RESUMEN
Systematic integration of lncRNA-disease associations is of great importance for further understanding their underlying molecular mechanisms and exploring lncRNA-based biomarkers and therapeutics. The database of long non-coding RNA-associated diseases (LncRNADisease) is designed for the above purpose. Here, an updated version (LncRNADisease v3.0) has curated comprehensive lncRNA (including circRNA) and disease associations from the burgeoning literatures. LncRNADisease v3.0 exhibits an over 2-fold increase in experimentally supported associations, with a total of 25440 entries, compared to the last version. Besides, each lncRNA-disease pair is assigned a confidence score based on experimental evidence. Moreover, all associations between lncRNAs/circRNAs and diseases are classified into general associations and causal associations, representing whether lncRNAs or circRNAs can directly lead to the development or progression of corresponding diseases, with 15721 and 9719 entries, respectively. In a case study, we used the data of LncRNADisease v3.0 to calculate the phenotypic similarity between human and mouse lncRNAs. This database will continue to serve as a valuable resource for potential clinical applications related to lncRNAs and circRNAs. LncRNADisease v3.0 is freely available at http://www.rnanut.net/lncrnadisease.
Asunto(s)
Bases de Datos de Ácidos Nucleicos , Enfermedad , ARN Largo no Codificante , Animales , Humanos , Ratones , Bases de Datos Genéticas , ARN Circular , ARN Largo no Codificante/genética , Enfermedad/genéticaRESUMEN
Background: The high prevalence of chronic obstructive pulmonary disease (COPD) in coronary artery disease (CAD) has been acknowledged over the past decade, although the cause/s remain uncertain due to differences in diagnoses. COPD has also become a leading CAD comorbidity, although again little is known about its interactions. This meta-analysis explored COPD prevalence in the global CAD population, as well as the influence of COPD on CAD. Methods: PubMed, Web of Science, Embase, and grey literature were searched until 26th November 2021. The prevalence of COPD was calculated, and data were grouped according to COPD diagnostic methods, interventions, region, economic status, etc. Outcomes including all-cause death, cardiac death, myocardial infarction, revascularization, stroke, heart failure, and respiratory failure were analyzed. This study was registered with PROSPERO (CRD No.42021293270). Results: There was an average prevalence of 14.2% for COPD in CAD patients (95% CI: 13.3-15.1), with diagnostics of COPD through spirometry, International Classification of the Diseases (ICD codes), and self-reported methods. Comorbid COPD-CAD patients were more likely to be smokers and suffer from cardiovascular and respiratory complications (all odds ratios [OR] > 1). COPD-CAD has higher mortality (hazard ratio [HR] 2.81, 95% CI: 2.40-3.29), and myocardial infarction, stroke, and respiratory failure rates (all HR > 1). Coronary artery bypass graft (CABG) reduces the need for revascularization (HR 0.43, 95% CI: 0.20-0.94) compared to percutaneous coronary intervention (PCI), without increasing mortality. Conclusions: The global prevalence of COPD is particularly high in CAD patients. COPD-CAD patients are more likely to encounter cardiovascular and respiratory complications and endure poorer outcomes. Limited evidence suggests that CABG may reduce the need for revascularization without increasing mortality, although further research is required to confirm these observations.
RESUMEN
BACKGROUND: Limited research has been conducted on the potential relationship between the dietary inflammation index (DII) and mortality, particularly in individuals with Helicobacter pylori (H. pylori) infection. This study aimed to investigate the association between the DII and H. pylori infection, as well as their respective impacts on all-cause mortality in a cohort of individuals with or without H. pylori infection. METHODS: Data from the 1999-2018 National Health and Nutrition Examination Survey (NHANES) were utilized for this study, with a final of 4370 participants included. Both univariable and multivariable-adjusted logistic regression analyses were employed to explore the relationship between H. pylori infection and pertinent covariates. Cox regression analysis, as well as restricted regression cubic spline analysis, were utilized to assess the association between DII and all-cause mortality among individuals with or without H. pylori infection. RESULTS: The findings demonstrated a positive correlation between DII scores and H. pylori infection, even after adjusting for potential confounding factors. Moreover, higher DII scores were significantly associated with an elevated risk of mortality exclusively in individuals with H. pylori infection, while no such association was observed in the uninfected population. Additional analysis using restricted cubic spline modeling revealed a positive linear relationship between DII scores as a continuous variable and the adjusted risk of all-cause mortality specifically in H. pylori-infected patients. CONCLUSION: The results of this study indicated that DII was positively correlated with an increased risk of H. pylori infection and was associated with a heightened risk of all-cause mortality solely in individuals with H. pylori infection. Consequently, DII might serve as a useful tool for risk stratification in the H. pylori-infected population among U.S. adults. Further research is warranted to elucidate the underlying mechanisms and potential clinical implications of these findings.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Adulto , Humanos , Encuestas Nutricionales , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/epidemiología , Dieta/efectos adversos , InflamaciónRESUMEN
BACKGROUND: The relationship between stress hyperglycemia and long-term prognosis in acute decompensated heart failure (ADHF) patients is unknown. This study investigated the associations of stress hyperglycemia with mortality and rehospitalization rates among ADHF patients with diabetes. METHODS: We consecutively enrolled 1904 ADHF patients. Among them, 780 were with diabetes. Stress hyperglycemia was estimated using the stress hyperglycemia ratio (SHR), which was calculated by the following formula: SHR = admission blood glucose/[(28.7 × HbA1c%) - 46.7]. All diabetic ADHF subjects were divided into quintiles according to the SHR. The primary endpoint was all-cause death at the 3-year follow-up. The secondary endpoints were cardiovascular (CV) death and heart failure (HF) rehospitalization at the 3-year follow-up. A Cox proportional hazards model and restricted cubic spline analysis were used to elucidate the relationship between the SHR and the endpoints in diabetic ADHF patients. Further analyses were performed to examine the relationships between SHR and the outcomes in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). RESULTS: A total of 169 all-cause deaths were recorded during a median follow-up of 3.24 years. Restricted cubic spline analysis suggested a U-shaped association between the SHR and the mortality and rehospitalization rates. Kaplan-Meier survival analysis showed the lowest mortality in the 2nd quintile (P = 0.0028). Patients categorized in the highest range (5th quintile) of SHR, compared to those in the 2nd quintile, exhibited the greatest susceptibility to all-cause death (with a hazard ratio [HR] of 2.76 and a 95% confidence interval [CI] of 1.63-4.68), CV death (HR 2.81 [95% CI 1.66-4.75]) and the highest rate of HF rehospitalization (HR 1.54 [95% CI 1.03-2.32]). Similarly, patients in the lowest range (1st quintile) of SHR also exhibited significantly increased risks of all-cause death (HR 2.33, 95% CI 1.35-4.02) and CV death (HR 2.32, 95% CI 1.35-4.00). Further analyses indicated that the U-shape association between the SHR and mortality remained significant in both HFpEF and HFrEF patients. CONCLUSION: Both elevated and reduced SHRs indicate an unfavorable long-term prognosis in patients with ADHF and diabetes.
Asunto(s)
Diabetes Mellitus , Insuficiencia Cardíaca , Hiperglucemia , Humanos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Readmisión del Paciente , Volumen Sistólico , Factores de Riesgo , Pronóstico , Hiperglucemia/diagnósticoRESUMEN
BACKGROUND: The impact of insulin resistance on the prognosis of heart failure with preserved ejection fraction (HFpEF) remains unknown. This study aimed to investigate the association between the triglyceride-glucose (TyG) index, an easily calculated marker of insulin resistance, and the long-term prognosis of HFpEF. METHODS: A total of 823 patients with HFpEF were enrolled in the study. The TyG index was determined using the formula ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). The primary endpoint was all-cause death. The secondary endpoints were cardiovascular (CV) death and heart failure (HF) rehospitalization. Restricted cubic spline, multivariate Cox proportional hazard models, and competing risk models were used for analyses. RESULTS: During a median follow-up period of 3.16 years, 147 (17.8%) all-cause deaths, 139 (16.8%) CV deaths, and 222 (27.0%) HF rehospitalizations occurred. Restricted cubic spline analysis revealed a J-shaped association between the TyG index and the mortality and rehospitalization rates. In the multivariate Cox proportional hazard models, compared with those in the lowest TyG index tertile, patients in the highest tertile exhibited the greatest susceptibility to all-cause death (HR 1.53, 95% CI 1.19-1.98) and CV death (HR 1.52, 95% CI 1.19-1.96). In the competing risk model, a significant association between the TyG index and HF rehospitalization was observed (HR 1.31, 95% CI, 1.07-1.61). CONCLUSION: A high TyG index is associated with an increased risk of mortality and rehospitalization in patients with HFpEF. The TyG index may serve as a promising prognostic marker for patients with HFpEF.
Asunto(s)
Insuficiencia Cardíaca , Resistencia a la Insulina , Humanos , Factores de Riesgo , Insuficiencia Cardíaca/diagnóstico , Biomarcadores , Volumen Sistólico , Triglicéridos , Glucemia , Pronóstico , Glucosa , Medición de RiesgoRESUMEN
Background: Few studies have focused on the impact of stress hyperglycemia on adverse outcomes in patients with acute myocarditis. We conducted the present study to assess the association between the stress hyperglycemia ratio (SHR) and poor prognosis in patients with acute myocarditis. Methods: From 2006 to 2020, 185 patients with acute myocarditis were enrolled. The SHR was defined as glucose at admission divided by estimated average glucose ([(1.59 × HbA1c %) - 2.59], glycated hemoglobin [HbA1c]). Participants were divided into two groups according to their SHR values. The primary endpoint was defined as in-hospital major adverse cardiovascular events (MACE), including death, heart transplantation, the need for mechanical circulatory support (MCS), and transfer to the intensive care unit (ICU). The secondary endpoint was defined as long-term MACE. Results: Subjects in the higher SHR group had more serious conditions, including lower systolic blood pressure, higher heart rate, higher white blood cell count, higher levels of alanine transaminase, troponin I, and C-reactive protein, and worse cardiac function. Multivariate logistic analysis showed that SHR > 1.12 (hazard ratio (HR): 3.946, 95% confidence interval (CI): 1.098-14.182; p = 0.035) was independently associated with in-hospital MACE in patients with acute myocarditis. Kaplan-Meier survival analysis and multivariate Cox analysis suggested that an SHR > 1.39 (HR: 1.931, 95% CI: 0.323-2.682; p = 0.895) was not significantly associated with long-term prognosis. Conclusions: SHR was independently associated with in-hospital adverse outcomes in patients with acute myocarditis but not with long-term prognosis.
RESUMEN
PURPOSE: It is unclear whether or not nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated fatty liver disease (MAFLD) is related to short sleep duration. A meta-analysis was conducted to determine if inadequate sleep time increased the risk of NAFLD/MAFLD. METHODS: A comprehensive systematic literature review was conducted in the Embase, PubMed, and Cochrane Library databases from inception to August 1, 2022. Studies examining the correlation between inadequate sleep time and the risk of NAFLD/MAFLD were included. We pooled the odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. RESULTS: This meta-analysis included fifteen studies involving a total of 261,554 participants. In the pooled analysis, short sleep duration was found to be strongly correlated with an increased risk of NAFLD/MAFLD (OR, 1.15; 95% CI, 1.04-1.28; P = 0.01), with a moderate degree of heterogeneity between studies (I2 = 71.92%, Q = 49.87, P < 0.01). The sensitivity analysis suggested that the primary outcome was robust, and there was no significant publication bias. CONCLUSION: This meta-analysis indicates that inadequate sleep duration is strongly correlated with an elevated risk of NAFLD/MAFLD. The findings suggest that obtaining an adequate amount of sleep may be useful for preventing NAFLD/MAFLD, which is especially important given the low rate of response to pharmacotherapy.
Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Duración del Sueño , Humanos , Privación de Sueño , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Sueño , Oportunidad RelativaRESUMEN
BACKGROUND AND AIMS: NAFLD has become a tremendous burden for public health; however, there is no drug for NAFLD therapy at present. Impaired endo-lysosome-mediated protein degradation is observed in a variety of metabolic disorders, such as atherosclerosis, type 2 diabetes mellitus, and NAFLD. Small integral membrane protein of lysosome/late endosome (SIMPLE) is a regulator of endosome-to-lysosome trafficking and cell signaling, but the role that SIMPLE plays in NAFLD progression remains unknown. Here we investigated SIMPLE function in NAFLD development and sophisticated mechanism therein. APPROACH AND RESULTS: This study found that in vitro knockdown of SIMPLE significantly aggravated lipid accumulation and inflammation in hepatocytes treated with metabolic stimulation. Consistently, in vivo experiments showed that liver-specific Simple-knockout (Simple-HKO) mice exhibited more severe high-fat diet (HFD)-induced, high-fat-high-cholesterol diet (HFHC)-induced, and methionine-choline-deficient diet (MCD)-induced steatosis, glucose intolerance, inflammation, and fibrosis than those fed with normal chow (NC) diet. Meanwhile, RNA-sequencing demonstrated the up-regulated signaling pathways and signature genes involved in lipid metabolism, inflammation, and fibrosis in Simple-HKO mice compared with control mice under metabolic stress. Mechanically, we found SIMPLE directly interact with epidermal growth factor receptor (EGFR). SIMPLE deficiency results in dysregulated degradation of EGFR, subsequently hyperactivated EGFR phosphorylation, thus exaggerating NAFLD development. Moreover, we demonstrated that using EGFR inhibitor or silencing EGFR expression could ameliorate lipid accumulation induced by the knockdown of SIMPLE. CONCLUSIONS: SIMPLE ameliorated NASH by prompting EGFR degradation and can be a potential therapeutic candidate for NASH.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Receptores ErbB/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , Animales , Biopsia , Células Cultivadas , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/genética , Dieta Alta en Grasa/efectos adversos , Receptores ErbB/antagonistas & inhibidores , Femenino , Técnicas de Silenciamiento del Gen , Hepatocitos , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Hígado/metabolismo , Hígado/patología , Lisosomas/metabolismo , Masculino , Ratones , Ratones Noqueados , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Proteínas Nucleares/genética , Cultivo Primario de Células , Proteolisis , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/genéticaRESUMEN
BACKGROUND AND AIMS: NAFLD prevalence has increased rapidly and become a major global health problem. Tumor necrosis factor α-induced protein 8-like 2 (TIPE2) plays a protective role in a cluster of liver diseases, such as autoimmune hepatitis, hepatitis B, and hepatocellular carcinoma. However, the function of TIPE2 in NAFLD remains unknown. Here, we investigated the role of TIPE2 in the development of NAFLD. APPROACH AND RESULTS: Our study found that in vitro overexpression or knockout of TIPE2 significantly ameliorated or aggravated lipid accumulation and inflammation in hepatocytes exposed to metabolic stimulation, respectively. Consistently, in vivo hepatic steatosis, insulin resistance, inflammation, and fibrosis were alleviated in hepatic Tipe2-transgenic mice but exaggerated in hepatic Tipe2-knockout mice treated by metabolic challenges. RNA sequencing revealed that TIPE2 was significantly associated with the mitogen-activated protein kinase pathway. Mechanistic experiments demonstrated that TIPE2 bound with transforming growth factor beta-activated kinase 1 (TAK1), prevented tumor necrosis factor receptor-associated factor 6-mediated TAK1 ubiquitination and subsequently inhibited the TAK1 phosphorylation and activation of TAK1-c-Jun N-terminal kinase (JNK)/p38 signaling. Further investigation showed that blocking the activity of TAK1 reversed the worsening of hepatic metabolic disorders and inflammation in hepatic-specific Tipe2-knockout hepatocytes and mice treated with metabolic stimulation. CONCLUSIONS: TIPE2 suppresses NAFLD advancement by blocking TAK1-JNK/p38 pathway and is a promising target molecule for NAFLD therapy.
Asunto(s)
Hepatocitos/metabolismo , Resistencia a la Insulina/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Quinasas Quinasa Quinasa PAM/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Animales , Dieta Alta en Grasa , Hepatocitos/patología , Inflamación , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Sistema de Señalización de MAP Quinasas/genética , Ratones , Ratones Noqueados , Ratones Transgénicos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , UbiquitinaciónRESUMEN
BACKGROUND: Non-diabetic coronary artery disease (CAD) patients are thought to encounter metabolic dysfunction and while these changes may be imperceptible to the patient they probably influence outcomes. At present, there is no system to support patients sensing these subtle changes, nor is there an established model for prognoses. The Atherogenic Index of Plasma (AIP) index has already proven useful for atherosclerosis although further research is needed, especially for those without hyperglycemia. METHODS: This is a prospective study of 5538 non-diabetic CAD patients who had received percutaneous coronary intervention (PCI). Participants were assigned to one of three groups according to their AIP index. High AIP index cases were then compared to low index patients according to major adverse cardiac events (MACE). Restricted cubic spline (RCS) analysis was also conducted to investigate interrelations between AIP index levels and hazard ratios (HR) for MACEs. RESULTS: Patients with a high AIP index encountered metabolic dysfunction compared to those with a low AIP index i.e., higher Body Mass Index (BMI), Total Cholesterol (TC), Triglycerides (TG), and uric acid as well as lower HDL-C. Each of the aforementioned interrelations were significant with p values of less than 0.001. There was also a significant increase in the number of MACEs in the high AIP index group compared to the low AIP index group (HR: 1.37, 95% CI 1.04-1.81; p = 0.025). A J-shaped RCS curve highlighted a change in the HR after the 0.18 juncture (HR per SD: 1.20, 95% CI 0.96-1.50). Further subgroup analysis supported the main findings, all with HRs greater than one. CONCLUSION: The AIP index could be used in prognostics for non-diabetic CAD patients 2 years after PCI. The relationship between hazard ratio and the AIP index appears to be J-shaped. Although, further multi-center studies designed for non-diabetic patients with potential metabolic dysfunction should be conducted to determine the value of the AIP index.
Asunto(s)
Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , China/epidemiología , HDL-Colesterol , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Humanos , Intervención Coronaria Percutánea/efectos adversos , Estudios Prospectivos , Factores de Riesgo , TriglicéridosRESUMEN
ABSTRACT: Over the past decade, histone deacetylases (HDACs) has been proven to manipulate development and exacerbation of cardiovascular diseases, including myocardial ischemia/reperfusion injury, cardiac hypertrophy, ventricular remodeling, and myocardial fibrosis. Inhibition of HDACs, especially class-I HDACs, is potent to the protection of ischemic myocardium after ischemia/reperfusion (I/R). Herein, we examine whether mocetinostat (MGCD0103, MOCE), a class-I selective HDAC inhibitor in phase-II clinical trial, shows cardioprotection under I/R in vivo and in vitro, if so, reveal its potential pharmacological mechanism to provide an experimental and theoretical basis for mocetinostat usage in a clinical setting. Human cardiac myocytes (HCMs) were exposed to hypoxia and reoxygenation (H/R), with or without mocetinostat treatment. H/R reduced mitochondrial membrane potential and induced HCMs apoptosis. Mocetinostat pretreatment reversed these H/R-induced mitochondrial damage and cellular apoptosis and upregulated CREB, p-CREB, and PGC-1α in HCMs during H/R. Transfection with small interfering RNA against PGC-1α or CREB abolished the protective effects of mocetinostat on cardiomyocytes undergoing H/R. In vivo, mocetinostat was demonstrated to protect myocardial injury posed by myocardial I/R via the activation of CREB and upregulation of PGC-1α. Mocetinostat (MGCD0103) can protect myocardium from I/R injury through mitochondrial protection mediated by CREB/PGC-1α pathway. Therefore, activation of the CREB/PGC-1α signaling pathway via the inhibition of Class-I HDACs may be a promising new therapeutic strategy for alleviating myocardial reperfusion injury.
Asunto(s)
Daño por Reperfusión Miocárdica , Animales , Apoptosis , Benzamidas , Inhibidores de Histona Desacetilasas/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Histona Desacetilasas/metabolismo , Histona Desacetilasas/farmacología , Histona Desacetilasas/uso terapéutico , Humanos , Isquemia/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/farmacología , Isoformas de Proteínas/uso terapéutico , Pirimidinas , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
BACKGROUND: The prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome. METHODS: We included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS). RESULTS: During the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (all p < 0.05). The positive relationship between LFS and MACCE was consistent in different subgroups. CONCLUSIONS: In ACS patients, increased LFS predicted an elevated risk of thrombotic events but not bleeding. LFS may contribute to thrombotic risk stratification after ACS.
RESUMEN
BACKGROUND: Success rate of transcatheter aortic valve replacement (TAVR) in aortic regurgitation (AR) patients is relatively low on account of the absence of calcified anchoring structures. Morphological classification and corresponding TAVR strategies for AR are lacking yet. METHODS: The AURORA study is a prospective, multicenter, single-arm cohort study to evaluate the safety and efficacy of transfemoral TAVR for severe AR in patients with high or prohibitive risk for surgery. Patients who are ≥ 65 years and diagnosed with severe pure AR as defined by the Echocardiographic Core Laboratory will be consecutively enrolled for further multidetector computed tomography (MDCT) scanning and multiplanar analyses. Based on a new anatomical classification and dual anchoring theory, patients will be classified into 4 types according to the level of the anchoring area. Types 1, 2 and 3 (at least 2 anchoring areas) will undergo the TAVR procedure with a domestic Chinese self-expanding valve (VitaFlow Valve, MicroPort, Shanghai, China), whereas type 4 (0 or 1 anchoring area) patients will be considered unsuitable for TAVR and will receive medical treatment. Our goal is to recruit 100 patients to account for 10% missing data or loss of patients to follow-up. Procedural, 30-day, 6-month and 12-month outcomes will be assessed according to Valve Academic Research Consortium-3 criteria. DISCUSSION: The AURORA study will establish a new AR anatomical classification based on dual anchoring theory through MDCT multiplanar measurement and assess the safety and efficacy of TAVR guided by this new classification and strategy in AR patients. TRIAL REGISTRATION: This Study was registered at Chinses Clinical Trial Registry. The registration number: ChiCTR2200055415; The date of registration: 9, January 2022; The URL of the registration: http://www.chictr.org.cn/showproj.aspx?proj=141209 .
Asunto(s)
Insuficiencia de la Válvula Aórtica , Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/etiología , Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , China , Estudios de Cohortes , Humanos , Estudios Prospectivos , Diseño de Prótesis , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
Growing evidences have revealed that a histone deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA) has anti-fibrotic effect in different diseases. In this study, we first evaluated whether SAHA could suppress cardiac fibrosis. Mice with MI-induced cardiac fibrosis were treated with SAHA by intraperitoneal injection and their cardiac function was improved after SAHA treatment. Results of western blotting and qRT-PCR in heart tissues suggested that TGFß1/P38 pathway was activated in MI mice, and this effect was reversed by SAHA. Cell proliferation assay suggested that SAHA could suppress TGF-ß1-induced cardiac fibroblasts proliferation. Furthermore, results of western blotting and qRT-PCR in cardiac fibroblasts depicted that SAHA may exert its anti-fibrotic effect through inhibiting TGF-ß1-induced P38 phosphorylation by promoting DUSP4 expression. Our findings may substantiate SAHA as a promising treatment for MI-induced cardiac fibrosis.
Asunto(s)
Cardiopatías , Animales , Fibroblastos , Fibrosis , Inhibidores de Histona Desacetilasas/farmacología , Sistema de Señalización de MAP Quinasas , Ratones , Proteínas Tirosina Fosfatasas , Factor de Crecimiento Transformador beta1/genética , Vorinostat/farmacologíaRESUMEN
BACKGROUND: Patients with atrial fibrillation (AF) and coronary stenting had a poor prognosis. This study aimed to assess the accuracy of CHA2DS2-VASc score for predicting and grading adverse clinical outcomes in this population. METHODS: We reviewed the clinical data of all patients with previously documented nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. The study population was divided into three groups: 1) Low CHA2DS2-VASc score, ⦠2 points, 2) Intermediate score, 3-4 points, and 3) High score, ⧠5 points. Major adverse cardiac/cerebrovascular events (MACCE) were defined as a composite of all-cause death, nonfatal myocardial infarction, repeat revascularization and ischemic stroke/systemic thromboembolism (IS/SE). RESULTS: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included, with the CHA2 DS2-VASc score of 3.6 ± 1.6. The median follow-up duration was 36.2 months. All-cause mortality increased 3 folds from the low score (4.8%) to the high score group (15.8%). The high score group had more IS/SE (7.4%) and MACCE (26.3%). The CHA2 DS2-VASc score ⧠5 points was independently associated with all-cause death (hazard ratio [HR]: 2.303, 95% confidence interval [CI]: 1.492- 3.555), IS/SE (HR: 4.169, 95% CI: 2.216-7.845) and MACCE (HR: 1.468, 95% CI: 1.113-1.936) on multivariate Cox proportional hazards regression. The area under the receiver operating characteristic curve of the CHA2DS2-VASc score was 0.644 (95% CI: 0.624-0.663) for all-cause death, 0.647 (95% CI: 0.627-0.666) for IS/SE, and 0.592 (95% CI: 0.572-0.611) for MACCE. DISCUSSION: CHA2DS2-VASc score was a reliable prognostic indicator in patients with AF and coronary stenting.
Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular , Masculino , Humanos , Femenino , Anciano , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Pronóstico , Accidente Cerebrovascular/complicaciones , Medición de Riesgo , Factores de RiesgoRESUMEN
Subclinical hypothyroidism and low T3 syndrome are commonly associated with an increased risk of cardiovascular disease (CVD) and mortality. We examined effects of T3 on T-tubule (TT) structures, Ca2+ mobilization and contractility, and clustering of dyadic proteins. Thyroid hormone (TH) deficiency was induced in adult female rats by propyl-thiouracil (PTU; 0.025%) treatment for 8 weeks. Rats were then randomized to continued PTU or triiodo-L-thyronine (T3; 10 µg/kg/d) treatment for 2 weeks (PTU + T3). After in vivo echocardiographic and hemodynamic recordings, cardiomyocytes (CM) were isolated to record Ca2+ transients and contractility. TT organization was assessed by confocal microscopy, and STORM images were captured to measure ryanodine receptor (RyR2) cluster number and size, and L-type Ca2+ channel (LTCC, Cav1.2) co-localization. Expressed genes including two integral TT proteins, junctophilin-2 (Jph-2) and bridging integrator-1 (BIN1), were analyzed in left ventricular (LV) tissues and cultured CM using qPCR and RNA sequencing. The T3 dosage used normalized serum T3, and reversed adverse effects of TH deficiency on in vivo measures of cardiac function. Recordings of isolated CM indicated that T3 increased rates of Ca2+ release and re-uptake, resulting in increased velocities of sarcomere shortening and re-lengthening. TT periodicity was significantly decreased, with reduced transverse tubules but increased longitudinal tubules in TH-deficient CMs and LV tissue, and these structures were normalized by T3 treatment. Analysis of STORM data of PTU myocytes showed decreased RyR2 cluster numbers and RyR localizations within each cluster without significant changes in Cav1.2 localizations within RyR clusters. T3 treatment normalized RyR2 cluster size and number. qPCR and RNAseq analyses of LV and cultured CM showed that Jph2 expression was T3-responsive, and its increase with treatment may explain improved TT organization and RyR-LTCC coupling.
Asunto(s)
Señalización del Calcio/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/metabolismo , Hipotiroidismo/tratamiento farmacológico , Triyodotironina/administración & dosificación , Animales , Calcio/metabolismo , Canales de Calcio Tipo L/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Expresión Génica , Hipotiroidismo/sangre , Hipotiroidismo/inducido químicamente , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Miocitos Cardíacos/metabolismo , Ratas , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Sarcolema/metabolismo , Sarcómeros/metabolismo , Resultado del Tratamiento , Triyodotironina/sangre , Función Ventricular/efectos de los fármacosRESUMEN
BACKGROUND: Evidence is limited regarding the association of healthy lifestyle including sleep pattern with the risk of complicated type 2 diabetes mellitus (T2DM) among patients with hypertension. We aimed to investigate the associations of an overall healthy lifestyle including a healthy sleep pattern with subsequent development of T2DM among participants with hypertension compared to normotension, and to estimate how much of that risk could be prevented. METHODS: This study examined six lifestyle factors with T2DM cases among hypertension (227,966) and normotension (203,005) and their interaction in the UK Biobank. Low-risk lifestyle factors were defined as standard body mass index (BMI), drinking alcohol in moderation, nonsmoking, engaging in moderate- to vigorous-intensity physical activity, eating a high-quality diet, and maintaining a healthy sleep pattern. RESULTS: There were 12,403 incident T2DM cases during an average of 8.63 years of follow-up. Compared to those with 0 low-risk lifestyle factors, HRs for those with 5-6 were 0.14 (95% CI 0.10 to 0.19) for hypertensive participants, 0.13 (95% CI 0.08 to 0.19) for normotensive participants, respectively (ptrend < 0.001). 76.93% of hypertensive participants were considerably less likely to develop T2DM if they adhered to five healthy lifestyle practices, increased to 81.14% if they followed 6-factors (with a healthy sleep pattern). Compared with hypertension adults, normotensive people gain more benefits if they stick to six healthy lifestyles [Population attributable risk (PAR%) 83.66%, 95% CI 79.45 to 87.00%, p for interaction = 0.0011]. CONCLUSIONS: Adherence to a healthy lifestyle pattern including a healthy sleep pattern is associated with lower risk of T2DM in hypertensives, and this benefit is even further in normotensives.
Asunto(s)
Diabetes Mellitus Tipo 2/prevención & control , Estilo de Vida Saludable , Hipertensión/terapia , Conducta de Reducción del Riesgo , Sueño , Adulto , Anciano , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Dieta Saludable , Ejercicio Físico , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
OBJECTIVE: This study aimed to evaluate the usefulness of the admission risk index (RI) to predict short-term and long-term outcomes in a broad population with ST-elevation myocardial infarction (STEMI) using data from the Chinese Acute Myocardial Infarction Registry. BACKGROUND: The RI was developed as a simple tool to predict risk of death in STEMI patients. The performance in predicting short-term and long-term risk of death in Chinese patients receiving percutaneous coronary intervention and conservative treatment for STEMI remains unclear. METHODS: Age, heart rate (HR), and systolic blood pressure (SBP) were used to calculate RI using (HR×[age/10]2 )/SBP. We used the prediction tool to predict mortality over 12 months. RESULTS: The C-index of the admission RI for predicting in-hospital, 1-, 6-, and 12-months mortality were 0.78, 0.78, 0.78, and 0.77, respectively, compared with 0.75 of the Global Registry in Acute Coronary Events score. Based on the receiver operating characteristic curve analysis, the RI was categorized into quintiles for convenient clinical use, and it revealed a nearly 15-fold gradient of increasing mortality from 2.29 to 32.5% (p < .0001) while RI >34 had the highest mortality. By categorizing into five different risk groups, the short-term and long-term mortality of patients receiving different treatments could be distinguished. CONCLUSIONS: RI based on three routine variables and easily calculated by any medical practitioner is useful for predicting in-hospital and long-term mortality in patients with STEMI at the initial consultation with clinicians.
Asunto(s)
Tratamiento Conservador/mortalidad , Técnicas de Apoyo para la Decisión , Indicadores de Salud , Intervención Coronaria Percutánea/mortalidad , Infarto del Miocardio con Elevación del ST/terapia , Factores de Edad , Anciano , Presión Sanguínea , China , Tratamiento Conservador/efectos adversos , Femenino , Frecuencia Cardíaca , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Admisión del Paciente , Intervención Coronaria Percutánea/efectos adversos , Valor Predictivo de las Pruebas , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/fisiopatología , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: To report the clinical outcomes of the RESTORE drug-coated balloon (DCB; Cardionovum, Bonn, Germany) for treatment of de novo small vessel disease (SVD) beyond 1 year. BACKGROUND: Previous reports have demonstrated the noninferiority of the RESTORE DCB to the RESOLUTE Integrity drug-eluting stent (DES; Medtronic, Minneapolis, Minnesota) in terms of 9-month in-segment percent diameter stenosis. METHODS: In the prospective, multicenter, noninferiority RESTORE SVD China trial, 230 patients with visually-estimated reference vessel diameter (RVD) ≥2.25 and ≤2.75 mm were randomized to DCB or DES in a 1:1 ratio stratified by diabetes and number of lesions treated. Furthermore, 32 patients with RVD ≥2.00 and <2.25 mm were enrolled in a nested very small vessel (VSV) registry. Clinical follow-up were performed at 2 years to evaluate target lesion failure (TLF) in both groups and the VSV cohort. RESULTS: Overall, 256 (97.7%) patients (115 and 109 in the DCB and DES groups, respectively, and 32 in the VSV cohort) completed 2 years of follow-up. There was no significant difference in TLF between the DCB and DES groups (5.2 vs. 3.7%, p = .75). Target lesion revascularization was acceptable at 1 month, 1 year, and 2 years, and did not differ significantly with DCB from that in the DES group (0.9 vs. 0%, p = 1.0, 4.4 vs. 2.6%, p = .72, 5.2 vs. 2.8%, p = .50, respectively). CONCLUSIONS: Compared to the second-generation DES, the RESTORE DCB did not increase the risk of clinical outcomes. Late catch-up phenomen requiring revascularization was not significant in this study.
Asunto(s)
Angioplastia Coronaria con Balón/instrumentación , Catéteres Cardíacos , Materiales Biocompatibles Revestidos , Enfermedad de la Arteria Coronaria/terapia , Stents Liberadores de Fármacos , Anciano , Angioplastia Coronaria con Balón/efectos adversos , China , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
In most developed countries, coronary artery disease (CAD), mostly caused by atherosclerosis of coronary arteries, is one of the primary causes of death. From 1990s to 2000s, mortality caused by acute MI declined up to 50%. The incidence of CAD is related with age, gender, economic, etc. Atherosclerosis contains some highly correlative processes such as lipid disturbances, thrombosis, inflammation, vascular smooth cell activation, remodeling, platelet activation, endothelial dysfunction, oxidative stress, altered matrix metabolism, and genetic factors. Risk factors of CAD exist among many individuals of the general population, which includes hypertension, lipids and lipoproteins metabolism disturbances, diabetes mellitus, chronic kidney disease, age, genders, lifestyle, cigarette smoking, diet, obesity, and family history. Angina pectoris is caused by myocardial ischemia in the main expression of pain in the chest or adjoining area, which is usually a result of exertion and related to myocardial function disorder. Typical angina pectoris would last for minutes with gradual exacerbation. Rest, sit, or stop walking are the usual preference for patients with angina, and reaching the maximum intensity in seconds is uncommon. Rest or nitroglycerin usage can relieve typical angina pectoris within minutes. So far, a widely accepted angina pectoris severity grading system included CCS (Canadian Cardiovascular Society) classification, Califf score, and Goldman scale. Patients with ST-segment elevated myocardial infarction (STEMI) may have different symptoms and signs of both severe angina pectoris and various complications. The combination of rising usage of sensitive MI biomarkers and precise imaging techniques, including electrocardiograph (ECG), computed tomography, and cardiac magnetic resonance imaging, made the new MI criteria necessary. Complications of acute myocardial infarction include left ventricular dysfunction, cardiogenic shock, structural complications, arrhythmia, recurrent chest discomfort, recurrent ischemia and infarction, pericardial effusion, pericarditis, post-myocardial infarction syndrome, venous thrombosis pulmonary embolism, left ventricular aneurysm, left ventricular thrombus, and arterial embolism.