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Statins, known as HMG-CoA reductase inhibitors, are widely utilized to reduce blood cholesterol levels and possess pleiotropic effects, including the influence on inflammation and macrophage proliferation. Despite their significant impact in diminishing the incidence of cardiovascular events and mortality, individual responses to statin therapy vary considerably. Understanding this variability is essential for optimizing treatment outcomes and minimizing adverse effects. The gut microbiota, a complex ecosystem of microorganisms within the gastrointestinal tract, plays a critical role in human health and disease. Emerging evidence has linked the gut microbiota to drug metabolism and response, with the potential to modulate the efficacy of statin therapy and its side effects. This review provides a comprehensive overview of the interaction between the gut microbiota and statins. It discusses how the gut microbiota can influence the therapeutic effects and side effects of statins and examines the mechanisms by which the gut microbiota affect statin response and cardiovascular diseases.

Aims: Heart failure (HF) is associated with profound changes in cardiac metabolism. At present, there is still a lack of relevant research to explore the key microbiome and their metabolites affecting the progression of HF. Herein, the interaction of gut microbiota and circulating free fatty acid (FFA) in HF patients and mice is investigated. Methods and Results: In HF patients, by applying metagenomics analysis and targeted FFA metabolomics, enriched abundance of Clostridium sporogenes (C.sp) in early and late stage of HF patients, which negatively correlated to saturated free fatty acid (SFA) levels, is identified. KEGG analysis further indicates microbiota gene enrichment in FFA degradation in early HF, and decreased gene expression in FFA synthesis in late HF. In HF mice (C57BL/6J) induced by isoproterenol (ISO), impaired intestinal permeability is observed, and decreased fecal C.sp and increased SFA are further validated. At last, by supplementing C.sp to ISO‐induced HF mice, the cardiac function, fibrosis, and myocardial size are partially rescued, together with decreased circulating SFA levels. Conclusions: Clostridium abundance is increased in HF, compensating cardiac function deterioration via downregulation of circulating SFA levels. The results demonstrate that the gut microbiota–SFA axis plays an important role in HF protection, which may provide a strategic advantage for the probiotic therapy development in HF.

Abstract Bile acids play important roles in lipid metabolism and glucose homeostasis. Limited research exist on the association between serum total bile acid (TBA) levels and major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS), particularly those with comorbid type 2 diabetes mellitus (T2DM). This study was conducted to examine the relationship between baseline serum TBA level and T2DM status in patients with ACS after percutaneous coronary intervention (PCI) and to identify the predictive value of TBA levels for a 2-year risk of MACEs. 425 ACS patients underwent PCI were recruited and divided into three groups based on baseline serum TBA concentration. An analysis of the association between the T2DM status and baseline serum TBA levels was conducted using univariate linear regression and multivariate linear regression. The predictive relevance of serum TBA levels was evaluated using the receiver operating characteristic (ROC) curve and Cox regression. Kaplan–Meier curves were employed to analyze the differences among groups in predicting MACEs over a 2-year follow-up period. Baseline serum TBA levels were higher in ACS patients who were diagnosed with T2DM (the median 3.6 µmol/L) than those without T2DM (the median 3.0 µmol/L). T2DM status in ACS patients was positively correlated with baseline serum TBA concentrations (β: 1.7, 95% confidence interval [CI] 0.3–3.0), particularly in the male (β: 2.0, 95% CI 0.3–3.6) and 50–69-year-old (β: 2.5, 95% CI 0.6–4.4) populations. The areas under the ROC curve of baseline serum TBA levels predicted MACEs in ACS and ACS-T2DM patients following PCI were 0.649 (95% CI 0.595–0.703) and 0.783 (95% CI 0.685–0.881), respectively. Furthermore, Cox regression analysis showed that baseline serum TBA level was associated with the occurrence of MACEs in patients with ACS after PCI over a 2-year follow-up period, especially in those diagnosed with T2DM, whose baseline TBA concentration was lower than 10.0 µmol/L. ACS Patients with T2DM had higher serum TBA levels. TBA level at baseline was an independent predictor of MACEs in ACS patients who underwent PCI, especially with comorbid T2DM.

Summary: Background: Limited data exists on how early-life weight changes relate to metabolic syndrome (MetS) risk in midlife. This study examines the association between long-term trajectories of body mass index (BMI), its variability, and MetS risk in Chinese individuals. Methods: In the Hanzhong Adolescent Hypertension study (March 10, 1987–June 3, 2017), 1824 participants with at least five BMI measurements from 1987 to 2017 were included. Using group-based trajectory modeling, different BMI trajectories were identified. BMI variability was assessed through standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Logistic regression analyzed the relationship between BMI trajectory, BMI variability, and MetS occurrence in midlife (URL: https://www.clinicaltrials.gov; Unique identifier: NCT02734472). Findings: BMI trajectories were categorized as low-increasing (34.4%), moderate-increasing (51.8%), and high-increasing (13.8%). Compared to the low-increasing group, the odds ratios (ORs) [95% CIs] for MetS were significantly higher in moderate (4.27 [2.63–6.91]) and high-increasing groups (13.11 [6.30–27.31]) in fully adjusted models. Additionally, higher BMI variabilities were associated with increased MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 2.30 [2.02–2.62], 1.22 [1.19–1.26], and 4.29 [3.38–5.45]). Furthermore, BMI trajectories from childhood to adolescence were predictive of midlife MetS, with ORs in moderate (1.49 [1.00–2.23]) and high-increasing groups (2.45 [1.22–4.91]). Lastly, elevated BMI variability in this period was also linked to higher MetS odds (ORs for SDBMI, VIMBMI, and ARVBMI: 1.24 [1.08–1.42], 1.00 [1.00–1.01], and 1.21 [1.05–1.38]). Interpretation: Our study suggests that both early-life BMI trajectories and BMI variability could be predictive of incident MetS in midlife. Funding: This work was supported by the National Natural Science Foundation of China No. 82070437 (J.-J.M.), the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University of China (No. XJTU1AF-CRF-2022-002, XJTU1AF2021CRF-021, and XJTU1AF-CRF-2023-004), the Key R&D Projects in Shaanxi Province (Grant No. 2023-ZDLSF-50), the Chinese Academy of Medical Sciences & Peking Union Medical College (2017-CXGC03-2), and the International Joint Research Centre for Cardiovascular Precision Medicine of Shaanxi Province (2020GHJD-14).

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is the main reason for cirrhosis and hepatocellular carcinoma. As a starting point for NAFLD, the treatment of nonalcoholic fatty liver (NAFL) is receiving increasing attention. Mice fed a high‐fat diet (HFD) and hereditary leptin deficiency (ob/ob) mice are important NAFL animal models. However, the comparison of these mouse models with human NAFL is still unclear. Methods In this study, HFD‐fed mice and ob/ob mice were used as NAFL animal models. Liver histopathological characteristics were compared, and liver transcriptome from both mouse models was performed using RNA sequencing (RNA‐seq). RNA‐seq data obtained from the livers of NAFL patients was downloaded from the GEO database. Global gene expression profiles in the livers were further analyzed using functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Results Our results showed that the biochemical parameters of both mouse models and human NAFL were similar. Compared with HFD‐fed mice, ob/ob mice were more similar in histologic appearance to NAFL patients. The liver transcriptome characteristics partly overlapped in mice and humans. Furthermore, in the NAFL pathway, most genes showed similar trends in mice and humans, thus demonstrating that both types of mice can be used as models for basic research on NAFL, considering the differences. Conclusion Our findings show that HFD‐fed mice and ob/ob mice can mimic human NAFL partly in pathophysiological process. The comparative analysis of liver transcriptome profile in mouse models and human NAFL presented here provides insights into the molecular characteristics across these NAFL models.

Summary: Epigenetic regulation of heart development remains incompletely understood. Here we show that LSD1, a histone demethylase, plays a crucial role in regulating cardiomyocyte proliferation during heart development. Cardiomyocyte-specific deletion of Lsd1 in mice inhibited cardiomyocyte proliferation, causing severe growth defect of embryonic and neonatal heart. In vivo RNA-seq and in vitro functional studies identified Cend1 as a target suppressed by LSD1. Lsd1 loss resulted in elevated Cend1 transcription associated with increased active histone mark H3K4me2 at Cend1 promoter. Cend1 knockdown relieved the cell-cycle arrest and proliferation defect caused by LSD1 inhibition in primary rat cardiomyocytes. Moreover, genetic deletion of Cend1 rescued cardiomyocyte proliferation defect and embryonic lethality in Lsd1 null embryos. Consistently, LSD1 promoted the cell cycle of cardiomyocytes derived from human-induced pluripotent stem cells by repressing CEND1. Together, these findings reveal an epigenetic regulatory mechanism involving the LSD1-CEND1 axis that controls cardiomyocyte proliferation essential for murine heart development.

Abstract Since the four working groups of the Chinese Society of Cardiology issued first expert consensus on coronary microvascular diseases (CMVD) in 2017, international consensus documents on CMVD have increased rapidly. Although some of these documents made preliminary recommendations for the diagnosis and treatment of CMVD, they did not provide classification of recommendations and levels of evidence. In order to summarize recent progress in the field of CMVD, standardize the methods and procedures of diagnosis and treatment, and identify the scientific questions for future research, the four working groups of the Chinese Society of Cardiology updated the 2017 version of the Chinese expert consensus on CMVD and adopted a series of measures to ensure the quality of this document. The current consensus has raised a new classification of CMVD, summarized new epidemiological findings for different types of CMVD, analyzed key pathological and molecular mechanisms, evaluated classical and novel diagnostic technologies, recommended diagnostic pathways and criteria, and therapeutic strategies and medications, for patients with CMVD. In view of the current progress and knowledge gaps of CMVD, future directions were proposed. It is hoped that this expert consensus will further expedite the research progress of CMVD in both basic and clinical scenarios.

Abstract Background Polymorphisms in microRNAs (miRNAs) play an important role in acute coronary syndromes (ACS). The purpose of this study was to assess the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with the development and prognosis of ACS and to explore the underlying mechanisms. Methods A case–control study of 1171 subjects was included to determine the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with ACS risk. An additional 612 patients with different miR-146a rs2910164 genotypes, who underwent percutaneous coronary intervention (PCI) were included in the validation cohort and followed for 14 to 60 months. The endpoint was major adverse cardiovascular events (MACE). A luciferase reporter gene assay was used to validate the interaction of oxi-miR-146a(G) with the IKBA 3'UTR. Potential mechanisms were validated using immunoblotting and immunostaining. Results The miR-146a rs2910164 polymorphism was significantly associated with the risk of ACS (Dominant model: CG + GG vs. CC, OR = 1.270, 95% CI (1.000–1.613), P = 0.049; Recessive model: GG vs. CC + CG, OR = 1.402, 95% CI (1.017–1.934), P = 0.039). Serum inflammatory factor levels were higher in patients with the miR-146a rs2910164 G allele than in those with the C allele. MiR-146a rs2910164 polymorphism in dominant model was associated with the incidence of MACE in post-PCI patients (CG + GG vs. CC, HR = 1.405, 95% CI (1.018–1.939), P = 0.038). However, the miR-34b rs4938723 polymorphism was not associated with the prevalence and prognosis of ACS. The G allele of miR-146a rs2910164 tends to be oxidized in ACS patients. The miRNA fractions purified from monocytes isolated from ACS patients were recognized by the 8OHG antibody. Mispairing of Oxi-miR-146a(G) with the 3'UTR of IKBA results in decreased IκBα protein expression and activation of the NF-κB inflammatory pathway. P65 expression was higher in atherosclerotic plaques from patients carrying the miR-146a rs2910164 G allele. Conclusion The variant of miR-146a rs2910164 is closely associated with the risk of ACS in Chinese Han population. Patients carrying miR-146a rs2910164 G allele may have worse pathological change and poorer post-PCI prognosis, partly due to the oxidatively modified miR-146a mispairing with 3′UTR of IKBA and activating NF-κB inflammatory pathways.

Abstract Background Increased circulating uric acid (UA) concentration may disrupt cardiac function in heart failure patients, but the specific mechanism remains unclear. Here, we postulate that hyperuremia induces sterol regulatory element binding protein 1 (SREBP1), which in turn activate hepatic fatty acid biosynthesis response, leading to cardiac dysfunction. Methods and results Increased circulating uric acid was observed in heart failure patients and inversely correlated to cardiac function. Besides, uric acid correlated to circulating lipids profile based on metabolomics in heart failure patients. Using cultured human hepatoellular carcinomas (HepG2) and Tg(myl7:egfp) zebrafish, we demonstrated that UA regulated fatty acid synthase (FASN) via SREBP1 signaling pathway, leading to FFA accumulation and impaired energy metabolism, which could be rescued via SREBP1 knockdown. In ISO treated zebrafish, UA aggravated heart failure via increased cardiovascular cavity size, decreased heart beats, pericardial edema and long-stretched heart deformation. Conclusions Our findings suggest that UA-SREBP1-FASN signaling exacerbates cardiac dysfunction during FFA accumulation. Identification of this mechanism may help in treatment and prevention of heart failure.

Objective:. Data comparing the outcomes of MiStent (Micell Technologies, Durham, North Carolina, USA) microcrystalline biodegradable polymer (BP) drug-eluting stent (DES) and those of another post-marketing BP-DES, TIVOLI (EssenTech, Beijing, China) are rare. This study sought to compare the angiographic efficacy and clinical outcomes of the microcrystalline BP sirolimus-eluting stent (SES) system MiStent and those of TIVOLI BP-SES. Methods:. The DESSOLVE-C trial was a prospective, single-blinded, multicenter, randomized trial (NCT02448524), which randomly assigned patients with de novo coronary lesions to receive MiStent or TIVOLI BP-SES by a 1:1 ratio. The primary endpoint was a non-inferiority comparison of in-stent late lumen loss (LLL) by quantitative coronary angiography at 9 months. The secondary endpoint was device-related clinical cardiovascular composite events (target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization) and 1-year outcomes. Results:. A total of 428 patients (216 patients in the MiStent group and 212 patients in the TIVOLI group) were enrolled and included in an intention-to-treat analysis. MiStent was not only non-inferior but superior to TIVOLI for in-stent LLL at 9 months ((0.23 ± 0.37) mm vs. (0.34 ± 0.48) mm, P for non-inferiority

Macrophages have been shown to have an important function in atherosclerosis. Here the authors show that, in human atherosclerotic plaques and mouse models, GSDME and pyroptosis promote atherosclerosis and inhibition of these pathways could reduce pathology associated with atherosclerotic disease.

Background: The coronary no-reflow (NR) phenomenon is an independent predictor of major adverse cardiac events (MACEs). This study aimed to establish a clinical and comprehensive nomogram for predicting NR in acute myocardial infarction (AMI) patients after primary percutaneous coronary intervention (pPCI). Methods: The multivariable logistic regression analysis was performed to determine the NR-related factors. A nomogram was established via several clinical and biochemical factors, and the performance was evaluated via discrimination, calibration, and clinical factors. Results: The study consisted of 3041 AMI patients after pPCI, including 2129 patients in the training set (70%) and 912 patients in the validation set (30%). The NR event was 238 in the training set and 87 in the validation set. The level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP), basophil count (BASO), neutrophil count (NEUBC), D-dimer, hemoglobin (Hb), and red blood cell distribution width (RDW.CV) in NR patients showed statistically significant differences. In the training set, the C-index was 0.712, 95% CI 0.677 to 0.748. In the validation set, the C-index was 0.663, 95% CI 0.604 to 0.722. Conclusions: A nomogram that may predict NR in AMI patients undergoing pPCI was established and validated. We hope this nomogram can be used for NR risk assessment and clinical decision-making and significantly prevent potentially impaired reperfusion associated with NR.

Abstract High-fat diet (HFD) has been implicated to promote colorectal cancer (CRC). Recently, oncogene Cyclophilin B (CypB) is reported to be induced by cholesterol. However, the role of CypB in CRC carcinogenesis and metastasis associated with HFD remains unknown. In the present study, we showed that HFD-induced CypB enhances proliferation and metastasis through an inflammation-driven circuit, including Signal Transducer and Activator of Transcription 3 (STAT3)-triggered transcription of lncRNA-PVT1, and its binding with CypB that promotes activation of STAT3. CypB was found to be upregulated in CRC, which was correlated with elevated body mass index and poor prognosis. HFD induced CypB expression and proinflammatory cytokines in colon of mice. Besides, CypB restoration facilitated growth, invasion and metastasis in CRC cells both in vitro and in vivo. Moreover, RIP sequencing data identified lncRNA-PVT1 as a functional binding partner of CypB. Mechanistically, PVT1 increased the phosphorylation and nuclear translocation of STAT3 in response to IL-6, through directly interaction with CypB, which impedes the binding of Suppressors Of Cytokine Signalling 3 (SOCS3) to STAT3. Furthermore, STAT3 in turn activated PVT1 transcription through binding to its promoter, forming a regulatory loop. Finally, this CypB/STAT3/PVT1 axis was verified in TCGA datasets and CRC tissue arrays. Our data revealed that CypB linked HFD and CRC malignancy by enhancing the CypB/STAT3/PVT1 feedforward axis and activation of STAT3.

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes when added to conventional statin therapy. This study aims to investigate the efficacy and safety of in-hospital initiation of PCSK9 inhibitors among patients with acute myocardial infarction (AMI) based on real-world experience. Methods and results Data were collected from the Biobank of the First Affiliated Hospital of Xi’an Jiaotong University between January 2016 and December 2020. A total of 7556 AMI patients were screened for eligibility. Propensity Score Match (PSM) was employed, and covariates were age, sex, admission blood pressure and lipid profiles. Eligible participants were (1) propensity-matched 1:2:2 of statin plus evolocumab (dual therapy) vs. statin vs. statin plus ezetimibe. Ninety-five statin plus evolocumab users achieved significantly decreased low density lipoprotein (LDL) levels (0.92 ± 0.62 mmol/L in the 1st month and 1.17 ± 0.73 in the 3rd month) and a promising attainment rate of LDL (79.5% in the 1st month and 80.0% in the 3rd month) compared to the other two groups. (2) Propensity-matched 1:2:2 of statin plus ezetimibe evolocumab (triple therapy) vs. statin vs. statin plus ezetimibe. Similarly, 75 triple medication users achieved significantly decreased LDL levels and a promising attainment rate of LDL compared to the other two groups. In-hospital mortality and readmission rates within 3 months were then analyzed, and a decreased readmission rate was observed with PCSK9i therapy. Conclusions Based on the present single-center real-world PSM-adjusted study, PCSK9i has been effective in short-term lipid control among AMI patients. The long-term effectiveness for reducing major cardiovascular events among AMI patients based on real-world experience remains to be explored. Trial registration The study was registered at ClinicalTrials.gov, ClinicalTrials.gov ID: NCT05184530 Graphical Abstract

In the bone marrow, dendritic cell development is governed by supporting cells, such as endothelial cells. Here authors show that expression of serine/threonine kinase 11 in endothelial cells regulates differentiation of dendritic cell precursors via modulating secretion of stem cell factor.

Abstract Nucleocapsid protein (NC) in the group-specific antigen (gag) of retrovirus is essential in the interactions of most retroviral gag proteins with RNAs. Computational method to predict NCs would benefit subsequent structure analysis and functional study on them. However, no computational method to predict the exact locations of NCs in retroviruses has been proposed yet. The wide range of length variation of NCs also increases the difficulties. In this paper, a computational method to identify NCs in retroviruses is proposed. All available retrovirus sequences with NC annotations were collected from NCBI. Models based on random forest (RF) and weighted support vector machine (WSVM) were built to predict initiation and termination sites of NCs. Factor analysis scales of generalized amino acid information along with position weight matrix were utilized to generate the feature space. Homology based gene prediction methods were also compared and integrated to bring out better predicting performance. Candidate initiation and termination sites predicted were then combined and screened according to their intervals, decision values and alignment scores. All available gag sequences without NC annotations were scanned with the model to detect putative NCs. Geometric means of sensitivity and specificity generated from prediction of initiation and termination sites under fivefold cross-validation are 0.9900 and 0.9548 respectively. 90.91% of all the collected retrovirus sequences with NC annotations could be predicted totally correct by the model combining WSVM, RF and simple alignment. The composite model performs better than the simplex ones. 235 putative NCs in unannotated gags were detected by the model. Our prediction method performs well on NC recognition and could also be expanded to solve other gene prediction problems, especially those whose training samples have large length variations.

Background & Aims: Cholesterol 25-hydroxylase (Ch25h), converting cholesterol to 25-hydroxycholesterol (25-HC), is critical in modulating cellular lipid metabolism and anti-inflammatory and antiviral activities. However, its role in nonalcoholic fatty liver disease remains unclear. Methods: Ch25h expression was detected in livers of ob/ob mice and E3 rats fed a high-fat diet (HFD). Gain- or loss-of-function of Ch25h was performed using Ch25h+/+ (wild type [WT]) mice receiving AAV8-Ch25h or Ch25h knockout (Ch25h-/-) mice. WT mice fed an HFD were administered with 25-HC. The Ch25h–LXRα–CYP axis was measured in primary hepatocytes isolated from WT and Ch25h-/- mice. Results: We found that Ch25h level was decreased in livers of ob/ob mice and E3 rats fed an HFD. Ch25h-/- mice fed an HFD showed aggravated fatty liver and decreased level of cytochrome P450 7A1 (CYP7A1), in comparison with their WT littermates. RNA-seq analysis revealed that the differentially expressed genes in livers of HFD-fed Ch25h-/- mice were involved in pathways of positive regulation of lipid metabolic process, steroid metabolic process, cholesterol metabolic process, and bile acid biosynthetic process. As gain-of-function experiments, WT mice receiving AAV8-Ch25h or 25-HC showed alleviated NAFLD, when compared with the control group receiving AAV8-control or vehicle control. Consistently, Ch25h overexpression significantly elevated the levels of primary and secondary bile acids and CYP7A1 but decreased those of small heterodimer partner and FGFR4. Conclusions: Elevated levels of Ch25h and its enzymatic product 25-HC alleviate HFD-induced hepatic steatosis via regulating enterohepatic circulation of bile acids. The underlying mechanism involves 25-HC activation of CYP7A1 via liver X receptor. These data suggest that targeting Ch25h or 25-HC may have therapeutic advantages against nonalcoholic fatty liver disease.

Abstract Aims This study aimed to compare the efficacy of angiotensin receptor‐neprilysin inhibitor (ARNI) therapy with angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) therapy for cardiovascular outcomes in patients with acute myocardial infarction (AMI). Methods and results Data were collected from the Biobank of the First Affiliated Hospital of Xi'an Jiaotong University between January 2016 and December 2020. A total of 7556 AMI patients were screened for eligibility. Propensity score matching based on age, sex, blood pressure, kidney function, baseline left ventricular ejection fraction (LVEF), and cardiovascular medication were conducted, resulting in 291 patients with AMI being assigned to ARNI, ACEI, and ARB group, respectively. Patients receiving ARNI had significantly lower rates of the composite cardiovascular outcome than ACEI {hazard ratio [HR] 0.51, [95% confidence interval (CI), 0.27–0.95], P = 0.02}, and ARB users [HR 0.47, (95%CI, 0.24–0.90), P = 0.02]. Patients receiving ARNI showed lower rates of cardiovascular death than ACEI [HR 0.37, (95%CI, 0.18–0.79), P = 0.01] and ARB users [HR 0.41, (95%CI, 0.18–0.95), P = 0.04]. Subgroup analysis indicated that patients with LVEF no more than 40% tend to benefit more from ARNI as compared with ACEI [HR 0.30, (95%CI, 0.11–0.86), P = 0.01] or ARB [HR 0.21, (95%CI, 0.04–1.1), P = 0.05]. Patients aged no more than 60 years exhibited reduced composite endpoints [HR for ARNI vs. ARB: 0.11, (95%CI, 0.03–0.46), P = 0.002]. Conclusions In patients with AMI, ARNI was superior to ACEI/ARB in reducing the long‐term adverse cardiovascular outcomes. Subgroup analysis further indicates that ARNI is more likely to benefit patients with LVEF less than 40% and aged less than 60 years.

Abstract. Objective:. This study aimed to estimate the proportion of non-obstructive coronary artery disease (CAD) patients in large percutaneous coronary intervention (PCI) centers in China. Methods:. The study was conducted at 6 large PCI centers in China from January 1, 2013 to December 31, 2015. Demographic and clinical data were collected from medical records, prescription records, and laboratory reports of patients with symptoms of angina who underwent coronary angiography (CAG). Results:. A total of 1713 patients were consecutively screened, 1600 of whom were included in the study. CAG showed that 300 patients had non-obstructive CAD while 1300 had obstructive CAD. Among the 300 patients with non-obstructive CAD, 203 displayed mild coronary stenosis (20%–49%) and 91 had normal coronary status (ie,

BackgroundThe current burden of dyslipidemia, the pre-hospital application of statins and the association of pre-hospital statins with the severity of coronary artery disease (CAD) and in-hospital outcomes in Chinese patients with first acute coronary syndrome (ACS) are very significant and remain unclear.MethodsA total of 41,183 patients who underwent coronary angiography and were diagnosed with ACS for the first time from a nationwide registry study (CCC-ACS) were enrolled. The severity of CAD was assessed using the CAD prognostic index (CADPI). The patients were classified into statin and non-statin groups according to their pre-hospital statin treatment status. Clinical characteristics, CADPI and in-hospital outcomes were compared, and a logistic regression analysis was performed to determine whether pre-hospital statin therapy is associated with in-hospital outcomes and CADPI. A sensitivity analysis was used to further explore the issues above.ResultsThe non-statin group had more in-hospital all-cause deaths (1.2 vs. 0.8%, P = 0.010). However, no association exists between statin pretreatment and in-hospital major adverse cardiovascular events (MACEs) or all-cause deaths in the entire population and subgroups (all P > 0.05). Surprisingly, statin pretreatment was associated with an 8.9% higher risk of severely obstructive CAD (CADPI ≥ 37) (OR, 1.089; 95% CI, 1.010–1.175, P = 0.028), and similar results were observed in subgroups of females, those aged 50 to 75 years, and patients with hypertension.ConclusionStatin pretreatment was not related to MACEs or all-cause death during hospital stay, but it was associated with a higher risk of increased angiographic severity in patients with first ACS.

BackgroundAcute coronary syndrome (ACS) is the most time-sensitive acute cardiac event that requires rapid dispatching and response. The medical priority dispatch system (MPDS), one of the most extensively used types of emergency dispatch systems, is hypothesized to provide better-quality prehospital emergency treatment. However, few studies have revealed the impact of MPDS use on the process of ACS care. ObjectiveThis study aimed to investigate whether the use of MPDS was associated with higher prehospital diagnosis accuracy and shorter prehospital delay for patients with ACS transferred by an emergency medical service (EMS), using a national database in China. MethodsThis retrospective analysis was based on an integrated database of China’s MPDS and hospital registry. From January 1, 2016, to December 31, 2020, EMS-treated ACS cases were divided into before MPDS and after MPDS groups in accordance with the MPDS launch time at each EMS center. The primary outcomes included diagnosis consistency between hospital admission and discharge, and prehospital delay. Multivariable logistic regression and propensity score–matching analysis were performed to compare outcomes between the 2 groups for total ACS and subtypes. ResultsA total of 9806 ACS cases (3561 before MPDS and 6245 after MPDS) treated by 43 EMS centers were included. The overall diagnosis consistency of the after MPDS group (Cohen κ=0.918, P

Defective reactive oxygen species (ROS) production by genetically determined variants of the NADPH oxidase 2 (NOX2) complex component, NCF4, leads to enhanced production of autoantibodies to collagen type II (COL2) and severe collagen-induced arthritis (CIA) in mice. To further understand this process, we used mice harboring a mutation in the lipid endosomal membrane binding site (R58A) of NCF4 subunit. This mutation did not affect the extracellular ROS responses but showed instead decreased intracellular responses following B cell stimulation. Immunization with COL2 led to severe arthritis with increased antibody levels in Ncf458A mutated animals without significant effects on antigen presentation, autoreactive T cell activation and germinal center formation. Instead, plasma cell formation was enhanced and had altered CXCR3/CXCR4 expression. This B cell intrinsic effect was further confirmed with chimeric B cell transfer experiments and in vitro LPS or CD40L with anti-IgM stimulation. We conclude that NCF4 regulates the terminal differentiation of B cells to plasma cells through intracellular ROS.

BackgroundContrast-induced acute kidney injury (CI-AKI) is a common complication of patients undergoing percutaneous coronary intervention (PCI). Data regarding the influence of sodium-glucose cotransporter-2 (SGLT2) inhibitor on the CI-AKI incidence and renal outcomes of patients undergoing PCI are limited. This study aimed to examine the real-world risk of CI-AKI in SGLT2 inhibitor users undergoing PCI.MethodsWe used longitudinal data from the medical records of the First Affiliated Hospital of Xi'an Jiaotong University. We selected SGLT inhibitor users and nonusers [patients with type 2 diabetes (T2D) without SGLT2 inhibitor prescription] undergoing PCI. We determined CI-AKI by the ESUR (European Society of Urogenital Radiology, AKIESUR) and KDIGO definition (Kidney Disease: Improving Global Outcomes, AKIKDIGO). We performed 1:1 nearest-neighbor propensity matching and calculated unadjusted odds ratios (ORs) and adjusted ORs (aORs; accounting for covariates poorly balanced) for AKI in primary and sensitivity analyses. We compared the renal function indicators in users and nonusers at 24, 48, and 72 h post-PCI.ResultsWe identified 242 SGLT2 inhibitor users and 242 nonusers in the cohort. The unadjusted ORs of CI-AKIESUR were 63% lower in users [OR: 0.37 (95% CI: 0.18–0.68); P = 0.01], which was unchanged [aOR: 0.37 (95% CI: 0.19–0.67); P < 0.01] post adjustment. These estimates did not qualitatively change across several sensitivity analyses. There was no significant difference in urea nitrogen, creatinine, and estimated glomerular filtration rate (eGFR) values between the two groups before PCI, and at 24 h, while the creatinine (48 and 72 h post-PCI) and CyC (24 and 48 h post-PCI) were significantly lower than those in the nonuser group (P < 0.05).ConclusionOur findings do not suggest an increased risk of CI-AKI associated with SGLT2 inhibitor use in patients with CAD and T2D undergoing PCI.

The expansion of the white adipose tissue during obesity is accompanied by increased cellular stress, but factors that protect adipocytes from cell death are not well known. Here the authors report that the transcriptional co-activators YAP and TAZ are activated in adipocytes during obesity, which increases adipocyte survival through the proapoptotic factor BIM.

Abstract Background Suboptimal coronary blood flow after primary percutaneous coronary intervention (PCI) is a complex multifactorial phenomenon. Although extensively studied, defined modifiable risk factors and efficient management strategy are lacking. This study aims to determine the potential causes of suboptimal flow and associated impact on 30-day outcomes in patients presenting with anterior ST-elevation myocardial infarction (STEMI). Methods We evaluated a total of 1104 consecutive patients admitted to our hospital from January 2016 to December 2018 with the diagnosis of anterior wall STEMI who had primary PCI. Results Overall, 245 patients (22.2%) had final post-PCI TIMI flow ≤2 in the LAD (suboptimal flow group) and 859 (77.8%) had final TIMI-3 flow (optimal flow group). The independent predictors of suboptimal flow were thrombus burden grade (Odds ratio (OR) 1.848; p

Abstract Background Underweight or obese status influences the prognosis of atrial fibrillation (AF). However, the association between stratification of body mass index (BMI) and in-hospital outcomes in patients with AF, remains lacking in China. Methods Using data from the Improving Care for Cardiovascular Disease in China-AF project, which was launched in February 2015 and recruited 150 hospitals in China, we compared characteristics, in-hospital treatments and clinical outcomes among the stratifications of BMI for Asians. Results A total of 15,867 AF patients with AF were enrolled, including 830 (5.23%) underweight, 4965 (31.29%) with normal weight, 3716 (23.42%) overweight, 5263 (33.17%) obese class I and 1093 (6.89%) obese class II participants. Compared with normal weight patients, underweight, overweight, and obese patients showed increased percentages of CHADS2 scores (3–6) and CHA2DS2-VASc scores (5–9). During hospitalization, overweight or obese patients showed greater use of rhythm control medications, anticoagulant drugs, and intervention therapies than underweight–normal weight patients. In adjusted logistic models, BMI was a strong predictor of in-hospital mortality. Especially, underweight BMI was associated with higher incidence of in-hospital mortality, with an adjusted odds ratio of 2.08 (95% confidence interval, 1.56–4.46; p = 0.04) than overweight and obese BMI. Conclusions Asian patients with AF and high BMI received more medical treatments and presented less adverse in-hospital outcomes compared with those with underweight–normal weight. Although low BMI may be associated with other comorbidities and advanced age, underweight BMI retained a negative correlation with all-cause mortality in the patients with AF during hospitalization.

Abstract Background Ischemic heart disease (IHD) is a common cardiovascular disorder associated with inadequate blood supply to the myocardium. Chronic coronary ischemia leads to ischemic cardiomyopathy (ICM). Despite their rising prevalence and morbidity, few studies have discussed the lipids alterations in these patients. Methods In this cross-sectional study, we analyzed serum lipids profile in IHD and ICM patients using a lipidomics approach. Consecutive consenting patients admitted to the hospital for IHD and ICM were enrolled. Serum samples were obtained after overnight fasting. Non-targeted metabolomics was applied to demonstrate lipids metabolic profile in control, IHD and ICM patients. Results A total of 63 and 62 lipids were detected in negative and positive ion mode respectively. Among them, 16:0 Lyso PI, 18:1 Lyso PI in negative ion mode, and 19:0 Lyso PC, 12:0 SM d18:1/12:0, 15:0 Lyso PC, 17:0 PC, 18:1–18:0 PC in positive ion mode were significantly altered both in IHD and ICM as compared to control. 13:0 Lyso PI, 18:0 Lyso PI, 16:0 PE, 14:0 PC DMPC, 16:0 ceramide, 18:0 ceramide in negative ion mode, and 17:0 PE, 19:0 PC, 14:0 Lyso PC, 20:0 Lyso PC, 18:0 PC DSPC, 18:0–22:6 PC in positive ion mode were significantly altered only in ICM as compared to IHD and control. Conclusion Using non-targeted lipidomics profiling, we have successfully identified a group of circulating lipids that were significantly altered in IHD and ICM. The lipids metabolic signatures shed light on potential new biomarkers and therapeutics for preventing and treating ICM.

Background and AimsMalnutrition is a well known risk factor for adverse outcomes in patients with cancer, cardiovascular disease (CVD) and chronic kidney disease, but epidemiological evidence on its relationship with the long-term risk of all-cause mortality and cardiovascular death is limited.MethodsA total of 20,116 adults from the United States National Health and Nutrition Examination Survey 2007–2014 were enrolled. The Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), Controlling Nutritional Status (CONUT) score, and Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI) were calculated at baseline. Cox regression and the Kaplan–Meier analysis were conducted when participants were divided into three groups according to the tertiles of objective nutritional scores. Restricted cubic spline was performed to further explore the shape of the relationship between all-cause mortality, cardiovascular death, and nutritional scores. In addition, the area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were conducted to assess which nutritional scores have the greatest predictive value for all-cause death and cardiovascular death in the general population.ResultsThe cumulative incidence of all-cause death and cardiovascular death was significantly higher in participants with a higher CONUT score, lower GNRI, and lower PNI. TCBI showed the worst performance on grading and risk assessment. After adjusting confounding factors, the lowest PNI and GNRI tertile and highest COUNT score were independently and significantly associated with increased risk of all-cause death (all P < 0.01) and cardiovascular death (all P < 0.05) analyzed by a multivariate Cox regression model. An L-shaped association between the HR (hazard ratio) of all-cause mortality and nutritional scores (GNRI, PNI and TCBI) was observed in the overall populations. In addition, the PNI had the highest predictive value for all-cause mortality [AUC: 0.684, 95% confidence interval (CI): 0.667–0.701] and cardiovascular death (AUC: 0.710, 95% CI: 0.672–0.749) in the general population compared with other nutritional scores.ConclusionThe poorer the nutritional status of the general population, the higher the all-cause mortality and cardiovascular mortality. The PNI score may provide more useful predictive values than other nutritional scores.

Inflammation and nutrition as main factors can affect the prognosis of patients with chronic total coronary occlusion (CTO) undergoing percutaneous coronary intervention (PCI). The C-reactive protein to albumin ratio (CAR) can clarify the inflammation and nutrition status, which are highly related to clinical outcomes. This study aims to investigate the association between CAR and adverse cardiovascular events in patients with CTO undergoing PCI. For this study, 664 patients were divided into three groups based on the tertiles of CAR. The primary endpoint was all-cause mortality and the secondary endpoint was major adverse cardiovascular events (MACE). Over a median follow-up of 33.7 months, the primary endpoint occurred in 64 patients (9.6%) and the secondary endpoint occurred in 170 patients (25.6%). The patients with higher CAR represented a worse prognosis with all-cause death and cardiovascular death after the adjustment for the baseline risk factors. Adding the CAR values raised the predictive value for the incidence of the all-cause death and cardiovascular death but not MACE. The capacity of prognosis prediction was improved after the addition of the CAR value to the traditional prediction model.

Heart failure (HF) is a complex clinical syndrome of which the incidence is on the rise worldwide. Cardiometabolic disorders are associated with the deterioration of cardiac function and progression of HF. Recently, there has been renewed interest in gut microbiota (GM) and its metabolites in the cardiovascular disease. HF-caused hypoperfusion could increase intestinal permeability, and a “leaky” bowel leads to bacterial translocation and make its metabolites more easily enter the circulation. Considerable evidence shows that the composition of microbiota and amino acids (AAs) has been altered in HF patients, and AAs could serve as a diagnostic and prognostic biomarker in HF. The findings indicate that the gut–amino acid–HF axis may play a key role in the progression of HF. In this paper, we focus on the interrelationship between the AA metabolism and GM alterations during the development of heart failure. We also discuss the potential prognostic and therapeutic value of the gut–amino acid–HF axis in the cortex of HF.

Abstract Background Despite revascularisation, a large proportion of acute coronary syndrome (ACS) patients continue to experience major adverse cardiovascular events (MACEs), which are worsened by diabetes mellitus (DM). Fibrinogen (FIB) is a risk factor for MACEs in coronary artery disease and often elevated in DM. However, the relationships between FIB, glucose metabolism (haemoglobin A1c [HbA1c] and fasting blood glucose [FBG]) and MACEs following percutaneous coronary intervention (PCI) in DM, non-DM or whole patients with ACS remains unknown. Methods A total of 411 ACS patients undergoing PCI were enrolled in this study. We compared baseline FIB levels between DM (n = 103) and non-DM (n = 308) patients and divided participants into three groups according to FIB level, i.e. FIB-L, FIB-M and FIB-H, to compare baseline characteristics and MACEs. Linear regression analysis of the relationship between glucose metabolism and FIB, Cox regression, survival and landmark analyses of MACEs were also performed over a median of 27.55 months of follow-up. Results Patients with DM had higher FIB levels than non-DM patients (3.56 ± 0.99 mg/dL vs. 3.34 ± 0.80 mg/dL, P

Increased methylglyoxal (MG) formation is associated with diabetes and its complications. In zebrafish, knockout of the main MG detoxifying system Glyoxalase 1, led to limited MG elevation but significantly elevated aldehyde dehydrogenases (ALDH) activity and aldh3a1 expression, suggesting the compensatory role of Aldh3a1 in diabetes. To evaluate the function of Aldh3a1 in glucose homeostasis and diabetes, aldh3a1−/− zebrafish mutants were generated using CRISPR-Cas9. Vasculature and pancreas morphology were analysed by zebrafish transgenic reporter lines. Corresponding reactive carbonyl species (RCS), glucose, transcriptome and metabolomics screenings were performed and ALDH activity was measured for further verification. Aldh3a1−/− zebrafish larvae displayed retinal vasodilatory alterations, impaired glucose homeostasis, which can be aggravated via pdx1 silencing induced hyperglycaemia. Unexpectedly, MG was not altered, but 4-hydroxynonenal (4-HNE), another prominent lipid peroxidation RCS exhibited high affinity with Aldh3a1, was increased in aldh3a1 mutants. 4-HNE was responsible for the retinal phenotype via pancreas disruption induced hyperglycaemia and can be rescued via l-Carnosine treatment. Furthermore, in type 2 diabetic patients, serum 4-HNE was increased and correlated with disease progression. Thus, our data suggest impaired 4-HNE detoxification and elevated 4-HNE concentration as biomarkers but also the possible inducers for diabetes, from genetic susceptibility to the pathological progression.

Innate and adaptive immune cell activation and infiltration is the key characteristic of tissue inflammation. The innate immune system is the front line of host defense in which innate immune cells are activated by danger signals, including pathogen- and danger-associated molecular pattern, and metabolite-associated danger signal. Innate immunity activation can directly contribute to tissue inflammation or immune resolution by phagocytosis and secretion of biologically active molecules, or indirectly via antigen-presenting cell (APC) activation-mediated adaptive immune responses. This review article describes the cellular and molecular interplay of innate-adaptive immune systems. Three major mechanisms are emphasized in this article for their role in facilitating innate-adaptive immunity interplay. 1) APC can be formed from classical and conditional innate immune cells to bridge innate-adaptive immune response. 2) Immune checkpoint molecular pairs connect innate and adaptive immune cells to direct one-way and two-way immune checkpoint reactions. 3) Metabolic reprogramming during immune responses leads to excessive cytosolic and mitochondrial reactive oxygen species (ROS) production. Increased NADPH oxidase-derived extracellular and intracellular ROS are mostly responsible for oxidative stress, which contributes to functional changes in immune cells. Further understanding of innate-adaptive immunity interplay and its underlying molecular basis would lead to the identification of therapeutic targets for immunological and inflammatory disease.

Abstract Aims We assessed the change from baseline in vitamin E, steroid hormones, adrenocorticotropic hormone (ACTH), and gonadotropins, overall and by lowest achieved low‐density lipoprotein‐cholesterol (LDL‐C) level, in patients with type 2 diabetes and dyslipidaemia after 12 weeks of treatment with evolocumab. Materials and Methods This was a prespecified analysis of vitamin E, cortisol, ACTH, gonadal hormones and gonadotropins in the 12‐week, placebo‐controlled BERSON trial of evolocumab in patients with type 2 diabetes and dyslipidaemia. In BERSON, 981 (451 in China) patients on daily atorvastatin 20 mg were randomized to placebo or one of two doses of evolocumab. We measured analyte levels at baseline and week 12 (vitamin E in all patients; steroid/gonadal hormones only in Chinese patients). Results In both the global and Chinese populations, absolute vitamin E levels decreased from baseline to week 12 by approximately 6 μmol/L (P

Objective: Adult human kidneys produce erythropoietin (EPO), which regulates red blood cell formation; however, whether EPO also functions directly on kidney development and controls diabetic kidney disease remains unknown. Here we analyzed the role of EPO in kidney development and under hyperglycemic conditions in zebrafish and in humans. Methods: Diabetic patients and respective controls were enrolled in two cohorts. Serum EPO level and urine protein change upon human EPO administration were then analyzed. Transient knockdown and permanent knockout of EPO and EPOR in renal TG(WT1B:EGFP) zebrafish were established using the morpholino technology and CRISPR/Cas9 technology. Zebrafish embryos were phenotypically analyzed using fluorescence microscopy, and functional assays were carried out with the help of TexasRed labeled 70 kDa Dextran. Apoptosis was determined using the TUNEL assay and Annexin V staining, and caspase inhibitor zVADfmk was used for rescue experiments. Results: In type 2 diabetic patients, serum EPO level decreased with the duration of diabetes, which was linked to reduced kidney function. Human recombinant EPO supplementation ameliorated proteinuria in diabetic nephropathy patients. In zebrafish, loss-of-function studies for EPO and EPOR, showed morphological and functional alterations within the pronephros, adversely affecting pronephric structure, leading to slit diaphragm dysfunction by increasing apoptosis within the pronephros. Induction of hyperglycemia in zebrafish embryos induced pronephros alterations which were further worsened upon silencing of EPO expression. Conclusions: EPO was identified as a direct renal protective factor, promoting renal embryonic development and protecting kidneys from hyperglycemia induced nephropathy. Keywords: Erythropoietin, Type 2 diabetes, Diabetic nephropathy, Zebrafish

Acute myocardial infarction (AMI) still seriously threatens the health of the people in our country. The situation is even more severe in the vast urban and rural areas in China. Timely treatment of AMI patients to reduce mortality and protect heart function is very important. Prehospital thrombolysis treatment has great significance in urban and rural areas outside the big cities. To this end, the Chinese Medical Doctor Association's chest pain professional committee and the Chinese Medical Rescue Association's Cardiovascular Emergency Sub-Commission organized relevant experts to formulate this consensus, aiming to help prehospital medical emergency personnel select the best treatment strategies for patients with AMI. However, the final decision on a specific patient should be made by the prehospital emergency personnel together with the patients and their family members.

The mechanism by which high-salt and low-potassium diet contributes to hypertension remains poorly understood. Plasma homocysteine (Hcys) is recognized as a primary mediator of blood pressure (BP) response to some diets. Therefore, the present study tried to investigate whether plasma Hcys and BP could be regulated by salt loading in normotensive salt-sensitive (SS) persons, and further explored whether potassium supplementation could reverse the effect. We enrolled 47 normotensive subjects, aged 29–65 years. The protocol included 7 days on a low-salt diet (3g/day, NaCl), 7 days on a high-salt diet (18g/day), and then a high-salt diet with potassium supplementation (4.5g/day) for 7 days. After high-salt intake, BP was significantly increased and potassium supplementation lowered it in the SS group. Plasma Hcys were higher in SS subjects than in salt-resistant (SR) subjects after salt loading (34.4 ± 17.0 μmol/L versus 19.16 ± 6.4 μmol/L, P < 0.01). Plasma Hcys in SS subjects was increased on a high-salt diet than on a low-salt diet (34.4 ± 17.0 μmol/L versus 16.5 ± 8.3 μmol/L, P < 0.01), but plasma Hcys was ameliorated by potassium supplementation (34.4 ± 17.0 μmol/L versus 20.9 ± 10.4 μmol/L, P < 0.01). In SS subjects, the change of mean arterial blood pressure (MBP) correlated significantly and positively with the alteration of plasma Hcys during low-salt to high-salt intake and high-salt to high-salt with potassium supplementation (r = 0.75, P < 0.001; r = 0.74, P < 0.001, respectively). Our results indicate that Hcys may partly mediate the impact of high-salt intake and potassium supplementation on BP in SS subjects.

Abstract Background Pioglitazone (PIO), a thiazolidinediones drug, is a well-known anti-diabetic medicine, but its anti-atherosclerotic effects remain controversial. Thus it is important to investigate the effects of PIO on atherogenesis and the relevant mechanisms. Methods For in vitro studies, primary cultured or AMP-activated protein kinase (AMPK) inhibited splenocytes were treated with oxidized low density lipoprotein (ox-LDL) or ox-LDL plus PIO. Percentage of T helper 17 (Th17) and regulatory T (Treg) cells were determined by flow cytometry. Expression of AMPK, interleukin-17 (IL-17) and forkhead box P3 (FoxP3) were detected by Western blots. For in vivo studies, apolipoprotein E–deficient (apoE−/−) mice fed with western diet were treated with PIO or vehicle for 8 weeks respectively. Percentage of Th17 and Treg cells in spleen were measured by immunohistochemical analysis. The atherosclerotic lesions were analyzed using oil red O staining, and collagen types I and III in atherosclerotic lesions were stained by Sirius red. Expression of IL-17 and FoxP3 were determined by quantitative polymerase chain reaction. Results In cultured primary splenocytes, PIO dramatically inhibited Th17 and raised Treg. Intriguingly, pharmacological and genetic AMPK inhibitions abolished PIO-induced Treg elevation and Th17 inhibition. Moreover, PIO significantly induced AMPK phosphorylation, decreased IL-17+ and increased FoxP3+ cells in spleen of apoE−/− mice. Finally, PIO did not alter plaque area, but intriguingly, stabilized atherosclerotic plaque through collagen induction in apoE−/− mice. PIO treatment also improved Th17/Treg balance in atherosclerotic lesions. Conclusions PIO exhibits anti-atherosclerotic effects for stabilization of atherosclerotic plaque through regulating the Th17/Treg balance in an AMPK-dependent manner.

Abstract Background Acute myocardial infarction (AMI) patients with type 2 diabetes mellitus are known to present with multiple vessel lesions during coronary angiography. The underlying mechanism remains elusive and there is a shortage of serum prediction markers. In this study, we investigate the relationship between admission HbA1c and severity of coronary artery stenosis and subsequent prognosis in AMI patients with or without diabetes. Research design and methods We measured admission HbA1c, and vessel scores based on the number of diseased coronary vessels with significant stenosis in 628 patients diagnosed with AMI. Simple and multi-regression analysis were performed to investigate the correlation between HbA1c and the severity of coronary artery stenosis. Major adverse cardiovascular events (MACE), including new-onset myocardial infarction, acute heart failure and cardiac death, were documented during the follow-up. 272 non-DM participants and 137 DM participants were separated into two groups based on HbA1c levels for survival analysis during a 2-year follow up. Results 448 non-DM patients and 180 DM patients were included in the initial observational analysis. 272 non-DM patients and 137 DM patients were included in the follow-up survival analysis. The admission HbA1c level was found to be significantly positively correlated to the number of affected vessels suffering from significant coronary artery stenosis both in DM (R square = 0.012; 95% CI 0.002 to 0.623, P = 0.049) and non DM patients (R square = 0.025; 95% CI 0.009 to 0.289, P = 0.037). Kaplan–Meier survival analysis revealed no significant difference with regard to different HbA1c levels either in DM or non-DM patients at the end of follow-up. Conclusions In patients with AMI, admission HbA1c is an important predictor for the severity of coronary artery stenosis in non-DM and DM patients. Further studies are needed to determine whether longer term follow-up could further identify the prognosis effect of HbA1c on MACE.

Introduction Acute coronary syndrome (ACS) is one of the leading causes of death. Depression and/or anxiety after ACS is common. Studies from developed countries have reported that the occurrence of anxiety or depression after ACS might increase the risk of cardiovascular events and mortality. However, the results varied, and are limited in developing countries. Therefore, well designed large-scale real-world study is needed to make further clarification. The main objective of this study is to evaluate whether depression or anxiety could affect the prognosis of patients with percutaneous coronary intervention (PCI) post-ACS.Method and analysis The study is a prospective, multicentre, cohort study, which will be performed at 12 large hospitals in northwest China and led by the First Affiliated Hospital of Xi'an Jiaotong University. A total of 5000 patients with PCI post-ACS will be enrolled and followed up for 2 years. Their depression and anxiety status will be evaluated with the Patient Health Questionnaire-9 or Generalised Anxiety Disorder-7 Assessment scales during the follow-up. A Cox proportional hazard model will be used to determine if depression/anxiety after PCI increase the risk of cardiovascular events. The impact of antidepression or antianxiety treatment on the cardiac prognosis will be explored as well among the patients with ACS who received the treatment after PCI.Ethics and dissemination This study has been approved by the ethics committee of the First Affiliated Hospital of Xi'an Jiaotong University (approval number: XJTU1AF2016LSL-036). The results will be published in research articles or conference papers.Trial registration number NCT03057691.

Introduction: The availability of reliable noninvasive markers for infarct-related artery patency status are very limited, otherwise could allow early identification of patients with patent IRA, for whom repeat thrombolysis or rescue percutaneous coronary intervention are not necessary. Methods: We conducted a single centered retrospective study of STEMI patients undergoing primary PCI to determine how various factors such as demographic characteristics, risk markers of coronary heart disease, clinical and blood parameters present differently in patients with higher coronary flow and patent infarct related artery from patients with total occlusion at the time of initial angiography and how they affect in outcome of the disease. Results: MPV level (11.96 fL vs. 10.92 fL, P < 0.001), Lp (a) level (179.57 nmol/l vs 141.16 nmol/l , p < 0.001), CK-MB (290.2 vs. 190.98, P < 0.001), total cholesterol level (4.11 mmol/L vs. 3.8 mmol/L, p < 0.02) in total occlusion group were higher than in the patent IRA group. Wall motion abnormality was 77.2% for 203 patients with total occlusion group and 54.2% for 83 patients with patent IRA group (P

BackgroundElevated high‐sensitivity C‐reactive protein (hsCRP) has been associated with increased risks of adverse outcomes of various cardiovascular diseases. The relationship between hsCRP and the prognosis of hypertrophic cardiomyopathy remains to be evaluated. Methods and ResultsThe study used an observational cohort methodology. A total of 490 patients were enrolled in the Fuwai Hospital from 2001 to 2011 and were followed for 3.7±2.0 years. According to the risk category of hsCRP, subjects in the high hsCRP group (>3.0 mg/L) had a higher risk of developing adverse events than the low hsCRP group (

The inflammatory response after polymer-based drug-eluting stent (DES) placement has recently emerged as a major concern. The biologic roles of peroxisome proliferator-activated receptor-γ (PPAR-γ) activators thiazolidinedione (TZD) remain controversial in cardiovascular disease. Herein, we investigated the antiinflammatory effects of pioglitazone (PIO) on circulating peripheral blood mononuclear cells (MNCs) in patients after coronary DES implantation. Methods and Results. Twenty-eight patients with coronary artery disease and who underwent DES implantations were randomly assigned to pioglitazone (30 mg/d; PIO) or placebo (control; Con) treatment in addition to optimal standard therapy. After 12 weeks of treatment, plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-9 (MMP-9) were significantly decreased in PIO group compared to the Con group (P=0.035, 0.011, 0.008, and 0.012, resp.). DES-induced mRNA expressions of IL-6, TNF-α, and MMP-9 in circulating MNC were significantly blocked by PIO (P=0.031, 0.012, and 0.007, resp.). In addition, PIO markedly inhibited DES-enhanced NF-κB function and DES-blocked PPAR-γ activity. Mechanically, DES induced PPAR-γ ubiquitination and degradation in protein level, which can be totally reversed by PIO. Conclusion. PIO treatment attenuated DES-induced PPAR loss, NF-κB activation, and proinflammation, indicating that PIO may have a novel direct protective role in modulating proinflammation in DES era.

Global Registry of Acute Coronary Events (GRACE) risk score and red blood cell distribution width (RDW) content can both independently predict major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS). We investigated the combined predictive value of RDW and GRACE risk score for cardiovascular events in patients with ACS undergoing percutaneous coronary intervention (PCI) for the first time. We enrolled 480 ACS patients. During a median follow-up time of 37.2 months, 70 (14.58%) patients experienced MACEs. Patients were divided into tertiles according to the baseline RDW content (11.30-12.90, 13.00-13.50, 13.60-16.40). GRACE score was positively correlated with RDW content. Multivariate Cox analysis showed that both GRACE score and RDW content were independent predictors of MACEs (hazard ratio 1.039; 95% confidence interval [CI] 1.024-1.055; p < 0.001; 1.699; 1.294-2.232; p < 0.001; respectively). Furthermore, Kaplan-Meier analysis demonstrated that the risk of MACEs increased with increasing RDW content (p < 0.001). For GRACE score alone, the area under the receiver operating characteristic (ROC) curve for MACEs was 0.749 (95% CI: 0.707-0.787). The area under the ROC curve for MACEs increased to 0.805 (0.766-0.839, p = 0.034) after adding RDW content. The incremental predictive value of combining RDW content and GRACE risk score was significantly improved, also shown by the net reclassification improvement (NRI = 0.352, p < 0.001) and integrated discrimination improvement (IDI = 0.023, p = 0.002). Combining the predictive value of RDW and GRACE risk score yielded a more accurate predictive value for long-term cardiovascular events in ACS patients who underwent PCI as compared to each measure alone.

There are several indigenous ethnic populations along the silk road in the Northwest of China that display clear differences in culture and social customs, perhaps as a result of geographic isolation and different linguistic traditions. However, extensive trade and other interactions probably facilitated the admixture of different gene pools between these populations over the last two millennia. To further explore the evolutionary relationships of the 13 ethnic populations residing in Northwest China and to reveal the features of population admixture, the 9 most-commonly employed CODIS loci (D3S1358, TH01, D5S818, D13S317, D7S820, CSF1PO, vWA, TPOX, FGA) were selected for genotyping and further analysis. Phylogenetic tree and principal component analysis revealed clear pattern of population differentiation between 4 populations living in Sinkiang Uighur Autonomous Region and other 9 populations dwelled in the upper regions of Silk Road. R matrix regression showed high-level gene flow and population admixture dose exist among these ethic populations in the Northwest region of China. Furthermore, the Mantel test suggests that larger percent of genetic variance (21.58% versus 2.3%) can be explained by geographic isolation than linguistic barriers, which matched with the contribution of geographic factors to other world populations.

BACKGROUND: Chronic hyperglycemia in type 2 diabetes increases the risk of microvascular events. However, there is continuing uncertainty about its effect on macrovascular outcomes and death. We conducted a meta-analysis of prospective studies to estimate the association of glycosylated hemoglobin level with the risk of all-cause mortality and cardiovascular outcomes among patients with type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: We systematically searched the MEDLINE database through April 2011 by using Medical Subject Heading search terms and a standardized protocol. We included prospective cohort studies that reported data of glycosylated hemoglobin level on the risk of incident cardiovascular events and all-cause mortality. Relative risk estimates (continuous and categorical variables) were derived or abstracted from each cohort study. Twenty six studies were included in this analysis with a mean follow-up rang of 2.2-16 years. The pooled relative risk associated with a 1% increase in glycosylated hemoglobin level among patients with type 2 diabetes was 1.15 (95% CI, 1.11 to 1.20) for all-cause mortality, 1.17 (95% CI, 1.12 to 1.23) for cardiovascular disease, 1.15 (95% CI, 1.10 to 1.20) for coronary heart disease, 1.11 (95% CI, 1.05 to 1.18) for heart failure, 1.11 (95% CI, 1.06 to 1.17) for stroke, and 1.29 (95% CI, 1.18 to 1.40) for peripheral arterial disease, respectively. In addition, a positive dose-response trend existed between glycosylated hemoglobin level and cardiovascular outcomes. CONCLUSIONS/SIGNIFICANCE: Chronic hyperglycemia is associated with an increased risk for cardiovascular outcomes and all-cause mortality among patients with type 2 diabetes, likely independently from other conventional risk factors.