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.     

Current Strategies for Atherosclerosis and Lowering Cholesterol

Atherosclerosis is a multifactorial disorder in which nutritional factors are closely related to a number of the manifestations of the disease. Sounder nutritional principles might therefore prevent atherosclerosis itself or its major complications. Optimising nutrients would diminish monocyte adhesion to endothelium, suppress platelet aggregation, prevent oxidative modification of lipoproteins, minimise activation of coagulant factors and reduce the flux of cholesterol and of atherogenic lipoproteins through plasma.

Optimising the mix of dietary fatty acids should have the highest priority. Emphasis should be placed on those fatty acids, such as those derived from fish, which modify several cardiovascular risk factors, including plasma lipids, blood pressure and coagulation factors. Reduction of risk factors is also achieved but to a lesser extent by reducing total fat intake, reducing dietary cholesterol, optimising the mix of starches and fibre and increasing plant foods generally.

A developing strategy is to identify genetic predisposition to environmentally induced hyperlipidaemia, since most forms of hyperlipidaemia reflect interactions between genetic and dietary factors.     

EPIDEMIOLOGICAL RISK FACTORS OF CORONARY HEART DISEASE ARE NOT CAUSAL IN ATHEROSCLEROSIS

Logic dictates that for scientific progress in atherogenesis “cause” must be the sole prequisite without which the disease cannot occur. Nor can it be assumed that statistical associations (risk factors) with coronary heart disease (CHD) are causal for atherosclerosis and extrapolations from correlations with CHD incidence to atherosclerosis are invalid. Any factor considered to play a role in atherogenesis requires pathological and experimental evidence consistent with the logic of Koch's specificity of cause and effect. Current epidemiological misuse and manipulation of cause and risk factors are contrary to the basic precepts of scientific logic and the fundamental need for precision in word usage. The term “risk factor”, because of the current deeply entrenched false concept of causality has retarded medical progress and should be abandoned. Its adherents, guilty of a disservice to the tenets of their discipline, have also sullied the scientific integrity of medicine as a whole.     

C‐reactive protein and tumor necrosis factor‐alpha in relation to insulin‐mediated glucose uptake,smoking and atherosclerosis

Objectives. To examine the hypothesis that serum concentration of C‐reactive protein (CRP) is inversely associated with insulin sensitivity and obesity, and that this may by mediated by tumor necrosis factor‐α (TNFα) and interleukin‐6 (IL‐6). Material and methods. Cross‐sectional, one‐center study of a population‐based sample of 58‐year‐old Swedish men (n = 98). Exclusion criteria were cardiovascular disease, clinical diabetes mellitus and/or continuous cardiovascular medication. Glucose infusion‐rate (euglycemic hyperinsulinemic clamp), adjusted for fat‐free mass, which together with total body fat was measured by dual‐energy X‐ray absorptiometry. Serum concentrations of CRP, TNFα, soluble TNFα receptor 2 (sTNFAR2), IL‐6 determined by ELISA. Ultrasound was used to measure intima‐media thickness (IMT) in both common carotid arteries, carotid bulbs and in the right femoral artery. Results. CRP was inversely associated with insulin sensitivity (r = ?0.28, p<0.01) and with total body fat (r = 0.31, p<0.01), but not independently of the TNFα and sTNFAR2 product. Serum CRP, TNFα, sTNFAR2, but not IL‐6, were associated with low insulin sensitivity, total body fat, abdominal obesity, hyperinsulinemia, hypertriglyceridemia, low HDL cholesterol and small LDL particles, i.e. the metabolic syndrome. These associations were independent of smoking and carotid and femoral artery IMT. Conclusions. Serum concentrations of CRP were related to insulin sensitivity and accompanying factors constituting the metabolic syndrome. The results indicate that this association may be mediated by adipose tissue and TNFα effects, the latter measured as the product of TNFα and sTNFAR2. This was a cross‐sectional study and causality cannot be proven.     

Albuminuria within the normal range and ultrasound‐assessed atherosclerosis in the AIR study: a 9‐year follow‐up of 58‐year‐old clinically healthy men

Background:Microalbuminuria, traditionally defined as 30–300 mg urinary albumin/24 h, predicts renal impairment and cardiovascular disease. Studies suggest that also a far lower urinary albumin excretion (UAE) can predict clinical outcome. Intima media thickness (IMT) is an established estimate of atherosclerosis. In this study, we investigated the predictive value of UAE within the normal rate (UAE–n) for the progression of IMT in the carotid and femoral arteries. Methods: We included 325 clinically healthy men with normoalbuminuria. Anthropometrics, urine and blood samples were taken and IMT in the carotid and femoral arteries were assessed by B–mode ultrasound at baseline and after 3 and 9 years. The annual progression rate of IMT (r–IMT) was calculated. Results: UAE–n correlated with carotid IMT at baseline and after 3 and 9 years, but not with r–IMT. In a regression analysis, only HDL and baseline IMT remained as statistically significant co–variates to mean IMT at 9 years. IMT in the femoral artery and r–IMT at any time–point did not correlate to baseline UAE. Conclusion: UAE–n was associated with carotid IMT after 3 and 9 years but not r–IMT or with femoral artery IMT. Carotid IMT after 9 years' follow–up was independently related to baseline IMT and HDL cholesterol. In this cohort of 58–year–old men, our interpretation is that UAE–n is not associated with the increase in carotid and femoral artery IMT observed after 9 years.     

Elimination of endoplasmic reticulum stress and cardiovascular,type 2 diabetic,and other metabolic diseases

Abstract

Multiple factors including unhealthy living habits influence the life-maintaining functions of the endoplasmic reticulum (ER) and induce ER stress and metabolic abnormalities. The ER responds to the disturbances by activating mechanisms that increase the capacity to eliminate ER stress. This article elucidates the effects of ER activation that eliminates both ER stress and associated cardiovascular, type 2 diabetic (DM2), and other metabolic diseases. ER-activating compounds eliminate ER stress by lowering elevated cholesterol, regress atherosclerosis, decrease cardiovascular mortality, reduce blood glucose and insulin, and, together with the normalization of glucose–insulin homeostasis, remove insulin resistance, pancreatic β-cell failure, and DM2. A deficient cytochrome P450 activity in hepatic ER leads to cholesterol accumulation that induces stress and xanthoma formation, whereas P450-activating therapy up-regulates apolipoprotein AI and LDLR genes, down-regulates apolipoprotein B gene, and produces an antiatherogenic plasma lipoprotein profile. The ER activation reduces the stress also by eliminating hepatic fat and converting saturated fatty acids (FAs) to unsaturated FAs. Cognitive processes require gene expression modification, and preclinical studies indicate that ER-activating therapy improves cognition. Promotion of healthy lifestyle choices and indicated therapies are key factors in the prevention and elimination of ER stress and associated global health problems.     

Hotter monitoring in the evaluation and rehabilitation of post-cerebrovascular accident patients

Coronary artery disease, overt or silent, is frequently present in patients who have suffered a cerebrovascular accident (CVA). Rehabilitation therapy of CVA patients is based mostly on physical activity, which may be limited by fear of overloading the cardiovascular system. Therefore, assessment of the severity of coronary heart disease in CVA patients is of utmost importance. In this study we assessed the usefulness of 24-hour electrocardiographic Holter monitoring in the evaluation of post-CVA patients during daily activities and rehabilitation. Of the 43 post-CVA patients, 24 (55.8%) revealed pathological changes on Holter monitoring and 17 (71%) had a history of coronary artery disease prior to CVA. Holter monitoring revealed mainly ventricular and atrial arrhythmias and in three patients detected transient ischaemic episodes. Only six patients (14%) showed aggravation of arrhythmia during rehabilitation therapy, without aggravation of ST-T changes. The mean maximum heart rate during regular daily activities was 104±20 beats/min, which was significantly higher than the mean maximum heart rate during physical therapy (100±18 beats/min; p < 0.01) and during occupational therapy (87±18 beats/min; p < 0.001). These findings indicate that more vigorous physical and occupational therapy can be prescribed to these patients. The performance of Holter monitoring in post-CVA patients is a valuable substitute to exercise testing, and is useful for cardiovascular evaluation during daily activities and rehabilitation therapy.     

冠心病冠脉优势型与血管病变数目及严重程度的相关性分析

目的 探讨冠心病中冠脉优势型与血管病变数目及疾病严重程度的关系,为冠心病危重度预测及分级提供理论依据。方法 选取2010年7月～2014年4月西安交通大学第二附属医院确诊的冠心病患者1654例为研究对象,行单中心回顾性观察性研究。根据病变累及部位分为3组：单支血管病变组（n=465）、双支血管病变组（n=414）和三支血管病变组(n=775）。再根据冠脉优势型将所有患者分为两组：右冠优势型（n=1500）、非右冠优势型（左冠优势型和均衡型,n=154）（考虑后两者所占比例偏低,将其合并）。将年龄、性别、吸烟史、是否患高血压、糖尿病及高脂血症作为协变量,利用Logistic回归模型分析何种冠脉优势型是冠心病血管病变数目增加的可能危险因素;比较Gensini评分,探讨冠脉优势型和冠心病严重程度的关系。结果 右冠优势型患三支血管病变的可能性是非右冠优势型的1.681倍（OR=1.681;95% CI=1.096～2.579; P=0.017）;但右冠优势型患双支血管病变的可能性与非右优势型比较,差异无〖JP2〗统计学意义（OR=1.212; 95%CI=0.781～1.880;P=0.392）。右冠优势型Gensini评分明显高于非右冠优势型（42.3±〖JP〗33.6 vs36.3±29.8,P=0.033）。结论 右冠优势型可能是三支血管病变的独立危险因素,并且右冠优势型会导致较严重的血管病变程度。     

双源CT低管电压降低冠状动脉CTA辐射剂量

目的 观察低管电压在体质指数(BMI)正常范围患者双源CT冠状动脉成像(CTA)中的应用,并评价其图像质量.方法 将65例BMI在正常范围并接受冠状动脉CTA检查的患者随机分为两组,A组管电压采用常规扫描120 kV,B组管电压采用100 kV,均采用回顾性心电门控螺旋扫描.对两组扫描的冠状动脉分别做图像处理,应用秩和检验比较两组患者冠状动脉段图像质量总体评分,两独立样本t检验比较两组患者的辐射剂量和对比剂用量. 结果 A组评价443段冠状动脉,B组评价451段冠状动脉.A组图像质量评价为优和良好的占97.74%,B组占97.56%.冠状动脉段图像质量评分两组之间比较差异无统计学意义(P=0.126).A组平均有效剂量为(15.04±2.42)mSv;B组平均有效剂量为(7.95±1.69)mSv,差异有统计学意义(P＜0.001).A组对比剂用量为(75.17±3.69)ml,B组对比剂用量为(62.27±3.42)ml,差异有统计学意义(P＜0.001). 结论 对于BMI在正常范围内的患者,冠状动脉CTA检查时管电压设为100 kV可在保证图像质量的同时显著降低辐射剂量和对比剂用量.     

64层螺旋CT对心功能不全患者冠状窦的评价

目的探讨64层CT冠状动脉血管成像(CTA)评价冠状窦(CS)的可行性,并观察心功能不全患者冠状窦口(CSO)的形态学变化。方法将24例经CTA证实无心脏和冠状动脉疾病的患者和24例不同程度充血性心功能不全患者的冠状动脉CTA检查数据进行图像处理,主要评价CS的图像质量、长度、CSO的直径和横截面积、冠状窦瓣的显示率,并比较心功能正常患者和充血性心功能不全患者的CSO大小有无差异。结果所有患者CS的图像质量评分均达3分,并均有较高的对比噪声比(CNR),心功能正常组CS平均长度(34.3±16.3)mm,与心功能不全组无显著差异(P>0.05),心功能不全组的CSO上下径和横截面积明显大于心功能正常组(P<0.05)。结论64层螺旋CT血管成像可以清晰显示CS,并能够对CSO的大小进行精确测量;心功能不全患者的CSO扩张,其上下径和横截面积大于心功能正常组。