Increased atherogenicity of low-density lipoprotein in heavy proteinuria

Background: Heavy proteinuria is associated with marked abnormalities of lipoprotein metabolism and increased risk of atherogenesis. It is possible that qualitative as well as quantitative changes occur in lipoproteins to contribute to increased cardiovascular risk; for example, it is known that LDL exhibits heterogeneity, with small, dense LDL III particles being more atherogenic. Methods: We investigated LDL subfractions (measured by density gradient ultracentrifugation), VLDL subfractions, and post-heparin lipases in 12 patients with primary glomerular disease and 24-h albuminuria >2.5 g. These were compared to 23 age- and sex-matched controls. Results: Total LDL concentrations were similar in proteinuric patients and controls; however, there was a shift in subfraction distribution. The larger LDL I and LDL II particles were lower in the proteinuric group (29±24 vs 62±26 mg/dl P=0.011 and 121±80 vs 197±74 mg/dl P=0.028), whereas the concentration of atherogenic LDL III (small dense) was higher (135±64 vs 75±71 mg/dl P=0.0016). The concentration of total VLDL and both its subfractions were increased in the patients with proteinuria. Post-heparin hepatic and lipoprotein lipase levels were similar to normal. Conclusions: These findings suggest that the atherogenicity of LDL is increased in patients with heavy proteinuria because of the redistribution towards smaller denser particles. Since small, dense LDL has a lower affinity for the LDL receptor, the altered nature of the lipoprotein in proteinuria may decrease its clearance by the receptor-mediated pathway and contribute to the reduced clearance of LDL observed in this population. This may contribute to progression of renal failure or the accelerated vascular disease found in patients with heavy proteinuria.     

Low-density lipoprotein subfraction profiles in chronic renal failure

Background: Small low-density lipoprotein (LDL) particle size, a newly recognized risk factor for cardiovascular disease in the general population, is frequently associated with hypertriglyceridaemia, the predominant plasma lipid abnormality present in uraemia. Methods: Plasma lipids and LDL subfraction profiles were examined in 33 non-dialysed patients with chronic renal failure (predial), 40 patients on continuous ambulatory peritoneal dialysis (CAPD), 42 haemodialysis patients (HD), 47 renal transplant recipients (RTR), and 44 controls. LDL subfractions separated by gel electrophoresis were scored by densitometric analysis (higher scores indicate profiles comprising smaller particles). Results: All groups with renal failure had significantly elevated (mean±SD) LDL scores (predial 1.36±0.6, CAPD 1.71±0.9, HD 1.68±0.9, RTR 1.92±0.8 vs control 0.87±0.4, all P<0.001), this being the only lipid abnormality detected in the predialysis patients. In CAPD and HD patients, LDL scores were associated with serum triglyceride (r=0.81, P<0.0001 and r=0.70, P<0.01 respectively), cholesterol (r=0.55, P<0.001 and r=0.49, P<0.01) and HDL-cholesterol (r=-0.43, P<0.01 and r=-0.51, P<0.01), whilst no such relationship was seen in the predialysis and RTR groups, suggesting that other factors were important. Conclusions: The presence of small LDL particles appears to be an early and unexplained feature of the uraemic dyslipidaemia. This abnormality persists after renal transplantation and may represent an important atherogenic risk factor. Key words: LD subfractions; renal failure; transplants      

Abnormal lipoprotein metabolism in diabetic nephropathy

It is well known that patients with diabetes have a high incidence of cardiovascular disease (CVD), and the incidence of CVD becomes substantially elevated with development of diabetic nephropathy. The mechanisms for dyslipidemia in diabetic nephropathy are multifactorial and complex. Long-term hyperglycemia causes generalized vascular endothelial damage, which reduces functional lipoprotein lipase, leading to increased triglyceride (TG) levels and decreased high-density lipoprotein cholesterol (HDL-C). In overt-diabetic nephropathy, hypoproteinemia markedly increases low-density lipoprotein cholesterol (LDL-C), and renal failure specifically increases remnant lipoproteins and decreases HDL-C and LDL-C. Overt diabetic nephropathy exhibits remarkable postprandial hypertriglyceridemia with hyper-apolipoprotein (apo) B48, a marker of chylomicron and its remnants. Apo CIII is a key inhibitor of lipolysis and particle uptake of TG-rich lipoproteins, which is specifically increased in advanced chronic kidney disease, irrespective of the presence of diabetes. LDL size becomes smaller with advanced stages of diabetic nephropathy, whereas LDL size is not reduced in hemodialysis patients (HD). HD patients have marked lower levels of HDL3-C than controls. HD patients also have substantially low apo AI and high serum amyloid A (SAA) levels, suggesting the replacement of apo AI by SAA is stimulated in HDL particles.     

Low-density lipoprotein subfraction profiles in dialysis patients

Summary: Uraemic dyslipidaemia is a major risk factor for cardiovascular disease in end-stage renal failure patients. In patients without renal failure, high levels and qualitative abnormalities of low-density lipoprotein (LDL) are known to be atherogenic. Recently, LDL subfraction analysis has associated premature coronary artery disease with a high prevalence of small, dense LDL particles characterizing the LDL subclass phenotype B. We therefore examined the lipid profiles, LDL subfraction distribution and phenotypes in our population of haemodialysis (HD; n = 30) and peritoneal dialysis patients (PD; n = 17), and compared them to 40 asymptomatic, non-uraemic volunteers. Dialysis patients had significantly higher triglyceride and VLDL cholesterol concentrations and lower HDL cholesterol and smaller LDL peak particle diameters. PD patients had significantly higher total cholesterol, glycated haemoglobin and fasting blood glucose levels with smaller LDL peak particle diameters (24.4 [0.1] vs 24.8 [0.1 nm] than HD. Both groups showed significant negative correlations between plasma triglyceride and LDL peak particle diameter, and positive correlations between HDL cholesterol and LDL peak particle diameter. All the PD patients expressed the B phenotype (LDL peak diameter ± 25.5 nm) compared to 73% of HD patients. This study demonstrates that HD and especially PD patients have atherogenic lipid profiles which are associated with a predominance of small dense LDL particles and the highly atherogenic LDL subclass phenotype B.     

Effects of atorvastatin versus probucol on low-density lipoprotein subtype distribution and renal function in hyperlipidemic patients with nondiabetic nephropathy

Objectives: Small dense low-density lipoprotein (LDL) plays an important role in glomerular injury through conversion to an oxidatively modified form of LDL. However, few studies have evaluated the effects of antilipidemic agents on the LDL particle size and renal function in hyperlipidemic patients with nondiabetic nephropathy. Methods: This study was a randomized crossover trial comparing the effects of atorvastatin (10 mg/day) and probucol (500 mg/day) administered for 24 weeks in 31 patients (urinary albumin excretion 0.3–2.0 g/day and creatinine clearance >30 mL/min/1.73 m). Lipid parameters, mean LDL particle diameter, creatinine clearance, and urinary albumin to creatinine excretion ratio were measured before and during treatment periods. Main findings: Atorvastatin and probucol significantly reduced the serum total cholesterol and LDL cholesterol concentrations. When stratified by mean baseline LDL particle size at 25.5 nm, atorvastatin increased (p < 0.05) LDL particle size from 24.6 ± 0.5 to 25.2 ± 0.9 nm only in the <25.5 nm (pattern B) group, whereas probucol decreased (p < 0.05) LDL size from 24.8 ± 0.9 to 24.2 ± 0.9 nm in the pattern B group and from 25.9 ± 0.5 to 24.6 ± 0.8 nm in the ≥25.5 nm (pattern A) group. No significant differences in urinary albumin/creatinine excretion ratio and creatinine clearance were observed in both groups during treatment. Conclusions: Only atorvastatin improved the LDL-subtype distribution in hyperlipidemic patients with nondiabetic nephropathy, although both agents exhibited no renoprotective action, suggesting that the effects on LDL-subtype distribution do not directly lead to renoprotection.     

Risk factors for hyperlipidemia in long-term pediatric renal transplant recipients

Hyperlipidemia (HL) is a common problem in adult renal transplant (TP) recipients, contributing to an increased risk of cardiovascular disease and chronic TP nephropathy. There are multiple causes of HL post renal TP in adult patients, including pre TP HL, immunosuppressive agents, renal dysfunction, hypoalbuminemia secondary to nephrotic syndrome, obesity, and conditions that lead to end-stage renal disease (ESRD). We evaluated the incidence and risk factors of HL in 62 pediatric renal TP recipients (15.4±4.2 years, range-3.0–22.3 years) with long-term (6.7±3.1 years) functioning [glomerular filtration rate (GFR) 66.7±23.2 ml/min per 1.73 m²] allografts. The mean serum cholesterol (C) level was 205.5±43.6 mg/dl. Thirty-two patients (51.6%) exhibited elevated serum C levels. The mean serum triglyceride (TG) level was 157.3±88.4 mg/dl. Serum TG levels were elevated in 32 patients (51.6%). In patients with elevated serum levels of either C or TG, the mean low-density lipoprotein level (LDL) was 138.6±44.1 mg/dl (normal <130 mg/dl) and the high-density lipoprotein (HDL) level 54.6±15.9 mg/dl (normal>34 mg/dl). Of those patients studied, 45.5% had high LDL levels, whereas 9.1% exhibited low HDL levels. The two risk factors for elevated serum C levels in our patient population were pre-TP HL and increased years since TP. The only risk factor for elevated serum TG levels was reduced GFR. A family history of HL had a significant deleterious impact upon serum levels of C (P=0.01), but did not affect serum TG levels (P=0.7). Years on dialysis prior to TP, history of prior TP, gender, body mass index, and disease leading to ESRD had no influence upon the development of post-TP HL. We conclude that post-renal TP HL is a significant problem in pediatric renal TP recipients. Received: 13 January 1999 / Revised: 19 May 1999 / Accepted: 21 May 1999     

Relationship of low-density lipoprotein and nephrolithiasis in different genders

Objective To investigate the relationship between dyslipidemia and nephrolithiasis in a population-based study. Methods All participants were investigated by questionnaires, physical examinations and laboratory tests including liver and renal function, lipid profile, serum fasting glucose, glycosylated hemoglobin. Nephrolithiasis was diagnosed by kidney B-ultrasonography. Subjects with estimated glomerular filtration rate (eGFR)＜60 ml?min-1?(1.73 m2)-1 were excluded. Results 10 316 individuals were enrolled with an average age of (54.88±10.27) years (range 17-88 years) and the ratio of male to female 1∶1.12. The prevalence of nephrolithiasis was 5.6%, 3.7% and 7.8% for whole population, women and men, respectively. In women, only eGFR in stone group was significantly lower than that in non-stone group (P＜0.05). However, participants in stone group were significantly older (P＜0.05), of higher blood pressure (P＜0.01), higher serum uric acid (P＜0.01), worse renal function (serum creatinine, P＜0.05; eGFR, P＜0.01), and higher low-density lipoprotein (LDL) (P＜0.05), compared with those in non-stone group in men. Logistic regression analysis showed that only eGFR (P＜0.05) was the independent influential factor for kidney stones in women; In men, LDL was an independent influential factor for nephrolithiasis with a hazard ratio of 1.149 (95%CI 1.003-1.317, P＜0.05), except for mean blood pressure and eGFR. After being divided into normal group, borderline high group and high LDL group according to the LDL level, with the increase of LDL, the prevalence of nephrolithiasis was significantly increased by 7.3%, 8.3% and 10.6% in men respectively. There was no significant relationship between total cholesterol, triglyceride, high-density lipoprotein and nephrolithiasis. Conclusions Dyslipidemia is associated with nephrolithiasis in men, and high LDL cholesterol is an independent risk factor for nephrolithiasis. Clinical lipid testing not only helps to reduce the risk of atherosclerotic disease, but also reduces the risk of kidney stones.     

High triglyceride level is associated with severe coronary artery disease in hypertensive subjects

Background. The contribution of triglycerides (TG) to the extent of coronary artery disease (CAD) in hypertensive patients remained unclear. Methods. Consecutive 821 (aged 64.5±11.5 years, 482 males) hypertensive patients undergoing coronary angiography were included. The relationship of TG levels (<150 vs. ≥150 mg/dl) to the extent of CAD in all patients was examined by multiple logistic regression, adjusting for other CAD risk factors. In the lipid group, low levels of HDL were also adjusted. Results. Higher levels of TG were found in subjects with severe CAD compared to those with no or minimal CAD. The adjusted odds ratios for high levels of TG in the severe CAD subgroup versus the no or minimal CAD subgroup were 5.20 (95% CI, 3.13 to 8.63) in all patients and 7.51 (95% CI, 3.19 to 17.65) in the lipid group. Conclusions. High levels of TG are strong clinical markers of greater extent of CAD in hypertensive subjects undergoing coronary angiography. The results may have clinical relevance for physicians in therapeutic decision making.     

Effects of Different Dialysis Modalities on Cardiac Autonomic Dysfunctions in End‐Stage Renal Disease Patients: One Year Prospective Study

Cardiac autonomic dysfunction (CAD) is a common problem in patients with end‐stage renal disease (ESRD) and may contribute to the risk of cardiac mortality. Long‐term effects of dialysis modalities on CAD in ESRD patients are not clear. In this one‐year prospective study, we studied the effects of different dialysis modalities on CAD in ESRD patients. The study consisted of 20 ESRD patients who had the indications for initiating dialysis therapy (13 hemodialysis and 7 CAPD patients) and 15 healthy controls (M/F: 5/10; age 30 ± 4). In all the subjects, first at the beginning of study (in patient groups just before initiating dialysis therapy) and then after 12 months, we studied 24 hours ECG‐Holter monitoring and heart rate variability parameters (time and frequency domain analysis parameters; SDNN: standard deviations of nn intervals, rMSSD: square root of the median of standard deviation, HRVI: heart rate variability index, LF/HF: low frequency/high frequency). In ESRD patients, before dialysis therapy, all the parameters of time domain analysis were significantly lower compared to control group (p = 0.001). In patient groups, after dialysis therapy (on the 12th month), significant improvement was observed in time domain analysis parameters (p = 0.001). When dialysis modalities were compared, the increase in the time domain analysis parameters was significantly greater in the CAPD group compared to hemodialysis (HD) group. Our findings suggest that CAD is frequent in ESRD patients, a dialysis therapy of 12 months can cause significant improvement on CAD and the ameliorative effect of CAPD is better than HD.     

Characteristics of low‐density and high‐density lipoprotein subclasses in pediatric renal transplant recipients

Renal transplant recipients often suffer from dyslipidemia which is one of the principal risk factors for cardiovascular disease. This study sought to determine characteristics of high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) particles and their associations with carotid intima‐media thickness (cIMT) in a group of pediatric renal transplant recipients. We also examined the influence of immunosuppressive therapy on measured LDL and HDL particle characteristics. HDL size and subclass distribution were determined using gradient gel electrophoresis, while concentrations of small, dense LDL (sdLDL)‐cholesterol (sdLDL‐C) and sdLDL‐apolipoprotein B (sdLDL‐apoB) using heparin‐magnesium precipitation method in 21 renal transplant recipients and 32 controls. Renal transplant recipients had less HDL 2b (P < 0.001), but more HDL 3a (P < 0.01) and 3b (P < 0.001) subclasses. They also had increased sdLDL‐C (P < 0.01) and sdLDL‐apoB (P < 0.05) levels. The proportion of the HDL 3b subclasses was a significant predictor of increased cIMT (P < 0.05). Patients treated with cyclosporine had significantly higher sdLDL‐C and sdLDL‐apoB concentrations (P < 0.05) when compared with those on tacrolimus therapy. Pediatric renal transplant recipients have impaired distribution of HDL and LDL particles. Changes in the proportion of small‐sized HDL particles are significantly associated with cIMT. Advanced lipid testing might be useful in evaluating the effects of immunosuppressive therapy.     

Pre‐existing Arterial Micro‐Calcification Predicts Primary Unassisted Arteriovenous Fistula Failure in Incident Hemodialysis Patients

Vascular access micro‐calcification is a risk factor for cardiovascular morbidity and mortality in hemodialysis (HD) patients but its influence on vascular access patency is still undetermined. Our study aimed to determine the impact of arterial micro‐calcification (AMiC) on the patency of vascular access in HD patients. One‐hundred fourteen HD patients receiving arteriovenous fistula (AVF) operation were included in this study. During the operation, we obtained partial arterial specimen and performed pathological examination by von Kossa stain to identify AMiC. We compared primary unassisted AVF failure within 1 year between positive and negative AMiC groups, and performed Cox regression analysis for evaluating risk factor of AVF failure. The incidence of AMiC was 37.7% and AVF failure occurred in 45 patients (39.5%). The AVF failure rate within 1 year was greater in the positive AMiC group than those in the negative AMiC group (53.5% vs. 31.0%, p = 0.02). Kaplan–Meier analysis showed that the positive AMiC group had a lower AVF patency rate than the negative AMiC group (p = 0.02). The presence of AMiC was an independent risk factor for AVF failure. In conclusion, preexisting AMiC of the vascular access is associated with primary unassisted AVF failure in incident HD patients.     

Oxidative stress in children on hemodialysis: value of autoantibodies against oxidized low-density lipoprotein

The principal causes of morbidity and mortality in children with chronic renal failure on maintenance hemodialysis are cardiovascular complications. Recently, it has been suggested that oxidative stress, chronic inflammation and malnutrition are risk factors for cardiovascular disease. However, to date, biomarkers of oxidative stress have not been well studied in children. The aim of this study was to investigate the relationship between oxidative stress and cardiovascular risk factors in children on hemodialysis therapy. Twenty-eight hemodialysis patients (13 females, 15 males; mean age 15.1 ± 2.5 years) and 20 healthy children (13 females, seven males; mean age 14.3 ± 2.7 years) were included in the study. Levels of antibodies to oxidized low-density lipoprotein (oLABs), high sensitivity C-reactive protein (hs-CRP), albumin, prealbumin, transferrin, and ferritin were measured. Antibodies to oxidized low-density lipoprotein (LDL) in hemodialysis patients were lower than those in the controls (P < 0.05). The patients with lower oLAB titers had higher levels of hs-CRP and ratio of erythropoietin to hematocrit (EPO/Htc), and lower levels of albumin, prealbumin, apolipoprotein A-1 (ApoA₁), and high-density lipoprotein (P < 0.05). Antibodies to oxidized LDL in hemodialysis patients with dyslipidemia were lower than those of patients with normal lipid profile (P < 0,05). This study showed that children treated by hemodialysis are exposed to oxidative stress and chronic inflammation. We suggest that oLAB levels are decreased in children on hemodialysis as a result of severe oxidative stress and that these antibodies are related to inflammation, anemia, malnutrition and dyslipidemia.     

Oxidised low‐density lipoprotein,a possible distinguishing lipid profile biomolecule between prostate cancer and benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) share common conditions such as lower urinary tract symptoms (LUTS) and dyslipidaemia. Whether an extensive lipid profile analysis could discriminate between BPH and PCa was the objective. Thirty‐six (36) BPH and twenty (20) PCa outpatients of a urology clinic plus forty (40) controls without LUTS, but normal PSA, were recruited. Body mass index (BMI), lipid profile (total cholesterol [CHOL], triglycerides [TG], high‐density lipoprotein [HDL], very‐low‐density lipoprotein [VLDL], low‐density lipoprotein [LDL] and Castelli's risk index I [CR I] [TC/HDL]), oxidised LDL, apolipoprotein E, ceramide and PSA were determined. Mean ages for BPH, PCa and control were 69 ± 13, 67 ± 10 and 53 ± 7 years respectively. Most parameters apart from BMI and HDL were significantly different compared to the control group. oxLDL for BPH versus control, PCa versus control and BPH versus PCa was significant (p < 0.001, p = 0.02 and p < 0.001 respectively). Ceramide showed significant group differences. Between BPH and PCa, total cholesterol, LDL and Apo E were significantly different (p = 0.00, p = 0.01 and p = 0.03 respectively). Apo E could potentially be a discriminating biomarker. Receiver operating characteristic curves for TPSA, Apo E and oxLDL demonstrated sensitivity of 69.44 and specificity of 88.24 for oxLDL, hence more discriminatory.     

Metabolism of low-density lipoprotein from patients with diabetic hypertriglyceridemia by cultured human skin fibroblasts

To test whether triglyceride-enriched low-density lipoprotein (LDL) obtained from subjects with diabetic hypertriglyceridemia is metabolized normally by cells, LDL was separated from seven healthy control subjects (fasting plasma glucose [FPG] 91 +/- 10 mg/dl [mean +/- SD], triglyceride [TG] 110 +/- 47 mg/dl), six diabetic normolipidemic patients (FPG 218 +/- 65 mg/dl; TG 139 +/- 75 mg/dl), six diabetic hypertriglyceridemic patients (FPG 214 +/- 71 mg/dl; TG 1915 +/- 1680 mg/dl), and five nondiabetic hypertriglyceridemic patients (FPG 92 +/- 8 mg/dl; TG 2013 +/- 1889 mg/dl). Binding of 125I-labeled LDL from hypertriglyceridemic subjects with and without diabetes to cultured skin fibroblasts was significantly decreased to 74 +/- 19% and 78 +/- 14% of that seen with LDL from normolipidemic nondiabetic subjects and diabetic normolipidemic controls (100 +/- 0%, 101 +/- 25%; P less than 0.005). Unlabeled LDL from hypertriglyceridemic subjects with and without diabetes failed to suppress LDL receptor activity and sterol synthesis from 14C-acetate as efficiently as unlabeled LDL from healthy subjects. The ability of LDL from hypertriglyceridemic subjects, whether diabetic or not, to suppress LDL binding was inversely related to the ratio of triglyceride to protein in LDL (r = 0.71, P less than 0.01) and showed a positive correlation with the LDL cholesterol/protein ratio (0.69, P less than 0.01). Thus, LDL from patients with hypertriglyceridemia, with or without coexistent diabetes, shows impaired binding to LDL receptors and less ability to downregulate LDL receptor activity and sterol synthesis than does LDL from normolipidemic diabetic and nondiabetic subjects. These findings suggest that factors associated with hypertriglyceridemia rather than with diabetes result in altered metabolism of LDL in these disorders.     

Serum oxidized low-density lipoprotein is inversely correlated to telomerase activity in peripheral blood mononuclear cells of haemodialysis patients

BACKGROUND: Telomerase preserves telomeres' function and structure preventing cellular senescence. Its activity is reduced in peripheral blood mononuclear cells (PBMC) of haemodialysis (HD) patients. The purpose of this study is to investigate the potential correlation between increased oxidative stress/inflammation and telomerase activity in PBMC of HD patients. METHODS: Telomerase activity was measured by PCR-ELISA in PBMC isolated from a group of 42 HD patients and 39 subjects with estimated glomerular filtration rate >or=80 mL/min (control group). Serum oxidized low-density lipoprotein (ox-LDL), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were also measured in both groups by ELISA. RESULTS: Ox-LDL was negatively correlated to percentage telomerase activity in PBMC (r = -0.506, P = 0.000 in the whole group of 81 HD and normal subjects and r = -0.559, P < 0.001 in HD patients). TNF was also inversely associated with percentage telomerase activity in the whole group studied (r = -0.492, P = 0.000) while IL-10 was not. In stepwise multiple linear regression, taking into consideration the most important characteristics of the HD patients and control group, the only significant predictors for percentage telomerase activity in PBMC were ox-LDL and TNF (beta = -0.421, t = -4.083, P = 0.000 and beta = -0.381, t = -3.691, P = 0.000, respectively) while examining separately HD patients, the predictors for the same parameter were ox-LDL and HD duration (beta = -0.671, t = -4.709, P = 0.000 and beta = -0.349, t = -2.447, P = 0.023, respectively). CONCLUSION: Ox-LDL serum level is inversely correlated to telomerase activity in PBMC of HD patients. Our study proposes a new consequence of increased oxidative stress in HD patients: the premature cellular senescence potentially related to atherosclerosis through LDL oxidation.     

Are the Anticardiolipin Antibodies a Risk Factor for Coronary Artery Disease in Chronic Renal Failure Patients?

Objective. It has been proposed that anticardiolipin (aCL) antibodies are a risk factor for coronary artery disease (CAD) in recently studies. In this study, we aimed to investigate the existence of coronary artery disease in dialysis patients who were aCL positive and undergoing hemodialysis and peritoneal dialysis due to end stage renal failure and also to determine its relationship with risk factors in patients with coronary artery disease. Methods. This study has been conducted in the end stage renal failure in 140 hemodialysis patients, 18 peritoneal dialysis patients, and 38 healthy controls. The urea, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, total protein, and albumin values are obtained. In all cases, aCL levels are investigated with ELISA method. Results. In the HD and CAPD patients, no significant relationship could be found between the age, gender, dialysis time, total cholesterol, HDL cholesterol, LDL cholesterol, total protein, and albumin values (p > 0.05). HD and CAPD vs. controls (aCL), 9.2% (13/140), 11.1% (2/18) vs. 2.6% (1/38), p = 0.002. No significant difference was noted between aCL-positive and -negative patients in serum urea, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, total protein, and albumin levels. The coronary artery disease was determined in three patients out of 16 patients with aCL positivity. Conclusion. The prevalence of aCL antibodies positivity in our study was similar to the prevalence of aCL positivity in other studies. Therefore, we do not think aCL antibodies positivity is a risk factor for coronary artery disease.     

Influence of low molecular weight heparin compared to conventional heparin for anticoagulation during haemodialysis on low density lipoprotein subclasses.

BACKGROUND: In haemodialysis (HD) patients, low density lipoprotein (LDL) particle distribution is characterized by a higher proportion of more atherogenic dense LDL. Though clinical studies showed favourable effects of low molecular weight (LMW) heparin compared to standard heparin on triglycerides (TG) and cholesterol (CH) in HD patients with hypertriglyceridaemia, it is not known if LMW heparin influences LDL subfraction pattern. Thus, the aim of this pilot study was to investigate if a switch to LMW heparin influences LDL subfractions and apolipoproteins. METHODS: Ten outpatients with fasting TG >230 mg/dl in the chronic HD programme on heparin for anticoagulation (AC) were switched to dalteparin (80 IU/kg body weight as a bolus). Blood samples were drawn for CH, TG, LDL-CH, HDL-CH, apolipoproteins (apo), very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and LDL subclasses at the beginning and after 12 months of therapy. Lipoproteins were isolated by preparative ultracentrifugation. Total LDL were fractionated into six density classes by equilibrium density gradient ultracentrifugation [(density in kg/l): LDL-1 1.019-1.031, LDL-2 1.031-1.034, LDL-3 1.034-1.037, LDL-4 1.037-1.040, LDL-5 1.040-1.044, LDL-6 1.045-1.063]. CH and TG were determined enzymatically, apolipoproteins by turbidimetry. RESULTS: In eight patients suitable for evaluation cholesterol decreased from 241 to 202 (P<0.05) and TG from 557 to 278 mg/dl (P<0.01), whereas LDL-CH and HDL-CH did not change significantly. A 28.2% decrease of VLDL (P<0.01) and a 19.3% decrease of IDL (P<0.05) paralleled by a significant drop of apoB were observed. Buoyant LDL subclasses increased (LDL-2, +34.3% and LDL-3, +20.3%) whereas dense LDL (LDL-5, -13.4% and LDL-6, -33.1%) decreased (P<0.05 for LDL-6). The ratio of buoyant LDL to dense LDL increased from 0.46+/-0.28 to 0.72+/-0.33 (P<0.05). CONCLUSION: In hypertriglyceridaemic HD patients, dalteparin improved metabolism of TG-rich lipoproteins, increased buoyant LDL and decreased potentially atherogenic dense LDL. Preservation of lipoprotein lipase by LMW heparin may be a possible mechanism to explain our findings.     

Effects of Testosterone on Lipid Peroxidation,Lipid Profiles and some Coagulation Parameters in Rabbits*

The purpose of this study was to investigate the effects of testosterone on some risk factors of atherosclerosis. Twenty‐four male New Zealand white rabbits were randomly divided into three groups of eight. The first group was used as control. Second group was injected with 10 mg of testosterone propionate. Third group was castrated bilaterally. At the end of 6 weeks, lipid peroxidation (LPO), lipid profile, fibrinogen (FBN) level and coagulation parameters were evaluated. Testosterone administration decreased the level of high‐density lipoprotein cholesterol (HDL‐C), while castration increased this level (P < 0.05). Triglyceride (TG) and total cholesterol (TC) levels in the castration group were significantly higher (P < 0.05) than those in the testosterone group. The ratio of HDL‐C:low‐density lipoprotein cholesterol (LDL‐C) decreased, while TC:HDL‐C ratio increased (P < 0.05) in the testosterone group. No significant differences were found in the LDL‐C and FBN levels among groups. However, there was a tendency for higher FBN level in the testosterone group. Testosterone administration resulted in an increase in the level of LPO (P < 0.05). Clotting time and prothrombin time prolonged in the castration group compared with testosterone group (P < 0.05). As a result, testosterone has exacerbating effect on atherosclerosis risk factors including lipid profile, LPO, FBN and coagulation system.     

尿酸联合脂蛋白a预测动脉粥样硬化高危人群肾动脉狭窄

目的 研究动脉粥样硬化高危人群中尿酸和脂蛋白a[Lp(a)]预测动脉粥样硬化性肾动脉狭窄( ARAS)的价值.方法 回顾性分析2008年10月至2011年4月在北京协和医院怀疑为ARAS,并接受肾动脉造影的190例患者的临床资料,其中89例诊为ARAS;部分患者同时接受了冠脉造影.对照组为年龄、性别匹配的180例同期本院常规体检人群.收集一般临床资料、血尿酸(UA)、Lp(a)、胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白( LDL)、Scr和C反应蛋白(CRP)等.分析ARAS患者的临床特点和相关危险因素,并利用二元Logistic回归分析尝试建立在高危人群中预测ARAS的临床决策工具.结果 ARAS患者的Scr、UA、Lp(a)和CRP水平显著地高于健康体检人群.高度怀疑ARAS或同时伴有冠状动脉病变而行肾动脉造影患者中,确诊ARAS组与非ARAS组生化指标、血脂、UA和肾功能差异均无统计学意义.二元Logistic回归分析显示,UA＞344μmol/L是ARAS发病的独立相关因素;且当UA＞344 μmol/L和Lp(a )＞242 mg/L时,预测ARAS的特异性达96％,阳性似然比为5.45,P=0.001,OR值为6.78,95％CI( 1.90～24.2),P=0.001.结论 ARAS的高危人群中,UA升高是ARAS的独立危险因素;UA联合Lp(a)对于预测ARAS有一定的临床意义.     

Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in haemodialysis patients

Aim: There is accumulating evidence that advanced glycation end products (AGE) play a role in cardiovascular disease (CVD) in patients with haemodialysis (HD). Carnitine deficiency is frequently observed in HD patients, which may also contribute to CVD. In this study, we examined whether carnitine deficiency was independently associated with increased tissue accumulation levels of AGE in HD patients. Methods: One hundred and twenty‐nine HD patients underwent determinations of blood chemistries including serum level of carnitine. Tissue AGE levels were evaluated by measuring skin autofluorescence with an AGE‐reader. Results: Serum carnitine levels were significantly lower, while skin AGE levels were significantly higher in HD patients compared with healthy controls (P < 0.001). In univariate analysis, β₂‐microglobulin (β₂‐MG) and carnitine (inversely) were correlated with skin AGE levels. Multiple stepwise regression analysis revealed that carnitine levels were one of the independent determinants of skin AGE levels (P = 0.024). When β₂‐MG‐adjusted skin AGE levels were stratified by serum carnitine levels, a statistical significance and dose‐response relationship were observed (P = 0.043). Furthermore, skin AGE levels were one of the independent determinants of serum carnitine levels as well (P = 0.012). Conclusion: The present study demonstrated that decreased carnitine levels were independently associated with increased skin AGE levels in HD patients. Since carnitine is reported to inhibit the formation of AGE in vitro, our study suggests that supplementation of carnitine may be a therapeutic target for preventing the accumulation of tissue AGE and subsequently reducing the risk of CVD in HD patients.