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1.
Eur J Pharmacol ; 911: 174559, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34637700

RESUMO

OBJECTIVE: In this study, it was hypothesized that klotho deficiency plays an essential role in cardiac ageing in vivo and demonstrated that supplementation with exogenous klotho protects against cardiomyocyte ageing in vitro. METHODS: We measured the lifespan of wild-type (WT) and klotho-hypomorphic mutant (KL-/-) mice and recorded the cardiac function of the mice through echocardiography. We used immunofluorescence staining to detect the LC3B (microtubule-associated protein light chain 3 B), Beclin 1, Bax and Bcl 2 proteins. In vitro, H9c2 cells were incubated with different levels of D-galactose (D-gal) with or without klotho. SA-ß-galactosidase staining and western blotting were performed to detect ageing-associated proteins (P53, P21 and P16), autophagy-associated proteins (LC3 II/LC3 I and Beclin 1) and apoptosis-associated proteins (Bax and Bcl 2). Moreover, one-step TUNEL apoptosis, CCK-8, cell morphology, Hoechst 33258 staining, lactate dehydrogenase (LDH) release, and caspase-3 activity assays were performed, and intracellular reactive oxygen species (ROS) levels were measured. RESULTS: Genetic klotho deficiency decreased lifespan and cardiac function in mice, impaired autophagic activity and increased apoptotic activity. Exogenous klotho attenuated cardiomyocyte ageing and reversed changes in autophagic and apoptotic activity caused by D-gal. Moreover, klotho supplementation prevented D-gal-induced oxidative stress and cytotoxicity. CONCLUSIONS: Klotho might have a protective effect on cardiac ageing via autophagy activation and apoptosis inhibition.

2.
Aging (Albany NY) ; 13(16): 20534-20551, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34432650

RESUMO

OBJECTIVE: The NOD-like receptor protein 3 (NOD-like receptor protein 3, NLRP3) inflammasome is associated with many physiological processes related to aging. We investigated whether NLRP3 inflammasome activation contributes to the pathogenesis of cardiocytes aging dissected the underlying mechanism. METHODS: H9c2 cells were treated with different concentrations of D-galactose (D-gal, 0, 2, 10 and 50 g/L) for 24 hours. The cytochemical staining, flow cytometry and fluorescence microscope analysis were employed to detect the ß-galactosidase (ß-gal) activity. Western blot analysis was used to detect the age-associated proteins (P53, P21) and NLRP3 inflammasome proteins [NLRP3, apoptosis-associated speck-like protein (ASC)]. Confocal fluorescent images were applied to capture the colocalization of NLRP3 and caspase-1. Intracellular reactive oxygen species (ROS) was measured using 2'7'-dichlorodihydrofluorescein diacetate (DCFH-DA) by flow cytometry and visualized using a fluorescence microscope. The IL-1ß, IL-18 and lactate dehydrogenase (LDH) release were also detected. RESULTS: D-gal induced-H9c2 cells caused cardiocytes' aging changes (ß-gal staining, CellEvent™ Senescence Green staining, P53, P21) in a concentration-dependent manner. NLRP3 inflammasomes were activated, IL-1ß, IL-18 and LDH release and ROS generation were increased in the cardiocytes aging progress. When MCC950 inhibited NLRP3 inflammasomes, it attenuated the cardiocytes aging, yet the ROS generation was similar. Inhibition of ROS by NAC attenuated cardiocytes aging and inhibited the NLRP3 inflammasome activation at the same time. NLRP3 inflammasome activation by nigericin-induced cardiocytes cells aging progress. CONCLUSIONS: NLRP3 inflammasome activation contributes to the pathogenesis of cardiocytes aging, and ROS generation may serve as a potential mechanism by which NLRP3 inflammasome is activated.

3.
Gut Microbes ; 13(1): 1-15, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34006193

RESUMO

The gut microbiota in the hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is poorly defined. We aim to uncover the characteristics of the gut microbiota in HBV-ACLF and in other HBV associated pathologies. We analyzed the gut microbiome in patients with HBV-ACLF or other HBV associated pathologies and healthy individuals by 16S rRNA sequencing and metagenomic sequencing of fecal samples. 212 patients with HBV-ACLF, 252 with chronic hepatitis B (CHB), 162 with HBV-associated cirrhosis (HBV-LC) and 877 healthy individuals were recruited for the study. CHB and HBV-LC patients are grouped as HBV-Other. We discovered striking differences in the microbiome diversity between the HBV-ACLF, HBV-Other and healthy groups using 16S rRNA sequencing. The ratio of cocci to bacilli was significantly elevated in the HBV-ACLF group compared with healthy group. Further analysis within the HBV-ACLF group identified 52 genera showing distinct richness within the group where Enterococcus was enriched in the progression group whilst Faecalibacterium was enriched in the regression group. Metagenomic sequencing validated these findings and further uncovered an enrichment of Lactobacillus casei paracasei in progression group, while Alistipes senegalensis, Faecalibacterium prausnitzii and Parabacteroides merdae dominated the regression group. Importantly, our analysis revealed that there was a rapid increase of Enterococcus faecium during the progression of HBV-ACLF. The gut microbiota displayed distinct composition at different phases of HBV-ACLF. High abundance of Enterococcus is associated with progression while that of Faecalibacterium is associated with regression of HBV-ACLF. Therefore, the microbiota features hold promising potential as prognostic markers for HBV-ACLF.


Assuntos
Insuficiência Hepática Crônica Agudizada/microbiologia , Bactérias/isolamento & purificação , Microbioma Gastrointestinal , Hepatite B Crônica/microbiologia , Insuficiência Hepática Crônica Agudizada/virologia , Adulto , Bactérias/classificação , Bactérias/genética , Progressão da Doença , Fezes/microbiologia , Feminino , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/virologia , Humanos , Masculino , Metagenômica , Pessoa de Meia-Idade
4.
Front Cardiovasc Med ; 8: 644405, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33834045

RESUMO

Introduction: Hypertension (HT) and atrial fibrillation (AF) often coexist. However, the causality between these two conditions remains to be determined. Methods: We used individual participant data from the Atherosclerosis Risk in Communities (ARIC) prospective cohort with 9,474 participants. HT was ascertained at visit 1 (1987-1989), and incident AF was identified by ECGs conducted during study examinations at each visit, hospital discharge codes, and death certificates. We used the Kaplan-Meier estimate to compute the cumulative incidence of AF by the HT subgroup. Then we used Cox hazard regression model to assess the association between HT and incident AF. The causality between genetically determined HT and AF was analyzed by the two-sample Mendelian randomization (MR) based on publicly summarized genome-wide association studies (GWASs) data. Results: A total of 1,414 cases (14.9%) of AF were identified during the follow-up period (median 24.1 years). After adjusting for all covariates, the hazard ratio between the participants with HT and incident AF was 1.50 [95% confidence interval (CI) 1.29-1.73]. In the HT → AF MR analysis, we detected a causal correlation between HT and AF (OR: 1.90, 95% CI 1.18-3.04, P = 0.01) with no evidence of heterogeneity from single-nucleotide polymorphisms. Besides, the genetically determined SBP and DBP (10 mmHg) were consistently associated with a higher risk of AF. Conclusions: In the ARIC study, the incident AF increased by 50% in patients with HT. In the MR analysis, our results supported causal inference between HT and AF.

5.
World J Diabetes ; 12(3): 261-277, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33758646

RESUMO

BACKGROUND: The causality between education and type 2 diabetes (T2DM) remains unclear. AIM: To identify the causality between education and T2DM and the potential metabolic risk factors [coronary heart disease (CHD), total cholesterol, low-density lipoprotein, triglycerides (TG), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting insulin, fasting glucose, and glycated hemoglobin] from summarized genome-wide association study (GWAS) data used a network Mendelian randomization (MR). METHODS: Two-sample MR and network MR were performed to obtain the causality between education-T2DM, education-mediator, and mediator-T2DM. Summary statistics from the Social Science Genetic Association Consortium (discovery data) and Neale Lab consortium (replication data) were used for education and DIAGRAMplusMetabochip for T2DM. RESULTS: The odds ratio for T2DM was 0.392 (95%CI: 0.263-0.583) per standard deviation increase (3.6 years) in education by the inverse variance weighted method, without heterogeneity or horizontal pleiotropy. Education was genetically associated with CHD, TG, BMI, WC, and WHR in the discovery phase, yet only the results for CHD, BMI, and WC were replicated in the replication data. Moreover, BMI was genetically associated with T2DM. CONCLUSION: Short education was found to be associated with an increased T2DM risk. BMI might serve as a potential mediator between them.

6.
Eur J Clin Invest ; 51(1): e13405, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32926588

RESUMO

BACKGROUND: In most situations, many patients undergoing coronary artery bypass graft (CABG) are on dual antiplatelet therapy (DAPT), which is also required after CABG. The adjustment of antiplatelet strategy remains controversial. In this study, we systematically review current guidelines, seeking consensus and controversies to facilitate clinical practice. METHODS AND RESULTS: Guidelines are searched in PubMed, Embase, ECRI Guidelines Trust and websites of guidelines organizations and professional society. Guidelines with recommendations of DAPT for patients undergo CABG are included. Two reviewers appraised guidelines with the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Relevant recommendations are extracted and summarized. A total of 14 guidelines meeting inclusion criteria are selected, with average AGREE II scores from 44% to 86%. Most guidelines score high in domains other than 'applicability'. Many guidelines are not detailed enough in reporting considerations behind recommendations. Current guidelines are consistent on the management of antiplatelet strategy before elective CABG and using DAPT after surgery for preventing graft vessel occlusion. Evidence is still lacking in urgent CABG and resumption of the previous DAPT after surgery. CONCLUSIONS: Current guidelines on DAPT in CABG are generally satisfying. Suspending P2Y12 inhibitors while aspirin continued before elective CABG is recommended, as well as 12 months of DAPT following CABG. More evidence is needed to guide antiplatelet therapy in urgent CABG and to prove the benefits of resuming previous DAPT.

7.
Int J Cardiol ; 324: 115-121, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33017630

RESUMO

INTRODUCTION: We aim to characterize the nature and magnitude of the prospective association between education and incident heart failure (HF) in the Atherosclerosis Risk in Communities (ARIC) Study and investigate any causal relevance to the association between them. METHODS: The final sample size was 12,315 in this study. Baseline characteristics between education levels were compared using 1-way ANOVA test, the Kruskal-Wallis test, or the χ2 test. We used the Kaplan-Meier estimate to compute the cumulative incident of HF by education levels and the difference in estimate was compared using the log-rank test. Cox hazard regression models were used to explore the association between education levels and incident HF. Two-sample Mendelian randomization (MR) based on publicly available summary-level data from genome-wide association studies (GWASs) was used to estimate the causal influence of the education and incident HF. RESULTS: During a median follow-up of 25.1years, 2453 cases (19.9%) of incident HF occurred. After multiple adjustments in the final model, participants in the intermediate and advanced education levels were still associated with 18% and 21% decreased rate of incident HF separately. In MR analysis, we detected a protective causal association between education and HF (P=0.005). CONCLUSIONS: Participants with higher education levels were associated with a decreased rate of incident HF. There was a causal association between education and HF.


Assuntos
Aterosclerose , Insuficiência Cardíaca , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Aterosclerose/genética , Estudo de Associação Genômica Ampla , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/genética , Humanos , Incidência , Análise da Randomização Mendeliana , Estudos Prospectivos , Fatores de Risco
9.
Artigo em Inglês | MEDLINE | ID: mdl-32994225

RESUMO

INTRODUCTION: Long-term changes of fasting blood glucose (FBG) in relation to lower-extremity peripheral artery disease (lower-extremity PAD) in people without diabetes has barely been reported. Our study aimed to investigate the association between FBG variability and the incidence of lower-extremity PAD in people without diabetes. RESEARCH DESIGN AND METHODS: We included 7699 participants without prior lower-extremity PAD and diabetes from the Atherosclerosis Risk in Communities study in the final analysis. At least two measurements of FBG were required during follow-up. Variability of FBG was identified using SD, coefficient of variation (CV), variability independent of the mean (VIM) and average real variability. Lower-extremity PAD was defined as an ankle brachial index <0.9, or hospitalization with a lower-extremity PAD diagnosis. Cox regression model was used to calculate HR for incidence of lower-extremity PAD and FBG variability. RESULTS: During a median follow-up of 19.5 years, 504 (6.5 %) lower-extremity PAD events were observed, 54.4% (n=274) were male, and 17.5% (n=88) were African-American. FBG variability was positively associated with incident lower-extremity PAD, with a linear relationship. HRs for CV and VIM were 1.015 (95% CI: 1.001 to 1.03; p=0.023), and 1.032 (95% CI: 1.004 to 1.06; p=0.022) for lower-extremity PAD, respectively. Participants in the lowest quartile of CV were at lower lower-extremity PAD risk compared with the highest ones (HR: 1.499, 95% CI: 1.16 to 1.938; p=0.002). CONCLUSIONS: Higher FBG variability was independently associated with increased prevalence of lower-extremity PAD in people without diabetes. TRIAL REGISTRATION NUMBER: NCT00005131.


Assuntos
Diabetes Mellitus , Doença Arterial Periférica , Glicemia , Diabetes Mellitus/epidemiologia , Jejum , Feminino , Humanos , Masculino , Doença Arterial Periférica/epidemiologia , Fatores de Risco
10.
Ther Adv Chronic Dis ; 11: 2040622320909040, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32523662

RESUMO

Background: We applied a network Mendelian randomization (MR) framework to determine the causal association between body mass index (BMI) and coronary heart disease (CHD) and explored whether glycated hemoglobin (HbA1c) and lipid parameters (total cholesterol, TC; low-density lipoprotein cholesterol, LDL; high-density lipoprotein cholesterol, HDL; triglycerides, TG) serve as causal mediators from BMI to CHD by integrating summary-level genome-wide association study data. Methods: Network MR analysis, an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed. Summary statistics from the GIANT consortium were used (n = 152,893) for BMI, CARDIoGRAMplusC4D consortium data were used (n = 184,305) for CHD, Global Lipids Genetics Consortium data were used (n = 108,363) for TC, LDL, HDL and TG, and MAGIC consortia data were used (n = 108,363) for HbA1c. Results: The inverse-variance-weighted-method estimate indicated that the odds ratio (95% confidence interval) for CHD was 1.562 (1.391-1.753) per 1 standard deviation (kg/m2) increase in BMI. Results were consistent in MR Egger method and weighted-median methods. MR estimate indicated that BMI was positively associated with HbA1c and TG, and negatively associated with HDL, but was not associated with TC or LDL. Moreover, HbA1c, TC, LDL, and TG were positively associated with CHD, yet there was no causal association between HDL and CHD. HbA1c was positively associated with TC, LDL, and HDL, but was not associated with TG. Conclusions: Higher BMI conferred an increased risk of CHD, which was partially mediated by HbA1c and lipid parameters. HbA1c and TG might be the main mediators in the link from BMI to CHD.

11.
Sleep Med ; 67: 232-236, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31978671

RESUMO

OBJECTIVE: Sleep is an essential physiological process that protects our physical and mental health. However, the causality of the association between sleep and coronary heart disease (CHD) is unknown. Mendelian randomization (MR), using genetic variants as instrumental variables to test for causality, can infer credible causal associations. We applied a two-sample MR framework to determine the causal association between sleep (sleeplessness, sleep duration, and daytime dozing) and CHD by integrating summary-level genome-wide association study (GWAS) data. METHODS: Data included in this study were the GWAS summary statistics datasets from the C4D Consortium for CHD; Neale Lab UKB-a:13 Consortium for sleeplessness; Neale Lab UKB-a:9 Consortium for sleep duration and Neale Lab UKB-a:15 Consortium for daytime dozing. The conventional MR approach (inverse variance weighted, IVW) method and Egger method were used. Heterogeneity was calculated using each of the different MR methods where possible. Horizontal pleiotropy was evaluated by p-value of the MR-Egger intercept. RESULTS: The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval, CI) for CHD was 3.924 (1.345-11.447) per standard deviation increase in sleeplessness (p = 0.012). Results were consistent in MR-Egger method (OR, 4.654; 95% CI, 1.191-18.186; p = 0.009). The genetically predicted sleeplessness was positively casually associated with CHD. The causal association between sleep duration (or daytime dozing) and CHD was not established. CONCLUSION: Our analysis provided evidence supporting a causal relationship between sleeplessness (not sleep duration or daytime dozing) and CHD.


Assuntos
Causalidade , Doença das Coronárias , Sono/fisiologia , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Sono/genética
12.
Eur J Epidemiol ; 35(2): 113-122, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31741136

RESUMO

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Low serum albumin level is linked to the emergence of many cardiovascular diseases, including AF. In this study, we aim to characterize the nature and magnitude of the prospective association between serum albumin and incident AF in the Atherosclerosis Risk in Communities (ARIC) Study and investigate any causal relevance to the association between them. ARIC Study is a population-based, prospective, cohort study of cardiovascular risk factors in four US communities, initially consisting of 15,792 participants, aged 45-64 years, recruited between 1987 and 1989 (visit 1). The final sample size was 12,833 in this study. Baseline (visit 1) characteristics were compared between groups using one-way ANOVA test, Chi square test, or Kruskal-Wallis test as appropriate. We used multivariable Cox' hazard regression models to assess the association between albumin and incident AF. Two-sample Mendelian randomization (MR) based on publicly available summary-level data from genome-wide association studies was used to estimate the causal influence of the serum albumin and incident AF. During a median follow-up of 25.1 years, 2259 (17.6%) participants developed incident AF. After multiple adjustment, serum albumin was inversely associated with incidence of AF [HR = 0.90, 95% CI 0.86-0.94, per SD (0.27 g/dL) increase; HR = 0.80, 95% CI 0.71-0.91, Q4 vs. Q1]. In MR analysis, we detected no evidence for a causal relation between serum albumin level and AF in inverse-variance weighted (IVW) method (odds ratio: 0.996, 95% CI 0.980-1.012, per 1 g/dL increase of albumin; P = 0.620) without evidence of heterogeneity between estimates from individual SNPs (Pheterogeneity = 0.981 [MR-Egger] and Pheterogeneity = 0.860 [IVW]) nor pleiotropy effect (Ppleiotropy = 0.193). The serum albumin level is independently inverse associated with incident AF in a linear pattern. However, MR analyses did not support a causal role of serum albumin in the etiology of AF.


Assuntos
Fibrilação Atrial/epidemiologia , Estudo de Associação Genômica Ampla/métodos , Análise da Randomização Mendeliana , Albumina Sérica/genética , Fibrilação Atrial/etiologia , Fibrilação Atrial/genética , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Albumina Sérica/metabolismo , Estados Unidos/epidemiologia
13.
Nutr Metab Cardiovasc Dis ; 30(2): 233-240, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-31648883

RESUMO

BACKGROUND AND AIMS: Evidence on the effect of omega-6 fats on coronary heart disease (CHD) risk remains inconclusive. We applied a network MR framework to determine the causal effects between omega-6 levels and CHD and the potential cholesterol metabolic risk factors (Total cholesterol, TC; Low-density lipoprotein cholesterol, LDL-C; High-density lipoprotein cholesterol, HDL-C; Triglycerides, TG) which might act as mediators in the link between omega-6 levels and CHD by integrating summary-level genome wide association study (GWAS) data. METHODS AND RESULTS: Network MR analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed to examine the causal effects between omega-6 levels and CHD and cholesterol metabolic risk factors. Summary statistics from the Kettunen et al. 's consortium were used (n = 13506) for omega-6, CARDIoGRAMplusC4D consortium data were used (n = 184305) for CHD, and GLGC consortia data were used (n = 108363) for TC, LDL-C, HDL-C, and TG. The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval [CI]) for CHD was 1.210 (1.118-1.310) per standard deviation increase in omega-6. Results were consistent in MR Egger method (OR, 1.418; 95% CI, 1.087-1.851; P = 0.050) and weighted median methods (OR, 1.239; 95% CI, 1.125-1.364; P = 0.000). Omega-6 was positively causal associated with TC, LDL-C, and TG but was not associated with HDL-C. Moreover, TC, LDL-C, and TG were positively associated with CHD. CONCLUSIONS: Using a network MR framework, we provided evidence supporting a positive causal relationship between omega-6 and CHD, which might be partially mediated by TC, LDL-C, and TG.


Assuntos
Doença das Coronárias/sangue , Doença das Coronárias/genética , Gorduras na Dieta/sangue , Dislipidemias/sangue , Dislipidemias/genética , Ácidos Graxos Ômega-6/sangue , Variação Genética , Biomarcadores/sangue , LDL-Colesterol/sangue , Doença das Coronárias/epidemiologia , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Dislipidemias/epidemiologia , Ácidos Graxos Ômega-6/administração & dosagem , Ácidos Graxos Ômega-6/efeitos adversos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Fatores de Proteção , Medição de Risco , Fatores de Risco , Triglicerídeos/sangue
14.
Eur J Prev Cardiol ; 26(16): 1693-1706, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31213079

RESUMO

BACKGROUND: Hypertensive patients are highly heterogeneous in cardiovascular prognosis and treatment responses. A better classification system with phenomapping of clinical features would be of greater value to identify patients at higher risk of developing cardiovascular outcomes and direct individual decision-making for antihypertensive treatment. METHODS: An unsupervised, data-driven cluster analysis was performed for all baseline variables related to cardiovascular outcomes and treatment responses in subjects from the Systolic Blood Pressure Intervention Trial (SPRINT), in order to identify distinct subgroups with maximal within-group similarities and between-group differences. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular outcomes and compare the effect of intensive antihypertensive treatment in different clusters. RESULTS: Four replicable clusters of patients were identified: cluster 1 (index hypertensives); cluster 2 (chronic kidney disease hypertensives); cluster 3 (obese hypertensives) and cluster 4 (extra risky hypertensives). In terms of prognosis, individuals in cluster 4 had the highest risk of developing primary outcomes. In terms of treatment responses, intensive antihypertensive treatment was shown to be beneficial only in cluster 4 (HR 0.73, 95% CI 0.55-0.98) and cluster 1 (HR 0.54, 95% CI 0.37-0.79) and was associated with an increased risk of severe adverse effects in cluster 2 (HR 1.18, 95% CI 1.05-1.32). CONCLUSION: Using a data-driven approach, SPRINT subjects can be stratified into four phenotypically distinct subgroups with different profiles on cardiovascular prognoses and responses to intensive antihypertensive treatment. Of note, these results should be taken as hypothesis generating that warrant further validation in future prospective studies.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Tomada de Decisões , Hipertensão/classificação , Idoso , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Resultado do Tratamento
15.
Cardiovasc Diabetol ; 18(1): 47, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961600

RESUMO

BACKGROUND: The cardiovascular (CV) safety in terms of heart failure among different classes of treatment remains largely unknown. We sought to assess the comparative effect of these agents on heart failure outcomes. METHODS: This study was registered in the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials were searched. For the primary outcomes reported previously, studies between Jan 1, 1980 and June 30, 2016 were screened, and subsequently updated till Jan 24, 2019. We performed network meta-analysis to obtain estimates for the outcomes of heart failure, in particular by rankograms for ranking of heart failure risk as well as by pairwise comparisons among all classes of anti-diabetic medications. RESULTS: A total of 91 trials were included, among which were 171,253 participants and 4163 reported cases of heart failure events. As for rankograms, the surface under the cumulative ranking curves (SUCRA) of sodium-glucose co-transporters 2 and thiazolidinediones were 93.4% and 4.3%, respectively, signifying the lowest and highest risk of heart failure, respectively. As for pairwise comparisons in the network, sodium-glucose co-transporters 2 were significantly superior to insulin (OR: 0.75, 95% CI 0.62-0.91), dipeptidyl peptidase 4 inhibitors (OR: 0.68, 95% CI 0.59-0.78), glucagon-like peptide-1 receptor agonists (OR: 0.65, 95% CI 0.54-0.78), and thiazolidinediones (OR: 0.46, 95% CI 0.27-0.77) in terms of heart failure risk. Furthermore, in an exploratory analysis among subjects with underlying heart failure or at risk of heart failure, the superiority of sodium-glucose co-transporters 2 was still significant. CONCLUSIONS: In terms of heart failure risk, sodium-glucose co-transporters 2 were the most favorable option among all classes of anti-diabetic medications.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/terapia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidade , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Humanos , Hipoglicemiantes/efeitos adversos , Incretinas/uso terapêutico , Substâncias Protetoras , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Resultado do Tratamento
16.
Cardiovasc Diabetol ; 17(1): 79, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29871636

RESUMO

BACKGROUND: Cardiovascular (CV) safety of one anti-diabetic medication over another remains partially delineated. We sought to assess the comparative effect on CV outcomes among novel anti-diabetic agents. METHODS: This study was registered with the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and Cochrane Library Central Register of Controlled Trials were searched between Jan 1, 1980, and June 30, 2016. Randomized controlled trials comparing anti-diabetic drugs with other comparators in adults with type 2 diabetes were included. We used network meta-analysis to obtain estimates for the outcomes of interests. In addition, post hoc correlation analysis of severe hypoglycemia and primary outcome as per ranking order was conducted. Outcomes were major adverse cardiovascular events (MACE) and all-cause mortality. RESULTS: A total of 170 trials (166,371 participants) were included. By class and by individual, sulfonylureas (SU) ranked last. Therefore, with SU as reference, categorically sodium-glucose co-transporter 2 inhibitor (SGLT2i), insulin (INS), glucagon-like peptide-1 receptor agonist, and dipeptidyl peptidase 4 inhibitor were significantly superior in term of MACE; as were SGLT2i and INS in term of all-cause mortality. Moreover, ranking orders of MACE and all-cause mortality were both positively correlated with that of severe hypoglycemia risk (by individual: R2 = 0.3178, P = 0.018; by class: R2 = 0.2574, P = 0.038). CONCLUSIONS: Novel anti-diabetic agents possess favorable CV safety profile, despite small but robust differences between individuals. In addition, increase in CV risk was again shown to be partly attributable to a concomitant increase in the risk of severe hypoglycemia, for which SU performed the worst.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/mortalidade , Hipoglicemiantes/efeitos adversos , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do Tratamento
17.
CNS Neurosci Ther ; 23(8): 657-666, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28628270

RESUMO

AIMS: Neuroinflammation contributed to the pathogenesis of multiple system atrophy (MSA). We aimed to detect the correlation between inflammatory mediators, such as Klotho (Klt), vitamin D (25(OH)D) and homocysteine (Hcy), and disease severity among MSA patients. METHODS: A total of 53 MSA patients, 65 PD patients, and 62 normal subjects were recruited in our cross-sectional study. Serum Klotho (Klt), vitamin D (25(OH)D), and homocysteine (Hcy) levels were measured. Several scales were undertaken to assess the motor/nonmotor function and cognitive impairment of MSA. RESULTS: Decreased Serum Klt and 25(OH)D levels and increased Hcy levels were found in patients with MSA, compared with healthy controls. These results were more pronounced in male patients. The three biomarkers also displayed differences between MSA and PD subgroups based on genders. Interestingly, Klt, 25(OH)D and Hcy levels associated with cognition impairment, motor dysfunction, mood/cardiovascular disorder among MSA patients. In addition, the combination of Klt, 25(OH)D and Hcy had a better diagnostic ability for distinguishing MSA patients from healthy subjects, as well as distinguishing male MSA patients from male PD patients. CONCLUSION: This study suggested that Klt, 25(OH)D and Hcy levels could be a potential predictor for MSA severity evaluation.


Assuntos
Glucuronidase/sangue , Homocisteína/sangue , Atrofia de Múltiplos Sistemas/sangue , Vitamina D/sangue , Biomarcadores/sangue , China , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/psicologia , Doença de Parkinson/sangue , Doença de Parkinson/psicologia , Prognóstico , Curva ROC , Índice de Gravidade de Doença , Caracteres Sexuais
18.
BMJ Open ; 7(5): e014894, 2017 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-28501813

RESUMO

OBJECTIVE: To investigate the relationship between job satisfaction, work stress, work-family conflict and turnover intention, and explore factors associated with turnover intention, among physicians in Guangdong Province, China. METHODS: From August to October 2013, physicians completed questionnaires and scales with regard to their job satisfaction, work stress, work-family conflict, and turnover intention. Binary logistic regression and structural equation modelling (SEM) were used in data analysis. RESULTS: A total of 3963 physicians were approached, with 3563 completing the questionnaire. The mean score of the overall perception of turnover intention of physicians who worked in Guangdong was 2.71 on a scale ranging from 1 to 6. Hours worked per week, working in an urban/rural area, type of institution, and age significantly impacted on turnover intention. Turnover intention was directly and negatively related to job satisfaction, and it was directly, indirectly and positively related to work stress and work-family conflict. CONCLUSION: Job satisfaction, work stress, work-family conflict, hours worked per week, working in an urban/rural area, types of institution and age are influencing factors of turnover intention. Reducing working hours, raising salary, providing more opportunities for career development and training, supporting and encouraging physicians by senior managers could potentially contribute to the reduction in turnover intention.


Assuntos
Satisfação no Emprego , Estresse Ocupacional/psicologia , Reorganização de Recursos Humanos/estatística & dados numéricos , Médicos , Tolerância ao Trabalho Programado/psicologia , Equilíbrio Trabalho-Vida/estatística & dados numéricos , Adulto , Atitude do Pessoal de Saúde , China/epidemiologia , Estudos Transversais , Feminino , Reforma dos Serviços de Saúde , Pesquisa sobre Serviços de Saúde , Humanos , Intenção , Masculino , Estresse Ocupacional/epidemiologia , Médicos/estatística & dados numéricos , Inquéritos e Questionários , Carga de Trabalho/estatística & dados numéricos , Adulto Jovem
19.
Int Heart J ; 58(2): 191-196, 2017 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-28320994

RESUMO

Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute kidney injury (AKI). Emerging evidence has revealed that soluble klotho (sklotho) could be a novel biomarker for early AKI diagnosis. The aims of this study were to assess the predictive role of sklotho for CIN and to develop a prediction nomogram in patients undergoing percutaneous coronary intervention (PCI). This study is registered on Clinicaltrials.gov (NCT 02650336).Patients aged 18 years or older undergoing planned PCI were prospectively recruited between May 2014 and July 2015. CIN was defined as an increase in serum creatinine of 0.5 mg/dL within 48-72 hours after the procedure. Plasma sklotho was measured by enzyme linked immunosorbent assay (ELISA). Stratified analysis, interaction test, covariate screening, and curve fitting were performed to explore the association between sklotho and CIN. A nomogram was then developed and validated using the bootstrapped technique.A total of 192 patients aged 54.75 ± 12.19 years were selected, 32 (16.7%) of whom were diagnosed with CIN. A logistic regression model indicated significant associations between CIN and sklotho, age > 75 years, diabetes, and the Mehran risk score. Saturation effects analysis detected a two-stage change between sklotho and CIN, with the inflection point was 477.4 pg/mL. The area under the ROC curve was 0.758 and the sensitivity and specificity of this point were 90.6% and 53.9%, respectively. A nomogram was developed for the prediction of CIN and showed a bootstrapped-corrected area under the curve value of 0.913. In addition, sklotho significantly increased the predictive value of the nomogram.A strong association between sklotho and CIN was identified in patients undergoing elective PCI. A lower level of sklotho would be well correlated with CIN. The nomogram with sklotho is a useful tool to predict CIN in patients who will undergo PCI.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Meios de Contraste/efeitos adversos , Glucuronidase/sangue , Injúria Renal Aguda/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Intervenção Coronária Percutânea
20.
BMJ Open ; 6(7): e011388, 2016 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-27436667

RESUMO

OBJECTIVES: This cross-sectional study aimed to explore job satisfaction among healthcare staff in Guangdong following the health system reforms in 2009, and to investigate the association between job satisfaction and work stress, work-family conflict and doctor-patient relationship. DESIGN: Cross-sectional survey. SETTING: The Fifth National Health Service Survey was carried out in Guangdong, China. PARTICIPANTS: All participants in this study were healthcare staff including physicians, nurses and public health staff from hospitals, health service centres and health clinics. A total of 6583 questionnaires were distributed and collected. After excluding the incomplete questionnaires, 5845 questionnaires were included for the analysis. OUTCOME MEASURES: Sociodemographic information and scores for evaluating job satisfaction, work stress, work-family conflict and doctor-patient relationship were obtained using the questionnaire developed by the National Health and Family Planning Commission of the People's Republic of China. To assess the significantly associated factors on job satisfaction of the healthcare staff in Guangdong, a binary logistic regression model was used. RESULTS: Based on the 5845 valid responses of the healthcare staff who worked in Guangdong, the mean score of overall perception of job satisfaction was 3.99 on a scale of 1-6. Among the sociodemographic variables, occupation, educational background, professional status, years of service, annual income and night shift frequency significantly influenced the level of job satisfaction. Work stress, work-family conflict and doctor-patient relationship also had significant effect on job satisfaction. CONCLUSIONS: The overall job satisfaction exceeded slightly dissatisfied (score 3) and approached slightly satisfied (score 4). Measures to enhance job satisfaction include the reduction of workload, increase of welfare, maintaining moderate stress and balancing work-family conflict. Moreover, relevant laws should be issued to protect the healthcare staff from violent acts.


Assuntos
Atitude do Pessoal de Saúde , Satisfação no Emprego , Estresse Ocupacional , Relações Médico-Paciente , Equilíbrio Trabalho-Vida , Carga de Trabalho , Adulto , China , Estudos Transversais , Feminino , Reforma dos Serviços de Saúde , Instalações de Saúde , Serviços de Saúde , Humanos , Renda , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Inquéritos e Questionários , Tolerância ao Trabalho Programado , Adulto Jovem
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