The inextricable link between atherosclerosis and prototypical inflammatory diseases rheumatoid arthritis and systemic lupus erythematosus

The increased burden of cardiovascular disease in patients with rheumatoid arthritis and systemic lupus erythematosus has recently become the focus of intense investigation. Proatherogenic risk factors and dysregulated inflammation are the main culprits, leading to enhanced atherosclerosis in subgroups of patients with inflammatory diseases. Common molecular pathways shared by atherosclerosis and inflammatory disease may be involved. In this review we map the key determinants of the increased incidence of cardiovascular disease in patients with inflammatory diseases at each step of the atherogenesis.     

N-3 vs. saturated fatty acids: Effects on the arterial wall

Cardiovascular disease is a leading cause of death worldwide. Atherosclerosis and unstable plaques are underlying causes for cardiovascular diseases. Cardiovascular disease is associated with consumption of diets high in saturated fats. In contrast there is increasing evidence that higher intakes of dietary n-3 fatty acids decrease risk for cardiovascular disease. Recent studies are beginning to clarify how n-3 compared with saturated fatty acids influence cardiovascular disease risk via pathways in the arterial wall. In this paper we will review studies that report on mechanisms whereby dietary fatty acids affect atherosclerosis through modulation of arterial wall lipid deposition, inflammation, cell proliferation, and plaque vulnerability.     

Morphological aspects of age-related adaptation of the arterial vessels of the human kidneys in various cardiovascular diseases

The investigation has been performed in 190 normal kidneys and at certain cardiovascular diseases (atherosclerosis of the abdominal aorta, hypertension, chronic ischemic cardiac disease and their combination). Principally similar morphological structures are mobilized in the process of the renal arterial bed adaptation both normal and at the cardio-vascular diseases studied. Transition from certain functional changes to the organic ones in the muscular tunic and in the elastic membranes of large arteries, in correlation of afferent and deferent glomerular arterioles of all cortical layers is stated, as well as adaptive rearrangement of the microvessels and of the juxtamedullary shunt.     

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。     

Cardiovascular disease in diabetes mellitus type 2: a potential role for novel cardiovascular risk factors

A major consequence of diabetes mellitus type 2 is the accelerated development of atherosclerosis. Assessment of conventional risk factors such as plasma lipids, lipoproteins and hypertension only partly account for the excessive risk of developing cardiovascular disease in this population. Increasing evidence has emerged suggesting that conditions associated with diabetes mellitus type 2, such as insulin resistance, hyperinsulinemia and hyperglycemia, may also play a significant role in regulating 'novel' cardiovascular risk factors. These factors and their potential roles in the development of atherosclerosis and cardiovascular events are discussed in this review.     

Taurine and atherosclerosis

Taurine is abundantly present in most mammalian tissues and plays a role in many important physiological functions. Atherosclerosis is the underlying mechanism of cardiovascular disease including myocardial infarctions, strokes and peripheral artery disease and remains a major cause of morbidity and mortality worldwide. Studies conducted in laboratory animal models using both genetic and dietary models of hyperlipidemia have demonstrated that taurine supplementation retards the initiation and progression of atherosclerosis. Epidemiological studies have also suggested that taurine exerts preventive effects on cardiovascular diseases. The present review focuses on the effects of taurine on the pathogenesis of atherosclerosis. In addition, the potential mechanisms by which taurine suppress the development of atherosclerosis will be discussed.     

Role of trace elements in primary arterial hypertension

A negative relationship between water hardness and cardiovascular mortality rate was demonstrated and became a source of interest regarding minerals and trace metals in the pathogenesis of atherosclerosis, cardiovascular diseases, and arterial hypertension. Higher incidences of sudden death, cerebrovascular diseases, arterial hypertension, and coronary heart disease have been reported in soft water areas. A major research effort has been devoted to the problem in an attempt to find a protective factor in hard water or a detrimental factor or element in soft water. The roles of calcium, magnesium, cobalt, lithium, vanadium, silicon, manganese, and copper have been considered potentially beneficial, whereas those of cadmium, lead, silver, zinc, and antimony have been considered potentially harmful. Cobalt and zinc have been attributed both roles. In the present article, the role of trace quantities of several elements in mineral water in the etiopathogenesis of primary arterial hypertension is reviewed. An erratum to this article is available at .     

Role of trace elements in primary arterial hypertension Is mineral water style or prophylaxis?

A negative relationship between water hardness and cardiovascular mortality rate was demonstrated and became a source of interest regarding minerals and trace metals in the pathogenesis of atherosclerosis, cardiovascular diseases, and arterial hypertension. Higher incidences of sudden death, cerebrovascular diseases, arterial hypertension, and coronary heart disease have been reported in soft water areas. Amajor research effort has been devoted to the problem in an attempt to find a protective factor in hard water or a detrimental factor or element in soft water. The roles of calcium, magnesium, cobalt, lithium, vanadium, silicon, manganese, and copper have been considered potentially beneficial, whereas those of cadmium, lead, silver, zinc, and thallium have been considered potentially harmful. Cobalt and zinc have been attributed both roles. In the present article, the role of trace quantities of several elements in mineral water in the etiopathogenesis of primary arterial hypertension is reviewed.     

The prevalence of cardiovascular disease risk factors in patients from Croatian Zagorje County treated at Department of Medicine, Zabok General Hospital from 2000 to 2006

The aim of the study was to assess the prevalence of risk factors for cardiovascular disease in patients treated for coronary heart disease (CHD) at Department of Medicine, Zabok General Hospital during the 2000-2006 period. Cardiovascular diseases are a group of diseases that occur due to arterial. The risk factors that lead to the development and occurrence of cardiovascular disease are hypertension, cigarette smoking, hyperholesterolemia, hypertriglyceridemia, diabetes mellitus and positive family history. Additional factors favoring the occurrence of cardiovascular disease include overweight, inadequate physical activity, and emotional stress. Data on all patients hospitalized and diagnosed with CHD at Department of Medicine, Zabok General Hospital during the 2000-2006 period were analyzed for the prevalence of risk factors for CHD, i.e. hypertension, cigarette smoking, hypercholesterolemia, hypertriglyceridemia, diabetes mellitus and positive family history of cardiovascular disease. Hypercholesterolemia was defined by a cholesterol level higher than 5.1 mmol/L, hypertension from history data and blood pressure measurement on admission greater than 140/90 mmHg, diabetes mellitus from history data, and hypertriglyceridemia by a triglyceride level greater than 1.7 mmol/L. Information on heredity and cigarette smoking was collected from history and a questionnaire filled out on admission. All laboratory values were determined on patient admission to the hospital. Analysis of the risk factors for CHD recorded in patients from Zagorje County during the 2000-2006 period revealed hypertension to be the most common risk factor in our patients. According to sex, CHD was found to show a male preponderance. According to age at admission, CHD predominated in the > 70 age group, which accounted for one third of all patients, followed by a comparable proportion of the 50-60 and 60-70 age groups, i.e. still active population groups. As CHD is one of the leading health threats worldwide, estimated to remain so at least by 2020, it is fully justified to invest all efforts in the study of cardiovascular disease. New research projects should be focused on the prevention and early detection of the disease, improvement of diagnosis procedures, introduction of novel therapeutic options, use of new concepts, and due survey of the measures taken. CHD poses great socioeconomic burden upon every community in industrialized societies because of the ever younger age at onset. Actions should be taken to improve awareness of the CHD risks and morbidity in the population at large, stimulating favorable lifestyle and dietary modifications, and one's own health awareness, in order to upgrade the control of risk factors for and morbidity of cardiovascular disease.     

Critical developmental periods in the pathogenesis of hypertension

Hypertension is one of the major risk factor of cardiovascular diseases, but after a century of clinical and basic research, the discrete etiology of this disease is still not fully understood. One reason is that blood pressure is a quantitative trait with multifactorial determination. Numerous genes, environmental factors as well as epigenetic factors should be considered. There is no doubt that although the full manifestation of hypertension and other cardiovascular diseases usually occurs predominantly in adulthood and/or senescence, the roots can be traced back to early ontogeny. The detailed knowledge of the ontogenetic changes occurring in the cardiovascular system of experimental animals during particular critical periods (developmental windows) could help to solve this problem in humans and might facilitate the age-specific prevention of human hypertension. We thus believe that this approach might contribute to the reduction of cardiovascular morbidity among susceptible individuals in the future.     

HDL revisited: new opportunities for managing dyslipoproteinaemia and cardiovascular disease

Low concentrations of high-density lipoprotein (HDL) cholesterol constitute a risk factor for coronary heart disease (CHD). There is increasing evidence that increasing HDL-cholesterol levels reduces cardiovascular risk. The phenotype of low HDL cholesterol with or without elevated triglycerides is common and it is characteristic of patients with central obesity, insulin resistance, hypertension and type 2 diabetes mellitus; conditions associated with increased cardiovascular risk and are part of the rubric of the metabolic syndrome. Epidemiological, experimental and clinical trial evidence suggests that there is a good rationale for raising HDL-cholesterol in these and other high-risk patients. The protective effect of HDL-cholesterol against atherosclerosis and cardiovascular disease is mediated by both enhanced reverse cholesterol transport (RCT) and by direct anti-atherosclerotic mechanisms. Recent studies have elucidated mechanisms whereby HDL acts to reduce cardiovascular risk, supporting the rationale for targeting of HDL with lipid-modifying therapy. Ongoing investigation of mechanisms by which HDL acts to reduce the risk of atherosclerosis will provide opportunities for the development of new therapeutic strategies to decrease the risk of atherosclerosis.     

The Association between the History of Cardiovascular Diseases and Chronic Low Back Pain in South Koreans: A Cross-Sectional Study

Background

Cardiovascular disease and related risk factors have been suggested as a mechanism leading to atherosclerosis of the lumbar vessels and consequent lumbar pain or sciatica. But there is continued controversy concerning its generalization. This study examined whether cardiovascular disease or its risk factors were associated with chronic low back pain (cLBP) in Koreans.

Methods

Health surveys and examinations were conducted on a nationally representative sample (n = 23,632) of Koreans. A total of 13,841 eligible participants (aged 20 to 89 years) were examined to determine the association between cardiovascular disease, the Framingham risk score, major cardiovascular risk factors (blood pressure, diabetes, cholesterol, and smoking habits) and chronic LBP.

Results

The total prevalence of cLBP was 16.6% (men: 10.8%, women: 21.1%) and that in patients with a history of cardiovascular diseases was 36.6% (men: 26.5%, women: 47.1%). The results showed that patients’ medical history of cardiovascular disease was significantly associated with cLBP in both men and women when adjusted for covariates (men: OR 2.16; 95%CI 1.34∼3.49; women: OR 2.26; 95%CI 1.51∼3.38). No association was observed between cLBP and the Framingham risk score, medication for hyperlipemia, hypertension, diabetes, and major cardiovascular risk factors (systolic blood pressure, total cholesterol, high density lipoprotein cholesterol, triglycerides, glucose and smoking habits) in either men or women.

Conclusions

The prevalence of cLBP is correlated to a history of cardiovascular disease, but not to the major cardiovascular risk factors from the Framingham study. Further studies on whether these results were affected by psychological factors in patients with a history of cardiovascular diseases or whether new potential risk factors from the artery atherosclerosis hypothesis applying to Koreans exist are needed.     

The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease

The Western-style diet is characterized by its highly processed and refined foods and high contents of sugars, salt, and fat and protein from red meat. It has been recognized as the major contributor to metabolic disturbances and the development of obesity-related diseases including type 2 diabetes, hypertension, and cardiovascular disease. Also, the Western-style diet has been associated with an increased incidence of chronic kidney disease (CKD). A combination of dietary factors contributes to the impairment of renal vascularization, steatosis and inflammation, hypertension, and impaired renal hormonal regulation. This review addresses recent progress in the understanding of the association of the Western-style diet with the induction of dyslipidemia, oxidative stress, inflammation, and disturbances of corticosteroid regulation in the development of CKD. Future research needs to distinguish between acute and chronic effects of diets with high contents of sugars, salt, and fat and protein from red meat, and to uncover the contribution of each component. Improved therapeutic interventions should consider potentially altered drug metabolism and pharmacokinetics and be combined with lifestyle changes. A clinical assessment of the long-term risks of whole-body disturbances is strongly recommended to reduce metabolic complications and cardiovascular risk in kidney donors and patients with CKD.     

Peripheral blood gene expression profiling for cardiovascular disease assessment

Whole blood gene expression profiling has the potential to be informative about dynamic changes in disease states and to provide information on underlying disease mechanisms. Having demonstrated proof of concept in animal models, a number of studies have now tried to tackle the complexity of cardiovascular disease in human hosts to develop better diagnostic and prognostic indicators. These studies show that genomic signatures are capable of classifying patients with cardiovascular diseases into finer categories based on the molecular architecture of a patient's disease and more accurately predict the likelihood of a cardiovascular event than current techniques. To highlight the spectrum of potential applications of whole blood gene expression profiling approach in cardiovascular science, we have chosen to review the findings in a number of complex cardiovascular diseases such as atherosclerosis, hypertension and myocardial infarction as well as thromboembolism, aortic aneurysm, and heart transplant.     

Does a causal relation between cardiovascular disease and periodontitis exist?

Inflammation is believed to play a central part in the pathogenesis of atherosclerosis, and much attention has been paid to the possible association between atherosclerosis and other inflammatory diseases. Periodontal disease is a common inflammatory disease affecting up to 50% of the adult population, and during the past two decades much research has focused on a possible association between periodontitis and cardiovascular disease. Here, we review the existing literature on the association between the two diseases.     

Diet and endothelial function

Endothelial dysfunction is one of the earliest events in atherogenesis. A consequence of endothelial damage is a lower availability of nitric oxide (NO), the most potent endogenous vasodilator. NO inhibits platelet aggregation, smooth muscle cell proliferation and adhesion of monocytes to endothelial cells. Endothelial dysfunction is present in patients with cardiovascular disease and/or coronary risk factors, such as hypertension, dyslipidemia, diabetes, smoking or hyperhomocysteinemia. At present, soluble markers and high resolution ultrasound of the brachial artery, have provided simple tools for the study of endothelial function and the effects of several interventions. It has been demonstrated that dietary factors may induce significant changes on vascular reactivity. Nutrients, such as fish oil, antioxidants, L-arginine, folic acid and soy protein have shown an improvement in endothelial function that can mediate, at least partially, the cardioprotective effects of these substances. Attention has been focused on dietary patterns in populations with lower prevalence of cardiovascular disease. There is some evidence suggesting that Mediterranean diet characterized by high consumption of vegetables, fish, olive oil and moderate wine consumption may have a positive effect on endothelial function. These results give us evidence on the significant role of diet on endothelial function and its impact on the pathogenesis of atherosclerosis.     

Morphofunctional characteristics of the intrinsic arterial vessels of the kidney in healthy subjects and in various cardiovascular diseases

The investigation has been performed in 132 kidneys of corpses of persons at various ages, 96 of them died from some cardiovascular diseases and 36--from mechanical asphyxia. Injection, macro-microscopical, histological, biometrical and variational-statistic methods have been used. The total section areas of the arterial vessels is determined, it characterizes the vascular bed capacity of the renal cortical and medullary parts. At atherosclerosis, hypertension and cardiac ischemia an essential decrease in the vascular bed capacity in the cortical part and its increase in the medullary part of the kidney is observed. An increasing diameter of the juxtamedullary glomeruli is supposed to intensify the juxtamedullary blood stream. The greatest changes in architectonics and capacity of the renal arterial bed is observed at hypertension combined with atherosclerosis, and the least--at a chronic cardiac ischemia.     

The role of caveolae in endothelial cell dysfunction with a focus on nutrition and environmental toxicants

Complications of vascular diseases, including atherosclerosis, are the number one cause of death in Western societies. Dysfunction of endothelial cells is a critical underlying cause of the pathology of atherosclerosis. Lipid rafts, and especially caveolae, are enriched in endothelial cells, and down-regulation of the caveolin-1 gene may provide protection against the development of atherosclerosis. There is substantial evidence that exposure to environmental pollution is linked to cardiovascular mortality, and that persistent organic pollutants can markedly contribute to endothelial cell dysfunction and an increase in vascular inflammation. Nutrition can modulate the toxicity of environmental pollutants, and evidence suggests that these affect health and disease outcome associated with chemical insults. Because caveolae can provide a regulatory platform for pro-inflammatory signalling associated with vascular diseases such as atherosclerosis, we suggest a link between atherogenic risk and functional changes of caveolae by environmental factors such as dietary lipids and organic pollutants. For example, we have evidence that endothelial caveolae play a role in uptake of persistent organic pollutants, an event associated with subsequent production of inflammatory mediators. Functional properties of caveolae can be modulated by nutrition, such as dietary lipids (e.g. fatty acids) and plant-derived polyphenols (e.g. flavonoids), which change activation of caveolae-associated signalling proteins. The following review will focus on caveolae providing a platform for pro-inflammatory signalling, and the role of caveolae in endothelial cell functional changes associated with environmental mediators such as nutrients and toxicants, which are known to modulate the pathology of vascular diseases.     

Prenatal exposure to glucocorticoids and adult disease

There is evidence to suggest that an individual's susceptibility to cardiovascular disease cannot be entirely explained by differences in life style factors (i.e., low physical activity, high fat/salt diet), or genetic causes, but may also be influenced by factors encountered during intrauterine life. Epidemiological studies found the link between low birth weight for gestational age (a broad index of sub-optimal intrauterine environment) and increased incidence of cardiovascular and metabolic diseases in adulthood. Many animal models in which the intrauterine environment was altered during early/late or throughout gestation demonstrated long-term effects on adult health. In general stress in early gestation is more likely to be associated with adult cardiovascular disease including hypertension, whereas late gestation stress may also be associated with adult hypotension in addition to metabolic/endocrine abnormalities. Two systems have been widely hypothesised to serve as mechanisms via which adverse prenatal influences impinge on adult cardiovascular and metabolic disease; hippocampal-hypothalamo-pituitary-adrenal axis (HHPA) and renin-angiotensin system (RAS). Interestingly, at least in our animal model of adult hypertension after brief/early prenatal glucocorticoid exposure, HHPA axis is not altered when studied either in late gestation or at several stages during adulthood. However, our more recent results, using the same animal model, suggest a major role for the central and renal RAS. This review will mainly focus on animal models and potential mechanisms via which a perturbed intrauterine environment (undernutrition or steroid exposure) lead to adult cardiovascular and/or metabolic disease.     

Impact of Cardiovascular Risk Factors on Carotid Intima-Media Thickness and Degree of Severity: A Cross-Sectional Study

Objective

Age, hypertension, dyslipidemia and diabetes are common cardiovascular risk factors (CVRFs) that contribute to the development of atherosclerosis in cardiovascular system including carotid artery disease. However, the impact of these risk factors on the increased carotid intima-media thickness (cIMT) and degree of carotid severity remains to be further clarified. This study aims to evaluate the relationship between CVRFs and degree of carotid severity and cIMT in high-risk subjects.

Methods

Four thousand and three hundred ninety-four subjects with one or more risk factors were retrospectively reviewed in this study. Patients were divided into different groups based on age, the type and quantity of CVRFs. cIMT and degree of carotid artery stenosis were measured and analyzed based on carotid ultrasound imaging with findings compared to the CVRFs to determine the correlation between these variables.

Results

Aging was significantly associated with degree of severity (P < 0.05) and cIMT was significantly increased with age (P < 0.05). Individual CVRF analysis shows that hypertension was more related to the degree of severity than dyslipidemia and diabetes with corresponding abnormal cIMT rates being 79.39%, 72.98% and 32.37%, respectively. The prevalence of carotid atherosclerosis were 20.06%, 22.88% and 28.63%, respectively corresponding to patients with zero, one and more than one chronic diseases. The percentage of abnormal cIMT in hypertensive patient group with dyslipidemia is significantly higher than the other groups (P< 0.05).

Conclusions

This study shows a direct correlation between the degree of carotid severity and cIMT and cardiovascular risk factors, especially with age and hypertension. Carotid atherosclerosis is closely related to the number of cardiovascular risk factors.