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2.
Ecotoxicol Environ Saf ; 203: 111044, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888613

RESUMO

BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) is associated with various adverse health outcomes. Although several mechanisms have been proposed including oxidative stress and inflammatory responses, the exact mechanism is still unknown. Few studies have investigated the mechanism linking PM2.5 and blood pressure (BP). In this study, we measured urinary metabolites and BP -related renin-angiotensin-aldosterone system (RAAS) to investigate the associations between ambient PM2.5 exposure and BP in healthy C57BL/6 mice. METHODS: The C57BL/6 mice were exposed to ambient concentrated PM2.5 or filtered air (FA) for 16 weeks. Systolic BP and diastolic BP were measured by noninvasive BP system. The urine metabolites were quantified using the untargeted metabolomics approach. The expression of RAAS-related proteins angiotensin-converting enzyme (ACE)2, angiotensin (Ang) II, Ang (1-7) and aldosterone (ALD) were measured using Western blot and ELISA kits. RESULTS: The metabolomics analysis demonstrated that PM2.5 exposure induced significant changes of some metabolites in urine, including stress hormones, amino acids, fatty acids, and lipids. Furthermore, there was an elevation of BP, increase of serous Ang II and ALD, along with the decrease of ACE2 and Ang (1-7) in kidney in the PM2.5-exposed mice compared with FA-exposed mice. CONCLUSIONS: The results demonstrated that PM2.5 exposure-induced BP elevation might be associated with RAAS activation. Meanwhile, PM2.5 exposure-induced changes of stress hormone and lipid metabolism might mediate the activation of RAAS. The results suggested that the systemic stress hormone and lipid metabolism was associated with the development of hypertension.


Assuntos
Poluentes Atmosféricos/toxicidade , Angiotensina I/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/induzido quimicamente , Material Particulado/toxicidade , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Acetilglucosaminidase/urina , Angiotensina I/sangue , Animais , Biomarcadores/sangue , Biomarcadores/urina , Hipertensão/urina , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metaboloma/efeitos dos fármacos , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , beta-Galactosidase/urina
3.
Emerg Med Clin North Am ; 38(4): 931-944, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981627

RESUMO

Emergency physicians must be prepared to rapidly diagnose and resuscitate patients with pulmonary embolism (PE). Certain aspects of PE resuscitation run counter to typical approaches. A specific understanding of the pathophysiology of PE is required to avoid cardiovascular collapse potentially associated with excessive intravenous fluids and positive pressure ventilation. Once PE is diagnosed, rapid risk stratification should be performed and treatment guided by patient risk class. Although anticoagulation remains the mainstay of PE treatment, emergency physicians also must understand the indications and contraindications for thrombolysis and should be aware of new therapies and models of care that may improve outcomes.


Assuntos
Embolia Pulmonar/terapia , Anticoagulantes/uso terapêutico , Biomarcadores/sangue , Angiografia por Tomografia Computadorizada , Estado Terminal , Ecocardiografia , Eletrocardiografia , Serviço Hospitalar de Emergência , Oxigenação por Membrana Extracorpórea , Hidratação , Humanos , Intubação Intratraqueal , Ácido Láctico/sangue , Trombólise Mecânica , Peptídeo Natriurético Encefálico/sangue , Óxido Nítrico/uso terapêutico , Oxigenoterapia , Fragmentos de Peptídeos/sangue , Sistemas Automatizados de Assistência Junto ao Leito , Respiração com Pressão Positiva , Embolia Pulmonar/classificação , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/fisiopatologia , Ressuscitação/métodos , Medição de Risco , Índice de Gravidade de Doença , Terapia Trombolítica , Troponina/sangue , Vasoconstritores/uso terapêutico
4.
Int Heart J ; 61(5): 1079-1083, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32879264

RESUMO

A Japanese girl with polycystic kidney disease (PKD) developed normally, but at 8 months of age, she was hospitalized for acute onset dyspnea. On the day after admission to hospital, her general condition suddenly became worse. An echocardiogram showed left ventricular dilatation with thin walls, severe mitral valve regurgitation, and a reduced ejection fraction. She died of acute cardiac failure 3 hours after the sudden change. Postmortem analysis with light microscopy showed disarray of cardiomyocytes without obvious infiltration of lymphocytes, and we diagnosed her heart failure as idiopathic dilated cardiomyopathy (DCM). Clinical exome sequencing showed compound heterozygous variants in JPH2 (p.T237A/p.I414L) and a heterozygous nonsense mutation in PKD1 (p.Q4193*). To date, several variants in the JPH2 gene have been reported to be pathogenic for adult-onset hypertrophic cardiomyopathy or DCM in an autosomal dominant manner and infantile-onset DCM in an autosomal recessive manner. Additionally, autosomal dominant polycystic kidney disease is a systemic disease associated with several extrarenal manifestations, such as cardiomyopathy. Here we report a sudden infant death case of DCM and discuss the genetic variants of DCM and PKD.


Assuntos
Cardiomiopatia Dilatada/genética , Proteínas de Membrana/genética , Proteínas Musculares/genética , Rim Policístico Autossômico Dominante/genética , Canais de Cátion TRPP/genética , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/patologia , Morte Súbita Cardíaca/etiologia , Evolução Fatal , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/etiologia , Heterozigoto , Humanos , Lactente , Insuficiência da Valva Mitral/etiologia , Miocárdio/patologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue
5.
Tumour Biol ; 42(9): 1010428320958603, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32964798

RESUMO

This study aimed to investigate whether changes in progastrin-releasing peptide (ProGRP) levels correlate with treatment response and can be used to optimize clinical management of patients with small-cell lung cancer. Patients with small-cell lung cancer (any stage) receiving chemotherapy were eligible. ProGRP was measured in serum/plasma at baseline and after each chemotherapy cycle using the Elecsys® ProGRP assay (Roche Diagnostics). Treatment response was assessed by computed tomography scan. The primary objective was to examine whether changes in ProGRP levels correlated with computed tomography scan results after two cycles of chemotherapy. The prognostic value of ProGRP among patients receiving first-line chemotherapy was also assessed. Overall, 261 patients from six centers were eligible. Among patients with elevated baseline ProGRP (>100 pg/mL), a ProGRP decline after Cycle 2 was associated with nonprogression (area under the curve: 84%; 95% confidence interval: 72.8-95.1; n = 141). ProGRP changes from baseline to end of Cycle 1 were predictive of response, as determined by computed tomography scan 3 weeks later (area under the curve: 87%; 95% confidence interval: 74.1-99.2; n = 137). This was enhanced by repeat measurements, with a 92% area under the curve (95% confidence interval: 85.3-97.8) among patients with ProGRP data after both Cycles 1 and 2 (n = 123); if a patient experienced a ≥25% decline in ProGRP after Cycle 1, and ProGRP remained stable or decreased after Cycle 2, the probability of finding progression on the interim computed tomography scan at the end of Cycle 2 was almost zero (sensitivity: 100%, specificity: 71%). Both ProGRP levels at baseline and at the end of first-line chemotherapy were prognostic; the latter provided a moderately improved hazard ratio of 2.43 (95% confidence interval: 1.33-4.46; n = 110) versus 1.87 (95% confidence interval: 1.04-3.37; n = 216). In summary, for patients with small-cell lung cancer and elevated baseline ProGRP levels, ProGRP may be a simple, reliable, and repeatable tool for monitoring response to chemotherapy and provide valuable prognostic information.


Assuntos
Neoplasias Pulmonares/sangue , Fragmentos de Peptídeos/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biomarcadores Tumorais/sangue , China , Europa (Continente) , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes/sangue , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tomografia Computadorizada por Raios X
6.
Medicine (Baltimore) ; 99(31): e21460, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756167

RESUMO

Volume status is a key parameter for cardiovascular-related mortality in dialysis patients. Although N-terminal pro-B-type natriuretic peptide (NT-proBNP), myeloperoxidase, copeptin, and pro-adrenomedullin have been reported as volume markers, the relationship between body fluid status and volume markers in dialysis patients is uncertain. Therefore, we investigated the utility of volume status biomarkers based on body composition monitor (BCM) analyses.We enrolled pre-dialysis, hemodialysis (HD), and peritoneal dialysis (PD) patients and age- and gender-matched healthy Korean individuals (N = 80). BCM and transthoracic echocardiography were performed and NT-proBNP, myeloperoxidase, copeptin, and pro-adrenomedullin concentrations were measured. Relative hydration status (ΔHS, %) was defined in terms of the hydration status-to-extracellular water ratio with a cutoff of 15%, and hyperhydrated status was defined as ΔHS > 15%.Although there were no significant differences in total body water, extracellular water, or intracellular water among groups, mean amount of volume overload and hyperhydrated status were significantly higher in HD and PD patients compared with control and pre-dialysis patients. Mean amount of volume overload and hyperhydrated status were also significantly associated with higher NT-proBNP and pro-adrenomedullin levels in HD and PD patients, although not with myeloperoxidase or copeptin levels. Furthermore, they were significantly associated with cardiac markers (left ventricular mass index, ejection fraction, and left atrial diameter) in HD and PD patients compared with those in the control and pre-dialysis groups.On the basis of increased plasma NT-proBNP and pro-adrenomedullin concentrations, we might be able to make predictions regarding the volume overload status of dialysis patients, and thereby reduce cardiovascular-related mortality through appropriate early volume control.


Assuntos
Biomarcadores/sangue , Líquidos Corporais/metabolismo , Doenças Cardiovasculares/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia , Adrenomedulina/sangue , Adulto , Composição Corporal/fisiologia , Doenças Cardiovasculares/diagnóstico por imagem , Estudos de Casos e Controles , Diálise/métodos , Diálise/tendências , Ecocardiografia/métodos , Feminino , Glicopeptídeos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Diálise Peritoneal/estatística & dados numéricos , Peroxidase/sangue , Precursores de Proteínas/sangue , Diálise Renal/estatística & dados numéricos , República da Coreia/epidemiologia , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem
7.
BMC Infect Dis ; 20(1): 580, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762658

RESUMO

BACKGROUND: Dengue virus (DENV) causes the hospitalisation of an estimated 500,000 people every year. Outbreaks can severely stress healthcare systems, especially in rural settings. It is difficult to discriminate patients who need to be hospitalized from those that do not. Earlier work identified thrombocyte count and subsequent function as a promising prognostic marker of DENV severity. Herein, we investigated the potential of quantitative thrombocyte function tests in those admitted in the very early phase of acute DENV infections, using Multiplate™ multiple-electrode aggregometry to explore its potential in triage. METHODS: In this prospective cohort study all patients aged ≥13 admitted to Universitas Airlangga Hospital in Surabaya, Indonesia with a fever (≥38 °C) between 25 January and 1 August 2018 and with a clinical suspicion of DENV, were eligible for inclusion. Exclusion criteria were a thrombocyte count below 100 × 109/L and the use of any medication with a known anticoagulant effect, nonsteroidal anti-inflammatory drugs and acetyl salicylic acid. Clinical data was collected and blood was taken on admission, day 1 and day 7. Samples were tested for acute DENV, using Panbio NS1 ELISA. Platelet aggregation using ADP-, TRAP- and COL-test were presented as Area Under the aggregation Curve (AUC). Significance was tested between DENV+, probably DENV, fever of another origin, and healthy controls (HC). RESULTS: A total of 59 patients (DENV+ n = 10, DENV probable n = 25, fever other origin n = 24) and 20 HC were included. We found a significantly lower thrombocyte aggregation in the DENV+ group, compared with both HCs and the fever of another origin group (p < .001). Low ADP AUC values on baseline correlated to a longer hospital stay in DENV+ and probable DENV cases. CONCLUSION: Thrombocyte aggregation induced by Adenosine diphosphate, Collagen and Thrombin receptor activating peptide-6 is impaired in human DENV cases, compared with healthy controls and other causes of fever. This explorative study provides insights to thrombocyte function in DENV patients and could potentially serve as a future marker in DENV disease.


Assuntos
Plaquetas/metabolismo , Vírus da Dengue/imunologia , Dengue/diagnóstico , Dengue/epidemiologia , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Difosfato de Adenosina/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Colágeno/metabolismo , Dengue/virologia , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/diagnóstico , Humanos , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Agregação Plaquetária , Contagem de Plaquetas , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
8.
Medicine (Baltimore) ; 99(31): e21492, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756181

RESUMO

Activation of the renin angiotensin system and renal oxidative stress (OS) are critical contributors in the progression of chronic kidney disease(CKD). Recent studies have confirmed that the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas(ACE2/Ang(1-7)/Mas) axis, the important components of renin angiotensin system, protected kidneys against damage by antagonizing angiotensin II and attenuating OS in rats with several nephropathy models, but its effect needs to be further evaluated in clinic. In this study, we aimed to detected serum ACE2/Ang (1-7)/Mas axis, OS conditions and described its clinical associations in patients with CKD at different stages.A total of 48 patients with CKD and 6 healthy controls (CT) were enrolled, and serum angiotensin converting enzyme (ACE), ACE2, Ang (1-7), 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined by ELISA. Serum extracellular glutathione peroxidase(eGSH-Px) activity and renal functions were determined by the biochemical method.Serum ACE and ACE2 levels in CKD stages 3 to 5 and serum Ang(1-7) levels in CKD stages 4 to 5 without Ang II receptor blockers treatment significantly increased compared to those in the CT group. However, ACE2 was decreased and Ang(1-7) level increased in early CKD stage with Ang II receptor blockers treatment. Higher serum 8-OHdG levels and lower eGSH-Px activity were noted in CKD stages 4 to 5. Serum 8-OHdG level was correlated with serum ACE2, Ang(1-7) expression. Estimated glomerular filtration rate (eGFR) was correlated with serum ACE, ACE2, Ang(1-7), 8-OHdG, Hcy levels and serum eGSH-Px activity. Multiple-regression analysis eGFR was predicted by ACE, Hcy, eGSH-Px, and also can be predicted by ACE2, Ang(1-7), Hcy in CT subgroup.The ACE2/Ang(1-7)/Mas axis is associated with OS, and both them were associated with eGFR in the progression of CKD. Activation of ACE2/Ang(1-7)/Mas axis may have renoprotective effect and can be a potential therapeutic target in patients with early CKD stages.


Assuntos
Angiotensina II/sangue , Angiotensina I/sangue , Estresse Oxidativo/fisiologia , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Insuficiência Renal Crônica/sangue , 8-Hidroxi-2'-Desoxiguanosina/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sistema Renina-Angiotensina/fisiologia
9.
Redox Biol ; 36: 101655, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32738789

RESUMO

Nox2 is responsible for artery dysfunction via production of reactive oxidant species. RNA viruses may activate Nox2, but it is unknown if this occurs in coronavirus 2019(Covid-19). Nox2 activation by soluble Nox2-derived peptide(sNox2-dp) was measured in patients hospitalized for Covid-19 (n = 182) and controls (n = 91). sNox2-dp values were higher in Covid-19 patients versus controls and in severe versus non severe Covid-19. Patients with thrombotic events(n = 35,19%) had higher sNox2-dp than thrombotic event-free ones. A logistic regression analysis showed that sNox2 and coronary heart disease predicted thrombotic events. Oxidative stress by Nox2 activation is associated severe disease and thrombotic events in Covid-19 patients.


Assuntos
Infecções por Coronavirus/metabolismo , NADPH Oxidase 2/metabolismo , Pneumonia Viral/metabolismo , Trombose/sangue , Idoso , Biomarcadores/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , NADPH Oxidase 2/química , Estresse Oxidativo , Pandemias , Fragmentos de Peptídeos/sangue , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Trombose/etiologia
10.
Nat Commun ; 11(1): 3820, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732919

RESUMO

Supercentenarians (those aged ≥110 years) are approaching the current human longevity limit by preventing or surviving major illness. Identifying specific biomarkers conducive to exceptional survival might provide insights into counter-regulatory mechanisms against aging-related disease. Here, we report associations between cardiovascular disease-related biomarkers and survival to the highest ages using a unique dataset of 1,427 oldest individuals from three longitudinal cohort studies, including 36 supercentenarians, 572 semi-supercentenarians (105-109 years), 288 centenarians (100-104 years), and 531 very old people (85-99 years). During follow-up, 1,000 participants (70.1%) died. Overall, N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6, cystatin C and cholinesterase are associated with all-cause mortality independent of traditional cardiovascular risk factors and plasma albumin. Of these, low NT-proBNP levels are statistically associated with a survival advantage to supercentenarian age. Only low albumin is associated with high mortality across age groups. These findings expand our knowledge on the biology of human longevity.


Assuntos
Envelhecimento/sangue , Biomarcadores/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Albumina Sérica/análise , Inquéritos e Questionários/estatística & dados numéricos , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Feminino , Humanos , Longevidade/fisiologia , Estudos Longitudinais , Masculino , Análise Multivariada , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida
11.
PLoS One ; 15(8): e0237364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764816

RESUMO

OBJECTIVES: Uromodulin has been associated with arterial hypertension in genome-wide association studies, but data from clinical and preclinical studies are inconsistent. We here analyzed the association of serum uromodulin (sUmod) with arterial hypertension and vasoactive hormones in a population-based study. METHODS: In 1108 participants of the KORA F4 study aged 62-81 years, sUmod was measured and the association of sUmod with arterial hypertension was assessed using logistic regression models. The associations of sUmod with renin and aldosterone and with the vasoconstrictive prohormone C-terminal pro-endothelin-1 (CT-proET-1) were analyzed in 1079 participants and in 618 participants, respectively, using linear regression models. RESULTS: After multivariable adjustment including sex, age, eGFR, BMI, fasting glucose, current smoking, previous stroke and myocardial infarction, sUmod was inversely associated with arterial hypertension (OR 0.78; 95% CI 0.68-0.91; p = 0.001). SUmod was not significantly associated with renin and aldosterone after adjustment for sex, age and eGFR. However, sUmod was inversely associated with CT-proET-1 (ß -0.19 ± 0.04; p < 0.001) after adjustment for sex, age, eGFR, BMI, arterial hypertension, fasting glucose, current smoking, previous stroke and myocardial infarction. The association with CT-proET-1 was stronger in participants with hypertension (ß -0.22 ± 0.04) than in normotensive participants (ß -0.13 ± 0.06; p for interaction hypertension = 0.003 in the model adjusted for hypertension). CONCLUSIONS: SUmod was inversely associated with arterial hypertension and the vasoconstrictive prohormone CT-proET-1, suggesting direct or indirect effects of sUmod on blood pressure regulation.


Assuntos
Endotelina-1/sangue , Hipertensão/sangue , Fragmentos de Peptídeos/sangue , Uromodulina/sangue , Idoso , Aldosterona/sangue , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Renina/sangue
12.
Am Heart J ; 228: 47-56, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32798787

RESUMO

AIMS: To investigate the effect of the sodium-glucose co-transporter-2 inhibitor empagliflozin on N-terminal pro-b-type natriuretic peptide (NT-proBNP) in patients with heart failure (HF) and reduced ejection fraction (HFrEF). METHODS AND RESULTS: Empire HF was an investigator-initiated, multi-center, double-blinded, placebo-controlled, randomized trial. Patients with mildly symptomatic HFrEF, mean (standard deviation (SD)) age 64 (11) years, 85% male, and mean left ventricular ejection fraction 29% (8), on recommended HF therapy were assigned to receive either empagliflozin 10 mg once daily or placebo for 12 weeks. The primary endpoint was the between-group difference in the change of NT-proBNP from baseline to 12 weeks. In total, 95 patients were assigned to empagliflozin and 95 to placebo. No significant difference in the change of NT-proBNP with empagliflozin versus placebo was observed [Empagliflozin: baseline, median (interquartile range (IQR)) 582 (304-1020) pg/mL, 12 weeks, 478 (281-961) pg/mL; Placebo: baseline, 605 (322-1070) pg/mL, 12 weeks, 520 (267-1075) pg/mL, adjusted ratio of change empagliflozin/placebo 0.98; 95% confidence interval (CI) 0.82-1.11, P = 0.7]. Further, no significant difference was observed in accelerometer-measured daily activity level [adjusted mean difference of change, empagliflozin versus placebo, -26.0 accelerometer counts; 95% CI -88.0 to 36.0, P = 0.4] or Kansas City Cardiomyopathy Questionnaire Overall Summary Score [adjusted mean difference of change, empagliflozin versus placebo 0.8; 95% CI -2.3 to 3.9, P = 0.6]. CONCLUSION: In low-risk patients with HFrEF with mild symptoms and on recommended HF therapy, empagliflozin did not change NT-proBNP after 12 weeks. Further, no change in daily activity level or health status was observed.


Assuntos
Acelerometria/métodos , Atividades Cotidianas , Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Disfunção Ventricular Esquerda/diagnóstico , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/efeitos adversos , Método Duplo-Cego , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Volume Sistólico
14.
PLoS Med ; 17(7): e1003121, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32673317

RESUMO

BACKGROUND: Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average effect on plasma lipids in humans and its safety profile. METHODS AND FINDINGS: We carried out a systematic review and meta-analysis of phase II and III randomized controlled trials on bempedoic acid (PROSPERO: CRD42019129687). PubMed (Medline), Scopus, Google Scholar, and Web of Science databases were searched, with no language restriction, from inception to 5 August 2019. We included 10 RCTs (n = 3,788) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]). Effect sizes for changes in lipids and high-sensitivity C-reactive protein (hsCRP) serum concentration were expressed as mean differences (MDs) and 95% confidence intervals (CIs). For safety analyses, odds ratios (ORs) and 95% CIs were calculated using the Mantel-Haenszel method. Bempedoic acid significantly reduced total cholesterol (MD -14.94%; 95% CI -17.31%, -12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD -18.17%; 95% CI -21.14%, -15.19%; p < 0.001), low-density lipoprotein cholesterol (MD -22.94%; 95% CI -26.63%, -19.25%; p < 0.001), low-density lipoprotein particle number (MD -20.67%; 95% CI -23.84%, -17.48%; p < 0.001), apolipoprotein B (MD -15.18%; 95% CI -17.41%, -12.95%; p < 0.001), high-density lipoprotein cholesterol (MD -5.83%; 95% CI -6.14%, -5.52%; p < 0.001), high-density lipoprotein particle number (MD -3.21%; 95% CI -6.40%, -0.02%; p = 0.049), and hsCRP (MD -27.03%; 95% CI -31.42%, -22.64%; p < 0.001). Bempedoic acid did not significantly modify triglyceride level (MD -1.51%; 95% CI -3.75%, 0.74%; p = 0.189), very-low-density lipoprotein particle number (MD 3.79%; 95% CI -9.81%, 17.39%; p = 0.585), and apolipoprotein A-1 (MD -1.83%; 95% CI -5.23%, 1.56%; p = 0.290). Treatment with bempedoic acid was positively associated with an increased risk of discontinuation of treatment (OR 1.37; 95% CI 1.06, 1.76; p = 0.015), elevated serum uric acid (OR 3.55; 95% CI 1.03, 12.27; p = 0.045), elevated liver enzymes (OR 4.28; 95% CI 1.34, 13.71; p = 0.014), and elevated creatine kinase (OR 3.79; 95% CI 1.06, 13.51; p = 0.04), though it was strongly associated with a decreased risk of new onset or worsening diabetes (OR 0.59; 95% CI 0.39, 0.90; p = 0.01). The main limitation of this meta-analysis is related to the relatively small number of individuals involved in the studies, which were often short or middle term in length. CONCLUSIONS: Our results show that bempedoic acid has favorable effects on lipid profile and hsCRP levels and an acceptable safety profile. Further well-designed studies are needed to explore its longer-term safety.


Assuntos
Anticolesterolemiantes/uso terapêutico , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Anticolesterolemiantes/efeitos adversos , Apolipoproteínas B/sangue , Colesterol/sangue , LDL-Colesterol/sangue , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Ácidos Dicarboxílicos/efeitos adversos , Ácidos Graxos/efeitos adversos , Humanos , Hipercolesterolemia/sangue , Fragmentos de Peptídeos/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
PLoS One ; 15(7): e0235640, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730268

RESUMO

BACKGROUND: Fluid overload is common in patients with diabetes and chronic kidney disease (DM and CKD; DMCKD) and can lead to structural and functional cardiac abnormalities including left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). Fluid overload represents a crucial step in the pathophysiological pathways to chronic heart failure in patients with end-stage renal disease. We evaluated the impact of fluid overload on cardiac alterations in patients with diabetes and non-dialysis-dependent CKD stage 5 (DMCKD5-ND) without intrinsic heart disease. METHODS: Bioimpedance spectroscopy, echocardiography, and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) measurement were performed in 135 consecutive patients on the same day. Patients were divided into groups by tertiles of overhydration/extracellular water (OH/ECW) per bioimpedance spectroscopy. RESULTS: Fluid balance markers including OH/ECW and NT-proBNP were significantly higher in the LVDD+LVH group. OH/ECW and its exacerbation were positively associated with the ratio between early mitral inflow and annular early diastolic velocities (E/e' ratio) and left ventricular mass index (LVMI). The prevalence of LVH progressively increased across increasing tertiles of OH/ECW. In multiple regression analyses, OH/ECW as a continuous and categorical variable was independently associated with the E/e' ratio and LVMI after adjustment for multiple confounding factors. CONCLUSIONS: Fluid overload was independently associated with LVDD and LVH in patients with DMCKD5-ND. Our study suggests that structural and functional cardiac abnormalities and volume status should be evaluated simultaneously in patients with early-stage DMCKD rather than only DMCKD5-ND, in addition to intensive blood pressure and glycemic control, regardless of evident cardiovascular disease.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Hidratação , Falência Renal Crônica/patologia , Idoso , Espectroscopia Dielétrica , Ecocardiografia , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/patologia , Falência Renal Crônica/terapia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Prevalência , Diálise Renal , Índice de Gravidade de Doença , Disfunção Ventricular Esquerda/patologia
16.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(6): 711-715, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32684218

RESUMO

OBJECTIVE: To investigate the significance of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the early assessment of neonatal cardiac dysfunction in sepsis. METHODS: The children diagnosed with neonatal sepsis and common infection neonates admitted to the department of pediatric neonatal intensive care unit (NICU) of Liaocheng People's Hospital from January 2016 to January 2019 were enrolled. Data of clinical sign, laboratory results, bedside echocardiography and survival data were collected, and the differences of clinical indexes were compared among sepsis patients with and without cardiac dysfunction and common infection. The risk factors of sepsis with cardiac dysfunction were analyzed by multivariate Logistic regression, and the early prediction value of NT-proBNP for neonatal septic cardiac dysfunction was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: There were 112 neonates with sepsis (49 with cardiac dysfunction and 63 without cardiac dysfunction) and 67 children with common infection included in the analysis. The onset time of neonates in septic cardiac dysfunction group was significantly earlier than that of septic non-cardiac dysfunction group and common infection group [hours: 52.9 (0, 180.3) vs. 53.9 (0, 183.6), 81.0 (45.6, 202.4), both P < 0.05]. Compared with the general infection group, albumin (ALB), white blood cell count (WBC), left ventricular ejection fraction (LVEF) in septic cardiac dysfunction group significantly decreased, NT-proBNP, hypersensitive C-reactive protein (hs-CRP)/ALB, pulmonary artery systolic pressure (PASP) significantly increased, while right ventricular (RV) and Tei index significantly increased [ALB (g/L): 24.1±3.8 vs. 27.8±3.6, WBC (×109/L): 12.7 (3.7, 18.9) vs. 15.4 (9.9, 23.2), LVEF: 0.626±0.123 vs. 0.700±0.021, NT-proBNP (ng/L): 20 230.6 (15 890.0, 35 000.0) vs. 7 324.5 (2 426.5, 13 890.0), hs-CRP/ALB: 0.33 (0.29, 0.81) vs. 0.06 (0.00, 0.21), PASP (mmHg, 1 mmHg = 0.133 kPa): 52.25±14.12 vs. 41.07±27.73, RV (mm): 10.74±2.42 vs. 8.55±1.41, Tei index: 0.52±0.03 vs. 0.30±0.04, all P < 0.05]. NT-proBNP and Tei index in septic cardiac dysfunction group were significantly higher than those in septic non-cardiac dysfunction group [NT-proBNP (ng/L): 20 230.6 (15 890.0, 35 000.0) vs. 13 057.6 (8 946.0, 35 000.0), Tei index: 0.52±0.03 vs. 0.39±0.02, both P < 0.05], and LVEF was significantly lower than that in septic non-cardiac dysfunction group (0.626±0.123 vs. 0.671±0.086, P < 0.05). Multivariate Logistic regression analysis showed that NT-proBNP, Tei index and hs-CRP/ALB were independent risk factors for cardiac dysfunction in sepsis neonates [odds ratio (OR) and 95% confidence interval (95%CI) were 8.73 (1.54-5.67), 1.97 (1.26-2.87), 1.87 (1.03-3.40) respectively, all P < 0.05]. ROC curve analysis showed that NT-proBNP, Tei index and hs-CRP/ALB had good predictive value for the occurrence of cardiac dysfunction in septic neonates, the area under ROC curve (AUC) was 0.81 (95%CI was 0.84-0.91), 0.78 (95%CI was 0.65-0.79) and 0.77 (95%CI was 0.61-0.77), respectively. The sensitivity and specificity of NT-proBNP were 80.0% and 79.0% respectively with 12 291.5 ng/L as the cut-off value, the sensitivity and specificity of Tei index were 74.0% and 77.0% respectively with 0.45 as the cut-off value, and the sensitivity and specificity of hs-CRP/ALB were 76.0% and 76.3% respectively with 0.10 as the cut-off value. CONCLUSIONS: NT-proBNP can be used as a diagnostic marker of early cardiac dysfunction, and for rapid diagnosis of neonatal cardiac dysfunction in sepsis. The application may guide clinicians to use drugs better to improve cardiac function and treatment effect.


Assuntos
Cardiopatias , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Sepse/complicações , Função Ventricular Esquerda , Biomarcadores , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Humanos , Recém-Nascido , Curva ROC , Volume Sistólico
17.
Medicine (Baltimore) ; 99(28): e20850, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664079

RESUMO

RATIONALE: With the development and standardization of modern chronic total occlusions (CTOs) recanalization technique, percutaneous coronary intervention has become a promising treatment alternative to surgery after bypass graft failure. Treatment of a native coronary CTO lesion is preferable to treatment of a saphenous vein graft (SVG) CTO supplying the same territory; however, technical expertise is required. PATIENT CONCERNS: This is a 69-year-old male with prior history of coronary artery bypass grafting presented with severe dyspnea at mild exertion (NYHA III) of 2 months duration. DIAGNOSIS: The patient was diagnosed as heart failure caused by ischemia after SVG failure (SVG to right coronary artery) according to electrocardiogram, plasma N-terminal pro-B-type natriuretic peptide levels, and coronary angiogram. INTERVENTIONS: We recanalized native right coronary artery CTO by retrograde approach using septal collaterals by surfing technique after recanalization of totally occluded left coronary artery. OUTCOMES: Dyspnea was relieved at discharge. At 6-month follow-up, the patient had no recurrence of dyspnea. LESSONS: In case of SVG failure, percutaneous coronary intervention of native vessel should be considered as a treatment option. Retrograde approach through native vessel is safe but has requirements for operators' volume, skill, and experience.


Assuntos
Vasos Coronários/cirurgia , Dispneia/etiologia , Insuficiência Cardíaca/diagnóstico , Veia Safena/transplante , Assistência ao Convalescente , Idoso , Angiografia Coronária/métodos , Ponte de Artéria Coronária/efeitos adversos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Eletrocardiografia/métodos , Oclusão de Enxerto Vascular/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Intervenção Coronária Percutânea/métodos , Resultado do Tratamento
19.
Hypertension ; 76(4): 1104-1112, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32673499

RESUMO

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P<0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50-7.47] P<0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33-7.09] P<0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18-6.36] P<0.001), and CK was 3.56 ([95% CI, 2.53-5.02] P<0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%-50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19-associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials.


Assuntos
Infecções por Coronavirus , Creatina Quinase Forma MB/sangue , Cardiopatias , Peptídeo Natriurético Encefálico/sangue , Pandemias , Fragmentos de Peptídeos/sangue , Pneumonia Viral , Troponina I/sangue , Betacoronavirus/isolamento & purificação , Biomarcadores/sangue , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Feminino , Cardiopatias/sangue , Cardiopatias/mortalidade , Cardiopatias/virologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos
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