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1.
Medicine (Baltimore) ; 99(35): e21891, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871919

RESUMO

To analyze the relationship between aortic measures and biometric parameters in a large cohort of consecutive patients undergoing computed tomography coronary angiography.1170 patients (717 men/453 women) performing computed tomography coronary angiography for coronary evaluation were retrospectively evaluated. Aortic diameters and areas were measured at reproducible anatomic landmarks, perpendicular to the axis of vessel, at the level of the aortic root (AoR), the sinotubular junction (STJ), and the tubular ascending aorta (TAo). Biometric parameters and cardiovascular risk factors were recorded.The average values of AoR, STJ, and TAo were 35.63 ±â€Š5.00 mm, 30.56 ±â€Š4.82 mm, 35.07 ±â€Š5.84 mm. Hypertension was significantly associated with aortic dimensions.Aortic measures were significantly different between men and women (37.56 ±â€Š4.77 mm vs 32.58 ±â€Š3.68 mm for AoR, 31.88 ±â€Š4.84 mm vs 28.47 ±â€Š3.98 mm for STJ and 35.93 ±â€Š5.86 mm vs 33.70 ±â€Š5.54 mm for TAo) (P < .001) and linearly increased with age. Low Spearman correlation coefficients were found and the correlation of TAo diameters with age displayed the highest values (ρ = 0.372 for male and ρ = 0.373 for female, P < .001). Multiple linear regression analysis models were compared by R. The best model used body surface area (BSA) and age as independent variables and TAo diameter as dependent variable (R = 0.29 for AoR; R = 0.21 for STJ, and R = 0.20 for TAo).In conclusion, in our population low correlation between aortic dimensions and biometric parameters highlights the difficulty of identifying normal ranges, as well as issues related to normalization using conventional biometric parameters.


Assuntos
Aorta/anatomia & histologia , Aorta/diagnóstico por imagem , Biometria , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/patologia , Angiografia Coronária , Tomografia Computadorizada por Raios X , Fatores Etários , Idoso , Superfície Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
2.
Cytokine Growth Factor Rev ; 54: 32-42, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32747157

RESUMO

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a 'Cytokine Super Cyclone'. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of 'trained immunity' in early protection against SARS-CoV2.


Assuntos
Vacina BCG/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/sangue , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Diabetes Mellitus/patologia , Humanos , Hipertensão/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Mycobacterium bovis/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/imunologia , Vacinação
3.
Nat Commun ; 11(1): 3861, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737316

RESUMO

Integrating results from genome-wide association studies (GWASs) and gene expression studies through transcriptome-wide association study (TWAS) has the potential to shed light on the causal molecular mechanisms underlying disease etiology. Here, we present a probabilistic Mendelian randomization (MR) method, PMR-Egger, for TWAS applications. PMR-Egger relies on a MR likelihood framework that unifies many existing TWAS and MR methods, accommodates multiple correlated instruments, tests the causal effect of gene on trait in the presence of horizontal pleiotropy, and is scalable to hundreds of thousands of individuals. In simulations, PMR-Egger provides calibrated type I error control for causal effect testing in the presence of horizontal pleiotropic effects, is reasonably robust under various types of model misspecifications, is more powerful than existing TWAS/MR approaches, and can directly test for horizontal pleiotropy. We illustrate the benefits of PMR-Egger in applications to 39 diseases and complex traits obtained from three GWASs including the UK Biobank.


Assuntos
Pleiotropia Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Análise da Randomização Mendeliana/estatística & dados numéricos , Modelos Genéticos , Transcriptoma , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Simulação por Computador , Bases de Dados Factuais , Gastroenteropatias/diagnóstico , Gastroenteropatias/genética , Gastroenteropatias/patologia , Humanos , Doenças do Sistema Imunitário/diagnóstico , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/patologia , Funções Verossimilhança , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/genética , Doenças Metabólicas/patologia , Herança Multifatorial , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/patologia , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia
4.
PLoS One ; 15(8): e0237751, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817673

RESUMO

BACKGROUND: In the developed world, cardiovascular diseases still contribute to mortality and morbidity, leading to significantly increased deaths in recent years. Thus, it is necessary for a layperson to provide the best possible basic life support (BLS) until professional help is available. Since information on current BLS knowledge in Germany is not available, but necessary to be able to make targeted improvements in BLS education, we conducted this study. METHODS: A cohort survey using convenience sampling (non-probability) method was conducted with questions found in emergency medicine education. People coming to the emergency room of two big university hospitals located in the South (Munich) and western part (Cologne) of Germany were asked to participate in the survey between 2016 and 2017. Primary outcome measures were the proportion of correct answers for each emergency scenario in relationship to age, region, profession and first-aid training. RESULTS: Altogether 1003 people (504 from Cologne; 499 from Munich) took part in the questionnaire. 54.7% were female and 45.3% were male aging from 19 to 52 with a mean of 37.2 years. Although over 90% had taken part in first aid training, many people were lacking first aid knowledge, with less than 10% choosing the correct frequency for chest compression. Hereby demographic factors had a significant influence (p<0.05) in the given answers (Friedmann-and-Wilcoxon Test). CONCLUSION: Overall, results of our survey indicate a clear lack of BLS knowledge. With this information, targeted measures for improving BLS knowledge should be conducted. Additionally, further studies on the feasibility and efficiency of teaching methods are needed.


Assuntos
Reanimação Cardiopulmonar/métodos , Doenças Cardiovasculares/prevenção & controle , Emergências/epidemiologia , Medicina de Emergência/normas , Adulto , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Feminino , Alemanha/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
5.
Clin Immunol ; 218: 108524, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32659373

RESUMO

The outbreak of SARS-CoV-2-associated pneumonia, a disease called COVID-19, has caused a pandemic worldwide. To investigate the immune responses after infection of SARS-CoV-2 in non-critical patients may help to better understand the disease progression. We collected 334 confirmed COVID-19 cases including 212 still in hospital with nucleic acid test positive on halfway for SARS-CoV-2 and 122 discharged from hospital, compared specific antibodies, immune cells, and cytokine changes between the hospitalized and discharged patients. The hospitalized patients had a longer illness time compared with discharged patients. Analysis of viral loads explained long-term or persistent infection of SARS-CoV-2, which existed with the median time of 18.5 days of the positive nucleic acid test. Serum analysis showed that the specific anti-N IgG antibody was positive in all detected patients after infection of two weeks. Neutrophils, Monocytes, NK cells, and CD4+ T cells significantly increased, while total lymphocytes and CD8+ T cells decreased from non-critical hospitalized patients after longer-term infection. Further analysis of the cytokines showed that IL-6, TNF-α, IFN-γ, IL-2, IL-4, and IL-10 from the hospitalized patients were significantly higher, indicating a potential of the increased CD4+ T cell differentiation.


Assuntos
Betacoronavirus/patogenicidade , Doenças Cardiovasculares/imunologia , Infecções por Coronavirus/imunologia , Diabetes Mellitus/imunologia , Imunidade Inata , Pneumopatias/imunologia , Neoplasias/imunologia , Pneumonia Viral/imunologia , Idoso , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/virologia , China/epidemiologia , Comorbidade , Convalescença , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Citocinas/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Diabetes Mellitus/virologia , Feminino , Hospitalização , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Pneumopatias/epidemiologia , Pneumopatias/patologia , Pneumopatias/virologia , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/patologia , Subpopulações de Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/patologia , Monócitos/virologia , Neoplasias/epidemiologia , Neoplasias/patologia , Neoplasias/virologia , Neutrófilos/imunologia , Neutrófilos/patologia , Neutrófilos/virologia , Pandemias , Alta do Paciente , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Fatores de Tempo , Carga Viral/imunologia
6.
Medicine (Baltimore) ; 99(27): e20794, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629663

RESUMO

BACKGROUND: Recently, trimethylamine N-oxide (TMAO) unexplained gut microbe has been proposed as a promising risk factor for atherosclerotic cardiovascular disease (CVD) pathogenesis and adverse events. The relationship of TMAO with coronary atherosclerotic burden has been evaluated in patients with stable coronary artery disease and ST-segment elevation myocardial infarction, but still needs to be explored in newly diagnosed non-ST-segment elevation myocardial infarction (NSTEMI) patients. MATERIAL AND METHODS: A prospective, single-center, SZ-NSTEMI trial (ChiCTR1900022366) is underway to investigate the relationship of TMAO with the severity and prognosis of coronary atherosclerosis in newly diagnosed NSTEMI patients who will undergo coronary angiography with primary percutaneous coronary intervention (pPCI). The primary endpoint of the study will be assessed the association of TMAO with coronary atherosclerotic severity quantify by the number of diseased coronary arteries and SYNTAX score after the coronary angiography. The secondary endpoints will be identified the TMAO as a prognostic biomarker for the short (1 month) and long-term (12 months) major cardiovascular and cerebrovascular events (MACCEs) rate including myocardial infarction, target vessel revascularization, stroke, heart failure, all-cause rehospitalization, and all-cause mortality after the pPCI. The blood samples will be collected from each patient before the procedure to measure the TMAO by isotope dilution high-performance liquid chromatography. In conclusion, SZ-NSTEMI will be the first cohort that will be investigated the association of TMAO with the severity and prognosis of coronary atherosclerotic burden in NSTEMI patients, aiming to identify TMAO as a predictor and a prognostic biomarker.


Assuntos
Aterosclerose/patologia , Doença da Artéria Coronariana/patologia , Metilaminas/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/patologia , Adolescente , Adulto , Idoso , Biomarcadores , Doenças Cardiovasculares/patologia , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
8.
BMJ ; 370: m2297, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669282

RESUMO

OBJECTIVE: To evaluate the associations between prediabetes and the risk of all cause mortality and incident cardiovascular disease in the general population and in patients with a history of atherosclerotic cardiovascular disease. DESIGN: Updated meta-analysis. DATA SOURCES: Electronic databases (PubMed, Embase, and Google Scholar) up to 25 April 2020. REVIEW METHODS: Prospective cohort studies or post hoc analysis of clinical trials were included for analysis if they reported adjusted relative risks, odds ratios, or hazard ratios of all cause mortality or cardiovascular disease for prediabetes compared with normoglycaemia. Data were extracted independently by two investigators. Random effects models were used to calculate the relative risks and 95% confidence intervals. The primary outcomes were all cause mortality and composite cardiovascular disease. The secondary outcomes were the risk of coronary heart disease and stroke. RESULTS: A total of 129 studies were included, involving 10 069 955 individuals for analysis. In the general population, prediabetes was associated with an increased risk of all cause mortality (relative risk 1.13, 95% confidence interval 1.10 to 1.17), composite cardiovascular disease (1.15, 1.11 to 1.18), coronary heart disease (1.16, 1.11 to 1.21), and stroke (1.14, 1.08 to 1.20) in a median follow-up time of 9.8 years. Compared with normoglycaemia, the absolute risk difference in prediabetes for all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke was 7.36 (95% confidence interval 9.59 to 12.51), 8.75 (6.41 to 10.49), 6.59 (4.53 to 8.65), and 3.68 (2.10 to 5.26) per 10 000 person years, respectively. Impaired glucose tolerance carried a higher risk of all cause mortality, coronary heart disease, and stroke than impaired fasting glucose. In patients with atherosclerotic cardiovascular disease, prediabetes was associated with an increased risk of all cause mortality (relative risk 1.36, 95% confidence interval 1.21 to 1.54), composite cardiovascular disease (1.37, 1.23 to 1.53), and coronary heart disease (1.15, 1.02 to 1.29) in a median follow-up time of 3.2 years, but no difference was seen for the risk of stroke (1.05, 0.81 to 1.36). Compared with normoglycaemia, in patients with atherosclerotic cardiovascular disease, the absolute risk difference in prediabetes for all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke was 66.19 (95% confidence interval 38.60 to 99.25), 189.77 (117.97 to 271.84), 40.62 (5.42 to 78.53), and 8.54 (32.43 to 61.45) per 10 000 person years, respectively. No significant heterogeneity was found for the risk of all outcomes seen for the different definitions of prediabetes in patients with atherosclerotic cardiovascular disease (all P>0.10). CONCLUSIONS: Results indicated that prediabetes was associated with an increased risk of all cause mortality and cardiovascular disease in the general population and in patients with atherosclerotic cardiovascular disease. Screening and appropriate management of prediabetes might contribute to primary and secondary prevention of cardiovascular disease.


Assuntos
Doenças Cardiovasculares/mortalidade , Doença das Coronárias/mortalidade , Estado Pré-Diabético/complicações , Acidente Vascular Cerebral/mortalidade , Idoso , Aterosclerose/complicações , Aterosclerose/epidemiologia , Aterosclerose/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/prevenção & controle , Estudos de Casos e Controles , Ensaios Clínicos como Assunto , Doença das Coronárias/epidemiologia , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Estado Pré-Diabético/epidemiologia , Risco , Fatores de Risco , Prevenção Secundária/métodos , Acidente Vascular Cerebral/epidemiologia
9.
PLoS Genet ; 16(7): e1008785, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32628676

RESUMO

To efficiently transform genetic associations into drug targets requires evidence that a particular gene, and its encoded protein, contribute causally to a disease. To achieve this, we employ a three-step proteome-by-phenome Mendelian Randomization (MR) approach. In step one, 154 protein quantitative trait loci (pQTLs) were identified and independently replicated. From these pQTLs, 64 replicated locally-acting variants were used as instrumental variables for proteome-by-phenome MR across 846 traits (step two). When its assumptions are met, proteome-by-phenome MR, is equivalent to simultaneously running many randomized controlled trials. Step 2 yielded 38 proteins that significantly predicted variation in traits and diseases in 509 instances. Step 3 revealed that amongst the 271 instances from GeneAtlas (UK Biobank), 77 showed little evidence of pleiotropy (HEIDI), and 92 evidence of colocalization (eCAVIAR). Results were wide ranging: including, for example, new evidence for a causal role of tyrosine-protein phosphatase non-receptor type substrate 1 (SHPS1; SIRPA) in schizophrenia, and a new finding that intestinal fatty acid binding protein (FABP2) abundance contributes to the pathogenesis of cardiovascular disease. We also demonstrated confirmatory evidence for the causal role of four further proteins (FGF5, IL6R, LPL, LTA) in cardiovascular disease risk.


Assuntos
Doenças Cardiovasculares/genética , Análise da Randomização Mendeliana , Proteoma/genética , Esquizofrenia/genética , Antígenos de Diferenciação/genética , Doenças Cardiovasculares/patologia , Proteínas de Ligação a Ácido Graxo/genética , Feminino , Fator 5 de Crescimento de Fibroblastos/genética , Estudos de Associação Genética/métodos , Humanos , Lipase Lipoproteica/genética , Linfotoxina-alfa/genética , Masculino , Locos de Características Quantitativas , Receptores Imunológicos/genética , Receptores de Interleucina-6/genética , Esquizofrenia/patologia
10.
PLoS One ; 15(7): e0236034, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702046

RESUMO

BACKGROUND: Evidence suggests that the single-disease paradigm does not accurately reflect the individual experience, with increasing prevalence of chronic disease multimorbidity, and subtle yet important differences in types of co-occurring diseases. Knowledge of multimorbidity patterns can aid clarification of individual-level burden and needs, to inform prevention and treatment strategies. This study aimed to estimate the prevalence of multimorbidity in Jamaica, identify population subgroups with similar and distinct disease profiles, and examine consistency in patterns identified across statistical techniques. METHODS: Latent class analysis (LCA) was used to examine multimorbidity patterns in a sample of 2,551 respondents aged 15-74 years, based on data from the nationally representative Jamaica Health and Lifestyle Survey 2007/2008 and self-reported presence/absence of 11 chronic conditions. Secondary analyses compared results with patterns identified using exploratory factor analysis (EFA). RESULTS: Nearly one-quarter of the sample (24.1%) were multimorbid (i.e. had ≥2 diseases), with significantly higher burden in females compared to males (31.6% vs. 16.1%; p<0.001). LCA revealed four distinct classes, including a predominant Relatively Healthy class, comprising 52.7% of the sample, with little to no morbidity. The remaining three classes were characterized by varying degrees and patterns of multimorbidity and labelled Metabolic (30.9%), Vascular-Inflammatory (12.2%), and Respiratory (4.2%). Four diseases determined using physical assessments (obesity, hypertension, diabetes, hypercholesterolemia) were primary contributors to multimorbidity patterns overall. EFA identified three patterns described as "Vascular" (hypertension, obesity, hypercholesterolemia, diabetes, stroke); "Respiratory" (asthma, COPD); and "Cardio-Mental-Articular" (cardiovascular disease, arthritis, mental disorders). CONCLUSION: This first study of multimorbidity in the Caribbean has revealed a high burden of co-existing conditions in the Jamaican population, that is predominantly borne by females. Consistency across methods supports the validity of patterns identified. Future research into the causes and consequences of multimorbidity patterns can guide development of clinical and public health strategies that allow for targeted prevention and intervention.


Assuntos
Análise de Classes Latentes , Multimorbidade , Adolescente , Adulto , Idoso , Asma/complicações , Asma/epidemiologia , Asma/patologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/patologia , Jamaica/epidemiologia , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/epidemiologia , Transtornos Mentais/patologia , Pessoa de Meia-Idade , Prevalência , Autorrelato , Fatores Sexuais , Adulto Jovem
11.
PLoS One ; 15(7): e0236665, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730313

RESUMO

This study aimed to examine the association between disability and cardiovascular (CV) disease incidence and mortality in Korea longitudinally, using a national representative sample. We used the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database, which includes information on the disability of the National Screening Program participants such as severity and type of disability, which were obtained from the Korean National Disability Registry. Cox proportional hazard models were used to evaluate the association between disability and CV disease incidence and mortality. We constructed four models with different levels of adjustment, in which Model 3 was a fully adjusted model. This study included 514,679 participants, and 7,317 CV deaths were reported within a mean follow up of 10.8 ± 3.9 years (maximum, 13.9 years). For 5,572,130 person-year (PY) follow-up, the CV mortality rate was 1.313 per 1,000 PY. In Models 1 and 2, CV disease incidence was significantly higher in participants with disability than in those without disability. In Model 3, the incidence was higher only among participants aged 50-64 years and severe disabled participants aged <50 years. CV mortality was significantly higher in participants with disability than in those without disability in all Models, and the mortality increased in both sexes in Models 1 and 2 but only increased in men in Model 3. Similar results were observed in the subgroup analysis of health behavior and chronic diseases. People with disability showed higher CV disease incidence and mortality than those without disability, regardless of the type of disability or risk factors for CV disease.


Assuntos
Doenças Cardiovasculares/epidemiologia , Pessoas com Deficiência/estatística & dados numéricos , Idoso , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/patologia , Comorbidade , Bases de Dados Factuais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Índice de Gravidade de Doença , Taxa de Sobrevida
12.
Adv Exp Med Biol ; 1207: 265-270, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671754

RESUMO

Autophagy is closely related to the pathogenesis and progression of cardiovascular diseases. Autophagy may be a therapeutic target for many cardiovascular diseases. In this chapter, we will summarize autophagy activators and inhibitors as potential drugs for cardiovascular diseases.


Assuntos
Autofagia , Doenças Cardiovasculares , Autofagia/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Progressão da Doença , Humanos
13.
Adv Exp Med Biol ; 1207: 731-736, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671790

RESUMO

Several major cardiovascular diseases, such as heart failure (HF) and atherosclerosis (AS), have been linked to autophagy dysfunction. The influence of autophagy on the occurrence and development of cardiovascular diseases has two sides. Generally, the induction of autophagy at a low level can provide energy and nutrients for cells through degradation of damaged organelles, protect cardiomyocytes and vascular endothelial cells, and stabilize atherosclerotic plaques. However, excessive autophagy may damage cardiomyocytes and vascular endothelial cells and even cause cell death. Therefore, the study on the role and mechanism of autophagy in the pathogenesis of cardiovascular diseases may not only provide new targets for the treatment of cardiac remodeling, myocardial ischemia and reperfusion injury, atherosclerosis and heart failure, but also provide clues for the developing new drugs on prevention and treatment of clinical cardiovascular diseases. In this chapter, we reviewed the research progress on resveratrol, curcumin, epigallocatechin-3-gallate, and cordyceps sinensis on their recent research progress for cardiovascular diseases. Regulating autophagy may be an effective strategy for the treatment of cardiovascular diseases in the future.


Assuntos
Autofagia/efeitos dos fármacos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia
14.
Lancet Diabetes Endocrinol ; 8(7): 572-581, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32559473

RESUMO

BACKGROUND: Maternal overweight and obesity might increase risks of adiposity and cardiovascular and metabolic diseases in offspring. We examined associations between maternal overweight and obesity severity and risk of cardiovascular diseases in young offspring. METHODS: In this population-based cohort study, we used data from live singleton births recorded in the Swedish Medical Birth Register. We calculated maternal BMI in early pregnancy from self-reported height and weight measurements at the first prenatal visit. We used multivariable Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% CIs. We calculated the proportion of the associations mediated through known consequences of obesity that also predicted cardiovascular diseases and did family case-control analyses. FINDINGS: We identified 2 230 115 live singleton infants (without congenital malformations) in Sweden registered between Jan 1, 1992, and Dec 31, 2016. Overall, 1741 (0·08%) offspring were diagnosed with a cardiovascular disease between ages 1 and 25 years. Cardiovascular disease rates by maternal BMI categories were 0·57 per 10 000 child-years (BMI 18·5-24·9 kg/m2; normal weight), 0·61 per 10 000 child-years (25·0-29·9 kg/m2; overweight), 0·67 per 10 000 child-years (30·0-34·9 kg/m2; obesity grade I), 1·02 per 10 000 child-years (35·0-39·9 kg/m2; obesity grade II), and 1·38 per 10 000 child-years (≥40·0 kg/m2; obesity grade III). Compared with offspring of mothers with normal BMI, HRs of cardiovascular diseases were 1·10 (95% CI 0·97-1·25) for overweight, 1·16 (0·95-1·43) for obesity grade I, 1·84 (1·36-2·49) for obesity grade II, and 2·51 (1·60-3·92) for obesity grade III. Risks of cerebrovascular diseases increased with maternal obesity severity and were partly mediated through asphyxia-related neonatal complications. The sibling-cohort analysis also indicated a positive trend between maternal BMI and cardiovascular disease rates. INTERPRETATIONS: Our findings indicate that maternal obesity might be a risk factor for cardiovascular diseases in childhood and early adulthood. These results need to be replicated and possible underlying mechanisms identified. FUNDING: Swedish Research Council for Health, Working Life and Welfare.


Assuntos
Doenças Cardiovasculares/etiologia , Obesidade Materna/complicações , Sobrepeso/complicações , Complicações na Gravidez/etiologia , Irmãos , Adolescente , Adulto , Biomarcadores/análise , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Suécia/epidemiologia , Adulto Jovem
15.
Lancet Diabetes Endocrinol ; 8(7): 616-627, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32559477

RESUMO

An increase in fat mass is considered to be an important risk factor for the worldwide increase in type 2 diabetes and cardiovascular disease. However, for a given fat mass, there is a large variability in the risk prediction of these cardiometabolic diseases. For example, some lean people unexpectedly have a risk of type 2 diabetes and cardiovascular disease that is similar to the increased risk that is observed in most people who have obesity. What both of these phenotypes have in common is a very characteristic fat distribution. As a result, much focus has been given on the strong predictive power of increased visceral fat mass. However, an analysis of the causes of type 2 diabetes and cardiovascular disease, as well as comparisons to rare diseases such as lipodystrophy and studying genetically determined fat distribution in the general population, suggest that an impaired ability to expand subcutaneous fat in the lower part of the body is also important for predicting the incidence of these cardiometabolic diseases. This Review, first, addresses the identification of distinct fat distribution phenotypes and their risk of cardiometabolic diseases by discussing findings from published studies that have applied precise quantification of different fat depots. Second, this Review provides support for the theory that a lower amount of lower-body fat mass is equally important to a high amount of visceral fat mass as a determinant of cardiometabolic diseases. Third, this Review discusses the genetic and lifestyle-related causes of metabolically healthy and unhealthy fat distribution. Finally, this Review summarises and appraises the effectiveness of lifestyle-related interventions and pharmacological interventions for reducing visceral adiposity and maintaining lower-body fat mass to prevent and treat cardiometabolic diseases.


Assuntos
Tecido Adiposo/patologia , Distribuição da Gordura Corporal , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/etiologia , Resistência à Insulina , Obesidade/complicações , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/patologia , Humanos , Fatores de Risco
16.
Eur J Endocrinol ; 183(3): R57-R73, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32508312

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a growing health problem with a global prevalence of over 25% and prevalence rates of over 60% in high-risk populations. It is considered the hepatic component of the metabolic syndrome and is associated with an increased risk of the development of various liver-associated and cardiometabolic complications. Given the complexity of NAFLD and associated comorbidities and complications, treatment requires interventions from a variety of different healthcare specialties. However, many clinicians are currently insufficiently aware of the potential harm and severity of NAFLD and associated comorbidities, complications and the steps that should be taken when NAFLD is suspected. Recognizing which patients suffer from non-progressive simple steatosis, metabolically active NASH with high risk of developing cardiovascular disease and which patients have a high risk of developing cirrhosis and hepatocellular carcinoma is important. Unfortunately, this can be difficult and guidelines towards the optimal diagnostic and therapeutic approach are ambivalent. Here we review the pathogenesis, diagnostics and treatment of NAFLD and discuss how multidisciplinary care path development could move forward.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/cirurgia , Humanos , Fígado/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/cirurgia
17.
Arterioscler Thromb Vasc Biol ; 40(8): 1818-1829, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32510978

RESUMO

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to ACE2 (angiotensin-converting enzyme 2). While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen. In severe cases, deterioration to acute respiratory distress syndrome necessitating mechanical ventilation, development of severe thrombotic events, or cardiac injury and dysfunction occurs. In this review, we highlight what is known to date about COVID-19 and cardiovascular risk, focusing in on the putative role of the endothelium in disease susceptibility and pathogenesis. Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. Given that the virus affects multiple organs, including the heart, it likely gains access into systemic circulation by infecting or passing from the respiratory epithelium to the endothelium for viral dissemination. Indeed, cardiovascular complications of COVID-19 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 expression, such as diabetes mellitus, hypertension, and cardiovascular disease. CONCLUSIONS: Rapidly emerging data on COVID-19, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.


Assuntos
Doenças Cardiovasculares/patologia , Infecções por Coronavirus/epidemiologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/patologia , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Citocinas/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Humanos , Pandemias/estatística & dados numéricos , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Prevalência , Medição de Risco , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença , Análise de Sobrevida
18.
J Immunol ; 205(2): 313-320, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32493812

RESUMO

Aging impairs immunity to promote diseases, especially respiratory viral infections. The current COVID-19 pandemic, resulting from SARS-CoV-2, induces acute pneumonia, a phenotype that is alarmingly increased with aging. In this article, we review findings of how aging alters immunity to respiratory viral infections to identify age-impacted pathways common to several viral pathogens, permitting us to speculate about potential mechanisms of age-enhanced mortality to COVID-19. Aging generally leads to exaggerated innate immunity, particularly in the form of elevated neutrophil accumulation across murine and large animal studies of influenza infection. COVID-19 patients who succumb exhibit a 2-fold increase in neutrophilia, suggesting that exaggerated innate immunity contributes to age-enhanced mortality to SARS-CoV-2 infection. Further investigation in relevant experimental models will elucidate the mechanisms by which aging impacts respiratory viral infections, including SARS-CoV-2. Such investigation could identify therapies to reduce the suffering of the population at large, but especially among older people, infected with respiratory viruses.


Assuntos
Envelhecimento/patologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Infecções Respiratórias/virologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/virologia , Citocinas/imunologia , Humanos , Influenza Humana/imunologia , Influenza Humana/patologia , Pandemias , Infecções Respiratórias/patologia , Vírus da SARS/fisiologia
19.
PLoS One ; 15(6): e0235333, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584904

RESUMO

Patient satisfaction is a useful predictor of adherence and outcomes of cardiovascular diseases (CVDs) treatment. This study explored the satisfaction of Vietnamese CVDs inpatients and outpatients using a scale specifically designed for CVDs patients and examined the factors associated with satisfaction towards CVDs treatment services. Interviews of 600 patients at the Hanoi Heart Hospital were conducted. We developed a measurement scale for both inpatient and outpatient services. Multivariate Tobit regression was used to determine the associated factors with patient satisfaction. For inpatients, Cronbach's alpha reported for the domains were in the range of 0.72-0.97, while for outpatients, Cronbach's alpha was within 0.61-0.97. Overall, patients were more satisfied with inpatient services (Mean = 81.8, SD = 5.8) than outpatient services (Mean = 79.7, SD = 5.2, p<0.05). In inpatients, the highest complete satisfaction was in "Attitude of Nurse" item (42.0%), the highest satisfaction score was in "Care and treatment" domain (Mean = 85.6, SD = 9.7) and the lowest in "Hospital facilities" domain (Mean = 78.3; SD = 9.2). Among outpatients, the highest complete satisfaction was in "Attitude of physicians when examining, guiding and explaining to the patient" item (19.7%), the highest satisfaction score was in "Attitude of medical staff" domain (Mean = 82.8; SD = 7.9) and the lowest in "Waiting time" domain (Mean = 76.6; SD = 8.2). People not having health insurances had significantly higher scores in "Waiting time", "Hospital facilities" and "Attitude of staff" domains (for outpatients) and in "Health service accessibility", "Hospital facilities" domains (for inpatients) as well as higher total satisfaction score than those having health insurance. Findings discovered through the application of the newly developed instrument showed low satisfaction regarding hospital facilities for inpatients and waiting time for outpatients, suggesting renovation efforts, while inferiority regarding patient satisfaction of health insurance covered patients compared to those without implied policy reform possibility. Further enhancement and validation of the developed instrument was required.


Assuntos
Doenças Cardiovasculares/terapia , Assistência à Saúde , Satisfação do Paciente , Adulto , Idoso , Atitude do Pessoal de Saúde , Doenças Cardiovasculares/patologia , Estudos Transversais , Acesso aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Vietnã
20.
Nature ; 584(7819): 136-141, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32581363

RESUMO

Clonally expanded blood cells that contain somatic mutations (clonal haematopoiesis) are commonly acquired with age and increase the risk of blood cancer1-9. The blood clones identified so far contain diverse large-scale mosaic chromosomal alterations (deletions, duplications and copy-neutral loss of heterozygosity (CN-LOH)) on all chromosomes1,2,5,6,9, but the sources of selective advantage that drive the expansion of most clones remain unknown. Here, to identify genes, mutations and biological processes that give selective advantage to mutant clones, we analysed genotyping data from the blood-derived DNA of 482,789 participants from the UK Biobank10. We identified 19,632 autosomal mosaic chromosomal alterations and analysed these for relationships to inherited genetic variation. We found 52 inherited, rare, large-effect coding or splice variants in 7 genes that were associated with greatly increased vulnerability to clonal haematopoiesis with specific acquired CN-LOH mutations. Acquired mutations systematically replaced the inherited risk alleles (at MPL) or duplicated them to the homologous chromosome (at FH, NBN, MRE11, ATM, SH2B3 and TM2D3). Three of the genes (MRE11, NBN and ATM) encode components of the MRN-ATM pathway, which limits cell division after DNA damage and telomere attrition11-13; another two (MPL and SH2B3) encode proteins that regulate the self-renewal of stem cells14-16. In addition, we found that CN-LOH mutations across the genome tended to cause chromosomal segments with alleles that promote the expansion of haematopoietic cells to replace their homologous (allelic) counterparts, increasing polygenic drive for blood-cell proliferation traits. Readily acquired mutations that replace chromosomal segments with their homologous counterparts seem to interact with pervasive inherited variation to create a challenge for lifelong cytopoiesis.


Assuntos
Evolução Clonal/genética , Células Clonais/metabolismo , Hematopoese/genética , Herança Multifatorial/genética , Adulto , Idoso , Alelos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Divisão Celular/genética , Aberrações Cromossômicas , Células Clonais/citologia , Células Clonais/patologia , Feminino , Predisposição Genética para Doença , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Humanos , Perda de Heterozigosidade/genética , Masculino , Pessoa de Meia-Idade , Mosaicismo , Reino Unido
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