The Pathology of Coronary Heart Disease

The distribution of coronary atherosclerosis in patients with ischemic heart disease is extensive, and involves at least two major coronary arteries. Thrombosis, occlusion by atheromatous debris and, infrequently, internal hemorrhage may produce final closure of the coronary artery. The anatomy of the coronary vessels, localization of occlusion, recanalization, the extent of intercoronary anastomoses and the physiological demands of the myocardium all affect the ultimate clinical expression of the basic occlusive process.     

Analysis of Gene Complexes Predisposing to Coronary Atherosclerosis

The following seven polymorphic marker loci of genes responsible for predisposition to coronary atherosclerosis (CAS) were studied: the ACE locus responsible for angiotensin-converting enzyme insertion/deletion polymorphism for the presence or absence of the Alu insertion in the gene; the F13,PLAT, and APOA1 loci, controlling the clotting factor 13, plasminogen-activating tissue factor, and apolipoprotein A, respectively; the MTHFR and AGT polymorphic loci responsible for point mutations in methylenetetrahydrofolate reductase and those in angiotensinogen, respectively, and the NOS3 locus controlling the number of tandem repeats in the nitric oxide synthase gene. These loci are located on different chromosomes and encode products involved into various metabolic pathways leading to CAS. In the populations studied, significant differences between healthy subjects and patients predisposed to cardiovascular diseases were revealed with regard to the above seven markers. The 174M allele (T174M polymorphism in the AGT gene) was significantly associated with coronary atherosclerosis. It was found that specific gene combinations are involved in the CAS development and determine variation in the pathogenetically important quantitative traits.     

The Relationship Between Serum Levels of Zn and Cu and Severity of Coronary Atherosclerosis

The essential trace elements play important roles in the maintainance of the normal structure and physiology of cells. Several research groups have demonstrated that they also play important roles in states of cardiovascular diseases. Our aim is to investigate whether there is a relationship between trace elements (Zn and Cu) and the degree of atherosclerosis. The sample consisted of 67 patients with coronary artery disease and 26 clinically healthy individuals. Ninety-three subjects were separated into four groups according to their Gensini scores, the number of diseased vessels, the presence of acute coronary syndrome, and ejection fraction. Each group was divided into three subgroups, and serum zinc and copper levels were measured for each individual. The serum levels of zinc and copper were found to be significantly lower in patients with atherosclerosis than in the control group, but there were no significant differences in the serum levels of Cu and Zn between severe atherosclerosis and mild atherosclerosis. In Spearman's rank correlation, the zinc and copper levels were correlated with the Gensini score and the number of diseased vessels. The present study revealed a relationship between the serum levels of zinc and copper and atherosclerosis, but not between these levels and the severity of the disease.     

冠心病患者颈动脉粥样硬化与血管内皮功能的临床研究价值

目的:探讨颈动脉粥样硬化与血管内皮功能与冠心病患者的相关性。方法:选取114例冠心病患者(54例单支病变和60例多支病变)为观察组和60例健康体检者为对照组,对两组患者动脉粥样硬化及血管内皮功能进行分析。结果:观察组患者TC、TG、HDL及血糖水平均高于对照组,观察组LDL水平显著低于对照组,两组比较差异有统计学意义(P<0.05);观察组患者颈动脉IMT、斑块积分及斑块数明显高于对照组(P<0.05),观察组FMD显著降低(P<0.05),多支病变组病变程度更严重(P<0.05)。结论:颈动脉粥样硬化与血管内皮功能可作为预测冠心病的重要指标,对预防和治疗冠心病具有重要意义。     

Visualization of Coronary Wall Atherosclerosis in Asymptomatic Subjects and Patients with Coronary Artery Disease Using Magnetic Resonance Imaging

Background

Magnetic resonance imaging (MRI) is sensitive to early atherosclerotic changes such as positive remodeling in patients with coronary artery disease (CAD). We assessed prevalence, quality, and extent of coronary atherosclerosis in a group of healthy subjects compared to patients with confirmed CAD.

Methodology

Twenty-two patients with confirmed CAD (15M, 7F, mean age 60.4±10.4 years) and 26 healthy subjects without history of CAD (11M, 15F, mean age 56.1±4.4 years) underwent MRI of the right coronary artery (RCA) and vessel wall (MR-CVW) on a clinical 1.5T MR-scanner. Wall thickness measurements of both groups were compared.

Principal Findings

Stenoses of the RCA (both < and ≥50% on CAG) were present in all patients. In 21/22 patients, stenoses detected at MRI corresponded to stenoses detected with conventional angiography. In 19/26 asymptomatic subjects, there was visible luminal narrowing in the MR luminography images. Fourteen of these subjects demonstrated corresponding increase in vessel wall thickness. In 4/26 asymptomatic subjects, vessel wall thickening without luminal narrowing was present. Maximum and mean wall thicknesses in patients were significantly higher (2.16 vs 1.92 mm, and 1.38 vs 1.22 mm, both p<0.05).

Conclusions

In this cohort of middle-aged individuals, both patients with stable angina and angiographically proven coronary artery disease, as well as age-matched asymptomatic subjects. exhibited coronary vessel wall thickening detectable with MR coronary vessel wall imaging. Maximum and mean wall thicknesses were significantly higher in patients. The vast majority of asymptomatic subjects had either positive remodeling without luminal narrowing, or non-significant stenosis.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00456950","term_id":"NCT00456950"}}NCT00456950     

Microparticle-Induced Coagulation Relates to Coronary Artery Atherosclerosis in Severe Aortic Valve Stenosis

Background

Circulating microparticles (MPs) derived from endothelial cells and blood cells bear procoagulant activity and promote thrombin generation. Thrombin exerts proinflammatory effects mediating the progression of atherosclerosis. Aortic valve stenosis may represent an atherosclerosis-like process involving both the aortic valve and the vascular system. The aim of this study was to investigate whether MP-induced thrombin generation is related to coronary atherosclerosis and aortic valve calcification.

Methods

In a cross-sectional study of 55 patients with severe aortic valve stenosis, we assessed the coronary calcification score (CAC) as indicator of total coronary atherosclerosis burden, and aortic valve calcification (AVC) by computed tomography. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation. Circulating MPs were characterized by flow cytometry according to the expression of established surface antigens and by measuring MP-induced thrombin generation.

Results

Patients with CAC score below the median were classified as patients with low CAC, patients with CAC Score above the median as high CAC. In patients with high CAC compared to patients with low CAC we detected higher levels of TATc, platelet-derived MPs (PMPs), endothelial-derived MPs (EMPs) and MP-induced thrombin generation. Increased level of PMPs and MP-induced thrombin generation were independent predictors for the severity of CAC. In contrast, AVC Score did not differ between patients with high and low CAC and did neither correlate with MPs levels nor with MP-induced thrombin generation.

Conclusion

In patients with severe aortic valve stenosis MP-induced thrombin generation was independently associated with the severity of CAC but not AVC indicating different pathomechanisms involved in coronary artery and aortic valve calcification.     

Identification of Hub Genes Associated with Abnormal Endothelial Function in Early Coronary Atherosclerosis

Biochemical Genetics - Abnormal coronary endothelial function is an important step in the development of atherosclerosis. Coronary atherosclerosis is one of the main causes of death worldwide. We...     

Social Stress,Visceral Obesity,and Coronary Artery Atherosclerosis in Female Primates

Our previous work in cynomolgus monkeys demonstrated significant relationships between (i) social reorganization stress and visceral fat deposition, and (ii) central fat deposition and coronary artery atherosclerosis (CAA). Nevertheless, direct relationships between CAA and visceral fat have not been demonstrated in people or animals, nor have relationships among stress, visceral obesity, and CAA been observed within a single study. Here, we examine the hypothesis that visceral obesity provides a link between social stress and CAA. Subjects were 41 socially housed females that consumed an atherogenic diet for 32 months. Social behavior and ovarian function were continuously recorded; dexamethasone suppression tests, telemetered overnight heart rate, BMI, visceral (VAT) and subcutaneous abdominal (SAT) adipose tissue were measured before necropsy. Females with high VAT:SAT were relatively subordinate, socially isolated, received more aggression and less grooming, desensitized to circulating glucocorticoids, had impaired ovarian function, higher heart rates late in the day, and more CAA than low VAT:SAT females. High‐BMI females had higher heart rates than low‐BMI females. Poor ovarian function in high VAT:SAT females is a novel observation suggesting the need for studies of fat distribution and ovarian function in women. The results of this study are the first to demonstrate a relationship between CAA and visceral obesity, and suggest that social stress may exacerbate CAA in part by increasing the ratio of visceral:subcutaneous fat mass in selected individuals susceptible to diet‐induced CAA. Further studies are needed to understand the complex and multifactorial temporal relationship among relative visceral obesity, physiological stress responses, and CAA.     

动脉硬化仿真模拟分析

目的：通过对血管中血液流动对血管的影响及血液内低密度脂蛋白（sLDL）微粒行为的模拟分析,研究动脉粥样硬化产生的血流动力学原因。方法：第一步,使用流体力学软件CFD,建立动脉血管弯曲分叉仿真模型;第二步,分析血液流动特性,跟踪血液中15—25纳米尺度范围类的sLDL粒子在动脉分叉模型中的流体力学行为,研究sLDL在血液流速稳定下在血管中的空间分布及流场特征分布。结果：血管起始段出现压强很高的区域。在动脉血管弯曲内侧处及分岔处的分支外侧血液流动较慢,并且在这些部位出现压强较高的区域。在血管弯曲外侧处及分岔点处,sLDL与血管壁发生碰撞的几率较其它位置较高,粒子在血管上沉积高发区域在这些部位呈斑块状分布。讨论及结论：在血管起始段的高压,可能是导致这一部分血管损伤,并进而引起动脉硬化形成的主要原因;在动脉血管弯曲外侧处及分岔点处出现的高压低速血流分布,一方面增大了血液中包括sLDL粒子在内的致病因子与血管壁的接触时间,另一方面则引起这些部位血清的侧漏加强,出现所谓的’浓度极化’现象,从而导致这些部位出现高浓度的sLDL分布,增大sLDL粒子与血管壁的接触几率;粒子在血管上沉积高发区域往往存在于动脉血管分岔点处,而在血管弯曲外侧处也有较高几率沉淀,呈斑状分布;长期性轻微性振动的剪切压力的作用使多数血管内皮细胞性质改变,促进动脉硬化形成。在动脉血管起始段、弯曲处及分岔点处血液的高压低速分布、sLDL粒子的高沉积率及低剪切应力等是动脉硬化产生及演化的重要因素.     

Coronary arterial calcification in rheumatoid arthritis: comparison with the Multi-Ethnic Study of Atherosclerosis

Introduction

Although cardiovascular morbidity and mortality are increased in rheumatoid arthritis, little is known about the burden of subclinical coronary atherosclerosis in these patients.

Methods

Using computed tomography, coronary artery calcification was measured in 195 men and women with rheumatoid arthritis aged 45 to 84 years without clinical cardiovascular disease and compared with 1,073 controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis.

Results

The prevalence of coronary calcification (Agatston score > 0) was significantly higher in men, but not women, with rheumatoid arthritis after adjusting for sociodemographic and cardiovascular risk factors (prevalence ratio = 1.19; P = 0.012). Among participants with prevalent calcification, those with rheumatoid arthritis had adjusted mean Agatston scores 53 units higher than controls (P = 0.002); a difference greater for men than women (P for interaction = 0.017). In all analyses, serum IL-6 attenuated the association between rheumatoid arthritis and coronary calcification, suggesting its role as a potential mediator of enhanced atherosclerosis. Notably, increasing severity of rheumatoid arthritis was associated with a higher prevalence and extent of coronary calcification among both men and women with rheumatoid arthritis, and for all age categories. The largest percentage difference in coronary arterial calcification between rheumatoid arthritis patients and their nonrheumatoid arthritis counterparts was observed in the youngest age category.

Conclusions

Increasing rheumatoid arthritis disease severity was associated with a higher prevalence and greater extent of coronary artery calcification, potentially mediated through an atherogenic effect of chronic systemic inflammation. Gender and age differences in association with coronary calcification suggest that preventive measures should be emphasized in men with rheumatoid arthritis, and considered even in younger rheumatoid arthritis patients with low levels of traditional cardiovascular risk factors.