Effect of Peritoneal Dialysis Solution Type on Serum Lipid Levels in End-Stage Renal Disease

Among the different cardiovascular risk factors, lipid abnormalities dominate the high mortality in chronic ambulatory peritoneal dialysis patients. So far, no data comparing the effect of standard glucose-containing, amino acid-containing, and icodextrin-containing peritoneal dialysis solutions on serum lipid concentrations in a chronic ambulatory peritoneal dialysis population are available. To determine the effect of peritoneal dialysis solutions on parameters of lipid metabolism, 67 subjects who had continued their usual dialysis for the last six months were enrolled in the study. Group A consisted of 18 patients who were receiving only glucose-based peritoneal dialysis solutions, group B consisted of 18 patients who were receiving glucose and amino acid-based peritoneal dialysis solutions, and group C consisted of 31 patients who were receiving glucose and icodextrin-based peritoneal dialysis solutions. Serum lipid parameters including total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride, and lipoprotein (a) were determined in all groups. No significant difference in serum lipid parameters was found between groups A, B, and C. These results demonstrate the lack of the effect of amino acid or icodextrin-based peritoneal solutions on dyslipidemia of CAPD patients.     

Lipids and lipoprotein(a) as risk factors for vascular disease in patients on renal replacement therapy

A large cohort of patients on renal replacement therapy werescreened for the presence of symptomatic arterial disease affectingthe coronary, cerebral or peripheral circulations. Ninety-twoof 325 patients were found to have vascular disease. Those withvascular disease had significantly higher median lipoprotein(a)[Lp(a)] levels than those without (38.4 vs 14.2 mg/dl, P<0.001),with a preponderance of Lp(a) levels greater than 30 mg/dl (58%vs 25% P<0.001). Apolipoprotein(a) [apo(a)] isoform distributionwas similar between the groups, but those with vascular diseasehad higher Lp(a) levels in the S2, S3/S4 and S4 isoform types.Comparison of 76 matched pairs of patients confirmed elevatedLp(a) levels in those with vascular disease. These patientsalso had significantly higher total cholesterol (6.66 vs 6.02mmol/l) and low-density lipoprotein cholesterol (4.49 vs 3.86mmol/l). Only Lp(a) was independently associated with vasculardisease (P=0.02). Elevated Lp(a) levels are significantly associatedwith the presence of vascular disease in patients on renal replacementtherapy and may constitute another risk factor for the developmentof such disease in these patients.     

Serum lipoprotein (a) concentrations in patients undergoing continuous ambulatory peritoneal dialysis

Lipoprotein (a) is a subspecies of low-density lipoprotein whichpossesses as part of its protein moiety a mutant form of plasminogentermed apolipo-protein (a), and which may be closely relatedto the risk of ischaemic heart disease and cerebral infarction.We have investigated the serum concentrations of lipoprotein(a) and other lipoproteins in 24 male patients on CAPD and comparedthem to healthy men (n= 100) and to age-matched healthy controls(n=38). The most striking finding was a substantial elevationof serum lipoprotein (a) in CAPD patients in whom it was 46.9(2.2–168) mg/dl (median and range) compared to 9.0 (<0.6–87.4)mg/dl in healthy control group and 6.7 (< 0.6–84.2)mg/dl in age-matched controls (both P<0.001). Patients, whencompared to healthy men, also had significantly increased serumtriglycerides (median and range, 1.94 (0.55–8.00) versus1.24 (0.36–4.40) mmol/1; P< 0.001), very-low-densitylipoprotein cholesterol (median and range, 0.98 (0.10–3.71)versus 0.46 (0.10–1.17) mmol/l; P<0.001), and lower-high-densitylipoprotein cholesterol (mean±1 sd, 1.26±0.29versus 1.35±0.31 mmol/l). Of these, however, only thedifference in very-low-density lipoprotein cholesterol remainedstatistically significant (P< 0.001) in comparison to age-matchedcontrols. The marked elevation of serum lipoprotein (a) in patientson CAPD may be due to increased hepatic synthesis as a consequenceof the substantial amounts of plasma proteins lost in the dialysate.Elevated serum lipoprotein (a) concentrations in CAPD patientsmay contribute to their risk of coronary artery disease.     

A single nucleotide polymorphism in the plasma PAF acetylhydrolase gene and risk of atherosclerosis in Japanese patients with peripheral artery occlusive disease

BACKGROUND: Plasma PAF-acetylhydrolase (PAF-AH) gene polymorphisms (G994 --> T in exon 9) and the resulting deficiency of enzyme activity were identified in the Japanese population. The objective of this study was to assess the joint effect of the polymorphism and hypercholesterolemia on risk of atherosclerosis. METHODS AND RESULTS: We performed a case-control study including 150 patients who underwent operation for peripheral arterial occlusive disease (PAOD) and 158 controls matched for age and sex. Genomic DNA was analyzed for the mutant allele by a specific polymerase-chain reaction. Plasma PAF-AH activity was measured in both groups. The patients with multiple atherosclerotic diseases showed higher levels of PAF-AH activities than the patients with only peripheral artery occlusive disease among normal genotypes. PAOD patients were assessed either with or without polymorphism or hypercholesterolemia in regard to accompanying coronary artery disease or stroke. The prevalence of the polymorphism was significantly more frequent in the patients with PAOD. The plasma PAF-AH activity was correlated with total cholesterol and LDL level, and inversely related with HDL in normal genotype (GG) PAOD patients. However, neither the correlation nor the inverse relation was found in patients with the polymorphism. Patients with both hypercholesterolemia and the polymorphisms revealed a relative risk for other atherosclerotic disease of 11.5 (6.0-40.3) compared with normal genotype and normal lipid level. CONCLUSION: The plasma PAF-AH gene polymorphism and hypercholesterolemia may interact and increase the risk of atherosclerosis.     

非高密度脂蛋白胆固醇与碱性磷酸酶水平的调查与分析

目的 调查广州某高校人群的非高密度脂蛋白胆固醇（non-HDLC）与碱性磷酸酶（ALP）水平，并结合血浆促动脉硬化指数（AIP）分析两指标的临床预测意义以及两指标之间的关系。方法 采用前瞻性研究对2011-2012年广州地区的某高校505例人群的完整体检资料进行统计分析，直接检测法得出血浆总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）等血脂的水平及ALP水平，根据公式计算出non-HDLC,结合AIP指数统计分析不同分组人群血浆non-HDLC水平和ALP水平，探讨non-HDLC对动脉粥样硬化评估的临床预测意义，以及骨代谢指标ALP与血脂之间的关系。结果 血脂non-HDLC、LDL-C水平60岁以前同年龄层不存在性别差异，血脂水平都在60岁以后出现高值，且存在性别差异;无论对血脂正常人群按TC或TG分层与否，与LDL-C，non-HDLC都呈现出与AIP更稳定更密切的相关性。60岁以上的男性、女性人群中ALP与血脂non-HDLC均呈正相关（r=0.520、0.226，P <0.001、P <0.05），而男性仅60岁以上的ALP值与AIP呈正相关（r=0.717，P <0.001）。结论 较以往单凭LDL-C值的判断，血脂non-HDLC值和AIP值的结合判断能提高临床上对动脉粥样硬化危险性评估的准确性。血脂与骨指标ALP也存在着密切的关系。     

同型半胱氨酸、超敏C反应蛋白、低密度脂蛋白胆固醇、D-二聚体与脑梗死的关系

目的：探讨血清同型半胱氨酸（Hcy）、血脂、超敏c反应蛋白（hs—CRP）、凝血功能、D-二聚体的变化与脑梗死的关系。方法：收集2012年3月-2013年2月于我院住院治疗的急性脑梗死患者172例为观察组,并根据病灶大小分为大梗死组、小梗死组和腔隙性脑梗死组。分别对3组患者入院后次日晨测定血清Hcy、血脂、hs—CRP、凝血功能、D-二聚体。100例健康体检者作为正常对照。结果：脑梗死患者血清Hcy、血脂、hs—CRP、纤维蛋白原（Fib）、D-二聚体水平均高于正常对照组,APTT和TT均低于正常对照组（P〈0．05）。血清Hcy水平与LDL、hs—CRP和血浆胁二聚体水平有一定相关性（r值分别为0．739,0．681和0．803,P〈0．01）。大梗死组、小梗死组血清Hcy、hs—CRP、LDL和血浆D-二聚体水平明显高于腔隙性脑梗死组（P〈0．05）,大梗死组血浆Fib水平明显高于腔隙性脑梗死组和小梗死组（P〈0．05）。脑梗死面积大小与血清Hcy、hs—CRP、LDL和血浆胁二聚体水平具有良好的相关性（r值分别为0．604、0．587、0．515、0．333,P〈0．05或P-〈0．01）。结论：血清Hcy、hs—CRP、LDL和D-二聚体水平升高可能是脑梗死的危险因素。     

LDL Hemoperfusion-A New Procedure for LDL Apheresis: First Clinical Application of an LDL Adsorber Compatible with Human Whole Blood

Abstract: To date, lipid apheresis procedures can remove low-density lipoprotein (LDL) cholesterol (LDL-C) only from plasma. Thus, initially plasma has to be separated from the blood cells, which increases the costs and complexity of the extracorporeal circuit. This paper describes the first clinical application of a new LDL adsorber that eliminates LDL directly from whole blood. The goal of this pilot study was to test the efficacy, safety, and feasibility of direct lipoprotein adsorption in patients. In a 2 center Phase II clinical trial, 12 hypercholesterolemic patients suffering from overt coronary or peripheral artery disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI, Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated polyacrylamide gel. The anticoagulation consisted of an initial heparin bolus followed by an acid citrate dextrose (ACD)-A infusion during the treatment. The processing of nearly 1 patient blood volume resulted in a reduction of LDL-C by 45 ± 8% and triglycerides by 23 ± 20%. HDL-C, fibrinogen, and cell counts were not significantly influenced. In a subgroup of 5 patients who exhibited elevated lipoprotein (a) (Lp[a]) levels, Lp(a) reduction was 43 ± 15% (all results corrected for plasma volume shifts). The sessions were clinically uneventful; the system was technically safe and easily handled. In conclusion, short-term LDL hemoperfusion by the DALI proved to be a safe, effective, and simple procedure for the treatment of patients suffering from symptomatic recalcitrant hypercholesterolemia. The present study represents a solid basis for the clinical long-term evaluation of this new technique in the future.     

Selective hemapheresis, an effective new approach in the therapeutic management of disorders associated with rheological impairment: mode of action and possible clinical indications

The in vitro measurement of whole-blood viscosity, plasma viscosity, and erythrocyte aggregability is easy to perform, but they only allow a partial insight into the complexity of blood flow characteristics; however, they permit definition of the rheological properties of new hemorheological therapeutic modalities such as extracorporeal plasma therapy as described in this paper. Under more theoretical aspects, it becomes obvious that such hemorheological approaches should either improve the vasomotoric properties of blood vessels, reduce the circulating red blood cell concentration, or improve the viscosity by reducing the concentration of hemorheologically relevant plasma proteins. In this review, the rheological effect of a single apheresis treatment with different devices was compared. Due to their differences in selectivity, the extracorporeal methods have different effects on the rheologically relevant plasma proteins, and, therefore, their rheological effectiveness differs remarkably. Today, the classical blood letting and plasma exchange treatment have been replaced by erythrapheresis and selective devices for extracorporeal plasma treatment, respectively. For more than 10 years, the following 5 more-or-less selective apheresis procedures are commercially available: immunoadsorption, differential filtration, polyanion adsorption by dextrane sulfate as well as by polyacrylate, and polyanion precipitation by heparin as polyanion. The last three procedures are semiselective and, therefore, relatively unspecific whereas immunoadsorption only affects the plasma lipoprotein concentration. Several studies have shown the effective use of extracorporeal hemorheotherapy for the treatment of various diseases including macro- and cryoglobulinemia, Raynaud's disease, hyperlipoproteinemia (often characterized by premature atherosclerosis and coronary heart disease and peripheral arterial occlusive disease), cerebral multi-infarct demention and acute ischemic stroke, sudden hearing loss, and acute occlusion of the central retinal artery.     

Lipid Parameters Including Lp(a) in Hemodialysis Patients

Chronic hemodialysis (CHD) patients have a high incidence and prevalence of atherosclerotic disease which may be related to numerous atherosclerotic risk factors. Among them dyslipidemia plays a significant role. Elevated Lp(a) levels, which are strongly associated with atherosclerosis, have been reported recently in uremic patients. The aim of our study was the determination of the levels of lipid parameters including Lp(a) in 151 CHD patients (76 male) aged 57 (12-81) years, who were on hemodialysis for a mean of 44.3 (range 1 to 189) months. Eighty-four normal individuals age and sex matched were used as controls. The median serum Lp(a) concentration in hemodialysis patients was 13 mg/dL compared with 6.5 mg/dL in healthy controls, p<0.001 by distribution-free Mann-Whitney test. The prevalence of subjects with Lp(a) levels above 25 mg/dL was significantly higher in CHD patients compared to normal subjects (30% vs. 8%, p<0.001). Even if CHD patients were matched for fasting lipid levels, they showed Lp(a) levels significantly higher than controls. No significant correlation was found between Lp(a) levels and either the age of the patients or the duration of hemodialysis. The etiology of primary renal disease did not influence the Lp(a) levels.     

急性脑出血中风与高血压和异常脂代谢关系的研究

目的探索高血压和异常脂代谢与急性脑出血中风的关系,探讨诱发脑出血中风危险因子。方法采用随机对照研究设计,对450例急性脑出血(ACH)患者和100例健康成人志愿者(HAV)的收缩压(SP)、舒张压(DP)值,及血清总胆固醇(TCH)、甘油三酯(TG)、高密脂蛋白胆固醇(HDL-CH)和低密度脂蛋白胆固醇(LDL-CH)含量,进行了检测和分析统计。结果与HAV组比较,ACH组的SP、DP、TCH、TG和LDL-CH平均值显著升高(P<0.0001),HDL-CH平均值显著降低(P<0.0001);双变量直线相关分析表明,随着ACH患者年龄的增加和SP、DP、TCH、TG、LDL-CH值的升高,患者的脑出血量逐渐增加(P<0.0005);逐步回归分析提示,患者脑出血量与SP、LDL-CH、HDL-CH和TCH值关系最密切,方程为Y=-13.3462+0.0656SP+1.2784LDL-CH+1.4051HDL-CH+0.6310TCH。结论年龄增长,SP、DP、TCH、TG、LDL-CH值显著升高,可能是诱发脑出血的危险因子;SP、TCH、LDL-CH值显著升高及HDL-CH值显著降低,可能是诱发脑出血的主要危险因子。     

Efficacy and safety of a new whole-blood low-density lipoprotein apheresis system (Liposorber D) in severe hypercholesterolemia

Low-density lipoprotein (LDL) apheresis is an extracorporeal modality to lower LDL cholesterol. While most of the devices eliminate LDL particles from plasma, a recently introduced whole-blood perfusion column (DALI) adsorbs lipoproteins directly from whole blood. We investigated the efficacy and safety of a new whole-blood LDL apheresis system (Liposorber D) in 10 patients with severe hypercholesterolemia in a multicenter trial. In 93 LDL aphereses, the mean reduction in LDL cholesterol and lipoprotein(a) was 62.2 +/- 11.5% and 55.6 +/- 16.9%, respectively (P < 0.01). If hemodilution during apheresis was considered, the reductions were 58.0 +/- 10.9 and 55.3 +/- 10.9%, respectively (P < 0.01), while high-density lipoprotein (HDL) cholesterol did not change significantly. Three mild episodes of hypocalcemia and two mild episodes of arterial hypotension were observed; however, LDL apheresis could be continued in each case. In conclusion, the new whole-blood LDL apheresis with Liposorber D is a safe, simple, and useful modality to reduce LDL cholesterol and lipoprotein(a) in cardiovascular high-risk patients.     

Use of fibrates in the metabolic syndrome:A review

The use of fibrates in the treatment of dyslipidaemia has changed significantly over recent years.Their role appeared clear at the start of this century.The Helsinki Heart Study and Veterans Affairs High-Density Cholesterol Intervention Trial suggested significant benefit,especially in patients with atherogenic dyslipidaemia.However,this clarity disintegrated following the negative outcomes reported by the Bezafibrate Infarction Prevention,Fenofibrate Intervention and Event Lowering in Diabetes and Action to Control Cardiovascular Risk in Diabetes randomised controlled trials.In this review we discuss these and other relevant trials and consider patient subgroups such as those with the metabolic syndrome and those needing treatment to prevent the microvascular complications associated with diabetes in whom fibrates may be useful.We also discuss observations from our group that may provide some explanation for the varying outcomes reported in large trials.The actions of fibrates in patients who are also on statins are interesting and appear to differ from those in patients not on statins.Understanding this is key as statins are the primary lipid lowering agents and likely to occupy that position for the foreseeable future.We also present other features of fibrate treatment we have observed in our clinical practice;changes in creatinine,liver function tests and the paradoxical high density lipoprotein reduction.Our purpose is to provide enough data for the reader to make objective decisions in their own clinical practice regarding fibrate use.     

Atherogenic lipid profile and lipoprotein(a) in relation to serum albumin in haemodialysis patients

Malnutrition in haemodialysis patients is associated with anincreased cardiovascular mortality. Lipoprotein(a) (Lp(a)) isan independent risk factor for atherosclerotic cardiovasculardisease. To evaluate the relationship between atherogenic lipidprofile and serum albumin in haemodialysis patients we measuredfasting serum Lp(a), total cholesterol (TC), high-density lipoprotein-cholesterol(HDL-C), triglyceride (TG), apoprotein A-I (ApoA-I), apoproteinB (ApoB) and albumin in 101 haemodialysis patients and in 46healthy subjects as a control. The haemodialysis patients weredivided into two groups on the basis of the level of serum albumin:group I, serum albumin <4.0 g/dl; group II, serum albumin>4.0 g/dl. Haemodialysis patients as a whole (n=101, 17.1 mg/dl (10.3–30.9))had higher serum Lp(a) than normal subjects (n = 46, 10.5 mg/dl(3.3–24)) (P<0.05). Lp(a) in group I (n = 38, 27.1mg/dl (14.6-35.0)) was significantly higher than in group II(n = 63, 14.5mg/dl(7.7–21.7), P<0.005) and normal subjects(P<0.0005). However, serum Lp(a) level of group II was notdifferent from those of normal subjects. There was a significantinverse correlation between serum Lp(a) and albumin concentration(r_s = -0.26, P<0.01). TC, TG, HDL-C, ApoA-I, ApoB, TC/HDL-C,and ApoA-I/ApoB ratios were not different between group I andgroup II. No correlation was found between albumin and TC, TG,HDL-C, TC/HDL-C, and ApoA-I/ApoB ratios. These results suggest that Lp(a) could be responsible for anincreased cardiovascular mortality in haemodialysis patientswith malnutrition.     

Serum lipoprotein (a) in renal transplant recipients receiving cyclosporin monotherapy

Coronary heart disease is more common in patients with chronicrenal failure and is a major cause of death after renal transplantation.Elevated serum lipoprotein (a) (Lp(a)) is a known risk factorfor coronary heart disease in the general population. We measured the serum concentration of Lp(a) in 58 renal transplantrecipients (40 male, 18 female) on cyclosporin monotherapy,and in 58 age- and sex-matched controls. Serum Lp(a) was significantlyelevated in the transplant patients with a median of 27.5 (range< 0.8–140.3) mg/dl compared to 7.6 (range <0.8–87.4)mg/dl in controls (P<0.001). Total serum cholesterol, low-densitylipoprotein cholesterol, and total triglyceride concentrationswere also significantly raised (P<0.001) in the transplantrecipients. The increased serum Lp(a) may contribute to the increased cardiovascularmorbidity associated with renal transplantation.     

Plasma levels of lipoprotein (a) do not predict progression of human chronic renal failure

Chronic renal failure is frequently accompanied by elevatedplasma levels of lipoprotein (a) [Lp(a)] Elevated Lp(a) levelshave been proposed to contribute not only to increased riskof atherosclerotic and thrombotic complications but also tothe progression of renal insufficiency. To investigate whetherhigher Lp(a) plasma concentrations are associated with an acceleratedrateof progression of renal insufficiency, we have correlated baselineplasma concentrations of Lp(a) with the progressive declineof renal function in an observational study of human chronicrenal disease. Forty-nine non-diabetic patients (40 men, ninewomen) were studied as part of an observational study of patientswith moderately advanced renal insufficiency. The average follow-uptime of the patient population was 3.1 years, and the mean rateof decline in glomer ular filtration rate (⁵¹Cr-EDTA clearance)was –2.8 (SD 4.1) ml/min/1.73 m² The mean plasma concentrationof Lp(a) at the beginning of the study was 19.2 (SD 18.6) mg/100ml with a median value of 12.2 mg/100 ml. There was no associationbetween the initial plasma concentration of Lp(a) and the rateof progression as assessed by linear regression analysis. Furthermore,the progression rate in patients with in the highest quartileof the Lp(a) distribution (30 mg/100 ml) did not differ fromthat in patients with lower levels of Lp(a). In contrast, increasedlevels of apolipoprotein (apo) B, low-density lipoprotein (LDL)-cholesterol,and proteinuria were all significantly associated with a morerapid decline in renal function. Based on these results, itwas concluded that elevated plasma levels of Lp(a) are not associatedwith an increased rate of progression of renal insufficiencyin human chronic renal disease. However, the results of thisstudy suggest that other apoB-containing lipoproteins may playa significant role in this process.     

Higher testosterone levels are associated with increased highdensity lipoprotein cholesterol in men with cardiovascular disease： results from the Massachusetts Male Aging Study

Aim： To study the relationship between circulating androgens （total testosterone [TT], free testosterone [IT] and dihydrotestosterone [DHT]） and high-density lipoprotein cholesterol （HDL-C） in men with and without cardiovascular disease （CVD）. Methods： Cross-sectional analyses included 1 661 baseline samples from the Massachusetts Male Aging Study （MMAS）, a population-based cohort of men ages 40-70 years. Serum hormones were measured by radioimmunoassay and HDL-C was determined following precipitation of the lower density lipoproteins. CVD was determined by self-report. Analyses were performed using multiple linear regression. Results： TT and HDL-C were positively correlated in the entire sample （r = 0.11, P = 0.0001）. After adjusting for confounders, we found this relationship was mostly limited to the 209 men with CVD. Among men with CVD, TT （P = 0.0004）, iT （P = 0.0172） and DHT （P = 0.0128） were all positively correlated with HDL-C, whereas in men without CVD only TT correlated with HDL-C （P = 0.0099）. Conclusion： Our results suggest that if androgens contribute to CVD in middle-aged men, the effect is not related to a suppressive effect of endogenous T on HDL-C. （Asian JAndrol 2008 Mar; 10： 193-200）     

冠心病患者焦虑抑郁与冠状动脉斑块稳定性的关系研究

目的探讨冠心病患者焦虑、抑郁与冠状动脉粥样硬化斑块稳定性的关系,为早期筛查负性情绪患者,减少不稳定斑块的发生提供参考。方法采用自编一般资料问卷,焦虑、抑郁自评量表对319例冠心病患者进行调查,通过光学相干断层成像技术行斑块稳定性分析。结果焦虑、抑郁发生率分别为31.3%、30.7%,15.7%患者同时存在焦虑抑郁。Logistic回归分析示,抑郁、低密度脂蛋白胆固醇对斑块稳定性有显著性影响(OR=1.062、1.322,均P<0.05)。结论抑郁及低密度脂蛋白胆固醇是冠状动脉斑块稳定性的主要影响因素。对冠心病患者应及早进行负性情绪及饮食行为的全面调查并实施针对性干预,以减少不稳定斑块的发生,预防心脏不良事件。