published equation based on age and mean blood pressure. The mortality information was obtained from the National Death Index database. Weighted Kaplan-Meier (KM) plot and weighted multivariable Cox regression was used to investigate the association of ePWV with all-cause and cardiovascular mortality risks. Restricted cubic spline was adopted to visualize the relationship between ePWV and mortality risks. Results: 8,916 participants with diabetes were included in this study and the median follow-up duration was ten years. The mean age of study population was 59.0 ± 11.6 years, 51.3% of the participants were male, representing 27.4 million patients with diabetes in weighted analysis. The increment of ePWV was closely associated with increased risks of all-cause mortality (HR: 1.46, 95% CI: 1.42-1.51) and cardiovascular mortality (HR: 1.59, 95% CI: 1.50-1.68). After adjusting for cofounding factors, for every 1 m/s increase in ePWV, there was a 43% increased risk of all-cause mortality (HR: 1.43, 95% CI: 1.38-1.47) and 58% increased of cardiovascular mortality (HR: 1.58, 95% CI: 1.50-1.68). ePWV had positive linear associations with all-cause and cardiovascular mortality. KM plots also showed that the risks of all-cause and cardiovascular mortality were significantly elevated in patients with higher ePWV. Conclusions: ePWV had a close association with all-cause and cardiovascular mortality risks in patients with diabetes.

Identification of key immune-related genes in dilated cardiomyopathy using bioinformatics analysis.

Dilated cardiomyopathy (DCM) is characterized by the left ventricular dilatation and impaired myocardial systolic dysfunction with high mortality and morbidity. However, the underlying mechanisms remain elusive. We first identified the differentially expressed genes (DEGs) between the DCM and control group using two expression profiles from GSE3585 and GSE84796. Enrichment analysis was conducted to explore the potential mechanisms underlying DCM. A total of four algorithms, including key module of MCODE, degree, maximum neighborhood component (MNC), and maximal clique centrality (MCC), were used to identify the hub genes within Cytoscape. The correlation between hub genes and infiltrated immune cells was evaluated to determine potential immune-related genes. The expression analysis and diagnosis value analysis of potential immune-related genes were performed. Finally, the expression analysis with GSE57338 and relationship analysis with the comparative toxicogenomics database (CTD) were performed to identify the key immune-related genes in DCM. A total of 80 DEGs were screened for DCM. Enrichment analysis revealed that DEGs were involved in the immune-related pathological process. Immune infiltration analysis indicated a potentially abnormal immune response in DCM. Four up-regulated genes (COL1A2, COL3A1, CD53, and POSTN) were identified as potential immune-related genes. Finally, three genes (COL1A2, COL3A1, and POSTN) were determined as the key immune-related genes in DCM via expression analysis with a validation set (GSE57338) and relationship analysis with CTD. Our study suggested that the upregulated COL1A2, COL3A1, and POSTN might be the key immune-related genes for DCM. Further studies are needed to validate the underlying mechanisms.

Glucose fluctuations aggravated the late sodium current induced ventricular arrhythmias via the activation of ROS/CaMKII pathway.

BACKGROUND: Recent evidence revealed that glucose fluctuation might be more likely to cause arrhythmia than persistent hyperglycemia, whereas its mechanisms were elusive. We aimed to investigate the effect of glucose fluctuation on the occurrence of ventricular arrhythmia and its mechanism. METHODS: Streptozotocin (STZ) induced diabetic rats were randomized to five groups: the controlled blood glucose (C-STZ) group, uncontrolled blood glucose (U-STZ) group, fluctuated blood glucose (GF-STZ) group, and GF-STZ rats with 100 mg/kg Tempol (GF-STZ + Tempol) group or with 5 mg/kg KN93 (GF-STZ + KN93) group. Six weeks later, the susceptibility of ventricular arrhythmias and the electrophysiological dysfunctions of ventricular myocytes were evaluated using electrocardiogram and patch-clamp technique, respectively. The levels of reactive oxygen species (ROS) and oxidized CaMKII (ox-CaMKII) were determined by fluorescence assay and Western blot, respectively. Neonatal rat cardiomyocytes and H9C2 cells in vitro were used to explore the underlying mechanisms. RESULTS: The induction rate of ventricular arrhythmias was 10%, 55%, and 90% in C-STZ group, U-STZ group, and GF-STZ group, respectively (P < 0.05). The electrophysiological dysfunctions of ventricular myocytes, including action potential duration at repolarization of 90% (APD90), APD90 short-term variability (APD90-STV), late sodium current (INa-L), early after depolarization (EAD) and delayed after depolarizations (DAD), as well as the levels of ROS and ox-CaMKII, were significantly increased in GF-STZ group. In vivo and ex vivo, inhibition of ROS or ox-CaMKII reversed these effects. Inhibition of INa-L also significantly alleviated the electrophysiological dysfunctions. In vitro, inhibition of ROS increase could significantly decrease the ox-CaMKII activation induced by glucose fluctuations. CONCLUSIONS: Glucose fluctuations aggravated the INa-L induced ventricular arrhythmias though the activation of ROS/CaMKII pathway.

Dietary Inflammatory Index and Its Association with the Prevalence of Coronary Heart Disease among 45,306 US Adults.

Inflammation plays a pivotal in the occurrence and development of coronary heart disease (CHD). We aim to investigate the association between the Dietary Inflammatory Index (DII) and CHD in the present study. In this cross-sectional study, adult participants from the National Health and Nutrition Examination Survey (NHANES) (1999-2018) were enrolled. The social demographic information, lifestyle factors, blood biochemical measurements, dietary information, and CHD status of all the participants were systematically collected. Multivariable logistic regression was adopted to investigate the association between the risk of CHD and the DII. Besides, restricted cubic spline (RCS) analysis was used to explore whether there was a nonlinear association of the DII and CHD. Subgroup analysis stratified by sex, age, race/ethnicity, and BMI was conducted to evaluate the association of the DII and CHD among different populations. A total of 45,306 adults from NHANES (1999-2018) were included. Compared with individuals without CHD, the DIIs of the participants with CHD were significantly elevated. A positive association was observed between the DII and CHD in multivariable logistic analysis after adjusting for age, sex, race/ethnicity, education levels, smoking, drinking, diabetes, hypertension, and body mass index (BMI). Results of RCS analysis suggested a nonlinear relationship between the DII and CHD. In addition, the increment of the DII had a greater impact on female individuals compared with male individuals. The DII is closely associated with the risk of CHD. For better prevention and treatment of CHD, more attention should be paid to controlling dietary inflammation.