Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in haemodialysis patients.

BACKGROUND: Dyslipidaemia, inflammation and oxidative stress are prominent risk factors that potentially cause vascular disease in haemodialysis patients. Dialysis modalities affect uraemic dyslipidaemia, possibly by modifying oxidative stress, but the effects of dialyser flux and membrane material on atherogenic remnant particles and oxidized low-density lipoproteins (LDL) are unknown. METHODS: We performed a randomized crossover study in 36 patients on haemodialysis to analyse the effect of dialyser flux and membrane material on plasma lipids, apolipoproteins and markers of inflammation and oxidative stress. Stable patients on low-flux dialysis with polysulphone for >/=6 weeks were assigned to high-flux polysulphone or high-flux modified cellulose with similar dialyser surface area and permeability characteristics and crossed over twice every 6 weeks. RESULTS: Thirty patients completed the study per protocol. Treatments with high-flux polysulphone and modified cellulose lowered serum triglyceride (by 20% and 10%, respectively; P<0.05) and remnant-like particle cholesterol by 32% (P<0.001) and 11% (NS) after the first 6 weeks of treatment. Oxidized LDL decreased significantly with high-flux polysulphone, but not with modified cellulose. Apolipoproteins CII and CIII were reduced, whereas the ratio CII/CIII was increased (all P<0.05). Acute-phase proteins and LDL and high-density lipoprotein cholesterol remained unaffected. CONCLUSIONS: This randomized crossover study demonstrates a potent effect of high-flux haemodialysis on uraemic dyslipidaemia. Polysulphone membrane material showed superiority on oxidatively modified LDL, an indicator of oxidative stress in haemodialysis patients.     

High-density lipoprotein subfractions,apolipoproteins and antipyrine clearance in normal subjects

Summary Serum high density lipoprotein (HDL) subfractions HDL₂ and HDL₃, apolipoproteins, and plasma antipyrine clearance (AP-CL) rate, an index of liver microsomal enzyme activity, were determined in 21 healthy subjects. High HDL cholesterol and HDL₂ cholesterol concentrations and HDL cholesterol/cholesterol and HDL₂/HDL₃ cholesterol ratios were associated with high AP-CL. Phenobarbital enhanced antipyrine elimination and increased the apolipoprotein A-I/A-II ratio. Subjects who had high AP-CL had a more antiatherogenic HDL subfraction and apolipoprotein profile than those with low AP-CL.     

Increased frequency of the rare PstI allele (P2) in a population of CAD patients in Northern Greece

Restriction fragment length polymorphisms (RFLPs) at the apolipoprotein AI-CIII-AIV gene cluster and their association with coronary artery disease (CAD) and lipid levels were studied in a Northern Greek population. Ninety-five patients with CAD and fifty-four normal controls, angio-graphically proven, were included in this study. Using genomic hybridization techniques, three polymorphic restriction sites were identified at this locus: the PstI at the 3' end of the apoAI gene, the SacI at the 3' non-coding region of the apoCIII gene and the PvuII at the intergenic region between the apoCIII-AIV genes. The rare allele (P2) arising from the absence of the PstI restriction site was observed with a significantly higher frequency (p<0.01) in patients compared to normals (0.11 vs 0.02). In contrast, the rare allele for the SacI polymorphic site had a similar distribution among patients and controls (0.12 vs 0.16). The same was observed for the PvuII RFLP (0.04 vs 0.05). Correlation of lipid and apolipoprotein AI levels with the three RFLPs revealed no significant association, although apo AI and HDL were lower in patients with the P2 allele. Thus, in this Greek population, only the PstI polymorphism, among the polymorphic restriction sites examined, appears to be associated with CAD.     

Restriction site polymorphism at the LPA (Lp(a) apoliprotein; apoliprotein(a)) locus

A restriction site polymorphism in the Lp(a) apolipoprotein gene (the LPA gene) is reported. The basis for the polymorphism is presence or absence of an MspI restriction site that appears to be 3' to the last kringle IV structure of the gene. The "1" gene (presence of the restriction site) has a frequency of 0.316 and the "2" gene (absence of the restriction site) has a frequency of 0.684. Both members of each of 67 monozygotic (MZ) twin pairs had the same genotype and there was Mendelian segregation of the DNA variants in 40 families with a total of 75 children. There was a lower proportion of people with genotype 1-1 in the top quartile than in the 3 bottom quartiles of the population distribution of Lp(a) lipoprotein levels but the difference did not reach statistical significance.     

Immunohistochemical localization of apolipoproteins A-I and B in human carotid arteries

Decreased plasma levels of apolipoprotein A-I (apo A-I) and increased plasma levels of apolipoprotein B (apo B) have been shown to correlate with increased risk of atherosclerosis. While many studies have investigated the plasma levels of these apolipoproteins with regard to their value as predictors of cardiovascular disease, comparatively little is known about their precise tissue localization in atherosclerotic plaques. The purpose of this study was to determine the tissue localization of apo A-I and apo B in atherosclerotic segments of human carotid arteries through the use of immunohistochemical techniques. With tissue samples obtained from surgery and autopsy, apo A-I and apo B were found to be present in atherosclerotic plaques and absent in normal arterial tissue. In the plaques, both apo A-I and apo B were found extracellularly, primarily in the lipid core, but also in connective tissue. In addition, both apo A-I and apo B were found intracellularly in foam cells. This similar intracellular and extracellular distribution of apo A-I and apo B was unexpected, in view of their differing associations with atherosclerosis.     

老年高血压患者的胰岛素抵抗及脂代谢异常的意义

目的：探讨老年高血压病患者的胰岛素抵抗（insulin resistance,IR）及脂代谢状况,指导老年高血压病的合理治疗。方法：测定210例老年高血压病患者及30例正常对照组的血清总胆固醇（TC）、甘油三酯（TG）、载脂蛋白A1(APO-A1）及载脂蛋白B（APO－B）,计算空腹胰岛素（FLns）／空腹葡萄糖（FBG）比值和胰岛素曲线下面积（RIAUC）／葡萄糖曲线下面积（GAUC）比值作为IR指标,并进行相关分析,对其中长期服用氯沙坦（≥6个月）患者的IR指标也进行了对比分析。结果：与正常对照组比较,老年高血压病组的TC、TG、APO－B、FLns、RIAUC、FLns/FBG及RIAUC／GAUC明显升高（P＜0．05－0．01）,APO－A1明显降低（P＜0．05）,并发冠心病组IR及脂代谢异常更明显（P＜0．05－0．01）,而且Flns/FBG及RIAUC／GAUC分别与平均动脉压、左室肌重量指数、TG及APO－B呈正相关,与APO－A1呈负相关。长期用氯沙坦患者IR指标改变轻于整体高血压病组。结论：老年高血压病也存在IR和脂代谢紊乱,且IR与脂代谢异常及左室肥厚的发生有关;氯沙坦对IR无不良影响。     

Effects of Three Treatment Modes on Plasma Lipids and Lipoproteins in Uraemic Patients

Plasma lipids, chemical composition of various lipoprotein fractions, apolipoprotein B concentrations and apolipoprotein E phenotypes were studied in 12 uraemic patients on conservative treatment (CT), in 16 patients on haemodialysis (HD) and in 18 patients on continuous ambulatory peritoneal dialysis treatment (CAPD). Plasma total cholesterol and triglyceride concentrations were increased in the CAPD patients in comparison to the HD patients and the control subjects. Moreover, the CAPD patients had higher LDL cholesterol concentration than the CT and HD patients. The HDL cholesterol concentration was lower in the HD and CAPD patients than in the control subjects. The chemical composition of lipoproteins in all fractions of the CT and HD patients and in VLDL, IDL and LDL fractions of the CAPD patients differed from those of the control subjects. The main differences were the increased proportion of triglycerides in VLDL and LDL fractions of all the patient groups and in HDL fraction of the CT and HD patients in comparison to the control subjects. Moreover, the proportion of cholesterol was increased in VLDL and IDL fractions of the CT and the CAPD patients and decreased in HDL fraction of the CT and HD patients compared to the control subjects. In conclusion, in addition to the alterations in the lipoprotein concentrations in uraemic patients there are also marked changes in the chemical composition of the lipoprotein particles that may further contribute to the accelerated atherosclerosis among uraemic patients. The abnormalities are particularly prevalent in CAPD patients.     

老年冠心病患者脂蛋白谱剖析

目的探讨老年冠心病患者的脂蛋白谱特点。方法以诊断明确的老年男性冠心病１４３例为观察对象，以年龄与生活水平相匹配的健康老年男性１４３名为对照，两组中均排除与脂代谢有关的其它疾病。以同一份血清用优选方法作１４项检查，包括总胆固醇（ＴＣ），甘油三酯（ＴＧ），高密度脂蛋白胆固醇及其亚类（ＨＤＬ－Ｃ、ＨＤＬ２－Ｃ、ＨＤＬ３－Ｃ），低密度脂蛋白胆固醇（ＬＤＬ－Ｃ），脂蛋白（ａ）〔Ｌｐ（ａ）〕，载脂蛋白（ａｐｏ）ＡⅠ、ＡⅡ、Ｂ、ＣⅠ、ＣⅡ、ＣⅢ和Ｅ。结果除ａｐｏＣⅠ、ＣⅢ两项外，其它１２项均值在冠心病组与对照组之间的差异均有显著性。逐步回归分析中顺次选入ａｐｏＡⅠ、ＬＤＬ－Ｃ与ＴＧ３项为优选指标，相关分析示Ｌｐ（ａ）是一项独立变量。结论在ＴＣ水平接近正常时，老年冠心病组最突出的改变是代表ＨＤＬ的５项参数均明显低下，其中以ａｐｏＡⅠ为最明显。临床上选用检验指标仍应以ＴＣ、ＴＧ、ＨＤＬ－Ｃ和ＬＤＬ－Ｃ为主，如果采用ａｐｏＡⅠ、Ｂ及Ｌｐ（ａ）测定，必须注意所用商品试剂的质量。     

Familial homozygous hypobetalipoproteinemia

An apparently new form of abetalipoproteinemia, homozygous hypobetalipoproteinemia, was studied in progeny of a mating of two parents each heterozygous for familial hypobetalipoproteinemia, which was characterized by three-generation vertical transmission on both maternal and paternal sides of the family. The two children, with an apparent homozygous form of hypobetalipoproteinemia, had, in addition to abetalipoproteinemia, acanthocytosis, intestinal etpithelial and hepatic steatosis and steatorrhea. No low desity lipoprotein (LDL) was detected by immunodiffusion with antisera to LDL or apoLDL. The defects in apolipoproteins in these two children were the same as those reported in children with abetalipoproteinemia inherited as an autosomal recessive trait. The genetic defect of hypobetalipoproteinemia, when homozygous, can lead to all of the known clinical and biochemical features of abetalipoproteinemia.     

Effect of simvastatin on high density lipoprotein subfractions and apolipoproteins in Type IIa hypercholesterolemia

Summary Changes in plasma concentrations of high density lipoproteins (HDL) and triglycerides may partly explain the ability of cholesterol-lowering drugs to decrease the incidence of coronary heart disease. We measured the response of fasting plasma lipids, lipoproteins, and apolipoproteins in 46 subjects with Type IIa hypercholesterolemia treated with simvastatin for 3 months. The initial dose of simvastatin (10 mg/day) was subsequently increased up to 40 mg/day if the plasma cholesterol concentration had not fallen below 5.2 mmol/l. Plasma concentrations of HDL cholesterol and of the apolipoproteins AI and AII were increased by simvastatin. The increase in HDL cholesterol (9%) was due to increases in both subfractions (HDL₂ 17%; HDL₃ 7%), changes that would be consistent with a beneficial effect on cardiovascular risk. Simvastatin decreased plasma triglyceride concentrations by 25%. Plasma total cholesterol concentrations fell by 35% after 3 months of treatment; this fall was proportional to the initial concentration and was due almost entirely to a 45% fall in low density lipoprotein cholesterol. In contrast, plasma concentrations of lipoprotein Lp(a) were not affected by simvastatin.