RESUMO
AIMS: Excess sodium causes the development of cardiovascular diseases in conjunction with enhancing renin-angiotensin-aldosterone system (RAAS). Natriuretic peptides are sodium regulators and prevent pathological cardiac alterations by counteracting RAAS. However, it is unknown whether natriuretic peptides inhibit the sodium effect in adverse cardiac alterations. Here, we investigated whether excess salt intake could exacerbate cardiac remodeling in mice with impaired natriuretic peptide signaling. MATERIALS AND METHODS: Mice lacking the gene encoding the natriuretic peptide receptor, guanylyl cyclase-A (GC-A), and wild-type mice were administered with either a vehicle substance or a subpressor dose of aldosterone (100ng/kg/min), alongside low salt (0.001% NaCl), normal salt (0.6% NaCl), or high salt diets (6.0% NaCl) for four weeks. Mice were then sacrificed and the hearts were evaluated by histology and RT-PCR. KEY FINDINGS: Salt load did not induce cardiac changes in vehicle and aldosterone groups in wild-type mice. On the other hand, cardiac hypertrophy and interstitial fibrosis were significantly exacerbated in a salt dependent manner in GC-A knockout (KO) mice administered aldosterone, and were associated with enhanced gene expression relevant to hypertrophy, fibrosis, and oxidative stress conditions. Of note, excess salt intake increased the expression of Sgk1, serum and glucocorticoid responsive kinase-1, in aldosterone-administered GC-A KO mice. These molecular changes were not observed in wild-type mice. SIGNIFICANCE: The results of the present study demonstrate that excess salt intake induced cardiac remodeling in conjunction with aldosterone administration in GC-A KO mice, indicating that GC-A signaling attenuated the deleterious salt effect in aldosterone-induced cardiac remodeling.
Assuntos
Aldosterona/administração & dosagem , Cloreto de Sódio/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Soluble fms-like tyrosine kinase-1 (sFlt-1), an endogenous inhibitor of vascular endothelial growth factor and placental growth factor, is involved in the pathogenesis of cardiovascular disease. However, the significance of sFlt-1 in heart failure has not been fully elucidated. We found that sFlt-1 is decreased in renal failure and serves as a key molecule in atherosclerosis. In this study, we aimed to investigate the role of the decreased sFlt-1 production in heart failure, using sFlt-1 knockout mice. sFlt-1 knockout mice and wild-type mice were subjected to transverse aortic constriction and evaluated after 7 days. The sFlt-1 knockout mice had significantly higher mortality (52% versus 15%; P=0.0002) attributable to heart failure and showed greater cardiac hypertrophy (heart weight to body weight ratio, 8.95±0.45 mg/g in sFlt-1 knockout mice versus 6.60±0.32 mg/g in wild-type mice; P<0.0001) and cardiac dysfunction, which was accompanied by a significant increase in macrophage infiltration and cardiac fibrosis, than wild-type mice after transverse aortic constriction. An anti-placental growth factor-neutralizing antibody prevented pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction. Moreover, monocyte chemoattractant protein-1 expression was significantly increased in the hypertrophied hearts of sFlt-1 knockout mice compared with wild-type mice. Monocyte chemoattractant protein-1 inhibition with neutralizing antibody ameliorated maladaptive cardiac remodeling in sFlt-1 knockout mice after transverse aortic constriction. In conclusion, decreased sFlt-1 production plays a key role in the aggravation of cardiac hypertrophy and heart failure through upregulation of monocyte chemoattractant protein-1 expression in pressure-overloaded heart.
Assuntos
Insuficiência Cardíaca/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Remodelação Ventricular/fisiologia , Análise de Variância , Animais , Biópsia por Agulha , Western Blotting , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Modelos Animais de Doenças , Ecocardiografia/métodos , Ensaio de Imunoadsorção Enzimática , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/patologia , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/análise , Distribuição Aleatória , Estatísticas não Paramétricas , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Remodelação Ventricular/genéticaAssuntos
Encefalopatias/induzido quimicamente , Diabetes Insípido Neurogênico/induzido quimicamente , Doxorrubicina/efeitos adversos , Ifosfamida/efeitos adversos , Neoplasias Retroperitoneais/tratamento farmacológico , Sarcoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Encefalopatias/diagnóstico por imagem , Diabetes Insípido Neurogênico/diagnóstico por imagem , Doxorrubicina/administração & dosagem , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Neoplasias Retroperitoneais/patologia , Medição de Risco , Sarcoma/patologia , Tomografia Computadorizada por Raios X/métodos , Síndrome de Werner/diagnóstico , Síndrome de Werner/terapiaRESUMO
BACKGROUND: Endothelial-mesenchymal transformation (EndMT) is essential for endocardial cushion formation during cardiac morphogenesis. We recently identified Tmem100 as an endothelial gene indispensable for vascular development. In this study, we further investigated its roles for EndMT during atrioventricular canal (AVC) cushion formation. RESULTS: Tmem100 was expressed in AVC endocardial cells, and Tmem100 null embryos showed severe EndMT defect in the AVC cushions. While calcineurin-dependent suppression of vascular endothelial growth factor (VEGF) expression in the AVC myocardium is important for EndMT, significant up-regulation of Vegfa expression was observed in Tmem100 null heart. EndMT impaired in Tmem100 null AVC explants was partially but significantly restored by the expression of constitutively-active calcineurin A, suggesting dysregulation of myocardial calcineurin-VEGF signaling in Tmem100 null heart. Moreover, Tmem100 null endocardial cells in explant culture did not show EndMT in response to the treatment with myocardium-derived growth factors, transforming growth factor ß2 and bone morphogenetic protein 2, indicating involvement of an additional endocardial-specific abnormality in the mechanism of EndMT defect. The lack of NFATc1 nuclear translocation in endocardial cells of Tmem100 null embryos suggests impairment of endocardial calcium signaling. CONCLUSIONS: The Tmem100 deficiency causes EndMT defect during AVC cushion formation possibly via disturbance of multiple calcium-related signaling events.
Assuntos
Embrião de Mamíferos/metabolismo , Transição Epitelial-Mesenquimal , Regulação da Expressão Gênica no Desenvolvimento , Cardiopatias Congênitas/embriologia , Coração/embriologia , Proteínas de Membrana/deficiência , Animais , Sinalização do Cálcio/genética , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Camundongos , Camundongos Mutantes , Miocárdio/metabolismo , Miocárdio/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Coronary artery disease and cardiac morphology and function were evaluated in 51 patients with hypertrophic cardiomyopathy (HCM), without typical chest pain, using cardiac computed tomography (CT). This study investigated the prevalence of coronary artery disease, the indicators of obstructive coronary stenosis, and the magnitude of left ventricular (LV) hypertrophy. The patients' mean coronary artery calcium score was 198.8 ± 312.0 and was positively correlated with the number of coronary risk factors (r = 0.32; P < 0.05). Of the 51 patients with HCM, 42 (82.4 %) had some degree of stenosis and 8 (15.7 %) had obstructive stenosis. Noncalcified and mixed plaques were detected in 14 (27.5 %) and 11 (21.6 %) patients, respectively. Multivariate logistic regression revealed that diabetes was an independent indicator of the presence of obstructive stenosis in HCM patients. Multivariate linear regression revealed that low estimated glomerular filtration rates and high triglyceride concentrations were independent indicators of higher LV mass indexes. In conclusion, cardiac CT revealed that coronary artery disease was common among patients with HCM. The presence of obstructive coronary stenosis and the magnitude of LV hypertrophy were related to the presence of diabetes, triglyceride levels, and estimated glomerular filtration rate.
Assuntos
Cardiomiopatia Hipertrófica/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Miocárdio/patologia , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Dor no Peito , Angiografia Coronária , Feminino , Coração/anatomia & histologia , Testes de Função Cardíaca , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Despite marked improvements in treatment strategies for heart failure (HF), the mortality rate of elderly patients with HF is still high. Detailed causes of death have not been fully understood. METHODS AND RESULTS: We studied 459 consecutive patients with acute decompensated HF (ADHF) emergently admitted to our hospital from 2007 to 2011. Patients were divided into 2 groups: <75 years old (younger group; n = 225) and ≥75 years old (elderly group; n = 234). All-cause death, cardiovascular death, and noncardiovascular death were assessed as adverse outcomes. Compared with the younger group, the elderly group was characterized by a higher proportion of women and hypertensive patients and higher left ventricular ejection fraction. During a mean follow-up of 20.7 months, a total of 174 patients (37.9%) died. All-cause death was significantly higher in the elderly group than in the younger group (46.6% vs 28.9%; P < .0001), and this difference was caused by an increase in noncardiovascular deaths (20.9% vs 9.3%; P < .001), especially deaths due to infection (10.7% vs 4.0%; P < .01). Cardiovascular deaths did not differ between the 2 groups. CONCLUSIONS: Noncardiovascular deaths, most of which were caused by infection, were frequent among elderly patients with ADHF.
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Doenças Transmissíveis/mortalidade , Insuficiência Cardíaca/mortalidade , Admissão do Paciente , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Causas de Morte/tendências , Doenças Transmissíveis/diagnóstico , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/tendências , Estudos RetrospectivosRESUMO
Patients with chronic kidney disease (CKD) die of cardiovascular diseases for unknown reasons. Blood vessel formation in plaques and its relationship with plaque stability could be involved with signaling through the Flt-1 receptor and its ligands, vascular endothelial growth factor, and the closely related placental growth factor (PlGF). Flt-1 also exists as a circulating regulatory splice variant short-inhibitory form (sFlt-1) that serves as a decoy receptor, thereby inactivating PlGF. Heparin releases sFlt-1 by displacing the sFlt-1 heparin-binding site from heparin sulfate proteoglycans. Heparin could provide diagnostic inference or could also induce an antiangiogenic state. In the present study, postheparin sFlt-1 levels were lower in CKD patients than in control subjects. More importantly, sFlt-1 levels were inversely related to atherosclerosis in CKD patients, and this correlation was more robust after heparin injection, as verified by subsequent cardiovascular events. Knockout of apolipoprotein E (ApoE) and/or sFlt-1 showed that the absence of sFlt-1 worsened atherogenesis in ApoE-deficient mice. Thus, the relationship between atherosclerosis and PlGF signaling, as regulated by sFlt-1, underscores the underappreciated role of heparin in sFlt-1 release. These clinical and experimental data suggest that novel avenues into CKD-dependent atherosclerosis and its detection are warranted.
Assuntos
Aterosclerose/etiologia , Insuficiência Renal Crônica/complicações , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/genética , Biomarcadores/sangue , Estudos de Casos e Controles , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Heparina/administração & dosagem , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Injeções Intravenosas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Estresse Oxidativo , Fator de Crescimento Placentário , Valor Preditivo dos Testes , Proteínas da Gravidez/sangue , Prognóstico , Isoformas de Proteínas , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/deficiência , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: Evaluation of left ventricular (LV) diastolic function is essential for the management of heart failure. We verified whether LV diastolic function could be evaluated by measuring the fractional area change (FAC) using cine cardiovascular magnetic resonance (CMR). METHODS: We collected clinical data from 59 patients who underwent echocardiography and cine CMR. Normal, impaired relaxation, pseudonormal, and restrictive LV filling were observed in 15, 28, 11, and 5 patients, respectively. We calculated FAC during the first 30% of diastole (diastolic-index%) in the short-axis view, by tracing the contours on only three MR cine images. RESULTS: The diastolic index was significantly lower (p < 0.0001) in patients with impaired relaxation (32.4 ± 7.5), pseudonormal filling (25.4 ± 5.6), and restrictive filling (9.5 ± 1.5) compared to those with normal diastolic function (67.7 ± 10.8), and the index decreased significantly with worsening of diastolic dysfunction. The diastolic index correlated positively with early diastolic mitral annular velocity measured by tissue Doppler imaging (r = 0.75, p < 0.0001), respectively. CONCLUSIONS: Measurement of FAC can be useful for the evaluation of LV diastolic function using cine CMR.
Assuntos
Imagem Cinética por Ressonância Magnética , Disfunção Ventricular Esquerda/diagnóstico , Função Ventricular Esquerda , Adulto , Idoso , Diástole , Ecocardiografia Doppler , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: Benefit of low-dose aspirin for primary prevention of cardiovascular events in diabetes remains controversial. The American Diabetes Association (ADA), the American Heart Association (AHA), and the American College of Cardiology Foundation (ACCF) recommend aspirin for high-risk diabetic patients: older patients with additional cardiovascular risk factors. We evaluated aspirin's benefit in Japanese diabetic patients stratified by cardiovascular risk. METHODS AND RESULTS: In the JPAD trial, we enrolled 2,539 Japanese patients with type 2 diabetes and no history of cardiovascular disease. We randomly assigned them to aspirin (81-100 mg daily) or no aspirin groups. The median follow-up period was 4.4 years. We stratified the patients into high-risk or low-risk groups, according to the US recommendation: age (older; younger) and coexisting cardiovascular risk factors. The risk factors included smoking, hypertension, dyslipidemia, family history of coronary artery disease, and proteinuria. Most of the patients were classified into the high-risk group, consisting of older patients with risk factors (n=1,804). The incidence of cardiovascular events was higher in this group, but aspirin did not reduce cardiovascular events (hazard ratio [HR], 0.83; 95% confidence interval [CI]: 0.58-1.17). In the low-risk group, consisting of older patients without risk factors and younger patients (n=728), aspirin did not reduce cardiovascular events (HR, 0.55; 95% CI: 0.23-1.21). These results were unchanged after adjusting for potential confounding factors. CONCLUSIONS: Low-dose aspirin is not beneficial in Japanese diabetic patients at high risk.
Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Complicações do Diabetes/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Adulto , Fatores Etários , Idoso , Povo Asiático , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Accumulating evidence suggests that hematopoiesis, especially erythropoiesis, is disturbed in heart failure (HF) for many reasons. Low hemoglobin and red blood cell distribution width have emerged as prognostic indicators of HF independent of classic predictors. The prognostic implication of mean corpuscular volume (MCV) in HF, however, is unknown. In this context, we investigated the relationship between MCV and prognosis of acute decompensated HF (ADHF). METHODS AND RESULTS: This retrospective cohort study consisted of 458 consecutive patients with ADHF who had emergency admission to hospital. Patients were divided into 2 groups: MCV ≤100fl (non-macrocytic group, n=400); and MCV >100fl (macrocytic group, n=58). The relationship between MCV and all-cause death was tested using Cox proportional hazard models, adjusting for other predictors. Mean patient age was 72.4 years and mean MCV was 93.0±7.1fl. Hemoglobin was significantly lower in the macrocytic group than the non-macrocytic group. During the mean follow-up of 20.8 months, a total of 173 deaths (37.9%) occurred. Kaplan-Meier analysis showed that all-cause death was significantly higher in the macrocytic group (log-rank P<0.0001). Cox proportional hazards analysis indicated that macrocytosis was an independent predictor of all-cause death (hazard ratio, 2.288; 95% confidence interval: 1.390-3.643; P=0.0015) after adjustment in the multivariate model. CONCLUSIONS: It is proposed for the first time that MCV is an independent predictor of all-cause death in patients with ADHF.
Assuntos
Índices de Eritrócitos , Insuficiência Cardíaca , Modelos Biológicos , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Eritropoese , Feminino , Seguimentos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
AIMS: Dilated cardiomyopathy (DCM) is characterized by ventricular dilation associated with systolic dysfunction, which could be caused by mutations in lamina/C gene (LMNA). LMNA-linked DCM is severe in males in both human patients and a knock-in mouse model carrying a homozygous p.H222P mutation (LmnaH222P/H222P). The aim of this study was to investigate the molecular mechanisms underlying the gender difference of LMNA-linked DCM. METHODS AND RESULTS: A whole-exome analysis of a multiplex family with DCM exhibiting the gender difference revealed a DCM-linked LMNA mutation, p.R225X. Immunohistochemical analyses of neonatal rat cardiomyocytes expressing mutant LMNA constructs and heart samples from the LMNA-linked DCM patients and LmnaH222P/H222P mice demonstrated a nuclear accumulation of androgen receptor (AR) and its co-activators, serum response factor, and four-and-a-half LIM protein-2. Role of sex hormones in the gender difference was investigated in vivo using the LmnaH222P/H222P mice, where male and female mice were castrated and ovariectomized, respectively, or treated with testosterone or an antagonist of AR. Examination of the mice by echocardiography, followed by the analyses of histological changes and gene/protein expression profiles in the hearts, confirmed the involvement of testicular hormone in the disease progression and enhanced cardiac remodelling in the LmnaH222P/H222P mice. CONCLUSION: These observations indicated that nuclear accumulation of AR was associated with the gender difference in LMNA-linked DCM.
Assuntos
Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/metabolismo , Lamina Tipo A/genética , Mutação , Receptores Androgênicos/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Cardiomiopatia Dilatada/patologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Mutantes , Miócitos Cardíacos/metabolismo , Orquiectomia , Ovariectomia , Linhagem , Ratos , Caracteres Sexuais , TransfecçãoRESUMO
OBJECTIVE: To investigate the predictive values of placental growth factor (PlGF) and its endogenous antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1), for the long-term prognosis of patients with stable coronary artery disease (CAD). Both PlGF and sFlt-1 play important roles in the pathological mechanisms of atherosclerosis. We recently demonstrated that the plasma levels of these molecules are correlated with the severity of coronary atherosclerosis. METHODS: We enrolled 464 patients with stable CAD who consecutively underwent coronary angiography. Baseline blood samples were collected from the femoral artery immediately before coronary angiography (after the administration of 20 units of heparin), and the plasma levels of PlGF and sFlt-1 were measured. A Cox proportional hazard regression analysis was performed to evaluate the relationship between these parameters and the occurrence of all-cause death (ACD) and total cardiovascular events (TCVE) during a median follow-up of 3.3 years. RESULTS: A total of 31 ACDs and 51 TCVEs occurred. Patients with higher PlGF/sFlt-1 ratios (>4.22×10(-2)) had a significantly higher risk of both ACD and TCVE than patients with lower ratios (<4.22×10(-2)) (hazard ratio [HR]: 3.32, 95% confidence interval [CI]: 1.43 to 7.72, p=0.005, and HR: 2.23, 95% CI: 1.23 to 4.03, p=0.008, respectively). A multivariate analysis showed the PlGF/sFlt-1 ratio to be an independent predictor for ACD, but not TCVE. CONCLUSION: The baseline PlGF/sFlt-1 ratio is an independent predictor of long-term adverse outcomes in patients with stable CAD.
Assuntos
Doença da Artéria Coronariana/sangue , Proteínas da Gravidez/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Idoso , Biomarcadores , Fármacos Cardiovasculares/uso terapêutico , Causas de Morte , Comorbidade , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/terapia , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea , Fator de Crescimento Placentário , Plasma , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Brain natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) are useful biomarkers for diagnosis and prediction of prognosis. Both of these peptides are elevated in patients with chronic kidney disease (CKD), but there is no evidence as to which peptide is the more suitable biomarker in patients with severe renal dysfunction. METHODS AND RESULTS: This retrospective cohort study evaluated patients with cardiovascular diseases (64.9±11.7 years, mean±SD). The end points were all-cause death and a composite end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for severe heart failure, and initiation of hemodialysis. Baseline plasma BNP and NT-proBNP levels, expressed as log-transformed data, were closely correlated in patients with CKD stages 1-3 (n=998) (r2=0.870, p<0.001), whereas for CKD stages 4-5 (n=85) there was a significant but weaker correlation (r2=0.209, p<0.001). During follow-up periods (51.3±0.4 months), 132 patients died and 202 patients reached the composite end point. The area under the receiver operating characteristic curve (AUROC) for BNP and NT-proBNP were similar for CKD stages 1-3. However, for CKD stages 4-5, the AUC for mortality for BNP was 0.713 and that for NT-proBNP was 0.760, while the AUC for the composite end point for BNP was 0.666 and that for NT-proBNP was 0.720. CONCLUSIONS: Both BNP and NT-proBNP are useful biomarkers for mortality and cardiovascular events, but NT-proBNP may be superior to BNP for CKD stages 4-5.
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Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Rim/fisiopatologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Determinação de Ponto Final , Feminino , Seguimentos , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
Purpose. To evaluate the influence of effective energy on computed tomography (CT) number in monoenergetic images (MEIs). Methods. Three bottle phantoms filled with water, oil, and a contrast agent were scanned at 100 and 140 kVp tube energy with a dual-source CT scanner. Cardiac dual-energy CT data was collected from 17 patients. CT numbers were measured in the 3 phantom materials and in the left ventricular cavity, myocardium, pericardial fat, and vertebral bone in MEIs from 40 to 190 keV. Results. In the phantoms, the mean CT number increased in oil whereas it decreased in the contrast agent as the energy level increased (P < 0.001). In clinical subjects, the mean CT numbers for the left ventricular cavity, myocardium, and vertebral bone were highest in the 40 keV images (P < 0.001) and decreased as the energy level increased. In contrast, the CT number for pericardial fat was lowest in the 40 keV images (P < 0.001) and increased with increasing energy. Conclusions. The influence of effective energy on CT number varies with material and tissue type in monoenergetic cardiac imaging, which could evaluate tissue characteristics through assessment of the changes in CT number associated with effective energies.
RESUMO
Members of the transforming growth factor-ß superfamily play essential roles in various aspects of embryonic development and physiological organ function. Among them, bone morphogenetic protein (BMP) 9 and BMP10 regulate embryonic vascular development by activating their endothelial receptor ALK1 (activin receptor-like kinase 1, also called Acvrl1). ALK1-mediated intracellular signaling is implicated in the etiologies of human diseases, but their downstream functional proteins are largely unknown. In this study, we identified Tmem100, a gene encoding a previously uncharacterized intracellular transmembrane protein, to be an embryonic endothelium-enriched gene activated by BMP9 and BMP10 through the ALK1 receptor. Tmem100 null mice showed embryonic lethality due to impaired differentiation of arterial endothelium and defects of vascular morphogenesis, which phenocopied most of the vascular abnormalities observed with the Acvrl1/Alk1 deficiency. The activity of Notch- and Akt-mediated signaling, which is essential for vascular development, was down-regulated in Tmem100 null mice. Cre-mediated deletion of Tmem100 in endothelial cells was sufficient to recapitulate the null phenotypes. These data indicated that TMEM100 may play indispensable roles downstream of BMP9/BMP10-ALK1 signaling during endothelial differentiation and vascular morphogenesis.
Assuntos
Receptores de Ativinas Tipo I/metabolismo , Artérias/embriologia , Diferenciação Celular/fisiologia , Endotélio Vascular/embriologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas de Membrana/metabolismo , Morfogênese/fisiologia , Receptores de Activinas Tipo II , Animais , Artérias/citologia , Northern Blotting , Southern Blotting , Western Blotting , Proteínas Morfogenéticas Ósseas/metabolismo , Endotélio Vascular/citologia , Fator 2 de Diferenciação de Crescimento/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Camundongos Endogâmicos BALB C , Análise em Microsséries , Reação em Cadeia da Polimerase em Tempo RealRESUMO
PURPOSE: Blood pressure (BP), age, and reduced renal function are major risk factors for white-matter lesions (WMLs) in the general population. However, it remains unclear whether or not the BP itself or other parameters related to the BP are associated with WMLs in hypertensive patients with well-controlled BP. We investigated the relationships of the presence of WMLs with the central systolic BP (cSBP) and estimated glomerular filtration rate (eGFR) in treated hypertensive patients. METHOD: We studied 185 hypertensive patients with median duration of hypertension, 10.0 years, whose BP is controlled to SBP and diastolic BP (DBP) of 139 ± 17 and 79 ± 10 mmHg, respectively. We measured cSBP and brain magnetic resonance imaging (MRI) was examined within 2 weeks after last BP and biological measurements. RESULTS: Patients with higher-grade WMLs, as assessed by the presence of Scheltens deep white-matter hyperintensity (SDWMH) in the frontal (grade 0-2 vs 3-6) and parietal areas (grade 0-2 vs 3-6) where small arteries are affected at earlier stage of hypertension, as well as that of Fazekas deep white-matter hyperintensity (FDWMH) (grade 2-3 vs 0-1) and Fazekas periventricular hyperintensity (FPVH) (grade 1-3 vs 0) were older, had higher serum creatinine levels, a longer duration of hypertension, and lower eGFR values. The grade of the WMLs was not associated with either the cSBP or the brachial SBP. In logistic regression analyses after adjustment for age, sex, cSBP, and hypertension duration, showed significant association between eGFR and WMLs. The patients with lower eGFR (<60 mL/minute/1.73 m(2)) tended to have higher grade WMLs. The odds ratio was 2.87 for FDWMH (P = 0.017), 1.99 for FPVH (P = 0.131), and 2.33 for SDWMH in the parietal area (P = 0.045). CONCLUSION: Presence of WMLs was associated with eGFR, but not with either the brachial SBP or cSBP in hypertensive patients with well-controlled BP.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Encéfalo/patologia , Hipertensão/tratamento farmacológico , Leucoencefalopatias/diagnóstico , Imageamento por Ressonância Magnética , Idoso , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Japão/epidemiologia , Leucoencefalopatias/epidemiologia , Leucoencefalopatias/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de TempoRESUMO
Dual-energy computed tomography (DE-CT) uses polyenergetic X-rays at 100- and 140-kVp tube energy, and generates 120-kVp composite images that are referred to as polyenergetic images (PEIs). Moreover, DE-CT can produce monoenergetic images (MEIs) at any effective energy level. We evaluated whether the image quality of coronary angiography is improved by optimizing the energy levels of DE-CT. We retrospectively evaluated data sets obtained from 24 consecutive patients using cardiac DE-CT at 100- and 140-kVp tube energy with a dual-source scanner. Signal-to-noise ratios (SNRs) were evaluated in the left ascending coronary artery in PEIs, and in MEIs reconstructed at 40, 50, 60, 70, 80, 90, 100, 130, 160 and 190 keV. Energy levels of 100, 120 and 140 kVp generated the highest SNRs in PEIs from 10, 12 and 2 patients, respectively, at 60, 70 and 80 keV in MEIs from 2, 10 and 10 patients, respectively, and at 90 and 100 keV in those from one patient each. Optimization of the energy level for each patient increased the SNR by 16.6% in PEIs (P < 0.0001) and by 18.2% in MEIs (P < 0.05), compared with 120-kVp composite images. The image quality of coronary angiography using DE-CT can be improved by optimizing the energy level for individual patients.
Assuntos
Doenças Cardiovasculares/diagnóstico por imagem , Angiografia Coronária/métodos , Tomografia Computadorizada por Raios X , Idoso , Análise de Variância , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos RetrospectivosRESUMO
AIMS: Morphological characteristics of non-significant coronary plaques (NSCPs) that develop rapid progression have not been fully elucidated. The aim of this study was to clarify the morphological characteristics of NSCPs in patients with coronary artery disease (CAD) using intravascular optical coherence tomography (OCT). METHODS AND RESULTS: Fifty-three consecutive CAD patients undergoing percutaneous coronary intervention were enrolled and 69 NSCPs (per cent diameter stenosis <50%) were identified on baseline angiogram. Baseline characteristics of NSCPs were evaluated by OCT, and patients were followed-up prospectively. At the second coronary angiography, the baseline OCT characteristics and plaque progression were correlated. During the 7-month follow-up period, 13 NSCPs showed angiographic progression and 56 NSCPs did not. Baseline minimum lumen diameter and diametric stenosis were similar between NSCPs with and without progression. Compared with NSCPs without progression, those with progression showed a significantly higher incidence of intimal laceration (61.5 vs. 8.9%, P < 0.01), microchannel (76.9 vs. 14.3%, P < 0.01), lipid pools (100 vs. 60.7%, P = 0.02), thin-cap fibroatheroma (TCFA) (76.9 vs. 14.3%, P < 0.01), macrophage images (61.5 vs. 14.3%, P < 0.01), and intraluminal thrombi (30.8 vs. 1.8%, P < 0.01). Univariate regression analysis showed that TCFA and microchannel images showed high correlation with subsequent luminal progression [odds ratio (OR): 20.0, P < 0.01 and OR: 20.0, P < 0.01, respectively]. CONCLUSION: Optical coherence tomography-based complex characteristics of TCFA and microchannel were the potential predictors of subsequent progression of NSCPs in patients with CAD.
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Doença da Artéria Coronariana/patologia , Placa Aterosclerótica/patologia , Tomografia de Coerência Óptica/métodos , Idoso , Angiografia Coronária/métodos , Estenose Coronária/patologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
AIMS: Ablation of right-sided accessory pathways (APs) is sometimes challenging because several anatomical features of the tricuspid annulus (TA) and surrounding structures differ from those of the mitral annulus. This study investigated the electrophysiological characteristics and efficacy of a non-contact mapping (NCM) system for catheter ablation of right-sided APs. METHODS AND RESULTS: We examined nine APs in six consecutive patients who underwent catheter ablation of right-sided APs with NCM. In Case 6, we compared NCM with contact activation mapping. Three of six patients had two APs, and one of these had previously failed ablation. We observed atrial activation during sinus rhythm or atrial pacing using a multiple-electrode array (MEA) deployed in the right atrium near the TA. Non-contact mapping identified the AP location as a peri-TA breakout point that appeared prior to or simultaneously with the delta wave onset in all APs. In Case 6 we confirmed that the peri-TA breakout identified by NCM corresponded to the earliest ventricular activation identified by contact mapping. We successfully ablated nine APs by radiofrequency (RF) energy application to the breakout sites, while one AP located just above the pole of the MEA required additional conventionally guided mapping and ablation. The mean RF duration was 189.8 ± 119.0 s. After 33.2 ± 9.4 months of follow-up, one para-hisian AP and one right lateral AP recurred, but these were successfully ablated in a second procedure using NCM. CONCLUSION: Non-contact mapping was able to identify the location of right-sided APs accurately and quickly.
Assuntos
Feixe Acessório Atrioventricular/diagnóstico , Feixe Acessório Atrioventricular/fisiopatologia , Técnicas Eletrofisiológicas Cardíacas/métodos , Síndrome de Wolff-Parkinson-White/diagnóstico , Síndrome de Wolff-Parkinson-White/fisiopatologia , Feixe Acessório Atrioventricular/cirurgia , Adulto , Ablação por Cateter , Eletrocardiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Tricúspide/fisiologia , Síndrome de Wolff-Parkinson-White/cirurgia , Adulto JovemRESUMO
BACKGROUND: Clinical studies using invasive modalities have reported that statin therapy stabilizes coronary plaque vulnerability. The serial changes of lipid-rich coronary plaques (LRCPs) during rosuvastatin treatment were evaluated non-invasively in patients with acute coronary syndrome (ACS) using dual-source computed tomography (DSCT). METHODS AND RESULTS: A total of 11 consecutive ACS patients, and 13 LRCPs were serially evaluated on DSCT before and 24 weeks after rosuvastatin treatment. Compared with the baseline, there was no change in post-treatment minimal lumen diameter, lumen volume, or longitudinal length of LRCPs. By contrast, the ratio of lipid core volume to plaque volume significantly decreased from 48.0 ± 9.9% to 43.7 ± 10.6% (P=0.04), and plaque volume decreased from 144.5 ± 85.5 mm³ to 119.8 ± 78.0 mm³ (P=0.07). The remodeling index of target LRCPs significantly decreased from 1.16 ± 0.10 to 1.06 ± 0.12 (P=0.02). Percent reduction of plaque volume was significantly greater in patients with a lower ratio of low-density lipoprotein to high-density lipoprotein (L/H ratio ≤ 1.5) at follow-up than patients with higher L/H ratio (>1.5; median -31.7% vs. -6.8%, P=0.03). CONCLUSIONS: Rosuvastatin therapy reduced the volume of lipid cores and LRCPs and increased the CT attenuation value of LRCPs. DSCT is an effective modality for the non-invasive evaluation of LRCPs in patients with ACS. ).