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Dual-energy CT in pulmonary vascular disease.
Vlahos, I, Jacobsen, MC, Godoy, MC, Stefanidis, K, Layman, RR
The British journal of radiology. 2022;(1129):20210699
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Abstract
Dual-energy CT (DECT) imaging is a technique that extends the capabilities of CT beyond that of established densitometric evaluations. CT pulmonary angiography (CTPA) performed with dual-energy technique benefits from both the availability of low kVp CT data and also the concurrent ability to quantify iodine enhancement in the lung parenchyma. Parenchymal enhancement, presented as pulmonary perfused blood volume maps, may be considered as a surrogate of pulmonary perfusion. These distinct capabilities have led to new opportunities in the evaluation of pulmonary vascular diseases. Dual-energy CTPA offers the potential for improvements in pulmonary emboli detection, diagnostic confidence, and most notably severity stratification. Furthermore, the appreciated insights of pulmonary vascular physiology conferred by DECT have resulted in increased use for the assessment of pulmonary hypertension, with particular utility in the subset of patients with chronic thromboembolic pulmonary hypertension. With the increasing availability of dual energy-capable CT systems, dual energy CTPA is becoming a standard-of-care protocol for CTPA acquisition in acute PE. Furthermore, qualitative and quantitative pulmonary vascular DECT data heralds promise for the technique as a "one-stop shop" for diagnosis and surveillance assessment in patients with pulmonary hypertension. This review explores the current application, clinical value, and limitations of DECT imaging in acute and chronic pulmonary vascular conditions. It should be noted that certain manufacturers and investigators prefer alternative terms, such as spectral or multi-energy CT imaging. In this review, the term dual energy is utilised, although readers can consider these terms synonymous for purposes of the principles explained.
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Beneficial Effects of Vitamin E Supplementation on Endothelial Dysfunction, Inflammation, and Oxidative Stress Biomarkers in Patients Receiving Hemodialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Nguyen, TTU, Yeom, JH, Kim, W
International journal of molecular sciences. 2021;(21)
Abstract
Inflammation and oxidative stress are closely related to cardiovascular complications and atherosclerosis, and have the potential to lead to an increase in death in patients receiving hemodialysis. Vitamin E has antioxidant and anti-inflammatory properties. We conducted a systematic review and meta-analysis to assess the effects of vitamin E supplementation on endothelial dysfunction, inflammation, and oxidative stress biomarkers in adult patients receiving hemodialysis. We searched the MEDLINE, EMBASE, Web of Science, and Cochrane Library databases and identified randomized controlled trials of adult patients receiving hemodialysis until 30 August 2021. A total of 11 trials with 491 randomized patients were included. The pooled data indicated that vitamin E supplementation significantly decreased intercellular adhesion molecule-1 [standardized mean difference (SMD): -1.35; 95% confidence interval (CI): -2.57, -0.13; p = 0.03, I2 = 89%], vascular cell adhesion molecule-1 (SMD: -1.08; 95% CI: -2.05, -0.11; p = 0.03, I2 = 81%), C-reactive protein (SMD: -0.41; 95% CI: -0.75, -0.07; p = 0.02, I2 = 64%), and malondialdehyde (SMD: -0.76; 95% CI: -1.26, -0.25; p = 0.003, I2 = 77%) levels, but not interleukin-6 levels compared to those in the control group. Our results suggest that vitamin E supplementation may help alleviate oxidative stress and both vascular and systemic inflammation in patients receiving hemodialysis.
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The Evolving Applications of Creatine Supplementation: Could Creatine Improve Vascular Health?
Clarke, H, Kim, DH, Meza, CA, Ormsbee, MJ, Hickner, RC
Nutrients. 2020;(9)
Abstract
Creatine is a naturally occurring compound, functioning in conjunction with creatine kinase to play a quintessential role in both cellular energy provision and intracellular energy shuttling. An extensive body of literature solidifies the plethora of ergogenic benefits gained following dietary creatine supplementation; however, recent findings have further indicated a potential therapeutic role for creatine in several pathologies such as myopathies, neurodegenerative disorders, metabolic disturbances, chronic kidney disease and inflammatory diseases. Furthermore, creatine has been found to exhibit non-energy-related properties, such as serving as a potential antioxidant and anti-inflammatory. Despite the therapeutic success of creatine supplementation in varying clinical populations, there is scarce information regarding the potential application of creatine for combatting the current leading cause of mortality, cardiovascular disease (CVD). Taking into consideration the broad ergogenic and non-energy-related actions of creatine, we hypothesize that creatine supplementation may be a potential therapeutic strategy for improving vascular health in at-risk populations such as older adults or those with CVD. With an extensive literature search, we have found only four clinical studies that have investigated the direct effect of creatine on vascular health and function. In this review, we aim to give a short background on the pleiotropic applications of creatine, and to then summarize the current literature surrounding creatine and vascular health. Furthermore, we discuss the varying mechanisms by which creatine could benefit vascular health and function, such as the impact of creatine supplementation upon inflammation and oxidative stress.
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Chronic venous disease: from symptoms to microcirculation.
Senra Barros, B, Kakkos, SK, De Maeseneer, M, Nicolaides, AN
International angiology : a journal of the International Union of Angiology. 2019;(3):211-218
Abstract
The recently published European Venous Forum (EVF) Guidelines 2018 update on the management of chronic venous disorders of the lower limbs has focused on several new aspects: a new place for early symptoms, new data on microcirculation alterations, and a re-evaluation of veno-active drugs (VADs), based on new criteria. The symposium "Chronic Venous Disease (CVD): From Symptoms to Microcirculation", held at the annual meeting of the EVF on 28 June 2018 in Athens, Greece, highlighted this perspective by answering three questions: What do symptoms mean and how do they influence our choice of investigations? Is there a link between symptoms and microcirculation alterations? How to choose the right VAD for the right patient based on the updated EVF guidelines? The answers given led the speakers to three conclusions: early symptoms reveal the initial stage of CVD and patients with C0S disease should be properly diagnosed, investigated, and treated; damage to the microcirculation is likely to be the first evidence of the onset of venous disease; Ruscus+HMC+VitC has proven efficacy in randomized controlled trials, and has been given a strong recommendation (Grade 1A) by the 2018 EVF guidelines for treatment of pain, heaviness, feeling of swelling, paresthesia, and edema, and should be considered as one of the preferred treatments to relieve these symptoms in CVD patients.
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Strategies for Achieving Healthy Vascular Aging.
Nowak, KL, Rossman, MJ, Chonchol, M, Seals, DR
Hypertension (Dallas, Tex. : 1979). 2018;(3):389-402
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Efficacy of Ruscus extract, HMC and vitamin C, constituents of Cyclo 3 fort®, on improving individual venous symptoms and edema: a systematic review and meta-analysis of randomized double-blind placebo-controlled trials.
Kakkos, SK, Allaert, FA
International angiology : a journal of the International Union of Angiology. 2017;(2):93-106
Abstract
INTRODUCTION Venoactive drugs (VADs) are considered an important component of the medical (conservative) treatment of chronic venous disorders (CVDs). However, the efficacy of certain VADs on one or more individual leg symptoms may have not been extensively studied to justify a high level or grade of recommendation in guidelines on CVD. The aim of the present systematic review and meta-analysis was to study the effectiveness of VADs containing Ruscus across the spectrum of defined venous symptoms. EVIDENCE ACQUISITION On November 14 2016, a literature search of the databases MEDLINE and Scopus was performed, supplemented by hand searching, to identify randomized double-blind placebo-controlled trials on Ruscus extracts in patients with CVD. EVIDENCE SYNTHESIS The main outcome measures were the effects of Ruscus on individual symptoms and leg edema, which were expressed as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). Trial quality of evidence was graded using the GRADE system. We identified 10 trials, mostly with low risk of bias, on 719 patients. On qualitative analysis, Ruscus significantly improved seven defined leg symptoms, including pain, heaviness, fatigue, feeling of swelling, cramps, itching and paresthesia compared to placebo. On quantitative analysis, Ruscus compared with placebo, assessed as a categorical variable, reduced leg pain (RR=0.35, P=0.01, number needed to treat [NNT] 5, with no heterogeneity), heaviness (RR=0.26, P<0.00001, NNT=2.4, with a small amount of heterogeneity), feeling of swelling (RR=0.53, P<0.0001, NNT=4, with considerable heterogeneity, minimized after sensitivity analysis), paresthesia (RR=0.27, P<0.0001, NNT=1.8), global symptoms (RR=0.54, P<0.00001, NNT=4.3) and the total number of venous symptoms (RR 0.41, P=0.002). Similarly, Ruscus compared to placebo, assessed as a continuous variable reduced pain (SMD=-0.80, 95% CI: -1.21 to -0.39), heaviness (SMD=-1.23, 95% CI: -1.60 to -0.86), fatigue (SMD -1.16, 95% CI: -1.71 to -0.61), feeling of swelling (SMD=-2.27, 95% CI: -3.83 to -0.70), and paresthesia (SMD=-0.86, 95% CI: -1.51 to -0.21). Regarding objective assessments of leg edema, the use of Ruscus compared with placebo reduced ankle circumference (SMD=-0.74, 95% CI: -1.01 to -0.47) and leg or foot volume (SMD=-0.61, 95% CI: -0.91 to -0.31). The existing evidence, where sufficient, was mostly of high quality. CONCLUSIONS Based on high quality evidence, Ruscus extracts are highly effective in reducing symptoms and edema of patients with CVD.
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Neurovascular manifestations of connective-tissue diseases: A review.
Kim, ST, Brinjikji, W, Lanzino, G, Kallmes, DF
Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences. 2016;(6):624-637
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Abstract
Patients with connective tissue diseases are thought to be at a higher risk for a number of cerebrovascular diseases such as intracranial aneurysms, dissections, and acute ischemic strokes. In this report, we aim to understand the prevalence and occurrences of such neurovascular manifestations in four heritable connective tissue disorders: Marfan syndrome, Ehlers-Danlos syndrome, Neurofibromatosis Type 1, and Loeys-Dietz syndrome. We discuss the fact that although there are various case studies reporting neurovascular findings in these connective tissue diseases, there is a general lack of case-control and prospective studies investigating the true prevalence of these findings in these patient populations. Furthermore, the differences observed in the manifestations and histology of such disease pathologies encourages future multi-center registries and studies in better characterizing the pathophysiology, prevalence, and ideal treatment options of neurovascular lesions in patents with connective tissue diseases.
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Regulation and involvement of matrix metalloproteinases in vascular diseases.
Amin, M, Pushpakumar, S, Muradashvili, N, Kundu, S, Tyagi, SC, Sen, U
Frontiers in bioscience (Landmark edition). 2016;(1):89-118
Abstract
Matrix metalloproteinases (MMPs) are a family of zinc dependent endopeptidases whose main function is to degrade and deposit structural proteins within the extracellular matrix (ECM). A dysregulation of MMPs is linked to vascular diseases. MMPs are classified into collagenases, gelatinases, membrane-type, metalloelastase, stromelysins, matrilysins, enamelysins, and unclassified subgroups. The production of MMPs is stimulated by factors such as oxidative stress, growth factors and inflammation which lead to its up- or down-regulation with subsequent ECM remodeling. Normally, excess activation of MMPs is controlled by their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). An imbalance of MMPs and TIMPs has been implicated in hypertension, atherosclerotic plaque formation and instability, aortic aneurysms and varicose vein wall remodeling. Also, recent evidence suggests epigenetic regulation of some MMPs in angiogenesis and atherosclerosis. Over the years, pharmacological inhibitors of MMPs have been used to modify or prevent the development of the disease with some success. In this review, we discuss recent advances in MMP biology, and their involvement in the manifestation of vascular disease.
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Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling.
Förstermann, U, Li, H
British journal of pharmacology. 2011;(2):213-23
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Abstract
Nitric oxide (NO) produced by the endothelium is an important protective molecule in the vasculature. It is generated by the enzyme endothelial NO synthase (eNOS). Similar to all NOS isoforms, functional eNOS transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH), via the flavins flavin adenine dinucleotide and flavin mononucleotide in the carboxy-terminal reductase domain, to the heme in the amino-terminal oxygenase domain. Here, the substrate L-arginine is oxidized to L-citrulline and NO. Cardiovascular risk factors such as diabetes mellitus, hypertension, hypercholesterolaemia or cigarette smoking reduce bioactive NO. These risk factors lead to an enhanced production of reactive oxygen species (ROS) in the vessel wall. NADPH oxidases represent major sources of this ROS and have been found upregulated in the presence of cardiovascular risk factors. NADPH-oxidase-derived superoxide avidly reacts with eNOS-derived NO to form peroxynitrite (ONOO(-)). The essential NOS cofactor (6R-)5,6,7,8-tetrahydrobiopterin (BH(4) ) is highly sensitive to oxidation by this ONOO(-). In BH(4) deficiency, oxygen reduction uncouples from NO synthesis, thereby converting NOS to a superoxide-producing enzyme. Among conventional drugs, compounds interfering with the renin-angiotensin-aldosterone system and statins can reduce vascular oxidative stress and increase bioactive NO. In recent years, we have identified a number of small molecules that have the potential to prevent eNOS uncoupling and, at the same time, enhance eNOS expression. These include the protein kinase C inhibitor midostaurin, the pentacyclic triterpenoids ursolic acid and betulinic acid, the eNOS enhancing compounds AVE9488 and AVE3085, and the polyphenolic phytoalexin trans-resveratrol. Such compounds enhance NO production from eNOS also under pathophysiological conditions and may thus have therapeutic potential.
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Vascular calcification in patients with chronic kidney disease: types, clinical impact and pathogenesis.
Román-García, P, Rodríguez-García, M, Cabezas-Rodríguez, I, López-Ongil, S, Díaz-López, B, Cannata-Andía, JB
Medical principles and practice : international journal of the Kuwait University, Health Science Centre. 2011;(3):203-12
Abstract
Vascular calcification plays a major role in cardiovascular disease, which is one of the main causes of mortality in chronic kidney disease patients. Vascular calcification is determined by prevalent traditional and uraemia-related (non-traditional) risk factors. It occurs mainly in the arteries, which are classified into three types according to their size and structural characteristics. In addition, vascular calcification has been associated with bone loss and fractures in chronic kidney disease patients and the general population, stressing the fact that both disorders can share pathogenetic pathways. The strategies to control vascular calcification involve several measures, chief among them the control of hyperphosphataemia. Furthermore, it has been recently described that strategies that reduce bone resorption and increase bone mineralization may decrease the risk of vascular calcifications; however, this approach still remains controversial. The mechanisms involved in vascular calcification are complex and not yet fully understood. Phosphorus plays a major role, while other factors related to bone formation have been recently identified.