Fenofibrate improves postprandial chylomicron clearance in II B hyperlipoproteinemia

In 11 patients with 1113 hyperlipoproteinemia we studied fasting lipids, lipoproteins, lipoprotein-modifying enzymes, and postprandial lipid metabolism after a standardized oral fat load supplemented with vitamin A before and 12 weeks after treatment with fenofibrate, a third-generation fibric acid derivative. Fasting plasma cholesterol, triglycerides, low-density lipoprotein cholesterol decreased significantly (P < 0.05, P < 0.01, P < 0.01), high-density lipoprotein subfraction 3 cholesterol increased significantly (P < 0.05), and high-density lipoprotein subfraction 2 cholesterol remained unchanged. Postprandial lipemia, i.e., the integrated postprandial triglyceride concentrations corrected for the fasting triglyceride level, and postprandial chylomicron concentrations, as assessed by biosynthetic labeling of chylomicrons with retinyl palmitate, decreased by 40.6% and 60.1% (P < 0.05; P < 0.05), respectively. The activity of lipoprotein lipase (LPL) increased by 33.6% (P < 0.05); the increase in LPL during fenofibrate treatment was positively correlated with the increase in high-density lipoprotein cholesterol (r = 0.84; P < 0.005). Hepatic lipase and cholesteryl ester transfer protein mass and activity remained unchanged. We conclude that lipid-lowering therapy with fenofibrate ameliorates fasting and, more profoundly, postprandial lipoprotein transport in hypertriglyceridemia by curbing postprandial triglyceride and chylomicron accumulation, at least in part, through an increase in LPL activity.Abbreviations LDL low-density lipoproteins - HDL high-density lipoproteins - LPL lipoprotein lipase - HL hepatic lipase - CETP cholesteryl ester transfer protein - CHD coronary heart disease - VLDL very low density lipoproteins - TG triglycerides - apo apolipoprotein Correspondence to: J.R. Patsch     

Increase in lipoprotein lipase during clofibrate treatment of hypertriglyceridemia in patients on hemodialysis.

In 11 hypertriglyceridemic patients on hemodialysis, clofibrate (1 to 1.50 g per week) reduced plasma triglyceride (-40 +/- 20%, P less than 0.001), very-low-density-lipoprotein triglyceride (-44 +/- 20%, P less than 0.001) and very-low-density lipoprotein cholesterol (-39 +/- 25%, P less than 0.01), and it increased high-density-lipoprotein cholesterol (82 +/- 106%, P less than 0.005). Low pretreatment lipoprotein-lipase activity in adipose-tissue specimens and postheparin plasma increased to normal with clofibrate, whereas low hepatic triglyceride lipase activity did not change. The reduced very-low-density-lipoprotein triglyceride correlated with the increased lipoprotein-lipase activity in adipose tissue (rs = 0.792, P less than 0.02, n = 8) and postheparin plasma (rs = 0.851, P less than 0.02, n = 8), whereas increased high-density-lipoprotein cholesterol correlated with changes in this activity in adipose tissue (rs = 0.696, P less than 0.06) and post-heparin plasma (rs = 0.679, P less than 0.10). There was no correlation between changes in hepatic triglyceride lipase activity and plasma lipids during treatment. Reduced lipoprotein-lipase activity may cause hypertriglyceridemia and decreased high-density-lipoprotein cholesterol in patients on hemodialysis; clofibrate may correct these abnormalities by increasing lipoprotein-lipase activity to normal.     

Effects of short-term melatonin administration on lipoprotein metabolism in normolipidemic postmenopausal women

OBJECTIVE: To investigate the effects of short-term administration of melatonin on lipoprotein metabolism in normolipidemic postmenopausal women. METHODS: Fifteen such women received 6.0 mg melatonin daily for 2 weeks. Blood was sampled before and after treatment. We measured concentrations of total cholesterol and total triglyceride in the plasma, as well as the levels of cholesterol, triglyceride, and protein in the very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Plasma apolipoprotein levels were determined by immunoturbidimetric assay. Activities of lipoprotein lipase, hepatic triglyceride lipase, and lecithin cholesterol acyltransferase were also determined by enzymatic analysis. RESULTS: Melatonin administration significantly increased the plasma levels of triglyceride by 27.2% (P < 0.05), of VLDL-cholesterol by 37.2% (P < 0.01), of VLDL-triglyceride by 62.2% (P < 0.001), and of VLDL-protein by 30.0% (P < 0.05). However, the plasma total cholesterol level and the concentration of lipid and protein in LDL and HDL were not significantly affected. Melatonin significantly increased the plasma levels of apolipoprotein C-II by 29.5% (P < 0.005), of C-III by 17.1% (P < 0.001), and of E by 7.6% (P < 0.05). The plasma levels of apolipoprotein A-I, A-II, and B were not altered. Melatonin significantly inhibited the activity of lipoprotein lipase by -14.1% (P < 0.05), but did not significantly affect the activities of hepatic triglyceride lipase or of lecithin cholesterol acyltransferase. CONCLUSIONS: Findings indicate that melatonin increases the plasma level of VLDL particles by inhibiting the activity of lipoprotein lipase, but may not affect the plasma levels of LDL and HDL particles in postmenopausal women with normolipidemia.     

Pathophysiologie und Therapie von Lipidstoffwechselstörungen bei Nierenerkrankungen

Summary Nephrotic syndrome, uremia, hemodialysis, peritoneal dialysis, and renal transplantation are accompanied by alterations in lipoprotein metabolism (Table 1). In nephrotic patients, total cholesterol, LDL, VLDL and triglycerides are elevated, while HDL may be increased, normal, or decreased. The pathophysiology includes increased hepatic synthesis of VLDL and cholesterol, decreased activity of lipoprotein lipase, and increased urinary excretion of HDL (Fig. 1). The risk of coronary heart disease (CHD) is increased in nephrotic patients, and elevated LDL-cholesterol may contribute to this risk. Cholesterol lowering diet and drugs are indicated. Presently, Lovastatin and Simvastatin are the most potent cholesterol lowering drugs in nephrotic patients with good evidence of long-term safety. Most patients with impaired renal function or on hemodialysis have moderate hypertriglyceridemia due to decreased lipoprotein lipase activity (Fig. 2). HDL may be slightly decreased. Although the risk of CHD is increased in these patients, triglyceride lowering drugs are not indicated, since no benefit can be expected. Peritoneal dialysis is accompanied by elevated VLDL in addition to hypertriglyceridemia. Reabsorption of large amounts of glucose from peritoneal dialysis fluid increases the carbohydrate load and stimulates hepatic VLDL synthesis. Cholesterol lowering therapy may be advantageous, but the experience is very limited. Side effects of lipid lowering drugs may be aggravated in renal failure. Total cholesterol, LDL, VLDL, and triglycerides are elevated in 50% of patients following renal transplantation. Corticosteroides and cyclosporin are major causes of hyperlipidemia. Cholesterol lowering therapy is indicated since the incidence of CHD is increased. Lipid lowering diet, triple immunosuppression with low dose cyclosporin, azathioprim, and prednisone, or conversion from cyclosporin to azathioprim are valuable measures to reduce cholesterol. Low-dose lovastatin (20 mg/24 h) seems to be an effective and safe cholesterol lowering drug in renal transplantation, while higher doses may induce rhabdomyolysis.

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Abkürzungsverzeichnis NS Nephrotisches Syndrom - LDL Low Density Lipoprotein Cholesterin - VLDL Very Low Density Lipoprotein Cholesterin - HDL High Density Lipoprotein Cholesterin - KHK Koronare Herzerkrankung - HMG-CoA 3-Hydroxy-3-Methylglutaryl-Coenzym A - NIH National Institute of Health - GFR Glomeruläre Filtrationsrate     

Deficiency of hepatic lipase activity in post-heparin plasma in familial hyper-alpha-triglyceridemia

Hyper-alpha-triglyceridemia is a rare dyslipoproteinemia characterized by a pronounced increase in the concentration of triglycerides in the plasma high density lipoprotein (HDL) fraction. One case with this condition, an apparently healthy 61-year-old man, has been studied. Additional lipoprotein abnormalities were present, such as abnormally cholesterol-rich very low density lipoproteins (VLDL) with retarded electrophoretic mobility (beta-VLDL) and triglyceride enrichment of low density lipoproteins (LDL). The patient's plasma concentration of apolipoproteins A-I, A-II and B were normal and those of C-I, C-II, C-III and E were elevated. No abnormal forms of the soluble apolipoproteins of VLDL and high density lipoproteins (HDL) were found after analysis by isoelectric focusing. Lecithin:cholesterol acyltransferase activities, plasma cholesterol esterification rates and lipid transfer protein activities were normal. Post-heparin plasma activity of hepatic lipase was virtually absent and that of lipoprotein lipase was reduced by 50%. In plasma of this patient, HDL was almost exclusively present as large triglyceride-rich particles corresponding in size to particles of the HDL2 density fraction. The only brother of the patient also had hyper-alpha-triglyceridemia together with the other lipoprotein abnormalities described for the index case and deficiency of postheparin plasma activity of hepatic lipase. The findings presented below support the hypothesis that one primary function of hepatic lipase is associated with degradation of plasma HDL2. Deficiency of this enzyme activity thus causes accumulation of HDL2 in plasma leading to hyper-alpha-triglyceridemia. The results further suggest that the abnormal chemical and electrophoretic properties of VLDL and LDL in plasma from the patient, reminiscent of type III hyperlipoproteinemia, are secondary to the lack of the action of hepatic lipase on the HDL particles.     

Impact of hormone replacement therapy on postprandial lipoproteins and lipoprotein(a) in normolipidemic postmenopausal women

In 43 normolipidemic postmenopausal women we studied fasting and postprandial (oral fat load with 50 g fat per square meter; blood sampling for 5 h) lipoprotein components and lipoprotein(a) levels before and with the administration of conjugated equine estrogens opposed by medrogestone (on days 11–21). Data was compared intraindividually; the second testing was performed during the last 5 days of the combined estrogen/progestogen phase of the third cycle. Fasting low-density lipoprotein (LDL) and total cholesterol concentrations decreased significantly; high-density lipoprotein (HDL) cholesterol, including subfractions HDL₂ and HDL₃, was not changed. Fasting triglyceride concentrations increased. All lipoprotein fractions measured showed a postprandial elevation with the exception of chylomicron cholesterol concentrations. There was a significant effect of hormone replacement therapy on the postprandial course of total cholesterol (decrease; P < 0.001), VLDL cholesterol (increase; P = 0.025), and the triglyceride proportion in the LDL plus HDL fraction (increase; P < 0.001). With hormone replacement therapy the postprandial curve of total triglycerides was increased only 1 h after the fat load while chylomicron triglyceride concentrations were lowered after 5 h. VLDL triglycerides were not influenced. In all patients with lipoprotein(a) levels above 10 mg/dl, this parameter decreased (about 25%). Although increasing fasting triglyceride concentrations, hormone replacement therapy does not bring about an exaggerated postprandial increase in triglycerides. Postprandial chylomicron clearance is evidently promoted. Hormone replacement therapy leads to a small increase in triglycerides in the LDL plus HDL fraction by inhibiting hepatic lipase activity. Moreover, the decrease in lipoprotein(a) levels may contribute to the antiatherosclerotic effect.Abbreviations: CEE conjugated equine estrogens - HDL high-density lipoproteins - HRT hormone replacement therapy - LDL low-density lipoproteins - TG triglycerides - VLDL very low density lipoproteins Correspondence to: U. Julius     

Effects of ethanol on lipids and atherosclerosis.

Moderate alcohol consumption is associated with an increase in plasma high density lipoprotein (HDL) cholesterol concentration and a decrease in low density lipoprotein (LDL) cholesterol concentration. Changes in the concentration and composition of lipoproteins are estimated to account for more than half of alcohol's protective effect for coronary heart disease. Alcohol intake also affects plasma proteins involved in lipoprotein metabolism: cholesteryl ester transfer protein, phospholipid transfer protein, lecithin:cholesterol acyltransferase, lipoprotein lipase, hepatic lipase, and phospholipases. In addition, alcohol intake may result in acetaldehyde modification of apolipoproteins. Furthermore, "abnormal" lipids, phosphatidylethanol and fatty acid ethyl esters are formed in the presence of ethanol and are associated with lipoproteins in plasma. Ethanol and ethanol-induced modifications of lipids may modulate the effects of lipoproteins on the cells in the arterial wall. The molecular mechanisms involved in these processes are complex, requiring further study to better understand the specific effects of ethanol in the pathogenesis of atherosclerosis. This review discusses the effects of ethanol on lipoproteins and lipoprotein metabolism, as well as the novel effects of lipoproteins on vascular wall cells.     

High-density lipoprotein and transport of cholesterol and triglyceride in blood

High-density lipoproteins (HDL) contain approximately 25% of the cholesterol and <5% of the triglyceride in the plasma of human blood. However, the dynamic exchange of lipids and lipid-binding proteins is not revealed by simply considering the mass of material at any point in time. HDL are the most complex of lipoprotein species with multiple protein constituents, which facilitate cholesterol secretion from cells, cholesterol esterification in plasma, and transfer of cholesterol to other lipoproteins and to the liver for excretion. They also play a major role in triglyceride transport by providing for activation of lipoprotein lipase, exchange of triglyceride among the lipoproteins, and removal of triglyceride rich remnants of chylomicrons and very-low-density lipoproteins after lipase action. In addition, antioxidative enzymes and phospholipid transfer proteins are important components of HDL. Many of the proteins of HDL are exchangeable with other lipoproteins, including chylomicrons and very-low-density lipoproteins. The constantly changing content of lipids and apolipoproteins in HDL particles generate a series of structures that can be analyzed by using separation techniques that depend on size or charge of the particles. Interaction of these various structures can be very different with cell surfaces depending on the size or apolipoprotein content. A series of different transport proteins preferentially exchange lipids with specific structures among the HDL but interact poorly or not at all with others. The role of these differing forms of HDL and their interactions with cells and other lipoprotein species in plasma is the subject of intense study stimulated by the potential for reducing atherogenesis. The strength of this is only partially indicated by the correlation of higher total levels of the HDL particles with reduced incidence of vascular disease in various clinical trials and epidemiological studies.     

Intraplatelet serotonin, beta-thromboglobulin, and histamine concentrations and thromboxane A2 synthesis in renal disease.

Intraplatelet serotonin (5-HT), beta-thromboglobulin (beta-TG), and histamine content as well as platelet total thromboxane A2 (TXA2) synthesizing capacity were measured in 53 patients with chronic renal disease: nephrotic syndrome (n = 18); end-stage renal failure (ESRF; n = 13); continuous ambulatory peritoneal dialysis (CAPD; n = 9); hemodialysis (HD; n = 13). These indices of platelet function were correlated with plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) concentrations. When compared with controls, intraplatelet 5-HT was significantly reduced in all patient groups studied and beta-TG was diminished in all patient groups except CAPD. Total platelet TXA2 synthesizing capacity was increased in ESRF and HD groups. Intraplatelet histamine content was not altered in any of the patient groups studied. There was a significant inverse correlation between intraplatelet 5-HT content on the one hand and plasma TC, LDL-C, and TG on the other. The depletion of intraplatelet 5-HT and beta-TG and the increase in total TXA2 synthesizing capacity are consistent with platelet activation in chronic renal disease. The correlation between these indices of platelet activation and TC, LDL-C, HDL-C, and TG suggests that changes in the concentrations of these lipids may contribute to the activation of platelets in these conditions.     

Plasma and hepatic lipid profiles in furazolidone-treated rats.

Rats were treated orally with furazolidone (FZ) at doses of 50, 100, and 200 mg/kg body weight for three consecutive days. The parameters determined in plasma included: total cholesterol, high density (HDL) cholesterol, low-density (VLDL+LDL) cholesterol, triglycerol (TAG), phospholipids (PL), and lipoprotein lipase. In the liver, cholesterol, TAG and phospholipid concentrations were measured. At the lowest dose used, no statistically significant effect on any of these parameters in plasma or liver was observed. The drug, dose-dependently, increased the concentrations of total cholesterol, VLDL cholesterol, TAG and PL in plasma. The activity of lipoprotein lipase was significantly decreased by FZ by about 45%. The hepatic cholesterol concentration was not significantly affected by any of the doses used. However, doses of 100 and 200 mg/kg produced fatty infiltration in the liver and significantly increased TAG level. The highest dose also decreased PL concentration.     

Positive correlation between circulating leptin levels and lipid lipoproteins in postmenopausal women administered hormone replacement therapy

Beneficial effects of hormone replacement therapy are reported on plasma concentrations of lipids and lipoproteins. Plasma leptin levels are reported to reflect lipid metabolism. We treated 40 healthy postmenopausal women with continuous combined HRT (0.625 mg conjugated equine estrogen and 2.5 mg medroxyprogesterone acetate orally) daily for 6 months and then investigated total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol, which are considered to be factors inducing cardiovascular disease (CVD). We measured the plasma levels of lipids and leptin, which are considered to be altered with HRT. Plasma leptin and lipid levels were measured at baseline and after 3 and 6 months of HRT. The plasma levels of leptin in PMW were not significantly reduced by HRT. Although the plasma levels of total cholesterol and LDL-cholesterol did not change by HRT, the administration of HRT significantly increased plasma levels of triglycerides and HDL-cholesterol in PMW. The correlation between leptin and total cholesterol or triglycerides was positive after HRT while these relations were not correlated at baseline. The correlation between lipid levels and leptin may explain the new role of leptin in plasma lipid levels in HRT.     

Effect of furosemide on the lipid abnormalities in chronic renal failure

The effect of furosemide on the lipoprotein profile and the activities of postherapin plasma lipases were studied in 12 patients with chronic renal failure. The concentrations of serum total, VLDL and LDL triglycerides were significantly higher and the concentration of HDL triglyceride was significantly lower in the patients with renal failure than in healthy controls. HDL cholesterol was significantly lower in the patients than in the controls. The activity of postherapin lipoprotein lipase was significantly lower in the patients than in the controls. The introduction of furosemide induced a significant increase in the concentrations of VLDL cholesterol and VLDL triglyceride. These changes were reversed when the drug treatment was discontinued. Postherapin lipase activities were not further altered by furosemide.     

Atypical type III hyperlipoproteinemia in a patient with Ig A myelomatosis

Summary We studied a 58-year-old woman with severe therapy-refractory hyperlipidemia, xanthomatosis, and multiple myeloma (immunoglobulin A, lambda light chain). The lipid disorder became evident about half a year prior to the expression of myelomatosis. Clinical symptoms were similar to those found in classical type III hyperlipoproteinemia but the underlying metabolic defect was different from the one described in this primary dyslipoproteinemia. The patient has the heterozygous apolipoprotein E3/2 phenotype and her VLDL-cholesterol/serum-triglyceride ratio is unusually low at 0.05. Evidence is given that the hyperlipoproteinemia is due to an impaired catabolism of intermediate density lipoproteins probably because of a reduced hepatic triglyceride lipase activity.Abbreviations AIH autoimmune hyperlipidemia - Chol cholesterol - HDL high density lipoproteins - HLP hyperlipoproteinemia - HTGL hepatic triglyceride lipase - IDL intermediate density lipoproteins - IEF isoelectric focusing - Ig immunoglobulin - LDL low density lipoproteins - LPL lipoprotein lipase - PL phospholipids - TG triglycerides - VLDL very low density lipoproteins     

The relation of risk factors to the development of atherosclerosis in saphenous-vein bypass grafts and the progression of disease in the native circulation. A study 10 years after aortocoronary bypass surgery

We examined 82 patients 10 years after saphenous-vein aortocoronary bypass surgery to determine their angiographic status and to relate those findings to the risk factors for coronary-artery disease. Of 132 grafts shown to be patent 1 year after surgery, only 50 were unaffected at 10 years. The remainder were narrowed (43) or occluded (39). Disease progression in coronary arteries without grafts was also frequent, both in vessels that were normal (15 of 32) and in those with minor stenosis (25 of 53). New lesions did not develop in 15 patients, whereas they did in 67--in the grafts, the native vessels, or both. There was no significant difference between the two groups in the incidence of hypertension, diabetes, or smoking, whereas plasma levels of very-low-density lipoproteins (VLDLs) and low-density lipoproteins (LDLs) were higher, and high-density lipoprotein (HDL) levels were lower in those with new disease than in those without. Univariate analysis showed that plasma cholesterol and triglyceride levels were significantly higher at the time of surgery and at the 10-year examination in those with new lesions. Multivariate analysis indicated that among the lipoprotein indexes, levels of HDL cholesterol and plasma LDL apoprotein B best distinguished the two groups. The findings indicate that atherosclerosis in these patients was a progressive disease, frequently affecting both the grafts and the native vessels, and that the course of such disease may be related to the plasma lipoprotein levels.     

Improvement in lipid profile by nocturnal hemodialysis in patients with end-stage renal disease

Dyslipidemia is associated with uremia and an increased risk of cardiovascular disease. The uremic dyslipidemia syndrome is characterized by an abnormal lipoprotein profile that results in (1) an elevation of triglyceride (TG) rich lipoproteins, very low density lipoprotein (VLDL), and intermediate density lipoprotein (IDL); (2) a reduction in high density lipoprotein (HDL) levels; and (3) a higher fraction of atherogenic, small dense low density lipoprotein (LDL). Nocturnal hemodialysis (NHD) is a home based renal replacement therapy that provides better control of uremia than conventional hemodialysis (CHD) and that may improve dyslipidemia. To test this hypothesis, we conducted a prospective cohort study of 11 patients with end-stage renal disease (ESRD) (age 38+/-3 years [mean+/-SEMI) before and after conversion from CHD to NHD. Weight, blood pressure (BP), serum hemoglobin (Hb), phosphate (PO4), and albumin (Alb) were assessed at baseline and at 3 months after conversion to NHD. Dialysis dose on CHD and NHD was assessed using equilibrated Kt/V (eKt/V). A 12 hour fasting lipid profile (total cholesterol [TC], TG, HDL, LDL, HDL/TC) was obtained once while on CHD and at 3 months after conversion to NHD. After conversion from CHD to NHD, eKt/V per session increased significantly (from 1.13+/-0.05 to 2.10+/-0.07; p < 0.05). TG level decreased significantly (from 2.05+/-0.30 to 1.01+/-0.14 mmol/L; p < 0.001), and HDL level increased significantly (from 1.17+/-0.13 to 1.65+/-0.14 mmol/L; p < 0.001). HDL/TC also increased significantly (from 0.26+/-0.03 to 0.35+/-0.02; p < 0.001). TC and LDL levels were unchanged. HDL levels increased and TG levels decreased in all patients. There was no difference in weight, Hb, and Alb. Systolic BP and PO4 were significantly lower, and there was a trend toward a reduction in cardiovascular medications. The mechanism for the improvement in lipid profile requires further study.     

Common haplotypes in five genes influence genetic variance of LDL and HDL cholesterol in the general population

We studied the association between common haplotypes in six relevant lipid metabolism genes with plasma lipid levels. We selected single-nucleotide polymorphisms (SNPs) in the cholesterol ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic triglyceride lipase (HL), low-density lipoprotein cholesterol receptor (LDLR), apolipoprotein E (ApoE) and lecithin-cholesterol acyltransferase (LCAT) genes, and studied 732 individuals from 184 German families. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) were similar to those reported in other European and American populations. Haplotypes derived from SNP combinations resulted in more significance and of a higher degree than did single SNPs in the genotype-phenotype association analysis. Reduction of the polygenic variance attributable to haplotypes was estimated using variance components analysis. Under the biometrical genetic model, allelic association of haplotypes was highly significant for HDL, LDL and the LDL/HDL ratio. The residual kinship correlation was reduced accordingly. The ApoE gene had a strong effect on trait variation; however, the other genes also contributed substantially. An epistatic interaction could not be demonstrated in this sample. The data are consistent with the notion that common genetic variants influence common traits.     

Lipoprotein and apoprotein levels in different types of dialysis

Cardiovascular disease is common in chronic renal failure and its progression during dialysis has been described. We evaluated lipoprotein and apoprotein profiles in 30 male and 28 female uremic patients on dialysis in order to compare the results with 30 male and 19 female non-uremic controls and to detect any differences in lipemic pattern due to different types of dialysis. The dyslipidemic picture typical of uremia was observed in both sexes, coupled with significant hypertriglyceridemia and an increase in the lipid components of the very low density lipoprotein (VLDL). There was also a significant reduction in high density lipoproteins (HDL) cholesterol and HDL2 cholesterol. Apo C levels were increased, whereas Apo AI and AII were diminished. Apo B levels were unchanged. We also evaluated their lipid profile in relation to three types of dialysis: hemodialysis, hemofiltration and continuous ambulatory peritoneal dialysis. Analysis of variance of three different types of dialysis performed for comparable periods of time showed that the parameters typically altered in uremia (Tg, VLDL, ApoC, ApoE) were uniform, whereas differences were observed in the variables indicative of cholesterol and phospholipid metabolism. The alterations of cholesterol metabolism in some subjects, in addition to the specific alterations of Tg metabolism, help explain the elevated prevalence of atherosclerotic complications in dialysed uremic patient.     

The hyperlipidemia of the nephrotic syndrome. Relation to plasma albumin concentration, oncotic pressure, and viscosity

Although hyperlipidemia is a common feature of the nephrotic syndrome, the distribution of cholesterol among the plasma lipoproteins and the mechanism of the enhanced hepatic synthesis of lipoprotein lipids are not well understood. We studied the distribution of cholesterol among the plasma lipoproteins, as well as the relation between total cholesterol and plasma albumin concentration, oncotic pressure, and viscosity in 20 consecutive adult patients with uncomplicated nephrotic syndrome. The total plasma cholesterol (mean +/- S.D., 302 +/- 100 mg per deciliter [7.8 +/- 2.6 mmol per liter]) and low-density-lipoprotein cholesterol concentrations (215 +/- 89 mg per deciliter [5.6 +/- 2.3 mmol per liter]) were elevated in most patients, but the high-density-lipoprotein cholesterol level was normal or low (46 +/- 18 mg per deciliter [1.2 +/- 0.5 mmol per liter]) in 95 per cent of the patients. Thus, many hypercholesterolemic patients with unremitting nephrotic syndrome may be at increased risk for atherosclerotic heart disease. A significant inverse correlation was found between the total plasma cholesterol concentration and both the plasma albumin concentration (r = -0.528) and the plasma oncotic pressure (r = -0.674), but not the plasma viscosity (r = +0.319). Enhanced hepatic synthesis of lipoprotein lipids may be stimulated by a decreased plasma albumin concentration or oncotic pressure but does not appear to be due to changes in plasma viscosity.     

Defective high-density lipoprotein composition in patients on chronic hemodialysis. A possible mechanism for accelerated atherosclerosis.

We determined serum high-density lipoprotein cholesterol content and analyzed the approtein structure of the various lipoprotein fractions in 21 patients on chronic hemodialysis. High-density lipoprotein cholesterol was significantly reduced in all patients as compared with 11 normal persons (mean +/-1 standard deviation: 26 +/- 13 vs. 52 +/- 9 mg per 100 ml; P less than 0.001) whether or not triglyceride levels were raised. In seven of those with Type IV hyperlipoproteinemia, protein content of high-density lipoprotein and its subfractions 1, 2 and 3 were also reduced (P less than 0.001) in parallel with reductions in cholesterol in these fractions. Apoprotein electrophoresis showed an increase in "arginine-rich" peptide in very-low-density lipoprotein and high-density lipoprotein fraction 1, and a reduction in apoprotein Cll in very-low-density and high-density lipoprotein. In addition to their reduced high-density lipoprotein cholesterol levels, a major factor in the atherosclerosis of these patients may be their abnormal high-density lipoprotein composition. Their raised triglyceride levels could be due to defective lipoprotein lipase activation by the reduced very-low-density lipoprotein apoprotein.