Endothelial dysfunction in adolescents and young adults with nonalcoholic liver disease

Nonalcoholic liver disease is a global public health problem that increases cardiovascular morbidity and mortality in these patients. This paper discusses endothelial dysfunction among patients (adolescents and young adults) with nonalcoholic liver disease. On the one hand, evidence suggests that cardiovascular disease is the leading cause of mortality in patients with advanced nonalcoholic liver disease and that nonalcoholic fatty liver is associated with an increased risk of cardiovascular disease independent of the presence of cardiovascular risk factors and metabolic syndrome components. On the other hand, nonalcoholic liver disease, especially the non-inflammatory form of nonalcoholic steatohepatitis, may not only be a marker of cardiovascular damage but also a factor involved in its pathogenesis. Such patients are candidates not only for the treatment of liver disease but also for the early treatment of cardiovascular risk factors because many of them, especially those with severe nonalcoholic liver disease, will develop major cardiovascular events and may eventually die of cardiovascular disease before the advanced liver disease occurs

Noninvasive Assessment of Preclinical Atherosclerosis

Initially considered as a semipermeable barrier separating lumen from vessel wall, the endothelium is now recognised as a complex endocrine organ responsible for a variety of physiological processes vital for vascular homeostasis. These include the regulation of vascular tone, luminal diameter, and blood flow; hemostasis and thrombolysis; platelet and leucocyte vessel-wall interactions; the regulation of vascular permeability; and tissue growth and remodelling. The endothelium modulates arterial stiffness, which precedes overt atherosclerosis and is an independent predictor of cardiovascular events. Unsurprisingly, dysfunction of the endothelium may be considered as an early and potentially reversible step in the process of atherogenesis and numerous methods have been developed to assess endothelial status and large artery stiffness. Methodology includes flow-mediated dilatation of the brachial artery, assessment of coronary flow reserve, carotid intimamedia thickness, pulse wave analysis, pulse wave velocity, and plethysmography. This review outlines the various modalities, indications, and limitations of available methods to assess arterial dysfunction and vascular risk

Vascular ultrasound and cardiovascular risk assessment

Vascular ultrasound is able to detect endothelial dysfunction, arterial structural remodeling and increased arterial stiffness. These alterations have been shown to be associated with established and emerging cardiovascular risk factors and with incident cardiovascular events. Therefore, vascular ultrasound has been proposed to evaluate the role of different risk factors in the initiation and progression of atherosclerotic process, to study vascular aging and the relationship between arterial stiffness and atherosclerosis, to assess the efficacy of life-style and therapeutic interventions, and to improve the estimation of individual cardiovascular risk. The present paper provides a critical overview of the clinical evidence appraising the association of flow-mediated dilation, carotid and femoral intima-media thickness and plaque presence as well as local arterial stiffness with cardiovascular risk factors and cardiovascular events

The use of subclinical vascular markers of atherosclerosis in youth

The foundations for cardiovascular disease (CVD) in adults are laid in childhood and accelerated by the presence of comorbid conditions. Early detection of manifestations of cardiovascular pathology is an important clinical objective to identify those at risk for subsequent cardiovascular morbidity and events, and to initiate behavioral and medical interventions to reduce risk. Children were once considered to be at low risk, but with the growing health concerns related to lifestyle, cardiovascular screening may be needed earlier. Several noninvasive procedures are available to assess the cumulative effect of these exposures. These include carotid ultrasound, flow-mediated dilation, pulse wave velocity and measures left ventricular mass. This dissertation analyzes the comorbid conditions that increase cardiovascular risk in youth, namely obesity and low physical fitness, using carotid intima-media thickness to objectively detect early manifestations of cardiovascular pathology. Until recently researchers have not used surrogate markers of subclinical atherosclerosis to examine the role of a single bout of exercise. Utilizing the acute exercise model can be advantageous as it allows for an efficient manipulation of exercise variables and permits greater experimental control of confounding variables. It is possible that the effects of a bout of exercise can predict the effects of chronic exercise. We analyze the physiological factors pertinent to arterial stiffness using arterial distensibility and pulse wave velocity in the context of acute exercise in children and adults. In some instances, those who amend their trajectory by not maintaining risk factors into adulthood experience reductions in subclinical markers to levels associated with never having had the risk factor. Though avoidance of risk factors in youth is ideal, there is still a window for intervention where long-lasting cardiovascular effects might be avoided. In this dissertation we present preliminary findings linking modifiable youth risk factors to subclinical markers of CVD in adulthood.As bases da doença cardiovascular (DCV) em adultos são estabelecidas na infância e aceleradas pela presença de comorbidades. A deteção precoce de manifestações da patologia cardiovascular é um objetivo clínico importante na identificação daqueles com risco de subsequente morbidade e eventos cardiovasculares, e no estabelecimento de intervenções comportamentais e médicas para reduzir o risco. As crianças já foram considerados de baixo risco, mas com as crescentes preocupações de saúde associadas ao estilo de vida, o rastreio cardiovascular é cada vez mais precoce. Vários procedimentos não invasivos estão disponíveis para avaliar o efeito cumulativo dessas exposições. Estes incluem ultrassom da artéria carótida, a dilatação fluxo-mediada, velocidade de onda de pulso e medidas da massa ventricular esquerda. Esta dissertação analisa comorbidades conhecidas que aumentam o risco cardiovascular em crianças e adolescentes, como a obesidade, pressão arterial elevada e baixa aptidão física, usando a espessura da parede intima-media da carótida para detetar objetivamente as manifestações precoces de patologia cardiovascular. Até recentemente, estes marcadores subclínicos de aterosclerose foram pouco utilizados para examinar os efeitos de uma única sessão de exercício físico. No entanto, a utilização do modelo de exercício agudo pode ser vantajoso, pois permite uma manipulação eficiente das variáveis do exercício e permite maior controle experimental de variáveis de enviezamento. É possível que os efeitos de uma sessão de exercício possam prever os efeitos do exercício crónico. Nesta dissertação analisamos os fatores fisiológicos associados à rigidez arterial usando a distensibilidade arterial e velocidade da onda de pulso no contexto de exercício agudo em crianças e adultos. Em alguns casos, aqueles que melhoram o seu perfil de risco de risco para as DCV até à idade adulta experienciam reduções em marcadores subclínicos de aterosclerose para níveis saudáveis. Embora a prevenção de fatores de risco na juventude seja o ideal, existe ainda uma janela para a intervenção em que os efeitos cardiovasculares de longa duração pode ser evitada. Nesta dissertação apresentamos resultados preliminares que ligam fatores de risco modificáveis na juventude com marcadores subclínicos de DCV na idade adulta

Three-dimensional Ultrasound Measurements of Carotid Atherosclerosis in Vulnerable Patient Populations

Atherosclerosis is a progressive disease that leads to plaque development and is associated with cardiovascular events such as myocardial infarction and stroke. Several biomarkers have been established as surrogates of plaque development yet none can provide direct, noninvasive, rapid measurements of atherosclerotic disease. Three-dimensional Ultrasound (3DUS) image acquisition is safe, inexpensive and fast, however 3DUS image measurements are limited due to time consuming manual image analyses. In addition, the true clinical meaning of 3DUS carotid imaging measurements has not yet been established. A semi-automated approach for the estimation of 3DUS Total Plaque Volume (TPV) was developed with similar variability and high agreement with manual measurements. 3DUS measurements such as Vessel Wall Volume (VWV) and TPV were shown to have similar associations of plaque and Intima-media Thickness (IMT) with age in males however this relationship did not exist in females. 3DUS measurements of carotid atherosclerosis can provide a more sensitive estimation of disease burden in vulnerable patient populations than traditional measures

2-D and 3-D high frame-rate Pulse Wave Imaging for the characterization of focal vascular disease

Cardiovascular diseases are major causes of morbidity and mortality in Western-style populations. Atherosclerosis and Abdominal Aortic Aneurysms (AAAs) are two prevalent vascular diseases that may progress without symptoms and contribute to acute cardiovascular events such as stroke and AAA rupture, which are consistently among the leading causes of death worldwide. The imaging methods used in the diagnosis of these diseases, have been reported to present several limitations. Given that both are associated with mechanical changes in the arterial wall, imaging of the arterial mechanical properties may improve early disease detection and patient care. Pulse wave velocity (PWV) refers to the velocity at which arterial waves generated by ventricular ejection travel along the arterial tree. PWV is a surrogate marker of arterial stiffness linked to cardiovascular mortality. The foot-to-foot method that is typically used to calculate PWV suffers from errors of distance measurements and time-delay measurements. Additionally, a single PWV estimate is provided over a relatively long distance, thus inherently lacking the capability to provide regional arterial stiffness measurements. Pulse Wave Imaging (PWI) is a noninvasive, ultrasound-based technique for imaging the propagation of pulse waves along the wall of major arteries and providing a regional PWV value for the imaged artery. The aim of this work was to enable PWI to provide more localized PWV and stiffness measurements within the imaged arterial segment and to further extend it into a 2-D and 3-D technique for the detection and monitoring of focal vascular disease at high temporal and spatial resolution. The improved modality was integrated with blood flow imaging modalities aiming to render PWI a comprehensive methodology for the study of arterial biomechanics in vivo. Spatial information was increased with the introduction of piecewise PWI. This novel technique was used to measure PWV within small sub-regions of the imaged vessel in murine aneurysmal (n = 8) and atherosclerotic aortas (n = 11) in vivo. It provided PWV and stiffness maps while capturing the progressive arterial stiffening caused by atherosclerosis. PWI was further augmented with a sophisticated adaptive algorithm, enabling it to optimally partition the imaged artery into relatively homogeneous segments, automatically isolating arterial stiffness inhomogeneities. Adaptive PWI was validated in silicone phantoms consisting of segments of varying stiffness and then tested in murine aortas in vivo. Subsequently, the conventional tradeoff between spatial and temporal resolution was addressed with a plane wave compounding implementation of PWI, allowing the acquisition of full field of view frames at over 2000 Hz. A GPU-accelerated PWI post-processing framework was developed for the processing of the big bulk of generated data. The parameters of coherent compounding were optimized in vivo. The optimized sequences were then used in the clinic to assess the mechanical properties of atherosclerotic carotids (n=10) and carotids of patients after endarterectomy (n=7), a procedure to remove the plaque and restore blood flow to the brain. In the case of atherosclerotic patients undergoing carotid endarterectomy, the results were compared against the histology of the excised plaques. Investigation of the mechanical properties of plaques was also conducted for the first time with a high-frequency transducer (18.5 MHz). Additionally, 4-D PWI was introduced, utilizing high frame rate 3-D plane wave acquisitions with a 2-D matrix array transducer (16x16 elements, 2.5 MHz). A novel methodology for PWV estimation along the direction of pulse wave propagation was implemented and validated in silicone phantoms. 4-D PWI provided comprehensive views of the pulse wave propagation in a plaque phantom and the results were compared against conventional PWI. Finally, its feasibility was tested in the carotid arteries of healthy human subjects (n=6). PWVs derived in 3-D were within the physiological range and showed good agreement with the results of conventional PWI. Finally, PWI was integrated with flow imaging modalities (Color and Vector Doppler). Thus, full field-of-view, high frame-rate, simultaneous and co-localized imaging of the arterial wall dynamics and color flow as well as 2-D vector flow was implemented. The feasibility of both techniques was tested in healthy subjects (n=6) in vivo. The relationship between the timings of the flow and wall velocities was investigated at multiple locations of the imaged artery. Vector flow velocities were found to be aligned with the vessel’s centerline during peak systole in the common carotid artery and interesting flow patterns were revealed in the case of the carotid bifurcation Consequently, with the aforementioned improvements and the inclusion of 3-D imaging, PWI is expected to provide comprehensive information on the mechanical properties of pathological arteries, providing clinicians with a powerful tool for the early detection of vascular abnormalities undetectable on the B-mode, while also enabling the monitoring of fully developed vascular pathology and of the recovery of post-operated vessels

Arterial Ultrasonography and Tonometry as Adjuncts to Cardiovascular Risk Stratification

Myocardial infarction and stroke often occur without prior warning in asymptomatic individuals. Identifying individuals at risk is important for cost-effective use of preventive therapies. Algorithms based on risk factors statistically associated with cardiovascular events classify individuals into high-risk, intermediate-risk, or low-risk categories. However, more than one-third of adults in the U.S. are in the intermediate-risk category, and decisions regarding therapy are challenging in this subset. Testing for alterations in arterial function and structure that predate cardiovascular events may help refine cardiovascular risk assessment in the intermediate-risk group and identify candidates for aggressive therapy. Vascular ultrasonography and tonometry are promising test modalities for assessment of arterial function and structure in asymptomatic subjects. Several prospective studies have shown that measures of arterial function and structure provide prognostic information incremental to conventional risk factors. Standardization of methodology and establishment of quality control standards in the performance of these tests could facilitate their integration into clinical practice as adjuncts to existing cardiovascular risk stratification algorithms

Multimodal cardiovascular magnetic resonance quantifies regional variation in vascular structure and function in patients with coronary artery disease: Relationships with coronary disease severity

<p>Abstract</p> <p>Background</p> <p>Cardiovascular magnetic resonance (CMR) of the vessel wall is highly reproducible and can evaluate both changes in plaque burden and composition. It can also measure aortic compliance and endothelial function in a single integrated examination. Previous studies have focused on patients with pre-identified carotid atheroma. We define these vascular parameters in patients presenting with coronary artery disease and test their relations to its extent and severity.</p> <p>Methods and Results</p> <p>100 patients with CAD [single-vessel (16%); two-vessel (39%); and three-vessel (42%) non-obstructed coronary arteries (3%)] were studied. CAD severity and extent was expressed as modified Gensini score (mean modified score 12.38 ± 5.3). A majority of carotid plaque was located in the carotid bulb (CB). Atherosclerosis in this most diseased segment correlated modestly with the severity and extent of CAD, as expressed by the modified Gensini score (R = 0.251, P < 0.05). Using the AHA plaque classification, atheroma class also associated with CAD severity (rho = 0.26, P < 0.05). The distal descending aorta contained the greatest plaque, which correlated with the degree of CAD (R = 0.222; P < 0.05), but with no correlation with the proximal descending aorta, which was relatively spared (R = 0.106; P = n. s.). Aortic distensibility varied along its length with the ascending aorta the least distensible segment. Brachial artery FMD was inversely correlated with modified Gensini score (R = -0.278; P < 0.05). In multivariate analysis, distal descending aorta atheroma burden, distensibility of the ascending aorta, carotid atheroma class and FMD were independent predictors of modified Gensini score.</p> <p>Conclusions</p> <p>Multimodal vascular CMR shows regional abnormalities of vascular structure and function that correlate modestly with the degree and extent of CAD.</p

Arterial stiffness increases with deteriorating glucose tolerance status - The Hoorn Study

Background - Type 2 diabetes (DM-2) and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease risk. In nondiabetic individuals, increased arterial stiffness is an important cause of cardiovascular disease. Associations between DM-2 and IGM and arterial stiffness have not been systematically investigated. Methods and Results - In a population-based cohort (n=747; 278 with normal glucose metabolism, 168 with IGM, and 301 with DM-2; mean age, 68.5 years), arterial stiffness was ultrasonically estimated by distensibility and compliance of the carotid, femoral, and brachial arteries and by the carotid elastic modulus. After adjustment for age, sex, and mean arterial pressure, DM-2 was associated with increased carotid, femoral, and brachial stiffness, whereas IGM was associated only with increased femoral and brachial stiffness. Carotid but not femoral or brachial stiffness increased from IGM to DM-2. Standardized βs (95% CI) for IGM and DM-2, compared with normal glucose metabolism, were -0.06 (-0.23 to 0.10) and -0.37 (-0.51 to -0.23) for carotid distensibility; -0.02 (-0.18 to 0.18) and -0.25 (-0.40 to -0.09) for carotid compliance; -0.05 (-0.23 to 0.13) and 0.25 (0.10 to 0.40) for carotid elastic modulus; -0.70 (-0.89 to -0.51) and -0.67 (-0.83 to -0.52) for femoral distensibility; and -0.62 (-0.80 to -0.44) and -0.79 (-0.94 to -0.63) for femoral compliance. The brachial artery followed a pattern similar to that of the femoral artery. Increases in stiffness indices were explained by decreases in distension, increases in pulse pressure, an increase in carotid intima-media thickness, and, for the femoral artery, a decrease in diameter. Hyperglycemia or hyperinsulinemia explained only 30% of the arterial changes associated with glucose tolerance. Adjustment for conventional cardiovascular risk factors did not affect these findings. Conclusions - IGM and DM-2 are associated with increased arterial stiffness. An important part of the increased stiffness occurs before the onset of DM-2 and is explained neither by conventional cardiovascular risk factors nor by hyperglycemia or hyperinsulinemia