Management of atherosclerotic renal artery stenosis

The management of atherosclerotic renal artery stenosis is controversial. Although it may appear intuitive that restoring normal blood flow to the kidney(s) is the treatment of choice, there are no data showing an obvious advantage of interventional therapy compared with medical therapy. In this article, we discuss the most recent advances in the treatment of atherosclerotic renal artery stenosis with a focus on randomized studies comparing medical treatment with angioplasty/stenting, particularly in patients with underlying renal dysfunction. The available data are still of limited quality but provide support against indiscriminate use of interventions, as these treatments appear no better than best medical treatment that focuses on blood pressure control, use of blockers of the renin–angiotensin system, and aggressive cardiovascular risk management.     

Update on the endocannabinoid-mediated regulation of gelatinase release in arterial wall physiology and atherosclerotic pathophysiology

Endocannabinoids are endogenous bioactive lipids ubiquitously distributed in several tissues (e.g., brain, adipose tissue, liver, heart and arterial vessels), which play a crucial role in atherosclerosis. Endocannabinoids have been shown to promote cell homeostasis and modulate inflammatory bioactivities mainly via the binding to transmembrane receptors (called cannabinoid type 1 and cannabinoid type 2 receptors, respectively). Although other cannabinoid receptors have been recently identified and shown to play a crucial role in cardiovascular pathophysiology, so far, the pharmacological targeting of both cannabinoid type 1 and cannabinoid type 2 receptors has been described as a promising therapeutic target in atherogenesis and associated inflammatory processes. In particular, endocannabinoids have been shown to modulate the release and activation of matrix degrading enzymes (i.e., matrix metalloproteinases [MMPs]) increasing intraplaque vulnerability. In this article the authors describe the pivotal regulatory activity of the endocannabinoid system on gelatinase (MMP-2 and -9) bioactivity in the arterial wall physiology and pathophysiology.     

Colesevelam hydrochloride in the management of dyslipidemia

Dyslipidemia is a highly heterogeneous group of disorders strongly influenced by both genetic and environmental factors. Dyslipidemia significantly increases risk for atherosclerotic disease and all of its various clinical manifestations. Identifying patients with dyslipidemia and initiating therapies aimed at normalizing the lipid profile has been demonstrated to significantly reduce the risk for myocardial infarction, stroke and cardiovascular mortality in both the primary and secondary prevention settings. Guidelines in Europe, Canada and the USA emphasize the need to reduce the burden of atherogenic lipoproteins in serum and to raise levels of high-density lipoproteins in patients at risk for cardiovascular events. Statins have emerged as front-line therapy for managing dyslipidemia, especially in patients with elevated serum levels of low-density lipoprotein cholesterol. As guidelines emphasize the need to reduce serum low-density lipoprotein cholesterol to lower levels, goal attainment can be challenging. The use of combination therapy increases the likelihood of therapeutic success for many patients. Furthermore, a significant percentage of patients with dyslipidemia either cannot achieve goals on statin monotherapy, choose not to take a statin or do not tolerate these drugs due to adverse side effects, such as myalgias, weakness or hepatotoxicity. This article summarizes the pharmacology, clinical efficacy and safety of colesevelam hydrochloride, a bile acid-binding resin. Bile acid-binding resins are orally administered anion-exchange resins that are not absorbed systemically. These agents bind bile acids and reduce their reabsorption at the level of the terminal ileum and prevent their enterohepatic recirculation. Colesevelam has a favorable side effect and toxicity profile and significantly impacts serum levels of lipoproteins when used as monotherapy or when used in combination with either statins or ezetimibe.     

Inflammation in coronary artery disease: potential role for immunomodulatory therapy

Understanding of the mechanisms underlying atherosclerotic disorders has evolved beyond the view of a progressive collection of lipids and cellular debris in the vascular wall. Current evidence has implicated inflammatory pathways as an important pathogenic mechanism in atherogenesis and plaque destabilization. Although not necessarily the primary event, inflammation and cytokine activation during plaque formation and destabilization may represent a common final pathway to various stimuli. Thus, it seems that not only ‘new’ risk factors, such as infections with various microorganisms, but also classic risk factors for cardiovascular disease, such as hyperlipidemia, hypertension and diabetes, may promote their atherogenic effects through inflammatory rersponses. Indeed, recent reports have suggested that traditional cardiovascular medications may attenuate atherogenesis and enhance plaque stability, at least partly through anti-inflammatory mechanisms. However, uncovering the inflammatory pathways in atherosclerosis has raised the possibility that newer treatment modalities should be more directly targeted against inflammatory mediators. Recently, a series of experimental studies have reported reduction of atherosclerosis by immunomodulatory therapy, such as chemokine blockade, interleukin-10 and immunization/vaccination against oxidized low-density lipoprotein and heat-shock protein. It is conceivable that some of these approaches will be tested clinically and, if successful, they could provide novel treatment strategies in coronary artery disease in humans.     

The role of infection and immunity in atherosclerosis

Cardiovascular diseases account for 20% of deaths worldwide, rising to 50% in developed countries. Current understanding of atherosclerosis derives from a combination of research in animals and cell cultures, analysis of human lesions, clinical investigations of patients with acute coronary syndromes and epidemiological studies of coronary artery disease. By measuring serologic titers in the serum of patients after cardiovascular events, it was observed that the greater the infectious exposure of a patient, the larger the atherosclerotic lesion extension. In addition, gene targeting or pharmacological inhibition of certain cytokines aggravates atherosclerosis in animal experiments. Other animal experiments have succeeded in proving that B cells play a protective role in atherosclerosis through induced immunity against oxidized low-density lipoprotein and other epitopes. Molecular mimicry might respond to the question of how infection may trigger vulnerability in previously stable atherosclerotic lesions. The FLU Vaccination Acute Coronary Syndromes trial enhanced the debate on atherosclerosis prevention by the application of antiflu vaccine. So far, antibiotics have failed to reduce cardiovascular risk, as recent trials could not demonstrate a statistically significant risk reduction. Having assumed atherosclerosis to be an inflammatory disease, the WHO considered the possible role of secondary prevention with antiflu vaccine.     

偏硅酸钠抑制家兔外周血白细胞活性氧的生成

高血脂时外周血白细胞引爆和激活,产生过多活性氧(reactive oxygen species,ROS),抑制过量的ROS产生对于控制动脉粥样硬化(atherosclerosis,AS)发生发展具有重要意义[1].以往研究发现偏硅酸钠( Na2 SiO3)有抗炎效应[2].本实验观察Na2 Si03对家兔外周血白细胞ROS的抑制作用,为NaSi03抗AS机制提供进一步资料.1材料与方法1.1动物:清洁级新西兰家兔(河北医科大学动物中心,合格证号:1004218),雄性,体质量1500 ～2000 g.1.2制备ox-LDL:从健康家兔耳中动脉取血,沉淀法提取低密度脂蛋白,置硫酸铜( CuSO4)溶液中37℃氧化24h得氧化低密度脂蛋白(ox-LDL).     

Carotid stenosis: a comparison between MR and spiral CT angiography

We performed a preliminary study comparing three-dimensional time-of-flight (3 D TOF) magnetic resonance angiography (MRA) and spiral CT angiography (SCTA) in the detection and assessment of internal carotid artery stenosis. Digital subtraction angiography (DSA) was the reference examination. We examined 20 patients with signs of cerebrovascular insufficiency, who underwent MRA, SCTA and DSA within a 3 day period. Both internal carotid arteries were assessed by three blinded readers for degree of stenosis at two different levels (bulb and remaining section) giving a total of 80 assessments. Interobserver variability, sensitivity, specificity, diagnostic accuracy, concordance, overestimation and underestimation were assessed. Interobserver variability was not statistically significant. MRA showed higher sensitivity, specificity, diagnostic accuracy and concordance than SCTA (92.0 % vs 80.8 %, 98.2 % vs 96.4 %, 96.3 % vs 91.3 % and 96.0 % vs 88.0 %, respectively). MRA gave rise to a 5.0 % overestimation rate, whereas SCTA occasioned a 7.5 % underestimation rate. These differences are not statistically significant. These results suggest that MRA is a more useful, noninvasive modality for assessment of the internal carotid artery with a more than 70 % stenosis. Received: 8 August 1997 Accepted: 10 October 1997     

经血管内栓塞治疗颈外动脉—海绵窦瘘

目的：探讨经血管内栓塞治疗３例颈外动脉海绵窦瘘的临床意义。材料和方法：３例颈外动脉海棉窦瘘均经股动脉入路栓塞，采用微螺旋圈和聚乙烯醇颗粒将瘘口闭塞。结果：术后患者临床症状显著改善。随访１个月至１年病情无复发。结论：颅内无血管杂音是其重要体征。将微导管置入瘘口是栓塞成功的关键     

大动脉炎颈动脉狭窄球囊扩张和内支架的治疗

目的：探讨应用球囊扩张和血管内支架治疗大支脉炎、颈动脉狭窄、材料和方法：３例大动脉炎性颈动脉狭窄的患者，狭窄段均超过８ｃｍ，１例单纯球囊扩张；２例球囊扩张后植入Ｗａｌｌｓｔｅｎｔ支架。结果：术后狭窄率均为０，达到了良好的治疗效果，单纯球囊扩张的动脉一年后动脉完全闭塞、西入血管内支架的２例，分别是在４．５个月和４个月检查，一例血管内支架的近端出现了再狭窄，另一例未出现再狭窄。结论：对于大动脉炎性长段