Endothelial dysfunction in patients with metabolic syndrome: a prospective study in a rural institute in India

Background: The objective was to evaluate endothelial dysfunction in patients with metabolic syndrome.Methods: This prospective, cross-sectional, hospital based observational study included 45 patients with metabolic syndrome and 20 age and sex matched controls who attended hypertension clinic, diabetes clinic, general medicine OPD and patients admitted in wards department of medicine, UPRIMS&R, Saifai, Etawah, UP, India. All patients who fulfilled inclusion criteria were subjected to the color Doppler of the brachial artery in the department of radio-diagnosis of the same institute.Results: Of the 45 patients with metabolic syndrome included in the study, 22 patients (48.9%) were males and 23 patients (51.1%) were females. Ten males (45.5%) had a waist circumference of >90 cm whereas 20 females (87%) had waist circumference of >80 cm. 9 males (40.9%) had abnormal waist hip ratio whereas 22 females (95.7%) had abnormal waist hip ratio. 43 patients (95.6%) had a SBP >130 mm of Hg whereas 39 patients (86.7%) had a DBP >85 mm of Hg. 24 patients (53.3%) had impaired fasting blood sugar i.e. >100 mg/dl ,25 patients (55.6%) had a TGL level >150 mg/dl, and 9 males (40.0%) had HDL < 40 mg/dl whereas 18 females (78.3%) had HDL value < 50 mg/dl respectively. The mean brachial artery baseline diameter were 3.50 ± 0.39 mm in males and 3.25 ± 0.29 mm in females respectively, FMD percentage was 14.91 ± 3.56 in females and 14.53 ± 4.02 in males, and GTN mediated dilatation were 27.67 ± 9.83% in females and 27.62 ± 6.85% in males respectively.Conclusion: Estimation of Endothelial Dysfunction in patients at risk of developing full blown Metabolic Syndrome may predict the cardiovascular morbidity and mortality in these individuals even before fulfilling the 3/5 criteria of NCEP/ATP III Guidelines for the diagnosis of metabolic syndrome.

Effect of Soy Isoflavone Protein and Soy Lecithin on Endothelial Function in Healthy Postmenopausal Women

The purpose of this study was to assess the effects of soy isoflavone protein concentrate and soy lecithin on endothelial function measured as flow mediated dilation (FMD) of the brachial artery in healthy postmenopausal women. In this randomized, double-blind, placebo controlled crossover trial, twenty-five subjects (mean age 61 years; BMI 25.46 kg/m2) were recruited from the general population of southwestern Connecticut. Subjects underwent endothelial function testing using high frequency ultrasound at baseline and following 4 weeks of each randomly assigned treatment with intervening 4-week washout periods. Treatment assignment included: soy isoflavone protein (SP, 25gm/day) or soy lecithin (SL, 20gm/day) alone with placebo for the alternative treatment; both active treatments; or double placebo. Main outcome measures were endothelial function, assessed as flow mediated dilation (FMD) of the brachial artery, and serum lipids. Twenty-two women completed the trial. Baseline FMD (pre-treatment FMD) was 8.60 + 7.20. No statistically significant (P \u3e 0.05) difference was seen in FMD between treatment assignments. A trend was suggested, however, with FMD highest after treatment with both soy protein and lecithin (7.50 + 9.85), followed by soy protein and placebo lecithin (5.51 + 10.11), placebo protein and soy lecithin (5.35 + 6.13), and lowest after double placebo (4.53 + 7.84). Soy isoflavone protein and soy lecithin significantly (P \u3c 0.05) increased HDL/LDL relative to baseline value (soy isoflavone protein and soy lecithin, 0.64 ± 0.19; soy isoflavone protein and placebo lecithin, 0.58 ± 0.17; placebo protein and soy lecithin, 0.65 ± 0.18; baseline, 0.49 ± 0.15). In this sample of healthy postmenopausal women, soy isoflavone protein and soy lecithin significantly improved the lipid profile. A favorable influence on endothelial function by soy isoflavone and soy lecithin was suggested but could not be confirmed statistically, possibly due to small sample size, timing of testing, dose, or delivery vehicle. Although soy protein consumption is generally recommended as part of a heart-healthy diet, its favorable effects on cardiovascular disease risk factors such as endothelial function and lipids have not been consistently demonstrated in clinical trials, and further investigation into its effects on specific cardiovascular outcomes is necessary before a substantial cardioprotective role for soy protein can be asserted

Biomarcatori ecografici di funzione e struttura vascolare nell'uomo Imaging biomarkers of vascular function and structure in humans

Cardiovascular (CV) disease is the first cause of mortality and morbidity in the world. Prevention of this condition, which is responsible of more than 2200 deaths per day only in United States, is a public health priority. Thus in the last decades great efforts have been made in the search of non-invasive biomarkers, able to identify the individual at risk for CV events in the asymptomatic, subclinical stage. Some biomarkers are currently recommended in order to improve stratification of CV risk, whereas other are considered useful only for research purposes. In particular, increased intima-media thickness of the common carotid artery (C-IMT), representing a marker of early atherosclerosis significantly correlated with coronary or cerebrovascular disease, has been considered as an intermediate stage in the continuum of vascular disease and as a predictor of CV risk. Current guidelines also introduced other vascular parameters evaluating mechanical and functional arterial properties of peripheral and central arteries. Increased aortic stiffness has been shown to predict future CV events and it has been recognized as a marker of subclinical target organ damage in hypertensive patients. Earlier vascular abnormalities, such as endothelial dysfunction in the peripheral arteries, have been also mentioned for their possible use in future. However, several questions in this field are still open, limiting the wide use of these tools in the clinical practice. The open issues concern methodological as well as pathophysiological and prognostic aspects, and in this thesis we will discuss only a small part of these ones. First, C-IMT and arterial stiffness represent two sides of vascular aging, atherosclerosis and arteriosclerosis respectively, and are generally considered structural alterations. The identification of a “functional” component in these alterations would be of interest, since it will suggest a possibility of reversibility of vascular aging. Second, vascular aging is a process involving the whole organism, while different techniques explore different districts. The quantification of the impact of different CV risk factors on different vascular districts might indicate the most adequate biomarker to use for future studies and suggest specific mechanisms of disease in different conditions. Third, vascular aging is often accompanied by cardiac and renal damage, but the relationship between organ damage in different districts is still largely unexplored. Fourth, while hypertension and diabetes have become the main cause of end-stage renal disease, and chronic kidney disease has been recognized as a main cause of CV events, to date early markers of renal vascular damage have not been developed. For this PhD thesis I examined cross-sectionally a cohort of healthy subjects and patients with traditional CV risk factors in order to elucidate some of the abovementioned aspects. My original contribution to the knowledge in this field consists in: - the demonstration of a “functional” component in aortic stiffness, that is present only in diabetic patients and relies on endothelium-mediated mechanisms; - the demonstration of a differential impact of different CV risk factors on carotid and aortic stiffness; - the demonstration, in hypertensive patients, of an additive role of carotid and aortic stiffness in determining cardiac organ damage; - the identification of a new marker of renal vascular damage. In the second part of the PhD thesis, I sought to demonstrate the usefulness of imaging biomarkers of vascular function and structure not only for risk stratification in patients with traditional CV risk factors, but also to explore CV consequences of non primarily CV diseases and conditions. We hypothesized that a comprehensive, multiparametric approach would be the best strategy to detect early vascular damage in one or more districts, possibly in a subclinical, reversible stage. This approach could allow identifying the “CV footprint” characterizing each condition, with a double aim: to elucidate the pathophysiology of CV complications in non-CV diseases and to propose the most useful test to be used in the clinical practice for screening and follow-up. During my PhD thesis I applied this strategy to some primarily non-CV conditions that might qualify as emerging CV risk factors, such as exposure to environmental and iatrogenic radiation doses, obstructive sleep apnea syndrome (OSAS) in the absence of traditional CV risk factors, and chronic exposure to hypobaric hypoxia at high altitude. My original contribution to the knowledge in this field consisted in: - the demonstration of a selective reduction of circulating endothelial progenitor cells, in the presence of preserved vascular function and structure, in young adults exposed during childhood to environmental radiation doses after the Chernobyl disaster and to therapeutic radioiodine treatment after thyroid cancer; - the demonstration that conduit artery endothelial dysfunction and impaired renal vasodilating capacity are part of the vascular phenotype of OSAS per se, since they are present even in the absence of traditional CV risk factors, while structural alterations such as arterial stiffness and increased C-IMT characterized only obese and/or hypertensive OSAS patients; - the demonstration that Himalayan high altitude dwellers, chronically living above 2500 meters of altitude, present a mainly microcirculatory endothelial dysfunction and a maladaptive carotid remodeling even in the absence of traditional CV risk factors

Cardiovascular magnetic resonance of the arterial wall

BACKGROUND Atherosclerosis is the single greatest cause of mortality and morbidity in the developed world. Cardiovascular magnetic resonance (CMR) is a non-invasive imaging technique which can interrogate the arterial wall and identify atherosclerotic disease. CMR can provide quantitative volumetric data of atherosclerosis burden which have begun to be used in clinical trials, however comparatively few studies have been performed. We aimed to validate this approach ex vivo, to use it to characterise a normal population in vivo, to further develop the methodology, and to apply the technique to novel ‘at risk’ populations. METHODS AND RESULTS We validated quantitative CMR arterial wall volume in post mortem carotid arteries against both a CMR comparator, and against histological data. For all correlations, R2 was greater than 0.95: (CMR v histology: lumen volume 354 vs 308mm3, p<0.01; arterial wall volume 388 vs 351 mm3, p<0.01; total volume 750 vs 665 mm3; p<0.01). We studied 100 normal subjects from age 20 to 69 to determine normal ranges and the effect of normal ageing. Wall volume and total vessel volume increased significantly with age in both sexes (p < 0.006), and this was more marked in males. The W/OW ratio also increased significantly with age (p < 0.001). We showed that a 3-dimensional CMR sequence performs 63% faster than a conventional 2-dimensional sequence, with twice the signal-to-noise ratio (SNR), and highly correlated results (vessel volume: difference = 1.7%, R2 = 0.93, p < 0.001; lumen volume: difference = 4.9%, R2 = 0.92, p < 0.001, wall volume: difference = 4.7%, R2 = 0.77, p < 0.001, W/OW ratio: difference = 5.8%, R2 = 0.30, p < 0.001). Finally, we characterised atherosclerotic burden and arterial health in two populations with Takayasu’s arteritis and systemic lupus erythematosus by CMR. Carotid arterial wall volume was elevated in both populations: TA = 1045mm3, SLE = 761mm3, normals = 640mm3, p < 0.001, and myocardial late gadolinium enhancement was found 27% of TA patients, and in 60% of those with SLE. CONCLUSIONS Cardiovascular magnetic resonance of the arterial wall is an accurate way of measuring carotid atherosclerosis burden. This thesis validates this approach, and provides valuable normal data. It compares new techniques with old, aiding technical development. Finally, it demonstrates how the technique can be used in practice in populations with accelerated atherosclerosis. These data indicate that arterial wall CMR is ready to be applied in larger clinical trials

Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world

Disfunção vascular nos doentes com coarctação da aorta tratada

RESUMO: As cardiopatias congénitas (CC) afetam aproximadamente 1% dos recémnascidos e são responsáveis pela maior proporção de mortalidade infantil nos países desenvolvidos. A coarctação da aorta (CoA), a 6ª CC mais frequente, consiste numa estenose da aorta descendente proximal. Se não for tratada, tem uma história natural desfavorável. A cirurgia, dilatação com balão e a implantação de stent são atualmente técnicas que podem atingir o objetivo de uma remoção eficaz e duradoura da estenose ístmica, sendo a decisão baseada na idade doente, anatomia da CoA e preferência do operador ou da instituição. Contudo, um bom resultado anatómico não evita morbilidade e mortalidade de longo prazo, apresentando cerca de metade dos doentes hipertensão arterial (HTA), e registando-se mortalidade precoce, maioritariamente devido a complicações cardiovasculares e acidentes vasculares cerebrais. O perfil tensional anómalo sugere que os resultados subótimos possam ser secundários a disfunção vascular, cuja existência foi bem documentada em doentes com CoA tratada. Existem anomalias intrínsecas da estrutura arterial e função, alterações da sensibilidade neuro-hormonal ou da regulação endócrina, e fatores adquiridos, como a idade do tratamento, que contribuem para esta disfunção vascular. Os maus resultados a longo prazo podem resultar igualmente do tipo de tratamento efetuado, que provavelmente impactam de modo diverso a rigidez do istmo aórtico e potencialmente comprometem as funções da aorta. Este efeito da modalidade terapêutica não foi até ao momento estudado. A CoA não é uma simples doença mecânica que fica resolvida quando é removido o obstáculo. Objetivos e Hipóteses: O objetivo deste estudo é comparar a função vascular entre diferentes modalidades terapêuticas de CoA. A hipótese principal é a de que os doentes submetidos a dilatação com balão têm melhor função vascular que os doentes submetidos a cirurgia ou implantação de stent, pois aquela modalidade terapêutica tem menor potencial para danificar a integridade e propriedades biomecânicas da parede da aorta do que estas. Métodos: Avaliação prospetiva da função vascular usando múltiplas modalidades não invasivas, de modo a comparar os resultados de três grupos de doentes com CoA, tratados com dilatação com cirurgia, balão ou implantação de stent, após controle das variáveis de confusão. Em doentes com CoA tratada com sucesso, comparámos prospectivamente a rigidez da aorta com tonometria de aplanação e ressonância magnética cardíaca; função endotelial com tonometria arterial periférica endotelial; analise da onda de pulso com tonometria de aplanação e tonometria arterial periférica endotelial; massa ventricular esquerda e anatomia do arco aórtico com ressonância magnética cardíaca; marcadores séricos de função endotelial, inflamação, função da parede arterial e matriz extracelular; e saúde cardiovascular ideal. A análises estatística incluiu ajuste para as variáveis de confusão. Resultados: O estudo foi realizado em sete grandes centros, de Portugal e Estados Unidos da América. Foram incluídos 75 doentes, tratado por cirurgia (n=28), dilatação com balão (n=23) e implantação de stent (n=24). Os grupos tiveram idade semelhante à data de inclusão, gravidade da CoA, gradiente residual e perfil metabólico, mas eram diferentes quanto à idade à data do tratamento. A HTA, rigidez da aorta, função endotelial e massa ventricular eram semelhantes entre os grupos. Contudo, o grupo da dilatação com balão tinha mais distensibilidade regional da aorta ascendente, menor tensão arterial (TA) sistólica durante o exercício, menos alteração da variação noturna da TA, e dose menor de biomarcadores inflamatórios. Os resultados permaneceram inalterados após ajuste das potenciais variáveis de confusão, incluindo idade à data do tratamento. Conclusões: A modalidade terapêutica não estava associada à presença de HTA, rigidez arterial global e função endotelial. Contudo, os doentes com dilatação com balão tinham um perfil de função vascular mais favorável, caracterizado por maior distensibilidade da aorta ascendente, TA noturna mais baixa, menor resposta hipertensiva no esforço e menores marcadores séricos de inflamação. São necessários mais estudos para confirmar se os nossos resultados poderão contribuir para o refinamento do paradigma de tratamento da CoA, ao adicionar ao objetivo de remoção da estenose, a preservação da função vascular, quando dois ou mais tratamentos são aplicáveis.ABSTRACT: Introduction: Congenital heart disease (CHD) affects approximately 1% of liveborns and accounts for the largest proportion of infant mortality in developed countries. Coarctation of the aorta (CoA), the 6th most common CHD, consists of a narrowing of the proximal descending aorta. If left untreated, it has an unfavorable natural history. Surgery, balloon dilation (BD) or stent implantation are all current treatments that can achieve a successful long-term removal of the stenosis, and the choice is based on age, CoA anatomy, and personal or institutional preference. Coarctation is not a mere mechanical disease that is treated by removing the increased afterload. In fact, a good anatomic result does not avoid long-term cardiovascular (CV) morbidity and mortality, with late systemic hypertension (HTN) in approximately half of the patients, and reduced life expectancy, mostly due to CV complications and stroke. The abnormal blood pressure (BP) phenotype suggests that the suboptimal results are likely due to abnormal vascular function, which has been well documented in patients with repaired CoA. There are inherent changes in the arterial structure and function, impaired neuronal sensitivity or endocrinal auto-regulation, and acquired features, such as age at treatment, that contribute to vascular dysfunction in CoA. The poor long-term vascular outcome may also be impacted by the different types of repair, which likely have differing effects on the stiffness of the repaired segment and potentially compromise both the conduit and cushioning functions of the aorta. The effects of treatment modality on long-term vascular function remain uncharacterized. Aims and Hypothesis: The goal of this study is to assess vascular function in this patient population for comparison among the treatment modalities. The central hypothesis of this study was that patients who have undergone successful BD will have better vascular function than patients who have undergone successful surgical repair or stenting since this modality is least likely to damage the integrity and biomechanical properties of the aortic wall. Methods: Prospective assessment of vascular function using multiple non-invasive modalities, and compare the results among the three groups of CoA patients previously treated using surgery, BD or stent implantation after frequency matching for confounding variables. In successfully repaired CoA patients, we prospectively compared aortic stiffness by applanation tonometry and cardiac magnetic resonance (CMR); endothelial function by endothelial pulse amplitude testing; pulse waveform analysis by applanation tonometry and endothelial pulse amplitude testing; BP phenotype by office BP, ambulatory BP monitoring, and BP response to exercise; left ventricular (LV) mass and aortic morphometrics by CMR; blood biomarkers of endothelial function, inflammation, vascular wall function, and extracellular matrix; and ideal cardiovascular health. In the statistical analysis, we adjusted for potential confounders. Results: This study was done in seven, large volume centers from Portugal and the United States of America. Participants included 75 patients treated with surgery (n=28), BD (n=23), or stent (n=24). Groups had similar age at enrollment, CoA severity, residual gradient, and metabolic profile but differed by age at treatment. Systemic HTN, aortic stiffness, endothelial function, and LV mass were similar among groups. However, BD had more distensible ascending aortas, lower peak systolic BP during exercise, less impairment in diurnal BP variation, and lower inflammatory biomarkers. The results were unchanged after adjustment for potential confounders, including age at treatment. Conclusions: Treatment modality was not associated with major vascular outcomes such as systemic HTN, global aortic stiffness, and endothelial function. However, BD patients had a better vascular phenotype profile characterized by higher ascending aorta distensibility, lower night-time BP, lower peak exercise BP and lower levels of inflammatory markers. Further studies are required to confirm if our results may contribute to refining the CoA treatment paradigm by adding to the goals of therapy the preservation of vascular function when two or more treatment techniques are applicable

Real-time diameter of the fetal aorta from ultrasound

The automatic analysis of ultrasound sequences can substantially improve the efficiency of clinical diagnosis. This article presents an attempt to automate the challenging task of measuring the vascular diameter of the fetal abdominal aorta from ultrasound images. We propose a neural network architecture consisting of three blocks: a convolutional neural network (CNN) for the extraction of imaging features, a convolution gated recurrent unit (C-GRU) for exploiting the temporal redundancy of the signal, and a regularized loss function, called CyclicLoss, to impose our prior knowledge about the periodicity of the observed signal. The solution is investigated with a cohort of 25 ultrasound sequences acquired during the third-trimester pregnancy check, and with 1000 synthetic sequences. In the extraction of features, it is shown that a shallow CNN outperforms two other deep CNNs with both the real and synthetic cohorts, suggesting that echocardiographic features are optimally captured by a reduced number of CNN layers. The proposed architecture, working with the shallow CNN, reaches an accuracy substantially superior to previously reported methods, providing an average reduction of the mean squared error from 0.31 (state-of-the-art) to 0.09 $$ackslashmathrmmm^2$$mm2, and a relative error reduction from 8.1 to 5.3%. The mean execution speed of the proposed approach of 289 frames per second makes it suitable for real-time clinical use

Metabolic syndrome – early cardio-metabolic, vascular and hepatic changes

Background: Metabolic syndrome (MetS) is a combination of several cardio-metabolic risk factors including obesity, hyperglycemia, hypertension and dyslipidemia. MetS has been associated with increased levels of apolipoprotein B (apoB) and low-density lipoprotein oxidation (OxLDL) and with an increased risk of cardiovascular disease and non-alcoholic fatty liver disease. Aims: To establish the relation of apoB and OxLDL with the MetS development and to determine the status of MetS as a risk factor for adverse liver changes and for subclinical atherosclerosis. Subjects and Methods: The present thesis is part of the two large scale population-based, prospective, observational studies. Cardiovascular Risk in Young Finns study was launched in 1980 including 3,596 subjects aged 3-18 years. Thereafter follow-up studies have been conducted regularly. In the latest follow-ups that were performed in 2001 (N=2,283) and 2007 (N=2,204), non-invasive ultrasound studies were introduced to the study protocol to measure subclinical atherosclerosis i.e. carotid intima-media thickness (IMT), carotid artery distensibility (Cdist) and brachial flow-mediated dilatation (FMD). Alanine-aminotransferase (ALT) and gammaglutamyltransferase (GGT) were measured in 2007 to assess liver function. The Bogalusa Heart Study is a long-term epidemiologic study of cardiovascular risk factors launched in 1972 in a biracial community of Bogalusa, Louisiana, USA. Total of 374 youths (aged 9-18 years at baseline in 1984-88) who underwent non-invasive ultrasound studies of the carotid artery as adults, were included in the analyses of the present thesis. Results: The odds ratios (95% confidence intervals) for MetS incidence during a 6-year follow-up by quartiles of apoB were 2.0(1.0-3.8) for the second quartile, 3.1(1.7-5.7) for the third quartile and 4.2(2.3-7.6) for the fourth quartile. OxLDL was not independently associated with incident MetS. Youth (aged 9-18 years) with MetS or with high body mass index were at 2-3 times the risk of having MetS, high IMT, and type 2 diabetes 24-years later as adults. IMT increased 79±7μm (mean±SEM) in subjects with MetS and 42±2μm in subjects without the MetS (P<0.0001) during 6- years. Subjects who lost the MetS diagnosis during 6-year follow-up had reduced IMT progression compared to persistent MetS group (0.036±0.005vs.0.079±0.010 mm, P=0.001) and reduced Cdist change compared to incident MetS group (-0.12±0.05vs.-0.38±0.10 %/mmHg, P=0.03) over 6-year follow-up. MetS predicted elevated ALT (β±SEM=0.380±0.052, P<0.0001 in men and 0.160±0.052, P=0.002 in women) and GGT (β±SEM=0.240±0.058, P<0.0001 in men and 0.262±0.053, P<0.0001 in women) levels after 6-years. Conclusions: These findings suggest that apoB may give additional information on early metabolic disturbances predisposing MetS. MetS may be used to identify individuals at increased risk of developing atherosclerosis and non-alcoholic liver disease. However, recovery from the MetS may have positive effects on liver and vascular properties.Siirretty Doriast