External validation of the SYNTAX score II 2020 in patients with chronic renal insufficiency.

BACKGROUND: The SYNTAX score Ⅱ 2020 (SSⅡ-2020) was created as a customized decision-making tool for individuals diagnosed with complex coronary artery disease (CAD). Nevertheless, there has been a scarcity of research investigating the long-term predictive significance of SSⅡ-2020 for patients with both CAD and chronic renal insufficiency (CRI) who undergo percutaneous coronary intervention (PCI). AIMS: We sought to showcase the prognostic capacity of SSII-2020 in evaluating long-term all-cause mortality (ACM) within this high-risk patient cohort. METHODS: A retrospective cohort comprising 1156 individuals diagnosed with CRI and exhibiting left main CAD, three-vessel CAD or both was included in this investigation. We categorized participants into three groups based on the optimal SSII-2020 threshold for predicting long-term ACM, determined using the X-tile software. RESULTS: At the median follow-up duration of 6.3 years, the ACM rates were determined to be 10% in the low, 17% in the moderate, and 28% in the high SSII-2020 groups (p < 0.001). Employing multivariate Cox regression analysis, it was observed that the high SSII-2020 group exhibited a 3.289-fold increased risk of ACM (95% confidence interval [CI]: 2.229-4.856, p < 0.001) compared with the low SSII-2020 group, whereas the high SSII-2020 group displayed a 1.757-fold (95% CI: 1.190-2.597, p = 0.005) in comparison to the median SSII-2020 groups. Compared with SSII, the SSII-2020 had an incremental value for predicting 7-year ACM (C-index: 0.662 vs. 0.534, p = 0.007; IDI: 0.016, p < 0.001). CONCLUSIONS: SSII-2020 enhances long-term ACM prediction, facilitates improved risk stratification, and improves clinical utility for PCI patients with complex CAD and CRI.

Prognostic impact of white blood cell counts on clinical outcomes in patients with chronic renal insufficiency undergoing percutaneous coronary intervention.

Objective: To determine whether the inclusion of white blood cell (WBC) counts in the SYNTAX score (SS) or SS II models could improve the models' performance for risk stratification in individuals with chronic renal insufficiency (CRI) following percutaneous coronary intervention (PCI). Methods: In total, 2,313 patients with CRI, who were subjected to PCI and had data available on in-hospital WBC (ih-WBC) counts, were recruited. Patients were divided into 3 groups as per their ih-WBC counts (low, medium, and high). The primary endpoints were all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints incorporated myocardial infarction, stroke, unplanned revascularization, and major adverse cardiovascular and cerebrovascular events (MACCEs). Results: During a median follow-up of 3 years, the high WBC group had the highest incidences of CM (2.4% vs. 2.1% vs. 6.7%; p < 0.001), ACM (6.3% vs. 4.1% vs. 8.2%; p < 0.001), unplanned revascularization (8.4% vs. 12.4% vs. 14.1%; p < 0.001), and MACCEs (19.3% vs. 23.0% vs. 29.2%; p < 0.001) among the three groups. Multivariable Cox regression analysis depicted that the risk of ACM and CM in the high WBC group was 2.577 (95% confidence interval [CI]: 1.504-4.415, p < 0.001) and 3.850 (95% CI: 1.835-8.080, p < 0.001) times that in the low WBC group after adjusting for other confounding factors. A combination of ih-WBC counts with SS or SS II significantly improved the risk assessment and prediction of ACM and CM. Conclusion: The ih-WBC counts was associated with the risk of occurrence of ACM, CM, unplanned revascularization, and MACCEs in individuals with CRI following PCI. It provides an incremental predictive value for the occurrence of ACM and CM when included in SS or SS II models.

The guiding value of hybrid resting full-cycle ratio and fractional flow reserve strategy for percutaneous coronary intervention in a Chinese real-world cohort with non-ST elevation acute coronary syndrome.

Objective: The study aimed to assess the correlation and agreement between resting full-cycle ratio (RFR) and fractional flow reserve (FFR), and evaluate the guiding value of a hybrid RFR-FFR strategy for percutaneous coronary intervention (PCI) in a Chinese real-world cohort with non-ST elevation acute coronary syndrome (NSTE-ACS). Materials and methods: A total of 109 patients with NSTE-ACS (149 diseased vessels), who underwent an invasive physiological assessment in Cangzhou Central Hospital, Hebei Medical University, were prospectively enrolled from September 2021 to May 2022. FFR ≤ 0.80 was used as the gold standard for coronary artery functional ischemia. We utilized the Pearson correlation and Bland-Altman analysis to assess the correlation and agreement between RFR and FFR. The diagnostic value of RFR predicting FFR ≤ 0.80 was evaluated in accordance with the receiver operating characteristic (ROC) curve. The hybrid RFR-FFR strategy, which was established according to determining the "gray zone" of RFR (FFR was further assessed using vasodilators only for diseased vessels in the "gray zone"), needed to afford over 95% global agreement with the FFR-only strategy. Results: Resting full-cycle ratio was significantly linearly linked with FFR (R 2 = 0.636, P < 0.001). The accuracy, specificity, and sensitivity for RFR ≤ 0.89 predicting FFR ≤ 0.80 were 81.2, 70.8, and 86.1%, respectively. The area under the ROC curve for RFR predicting FFR ≤ 0.80 was 0.881 (P < 0.001), and the cutoff value was 0.90. The "gray zone" of RFR was 0.85-0.93. The positive and negative predictive values of the hybrid RFR-FFR strategy were 0.95 and 0.93, respectively. The hybrid RFR-FFR strategy exhibited an agreement of 96.0% with FFR and obviated the need for a vasodilator by 60.4%. Conclusion: Resting full-cycle ratio and FFR have high correlation and consistency. The hybrid RFR-FFR strategy highlights considerably enhanced agreement with the FFR-only strategy, whilst making the requirement of vasodilator administration less than a half.

The Incremental Prognostic Value of the Clinical Residual SYNTAX Score for Patients With Chronic Renal Insufficiency Undergoing Percutaneous Coronary Intervention.

Background: The residual SYNTAX score (RSS) is considered a powerful prognostic indicator for determining a reasonable revascularization strategy in patients undergoing percutaneous coronary intervention (PCI), but the absence of clinical parameters is one of the limitations of RSS, especially in the chronic renal insufficiency (CRI) comorbidity setting. The present work aimed to investigate the incremental prognostic value of clinical residual SYNTAX score (CRSS) compared with RSS in CRI cases after PCI. Methods: Totally 2,468 consecutive CRI cases who underwent PCI from January 2014 to September 2017 were included in this retrospective analysis. CRSS was obtained by multiplying RSS by the modified ACEF score. Individuals with CRSS >0 were considered to have incomplete revascularization and stratified by CRSS tertiles, the remaining cases constituted the complete revascularization (CR) group. The outcomes between these groups were compared. Results: At a median follow-up of 3 years, compared with CR group, individuals with CRSS >12 showed elevated rates of all clinical outcomes, and those with CRSS ≤ 12 showed similar all-cause and cardiac mortality rates. In multivariable analysis, CRSS was a powerful independent predictive factor of all clinical outcomes. The net reclassification improvement levels of CRSS over RSS for all-cause and cardiac mortality rates were 10.3% (p = 0.007) and 16.4% (p < 0.001), respectively. Compared with RSS, CRSS markedly ameliorated all-cause and cardiac mortality risk stratification. Conclusions: Compared with RSS, CRSS has incremental predictability for long-term all-cause and cardiac mortality in CRI cases following PCI.

WITHDRAWN: Exosome-derived long non-coding RNA ZFAS1 controls cardiac fibrosis in chronic kidney disease.

This paper was originally published in Aging Advance Online Publications on February 26, 2021. In compliance with Aging's withdrawal policy, the paper was withdrawn in its entirety. It will not appear in Aging internal or any external indexes or archives.

Characterization of an Aging-Based Diagnostic Gene Signature and Molecular Subtypes With Diverse Immune Infiltrations in Atherosclerosis.

Objective: Advancing age is a major risk factor of atherosclerosis (AS). Nevertheless, the mechanism underlying this phenomenon remains indistinct. Herein, this study conducted a comprehensive analysis of the biological implications of aging-related genes in AS. Methods: Gene expression profiles of AS and non-AS samples were curated from the GEO project. Differential expression analysis was adopted for screening AS-specific aging-related genes. LASSO regression analysis was presented for constructing a diagnostic model, and the discriminatory capacity was evaluated with ROC curves. Through consensus clustering analysis, aging-based molecular subtypes were conducted. Immune levels were estimated based on the expression of HLAs, immune checkpoints, and immune cell infiltrations. Key genes were then identified via WGCNA. The effects of CEBPB knockdown on macrophage polarization were examined with western blotting and ELISA. Furthermore, macrophages were exposed to 100 mg/L ox-LDL for 48 h to induce macrophage foam cells. After silencing CEBPB, markers of cholesterol uptake, esterification and hydrolysis, and efflux were detected with western blotting. Results: This study identified 28 AS-specific aging-related genes. The aging-related gene signature was developed, which could accurately diagnose AS in both the GSE20129 (AUC = 0.898) and GSE43292 (AUC = 0.685) datasets. Based on the expression profiling of AS-specific aging-related genes, two molecular subtypes were clustered, and with diverse immune infiltration features. The molecular subtype-relevant genes were obtained with WGCNA, which were markedly associated with immune activation. Silencing CEBPB triggered anti-inflammatory M2-like polarization and suppressed foam cell formation. Conclusion: Our findings suggest the critical implications of aging-related genes in diagnosing AS and modulating immune infiltrations.

miR-206 Inhibits Cell Proliferation and Extracellular Matrix Accumulation by Targeting Hypoxia-Inducible Factor 1-alpha (HIF-1α) in Mesangial Cells Treated with High Glucose.

BACKGROUND The goal of this study was to investigate the expression of miR-206 in human glomerular mesangial cells (hMCs) treated by exposure to high glucose (HG) levels, to assess the influence of miR-206 on the proliferation and extracellular matrix (ECM) deposition of hMCs, and to investigate the potential mechanisms of action. MATERIAL AND METHODS The level of miR-206 was detected by RT-qPCR. MTT assay and colony formation assay were used to assess hMCs cell proliferation ability. Western blotting was carried out to measure the expression of related proteins. Bioinformatics software (http://www.targetscan.org) was used to predict the potential target genes of miR-206, and dual-luciferase reporter assay was used to confirm this prediction. RESULTS Our results suggest that the level of miR-206 was downregulated in HG-treated hMCs. Cell proliferation was promoted in HG-induced hMCs, while this phenomenon was significantly reversed with miR-206 mimics. miR-206 mimics significantly enhanced p21 expression and decreased cyclin D1 and CDK2 expressions, but the opposite was found in HG-induced hMCs. Moreover, the level of ECM proteins was notably increased in hMCs treated with HG, which was also significantly reversed by miR-206 mimics. miR-206 inhibitor had the opposite effects. Furthermore, HIF-1alpha was found to be a direct target of miR-206, and was negatively regulated by miR-206 in hMCs. miR-206 can target HIF-1alpha to modulate cell proliferation and ECM accumulation. CONCLUSIONS Collectively, our results suggest that miR-206 plays a vital role in HG-treated hMCs through inhibiting cell proliferation and ECM accumulation, partly via targeting HIF-1alpha.

miR-125a-5p inhibits the expression of NLRP3 by targeting CCL4 in human vascular smooth muscle cells treated with ox-LDL.

Recent findings have revealed that aberrant miR-125a-5p expression is involved in the development of atherosclerosis. The present study aimed to investigate the precise mechanism of microRNA (miR)-125a-5p in atherosclerosis. Human vascular smooth muscle cells (HVSMCs) were treated with 20 µg/ml oxidized low-density lipoprotein (ox-LDL) for 24 h and were employed as in vitro models of atherosclerosis. Reverse transcription quantitative (RT-qPCR) assays were used to detect miR-125a-5p levels. Immunofluorescence analysis was conducted to assess α-smooth muscle actin (α-SMA) expression. Western blotting and RT-qPCR assays were performed to measure the expression levels of NACHT, LRR and PYD domains-containing protein 3 (NLRP3), apoptosis associated speck-like protein (ASC), caspase-1, active interleukin (IL)-1ß and C-C motif chemokine 4-like (CCL4). Furthermore, the association between miR-125a-5p and CCL4 was assessed using a double luciferase analysis. In addition, VSMCs were transfected with miR-125a-5p mimics (30 nM), miR-125a-5p inhibitor (100 nM) or small interfering RNA against CCL4 (si-CCL4, 50 pM), respectively to further investigate the function of miR-125a-5p in ox-LDL-treated HVSMCs. The present study found that the expression levels of miR-125a-5p were significantly downregulated in HVSMCs, whereas the expression levels of α-SMA, NLRP3, ASC, caspase-1, IL-1ß and CCL4 were markedly upregulated following ox-LDL treatment. Overexpression of miR-125a-5p in the absence of ox-LDL treatment decreased NLRP3, IL-1ß and CCL4 expression, whereas inhibition of miR-125a-5p exhibited the opposite effects. The results of double luciferase analysis confirmed that CCL4 was a direct target of miR-125a-5p. Moreover, transfection of si-CCL4 into HVSMCs significantly decreased the ox-LDL-induced expression of NLRP3, ASC, caspase-1 and IL-1ß proteins. Taken collectively, the results of the present study suggested that miR-125a-5p could negatively regulate the NLRP3 inflammasome by targeting CCL4 in ox-LDL-treated HVSMCs. The data provide new insight to the inhibition of atherosclerosis progression.

Non-high-density lipoprotein cholesterol and risk of cardiovascular disease in the general population and patients with type 2 diabetes: A systematic review and meta-analysis.

AIMS: To examine the relationship of non-high-density lipoprotein cholesterol (non-HDL-C) level with cardiovascular disease (CVD) risk in type 2 diabetes patients and the general population by conducting a meta-analysis. METHODS: We made a comprehensive literature search for relevant observational studies investigating the relationship of non-HDL-C level with CVD risk in the general population and type 2 diabetes patients using the PubMed and Embase databases. Pooled risk ratio (RR) with 95% confidence intervals (CI) was calculated for the highest versus the reference lower non-HDL-Cl. RESULTS: A total of 13 studies with 156,381 individuals were included. The pooled RR of CVD was 1.59 (95% CI 1.46-1.72) in the general population and 1.99 (95% CI 1.57-2.51) in type 2 diabetes patients. Subgroup analysis showed the similar effect of non-HDL-C on CVD risk between men (RR1.98; 95% CI 1.70-2.30) and women (RR 1.63; 95% CI 1.35-1.96). However, elevated non-HDL-C was not associated with higher risk of cardiovascular mortality in the general population (RR 1.64; 95% CI 0.96-2.80) and type 2 diabetes patients (RR 1.08; 95% CI 0.57-2.07). CONCLUSIONS: Elevated non-HDL-C level is associated with an increased risk of CVD in the general population and type 2 diabetes patients.

Association of early menopause with angiographically-derived SYNTAX score: Observational study.

Association of early menopause with increased risk of cardiovascular events has been confirmed in previous studies. SYNTAX score (SX-score) can comprehensively quantify severity of coronary artery disease (CAD) and predict the outcomes of patients with CAD. However, the association of early menopause with SX-score has never been reported.We prospectively included 1875 consecutive postmenopausal patients who underwent coronary angiography (CAG) and were angiographically diagnosed with CAD from January 2011 to December 2013. SX-score was calculated using the SX-score algorithm based on diagnostic angiogram. Ordinal logistic regression analysis was used to investigate the association between early menopause and SX-score.Patients with early menopause were more likely to have a history of hypertension, diabetes, hyperlipidemia, and less likely to smoking. Besides, they have higher fasting glucose, hemoglobin A1C (HbA1c), total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), and body mass index (BMI) compared with the patients without early menopause. Moreover, patients with early menopause have higher SX-score and multi-vessel diseases. Ordinal logistic regression analysis showed that age, hypertension, diabetes, and early menopause exerted independent influences on SX-score. The patients undergone oophorectomy, early menopause was highly associated with SX-score.Early menopause was an independent predictor of SX-score in postmenopausal patients with CAD.

Abnormal expression of miR­133a in patients with acute myocardial infarction following radical surgery for gastric cancer and the underlying mechanism.

The present study aimed to investigate the expression of microRNA (miR)­133a in patients with or without acute myocardial infarction (AMI) following radical surgery for gastric cancer, and to explore its underlying mechanisms. Blood samples were collected from patients with or without AMI in order to detect the expression levels of miR­133a and endothelial injury markers. In addition, an AMI rat model was established. Reverse transcription­quantitative polymerase chain reaction was used to detect the mRNA expression levels of miR­133a and B­cell lymphoma 2­like 1 (Bcl2l1). In addition, an ELISA assay was used for endothelial injury marker analysis. To investigate the effects of miR­133a on human umbilical vein endothelial cells (HUVECs), a miR­133a inhibitor was used. Cell proliferation and apoptosis were subsequently detected using an MTT assay and flow cytometry. Western blot analysis was also conducted to detect Bcl2l1 protein expression. The results suggested that patients with AMI exhibited significantly increased expression of endothelial injury markers (von Willebrand factor, heart­type fatty acid­binding protein and cardiac troponin I) and miR­133a in blood samples compared with patients without AMI. In addition, treatment with a miR­133a mimic was able to upregulate the expression of endothelial injury markers in an AMI rat model, whereas treatment with a miR­133a inhibitor had the opposite effect. Furthermore, cellular experiments indicated that a miR­133a inhibitor could promote HUVEC proliferation and reduce cell apoptosis. The present results also confirmed that miR­133a directly targets Bcl2l1 and negatively regulates Bcl2l1 expression. In conclusion, the results of the present study suggested that miR­133a was involved in the endothelial injury process after AMI by targeting Bcl2l1.

miRNA­145 inhibits myocardial infarction­induced apoptosis through autophagy via Akt3/mTOR signaling pathway in vitro and in vivo.

The present study investigated the effects of micro (mi)RNA­145 on acute myocardial infarction (AMI) and the potential underlying mechanism. A total of 6 AMI and 6 normal rat tissues were investigated for the present study. It was demonstrated that miRNA­145 expression was downregulated in the AMI rat model, compared with the control group. Downregulation of miRNA­145 increased cardiac cell apoptosis, suppressed phosphorylated (p)­RAC­Î³ serine/threonine­protein kinase (Akt3) and p­mechanistic target of rapamycin (mTOR) protein expression levels and suppressed autophagy in an in vitro model of AMI. However, overexpression of miRNA­145 decreased cardiac cell apoptosis, induced p­Akt3 and p­mTOR protein expression and promoted autophagy in the in vitro model of AMI. The inhibition of Akt3 (GSK2110183, 1 nM) decreased the effect of the miRNA­145 upregulation on cell apoptosis in the in vitro model of AMI. Chloroquine diphosphate (5 µM) inhibited the regulatory effect of miRNA­145 upregulation on autophagy to adjust cell apoptosis, in the in vitro model of AMI. The results of the present study demonstrate that miRNA­145 inhibits myocardial infarction­induced apoptosis via autophagy associated with the Akt3/mTOR signaling pathway in vivo and in vitro.

Weighted gene co­expression network analysis in identification of key genes and networks for ischemic­reperfusion remodeling myocardium.

Acute myocardial infarction induces ventricular remodeling, which is implicated in dilated heart and heart failure. The pathogenical mechanism of myocardium remodeling remains to be elucidated. The aim of the present study was to identify key genes and networks for myocardium remodeling following ischemia­reperfusion (IR). First, the mRNA expression data from the National Center for Biotechnology Information database were downloaded to identify differences in mRNA expression of the IR heart at days 2 and 7. Then, weighted gene co­expression network analysis, hierarchical clustering, protein­protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to identify key genes and networks for the heart remodeling process following IR. A total of 3,321 differentially expressed genes were identified during the heart remodeling process. A total of 6 modules were identified through gene co­expression network analysis. GO and KEGG analysis results suggested that each module represented a different biological function and was associated with different pathways. Finally, hub genes of each module were identified by PPI network construction. The present study revealed that heart remodeling following IR is a complicated process, involving extracellular matrix organization, neural development, apoptosis and energy metabolism. The dysregulated genes, including SRC proto­oncogene, non­receptor tyrosine kinase, discs large MAGUK scaffold protein 1, ATP citrate lyase, RAN, member RAS oncogene family, tumor protein p53, and polo like kinase 2, may be essential for heart remodeling following IR and may be used as potential targets for the inhibition of heart remodeling following acute myocardial infarction.

MicroRNA-24 inhibits the proliferation and migration of endothelial cells in patients with atherosclerosis by targeting importin-α3 and regulating inflammatory responses.

The aim of the present study was to measure the level of microRNA (miRNA or miR)-24 in the serum of patients with atherosclerosis and to investigate the effect of miR-24 on the expression of importin-α3 and tumor necrosis factor (TNF)-α, as well as the proliferation and migration of vascular endothelial cells. A total of 30 patients with atherosclerosis admitted to hospital between January and June 2016 were enrolled in the present study; 30 healthy subjects with a similar age range were enrolled as controls. Peripheral blood (10 ml) was collected from all participants. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-24 mimic using Lipofectamine 2000. TargetScan was used to elucidate whether importin-α3 (KPNA4) was a target gene of miR-24. Expression levels of miR-24 and mRNAs were measured using reverse transcription-quantitative polymerase chain reaction, and protein expression was determined using western blotting. Cell Counting Kit 8 assay was used to assess the proliferation of HUVECs, and a Transwell assay was performed to detect the migration of HUVECs. Expression of miR-24 in peripheral blood from patients with atherosclerosis was significantly lower when compared with healthy subjects (P<0.05). Overexpression of miR-24 was demonstrated to significantly inhibit the transcription and translation of the importin-α3 gene (P<0.05) and negatively regulate the expression of endothelial inflammatory factor TNF-α (P<0.05). Furthermore, overexpression of miR-24 significantly inhibited the proliferation and migration of HUVECs (P<0.05), and miR-24 knockdown significantly promoted these processes (P<0.05). The results of the present study suggest that miR-24 exerts its effect in atherosclerosis by blocking the nuclear factor-κB signaling pathway, regulating inflammation in endothelial cells, and inhibiting the proliferation and migration of vascular endothelial cells.

Correlation between genetic polymorphisms within the MAPK1/HIF-1/HO-1 signaling pathway and risk or prognosis of perimenopausal coronary artery disease.

BACKGROUND: Mitogen-activated protein kinase-1 (MAPK1), as well as its downstream factors of hypoxia-inducible factor-1 (HIF-1) and heme oxygenase-1 (HO-1), have been documented to be involved in modulating development of coronary artery disease (CAD). HYPOTHESIS: Genetic mutations within the MAPK1/HIF-1/HO-1 signaling pathway could alter the risk of perimenopausal CAD in Chinese patients. METHODS: Peripheral blood samples were gathered from 589 CAD patients and 860 healthy controls, and 12 potential single-nucleotide polymorphisms (SNPs) were obtained from HapMap database and previously published studies. Genotyping of SNPs was implemented with the TaqMan SNP Genotyping Assays. Odds ratios (OR) and 95% confidence intervals (CI) were utilized to evaluate the correlations between SNPs and CAD risk. RESULTS: Regarding MAPK1 , rs6928 (OR: 1.71, 95% CI: 1.47-1.98, P < 0.05), rs9340 (OR: 0.85, 95% CI: 0.73-0.99, P < 0.05), and rs11913721 (OR: 0.70, 95% CI: 0.52-0.95, P < 0.05) were remarkably associated with susceptibility to perimenopausal CAD. Of these, rs9340 and rs11913721 were also regarded as protective factors for perimenopausal CAD patients. Moreover, results of HIF-1 indicated noticeable correlations between combined SNPs of rs1087314 and rs2057482 and risk of perimenopausal CAD (OR: 1.24, 95% CI: 1.01-1.53, P < 0.05; and OR: 0.71, 95% CI: 0.55-0.91, P < 0.05, respectively). Nonetheless, rs2071746 in HO-1 was found to be only associated with perimenopausal CAD risk (OR: 0.67, 95% CI: 0.58-0.78, P < 0.05). CONCLUSIONS: The genetic mutations within MAPK1 (rs6928, rs9340, rs11913721), HIF-1 (rs1087314, rs2057482), and HO-1 (rs2071746) could alter susceptibility to perimenopausal CAD in this Chinese population.

Associations of proteins relevant to MAPK signaling pathway (p38MAPK-1,HIF-1 and HO-1) with coronary lesion characteristics and prognosis of peri-menopausal women.

BACKGROUND: The present study was intended to explore whether three proteins within MAPK signaling pathway (i.e. p38MAPK-1, HIF-1 and HO-1) were correlated with peri-menopausal women's coronary lesion features and prognosis. METHODS: Altogether 1449 peri-menopausal women were divided into non-coronary artery disease (CAD) group (n = 860) and CAD group (n = 589), including 167 pre-menopausal CAD populations and 422 post-menopausal CAD populations. General information about CAD risk parameters were gathered, including age, family history of CAD or hypertension or diabetes mellitus, bilirubin, cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and so on. Coronary angiography results were judged, and CAD score was calculated with application of Genisin scoring method. Besides, detection of MAPK-1 levels was implemented with Strept Avidin-Biotin Complex (SABC) method, while HIF-1 and HO-1 expressions in the serum were determined utilizing ELISA detection kit. Correlations among protein expressions, characteristics of coronary lesions and prognosis of CAD populations were finally evaluated. RESULTS: Hypertension, hyperlipoidemia, diabetes and smoking history were more prevalent among postmenopausal CAD women than premenopausal CAD women (P < 0.05). Furthermore, postmenopausal women seemed to be significantly associated with multiple (i.e. double and triple) vessel lesions and severe lesion types (type B and C), when compared with premenopausal CAD group (P < 0.05). Similarly, remarkably elevated expressions of p38MAPK-1, HIF-1 and HO-1 were found within postmenopausal CAD populations in comparison to premenopausal ones (P < 0.05). The internal CysC, hs-CRP, TG and LDL-C concentrations all accorded with the following tendency: postmenopausal CAD women > premenopausal CAD women > non-CAD women. Moreover, p38MAPK-1, HIF-1 and HO-1 expressions were up-regulated with increasing number of vessel lesions and severity of coronary lesions among peri-menopausal women. Besides, among both pre-menopausal and post-menopausal CAD groups, positive correlations could be observed between MAPK-1 and TG (r s = 0.271; r s = 0.476), between HIF-1α and LDL-C (r s = 0.077; r s = 0.470), as well as between HO-1 and CysC (r s = 0.492; r s = 0.190) or hs-CRP (r s = 0.569; r s = 0.542) (all P < 0.05). MAPK-1, HIF-1α and HO-1 were also, respectively, positively correlated with CysC (r s = 0.415), hs-CRP (r s = 0.137), and TG (r s = 0.142), regarding post-menopausal CAD women (all P < 0.05). Finally, only SBP and TG were regarded as independent risk factors for CAD prognosis (i.e. high Genisin score) among premenopausal women (OR = 1.02, 95%CI: 1.01-1.18, P = 0.043; OR = 1.82, 95%CI: 1.01-3.33, P = 0.047). CONCLUSIONS: Expressions of p38MAPK-1, HIF-1 and HO-1 could serve as predictive roles for coronary lesions among peri-menopausal women.

Anti-VEGF Therapy with Bevacizumab--limited cardiovascular toxicity.

PURPOSE: This analysis was conducted to evaluate cardiovascular toxicity of commonly used anti-VEGF therapeutic agent, bevacizumab, in treating patients with cancer. METHODS: Clinical studies evaluating the efficacy and safety of bevacizumab-based regimens on response and safety for patients with cancer were identified using a predefined search strategy, allowing cardiovascular toxicity and other side effects of treatment to be estimated. RESULTS: In bevacizumab based regimens, 4 clinical studies including 282 patients with advanced cancer (including gliomas, cervical, breast and ovarian cancer) were considered eligible for inclusion. These bevacizumab-based regimens included docetaxel, irinitecan and carboplatin. Systematic analysis suggested that, of 282 patients treated by bevacizumab based regimens, hypertension and thrombo-embolism occurred in 2.5% (7/282), while only 3 patients reported cardiovascular events (1.1%). No treatment related death occurred in bevacizumab based treatment. CONCLUSION: This systemic analysis suggests that bevacizumab based regimens are associated with reasonable and accepted cardiovascular toxicity when treating patients with gliomas, cervical, breast and ovarian cancer.

Association of mild to moderate kidney dysfunction with coronary artery calcification in patients with suspected coronary artery disease.

OBJECTIVES: To report the association between kidney dysfunction and coronary artery calcification (CAC) score (CACS) among patients with clinically suspected coronary artery disease (CAD). METHODS: We prospectively included 1,572 consecutive patients with clinically suspected CAD who underwent ECG-gated cardiac CT scans using 64-multidetector row computed tomography. CACS was quantified using a previously described method. Renal function was assessed by the estimated glomerular filtration rate (eGFR). Ordinal logistic regression and Pearson correlation were used to analyze the association between eGFR and CACS. RESULTS: Patients with higher CACS were older, more had a history of hypertension, diabetes and tobacco use, and they were more likely to have an atherogenic lipid profile, higher systolic blood pressure, diastolic blood pressure, hemoglobin A1c, body mass index and C-reactive protein (CRP) and lower eGFR when compared with those patients without CAC or with lower CACS. The unadjusted correlation coefficient of eGFR and CACS was -0.259 (p < 0.001). This remained significant after adjustment for age, gender, hypertension, diabetes, hyperlipidemia, tobacco use and CRP (R = -0.156, p < 0.001). Ordinal logistic regression analysis showed that age, hypertension, diabetes, CRP and eGFR exerted independent influences on CACS. CONCLUSIONS: Kidney dysfunction was an independent predictor of CACS in patients with clinically suspected CAD. Further prospective multicenter studies are needed to confirm this finding.