Low–Density Lipoprotein Apheresis Versus Lipid Lowering Drugs in the Treatment of Severe Hypercholesterolemia: Four Years' Experience

Abstract: Elevated lipoprotein concentrations seem to be linked strongly in a dose dependent manner to an increased incidence of atherosclerosis. A total of 47 patients suffering from severe hyperlipidemia were matched to treatment with LDL apheresis (Baxter, Kaneka, Li–popak; 24 patients, aged 50.2 ±11.5 years), diet, and/or lipid–lowering drugs or with diet and lipid–lowering drugs only (23 patients, aged 48.8 ±11.8 years). After treatment periods of 49.8 ±13.4 months (apheresis group, 2,396 treatment sessions) and 38.6 ± 15.1 months (drug group), the ensuing results revealed significant differences (p <0.0001): –47.3% versus –12.1% for total cholesterol, –46.9% versus –21.8% for LDL, +8.4% versus +0.9% for HDL, –52.0% versus – 13.1% for the LDL/HDL ratio, –36.4% versus –16.2% for triglycerides, and –25.9% versus + 1.5% for lipoprotein (a). In the apheresis group, one patient died of myocardial infarction; in the drug group, there was one nonfatal myocardial infarction and the manifestation of coronary heart disease in 3 cases. There were no severe side effects in either group. All patients in the apheresis group responded to therapy. The present trial suggests that a continuing reduction in serum lipid concentrations may lower, in a dose dependent manner, the risk for development and progression of coronary heart disease. Regarding clinical and laboratory results, LDL apheresis seems to be safe, effective therapy for treatment of severe hyperlipidemia.     

单核细胞流变特性异常在动脉粥样硬化进程中的作用

目的：了解单核细胞流变特性异常在动脉粥样硬化进程的作用。方法：大耳白兔６０只随机分为实验组（ＡＧ）４０只及对照组（ＣＧ）２０只，ＡＧ给予胆固醇ｌｇ．ｄ＾－１只＾－１在喟养的第２，４，８和１２周分别抽血检测单核细胞变形性，膜脂流动性及单核细胞（Ｃａ＾２＋０ｉ。结果：在兔ＡＳ阶段性进程中，单核细胞变形性，膜脂流动性下降趋势，细胞内（Ｃａ＾２＋）ｉ呈上升趋势，膜流动性与细胞内（Ｃａ＾２＋）ｉ呈负相关，变     

Arterial response to excimer and argon laser irradiation in the atherosclerotic swine

Injury associated with laser-induced tissue ablation may be reduced by using pulsed energy delivery at low repetition rates, as opposed to using continuous wave energy delivery. This study was designed to examine the similarities and differences between these two systems as regards the healing process, and to examine whether one is superior to the other. In order to test this postulate, the healing response of normal and atherosclerotic aorta were examined after exposure in vivo to argon and excimer (XeCl 308 nm) laser radiation in hypercholesterolemic swine. Swine were fed hyperlipidemic diets for eight months following balloon denudation of the descending aorta. Following general anaesthetic, the descending aorta was isolated and laser burns were made on both normal and atherosclerotic intima using a continuous wave argon laser delivered through a 50 diameter quartz fibre, and a XeCl excimer laser carried through a 1 mm diameter fibre. Energy levels of 3 to 5 J were applied with the argon laser. The pulse duration for the excimer laser was 30 ns and craters were produced using 10 to 60 pulses at a repetition rate of 20 Hz and an energy density of 2 J cm^–2.Forty-eight hours after laser application, craters created by both lasers were filled with thrombus material. Argon burns were surrounded by thermal and acoustic injury which was not seen with excimer burns. Three weeks after laser application all crater surfaces were reconstituted. Unlike the excimer burns, argon craters demonstrated necrosis well beyond the crater margins and were characterized by multinucleate giant-cell reaction surrounding char debris. By nine weeks both excimer and argon laser burns were covered by fibrous tissue but could be distinguished by the fact that char debris and subjacent tissue injury arose with the argon burns.The results suggest that both lasers can be used to remove focal atherosclerotic plaque from arteries without inducing excessive thrombogenicity. Rapid healing is observed with both; however, damage to surrounding tissue is significantly greater with a continuous energy delivery laser as opposed to pulsed energy delivery.Work supported in part by: Heart and Stroke Foundation of Ontario, Grant-in-Aid No. 5-17     

Intermediate filament expression in human vascular smooth muscle and in arteriosclerotic plaques

Summary Different regions of human aorta and of other human arteries obtained at autopsy were analyzed with regard to their topography and to the different stages of arteriosclerosis. Material was studied by immunocytochemical techniques with antibodies specific for either desmin (D) or for vimentin (V), the two types of intermediate filament proteins present in vascular smooth muscle cells. In normal arteries endothelial cells as well as the adjacent intimal cells were D–V+. In the media D+V+ as well as D–V+ cells were present, with the relative numbers of each cell type dependent on the particular blood vessel. When cells in arteriosclerotic plaques at different stages of development were examined an occasional plaque showed cells of the D+V+ type. In the majority of plaques however the cells were V– D+. In plaques where severe ulceration and necrotic material was present D–V+ cells were found at the border of the lesion: foam cells when they could be identified appeared to be D–V+.     

Declining density of intimal smooth muscle cells and age as preconditions for atheronecrosis in the basilar artery

The aging basilar artery has some differences and some similarities when compared with the aorta and coronary arteries. As the non-necrotic intimal thickness increases over time, the number of smooth muscle cells reaches a steady state around age 25–30 years in the coronaries and aorta, but continues to increase in the basilar artery, even to 90 years of age. The numbers of cells per unit of tissue (the cell density) declines with age, and the patterns of decline are quantitatively similar in all three arterial segments. All arteries so far examined behave alike in showing that atheronecrosis emerges in those specimens that have sufficiently low density of intimal smooth muscle cells. These results identify low intimal cell density as a criterion for recognizing arteries that are prone to atheronecrosis. One possible explanation is that depopulation of the fibrotically thickened and aged intima, by spreading apart the smooth muscle cells with expanding matrix materials, could be the conditioning factor that brings about the intrusion of atheronecrosis.     

Coronary arterial lesions in sexually mature non-layers,layers, and roosters

Summary The effects of hereditary hyperlipidemia on coronary artery atherosclerosis were studied in 77 White Leghorn (DeKalb strain) chickens ranging from 4 to 13 months in age. After pubescence, the plasma levels of triglyceride and cholesterol in non-laying hens ranged 2- to 3-fold and 2- to 7-fold higher compared to layers. Serial sectioning revealed that most lesions were found in the proximal portions of both the left and right coronary arteries. Ultrastructurally, lesions in the roosters contained no foam cells, whereas some foam cells and small amounts of stainable lipid were observed in the thickened intima of layers. Half of the non-layers had stenotic lesions characterized by many foam cells, necrotic foci, and heavy stromal lipid deposits. Continuous permeation of excess plasma lipids into the arterial wall appeared to be an important factor in the development of coronary lesions.     

Presence of autoantibodies to apolipoprotein A-1 in patients with acute coronary syndrome further links autoimmunity to cardiovascular disease

Anti-apolipoprotein A-1 (Apo A-1) autoantibodies were described in autoimmune disorders such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and might be involved in the genesis of arterial and venous thrombotic events. To investigate the presence of these autoantibodies in patients with acute coronary syndrome (ACS) without other features of autoimmunity, we set up an enzyme-linked immunosorbent assay (ELISA) for anti-Apo A-1 antibodies. We used it to investigate their prevalence in ACS as compared to SLE and APS and correlated them to plasma Apo A-1 and serum amyloid A protein (SAA) concentrations. The prevalence of anti-Apo A-1 autoantibodies in the healthy control group was 1% (1/92), but was significantly higher in other groups: 21% (11/53) in ACS group (P=0.001), 13% (12/92) in SLE and/or APS group (P=0.005). Multiple linear regression revealed a significant correlation between plasma Apo A-1 (r=-0.72, P=0.013), plasma SAA concentration (r=0.76, P=0.0066) and anti-Apo A-1 IgG titre in ACS patients. The presence of anti-Apo A-1 autoantibodies in patients with ACS highlights an additional link between autoimmunity, inflammation and atherosclerosis.     

Effects of social factors on adrenal weight and related physiology of Macaca fascicularis

Increased adrenal cortical activity and hypertrophy of adrenal glands associated with defeat and social subordination have been reported frequently in small mammals; these adrenal changes have been linked to impairments in immune response, glucose metabolism and reproductive performance. Similar studies in primates have produced variable results. The current study was undertaken to illuminate the effects of social status on the adrenal gland and to examine concurrent effects of social variables on other physiological systems in Macaca fascicularis, in an initial exploration of the hypothesis that high and low social status have different physiological consequences. Sixty adult male M. fascicularis were housed in social groups of n = 5, under either stable or unstable social conditions. It was found that subordinate animals had heavier adrenal glands and somewhat higher plasma glucose concentrations than dominants. In contrast, dominants had higher blood pressure and worsened atherosclerosis, under some conditions, than subordinates. These data appear to offer preliminary support for Henry and Stephen's hypothesis of differential arousal of dominant and subordinate animals.     

脑梗塞患者颈动脉粥样硬化斑块的超声研究

目的探讨脑梗塞患者颈动脉粥样硬化病变程度和特征,评价彩色多普勒超声对该粥样斑块的诊断价值.方法应用HP5500超声仪,对35例脑梗塞患者和46例正常人进行颈动脉检查.结果脑梗塞组颈动脉粥样硬化斑块检出率、斑块记分均显著高于对照组[分别为85.7%和21.7%,P＜0.01;(6.745±3.214)mm和(3.408±3.613)mm,P＜0.001],且脑梗塞组软斑比例为55.8%,显著大于对照组33.3%(P＜0.01),脑梗塞组斑块表面不规则即Ⅱ、Ⅲ度的比例亦显著大于对照组(41.9%/11.1%,11.6%/0%,P＜0.05).结论脑梗塞的发生与颈动脉粥样硬化病变密切相关;软斑块是发生脑梗塞的主要危险;超声检查对颈动脉粥样硬化具有诊断价值,可为脑梗塞的预防与治疗提供参考资料.     

槲皮素、异鼠李素对Cu2+介导极低密度脂蛋白氧化修饰的影响

目的　观察槲皮素 (Que)及异鼠李素 (Iso)对 Cu2 +介导的极低密度脂蛋白 (VL DL)氧化修饰的影响。方法　采用一次性密度梯度离心法分离人血浆 VL DL,用 Cu2 +进行体外氧化修饰 ,抗氧化组在温育前加入不同浓度的 Que和 Iso。分别检测脂蛋白中丙二醛 (MDA)、维生素 E(Vit E)及超氧化物歧化酶 (SOD)活性。结果　Que和 Iso可明显降低 OX- VL DL 中 MDA含量 ,延缓 OX- VL DL 中 Vit E含量的减少 ;显著提高脂蛋白中 SOD活性。结论　 Que和 Iso可显著抑制 Cu2 +诱导的 VL DL 的氧化修饰 ,且二者的作用相近 ,这与其抗自由基氧化活性密切相关。