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OBJECTIVE: Atrial fibrillation (AF) is a common arrhythmia that increases morbidity and mortality, as well as healthcare costs. The induction of AF (IAF) during programmed atrial pacing in an electrophysiological study (EPS) is a prevalent phenomenon that has been underappreciated by electrophysiologists. Despite extensive research on AF, only a few studies have focused on this phenomenon. The aim of our study was to investigate the association between history of AF and IAF and the underlying pathophysiological factors such as arterial stiffness, subclinical atherosclerosis, and impaired endothelial function. METHODS: This cross-sectional and observational study included 87 patients who had palpitations and were scheduled for EPS. Patients underwent biochemical investigations, transthoracic echocardiography, carotid ultrasound, carotid-femoral artery pulse wave velocity (PWV), and flow-mediated dilatation (FMD) measurements before EPS. Patients were divided into two groups, AF-induced and non-induced in EPS, for further statistical analysis. RESULTS: AF was induced in 16 of 87 patients (18.3%) included in the analysis. The FMD (%) was significantly lower (16.01 ± 10.1 vs. 8.7 ± 5.7, P = 0.022) and, remarkably, the proportion of patients with a history of AF was significantly higher (2.8% vs. 37.5%, P < 0.001) in the IAF group. ROC analysis showed that a documented AF and FMD predicted IAF, with AUC of 0.741 (p = 0.012) and 0.740 (p = 0.001), respectively. Logistic regression analysis revealed that FMD and history of AF were strong predictors of IAF (odds ratio [OR], 0.853; 95% confidence interval [CI] 0.737-0.988; P = 0.034, OR: 10.1, 95% CI 4.9-20.5; P = 0.003, respectively). CONCLUSION: Endothelial dysfunction and documented AF were associated with IAF during EPS.

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Fibrilación Atrial , Endotelio Vascular , Humanos , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/diagnóstico , Femenino , Masculino , Estudios Transversales , Persona de Mediana Edad , Endotelio Vascular/fisiopatología , Endotelio Vascular/diagnóstico por imagen , Anciano , Rigidez Vascular/fisiología , Técnicas Electrofisiológicas Cardíacas/métodos

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INTRODUCTION: Anomalous cerebral blood flow (CBF) is evident in bipolar disorder (BD), however the extent to which CBF reflects peripheral vascular function in BD is unknown. This study investigated endothelial function, an index of early atherosclerosis and cardiovascular disease risk, in relation to CBF among youth with BD. METHODS: Participants included 113 youth, 13-20 years old (66 BD; 47 healthy controls [HC]). CBF was measured using arterial spin labeling with 3T MRI. Region of interest analyses (ROI; global grey matter, middle frontal gyrus, anterior cingulate cortex, temporal cortex, caudate) were undertaken alongside voxel-wise analyses. Reactive hyperemia index (RHI), a measure of endothelial function, was assessed non-invasively via pulse amplitude tonometry. General linear models were used to examine RHI and RHI-by-diagnosis associations with CBF, controlling for age, sex, and body mass index. Bonferroni correction for multiple comparisons was used for ROI analyses, such that the significance level was divided by the number of ROIs (α = 0.05/5 = 0.01). Cluster-extent thresholding was used to correct for multiple comparisons for voxel-wise analyses. RESULTS: ROI findings were not significant after correction. Voxel-wise analyses found that higher RHI was associated with lower left thalamus CBF in the whole group (p < 0.001). Additionally, significant RHI-by-diagnosis associations with CBF were found in three clusters: left intracalcarine cortex (p < 0.001), left thalamus (p < 0.001), and right frontal pole (p = 0.006). Post-hoc analyses showed that in each cluster, higher RHI was associated with lower CBF in BD, but higher CBF in HC. CONCLUSION: We found that RHI was differentially associated with CBF in youth with BD versus HC. The unanticipated association of higher RHI with lower CBF in BD could potentially reflect a compensatory mechanism. Future research, including prospective studies and experimental designs are warranted to build on the current findings.

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Trastorno Bipolar , Circulación Cerebrovascular , Imagen por Resonancia Magnética , Humanos , Femenino , Masculino , Adolescente , Circulación Cerebrovascular/fisiología , Trastorno Bipolar/fisiopatología , Trastorno Bipolar/diagnóstico por imagen , Adulto Joven , Encéfalo/fisiopatología , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Endotelio Vascular/fisiopatología , Endotelio Vascular/diagnóstico por imagen , Hiperemia/fisiopatología , Hiperemia/diagnóstico por imagen

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BACKGROUND: Youth-onset type 2 diabetes (Y-T2D) is associated with increased risk for coronary atherosclerotic disease, but the timing of the earliest pathological features and evidence of cardiac endothelial dysfunction have not been evaluated in this population. Endothelial function magnetic resonance imaging may detect early and direct endothelial dysfunction in the absence of classical risk factors (severe hyperglycemia, hypertension, and hyperlipidemia). Using endothelial function magnetic resonance imaging, we evaluated peripheral and coronary artery structure and endothelial function in young adults with Y-T2D diagnosed ≤5 years compared with age-matched healthy peers. We isolated and characterized plasma-derived small extracellular vesicles and evaluated their effects on inflammatory and signaling biomarkers in healthy human coronary artery endothelial cells to validate the imaging findings. METHODS: Right coronary wall thickness, coronary artery flow-mediated dilation, and brachial artery flow-mediated dilation were measured at baseline and during isometric handgrip exercise using a 3.0T magnetic resonance imaging. Human coronary artery endothelial cells were treated with Y-T2D plasma-derived small extracellular vesicles. Protein expression was measured by Western blot analysis, oxidative stress was measured using the redox-sensitive probe dihydroethidium, and nitric oxide levels were measured by 4-amino-5-methylamino-2',7'-difluororescein diacetate. RESULTS: Y-T2D (n=20) had higher hemoglobin A1c and high-sensitivity C-reactive protein, but similar total and LDL (low-density lipoprotein)-cholesterol compared with healthy peers (n=16). Y-T2D had greater coronary wall thickness (1.33±0.13 versus 1.22±0.13 mm; P=0.04) and impaired endothelial function: lower coronary artery flow-mediated dilation (-3.1±15.5 versus 15.9±17.3%; P<0.01) and brachial artery flow-mediated dilation (6.7±14.7 versus 26.4±15.2%; P=0.001). Y-T2D plasma-derived small extracellular vesicles reduced phosphorylated endothelial nitric oxide synthase expression and nitric oxide levels, increased reactive oxygen species production, and elevated ICAM (intercellular adhesion molecule)-mediated inflammatory pathways in human coronary artery endothelial cells. CONCLUSIONS: Coronary and brachial endothelial dysfunction was evident in Y-T2D who were within 5 years of diagnosis and did not have severe hyperglycemia or dyslipidemia. Plasma-derived small extracellular vesicles induced markers of endothelial dysfunction, which corroborated accelerated subclinical coronary atherosclerosis as an early feature in Y-T2D. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02830308 and NCT01399385.

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Diabetes Mellitus Tipo 2 , Endotelio Vascular , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Edad de Inicio , Células Cultivadas , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Vasos Coronarios/patología , Vasos Coronarios/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Endotelio Vascular/diagnóstico por imagen , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Endotelio Vascular/fisiopatología , Vesículas Extracelulares/metabolismo , Imagen por Resonancia Magnética , Óxido Nítrico/metabolismo , Estrés Oxidativo , Investigación Biomédica Traslacional

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Flow-mediated dilation (FMD) is a common measure of endothelial function and an indicator of vascular health. Automated software methods exist to improve the speed and accuracy of FMD analysis. Compared with commercial software, open-source software offers similar capabilities at a much lower cost while allowing for increased customization specific to users' needs. We introduced modifications to an existing open-source software, FloWave.us to better meet FMD analysis needs. The purpose of this study was to compare the repeatability and reliability of the modified FloWave.us software to the original software and to manual measurements. To assess these outcomes, duplex ultrasound imaging data from the popliteal artery in older adults were analyzed. The average percent FMD for the modified software was 6.98 ± 3.68% and 7.27 ± 3.81% for observer 1 and 2 respectively, compared with 9.17 ± 4.91% and 10.70 ± 4.47% with manual measurements and 5.07 ± 31.79% with the original software for observer 1. The modified software and manual methods demonstrated higher intraobserver intraclass correlation coefficients (ICCs) for repeated measures for baseline diameter, peak diameter, and percent FMD compared with the original software. For percent FMD, the interobserver ICC was 0.593 for manual measurements and 0.723 for the modified software. With the modified method, an average of 97.7 ± 2.4% of FMD videos frames were read, compared with only 17.9 ± 15.0% frames read with the original method when analyzed by the same observer. Overall, this work further establishes open-source software as a robust and viable tool for FMD analysis and demonstrates improved reliability compared with the original software.NEW & NOTEWORTHY This study improves edge detection capabilities and implements noise reduction strategies to optimize an existing open-source software's suitability for flow-mediated dilation (FMD) analysis. The modified software improves the precision and reliability of FMD analysis compared with the original software algorithm. We demonstrate that this modified open-source software is a robust tool for FMD analysis.

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Programas Informáticos , Vasodilatación , Humanos , Masculino , Anciano , Reproducibilidad de los Resultados , Femenino , Vasodilatación/fisiología , Arteria Poplítea/fisiología , Arteria Poplítea/diagnóstico por imagen , Persona de Mediana Edad , Flujo Sanguíneo Regional/fisiología , Endotelio Vascular/fisiología , Endotelio Vascular/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Velocidad del Flujo Sanguíneo/fisiología

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BACKGROUND AND PURPOSE: Successful post-flow-diverter endoluminal reconstruction is widely believed to require endothelial overgrowth of the aneurysmal inflow zone. However, endothelialization/neointimal overgrowth is a complex process, over which we currently have very limited influence. Less emphasized is vascular remodeling of the target arterial segment, the dynamic response of the vessel to flow-diverter implantation. This process is distinct from flow modifications in covered branches. It appears that basic angiographic methods allow simple and useful observations. The purpose of this article was to quantitatively evaluate observable postimplantation changes in target vessels following deployment of Pipeline endoluminal constructs. MATERIALS AND METHODS: One hundred consecutive adults with unruptured, previously untreated, nondissecting aneurysms treated with the Pipeline Embolization Device with Shield Technology and the availability of follow-up conventional angiography were studied with 2D DSA imaging. Target vessel size; Pipeline Embolization Device diameter; endothelial thickness; and various demographic, antiplatelet, and device-related parameters were recorded and analyzed. RESULTS: The thickness of neointimal overgrowth (mean, 0.3 [SD, 0.1] mm; range, 0.1-0.7 mm) is inversely correlated with age and is independent of vessel size, smoking status, sex, and degree of platelet inhibition. The decrease in lumen diameter caused by neointimal overgrowth, however, appears counteracted by outward remodeling (dilation) of the target arterial segment. This leads to an increase in the diameter with a corresponding decrease in length (foreshortening) of the implanted Pipeline Embolization Device. This physiologic remodeling process affects optimally implanted devices and is not a consequence of stretching, device migration, vasospasm, and so forth. A direct, linear, statistically significant relationship exists between the degree of observed outward remodeling and the diameter of the implanted Pipeline Embolization Device relative to the target vessel. Overall, remodeled arterial diameters were reduced by 15% (SD, 10%) relative to baseline and followed a normal distribution. Clinically relevant stenosis was not observed. CONCLUSIONS: Vessel healing involves both outward remodeling and neointimal overgrowth. Judicial oversizing could be useful in specific settings to counter the reduction in lumen diameter due to postimplant neointimal overgrowth; however, this overszing needs to be balanced against the decrease in metal coverage accompanying the use of oversized devices. Similar analysis for other devices is essential.

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Aneurisma Intracraneal , Remodelación Vascular , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/terapia , Embolización Terapéutica/métodos , Embolización Terapéutica/instrumentación , Endotelio Vascular/diagnóstico por imagen , Resultado del Tratamiento , Anciano de 80 o más Años , Stents , Prótesis Vascular

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OBJECTIVE: To investigate whether women with unexplained recurrent pregnancy loss have impaired arterial vascular health compared with controls, and to evaluate whether this is modifiable by exercise. DESIGN: Experimental case-control pilot study. SETTING: University medical centre in the Netherlands. POPULATION: Twelve women with unexplained recurrent pregnancy loss, 11 nulliparous women and 19 primiparous women with a history of uncomplicated pregnancies. METHODS: In all three groups we measured baseline characteristics, metabolic components and arterial vascular health, and repeated this in women with unexplained recurrent pregnancy loss after 1 month of protocolled and supervised cycle training. MAIN OUTCOME MEASURES: Differences in arterial vascular health between women with unexplained recurrent pregnancy loss and controls, and the effect of exercise on arterial vascular health in women with unexplained recurrent pregnancy loss. RESULTS: Women with unexplained recurrent pregnancy loss have a significantly increased carotid intima media thickness in comparison with both controls (both P < 0.01), a significantly decreased brachial endothelial dependent flow-mediated vasodilation in comparison with both controls (nulliparous: P < 0.01; primiparous: P = 0.05) and a significantly decreased femoral endothelial dependent flow-mediated vasodilation in comparison with primiparous women (P = 0.01). The endothelium independent glyceryl trinitrate response was similar in all groups. With 1 month of exercise, the carotid intima media thickness decreased significantly by 7% (P = 0.05) and the femoral FMD increased significantly by 10% (P = 0.01) in women with unexplained recurrent pregnancy loss. CONCLUSIONS: Women with unexplained recurrent pregnancy loss have an impaired vascular health in comparison with controls. This impaired arterial vascular health can be improved by exercise.

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Aborto Habitual , Grosor Intima-Media Carotídeo , Embarazo , Humanos , Femenino , Vasodilatación/fisiología , Endotelio Vascular/diagnóstico por imagen , Endotelio Vascular/fisiología , Estudios de Casos y Controles , Proyectos Piloto

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OBJECTIVE: The objective of this study is to investigate the effect of endodontic treatment on flow-mediated dilatation (FMD) and carotid intima-media thickness (c-IMT) in patients with apical periodontitis (AP). MATERIAL AND METHOD: The study includes 32 young men having AP with a mean age of 25.78 years free from cardiovascular disease (CVD) and its risk factors, including periodontitis. All subjects underwent complete physical and dental examination, echocardiography, and ultrasound assessment of FMD on the brachial artery and c-IMT on the carotid artery at baseline and 12 months after the endodontic treatment. Data were analyzed using paired Student's t-test and Pearson's correlation coefficient (r) test using SPSS 26 version. RESULTS: Endodontic treatment leads to the improvement of FMD significantly from a pooled baseline value of 4.84 ± 1.55% to 7.68 ± 2.08% (p < 0.05). The study also depicts a statistically significant difference between c-IMT (mean = 0.62 ± 0.11 mm) before treatment as compared to 12 months after treatment (mean = 0.59 ± 0.11 mm) (p < 0.05). CONCLUSION: Endodontic treatment leads to improved FMD and decreased c-IMT suggesting that treating AP can be help revert the early stages of CVD. CLINICAL RELEVANCE: AP could be a potential etiological factor of future CVD and should be treated as soon as diagnosed.

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Aterosclerosis , Enfermedades Cardiovasculares , Masculino , Humanos , Adulto , Grosor Intima-Media Carotídeo , Estudios Prospectivos , Vasodilatación , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/terapia , Aterosclerosis/complicaciones , Factores de Riesgo , Ultrasonografía , Endotelio Vascular/diagnóstico por imagen

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BACKGROUND: Acute kidney injury (AKI) is a common complication of sepsis, with the burden of long hospital admission. Early prediction of AKI is the most effective strategy for intervention and improvement of the outcomes. OBJECTIVE: In our study, we aimed to investigate the predictive performance of the combined model using ultrasound indices (grayscale and Doppler indieces), endothelium injury (E-selectin, VCAM-1, ICAM1, Angiopoietin 2, syndecan-1, and eNOS) as well as inflammatory biomarkers (TNF-a, and IL-1ß) to identify AKI. METHODS: Sixty albino rats were divided into control and lipopolysaccharide (LPS) groups. Renal ultrasound, biochemical and immunohistological variables were recorded 6 hrs, 24 hrs, and 48 hrs after AKI. RESULTS: Endothelium injury and inflammatory markers were found to be significantly increased early after AKI, and correlated significantly with kidney size reduction and renal resistance indices elevation. CONCLUSIONS: Using area under the curve (AUC), the combined model was analyzed based on ultrasound and biochemical variables and provided the highest predictive value for renal injury.

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Lesión Renal Aguda , Sepsis , Humanos , Endotelio Vascular/diagnóstico por imagen , Curva ROC , Lesión Renal Aguda/diagnóstico por imagen , Biomarcadores , Ultrasonografía

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Role of flow-mediated dilatation (FMD) testing in the assessment of the macrovascular dysfunction in systemic sclerosis (SS) and correlation of FMD values with disease severity. Twenty-five patients of SS and 25 healthy age-matched controls were recruited. Modified Rodnan skin thickness score (MRSS) was used for skin thickness assessment. FMD values were measured in the brachial artery. FMD values done at baseline before the initiation of treatment were lower in SSc patients (4.044 ± 2.742) compared to the healthy controls (11.076 ± 5.896) (P < 0.05). Comparison of FMD values between patients with limited cutaneous systemic sclerosis (LSSc) and diffuse cutaneous systemic sclerosis (DSSc) showed a trend toward lower in LSSc (3.182 ± 2.482) as compared to DSSc patients (5.111 ± 2.711); however, the difference was not statistically significant. Patients with lung manifestations on high-resolution CT chest showed lower FMD values (2.66 ± 2.23) compared to those without HRCT changes (6.45 ± 2.56) (P < 0.05). We demonstrate that FMD values in SSc patients were lower when compared to healthy controls. Patients with SS having pulmonary manifestations showed a lower value of FMD. Key Points • FMD is a simple non-invasive tool to assess the endothelial function in patients with systemic sclerosis. • Lower values of FMD in systemic sclerosis suggest that the endothelial dysfunction and values can also be correlated with other organ involvement such as lung and skin involvement. So, lower FMD values might be a useful marker for disease severity.

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Esclerodermia Difusa , Esclerodermia Sistémica , Humanos , Dilatación , Arteria Braquial/diagnóstico por imagen , Centros de Atención Terciaria , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico por imagen , Esclerodermia Difusa/complicaciones , Vasodilatación , Endotelio Vascular/diagnóstico por imagen

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BACKGROUND: Kawasaki disease (KD) is an acute febrile vasculitis. Patients with previous KD have increased risk of coronary arterial aneurysms (CAA) and early-onset arteriosclerosis. Endothelial dysfunction is the earliest manifestation of arteriosclerosis. We aimed to explore the endothelial function and clinical characteristics of patients with previous KD. METHODS: In this case-control study, we investigated childhood KD patients, with and without CAA, and a group of healthy controls. We obtained the anthropometric measurements, metabolic markers, vascular ultrasonography evaluating arterial stiffness and flow-mediated dilatation (FMD), and clinical information obtained by reviewing the patients' charts. Continuous variables were compared using non-parametric analyses and categorical variables, using the chi-square or Fisher's exact tests. RESULTS: Seventy KD patients (median current age, 12.95 years; median follow-up duration, 10.88 years) and 14 healthy controls were recruited. FMD was significantly lower in the CAA group (n = 15) than the control group (FMDs: 5.59% [interquartile range, 3.99-6.86%] vs. 7.49% [5.96-9.42%], p = 0.049; diastolic FMD: 6.48% [4.14-7.32%] vs. 7.87% [6.19-9.98%], p = 0.042). The CAA group had a higher percentage of impaired FMD and the significantly largest coronary segments of the three groups. Other parameters including metabolic markers, carotid intima-media thickness, and arterial stiffness were not statistically different. CONCLUSION: KD patients, especially those with CAAs, may have impaired endothelial function. FMD may be a good indicator of endothelial dysfunction for use in long-term follow-up of KD patients.

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Síndrome Mucocutáneo Linfonodular , Humanos , Niño , Adolescente , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Endotelio Vascular/diagnóstico por imagen , Fiebre

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BACKGROUND: Carotid stiffening is found to be present in patients with type 2 diabetes mellitus (T2DM) together with endothelial dysfunction and it remains unclear about the role of carotid elasticity in the development of diabetic vascular damage. The aim of the study was to investigate changes and significance of carotid artery elasticity in diabetic patients with or without microvascular complications using velocity vector imaging (VVI) analysis. METHODS: Fifty participants were enrolled and divided into health Control group, the uncomplicated DM (uDM) group and the complicated DM (cDM) group. All of them underwent carotid ultrasound examinations. VVI was used to evaluate the common carotid artery (CCA) elasticity and intima-media thickness (IMT) was also measured. Flow-mediated dilation (FMD) was performed to detect the vascular endothelial function. Then differences and correlations of variables between three groups were compared and analyzed. RESULTS: CCA elasticity measured by VVI decreased significantly between three groups (p < 0.05), while FMD decreased significantly only in cDM group (p < 0.01) and only IMT in cDM group was significantly thicker than that of Control group (p < 0.05). Representative VVI variables were independently, negatively related to the known duration and microalbuminuria (p < 0.05). All VVI variables were significantly correlated with FMD (0.5 ≤ |r | <0.8, p < 0.001), and just a small part of VVI variables were significantly correlated with IMT (0.3 ≤ |r | <0.5, p < 0.05). CONCLUSION: Compared with FMD, CCA elasticity measured by VVI showed more obvious changes in diabetic patients with different levels of vascular damage and may be considered as an alternative indicator in evaluating arterial status of T2DM.

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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Grosor Intima-Media Carotídeo , Arterias Carótidas/diagnóstico por imagen , Arteria Carótida Común/diagnóstico por imagen , Elasticidad , Endotelio Vascular/diagnóstico por imagen , Arteria Braquial/diagnóstico por imagen , Ultrasonografía , Vasodilatación

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OBJECTIVE: Endothelial dysfunction is an initial stage of the atherogenic process, which can be evaluated by a noninvasive method (flow-mediated dilation - FMD) and has a well-established prognostic value for cardiovascular (CV) risk. Currently, there is no evidence of increased CV mortality in Behc¸et's disease (BD), although its association with endothelial dysfunction has been described. There are still doubts in the literature whether the presence of chronic vascular inflammation might trigger the development of atherosclerosis, despite BD remission, which is why this study was conducted. METHODS: We analyzed 24 subjects in this cross-sectional study (12 patients with BD in remission and 12 subjects matched by gender age). Endothelial function was analyzed via FMD. RESULTS: The lowest median for FMD was presented by the BD group (2.025% - interquartile range (IQR) 7.785 versus 5.46% - IQR 3.625, P » .18). The median total cholesterol in the BD group was lower than the controls (168 mg dL-1 - IQR 46 and 216.5 mg dL-1 - IQR 54, respectively, P » .0193). In the right carotid artery, the intima-media thickness was equal to 0.740 - IQR 0.16 for the patients and 0.740 - IQR 0.11 for the controls (P » .9473); on the left, 0.725 - IQR 0.13 and 0.745 - IQR 0.120 (P » .4333), respectively. CONCLUSION: The lower median trend of FMD in patients with BD suggests endothelial dysfunction, despite clinical remission of the inflammatory disease, although our study is limited by the sample size and greater use of statins in BD group.

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Síndrome de Behçet , Síndrome de Behçet/complicaciones , Síndrome de Behçet/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Estudios Transversales , Endotelio Vascular/diagnóstico por imagen , Humanos , Pronóstico

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BACKGROUND AND AIMS: Clinical atherosclerosis manifestations are different in women compared to men. Since endothelial shear stress (ESS) is known to play a critical role in coronary atherosclerosis development, we investigated differences in anatomical characteristics and endothelial shear stress (ESS)-related plaque growth in human coronary arteries in men compared to women. METHODS: 1183 coronary arteries (male/female: 944/239) from the PREDICTION study were studied for differences in artery/plaque and ESS characteristics, and ESS-related plaque progression (6-10 months follow-up) among men and women and after stratification for age. All characteristics were derived from IVUS-based vascular profiling and reported per 3 mm-segments (13,030 3-mm-segments (male/female: 10,465/2,565)). RESULTS: Coronary arteries and plaques were significantly smaller in females compared to males; but no important differences were observed in plaque burden, ESS and rate of plaque progression. Change in plaque burden was inversely related to ESS (p<0.001) with no difference between women versus men (ß: -0.62 ± 0.13 vs -0.68 ± 0.05, p=0.62). However, stratification for age demonstrated that ESS-related plaque growth was more marked in young women compared to men (<55 years, ß: -2.02 ± 0.61 vs -0.33 ± 0.10, p=0.007), reducing in magnitude over the age-categories up till 75 years. CONCLUSIONS: Coronary artery and plaque size are smaller in women compared to men, but ESS and ESS- related plaque progression were similar. Sex-related differences in ESS-related plaque growth were evident after stratification for age. These observations suggest that although the fundamental processes of atherosclerosis progression are similar in men versus women, plaque progression may be influenced by age within gender.

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Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Anciano , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Progresión de la Enfermedad , Endotelio Vascular/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ultrasonografía Intervencional

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BACKGROUND: Patients with Type 1 diabetes (T1D) have an increased risk of developing atherosclerosis and complications as myocardial infarction and peripheral artery disease. The thickening of the carotid wall and the brachial artery dysfunction are early and preclinical manifestations of atherosclerosis. The standard marker of care for assessment of glycemic control, glycated hemoglobin, does not associate with early atherosclerosis. We have hypothesized that the emerging metric of glycemic control, as the time spent in the target range (TIR), might be associated with carotid thickening and endothelial dysfunction. According to the hypothesis, we have designed the present research with the aim to evaluate the association between TIR collected in the short and long term and the measures of arterial morphology and function in patients with T1D. METHODS: In our study, 70 patients and 35 healthy controls underwent ultrasound vascular study to measure carotid artery intima-media thickness (IMT) and brachial artery endothelial function by the flow-mediated dilation (FMD) technique. TIR was collected by a continuous glucose monitoring system for 2 weeks, 3 months, and 6 months before the vascular study. RESULTS: Patients with T1D showed a significantly higher carotid IMT (mean±SE, 644±19 vs. 568±29 µ; p= 0.04) and a significantly lower FMD (mean±SE, 7.6±0.4 vs. 9.8±0.6%; p=0.01) compared with control subjects. No significant relationship between IMT, FMD, and TIR collected in the short and long term emerged. CONCLUSIONS: Young patients with T1D have early vascular abnormalities. The percent of TIR does not correlate with preclinical atherosclerosis. This finding underlines the complexity of the interplay between diabetes and atherosclerosis.

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Aterosclerosis , Diabetes Mellitus Tipo 1 , Aterosclerosis/etiología , Glucemia , Automonitorización de la Glucosa Sanguínea/efectos adversos , Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Diabetes Mellitus Tipo 1/complicaciones , Endotelio Vascular/diagnóstico por imagen , Humanos , Ultrasonografía/efectos adversos , Vasodilatación

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CONTEXT: Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-aged/older men is associated with increased CVD risk. OBJECTIVE: We hypothesized that low testosterone contributes to age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. METHODS: This cross-sectional study included 58 healthy, nonsmoking men categorized as young (N = 20; age 29 ± 4 years; testosterone 500 ± 58 ng/dL), middle-aged/older with higher testosterone (N = 20; age 60 ± 6 years; testosterone 512 ± 115 ng/dL), and middle-aged/older lower testosterone (N = 18; age 59 ± 8 years; testosterone 269 ± 48 ng/dL). Brachial artery flow-mediated dilation (FMDBA) was measured during acute infusion of saline (control) and vitamin C (antioxidant). Markers of oxidative stress (total antioxidant status and oxidized low-density lipoprotein cholesterol), inflammation (interleukin [IL]-6 and C-reactive protein [CRP]), and androgen deficiency symptoms were also examined. RESULTS: During saline, FMDBA was reduced in middle-aged/older compared with young, regardless of testosterone status (P < 0.001). FMDBA was reduced in middle-aged/older lower testosterone (3.7% ± 2.0%) compared with middle-aged/older higher testosterone (5.7% ± 2.2%; P = 0.021), independent of symptoms. Vitamin C increased FMDBA (to 5.3% ± 1.6%; P = 0.022) in middle-aged/older lower testosterone but had no effect in young (P = 0.992) or middle-aged/older higher testosterone (P = 0.250). FMDBA correlated with serum testosterone (r = 0.45; P < 0.001), IL-6 (r = -0.41; P = 0.002), and CRP (r = -0.28; P = 0.041). CONCLUSION: Healthy middle-aged/older men with low testosterone appear to have greater age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. These data suggest that low testosterone concentrations may contribute to accelerated vascular aging in men.

Asunto(s)

Envejecimiento/metabolismo , Enfermedades Cardiovasculares/epidemiología , Endotelio Vascular/fisiopatología , Testosterona/deficiencia , Adolescente , Adulto , Anciano , Envejecimiento/sangre , Envejecimiento/inmunología , Velocidad del Flujo Sanguíneo , Enfermedades Cardiovasculares/inmunología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Estudios Transversales , Endotelio Vascular/diagnóstico por imagen , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo/inmunología , Pletismografía , Testosterona/sangre , Ultrasonografía Doppler , Adulto Joven

RESUMEN

Objectives: Endothelial dysfunction in the fetuses of women with gestational diabetes mellitus (GDM) is associated with their subsequent cardiovascular events. Prenatal assessment of endothelial function in fetuses exposed to intrauterine hyperglycemic environment remains challenging. The aim of this study was to assess the fetal vascular endothelial function in GDM patients using color M-mode derived aortic propagation velocity (APV) and evaluate the correlation of APV with endothelial function biomarkers. Methods: This observational cross-sectional study included 31 gestational diabetic mothers and 30 healthy pregnant mothers from August 2019 to January 2020. Clinical data were compared between the groups. Fetal APV was measured using color M-mode echocardiography at late gestation. Concentrations of endothelial biomarkers including von Willebrand Factor (vWF), vascular endothelial-cadherin and endothelin-1 in umbilical cord serum were assessed. Measurements between diabetic group and controls were compared. Results: vWF was the only endothelial functional marker that differed between the two groups. Fetuses in the GDM group had significantly lower APV levels and higher vWF levels compared with the healthy controls (P < 0.05). There was a moderate but significant correlation between APV and vWF (r =-0.58, P < 0.001). There were no associations between APV and ventricular wall thickness or umbilical artery pulsatility index. Conclusions: Color M-mode propagation velocity of aorta is a non-invasive, practical method that correlates well with GDM and fetal endothelial function. This novel metric could contribute to recognizing early vascular functional alterations and hence represents a potential strategy for early risk factor surveillance and risk modification.

Asunto(s)

Velocidad del Flujo Sanguíneo/fisiología , Diabetes Gestacional/diagnóstico por imagen , Ecocardiografía Doppler en Color/métodos , Endotelio Vascular/diagnóstico por imagen , Diagnóstico Prenatal/métodos , Adulto , Glucemia/metabolismo , Estudios Transversales , Diabetes Gestacional/sangre , Endotelio Vascular/metabolismo , Femenino , Humanos , Recién Nacido , Masculino , Embarazo

RESUMEN

OBJECTIVES: Osteoprotegerin (OPG), a well-known protein that inhibits osteoclast formation and activity, might also be a potential marker for identifying patients with high cardiovascular risk. This study aimed to compare OPG levels, FMD, and CIMT measurements in subjects with vs. without diabetes and investigate the association of serum osteoprotegerin level with the early atherosclerotic markers, endothelial function, and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (DM2). METHODS: Forty-nine patients with DM2 (F/M: 26/23, 49.3 ± 10.0 years) and 45 healthy volunteers (F/M: 26/19, 48.3 ± 7.5 years) were included in this cross-sectional study. Serum OPG levels were measured by solid-phase enzyme-linked immunosorbent assay (ELISA). Fasting plasma glucose (FPG) and HbA1c levels were measured. CIMT was measured by B-mode ultrasound, and endothelial function was evaluated via flow-mediated dilation (FMD) of the brachial artery with Doppler ultrasonography. RESULTS: Serum OPG levels were significantly higher in patients with DM2 (617.0 ± 111.0 pg/mL) compared to controls (481.0 ± 96.0 pg/mL, p < 0.001). While CIMT in diabetic patients (0.65 + 0.13 mm) was higher than controls (0.54 ± 0.10 mm, p = 0.009), FMD measurement was lower in DM2 group (4.2% ± 3.1 mm vs. 7.6% ± 4.1 mm, p = 0.01). Univariate analysis showed that OPG was associated with the presence of diabetes (OR: 6.999, p = 0.001, R2: 15.1%) and hypertension (OR = 6.925, p = 0.001, R2: 13.2%). There was no relationship between OPG levels and CIMT or FMD. CONCLUSION: Osteoprotegerin and CIMT levels were increased, and FMD measurements were decreased in patients with DM2. No association between CIMT, FMD, and OPG measurements was observed. The presence of DM and hypertension were associated with circulating OPG levels.

Asunto(s)

Grosor Intima-Media Carotídeo , Diabetes Mellitus Tipo 2 , Endotelio Vascular , Osteoprotegerina/sangre , Adulto , Biomarcadores/análisis , Biomarcadores/sangre , Glucemia/análisis , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/fisiopatología , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Diabetes Mellitus Tipo 2/fisiopatología , Endotelio Vascular/diagnóstico por imagen , Endotelio Vascular/fisiopatología , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipertensión/sangre , Masculino , Persona de Mediana Edad , Ultrasonografía

RESUMEN

Endothelial dysfunction is one of the hallmarks of vascular abnormalities in metabolic diseases and has been repeatedly demonstrated in coronary and peripheral circulation in mice fed high-fat diet (HFD), particularly after long-term HFD. However, the temporal relationship between development of coronary microvascular endothelial dysfunction and deterioration in diastolic and systolic cardiac function after short-term feeding with HFD has not yet been studied. This study aimed to correlate the changes in coronary microvascular endothelial function and global cardiac performance indices in vivo after short-term feeding with HFD in mice. Short-term feeding with a HFD (60% fat + 1% cholesterol) resulted in severely impaired coronary microvascular function, as evidenced by the diminished effect of nitric oxide synthase inhibition (by L-NAME) assessed using T1 mapping via in vivo MRI. Deterioration of coronary microvascular function was detected as early as after 7 days of HFD and further declined after 8 weeks on a HFD. HFD-induced coronary microvascular dysfunction was not associated with impaired myocardial capillary density and was present before systemic insulin resistance assessed by a glucose tolerance test. Basal coronary flow and coronary reserve, as assessed using the A2A adenosine receptor agonist regadenoson, were also not altered in HFD-fed mice. Histological analysis did not reveal cardiomyocyte hypertrophy or fibrosis. Increased lipid accumulation in cardiomyocytes was detected as early as after 7 days of HFD and remained at a similar level at 8 weeks on a HFD. Multiparametric cardiac MRI revealed a reduction in systolic heart function, including decreased ejection rate, increased end-systolic volume and decreased myocardial strain in diastole with impaired ejection fraction, but not until 4 weeks of HFD. Short-term feeding with HFD resulted in early endothelial dysfunction in coronary microcirculation that preceded alteration in cardiac function and systemic insulin resistance.

Asunto(s)

Vasos Coronarios/fisiopatología , Dieta Alta en Grasa/efectos adversos , Microvasos/fisiopatología , Isquemia Miocárdica/fisiopatología , Animales , Circulación Coronaria/fisiología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Modelos Animales de Enfermedad , Endotelio Vascular/diagnóstico por imagen , Endotelio Vascular/patología , Corazón/diagnóstico por imagen , Humanos , Resistencia a la Insulina , Masculino , Ratones , Microvasos/diagnóstico por imagen , Microvasos/patología , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/etiología , Isquemia Miocárdica/patología

RESUMEN

BACKGROUND: Pulmonary hypertension (PH) complicating idiopathic pulmonary fibrosis (IPF) is associated to worse outcome. There is a great need for a non-invasive diagnostic modality to detect and evaluate the severity of pulmonary vascular disease (PVD). 99mTc-PulmoBind is a novel imaging agent that binds to the adrenomedullin (AM) receptor on the pulmonary microvascular endothelium. SPECT imaging employing the endothelial cell tracer 99mTc-PulmoBind was used to assess PVD associated with lung fibrosis. METHODS: Rats with selective right lung bleomycin-induced fibrosis were compared to control rats. SPECT imaging was performed after three weeks with 99mTc-PulmoBind and 99mTc-macroaggregates of albumin (MAA). PH and right ventricular (RV) function were assessed by echocardiography. Lung perfusion was evaluated by fluorescent microangiography. Lung AM receptor expression was measured by qPCR and by immunohistology. Relevance to human IPF was explored by measuring AM receptor expression in lung biopsies from IPF patients and healthy controls. RESULTS: The bleomycin group developed preferential right lung fibrosis with remodeling and reduced perfusion as assessed with fluorescent microangiography. These rats developed PH with RV hypertrophy and dysfunction. 99mTc-PulmoBind uptake was selectively reduced by 50% in the right lung and associated with reduced AM receptor expression, PH and RV hypertrophy. AM receptor was co-expressed with the endothelial cell protein CD31 in alveolar capillaries, and markedly reduced after bleomycin. Quantitative dynamic analysis of 99mTc-PulmoBind uptake in comparison to 99mTc-MAA revealed that the latter distributed only according to flow, with about 60% increased left lung uptake while left lung uptake of 99mTc-PulmoBind was not affected. Lung from human IPF patients showed important reduction in AM receptor expression closely associated with CD31. CONCLUSIONS: SPECT imaging with 99mTc-PulmoBind detects PVD and its severity in bleomycin-induced lung fibrosis. Reduced AM receptor expression in human IPF supports further clinical development of this imaging approach.

Asunto(s)

Adrenomedulina/análogos & derivados , Bleomicina/toxicidad , Endotelio Vascular/metabolismo , Hipertensión Pulmonar/metabolismo , Fragmentos de Péptidos/metabolismo , Fibrosis Pulmonar/metabolismo , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adrenomedulina/metabolismo , Animales , Antibióticos Antineoplásicos/toxicidad , Endotelio Vascular/diagnóstico por imagen , Endotelio Vascular/efectos de los fármacos , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/diagnóstico por imagen , Masculino , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/diagnóstico por imagen , Radiofármacos/metabolismo , Ratas , Ratas Wistar

RESUMEN

Dialysis vascular access remains vitally important to maintain life and functional capacity with end stage renal disease. Angioplasty is an integral part of maintaining dialysis access function and patency. To understand the effect of angioplasty balloon dilation on vascular wall mechanics, we conducted a clinical study to evaluate the elastic modulus of the anastomosis in five subjects with anastomosis stenoses, before and after six angioplasty procedures, using B-mode ultrasound DICOM data. A novel and open source vascular ultrasound high-resolution speckle tracking software tool was used. The median lumen diameter increased from 3.4 to 5.5 mm after angioplasty. Meanwhile, the median elastic modulus of the 18 measurements at the anastomosis increased by 52.2%, from 2.24 × 103 to 3.41 × 103 mmHg. The results support our hypothesis that the structural changes induced in the vessel wall by balloon dilation lead to reduced vascular compliance and a higher elastic modulus of the vessel wall.

Asunto(s)

Angioplastia de Balón , Endotelio Vascular/fisiopatología , Diálisis Renal , Anciano , Anastomosis Quirúrgica , Módulo de Elasticidad , Endotelio Vascular/diagnóstico por imagen , Humanos , Fallo Renal Crónico/terapia , Persona de Mediana Edad , Ultrasonografía