Rural, suburban and urban differences in the self-diagnosis of coronary heart disease in the United States

This study explores rural, suburban and urban differences in coronary heart disease (CHD) using the 2005 Behavior Risk Factor Surveillance Survey conducted in the United States. Although areal context is not often considered in morbidity studies, this study evaluates the importance of place of residence given that areas offer differential access to health infrastructures and different contextual factors that could affect health. Also examined is the role of geographic heterogeneity on the recent racial divergence in CHD in the United States. Results indicate that area of residence is associated with CHD diagnosis, net of health and demographic variables. The area-stratified analysis documents that rural residents are most impacted by exercise and smoking, while being male or above age 50 are most detrimental for suburban residents. In addition, the racial divergence in CHD is driven by differences in rural locales. These findings indicate a disparate impact of geography on CHD and highlight the need for health research to take into account areal context.     

Cholesterol and vitamins: revisited study

The link between low density lipoprotein and coronary heart disease has been widely studied. Oxidized LDL damages the artery wall, and a diet rich in vitamins and low in saturated fat and cholesterol may reduce this risk. Not only hypercholesterolemia but also low levels of high density lipoprotein cholesterol are critical risk factors for atherosclerosis and related diseases. It has been reported that high doses of B complex vitamin may be useful in lowering blood cholesterol and triglyceride levels in the body, however the use of this compound has been limited by an annoying flush and concern for toxicity. Niacin is a B-complex vitamin with anti-atherosclerotic properties and is an effective medication for raising high density lipoprotein. The combination of niacin with other lipid-lowering drugs, such as statins, reduces the dynamic of atherosclerosis disease. In addition, vitamin E is one of the most important lipid soluble anti-oxidants in humans, and reduces atherosclerosis plaque, coronary artery diseases and myocardial infarction. Vitamin E protects the integrity of membranes by inhibiting lipid peroxidation. In this study we revisited the interrelationship between cholesterol, low density lipoproteins and vitamins.     

Autophagy as mechanism for cell death in degenerative aortic valve disease

Once degenerative aortic valve disease becomes symptomatic, valve replacement is necessary for prognostic and symptomatic reasons. In elderly patients, symptoms of degenerative aortic valve can often be doubtful. Therefore, it is difficult but important to distinguish patients who need surgery from those who do not. Estimation of the rate of the progression of this disease can be helpful herein because one needs to bear in mind that aortic valve degeneration is an active process, which can influence the rate of progression. Recently, autophagy was discovered as a mechanism of cell death in different cardiovascular diseases such as atherosclerosis, aortic valve degeneration, heart failure and at regions around heart infarctions. Thus understanding autophagy in all its details can be helpful to contribute insights into the cell death machinery of cardiovascular diseases. This could open ways for inhibition of cell death in cardiovascular disease and possibly define targets for future drug design.     

Genetics of arterial prothrombotic risk states

Coronary artery disease is a leading cause of death worldwide and the largest killer of men and women in the United States. The pathophysiology of myocardial infarction is multifactorial, and numerous physiologic systems converge to dictate the formation of the two fundamental lesions, thrombosis and atherosclerosis. In this review we address genetic aspects of arterial thrombosis and the key thrombotic factors that have been associated with the increased risk for its development. Specifically, we consider components of coagulation, fibrinolysis, and platelet adhesive receptors, and we review the genetic epidemiology and in vitro laboratory data regarding their risk for the acute coronary syndromes. In combination with traditional risk factor assessment, in the near future these inherited markers can be used to manage patients with vascular disease through a better utilization of invasive or expensive diagnostic testing, as well as pharmacologic intervention.     

Cytochrome P450 et activation génétique — de la pharmacologie à l’élimination du cholestérol et à la régression de l’athérosclérose

Background

Lipoproteins are closely associated with the atherosclerotic vascular process. Elevated levels of highdensity lipoprotein cholesterol (HDL-C) and apolipoprotein AI (apo AI) in plasma indicate a low probability of coronary heart disease (CHD) together with enhanced longevity, and elevated levels of low-density lipoproteincholesterol (LDL-C) and apo B indicate an increased risk of CHD and death. Studies linking gene activation and the induction of cytochrome P450 with elevated plasma levels of apo AI and HDL-C and lowered plasma levels of LDL-C presented a new potential approach to prevent and treat atherosclerotic disease.

Objective and methods

This is a review aimed at clarifying the effects of P450-enzymes and gene activation on cholesterol homeostasis, the atherosclerotic vascular process, prevention and regression of atherosclerosis and the manifestation of atherosclerotic disease, particularly CHD, the leading cause of death in the world.

Results

P450-enzymes maintain cellular cholesterol homeostasis. They respond to cholesterol accumulation by enhancing the generation of hydroxycholesterols (oxysterols) and activating cholesterol-eliminating mechanisms. The CYP7A1, CYP27A1, CYP46A1 and CYP3A4 enzymes generate major oxysterols that enter the circulation. The oxysterols activate — via nuclear receptors — ATP-binding cassette (ABC) A1 and other genes, leading to the elimination of excess cholesterol and protecting arteries from atherosclerosis. Several drugs and nonpharmacologic compounds are ligands for the liver X receptor, pregnane X receptor and other receptors, activate P450 and other genes involved in cholesterol elimination, prevent or regress atherosclerosis and reduce cardiovascular events.

Conclusions

P450-enzymes are essential in the physiological maintenance of cholesterol balance. They activate mechanisms which eliminate excess cholesterol and counteract the atherosclerotic process. Several drugs and nonpharmacologic compounds induce P450 and other genes, prevent or regress atherosclerosis and reduce the occurrence of non-fatal and fatal CHD and other atherosclerotic diseases.     

Vascular smooth muscle cell proliferation in the pathogenesis of atherosclerotic cardiovascular diseases

Atherosclerosis is the principal cause of myocardial infarction, stroke, and peripheral vascular disease, accounting for nearly half of all mortality in developed countries. For example, it has been estimated that atherosclerosis leads to approximately 500,000 deaths from coronary artery disease and 150,000 deaths from stroke every year in the United States (American Heart Association, 1996). Percutaneous transluminal angioplasty has become a well-established technique for revascularization of occluded arteries. However, the long-term efficacy of the procedure remains limited by progressive vessel renarrowing (restenosis) within the following few months after angioplasty. Abnormal vascular smooth muscle cell (VSMC) proliferation is thought to play an important role in the pathogenesis of both atherosclerosis and restenosis. Accordingly, considerable effort has been devoted to elucidate the mechanisms that regulate cell cycle progression in VSMCs. In the present article, we will review the different factors that are involved in the control of VSMC proliferation, especially in the context of cardiovascular disease. Ultimately, a thorough understanding of these regulatory networks may lead to the development of novel drug and gene therapies for the treatment of cardiovascular diseases. Therapeutic approaches that targeted specific cell-cycle control genes or growth regulatory molecules which effectively inhibited neointimal lesion formation will be also discussed.     

药物作用靶点研究最新进展

通过对我国学者近2年在国内外发表的相关论文进行检索和整理,分类综述针对神经退行性疾病（如阿尔茨海默病、帕金森病等）、心血管疾病（如高血压、心律失常、心衰、冠心病、心肌梗死、动脉粥样硬化等）、脑血管疾病、代谢类疾病（如肥胖症、血脂异常、脂肪肝、糖尿病等）、感染性疾病（如艾滋病、流感、结核病等）、恶性肿瘤、自身免疫性疾病等多种疾病的药物作用靶点研究最新进展。     

Hyperuricemia and untreated gout are poor prognostic markers among those with a recent acute myocardial infarction

Introduction  

Patients with a history of myocardial infarction (MI) are often at risk for complications, including subsequent MI and death. Use of prognostic markers may aid in preventing these poor outcomes. Hyperuricemia is associated with increased risk for coronary heart disease (CHD) and/or mortality; however, it is unknown if serum urate (sUA) levels predict outcomes in patients with previous MI. The purpose of this study was to assess hyperuricemia as a biomarker of CHD outcomes in such patients.     

The nature of the problem: an overview of acute coronary syndromes and myocardial infarction

The leading cause of death worldwide is coronary heart disease (CHD). This often presents with atherosclerotic plaque rupture, leading to a partial or complete obstruction of coronary artery flow, and resulting ischemia or infarction of myocardial tissue. There are risk factors which can predict CHD risk, and the treatment of some risk factors can reduce the likelihood of developing an acute coronary syndrome (ACS). While the incidence of CHD may be decreasing in the developed world, significant increases are projected in the developing world. In addition to the immediate adverse events associated with ACS, these patients have long-term increases in morbidity and mortality, which make the worldwide epidemic of CHD a leading public health issue.     

60-kDa heat shock protein of Chlamydia pneumoniae is a target of T-cell immune response

Inflammatory processes contribute to the pathogenesis and complications of atherosclerosis and coronary heart disease (CHD). Several findings indicate that chlamydial heat shock proteins (HSP) may represent a particularly strong antigenic stimulus, able to induce specific humoral (Ab) and T-cell-mediated immune responses (CMI) linking infection by Chlamydia pneumoniae (CP) to immuno-pathological sequelae such as atherosclerosis and CHD. We have here evaluated the ability of chlamydial recombinant (r) HSP60 and rHSP10 to induce specific immune responses in human peripheral blood lymphocytes and in murine models. rHSP60, but not rHSP10, was shown to induce proliferation and Interferon-gamma secretion in lymphocytes of randomly selected blood donors, as well as to generate and detect delayed-type hypersensitivity response in HSP60-vaccinated mice. Overall, the present study provides new hints to evaluate a previous exposition to CP using rHSP60 in humans. Thus the evaluation of specific HSP60 CMI response in healthy subject could be useful to monitor the reactivity to Chlamydia pneumoniae possibly providing a link to CHD pathologies.     

Cholesterol metabolism modulators and the future of atherosclerosis therapy

Atherosclerosis is a disease characterized by lipid accumulation in the vascular wall leading to myocardial infarction or stroke. Hypercholesterolemia is an important risk factor and current treatments are largely based on cholesterol lowering. In spite of proven efficacy of existing drugs, like statins, cardiovascular diseases still remain the most common cause of death in industrialised countries. Many new molecular targets are being studied to improve atherosclerosis treatment and reduce the number of deaths. The action on these targets could lead to a decrease of blood cholesterol levels or produce a direct anti-atherosclerotic effect on the vascular wall. A cholesterol lowering effect could be achieved by reducing cholesterol synthesis (squalene synthase inhibitors), intestinal cholesterol absorption as well as intestinal and liver lipoprotein secretion (microsomal transfer protein inhibitors, acyl-coenzyme A-cholesterol acyltransferase inhibitors) or by increasing fecal excretion of bile acids (ileal sodium-dependent bile acid transporter inhibitors). An anti-atherosclerotic effect on the vascular wall could be achieved by reducing the inflammation via activation of peroxisome proliferator activated receptors, or, more particularly, could consist of decreased expression of adhesion molecules and chemoattractant proteins. Increasing the adenosine triphosphate-binding cassette A1 protein and inhibiting acyl-coenzyme A :cholesterol acyltransferase 1 activity could slow down formation of foam cells, which are a hallmark of atherosclerosis. Finally, the cholesterol fraction carried by high density lipoproteins, which is inversely correlated to cardiovascular risk, could be increased by cholesterol ester transfer protein inhibitors. All of these new classes of compounds are currently studied by pharmaceutical companies and are in different phases of development (preclinical or clinical).     

Nanotechnology for synthetic high-density lipoproteins

Atherosclerosis is the disease mechanism responsible for coronary heart disease (CHD), the leading cause of death worldwide. One strategy to combat atherosclerosis is to increase the amount of circulating high-density lipoproteins (HDL), which transport cholesterol from peripheral tissues to the liver for excretion. The process, known as reverse cholesterol transport, is thought to be one of the main reasons for the significant inverse correlation observed between HDL blood levels and the development of CHD. This article highlights the most common strategies for treating atherosclerosis using HDL. We further detail potential treatment opportunities that utilize nanotechnology to increase the amount of HDL in circulation. The synthesis of biomimetic HDL nanostructures that replicate the chemical and physical properties of natural HDL provides novel materials for investigating the structure-function relationships of HDL and for potential new therapeutics to combat CHD.     

HDL and triglyceride as therapeutic targets

PURPOSE OF REVIEW: Epidemiological studies have shown that plasma HDL-cholesterol is inversely related to coronary artery disease and that there is an inverse relationship between HDL-cholesterol and triglyceride levels, but it is now demonstrated that hypertriglyceridemia is an independent risk factor for coronary heart disease (CHD). The goal of this review is to discuss if triglycerides and HDL-cholesterol could be therapeutic targets to reduce cardiovascular risk. RECENT FINDINGS: Triglyceride measurement is not informative on the specificity of the triglyceride-rich lipoproteins present in the plasma because some of these are not atherogenic (chylomicrons, large VLDLs) while others are highly atherogenic (small VLDLs, remnants, IDL...). Statins, in addition to reducing LDL-cholesterol, significantly reduced atherogenic remnant lipoprotein cholesterol levels. 4S, CARE+LIPID, and AFCAPS/TexCAPS studies, suggested enhanced therapeutic potential of statins for improving triglyceride and HDL-cholesterol levels in patients with CHD. A fibrate (gemfibrozil) was shown to reduce death from CHD and non-fatal myocardial infarction in secondary prevention of CHD in men with low levels of HDL-cholesterol (VA-HIT); during the treatment these levels predicted the magnitude of reduction in risk for CHD events. SUMMARY: ATP III recommendations state, on triglycerides and HDL-cholesterol as targets to reduce cardiovascular risk: (1) that lowering LDL-cholesterol levels is the primary target of therapy, (2) a secondary target is to achieve a triglyceride level < 150 mg/dL and (3) clinical trial data are considered to be insufficient to support recommended a specific HDL-cholesterol goal even if HDL-cholesterol < 40 mg/dL is considered to be a major risk factor of CHD.     

冠心病全基因组关联研究进展

近年来全基因组关联研究在世界范围内发展迅猛,研究者应用全基因组关联研究策略发现了一系列疾病的相关基因或变异,将疾病的基因组研究推向一个新的阶段。冠心病是一种由环境因素和遗传因素共同作用导致的复杂疾病,且是世界范围内死亡和致残的首要原因之一,世界各地的研究者应用此策略发现了候选基因关联研究未曾发现的多个冠心病相关易感区域。文章对近年来世界范围内针对冠心病的全基因组关联研究取得的重要进展进行简要总结,然后就现阶段全基因组关联研究所面临的挑战以及对未来研究的发展趋势进行分析阐述,为进一步探究冠心病的遗传机制提供指导。     

Autophagy as Mechanism for Cell Death in Degenerative Aortic Valve Disease: An Underestimated Phenomenon in Cardiovascular Diseases

Once degenerative aortic valve disease becomes symptomatic, valve replacement is necessary for prognostic and symptomatic reasons. In elderly patients, symptoms of degenerative aortic valve can often be doubtful. Therefore, it is difficult but important to distinguish patients who need surgery from those who do not. Estimation of the rate of the progression of this disease can be helpful herein because one needs to bear in mind that aortic valve degeneration is an active process, which can influence the rate of progression. Recently, autophagy was discovered as a mechanism of cell death in different cardiovascular diseases such as atherosclerosis, aortic valve degeneration, heart failure and at regions around heart infarctions. Thus understanding autophagy in all its details can be helpful to contribute insights into the cell death machinery of cardiovascular diseases. This could open ways for inhibition of cell death in cardiovascular disease and possibly define targets for future drug design.

Addendum to:

Histological Evaluation of Autophagic Cell Death in Calcified Aortic Valve Stenosis

P. Somers, M. Knaapen, M. Kockx, H. Bortier and W. Mistiaen W

J Heart Valve Dis 2006;15:43-8     

皂苷类成分对血管内皮细胞功能的调节作用研究进展

血管内皮细胞在维持血管生理稳态中发挥了重要的作用,其功能障碍是动脉粥样硬化、冠心病、脑卒中、肿瘤等多种重大疾病发生发展的病理基础,调节血管内皮细胞功能是防治上述疾病的主要途径之一。大量研究表明,皂苷类成分可通过改善血管内皮功能达到治疗疾病的目的。综述了近年来报道的皂苷类成分调节血管内皮功能的研究进展,旨在为皂苷类成分作用机制的阐明和相关重大疾病的防治提供一定参考。     

Plasma lipids and lipoprotein patterns in angiographically graded atherosclerosis of the legs and in coronary heart disease.

The prevalence and type of plasma lipoprotein abnormalities were determined in 114 French-Canadian patients with angiographically proven peripheral vascular disease (PVD). The severity of atherosclerosis was positively correlated with plasma triglyceride concentration, especially in the younger patients (r = 0.29, P less than 0.05), and (not significantly) with plasma cholesterol concentration. Of the risk factors believed to predispose individuals to atherosclerosis, cigarette smoking was the most frequently found in the PVD patients (72.8%), especially among the men. Combination of two or more risk factors was the rule. Findings were compared with those in 114 patients who had undergone coronary angiography for suspected coronary heart disease (CHD). The CHD patients were, on average, younger by 10 years. Hyperlipidemia was present in 58.8% of CHD patients, compared with 43.9% of PVD patients. A far higher proportion of CHD patients showed the type II plasma lipoprotein pattern (24.6% v. 7.9%), although the type IV pattern was more common in both groups (31.6% and 28.9%, respectively). A high proportion of all patients (56.1% with PVD and 41.2% with CHD) showed a normal lipoprotein pattern on paper electrophoresis.     

Mutation C3256T of Mitochondrial Genome in White Blood Cells: Novel Genetic Marker of Atherosclerosis and Coronary Heart Disease

This study was undertaken to examine the association between the level of heteroplasmy for the mutation C3256T in human white blood cells and the extent of carotid atherosclerosis, as well as the presence of coronary heart disease (CHD), the major clinical manifestation of atherosclerosis. Totally, 191 participants (84 men, 107 women) aged 65.0 years (SD 9.4) were recruited in the study; 45 (24%) of them had CHD. High-resolution B-mode ultrasonography of carotids was used to estimate the extent of carotid atherosclerosis by measuring of the carotid intima-media thickness (cIMT). DNA samples were obtained from whole venous blood, and then PCR and pyrosequencing were carried out. On the basis of pyrosequencing data, the levels of C3256T heteroplasmy in DNA samples were calculated. The presence of the mutant allele was detected in all study participants; the level of C3256T heteroplasmy in white blood cells ranged from 5% to 74%. The highly significant relationship between C3256T heteroplasmy level and predisposition to atherosclerosis was revealed. In individuals with low predisposition to atherosclerosis the mean level of C3256T heteroplasmy was 16.8%, as compared to 23.8% in moderately predisposed subjects, and further to 25.2% and 28.3% in significantly and highly predisposed subjects, respectively. The level of C3256T heteroplasmy of mitochondrial genome in human white blood cells is a biomarker of mitochondrial dysfunction and risk factor for atherosclerosis; therefore, it can be used as an informative marker of genetic susceptibility to atherosclerosis, coronary heart disease and myocardial infarction.     

Hippo信号通路与心血管发育及疾病调控

心血管疾病已成为中国乃至全球首位死亡原因,探索心血管系统发育及调控异常的原因及相关机制可以为心血管疾病的预防和治疗提供重要的科学依据。Hippo信号通路是新近发现的在调节器官大小、细胞增殖及凋亡、干细胞命运等方面具有重要功能的一条信号通路。Hippo信号通路的不同成分参与心脏血管的发育和心血管细胞增殖、分化等功能调控,影响损伤后修复及再生等过程,该通路调节异常可引起心血管疾病,如心梗、心肌肥大、血管内膜增生、动脉硬化等。本文综述了Hippo信号通路对心血管系统发育和疾病调控的相关研究及最新进展,以期为Hippo通路在心血管疾病的发病机制及临床转化研究提供潜在的理论基础。     

Quest for novel cardiovascular biomarkers by proteomic analysis

Atherosclerosis, and the resulting coronary heart disease and stroke, is the most common cause of death in developed countries. Atherosclerosis is an inflammatory process that results in the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in the acute clinical complications of myocardial infarction (MI) and stroke. Although certain risk factors (dyslipidemias, diabetes, hypertension) and humoral markers of plaque vulnerability (C-reactive protein, interleukin-6, 10 and 18, CD40L) have been identified, a highly sensitive and specific biomarker or protein profile, which could provide information on the stability/vulnerability of atherosclerotic lesions, remains to be identified. In this review, we report several proteomic approaches which have been applied to circulating or resident cells, atherosclerotic plaques or plasma, in the search for new proteins that could be used as cardiovascular biomarkers. First, an example using a differential proteomic approach (2-DE and MS) comparing the secretome from control mammary arteries and atherosclerotic plaques is displayed. Among the different proteins identified, we showed that low levels of HSP-27 could be a potential marker of atherosclerosis. Second, we have revised several studies performed in cells involved in the pathogenesis of atherosclerosis (foam cells and smooth muscle cells). Another approach consists of performing proteomic analysis on circulating cells or plasma, which will provide a global view of the whole body response to atherosclerotic aggression. Circulating cells can bear information reflecting directly an inflammatory or pro-coagulant state related to the pathology. As an illustration, we report that circulating monocytes and plasma in patients with acute coronary syndromes has disclosed that mature Cathepsin D is increased both in the plasma and monocytes of these patients. Finally, the problems of applying proteomic approach directly to plasma will be discussed. The purpose of this review is to provide the reader with an overview of different proteomic approaches that can be used to identify new biomarkers in vascular diseases.