Atherosclerosis

Is atherosclerosis a cellular or humoral mediated autoimmune disease?     

Atherosclerosis

It is generally considered that the genetics of atherosclerosis and its complications involves a large number of genes with common alleles having weak effects on disease risk but possibly interacting with each other and with nongenetic factors. In such a complex system, absence of marginal effects (effects of polymorphisms considered one at a time) is insufficient to exclude the implication of a polymorphism on disease risk. Investigating polymorphisms and even genes one by one is no longer appropriate. It is necessary to focus on biological systems and integrate the contribution of genetic as well as non-genetic factors and their interactions. Hopefully, system genetics will ultimately improve our understanding of the genetic architecture of complex traits. “Irecognized that an organism must never be looked upon as a mere mosaic of ‘unit characters’, each determined by a single gene, but rather as a network of interaction systems.”—Sewall Wright     

Serum Uric Acid Levels and Subclinical Atherosclerosis: Results From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

High serum uric acid (sUA) has been associated with coronary artery calcium (CAC) and increased carotid intima-media thickness (cIMT) in people at high cardiovascular risk. However, association is unclear in apparently healthy individuals. Our study aims to evaluate association between sUA and subclinical atherosclerosis measures: CAC and increased cIMT, in apparently healthy adults enrolled in ELSA-Brasil. A total of 4096 participants without previous coronary artery disease, stroke, and use of urate-lowering drugs, underwent CAC and cIMT assessment. All analyses were stratified by sex. Serum uric acid categorized by quintiles was the exposure variable. Thorough cardiovascular risk factor evaluation was performed, and association between sUA quintiles and CAC and cIMT was analyzed by linear regression using ln(CAC + 1) and cIMT, both as continuous variables. Median age of the sample was 49.0 (44.0-56.0) years (women: 55.1%; 59.1% were white). Mean values of sUA were 6.5 ± 1.4 mg/dL for men, and 4.9 ± 1.2 mg/dL for women. The highest quintile (Q5) of sUA was independently associated with cIMT in women (beta-coefficient: 0.022; 95% CI: 0.007-0.036; P = 0.003) and men (beta-coefficient: 0.020; 95% CI: 0.002-0.038; P = 0.032). Regarding CAC, no association was found: men's Q5 (beta-coefficient: -0.142; 95% CI: -0.436 to 0.153; P = 0.347) and women's Q5 (beta-coefficient: 0.046; 95% CI: -0.152 to 0.245; P = 0.647). In this cohort, the highest sUA quintiles were independently associated with cIMT in both women and men. No association was found between sUA and the presence of CAC.     

颈动脉粥样硬化对冠心病的预测价值

目的：研究超声检测颈动脉粥样硬化对冠心病的预测价值。方法：应用彩色多普勒超声仪观察230例冠心病患者与41例非冠心病患者颈动脉内膜-中膜厚度（IMT）、斑块形成情况和斑块积分。结果：颈动脉IMT与斑块发生率和斑块积分在冠心病组明显高于对照组（P〈0．05）。结论：超声检查颈动脉硬化可在一定程度上反映冠状动脉粥样硬化情况,可帮助评估预后。     

Measurement of Atherosclerosis: Development of an Atherosclerosis Severity Index

Treatment of hypertension has succeeded in preventing the complications attributable to pressure, including heart failure and the arteriolar complications such as brain hemorrhage and renal failure. Recent understanding that antihypertensive drugs have effects on lipoproteins and flow disturbances that may be important in atherosclerosis progression, and the recent development of drugs that are more effective in treating hyperlipidemia, have given impetus to the design of studies to test whether interventions are anti-atherosclerotic. Since studies depending on clinical endpoints by necessity consume vast resources, it is desirable to develop methods for measurement of atherosclerosis, in order to make it possible to conduct intervention studies efficiently. Because angiographic methods are costly and associated with risk, and many patients are unable or unwilling to undergo followup angiography at the end of a study, we are developing an atherosclerosis severity index based on clinical and noninvasive ultrasound assessment. This scale can be used as a surrogate outcome in place of, or complementary to angiographic measurement of atherosclerosis, to avoid costly loss of subjects in intervention studies. It has the additional advantage that it is suitable for repeated assessment over time, permitting the power of analyses such as life table analysis which look at time to development of endpoints.     

Regression of Atherosclerosis

Atherosclerotic cardiovascular disease (CVD) is a complex disorder that leads to premature death and hospitalization. Several drugs have been, or are currently being tested for their ability to reduce cardiovascular mortality and/or promote regression of atherosclerotic lesions. In addition to "hard end point" clinical trials in which total and cardiovascular mortality as well as risk of incident myocardial infarction are considered as outcomes, trials with surrogate end points using imaging biomarkers can rapidly assess the efficacy of new cardiovascular drugs. Low-density lipoprotein-based therapies with statins have been shown to promote atherosclerosis regression, and several other drugs targeting high-density lipoproteins or inflammation/oxidation are currently being tested in both outcomes and imaging trials in which atherosclerosis regression is anticipated. In this review, we focus on the latest progress in CVD and highlight novel drugs that tackle atherosclerosis as well as the currently used and upcoming imaging techniques to optimally measure atherosclerosis progression.     

Atherosclerosis Imaging and the Canadian Atherosclerosis Imaging Network

Atherosclerosis exacts a large toll on society in the form of cardiovascular morbidity, mortality, and resource use and is exacerbated by the epidemics of obesity and diabetes. Consequently, there is a critical need for more-effective methods of diagnosis, treatment, and prevention of the complications of atherosclerosis. Careful and well-conducted large population studies are needed in order to truly understand the natural history of the disease, its imaging biomarkers, and their links to patient outcomes. The Canadian Atherosclerosis Imaging Network (CAIN) is a unique research network funded by the Canadian Institutes of Health Research and the Canada Foundation for Innovation and designed to address these needs and to enable large population-based imaging studies. The central objective of CAIN is to move innovations in imaging toward their broad application in clinical research and clinical practice for the improved evaluation of cardiac and neurologic vascular disease. CAIN is established as an international resource for studying the natural history, progression, and regression of atherosclerosis, as well as novel therapeutic interventions aimed at atherosclerosis. The network represents Canada's leading atherosclerosis imaging experts, embodying both basic imaging science and clinical imaging research. The network is improving methods of detection and treatment of atherosclerosis and, through a better understanding of the underlying disease itself, improving strategies for disease prevention. The benefits are expected to appear in the next 2 to 3 years. CAIN will drive innovation in imaging technology within the field of cardiology and neurology and improve health outcomes in Canada and worldwide.     

Atherosclerosis imaging

Atherosclerosis imaging has become increasingly important in the understanding of the natural history of coronary artery disease and the processes leading to luminal narrowing, as well as in the assessment of disease burden and therapy efficacy. Intravascular ultrasound (IVUS) has emerged as the new gold standard for atherosclerosis imaging because it provides cross-sectional images of both the arterial wall and lumen with excellent resolution, reveals the diffuse nature of atherosclerosis and the involvement of reference segments, and takes into account vessel wall remodelling. In addition to its clinical indications, IVUS is now widely used as the primary efficacy assessment measure of several antiatherosclerotic approaches in randomized clinical trials. The advantages of using IVUS include its ability to reveal antiatherosclerotic effects within a relatively short period of time and with a reasonable sample size, in contrast to trials assessing angiographic changes or clinical events. IVUS can also help to determine dose-response relationships in the development of novel pharmacological agents. IVUS is currently the ideal imaging modality for clinical trials examining the progression or regression of atherosclerosis.     

Atherosclerosis regression

Atherosclerosis follows the deposition, retention, and oxidative modification of lipoproteins, especially low-density lipoprotein (LDL) in the walls of large arteries. Uptake of oxidized LDL results in the formation of macrophage foam cells. Proliferation of vascular smooth muscle cells and secretion of extracellular matrix contribute "fibrous" components of the plaque, whereas ongoing accumulation of lipid and inflammatory cell debris forms the necrotic lipid core of the mature atherosclerotic plaque. Both the size and composition of plaques determine the clinical course. In particular, a large lipid core, thin fibrous cap, dense inflammatory cell infiltrate, and proteolytic enzyme activity are associated with adverse risk. Atherosclerosis has often been considered a relentlessly progressive disease. However, new imaging techniques that can quantify plaque burden and provide insights into some of the specific plaque components have allowed regression to be mapped for the first time. In this article, drugs targeting atherosclerosis that have potential or proven benefit in atherosclerosis regression are discussed.     

家兔颈动脉粥样硬化对自身肾动脉粥样硬化及肾功能的影响

目的研究家兔颈动脉粥样硬化对肾动脉粥样硬化的影响,并探讨可能的机制。方法16只家兔随机分成高脂饲料加颈动脉空气干燥术组（手术组）和高脂饲料加假手术组（对照组）,手术前及术后8周测定家兔血肌酐、血管紧张素Ⅱ（AngⅡ）水平,处死后作病理检查,测量及比较颈动脉和肾动脉动脉内膜中膜比值。结果两组的血肌酐水平差异无统计学意义（P＞0.05）,但手术组的AngⅡ水平（43.23±0.12）pg/ml,较对照组（37.02±0.42）pg/ml升高,差异有统计学意义（P＜0.05）。手术组的颈动脉内膜中膜比值（1.28±0.08）较对照组（0.04±0.02）高,差异有显著统计学意义（P＜0.01）,同时手术组肾动脉内膜中膜比值（0.45±0.11）也较对照组（0.12±0.04）高,差异有统计学意义（P＜0.05）。结论颈动脉粥样硬化的形成加重了肾动脉粥样硬化的程度,肾素血管紧张素系统的激活可能是机制之一。     

老年人颈动脉粥样硬化与冠状动脉粥样硬化的关系

为探讨老年人颈动脉粥样硬化与冠状动脉粥样硬化的关系,对94例进行冠状动脉造影的老年患者进行颈动脉超声检查。颈动脉粥样硬化斑块积分采用Sutton法,结果发现,冠状动脉病变单支组和多支组内膜一中膜厚度,斑块积分显著高于正常组,冠状动脉病变多支组显著高于单支组（P均＜0．05）,斑块指数与年龄,吸烟,低密度脂蛋白胆固醇／高密度脂蛋白胆固醇比值,收缩压以及高血压病程及程度密切相关,结果提示,颈动脉粥样硬化与冠状动脉粥样硬化的病变是平行的。     

感染和动脉弱样硬化

以动脉粥样硬化为病理基础的心脑血管疾病是目前发病率和死亡率最高的疾病。继续寻找动脉粥样硬化的发病机制 ,以采取切实有效的措施延迟和逆转动脉粥样硬化病变的进展 ,从而降低心脑血管疾病 (急性心肌梗死、脑卒中 )的死亡率 ,仍是目前和今后一段时间内心脑血管疾病研究领域中最重要的课题。目前认为动脉粥样硬化是一个缓慢而复杂的病理过程。血管内皮的损伤和血管内皮功能的减退是引起动脉粥样硬化的始动因素。高血压、高脂血症、糖尿病、吸烟等可能损害血管内皮。血管内皮受损后引起内皮下胶原组织暴露 ,促发血小板粘附聚集 ,使氧自由基…     

颅内动脉粥样硬化的预后

颅内动脉粥样硬化可能存在种族差异，白人颅内动脉粥样硬化性狭窄的发生率较低，发生卒中的风险也较低；而亚洲人颅内动脉粥样硬化性狭窄发生率较高，是卒中复发和血管事件相关性死亡的重要预测因素。经皮腔内血管成形术和支架置入术联合药物治疗能起到较好的预防卒中复发的作用。