Inflammatory biomarkers, angiogenesis and lymphangiogenesis in epicardial adipose tissue correlate with coronary artery disease.

In this study, we explored the relationship between inflammatory adipokine levels and coronary artery disease (CAD). We collected subcutaneous adipose tissues(SAT), pericardial adipose tissues(PAT), and epicardial adipose tissues (EAT) and serum samples from 26 inpatients with CAD undergone coronary artery bypass grafting and 20 control inpatients without CAD. Serum inflammatory adipokines were measured by ELISA. Quantitative real-time PCR and western blot were used to measure gene and protein expression. Adipocyte morphology was assessed by H&E staining. Immunohistochemistry and immunofluorescence were used to measure endothelial and inflammatory markers. Serum pro- and anti-inflammatory adipokine levels were higher and lower, respectively, in the CAD group than those in the control group (P < 0.05). In CAD, the pro-inflammatory adipokine levels via ELISA in EAT and PAT were elevated. Pro-inflammatory adipokine mRNA expression was increased, while anti-inflammatory adipokine mRNA expression decreased, in CAD relative to NCAD in EAT and PAT rather than SAT. In EAT, adipocyte area and macrophage-specific staining were lower, while lymphatic vessel marker expression was higher in CAD. Additionally, the endothelial marker expression in EAT was higher than PAT in CAD. The three tissue types had different blood vessel amounts in CAD. The regulation and imbalance expression of the novel biomarkers, including inflammatory adipokine, macrophage infiltration, angiogenesis, and lymphangiogenesis in EAT and PAT, may be related to the pathogenesis of CAD. The serum levels of inflammatory adipokines may correlate to CAD, which requires large sample size studies to get further validation before clinic practice.

Associations between serum electrolyte and short-term outcomes in patients with acute decompensated heart failure.

INTRODUCTION: There is a dearth of comprehensive studies on the association between serum electrolyte and adverse short-term prognosis of Chinese patients with acute decompensated heart failure (ADHF). PATIENTS AND METHODS: A total of 5166 patients with ADHF were divided into four serum electrolyte-related study populations (potassium (n = 5145), sodium (n = 5135), chloride (n = 4966), serum total calcium (STC) (n = 4143)) under corresponding exclusions. Different logistic regression models were utilized to gauge the association between these electrolytes or the number of electrolyte abnormalities and the risk of a composite of all-cause mortality or 30-day heart failure (HF) readmission. RESULTS: In multivariable adjusted analysis, patients with potassium below 3.5 mmol/L (odds ratios (ORs) 1.45; 95% confidence interval (CI):1.07-1.95), 4.01-4.50 mmol/L (OR: 1.29, CI: 1.02-1.62), 4.51-5.00 mmol/L (OR: 1.43, CI: 1.08-1.90) and above 5.00 mmol/L (OR: 1.74, CI: 1.21-2.51) had an increased risk of outcome when compared with potassium at 3.50-4.00 mmol/L. Sodium levels were inversely related to the risk of a composite outcome (<130 mmol/L: OR: 2.73 (95% CI, 1.81-4.12); 130-134 mmol/L: OR, 1.97 (CI, 1.45-2.68); 135-140 mmol/L: OR, 1.45 (CI, 1.17-1.81); p for trend < 0.001) in comparison with sodium at 141-145 mmol/L. Chloride < 95 mmol/L corresponded to a higher risk of a composite outcome with an OR of 1.65 (95% CI, 1.16-2.37) in contrast to chloride levels at 101-105 mmol/L. In addition, the adjusted ORs (95% CI) for a composite outcome comparing the STC < 2.00 and 2.00-2.24 vs. 2.25-2.58 mmol/L were 0.98 (0.69-1.43) and 1.13 (0.89-1.44), respectively. Besides that, the number of electrolyte abnormalities was positively related to the risk of a composite outcome (N = 1, OR 1.40, 95% CI: 1.13-1.73; N = 2, OR 2.51, 95% CI: 1.85-3.42; N = 3, OR 2.47, 95% CI: 1.45-4.19; p for trend < 0.001) in comparison with N = 0. CONCLUSIONS: A deviation of potassium levels from 3.50 to 4.00 mmol/L, lower sodium levels and hypochloremia were associated with poorer short-term prognosis of ADHF. Furthermore, the number of electrolyte abnormalities positively correlated with adverse short-term prognosis of patients with ADHF. Key MessagesADHF patients with baseline serum potassium at first half part of normal range (3.50-4.00 mmol/L) may herald the lowest risk of recent cardiovascular events.Serum sodium and chloride levels exhibit discrepancies in terms of risk of short-term adverse events of ADHF patients.The number of electrolyte abnormalities is a significant predictor of poor short-term prognosis in patients with ADHF. CLINICAL TRIAL REGISTRATION URL: http://www.chictr.org.cn/showproj.aspx?proj=23139. Unique identifier: ChiCTR-POC-17014020.

Correlation between serum Dickkopf-1 (DKK1) levels and coronary artery stenosis.

BACKGROUND AND AIMS: To study the correlation between the level of serum Dickkopf-1 (DKK1) and the degree of coronary artery stenosis in patients with coronary atherosclerotic heart disease. METHODS AND RESULTS: In 2018, general data and biochemical indexes of 311 patients who underwent coronary angiography were recorded. Before procedure, arterial blood was drawn and the concentrations of DKK1, retinol binding protein 4 (RBP4), plasminogen activator inhibitor (PAI-1) were measured. Based on coronary angiography results, subjects were divided into a coronary heart disease (CHD) group; and a non-coronary heart disease (non-CHD)group. The CHD group was divided into three subgroups: the low Gensini score; the middle Gensini score; and the high Gensini score subgroups. Compared with those of the non-CHD group, DKK1, RBP4 and PAI-1 of the CHD group were significantly higher, while the OC was lower. DKK1,RBP4 and PAI-1 levels of the middle and high Gensini subgroups were significantly higher, compared with that of the low Gensini subgroup. Differences between osteocalcin (OC), beta-isomerized C-terminal telopeptidase (ß-CTX), and 25(OH)2D3 of the three subgroups were not significant. Correlation between DKK1 and the inflammatory factors, RBP4 and PAI-1, was positive. Correlation between DKK1 and ß - CTX, 25(OH)2D3 and OC was not significant. DKK1 was a risk factor for CHD. The degree of coronary artery stenosis was related to DKK1 concentration. CONCLUSIONS: Serum DKK1 levels in coronary heart disease patients were significantly higher, and positively correlated with the degree of coronary artery stenosis. DKK1 level is an independent risk factor for coronary heart disease.

miR-195-3p/BDNF axis regulates hypoxic injury by targeting P-ERK1/2 expression.

OBJECTIVES: Coronary heart disease (CHD) is the most common heart disease and the leading cause of cardiovascular deaths worldwide. Decreased endothelial cell (EC) proliferation, increased apoptosis, inflammation, and vascular dysfunction are considered vital factors in CHD. In this study, we aimed to determine the expression and role of microRNA-195-3p and brain-derived neurotrophic factor (BDNF) in hypoxic-treated human umbilical vein endothelial cells (HUVECs). MEASURES: We induced hypoxia in HUVECs using the "anaerobic tank method." RESULTS: We found that the levels of microRNA-195-3p and BDNF were upregulated and apoptosis was increased. Furthermore, we found that BDNF/P-ERK1/2 regulated the expression of the mitochondrial apoptosis pathway proteins Bcl-2/BAX, which was downregulated under hypoxic conditions. Finally, the microRNA-195-3p inhibitor downregulated BDNF and P-ERK1/2, upregulated the Bcl-2/BAX axis, and partially reversed the effects of hypoxic-induced injury in HUVECs. CONCLUSIONS: Therapeutic intervention using the microRNA-195-3p/BDNF/P-ERK1/2/Bcl-2/BAX axis could maintain EC function under hypoxic conditions, improve cell activity, and serve as a new treatment strategy for CHDs.

Validation and derivation of short-term prognostic risk score in acute decompensated heart failure in China.

BACKGROUND: Few prognostic risk scores (PRSs) have been routinely used in acute decompensated heart failure (ADHF). We, therefore, externally validated three published PRSs (3A3B, AHEAD, and OPTIME-CHF) and derived a new PRS to predict the short-term prognosis in ADHF. METHODS: A total of 4550 patients from the Heb-ADHF registry in China were randomly divided into the derivation and validation cohorts (3:2). Discrimination of each PRS was assessed by the area under the receiver operating characteristic curve (AUROC). Logistic regression was exploited to select the predictors and create the new PRS. The Hosmer-Lemeshow goodness-of-fit test was used to assess the calibration of the new PRS. RESULTS: The AUROCs of the 3A3B, AHEAD, and OPTIME-CHF score in the derivation cohort were 0.55 (95% CI 0.53-0.57), 0.54 (95% CI 0.53-0.56), and 0.56 (95% CI 0.54-0.57), respectively. After logistic regression analysis, the new PRS computed as 1 × (diastolic blood pressure < 80 mmHg) + 2 × (lymphocyte > 1.11 × 109/L) + 1 × (creatinine > 80 µmol/L) + 2 × (blood urea nitrogen > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used), with a better AUROC of 0.67 (95% CI 0.64-0.70) and a good calibration (Hosmer-Lemeshow χ2 = 3.366, P = 0.186). The results in validation cohort verified these findings. CONCLUSIONS: The short-term prognostic values of 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients were all poor, while the new PRS exhibited potential predictive ability. We demonstrated the QRS fraction of electrocardiogram as a novel predictor for the short-term outcomes of ADHF for the first time. Our findings might help to recognize high-risk ADHF patients.

MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression.

Cardiac hypertrophy is a common pathological process of various cardiovascular diseases, which is often accompanied with structural and electrical remodeling, and can even lead to sudden cardiac death. However, its molecular mechanism still remains largely unknown. Here, we induced cardiomyocyte hypertrophy by angiotensin II (Ang II), and found that miR-27a-3p and hypertrophy-related genes were up-regulated. Further studies showed that miR-27a-3p-inhibitor can alleviate myocardial hypertrophy and electrical remodeling. Moreover, luciferase assay confirmed that miR-27a-3p could regulate the expression of downstream Hoxa10 at the transcriptional level by targeting at its 3'UTR. At the same time, the protein expression of Hoxa10 was significantly reduced in Ang II-treated cardiomyocytes. Furthermore, overexpression of Hoxa10 can reverse myocardial hypertrophy and electrical remodeling induced by Ang II in cardiomyocytes. Finally, we found that Hoxa10 positively regulated the expression of potassium channel protein Kv4.3 which was down-regulated in hypertrophic cardiomyocytes. Taken together, our results revealed miR-27a-3p/Hoxa10/Kv4.3 axis as a new mechanism of Ang II-induced cardiomyocyte hypertrophy, which provided a new target for clinical prevention and treatment of cardiac hypertrophy and heart failure.

Prognostic value of peripheral blood inflammatory cell subsets in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

OBJECTIVE: This study aimed to investigate the predictive value of inflammatory cells in peripheral blood on the prognosis of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: Patients (n=1558) were consecutively enrolled and the median follow-up was 1142 days. Patients were divided into the major adverse cardiac events (MACE) 1 group (n=63) (all-cause mortality [n=58] and rehospitalization for severe heart failure [n=5], no MACE1 group (n=1495), MACE2 group (n=38) (cardiac mortality [n=33] and rehospitalization for severe heart failure [n=5]), and no MACE2 group (n=1520). The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) were analyzed. RESULTS: The NLR, MLR, and PLR were higher in the MACE groups than in the no MACE groups. Different subsets of inflammatory cells had similar diagnostic values for MACE. Kaplan-Meier curves showed that the survival time gradually decreased with an increase in the degree of risk as determined by the NLR, MLR, and PLR. The risk of MACE was highest in the extremely high-risk group. CONCLUSION: Peripheral blood inflammatory cell subsets can predict MACE in patients with ACS undergoing PCI. These cell subsets could be important laboratory markers for the prognosis and clinical treatment of these patients.

Association between triglyceride glucose index and coronary artery disease with type 2 diabetes mellitus in middle-aged and elderly people.

ABSTRACT: This study aimed to investigate the correlation between triglyceride glucose (TyG) index and coronary artery disease (CAD) with type 2 diabetes mellitus (T2DM) and identify the risk associated TyG index in different subgroups.A total of 1665 eligible inpatients (CAD with T2DM group [n = 680], non-coronary artery disease without T2DM [n = 985]) were consecutively enrolled in this study. They were assigned into 4 subgroups: middle-aged, elderly, male, and female subgroups. Receiver operating characteristic curve diagnostic test and a logistic regression model was established to analyze the risk factors for CAD with T2DM.TyG index is an independent risk factor for patients with CAD with T2DM. The risk of increased TyG index is greater in the middle-aged and male subgroups than in the elderly and female subgroups, respectively (all P < .05). The specificity and the positive predictive value of the TyG index is greater than the sensitivity and the negative predictive value, respectively (all P < .05).Increased TyG index is a new independent risk factor for CAD with T2DM, and its risk is higher in the middle-aged and male subgroups than in the elderly and female subgroups, respectively. TyG index may be used as a clinical predictor of CAD with T2DM.

Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission.

In this study, we analyzed the role of mammalian STE20-like protein kinase 2 (Mst2), a serine-threonine protein kinase, in Lipopolysaccharides (LPS)-mediated inflammation and apoptosis in the H9C2 cardiomyocytes. Mst2 mRNA and protein levels were significantly upregulated in the LPS-treated H9C2 cardiomyocytes. LPS treatment induced expression of IL-2, IL-8, and MMP9 mRNA and proteins in the H9C2 cardiomyocytes, and this was accompanied by increased caspase-3/9 mediating H9C2 cardiomyocyte apoptosis. LPS treatment also increased mitochondrial reactive oxygen species (ROS) and the levels of antioxidant enzymes, such as GSH, SOD, and GPX, in the H9C2 cardiomyocytes. The LPS-treated H9C2 cardiomyocytes showed lower cellular ATP levels and mitochondrial state-3/4 respiration but increased mitochondrial fragmentation, including upregulation of the mitochondrial fission genes Drp1, Mff, and Fis1. LPS-induced inflammation, mitochondrial ROS, mitochondrial fission, and apoptosis were all significantly suppressed by pre-treating the H9C2 cardiomyocytes with the Mst2 inhibitor, XMU-MP1. However, the beneficial effects of Mst2 inhibition by XMU-MP1 were abolished by carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP), a potent activator of mitochondrial fission. These findings demonstrate that Mst2 mediates LPS-induced cardiomyocyte inflammation and apoptosis by increasing mitochondrial fission.

Association of lymphocyte-to-monocyte ratio with total coronary plaque burden in patients with coronary artery disease.

BACKGROUND: Lymphocyte-to-monocyte ratio (LMR) is involved in all stages of coronary atherosclerosis and related to coronary artery disease (CAD). However, the correlation between LMR and the coronary plaque burden of CAD is not clearly elucidated. Therefore, this study aimed to investigate their correlation in patients with CAD. METHODS: A total of 1953 consecutive eligible inpatients with suspected CAD were retrospectively included in this study. They were assigned into CAD (n = 564) and non-CAD groups (n = 1389). All patients underwent coronary computed tomographic angiography to evaluate coronary stenosis and coronary artery calcification (CAC). Spearman's tests were used to analyze the correlation between CAC score and LMR. Multivariate logistic regression models were set up to assess the risk factors of CAD. RESULTS: Patients with CAD had lower LMR value than patients without CAD (P = 0.001). LMR was negatively correlated with CAC score and was an independent risk factor of CAC score (P < 0.05). Multivariate logistic regression model showed that LMR ≤4.8 was a newly independent risk factor of CAD (all P < 0.05). Additionally, the new risk score model was compared with the Framingham model and showed that NRI was 4.9%, which proved that the new risk score model improved the prediction capability of CAD. CONCLUSION: LMR ≤4.8 is a new independent risk factor of CAD. LMR value was negatively correlated with CAC score and could be used as a new marker to evaluate the coronary plaque burden of CAD.

Association between new circulating proinflammatory and anti-inflammatory adipocytokines with coronary artery disease.

BACKGROUND: The aim of this study was to evaluate the diagnostic and risk predictive value of emerging proinflammatory and anti-inflammatory adipocytokines on coronary artery disease (CAD). PATIENTS AND METHODS: The study involved 259 inpatients suspected acute coronary syndrome who underwent coronary angiography. Demographic, clinical characteristics, and coronary artery stenosis rated by Gensini score were collected by cardiovascular doctors. The levels of serum inflammatory adipocytokines were evaluated by ELISA. The correlations of the cytokines with clinical parameters were assessed. Receiver operating characteristic curves were constructed for the diagnosis of CAD. RESULTS: The 259 inpatients were assigned to the CAD (n = 180) and control groups (n = 79). Compared with the control group, the CAD group displayed significantly higher serum levels of retinol-binding protein-4 (RBP4), pentraxin 3 (PTX3), galectin-3 (GAL-3), and plasminogen activator inhibitor (PAI-1), and significantly lower levels of netrin-1 (NTN1), interleukin-37 (IL-37), and adiponectin (ADP) (all P < 0.05). PAI-1 was significantly upregulated, and IL-37 and ADP were significantly downregulated in the three-vessels CAD subgroup compared to the one- and two-vessels CAD subgroups (P < 0.05). The RBP4, PTX3, GAL-3, PAI-1, and IL-37 inflammatory cytokines were significantly positively correlated with Gensini score, and ADP was negatively correlated (all P < 0.001). IL-37 was a more accurate anti-inflammatory biomarker than NTN1 and ADP. Combining cytokines significantly increased the sensitivity and specificity. CONCLUSION: The inflammatory adipocytokines GAL-3, RBP4, PTX3, NTN1, and IL-37 were more effective than the classical biomarkers PAI-1 and ADP in the diagnosis and risk assessment of CAD patients.

Tai Chi Exercise for the Quality of Life in a Perimenopausal Women Organization: A Systematic Review.

BACKGROUND: Improvement of the quality of life in perimenopausal women has recently become an important global health issue. Extensive research reports provide evidence of Tai Chi for the quality of life, but no systematic review has individually investigated Tai Chi as a main intervention on the quality of life in perimenopausal women. OBJECTIVE: To assess clinical evidence of Tai Chi for the quality of life in perimenopausal women. METHODS: Studies related to the effect of Tai Chi on the quality of life in perimenopausal women in the databases of China and abroad were searched. RevMan version 5.2 software was used, and the Medical Outcomes Study 36-item short form health survey (SF-36) and bone mineral density (BMD) were selected as evaluation indices. RESULTS: Five trials were included. The results of this study showed that Tai Chi had a significant effect on bodily pain, general health, vitality, mental health of SF-36, and the spine dimension of BMD, as supported by the following data: bodily pain (Standard Mean Difference [SMD] = -3.63; 95% confidence interval [CI] [-6.62, -0.64]; p = .02); general health (SMD = -5.08; 95% CI [-7.60, -2.56]; p < .0001); vitality (SMD = -5.67; 95% CI [-8.54, -2.81], p = .0001); mental health (SMD = -2.51; 95% CI [-4.82, -0.20], p = .03); and spine dimension of BMD (SMD = -0.06; 95% CI [-0.10, -0.01]; p = .01). However, Tai Chi had no effect on physical function, emotional health, social function, role-physical of SF-36, and the hip dimension of BMD, as supported by the following data: physical function (SMD = -1.79; 95% CI [-5.15, 1.57]; p = .30); emotional health (SMD = -2.90; 95% CI [-7.23, 1.43], p = .19]; social function (SMD = -2.23, 95% CI [-5.08, 0.61], p = .12; role-physical (SMD = - 1.18; 95% CI [-4.84, 2.47], p = .53; and hip dimension of BMD (SMD = -0.01; 95% CI [-0.03, 0.01]; p = .31). LINKING EVIDENCE TO ACTION: This systematic review found significant evidence for Tai Chi improving bodily pain, general health, vitality, mental health of SF-36, and the spine dimension of BMD in patients with perimenopausal syndrome. Findings suggest that Tai Chi might be recommended as effective and safe adjuvant treatment for patients with perimenopausal syndrome. More high-quality randomized controlled trials are urgently needed to confirm these results.

[Correlation between electrocardiogram, myocardial biomarkers and left ventricular dysfunction in acute anterior ST segment elevation myocardial infarction].

OBJECTIVE: To analyze the correlation between ST segment elevation, Q wave and peak biomarkers with left ventricular dysfunction in patients with acute anterior ST elevation myocardial infarction (STEMI). METHODS: A total of 138 consecutive inpatients with acute anterior STEMI, left anterior descending branch as the convict vessel, from January 2009 to January 2012 in our hospital were enrolled in this study. They were divided into reperfusion (n = 92) and non-reperfusion group(n = 46). Clinical data, electrocardiogram, peak biomarkers, type B natriuretic peptide (BNP) were collected by physicians and the patients were followed up three months. RESULTS: The sum of the ST segments elevation, Q waves and Q wave leads in anterior STEMI were positive correlation with the Killip grades, myocardium biomarkers, BNP and left ventricle end diastolic diameters (LVEDD) [γ, 0.52-0.75, P < 0.01], while negative correlation with left ventricle ejection fraction (LVEF) [γ, -0.63--0.95, P < 0.01]. The sum of R wave altitude was negative correlation with myocardium biomarkers, BNP and LVEDD in three months after the onset of STEMI [γ, -0.48--0.79, P < 0.01], while positive correlation with LVEF [γ, 0.73-0.82, P < 0.01]. BNP, one of the best markers of left heart dysfunction, was found to be strongly negative correlation with LVEF in acute stage and three months after the onset of STEMI [γ , -0.92, -0.80, P < 0.01]. CONCLUSION: There are close correlations between electrocardiogram, myocardial biomarkers and left ventricular dysfunction in acute anterior ST segment elevation myocardial infarction, which may be strong predictors for the short-term prognosis.