LCAT-dependent conversion of prebeta1-HDL into alpha-migrating HDL is severely delayed in hemodialysis patients

Prebeta1-HDL is a minor HDL subfraction that acts as an efficient initial acceptor of cell-derived free cholesterol. During 37 degrees C incubation, plasma prebeta1-HDL decreases over time due to its conversion to alpha-migrating HDL by lecithin:cholesterol acyltransferase (LCAT). This conversion may be delayed in hemodialysis patients who have decreased LCAT activity. To clarify whether LCAT-dependent conversion of prebeta1-HDL to alpha-migrating HDL is delayed in hemodialysis patients, prebeta1-HDL concentrations were determined in 45 hemodialysis patients and 45 gender-matched control subjects before and after 37 degrees C incubation with and without the LCAT inhibitor. It was found that the baseline prebeta1-HDL concentration in hemodialysis patients was more than twice that in the controls (44.9 +/- 21.4 versus 19.8 +/- 6.7 mg/L apoAI; P < 0.001). After 2-h incubation, the LCAT-dependent decrease in prebeta1-HDL in hemodialysis patients was about one-third of that in the controls (30 +/- 27 versus 97 +/- 17% of baseline; P < 0.01). The LCAT-dependent rate of decrease in prebeta1-HDL levels (DR(prebeta1)) was the same for samples from hemodialysis patients exhibiting normal (> or =1.03 mmol/L) and low HDL-cholesterol levels (32 +/- 32 versus 28 +/- 23% of baseline; NS). DR(prebeta1) was positively correlated with LCAT activity (r = 0.617; P < 0.001). In conclusion, the LCAT-dependent conversion of prebeta1-HDL to alpha-migrating HDL is severely delayed in hemodialysis patients. The impaired catabolism of prebeta1-HDL may accelerate atherosclerosis in hemodialysis patients.     

Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome

The metabolic syndrome is characterized by insulin resistance and abnormal apolipoprotein AI (apoAI) and apolipoprotein B-100 (apoB) metabolism that may collectively accelerate atherosclerosis. The effects of atorvastatin (40 mg/day) and micronised fenofibrate (200 mg/day) on the kinetics of apoAI and apoB were investigated in a controlled cross-over trial of 11 dyslipidemic men with the metabolic syndrome. ApoAI and apoB kinetics were studied following intravenous d(3)-leucine administration using gas-chromatography mass spectrometry with data analyzed by compartmental modeling. Compared with placebo, atorvastatin significantly decreased (P < 0.001) plasma concentrations of cholesterol, triglyceride, LDL cholesterol, VLDL apoB, intermediate-density lipoprotein (IDL) apoB, and LDL apoB. Fenofibrate significantly decreased (P < 0.001) plasma triglyceride and VLDL apoB and elevated HDL(2) cholesterol (P < 0.001), HDL(3) cholesterol (P < 0.01), apoAI (P = 0.01), and apoAII (P < 0.001) concentrations, but it did not significantly alter LDL cholesterol. Atorvastatin significantly increased (P < 0.002) the fractional catabolic rate (FCR) of VLDL apoB, IDL apoB, and LDL apoB but did not affect the production of apoB in any lipoprotein fraction or in the turnover of apoAI. Fenofibrate significantly increased (P < 0.01) the FCR of VLDL, IDL, and LDL apoB but did not affect the production of VLDL apoB. Relative to placebo and atorvastatin, fenofibrate significantly increased the production (P < 0.001) and FCR (P = 0.016) of apoAI. Both agents significantly lowered plasma triglycerides and apoCIII concentrations, but only atorvastatin significantly lowered (P < 0.001) plasma cholesteryl ester transfer protein activity. Neither treatment altered insulin resistance. In conclusion, these differential effects of atorvastatin and fenofibrate on apoAI and apoB kinetics support the use of combination therapy for optimally regulating dyslipoproteinemia in the metabolic syndrome.     

Lipids and apolipoprotein profiles in men with aneurysmal and stenosing aorto-iliac atherosclerosis

The plasma lipids, lipoproteins and apolipoproteins have been compared in two groups of men with aorto-iliac atherosclerosis: Aneurysmal disease (n = 42) and stenosing disease (n = 86). The mean age of the men aneurysmal disease was 67.5 +/- 5.8 years and the mean age of the men with stenosing disease was 65.0 +/- 6.1 years: There was no significant different in body mass indices or smoking habits between the groups. The patients with aneurysmal disease had lower levels of plasma cholesterol than patients with stenosing disease (5.53 +/- 1.17 versus 6.11 +/- 1.20 mmol/L, P less than 0.05), but carried more cholesterol in VLDL compared to patients with stenosing disease (1.00 +/- 0.90 versus 0.60 +/- 65 mmol/L, P less than 0.05). Significantly lower concentration of apolipoprotein AI and HDL-cholesterol in patients with aneurysmal disease (ApoAI 1.01 +/- 0.31 versus 1.18 +/- 0.31 mmol/L, P less than 0.02, HDL 0.93 +/- 0.53 versus 1.13 +/- 0.34, P less than 0.05) was another characteristic difference between these two groups of patients with peripheral arterial disease. Otherwise, there were no obvious differences in the levels of plasma triglyceride, VLDL-triglyceride, LDL-cholesterol, and apolipoproteins B, C-III and E between the two groups. Although lipid and apolipoprotein profiles may not discriminate between aneurysmal and stenosing disease, different types of lipoprotein particles may contribute to the atherosclerotic process characterising both diseases.     

Relationship of phospholipid transfer protein activity to HDL and apolipoprotein B-containing lipoproteins in subjects with and without type 1 diabetes

Patients with type 1 diabetes have greatly increased phospholipid transfer protein (PLTP) activity and have an altered HDL subclass distribution. In 195 patients with type 1 diabetes and in 194 men and women aged 30-55 years, we examined the relationship of PLTP activity to HDL and examined whether PLTP activity contributes to differences in HDL found in type 1 diabetes. PLTP activity was measured using an exogenous substrate assay. Average HDL particle size and HDL subclasses were measured using nuclear magnetic resonance spectroscopy. Apolipoprotein AI (apoAI) and apoAII were measured by immunoturbidimetry. The amount of apoAI present in LpAI was measured using a differential electroimmunoassay, and the amount of apoAI in LpAIAII was inferred from the apoAI and LpAI data. Higher PLTP activity was associated with more large HDL (P < 0.001) and less small HDL (P < 0.01), more apoAI and apoAII (both at P < 0.001), and more apoAI in both LpAI and LpAIAII (P = 0.02 and P < 0.001, respectively). These associations were independent of other lipids and enzyme activities. Adjusting for PLTP activity halved the difference between subjects with and without diabetes in apoA1 (from 10.1 mg/dl higher in subjects with diabetes to 4.6 mg/dl higher) and large HDL (2.4 micro mol/l higher to 1.2 micro mol/l higher) and reduced the difference in HDL size (from 0.31 nm higher to 0.26 nm higher). PLTP activity was also positively associated with apoB, total VLDL and LDL particle number, and IDL level in subjects with diabetes. These data support the idea that PLTP is a major factor in HDL conversion and remodeling in humans and that higher PLTP activity makes an important contribution to the higher apoAI levels and altered HDL subclass distribution in type 1 diabetes. They also support a role for PLTP in the metabolism of apoB-containing lipoproteins.     

Effects of omega-3 fish oils on plasma lipids, lipoprotein composition, and postheparin lipoprotein lipase in women with IDDM

Because the apparent reduction in cardiovascular risk noted in nondiabetic populations that ingest diets rich in marine lipids containing omega-3 fatty acids is believed to result in part from their capacity to modify the composition and physicochemical behavior of lipoproteins, we sought to determine whether dietary supplementation with marine lipids might favorably affect lipoprotein composition in insulin-dependent diabetes mellitus (IDDM). Eight normolipidemic IDDM women (mean +/- SD age 29.8 +/- 4.7 yr) were studied before and 3 mo after receiving a marine-lipid concentrate (Super-EPA) containing 6 g omega-3 fatty acids and a total of 12 mg of cholesterol daily. Weight, insulin requirements, and glycosylated hemoglobin remained stable. After treatment, mean +/- SD plasma triglyceride (TG) levels fell (before, 81.7 +/- 22 mg/dl; after, 69.19 +/- 17; P less than 0.025). High-density lipoprotein2 (HDL2) cholesterol (before, 10.98 +/- 5.45 mg/dl; after, 18.43 +/- 7.93; P less than 0.01), its major apolipoprotein A-I (apoAI), and the major phospholipids (sphingomyelin and lecithin) all rose significantly. ApoB and plasma and low-density lipoprotein cholesterol levels and HDL3 composition were unchanged. Postheparin hepatic and lipoprotein lipase activities were unaffected by marine lipids. These data indicate that women with IDDM experience apparently beneficial effects on TG and HDL2 from dietary supplementation with omega-3 fatty acids administered in a low-cholesterol-containing oil without adversely affecting overall diabetes management. If these changes in lipoprotein concentration and composition prove to have antiatherogenic consequences and are free of long-term toxicity, these agents may have a role in the therapy of IDDM patients.     

Hepatic HDL receptor, SR-B1 and Apo A-I expression in chronic renal failure.

BACKGROUND: Chronic renal failure (CRF) is associated with hypertriglyceridaemia and depressed plasma high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I (Apo A-I) concentrations. Uraemic hypertriglyceridaemia is due, in part, to lipoprotein lipase and hepatic lipase deficiencies, which are causally linked to excess parathormone (PTH). This study was designed to test the hypothesis that depressed plasma concentration and abnormal composition of HDL in CRF may be due to dysregulation of hepatic expression of Apo A-I and/or the newly discovered HDL receptor. METHODS: Hepatic Apo A-I and HDL receptor mRNA abundance (Northern blot), and HDL receptor protein mass (Western blot) were determined in CRF rats (5/6 nephrectomy), parathyroidectomized CRF rats (CRF-PTx) and sham-operated controls. RESULTS: The CRF group exhibited normal hepatic HDL receptor mRNA and HDL receptor protein abundance coupled with reduced hepatic Apo A-I mRNA. Hepatic Apo A-I mRNA, HDL receptor mRNA and protein abundance were not affected by PTx. CONCLUSIONS: CRF results in the down-regulation of hepatic Apo A-I gene expression, which accounts for the known reduction in plasma Apo A-I concentration. However, CRF does not affect HDL receptor mRNA or protein expression in this model. Neither Apo A-I nor HDL receptor expression were modified by PTx in CRF rats.     

Serum paraoxonase activity in uremic predialysis and hemodialysis patients

BACKGROUND: Paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated enzyme and has been shown to reduce the susceptibility of low-density lipoprotein (LDL) to lipid peroxidation. This study aimed to investigate the activity and phenotype distribution of serum paraoxonase in uremic patients, and to evaluate the correlations of uremia-associated substances (urea, creatinine (Cr) and uric acid) with paraoxonase activity. METHODS: Twenty-eight patients with chronic renal failure (CRF), 44 patients with CRF undergoing hemodialysis (HD) and 26 healthy controls were included in this study. Paraoxon or phenylacetate was used as a substrate for measuring paraoxonase and arylesterase activity, respectively. The double substrate method was used to assign phenotypes. Serum lipid parameters were determined by routine laboratory methods. RESULTS: Paraoxonase activity, HDL-cholesterol and apolipoprotein (apo) AI levels were found to be significantly lower in HD patients than in controls. However, HDL-standardized paraoxonase activity (PON activity/HDL) was not different in the HD patients compared to controls. Arylesterase activity was significantly lower in both CRF and HD patients than in controls. Paraoxonase phenotype distribution was not different among the groups according to the double substrate method. Serum paraoxonase and arylesterase activities correlated inversely with serum urea and Cr levels. CONCLUSION: Patients on long-term HD have reduced paraoxonase/arylesterase activities and this could be related to reduced HDL-cholesterol and apo AI levels, as well as increased urea and Cr levels in uremia.     

Lipoprotein (a): Relationship to vascular disease in dialysis and renal transplantion

Summary: Serum lipids and lipoprotein (a) concentrations were measured in 91 renal transplant and 60 dialysis patients and correlations sought with clinically evident vascular disease. Serum lipoprotein (a) concentrations were greater than 300 mg/L in 24% of the renal transplant recipients and 40% of the dialysis patients. In the renal transplant recipients, low high density lipoprotein (HDL) cholesterol ( P <0.05) and high total cholesterol to HDL cholesterol ratio ( P <0.01) were more strongly associated with the presence of vascular disease than was elevated lipoprotein (a). In the dialysis patients, a low serum albumin ( P <0.05) and low serum creatinine ( P <0.001), indicative of a poor nutritional state, were associated with the presence of vascular disease. A high total serum cholesterol to HDL cholesterol ratio ( P <0.05) was indicative of ischaemic heart disease, and high total serum cholesterol ( P <0.01) and low density lipoprotein (LDL) cholesterol ( P <0.01) of cerebrovascular disease. In the subpopulation on CAPD, elevated lipoprotein (a) levels were associated with cerebrovascular disease ( P <0.01). the present study demonstrates that an elevation in serum lipoprotein (a) concentration is not as strongly associated with the presence of vascular disease in patients with end-stage renal failure as are the total serum cholesterol, HDL and LDL cholesterol and the ratio of total cholesterol to HDL cholesterol.     

Plasma atrial natriuretic peptide and its relation to the renin-angiotensin-aldosterone system in patients with chronic renal failure.

To determine the relationship between plasma immunoreactive atrial natriuretic peptide (i-ANP) and renin-angiotensin-aldosterone system (RAAS), plasma i-ANP, plasma renin activity (PRA) and plasma aldosterone (PA) were assayed in 29 patients (19 hypertensive and 10 normotensive) with chronic renal failure (CRF), and in 10 healthy subjects. Hypertensive patients had higher i-ANP values than normotensive patients and controls (P less than 0.05 and P less than 0.01 respectively). There was no significant correlation between plasma i-ANP and creatinine concentrations in hypertensive patients, whereas this correlation was statistically significant in normotensive patients (r = 0.70, P less than 0.01). Other positive correlations were between plasma i-ANP and systolic blood pressure in hypertensive patients (r = 0.69, P less than 0.01) and between plasma ANP and mean arterial pressure in normotensive patients (r = 0.63, P less than 0.01). There was significant negative correlation between plasma ANP and fractional sodium excretion (FENa) in hypertensive patients (r = -0.47, P less than 0.05), though there was significant positive correlation in normotensive patients (r = 0.80, P less than 0.01). Hypertensive patients, with the exception of one anuric patient and another with atrial fibrillation, had a significant negative correlation between FENa and systolic arterial blood pressure (r = 0.64, P less than 0.01). The patient group had increased PRA and PA values (P less than 0.01 and P less than 0.001 respectively) and showed positive correlation with mean arterial pressure (MAP) (r = 0.71, P less than 0.001 and r = 0.58, P less than 0.01 respectively). These results show that increased concentrations of immunoreactive ANP circulate in CRF together with activated RAAS. We demonstrate that elevated ANP cannot affect blood pressure and natriuresis in hypertensive patients with CRF, whose RAAS is activated.     

Modulation of plasma and platelet vasopressin by cardiac function in patients with heart failure

Two groups of patients with congestive heart failure were studied, one with elevated (Group I) and another (Group II) with suppressed plasma concentrations of vasopressin. The mean plasma arginine vasopressin (AVP) concentration in the 17 patients in group I was 3.1 +/- 0.4 pg/mliter whereas the eight patients in group II had plasma concentration less than 0.5 pg/mliter. Platelet AVP concentrations were also higher in the Group I than Group II patients (7.8 +/- 1.5 vs. 2.2 +/- 0.7 pg/mliter, P less than 0.001). Plasma effective osmolality (262 vs. 268 mOsm/kg H2O, P less than 0.05) and plasma sodium concentration (134 vs. 137 mEq/liter, P less than 0.05) were lower in Group I. The Group I patients had a lower cardiac index (CI, 1.9 vs. 2.5 liter/min/m2, P less than 0.05) and higher pulmonary capillary wedge pressure (PCWP, 30 vs. 22 mm Hg, P less than 0.02), plasma renin activity (4.4 vs. 2.0 ng/mliter/hr, P less than 0.01), and plasma aldosterone (74 vs. 10 ng/dliter, P less than 0.001) than the Group II patients. The Group I patients also excreted a smaller percentage of a 15 mliter/kg waterload (31 vs. 57%, P less than 0.005). Group I patients then were treated with agents to decrease cardiac afterload, either captopril or prazosin. CI increased (1.9 to 2.1 liter/min/m2, P less than 0.001) and PCWP decreased (30 to 27 mm Hg, P less than 0.001). This improved cardiac performance was associated with enhanced water excretion (31 vs. 52%, P less than 0.001) and decreased minimal urinary osmolality (375 vs. 208 mOsm/kg H2O, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Rate of weight loss after vertical banded gastroplasty in morbid obesity: relationship to serum lipids and uric acid

The relationship between postoperative weight loss after vertical banded gastroplasty in morbidly obese patients and preoperative serum triglycerides, cholesterol, HDL-cholesterol, uric acid and fasting plasma glucose was evaluated. The rate of weight loss, calculated as a percentage of original weight, was determined at three and six months after surgery. There was a significant correlation between rate of weight loss at three months and preoperative serum uric acid (r = -0.60, p less than 0.01). and also with the total cholesterol: HDL-cholesterol ratio (r = 0.61, P less than 0.01). At six months, the rate of weight loss correlated with preoperative serum triglycerides (r = -0.54, p less than 0.02) and total cholesterol: HDL cholesterol ratio (r = 0.44, p less than 0.05). The reasons for the predictive value of these biochemical parameters is unknown and deserves further study.     

Lipoprotein abnormalities in patients with secondary renal amyloidosis

The prevalance of hyperlipidemia in chronic renal failure (CRF) patients is higher than in general population. Secondary amyloidosis is a common cause of CRF in Turkey. In this study, 25 patients with CRF due to secondary renal amyloidosis (amyloid-CRF), 15 patients with CRF without amyloidosis-CRF and 17 healthy controls were studied for serum lipid parameters. The mean serum lipoprotein (a) [LP(a)] level in the patients with amyloid-CRF was significantly higher than in the controls (p < 0.01). The mean serum apolipoprotein B (Apo B), apolipoprotein E (Apo E) and triglyceride levels in the patients with amyloid-CRF were very significantly higher than in the controls (p < 0.001). The mean serum total cholesterol, low- density lipoprotein (LDL) levels in the patients with amyloid-CRF were higher than in the controls (p < 0.05). The mean serum apo AI levels in the patients with amyloid-CRF was very significantly lower than in the controls (p < 0.001).The mean serum high-density lipoprotein (HDL) in the patients with amyloid-CRF was lower than in the controls (p < 0.05). The mean serum Lp (a), Apo AI, Apo B and Apo E levels in the patients with amyloid-CRF were significantly higher than in the patients with CRF (p < 0.01). The mean serum total cholesterol, trigliserides, LDL and HDL levels in the patients with amyloid-CRF were higher than in the patients with CRF (p < 0.05).There was not any correlation with serum lipid parameters and serum albumin and urine protein levels (p < 0.05).Our study suggests that serum lipid parameters are abnormal and might be the risk factor of atherosclerotic vascular disease and contribute to renal disease progression in the patients with secondary renal amyloidosis and lipid abnormalities were different from CRF with various etiology, without amyloidosis. This revised version was published online in June 2006 with corrections to the Cover Date.     

Down-regulation of hepatic lecithin:cholesterol acyltransferase gene expression in chronic renal failure

BACKGROUND: Chronic renal failure (CRF) is associated with premature arteriosclerosis, impaired high-density lipoprotein (HDL) maturation, increased pre-beta HDL (a lipid-poor HDL species), reduced HDL/total cholesterol ratio, hypertriglyceridemia, and depressed lipolytic activity. The latter has been, in part, attributed to elevated pre-beta HDL, which is a potent inhibitor of lipoprotein lipase (LPL). Accumulation of cholesterol in the arterial wall is a critical step in atherogenesis, and HDL-mediated cholesterol removal from peripheral tissues mitigates atherosclerosis. Lecithin:cholesterol acyltransferase (LCAT) is essential for maturation of HDL and cholesterol removal by HDL from peripheral tissues. Earlier studies have revealed depressed plasma LCAT enzymatic activity in patients with CRF. This study was conducted to determine whether impaired LCAT activity can be confirmed in CRF animals and if so whether it is due to down-regulation of hepatic LCAT expression. METHODS: Hepatic tissue LCAT mRNA and plasma LCAT enzymatic activity were measured in male Sprague-Dawley rats six weeks after excisional 5/6 nephrectomy or sham operation. RESULTS: Compared with the controls, the CRF group exhibited a significant reduction of hepatic tissue LCAT mRNA abundance. The reduction in hepatic LCAT mRNA was accompanied by a marked reduction of plasma LCAT activity and elevation of serum-free cholesterol in the CRF animals. LCAT activity correlated positively with the HDL/total cholesterol ratio and inversely with free cholesterol and triglyceride concentrations. CONCLUSIONS: CRF leads to a marked down-regulation of hepatic LCAT mRNA expression and plasma LCAT activity. This abnormality can impair HDL-mediated cholesterol uptake from the vascular tissue and contribute to cardiovascular disease. In addition, LCAT deficiency can, in part, account for elevated serum-free cholesterol, reduced HDL/total cholesterol, and elevated pre-beta HDL in CRF. The latter can, in turn, depress lipolytic activity and hinder triglyceride-rich lipoprotein clearance in CRF.     

Lipoprotein profiles at different stages of chronic renal insufficiency

BACKGROUND: Lipoprotein abnormalities characteristic of renal dyslipoproteinemia are significantly associated with different stages of chronic renal insufficiency. The renal dyslipoproteinemia may contribute not only to accelerated development of atherosclerosis but also to progression of human chronic renal insufficiency. METHODS: The purpose of the studies was to estimate the lipid and lipoprotein profiles in 52 not dialysed patients with various renal insufficiency advancement. Basing on creatinine level the patients were divided into 3 groups. CR1-A--serum creatinine 2-5 mg/dL (n = 16), CR1-B--serum creatinine 5-10 mg/dL (n = 19), CR1-C--serum creatinine > 10 mg/dL (n = 17). RESULTS: In CR1-A and CR1-B dyslipoproteinemia was found at different stages of renal insufficiency which was manifested by the significant increase of TG, TC, LDL-C, apo B levels and TC/HDL-C, LDL-C/HDL-C ratios and significant decrease of HDL-C level and apo AI/apoB, HDL-C/apoAI ratios in comparison with controls. We also observed decreased TG, TC, LDL-C, apo AI, apo B levels and TC/HDL-C, LDL-C/HDL-C ratios and unchanged HDL-C level and apo AI/apoB, HDL-C/apoAI ratios in cm-c in comparison to CR1-A. The decrease of the lipoprotein parameters in CR1-C might result from malnutrition (statistically decreased albumin level) and metabolism disturbances connected with the renal insufficiency advancement. Negative correlation between IG, HDL-C levels (r = -0.43, p < 0.001) and TG, IIDL-C/apoAI (r = -0.56; p < 0.001) were found, which confirmed the abnormal composition of HDL molecules and indicated a high risk of atherosclerosis. CONCLUSION: Our results may indicate that of atherosclerosis in CR1 patients is connected with dyslipoproteinemia and disturbances in HDL molecular composition and with different stages of chronic renal insufficiency.     

Hyporeninemic hypoaldosteronism in diabetic patients with chronic renal failure

Plasma renin activity, plasma aldosterone levels and renal tubular capacity to excrete hydrogen ions were studied in 13 patients suffering from diabetes mellitus with a creatinine clearance of less than 40 ml/min. The results were compared with those obtained in a control group, in a group of nondiabetic subjects with chronic renal failure (CRF) and in a group of diabetic patients without CRF. Twelve of the thirteen diabetic patients with CRF had data characteristic of hyporeninemic hypoaldosteronism associated with type IV renal tubular acidosis. On comparing the results with those of the other two groups of patients, it was observed that the manifestations of the latter two groups considered separately were different from those of the problem group, although in the diabetic patients with normal glomerular filtration rate (GFR) hyporeninism but not hypoaldosteronism was present accompanied by a lower net acid excretion (p less than 0.001) due to a lower excretion of NH4 (p less than 0.05) and titratable acid (p less than 0.001) when the patients were challenged with an NH4Cl overload. We believe that a conjunction of diabetes and renal failure is necessary for the diabetic patients with a decrease in GFR to show hyporeninemic hypoaldosteronism and type IV tubular acidosis.     

Lipoprotein abnormalities in hyperlipidemic and normolipidemic men on hemodialysis with chronic renal failure.

Lipids, lipoproteins, apolipoproteins (apo) and apo E polymorphism were determined in 101 men with chronic renal failure (CRF) were were on hemodialysis and 101 healthy controls matched for age and sex. Patients with CRF on hemodialysis had significantly higher levels of serum triglycerides, very-low-density lipoprotein (VLDL) cholesterol, intermediate-density lipoproteins (IDL), and lower levels of low- and high-density lipoproteins (LDL and HDL, respectively) than controls. Regarding apolipoproteins, serum apo B concentrations were decreased. Apo C-III concentrations in sera and in VLDL and HDL fractions were significantly increased in 35 hemodialysis patients compared with 32 controls. Seventy-eight of the 101 CRF patients had normal serum cholesterol and triglycerides (less than 5.2 mmol/liter and less than 2.3 mmol/liter, respectively). However, this subgroup also showed a significant increase in VLDL-triglycerides and serum apo E concentration in addition to changes observed in the group as a whole. Apo E polymorphism in our study population did not differ from that reported for other European populations. According to the different apo E phenotypes, lipids and lipoprotein composition showed no significant differences in controls or patients. We conclude that accumulation of triglyceride-rich lipoproteins in patients with CRF on hemodialysis may thus be at least in part related to the enrichment of apo C-III in VLDL and HDL fractions. Lipoprotein profile in hemodialysis patients, including those with normal serum cholesterol and triglyceride levels, is consistent with high cardiovascular risk.     

Extracorporeal treatment of familial hypercholesterolemia with monoclonal antibodies to low-density lipoprotein

Plasma exchange (PE) is considered the most effective nonsurgical treatment modality for the reduction of low-density lipoprotein (LDL) in patients with familial hypercholesterolemia (FH). However, the concomitant reduction of high-density lipoprotein (HDL) and the necessity and cost of using blood products are major drawbacks of PE. We studied the effects of selective LDL reduction using monoclonal anti-LDL antibodies in an investigational immunoadsorption (IA) system. Results were compared with the effects of PE. During the study period, two homozygous FH patients with baseline cholesterol levels greater than 10.34 mmol/L (400 mg/dL) were treated sequentially for a combined total of 37 IA treatments and the results were compared with a total of 19 sequential PE treatments. The IA system consisted of on-line plasma processing over two columns of monoclonal anti-LDL antibodies in alternating cycles of column adsorption and regeneration. No replacement solution was needed. PE was performed with a centrifugal plasma separator using 5% albumin as replacement solution. Results showed that the reduction of lipids with IA was 43% +/- 0.9% for cholesterol, 51% +/- 1.0% for LDL, and 19% +/- 1.3% for HDL, resulting in a reduction in the LDL to HDL ratio of 41% +/- 1.7%. Compared with IA, percent reduction by PE was significantly greater (P less than 0.001) for all lipids, but was nonselective (cholesterol, 74% +/- 1.0%; LDL, 77% +/- 1.2%; HDL, 73% +/- 2.7%), and therefore the reduction of the LDL to HDL ratio was only 6% +/- 3.6%, which was significantly less than for IA (P less than 0.001). Pretreatment HDL concentration appeared to increase with repetitive IA treatment, but decreased back to prestudy levels with repetitive PE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma lipoproteins and lecithin:cholesterol acyltransferase distribution in patients on dialysis

Plasma lipoproteins and LCAT activity were studied using a single spin density gradient separation and an exogenous substrate enzyme assay in 41 patients on chronic hemodialysis and in 11 normal subjects. The plasma HDL cholesterol was markedly decreased (33 vs. 63 mg/dl, P less than 0.001) while total and LDL-cholesterol were unchanged in the patients. Plasma LCAT activity was significantly lower in the patient group (42 vs. 59 nmoles/4 hr/ml, P less than 0.001), but the distribution of activity (studied in 13 dialysis patients and 12 control subjects) was not different between the two groups: 90% being associated with HDL and VHDL lipoprotein fractions. To examine the possible genetic influence on the development of hypertriglyceridemia in the patient group, we examined the ratio of apolipoproteins E3/E2 and CII/CIII in ten of the patients and another group of 13 control subjects. The frequency of heterozygotes for E3 deficiency was not different between the patient (one of ten) and the control (two of 13) groups. While the patient group had lower CII/CIII ratio, the figures did not reach statistical significance. The low LCAT activity in the face of higher plasma triglycerides and low HDL may contribute to impaired lipolysis previously documented in uremic patients. A follow-up study performed 1 year after the initial study confirmed the decreased HDL (51 vs. 71 mg/dl, P less than 0.01) and LCAT activity (50 vs. 59 nmoles/hr/ml, P less than 0.02) in an exogenous substrate system (N = 20). LCAT measured using the endogenous substrate was not significantly different from the control group (49 vs. 55 nmoles/hr/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Whole-plasma and high-density lipoprotein subfraction surface lipid composition in IDDM men

To determine whether compositional abnormalities are present in high-density lipoprotein (HDL) in patients with insulin-dependent diabetes mellitus (IDDM) that might negate its putatively protective cardiovascular effects, we studied the plasma lipoproteins of 12 men with varying degrees of clinical control (mean fasting glucose 193 +/- 10 mg/dl, mean glycoalbumin greater than 73% above control mean). The diabetic patients' basal plasma triglyceride, total- and free- (unesterified) cholesterol, HDL cholesterol (HDL-chol), and apolipoprotein AI, AII, and B concentrations were similar to those of control subjects, but the free-cholesterol-to-lecithin ratio, a new index of cardiovascular disease risk, was significantly increased in their plasma (0.97 +/- 0.14 vs. 0.88 +/- 0.07, P less than .02) and their very-low-density lipoprotein (VLDL)-low-density lipoprotein (LDL) subfraction (1.50 +/- 0.51 vs. 1.08 +/- 0.15, P less than .005). Although HDL2-chol was similar in diabetic and control groups, the HDL2-chol-to-free-cholesterol ratio (diabetic vs. control, 4.64 +/- 1.7 vs. 1.96 +/- 1.0 mumol/ml, P less than .025) and the sphingomyelin-to-lecithin ratio (0.23 +/- 0.08 vs. 0.20 +/- 0.09, P less than .025) were both significantly increased in the IDDM group. HDL3-chol was higher in the IDDM than in the control subjects (diabetic vs. control, 38.6 +/- 5.2 vs. 32.7 +/- 2.7 mg/dl, P less than .005). In contrast to whole plasma and the VLDL + LDL subfraction, the free-cholesterol-to-lecithin ratio of IDDM and control HDL subfractions were similar.(ABSTRACT TRUNCATED AT 250 WORDS)     

ApoA- and apoB-containing lipoproteins and Lp(a) concentration in non-dialyzed patients with chronic renal failure

BACKGROUND: End-Stage renal disease is associated with accelerated atherosclerosis and a high incidence of cardiovascular disease. METHODS: The serum levels of lipids and apolipoproteins and Lp(a) were determined in 51 patients with chronic renal failure (CRF) with various advancement, without interference of factors which might disturb Lp(a) metabolism and with proteinuria less than 0.5 g/24 h. The patients studied were divided into two groups: patients with moderate renal failure (CRF-M) and creatinine levels of 2-6mg/dL n = 27; and predialysis patients with end stage renal disease (ESRD) and creatinine levels higher than 8.5 mg/dL n=24. RESULTS: In both studied groups serum concentrations of triglycerides (TG), total apoCIII, apoCIIInonB, apoB:CIII were statistically increased, (except total cholestrol (TC) and LDL-cholestrol (LDL-C), apoB, total apoE, apoEnonB, apoB:E), while the levels of HDL-cholestrol (HDL-C) and apoAl significantly decreased. Lipid and lipoprotein ratios as risk factors of atherosclerosis were similar in both groups. The TC/HDL-C ratio increased, while that of HDL-C/ apoAI and apoAI/apoCIII decreased. Serum Lp(a) concentrations were significantly increased in both studied groups. The medians and ranges of Lp(a) concentration were similar in both groups. Serum Lp(a) levels correlated with total cholesterol (r=0.295; p < 0.05), LDL-C (r = 0.312; p < 0.05) and apoB (r = 0.215; p < 0.05). In addition, no correlation was found between Lp(a) levels and albumin concentrations (r = 0.126; p = 0.421). CONCLUSION: Our results may indicate that the reduced levels of apoA-containing lipoproteins and increased TG-rich apoB-containing lipoproteins and Lp(a) indicated a clear atherogenic pattern in early renal disease. Increased Lp(a) concentration may result in nonspecific synthesis or catabolism disturbances. Measurement and monitoring of lipoprotein family profiles offers a new means for selecting appropriate therapies targeted for normalizing dyslipidemia in non-dialyzed patients.