The prognostic value of dynamic changes in SII for the patients with STEMI undergoing PPCI.

BACKGROUND: Predicting the prognosis of primary percutaneous coronary intervention(PPCI) in ST-segment elevation myocardial infarction (STEMI) patients in the perioperative period is of great clinical significance. The inflammatory response during the perioperative period is also an important factor. This study aimed to investigate the dynamic changes in the systemic immune inflammatory index (SII) during the perioperative period of PPCI and evaluate its predictive value for in-hospital and out-of-hospital outcomes in patients with STEMI. METHODS: This retrospective study included 324 consecutive patients with STEMI who were admitted to the cardiac care unit. Blood samples were collected before PPCI, 12 h (T1), 24 h, 48 h after PPCI, the last time before hospital discharge (T2), and 1 month after hospital discharge. The SII was calculated as (neutrophils×platelets)/lymphocytes. Based on whether the primary endpoint occurred, we divided the patients into event and non-event groups. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors that might influence the occurrence of the primary endpoint. Dynamic curves of SII were plotted, and receiver operating characteristic (ROC) curves were drawn for each node to calculate the optimal critical value, sensitivity, and specificity to assess their predictive ability for in-hospital and out-of-hospital courses. Kaplan-Meier curves were used to analyze the differences in survival rates at different SII inflammation levels. RESULTS: High levels of SII were individually related to the occurrence of the in-hospital period and long-term outcomes during the post-operative follow-up of STEMI patients (in-hospital SII: T1:OR 1.001,95%CI 1.001-1.001, P < 0.001; SII following hospital discharge: T1M: OR 1.008,95%CI 1.006-1.010, P < 0.001). Patients with high SII levels had lower survival rates than those with low SII levels. The analysis showed that the SII 12 h after (T1) and SII 1 month (T1M) had excellent predictive values for the occurrence of in-hospital and out-of-hospital outcomes, respectively (AUC:0.896, P < 0.001; AUC:0.892, P < 0.001). CONCLUSION: There is a significant relationship between the dynamic status of SII and prognosis in patients with STEMI. This study found that the 12 h and SII 1 month affected in-hospital and out-of-hospital outcomes, respectively. Consequently, we focused on the dynamic changes in the SII.

Development and Validation of a Nomogram for Predicting All-Cause Mortality in Patients with Hemodialysis Having Pulmonary Hypertension.

INTRODUCTION: Patients with end-stage renal disease receiving hemodialysis (HD) have a high morbidity and mortality rate associated with pulmonary hypertension (PH). A nomogram was developed to predict all-cause mortality in HD patients with PH. In this study, we aimed to validate the usefulness of this nomogram. METHODS: A total of 274 HD patients with PH were hospitalized at the Affiliated Hospital of Xuzhou Medical University between January 2014 and June 2019 and followed up for 3 years. Echocardiography detected PH when the peak tricuspid regurgitation velocity (TRV) was more than 2.8 m/s. To evaluate the all-cause mortality for long-term HD patients with PH, Cox regression analysis was performed to determine the factors of mortality that were included in the prediction model. Next, the area under the receiver-operating characteristic curve (AUC-ROC) was used to assess the predictive power of the model. Calibration plots and decision curve analysis (DCA) were used to assess the accuracy of the prediction results and the clinical utility of the model. RESULTS: The all-cause mortality rate was 29.20% throughout the follow-up period. The nomogram comprised six commonly available predictors: age, diabetes mellitus, cardiovascular disease, hemoglobin, left ventricular ejection fraction, and TRV. The 1-year, 2-year, and 3-year AUC-ROC values were 0.842, 0.800, and 0.781, respectively. The calibration curves revealed excellent agreement with the nomogram, while the DCA demonstrated favorable clinical practicability. CONCLUSION: The first developed nomogram for predicting all-cause mortality in HD patients with PH could guide clinical decision-making and intervention planning.

SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury.

BACKGROUND: Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca 2+ homeostasis. The present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation (small ubiquitin-like modifier) process after ischemia/reperfusion injury (I/RI) in vitro and in vivo . METHODS: Calcium transient and systolic/diastolic function of cardiomyocytes isolated from Serca2a knockout (KO) and wild-type mice with I/RI were compared. SUMO-relevant protein expression and localization were detected by quantitative real-time PCR (RT-qPCR), Western blotting, and immunofluorescence in vitro and in vivo . Serca2a-SUMOylation, infarct size, and cardiac function of Senp1 or Senp2 overexpressed/suppressed adenovirus infected cardiomyocytes, were detected by immunoprecipitation, triphenyltetrazolium chloride (TTC)-Evans blue staining, and echocardiography respectively. RESULTS: The results showed that the changes of Fura-2 fluorescence intensity and contraction amplitude of cardiomyocytes decreased in the I/RI groups and were further reduced in the Serca2a KO + I/RI groups. Senp1 and Senp2 messenger ribose nucleic acid (mRNA) and protein expression levels in vivo and in cardiomyocytes were highest at 6 h and declined at 12 h after I/RI. However, the highest levels in HL-1 cells were recorded at 12 h. Senp2 expression increased in the cytoplasm, unlike that of Senp1. Inhibition of Senp2 protein reversed the I/RI-induced Serca2a-SUMOylation decline, reduced the infarction area, and improved cardiac function, while inhibition of Senp1 protein could not restore the above indicators. CONCLUSION: I/RI activated Senp1 and Senp2 protein expression, which promoted Serca2a-deSUMOylation, while inhibition of Senp2 expression reversed Serca2a-SUMOylation and improved cardiac function.

Preliminary assessment of cardiotoxicity in chimeric antigen receptor T cell therapy: a systematic review and meta-analysis.

As a novel anticancer therapy, chimeric antigen receptor T (CAR T) cell therapy may lead to cardiotoxic reactions. However, the exact incidence remains unclear. Our study aimed to preliminarily assess the prevalence of cardiotoxicity after CAR T cell treatment using a systematic review and meta-analysis. PubMed, Embase, Web of Science, and Cochrane databases were searched for potentially relevant studies. All types of relevant clinical studies were screened and assessed for risk bias. In most instances, random-effect models were used for data analysis, and heterogeneity between studies was evaluated. Standard quality assessment tools were used to assess quality. The study was registered with PROSPERO (CRD42022304611). Eight eligible studies comprising 3567 patients, including seven observational studies and one controlled study, were identified. The incidence of cardiovascular events was 16.7% [95% confidence interval (CI) 0.138-0.200, P < 0.01)]. Arrhythmia was the most common disorder, with an incidence of 6.5% (95% CI 0.029-0.115, P < 0.01). The occurrence of cardiotoxicity was associated with cytokine release syndrome (CRS), with a prevalence of 18.7% (95% CI 0.107-0.315, P < 0.01). Moreover, such adverse reactions were more common when CRS > 2 (OR = 0.07, 95% CI 0.02-0.29, P < 0.01). The risk of cardiotoxicity was not notably higher in patients receiving CAR T cell therapy than in those receiving traditional anticancer treatment. However, sufficient attention should be paid to this. And further evidence from large-scale clinical trials are needed.

Diagnostic value of parameters derived from planar MUGA for detecting HFpEF in coronary artery disease patients.

BACKGROUND: In recent years, heart failure with preserved ejection fraction (HFpEF) has received increasing clinical attention. To investigate the diagnostic value of diastolic function parameters derived from planar gated blood-pool imaging (MUGA) for detecting HFpEF in coronary atherosclerotic heart disease (coronary artery disease, CAD) patients. METHODS: Ninety-seven CAD patients with left ventricular ejection fraction ≥ 50% were included in the study. Based on the left ventricular end-diastolic pressure (LVEDP), the patients were divided into the HFpEF group (LVEDP ≥ 16 mmHg, 47 cases) and the normal LV diastolic function group (LVEDP < 16 mmHg, 50 cases). Diastolic function parameters obtained by planar MUGA include peak filling rate (PFR), filling fraction during the first third of diastole (1/3FF), filling rate during the first third of diastole (1/3FR), mean filling rate during diastole (MFR), and peak filling time (TPF). Echocardiographic parameters include left atrial volume index (LAVI), peak tricuspid regurgitation velocity (peak TR velocity), transmitral diastolic early peak inflow velocity (E), average early diastolic velocities of mitral annulars (average e'), average E/e' ratio. The diastolic function parameters obtained by planar MUGA were compared with those obtained by echocardiography to explore the clinical value of planar MUGA for detecting HFpEF. RESULTS: The Receiver-operating characteristic curve analysis of diastolic function parameters obtained from planar MUGA and echocardiography to detect HFpEF showed that: among the parameters examined by planar MUGA, the area under the curve (AUC) of PFR, 1/3FF, 1/3FR, MFR and TPF were 0.827, 0.662, 0.653, 0.663 and 0.809, respectively. Among the echocardiographic parameters, the AUCs for average e', average E/e' ratio, peak TR velocity, and LAVI values were 0.747, 0.706, 0.735, and 0.633. The combination of PFR and TPF showed an AUC of 0.856. PFR combined with TPF value demonstrated better predictive value than average e' (Z = 2.020, P = 0.043). CONCLUSION: Diastolic function parameters obtained by planar MUGA can be used to diagnose HFpEF in CAD patients. PFR combined with TPF was superior to the parameters obtained by echocardiography and showed good sensitivity and predictive power for detecting HFpEF.

Effects of Remote Ischemic Preconditioning on Decreasing Troponin Release in Patients Not Taking Sulfonylureas After Cardiac Surgery - A Meta-Analysis.

INTRODUCTION: Remote ischemic preconditioning (RIPC) is a new noninvasive myocardial protection strategy that uses blood pressure cuf inflation to simulate transient non-fatal ischemia to protect the myocardium and reduce ischemia-reperfusion injury. Sulfonylureas may mask the effects of RIPC due to their cardioprotec-tive effect. This meta-analysis aimed to evaluate whether RIPC, in the absence of sulfonylureas, reduces troponin release in patients undergoing cardiac surgery. METHODS: We conducted a meta-analysis of randomized controlled clinical trials to determine whether RIPC can reduce postoperative troponin release in cardiac surgery patients undergoing cardiopulmonary bypass without treatment with sulfonylureas. The data were normalized to equivalent units prior to the analysis. A random-effects model was used to provide more conservative estimate of the effects in the presence of known or unknown heterogeneity. RESULTS: Six studies with a total of 570 participants were included. The analysis showed that troponin release was lower in the RIPC group than in the control group at six hours (test of standardized mean differences = 0, Z=3.64, P<0.001) and 48 hours (Z=2.72, P=0.007) postoperatively. When the mean of cross-clamping time was > 60 minutes, RIPC reduced troponin release at six hours (Z=2.84, P=0.005), 24 hours (Z=2.64, P=0.008), and 48 hours (Z=2.87, P=0.004) postoperatively. CONCLUSION: In cardiac surgery patients who are not taking sulfonylureas, RIPC can reduce troponin release at six and 48 hours postoperatively; hence, RIPC may serve significant benefits in certain cardiac surgery patients.

Development and validation of a risk nomogram model for predicting pulmonary hypertension in patients with stage 3-5 chronic kidney disease.

OBJECTIVES: The occurrence of pulmonary arterial hypertension (PAH) can greatly affect the prognosis of patients with chronic kidney disease (CKD). We aimed to construct a nomogram to predict the probability of PAH development in patients with stage 3-5 CKD to guide early intervention and to improve prognosis. METHODS: From August 2018 to December 2021, we collected the data of 1258 patients with stage 3-5 CKD hospitalized at the Affiliated Hospital of Xuzhou Medical University as a training set and 389 patients hospitalized at Zhongda Hospital as a validation set. These patients were divided into PAH and N-PAH groups with pulmonary arterial systolic pressure ≥ 35 mmHg as the cutoff. The results of univariate and multivariate logistic regression analyses were used to establish the nomogram. Then, areas under the receiver operating characteristic curve (AUC-ROCs), a calibration plot, and decision curve analysis (DCA) were used to validate the nomogram. RESULTS: The nomogram included nine variables: age, diabetes mellitus, hemoglobin, platelet count, serum creatinine, left ventricular end-diastolic diameter, left atrial diameter, main pulmonary artery diameter and left ventricular ejection fraction. The AUC-ROCs of the training set and validation set were 0.801 (95% confidence interval (CI) 0.771-0.830) and 0.760 (95% CI 0.699-0.818), respectively, which showed good discriminative ability of the nomogram. The calibration diagram showed good agreement between the predicted and observed results. DCA also demonstrated that the nomogram could be clinically useful. CONCLUSION: The evaluation of the nomogram model for predicting PAH in patients with CKD based on risk factors showed its ideal efficacy. Thus, the nomogram can be used to screen for patients at high risk for PAH and has guiding value for the subsequent formulation of prevention strategies and clinical treatment.

Effects of Remote Ischemic Preconditioning on Decreasing Troponin Release in Patients Not Taking Sulfonylureas After Cardiac Surgery - A Meta-Analysis

ABSTRACT Introduction: Remote ischemic preconditioning (RIPC) is a new noninvasive myocardial protection strategy that uses blood pressure cuf inflation to simulate transient non-fatal ischemia to protect the myocardium and reduce ischemia-reperfusion injury. Sulfonylureas may mask the effects of RIPC due to their cardioprotec-tive effect. This meta-analysis aimed to evaluate whether RIPC, in the absence of sulfonylureas, reduces troponin release in patients undergoing cardiac surgery. Methods: We conducted a meta-analysis of randomized controlled clinical trials to determine whether RIPC can reduce postoperative troponin release in cardiac surgery patients undergoing cardiopulmonary bypass without treatment with sulfonylureas. The data were normalized to equivalent units prior to the analysis. A random-effects model was used to provide more conservative estimate of the effects in the presence of known or unknown heterogeneity. Results: Six studies with a total of 570 participants were included. The analysis showed that troponin release was lower in the RIPC group than in the control group at six hours (test of standardized mean differences = 0, Z=3.64, P<0.001) and 48 hours (Z=2.72, P=0.007) postoperatively. When the mean of cross-clamping time was > 60 minutes, RIPC reduced troponin release at six hours (Z=2.84, P=0.005), 24 hours (Z=2.64, P=0.008), and 48 hours (Z=2.87, P=0.004) postoperatively. Conclusion: In cardiac surgery patients who are not taking sulfonylureas, RIPC can reduce troponin release at six and 48 hours postoperatively; hence, RIPC may serve significant benefits in certain cardiac surgery patients.

A Clinical Nomogram Based on the Triglyceride-Glucose Index to Predict Contrast-Induced Acute Kidney Injury after Percutaneous Intervention in Patients with Acute Coronary Syndrome with Diabetes Mellitus.

The aim of the study was to investigate the factors influencing contrast-induced acute kidney injury (CI-AKI) after percutaneous intervention (PCI) in patients with acute coronary syndrome (ACS) with diabetes mellitus (DM). A total of 1073 patients with ACS combined with DM who underwent PCI at the Affiliated Hospital of Xuzhou Medical University were included in this study. We divided the patients into the CI-AKI and non-CI-AKI groups according to whether CI-AKI occurred or not. The patients were then randomly assigned to the training and validation sets at a proportion of 7 : 3. Based on the results of the LASSO regression and multivariate analyses, we determined that the subtypes of ACS, age, multivessel coronary artery disease, hyperuricemia, low-density lipoprotein cholesterol, triglyceride-glucose index, and estimated glomerular filtration rate were independent predictors on CI-AKI after PCI in patients with ACS combined with DM. Using the above indicators to develop the nomogram, the AUC-ROC of the training and validation sets were calculated to be 0.811 (95% confidence interval (CI): 0.766-0.844) and 0.773 (95% CI: 0.712-0.829), respectively, indicating high prediction efficiency. After verification by the Bootstrap internal verification, we found that the calibration curves showed good agreement between the nomogram predicted and observed values. And the DCA results showed that the nomogram had a high clinical application. In conclusion, we constructed and validated the nomogram to predict CI-AKI risk after PCI in patients with ACS and DM. The model can provide a scientific reference for predicting the occurrence of CI-AKI and improving the prognosis of patients.

Novel grading system for ischemia‒reperfusion injury manifestations in patients with acute ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.

To establish a simple myocardial ischemia‒reperfusion injury (MIRI) manifestation grading system based on clinical manifestations and coronary angiography during primary percutaneous coronary intervention (PPCI). All STEMI patients treated with PPCI from June 2018 to November 2019 were included. According to the MIRI manifestation grade, patients were divided into four grades (I-IV). Laboratory and clinical indicators of the patients and the occurrence of major adverse cardiac events (MACEs) within one year of follow-up were analyzed. A total of 300 patients were included. The higher the MIRI manifestation grade, the lower was the high-density lipoprotein cholesterol (HDL-C); the higher were the C-reactive protein (CRP), lipoprotein(a) [LP(a)], and peak levels of high-sensitivity troponin T (hs-cTnT), creatine kinase (CK-MB), and N-terminal pro-B-type natriuretic peptide (NT-proBNP); and the higher were the proportions of right coronary artery (RCA) and multivessel lesions (P < 0.05). The left ventricular end-diastolic dimension (LVEDD) and E/e' values of patients with higher grades were significantly increased, while the LVEF, left ventricular short-axis functional shortening (LVFS) and E/A values were significantly decreased (P < 0.05). The one-year cumulative incidence of major adverse cardiac events (MACEs) in patients with grade I-IV disease was 7.7% vs. 26.9% vs. 48.4% vs. 93.3%, respectively, P < 0.05. The higher the MIRI manifestation grade, the more obvious is the impact on diastolic and systolic function and the higher is the cumulative incidence of MACEs within one year, especially in patients with multivessel disease, low HDL-C, high CRP, high LP(a) levels, and the RCA as the infarction-related artery.

Development and Validation of a Nomogram Model for Predicting the Risk of Readmission in Patients with Heart Failure with Reduced Ejection Fraction within 1 Year.

The high incidence of readmission for patients with reduced ejection fraction heart failure (HFrEF) can seriously affect the prognosis. In this study, we aimed to build a simple predictive model to predict the risk of heart failure (HF) readmission in patients with HFrEF within one year of discharge from the hospital. This retrospective study enrolled patients with HFrEF evaluated in the Heart Failure Center of the Affiliated Hospital of Xuzhou Medical University from January 2018 to December 2020. The patients were allocated into the readmission or nonreadmission group, according to whether HF readmission occurred within 1 year of hospital discharge. Subsequently, all patients were randomly divided into training and validation sets in a 7 : 3 ratio. A nomogram was established according to the results of univariate and multivariate logistic regression analysis. Finally, the area under the receiver operating characteristic curve (AUC-ROC), calibration plot, and decision curve analysis (DCA) were used to validate the nomogram. Independent risk factors for HF readmission of patients with HFrEF within 1 year of hospital discharge were as follows: age, body mass index, systolic blood pressure, diabetes mellitus, left ventricular ejection fraction, and angiotensin receptor-neprilysin inhibitors. The AUC-ROC of the training and validation sets were 0.833 (95% confidence interval (CI): 0.793-0.866) and 0.794 (95% CI: 0.727-0.852), respectively, which have an excellent distinguishing ability. The predicted and observed values of the calibration curve also showed good consistency. DCA also confirmed that the nomogram had good clinical value. In conclusion, we constructed an accurate and straightforward nomogram model for predicting the 1-year HF readmission risk in patients with HFrEF. This nomogram can guide early clinical intervention and improve patient prognosis.

Estrogen inhibits endoplasmic reticulum stress and ameliorates myocardial ischemia/reperfusion injury in rats by upregulating SERCA2a.

BACKGROUND: The incidence of coronary heart disease (CHD) in premenopausal women is significantly lower than that of men of the same age, suggesting protective roles of estrogen for the cardiovascular system against CHD. This study aimed to confirm the protective effect of estrogen on myocardium during myocardial ischemia/reperfusion (MI/R) injury and explore the underlying mechanisms. METHODS: Neonatal rat cardiomyocytes and Sprague-Dawley rats were used in this study. Different groups were treated by bilateral ovariectomy, 17ß-estradiol (E2), adenoviral infection, or siRNA transfection. The expression of sarcoplasmic reticulum Ca2+ ATPase pump (SERCA2a) and endoplasmic reticulum (ER) stress-related proteins were measured in each group to examine the effect of different E2 levels and determine the relationship between SERCA2a and ER stress. The cell apoptosis, myocardial infarction size, levels of apoptosis and serum cardiac troponin I, ejection fraction, calcium transient, and morphology changes of the myocardium and ER were examined to verify the effects of E2 on the myocardium. RESULTS: Bilateral ovariectomy resulted in reduced SERCA2a levels and more severe MI/R injury. E2 treatment increased SERCA2a expression. Both E2 treatment and exogenous SERCA2a overexpression decreased levels of ER stress-related proteins and alleviated myocardial damage. In contrast, SERCA2a knockdown exacerbated ER stress and myocardial damage. Addition of E2 after SERCA2a knockdown did not effectively inhibit ER stress or reduce myocardial injury. CONCLUSIONS: Our data demonstrate that estrogen inhibits ER stress and attenuates MI/R injury by upregulating SERCA2a. These results provide a new potential target for therapeutic intervention and drug discovery in CHD. Video Abstract.

Post-PCI quantitative flow ratio predicts 3-year outcome after rotational atherectomy in patients with heavily calcified lesions.

BACKGROUND: The study sought to investigate the clinical predictive value of quantitative flow ratio (QFR) for the long-term outcome in patients with heavily calcified lesions who underwent percutaneous coronary intervention (PCI) following rotational atherectomy (RA). METHODS: In this retrospective study, 393 consecutive patients from 2009 to 2017 were enrolled. The QFR of the entire target vessel (QFRv) and the QFR of the stent plus 5 mm proximally and distally (in-segment) (QFRi) were measured. The primary endpoint was target lesion failure (TLF), including target lesion-cardiac death (TL-CD), target lesion-myocardial infarction (TL-MI), and clinically driven-target lesion revascularization (CD-TLR). RESULTS: A total of 224 patients with 224 calcified lesions completed the clinical follow-up, and 52 patients had TLF. There was no significant difference in QFRv post-PCI between non-TLF and TLF groups (p > .05). However, QFRi post PCI was significantly higher in the non-TLF group than in the TLF group. Multivariate Cox regression showed that QFRi post-PCI was an excellent predictor of TLF after a 3-year follow-up (HR 1.7E-8 [5.3E-11 -5.6E-6 ]; p < .01). Furthermore, receiver-operating characteristic curve analysis demonstrated that the optimal cutoff value of QFRi for predicting the long-term TLF was 0.94 (area under the curve: 0.826, 95% confidence interval: 0.756-0.895; sensitivity: 89.5%, specificity: 69.2%; p < .01). The QFRi ≤ 0.94 post-PCI was negatively associated with TLF, including TL-CD, TL-MI, and CD-TLR (p < .01). CONCLUSIONS: QFRi post-PCI showed a high predictive value for TLF for during a 3-year follow-up in patients who underwent PCI following RA; specifically, lower QFRi values post-PCI were associated with worse TLF.

Identification of Differentially Expressed Genes and Pathways in Human Atrial Fibrillation by Bioinformatics Analysis.

INTRODUCTION: Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, but the molecular mechanisms underlying AF are not known. We aimed to identify the pivotal genes and pathways involved in AF pathogenesis because they could become potential biomarkers and therapeutic targets of AF. METHODS: The microarray datasets of GSE31821 and GSE41177 were downloaded from the Gene Expression Omnibus database. After combining the two datasets, differentially expressed genes (DEGs) were screened by the Limma package. MicroRNAs (miRNAs) confirmed experimentally to have an interaction with AF were screened through the miRTarBase database. Target genes of miRNAs were predicted using the miRNet database, and the intersection between DEGs and target genes of miRNAs, which were defined as common genes (CGs), were analyzed. Functional and pathway-enrichment analyses of DEGs and CGs were performed using the databases DAVID and KOBAS. Protein-protein interaction (PPI) network, miRNA- messenger(m) RNA network, and drug-gene network was visualized. Finally, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to validate the expression of hub genes in the miRNA-mRNA network. RESULTS: Thirty-three CGs were acquired from the intersection of 65 DEGs from the integrated dataset and 9777 target genes of miRNAs. Fifteen "hub" genes were selected from the PPI network, and the miRNA-mRNA network, including 82 miRNAs and 9 target mRNAs, was constructed. Furthermore, with the validation by RT-qPCR, macrophage migration inhibitory factor (MIF), MYC proto-oncogene, bHLH transcription factor (MYC), inhibitor of differentiation 1 (ID1), and C-X-C Motif Chemokine Receptor 4 (CXCR4) were upregulated and superoxide Dismutase 2 (SOD2) was downregulated in patients with AF compared with healthy controls. We also found MIF, MYC, and ID1 were enriched in the transforming growth factor (TGF)-ß and Hippo signaling pathway. CONCLUSION: We identified several pivotal genes and pathways involved in AF pathogenesis. MIF, MYC, and ID1 might participate in AF progression through the TGF-ß and Hippo signaling pathways. Our study provided new insights into the mechanisms of action of AF.

Prevalence of cardiovascular diseases in relation to total bone mineral density and prevalent fractures: A population-based cross-sectional study.

BACKGROUND AND AIM: We aimed to explore the relationship between total BMD and prevalent fractures and the risk of CVD in a female population in the United States (US). METHODS AND RESULTS: We undertook cross-sectional analyses of a female population participating in the US National Health and Nutrition Examination Survey (NHANES). Generalized linear models and restricted cubic spline curves were used to examine the association between total BMD and CVD. Subgroup analyses were also undertaken. A total of 13,707 women were enrolled. The restricted cubic spline curve revealed a linear and negative association between total BMD and CVD. The inflection point for the curve was identified at total BMD = 1.085 g/cm2. A negative relationship between total BMD and the prevalence of individual CVDs (angina and stroke) was noted (P < 0.05). In subgroup analyses stratified by race/ethnicity, hypertension, diabetes mellitus, and physical activity, a negative association existed in women who were non-Hispanic White, without hypertension, without diabetes mellitus, and who never participated in physical activity, respectively. In subgroup analyses stratified by age, this association also differed based on age. In addition, participants without history of fracture had significant lower probability of experiencing individual CVDs (angina pectoris, heart attack, and stroke) compared with those with history of fracture. CONCLUSIONS: We revealed a reduced prevalence of CVD associated with increased total BMD in a female population in the US. CVD risk decreased significantly if total BMD >1.085 g/cm2. Additionally, fracture-free individuals had much reduced odds of developing CVD.

Efficacy and Safety of Lipid-Lowering Drugs of Different Intensity on Clinical Outcomes: A Systematic Review and Network Meta-Analysis.

There have been many meta-analyses for statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) to evaluate clinical outcomes, but the efficacy and safety of different intensity of these three drugs on clinical outcomes was absent. PCSK9i, ezetimibe, and statins were divided into seven interventions as follows: including PCSK9i + high-intensity statins (P9i+HT), PCSK9i + moderate-intensity statins (P9i+MT), ezetimibe + high-intensity statins (Eze+HT), ezetimibe + moderate-intensity statins (Eze+MT), high-intensity statins (HT), moderate-intensity statins (MT), and low-intensity statins (LT). The risk ratios (RR) and 95% confidence intervals (CI) were calculated to evaluate the clinical outcomes in all randomized controlled trials included. In traditional meta-analysis, the more intensive treatment had a lower risk of all-cause mortality (RR 0.91, 95% CI 0.88-0.95), cardiovascular mortality (RR 0.89, 95% CI 0.86-0.92), myocardial infarction (RR 0.79, 95% CI 0.77-0.81), coronary revascularization (RR 0.80, 95% CI 0.76-0.84), and cerebrovascular events (RR 0.84, 95% CI 0.80-0.88) compared with the less intensive treatment. However, the more intensive treatment had a higher risk of new-onset diabetes (RR 1.08, 95% CI 1.04-1.12). The network meta-analysis demonstrated that P9i+HT, P9i+MT, HT, and MT were significantly associated with a risk reduction in coronary revascularization and cerebrovascular events compared with PLBO. LT could effectively reduce the risk of cardiovascular mortality (RR 0.71, 95% CI 0.54-0.92), MI (RR 0.67, 95% CI 0.54-0.82), and coronary revascularization (RR 0.77, 95% CI 0.65-0.91) compared with PLBO. P9i+HT was superior to HT in reducing the risk of MI (RR 0.78, 95% CI 0.68-0.90), coronary revascularization (RR 0.84, 95% CI 0.73-0.96), and cerebrovascular events (RR 0.78, 95% CI 0.64-0.95). However, compared with PLBO, P9i+HT, HT, and MT could increase the risk of new-onset diabetes (RR 1.23, 95% CI 1.11-1.37; RR 1.23, 95% CI 1.14-1.33; RR 1.09, 95% CI 1.02-1.15, respectively). In conclusion, PCSK9i added to background statins may be recommended as preferred lipid-lowering therapy, and did not increase the additional risk of new-onset diabetes. The safety and efficacy of ezetimibe was not superior to that of statins. LT can be recommended as the initial therapy.

MicroRNA-146a Serves as a Biomarker for Adverse Prognosis of ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: This study is aimed at exploring the underlying molecular mechanisms of ST-segment elevation myocardial infarction (STEMI) and provides potential clinical prognostic biomarkers for STEMI. METHODS: The GSE60993 dataset was downloaded from the GEO database, and the differentially expressed genes (DEGs) between STEMI and control groups were screened. Enrichment analysis of the DEGs was subsequently performed using the DAVID database. A protein-protein interaction network was constructed, and hub genes were identified. The hub genes in patients were then validated by quantitative reverse transcription-PCR. Furthermore, hub gene-miRNA interactions were evaluated using the miRTarBase database. Finally, patient data on classical cardiovascular risk factors were collected, and plasma microRNA-146a (miR-146a) levels were detected. An individualized nomogram was constructed based on multivariate Cox regression analysis. RESULTS: A total of 239 DEGs were identified between the STEMI and control groups. Expression of S100A12 and miR-146a was significantly upregulated in STEMI samples compared with controls. STEMI patients with high levels of miR-146a had a higher risk of major adverse cardiovascular events (MACEs) than those with low levels of miR-146a (log-rank P = 0.034). Multivariate Cox regression analysis identified five statistically significant variables, including age, hypertension, diabetes mellitus, white blood cells, and miR-146a. A nomogram was constructed to estimate the likelihood of a MACE at one, two, and three years after STEMI. CONCLUSION: The incidence of MACEs in STEMI patients expressing high levels of miR-146a was significantly greater than in those expressing low levels. MicroRNA-146a can serve as a biomarker for adverse prognosis of STEMI and might function in its pathogenesis by targeting S100A12, which may exert its role via an inflammatory response. In addition, our study presents a valid and practical model to assess the probability of MACEs within three years of STEMI.

The association between manganese exposure with cardiovascular disease in older adults: NHANES 2011-2018.

The aim of the current study was to explore possible connections between manganese exposure and the prevalence of cardiovascular disease (CVD) in older US adults. The relationship between serum manganese levels and CVD was explored in 2427 people aged 60 years and over using data from the National Health and Nutrition Examination Survey (NHANES) (2011-2018). Multivariate linear regression analysis was performed to investigate associations between CVD risk factors and serum manganese concentration. The relationship between manganese levels and the prevalence of CVD was probed using generalized linear models and restricted cubic spline curves. Stratified subgroup analysis was subsequently constructed to rule out spurious interactions between variables and manganese. Compared with the lowest quartile, the modified odds ratios (ORs) with 95% confidence intervals (CIs) for CVD prevalence across the manganese quartiles were 0.71 (OR: 0.51; CI: 1.00), 0.70 (0.50, 0.99), and 0.49 (0.34, 0.72). In the full adjusted model, a prominent negative relationship was observed between serum manganese concentration and CVD. A restricted cubic spline curve was used to show a nonlinear negative relationship between manganese concentration and CVD. In summary, manganese levels are negatively correlated with the risk of CVD in a nation-wide study of older US adults.

Development and Validation of a Risk Nomogram Model for Predicting Revascularization After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome.

OBJECTIVE: Percutaneous coronary intervention (PCI) is one of the most effective treatments for acute coronary syndrome (ACS). However, the need for postoperative revascularization remains a major problem in PCI. This study was to develop and validate a nomogram for prediction of revascularization after PCI in patients with ACS. METHODS: A retrospective observational study was conducted using data from 1083 patients who underwent PCI (≥6 months) at a single center from June 2013 to December 2019. They were divided into training (70%; n = 758) and validation (30%; n = 325) sets. Multivariate logistic regression analysis was used to establish a predictive model represented by a nomogram. The nomogram was developed and evaluated based on discrimination, calibration, and clinical efficacy using the concordance statistic (C-statistic), calibration plot and decision curve analysis (DCA), respectively. RESULTS: The nomogram was comprised of ten variables: follow-up time (odds ratio (OR): 1.01; 95% confidence interval (CI): 1.00-1.03), history of diabetes mellitus (OR: 1.83; 95% CI: 1.25-2.69), serum creatinine level on admission (OR: 0.99; 95% CI: 0.98-1.00), serum uric acid level on admission (OR: 1.005; 95% CI: 1.002-1.007), lipoprotein-a level on admission (OR: 1.0021; 95% CI: 1.0013-1.0029), low density lipoprotein cholesterol level on re-admission (OR: 1.33; 95% CI: 0.10-0.47), the presence of chronic total occlusion (OR: 3.30; 95% CI: 1.93-5.80), the presence of multivessel disease (OR: 4.48; 95% CI: 2.85-7.28), the presence of calcified lesions (OR: 1.63; 95% CI: 1.11-2.39), and the presence of bifurcation lesions (OR: 1.82; 95% CI: 1.20-2.77). The area under the receiver operating characteristic curve values for the training and validation sets were 0.765 (95% CI: 0.732-0.799) and 0.791 (95% CI: 0.742-0.830), respectively. The calibration plots showed good agreement between prediction and observation in both the training and validation sets. DCA also demonstrated that the nomogram was clinically useful. CONCLUSION: We developed an easy-to-use nomogram model to predict the risk of revascularization after PCI in patients with ACS. The nomogram may provide useful assessment of risk for subsequent treatment of ACS patients undergoing PCI.