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.     

Relevance of lipoprotein cholesterol levels measured by HPLC method to appearance midband on electrophoresis and remnant-like particle (RLP)-cholesterol levels

We have recently developed an HPLC method able to separate five lipoproteins (HDL, LDL, IDL, VLDL and chylomicron) followed by cholesterol measurement on each lipoprotein. As an application of this method, this study focused on analyses of triglyceride (TG)-rich lipoproteins, one of risk factor for atherosclerosis. The appearance of midband on electrophoresis is conceivably implicated in atherogenesis. The present study revealed that cholesterol levels in VLDL, IDL and LDL were significantly higher in midband-positive sera than negative sera. Cholesterol levels in remnant-like proteins, another atherogenic indicator, were significantly related to those in VLDL and Chylomicron measured by the present HPLC method. In conclusion, this novel HPLC method can provide valuable information for analyses on TG-rich lipoproteins.     

Lipoprotein (a), low-density,intermediate-density lipoprotein,and blood pressure in a young male population

Summary Both hypercholesterolemia and hypertension are risk factors for atherosclerotic vascular disease, and elevated cholesterol levels occur more frequently than expected in patients with hypertension. Elevated levels of intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL) were shown to be atherogenic, and LDL, comprising the major cholesterol-carrying fraction in human plasma, are structurally related to lipoprotein (a) [Lp(a)], a further risk factor for atherosclerosis. In the present study we investigated 200 male employees (mean age 26±7 years) to determine whether the relationship of IDL and Lp(a) to systemic blood pressure is similar to the reported correlations between total and LDL cholesterol and systemic blood pressure. To this end blood pressure was measured several times in each individual, and lipids, lipoprotein-cholesterol, apolipoprotein B (apo B), and Lp(a) were determined in fasting serum. IDL cholesterol and apo B, the main protein component of IDL and LDL correlated with blood pressure. However, levels of Lp(a) correlated neither with systolic or diastolic blood pressure nor with lipoprotein cholesterol, body weight, or age. Although IDL and Lp(a) are considered lipoprotein risk factors for atherosclerosis, levels of Lp(a), unlike IDL, are not related to blood pressure, body weight, or age. Our data suggest different metabolic and pathophysiological mechanisms of the risk factors, IDL, LDL, and Lp(a).Abbreviations VLDL very low density lipoprotein - IDL intermediate-density lipoprotein - LDL low-density lipoprotein - ApoB Apolipoprotein B - Lp(a) lipoprotein (a) - BMI body mass index Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

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     

Cholesterol lipoproteins,triglycerides, rural-urban differences and prevalence of dyslipidaemia among males in Rajasthan

To develop profiles of serum cholesterol lipoproteins and triglycerides, influence of rural versus urban lifestyle in their levels and prevalence of dyslipidaemias, we studied cohorts of male population in Rajasthan. Fasting blood samples were obtained from 401 men (age range 20-73 years) randomly selected from a larger sample of 3397 during a comprehensive cardiovascular risk factor survey in rural (202 men) and urban (199 men) populations. Serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides (TG) were determined and correlated with age and anthropometric variables. The lipid levels were classified according to US National Cholesterol Education Program (NCEP) guidelines. The mean +/- SD levels in mg/dl were, total cholesterol 170.5 +/- 40, LDL cholesterol 102.1 +/- 36, HDL cholesterol 43.6 +/- 12 and TG 124.0 +/- 50. The mean levels in rural vs. urban population were total cholesterol 165 +/- 37 vs. 176 +/- 43 (p = 0.008), LDL cholesterol 97 +/- 33 vs. 108 +/- 39 (p = 0.003), HDL cholesterol 44 +/- 13 vs. 43 +/- 12 (p = 0.44) and TG 122 +/- 46 vs 126 +/- 55 (p = 0.41). There was significant positive correlation of age and body-mass index with total and LDL cholesterol and triglycerides but not with HDL cholesterol. When classified according to the NCEP guidelines high total cholesterol (> or = 240 mg/dl) and LDL cholesterol (> or = 160 mg/dl) was in 33 (8.3%). Borderline high total cholesterol (200-239) was in 64 (16%) and borderline high LDL cholesterol (130-159) in 55 (13.7%). Borderline high triglyceride (200-400 mg/dl) was in 33 (8.2%) and severe hypertriglyceridaemia in none. Low HDL cholesterol (< 35 mg/dl) was in 96 (23.9%) and protective level of HDL cholesterol (> or = 60 mg/dl) in 47 (11.7%). In urban as compared to rural men the prevalence of hypercholesterolaemia > 200 mg/dl (28% vs 22%) and hyper LDL cholesterolaemia (26% vs 18%) were significantly more.     

Reduced plasma concentrations of total, low density lipoprotein and high density lipoprotein cholesterol in patients with Gaucher type I disease

Plasma lipid and serum apoprotein concentrations were determined in twenty-nine individuals with Gaucher type I disease. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol were all significantly reduced in the patients with Gaucher disease compared to a group of matched control subjects. Total, LDL and HDL cholesterol were lower in males than in females with Gaucher disease. These sex differences appeared to be inversely correlated with the severity of disease manifestations which were greater in the males. Serum levels of apoprotein-B and apoprotein-AI, the major structural apoproteins of LDL and HDL, respectively, were decreased in the subjects with Gaucher disease. Thus, the reductions in LDL and HDL cholesterol were associated with reduced numbers of lipoprotein particles in plasma. In contrast, apoprotein-E, a protein which is secreted by several tissues, including activated macrophages and which may mediate hepatic catabolism of lipoproteins, was elevated in the patients. Since macrophages may also catabolize lipoproteins, Gaucher disease may serve as a model for the effect of activated macrophages upon human lipoprotein metabolism.
This work was supported by the following grants: USPHS HL 23077, HD 07105, HL 25752, CA 31656 and RR-71 from the National Institutes of Health; 1–273 and 1–578 from the March of Dimes Birth Defects Foundation; grant from the New York Heart Assocation. Dr. Ginsberg is a recipient of a Research Career Development Award HL 00949 and is an Irma T. Hirschl Career Scientist. Dr. Grabowski is a recipient of a Clinical Investigator Award HD 00386.     

Separation of bovine plasma lipoproteins by a rapid ultracentrifugation method

The recently described method of centrifugation with iodixanol for the rapid separation of human plasma lipoproteins was adapted to separate bovine plasma lipoproteins. Density gradients were generated by mixing plasma with iodixanol 12% (w/v), followed by centrifugation at 350,000 g and 16 degrees C for 3 h 10 min in a vertical rotor. Gradients were unloaded dense-end first into 10 fractions. Human very low density lipoprotein (VLDL; density < 1.011 g/ml), low density lipoprotein (LDL; density = 1.016-1.039 g/ml) and high density lipoprotein (HDL; density = 1.039-1.090 g/ml) were resolved well at densities considerably lower than those traditionally reported in salt gradients. In gradients generated from 12% iodixanol, bovine LDL and HDL exhibited even lower densities (1.016-1.028 and 1.016-1.048 g/ml, respectively) with all lipoproteins occurring at the lower density region of the gradient. In contrast, density gradients generated from layers of equal volumes of 6% and 12% iodixanol readily separated bovine HDL from VLDL, whilst LDL still overlapped with HDL. The latter accounts for >80% of all bovine lipoproteins and exists as two populations, namely light and heavy HDL. Gradients generated from two layers of iodixanol recovered bovine HDL in five fractions. The hypercholesterolaemia associated with lactation resulted in a modest shift in the profile of HDL cholesterol towards lipoprotein particles of lower density (light HDL). Significant between-farm differences were also detected in the density profiles of bovine plasma cholesterol. This new method is suitable for use in research and diagnosis in relation to lipoprotein metabolism disorders in cows.     

Very low density lipoprotein apolipoprotein B metabolism in humans

Summary The human plasma lipoproteins encompass a broad spectrum of particles of widely varying physical and chemical properties whose metabolism is directed by their protein components. Apolipoprotein B₁₀₀ (apo B₁₀₀) is the major structural protein resident in particles within the Svedberg flotation range 0–400. The largest of these, the very low density lipoprotein (VLDL), rich in triglyceride, are metabolised by sequential delipidation through a transient intermediate density lipoprotein (IDL) to cholesterol-rich low density lipoproteins (LDL). Several components contribute to the regulation of this process, including (a) the lipolytic enzymes lipoprotein lipase and hepatic lipase (b), apolipoproteins B, CII, CIII and E, and (c) the apolipoprotein B/E or LDL receptor. Lipoprotein lipase acts primarily on large VLDL of Sf 60–400. Hepatic lipase on the other hand seems to be critical for the conversion of smaller particles (Sf 12–60) to LDL (Sf 0–12). Although most apo B₁₀₀ flux is directed to the production of the delipidation end product LDL, along the length of the cascade there is potential for direct removal of particles from the system, probably via the actions of cell membrane receptors. This alternative pathway is particularly evident in hypertriglyceridaemic subjects, in whom the delipidation process is retarded.VLDL metabolism shows inter subject variability even in normal individuals. In this regard, apolipoprotein E plays an important role. Normolipidaemic individuals homozygous for the apo E₂ variant exhibit gross disturbances in the transit of B protein through the VLDL-IDL-LDL chain.Abbreviations apo B, C, E Apolipoprotein B, C, E - CETP Cholesteryl ester transfer protein - FCH Familial combined hyperlipidaemia - FH Familial hypercholesterolaemia - FHTG Familial hypertriglyceridaemia - HDL High density lipoprotein - HL Hepatic lipase - IDL Intermediate density lipoprotein - LDL Low density lipoprotein - LpL Lipoprotein lipase - RFLP Restriction fragment length polymorphism - Sf Svedberg flotation coefficient - VLDL Very low density lipoprotein - WHHL Watanabe heritable hyperlipidemic     

Low density lipoprotein-containing circulating immune complexes and coronary atherosclerosis

Blood serum of most patients with coronary heart disease (CHD) caused a 2- to 5-fold increase in the lipid content of smooth muscle cells cultured from unaffected human aortic intima, i.e., possessed an atherogenic potential manifested in culture. Treatment of the CHD patients' serum with 2.5% polyethylene glycol 6000 removed the circulating immune complexes. The serum subjected to this treatment lost its atherogenic properties, i.e., failed to increase the content of lipids in cultured cells. Incubation of smooth muscle cells derived from human aortic intima with circulating immune complexes isolated from an atherogenic patient's serum caused a 1.5- to 3-fold rise in the intracellular cholesterol. Circulating immune complexes contained apolipoprotein B (apo B), but not apolipoproteins A1 and E. The apo B content strongly correlated with the total cholesterol content. The cholesterol/apo B ratio of the complexes was characteristic of low density lipoproteins (LDL), but not of very low density lipoproteins or intermediate density lipoproteins. The composition of the main lipid classes in these complexes was similar to that in LDL. Blood sera of most (90%) CHD patients was characterized by a high cholesterol and apolipoprotein B content in circulating immune complexes. The ability of these sera to induce lipid accumulation in cultured cells directly correlated with the cholesterol and apolipoprotein B level of circulating immune complexes (r = 0.91). These findings suggest that the atherogenic potential of CHD patients' blood serum is due to LDL-containing immune complexes.     

The effect of oestrogen implants on high density lipoproteins and its subfractions in women in their pre-mature menopause

Oestrogen is recognized as having profound effects on lipid and lipoprotein levels. It is also considered as the agent protecting the pre-menopausal woman from arteriosclerotic cardiovascular disease. High density lipoprotein (HDL) has also been ascribed a protective role against the development of arteriosclerosis. The effect of natural oestrogen (17β-oestradiol) administered in the form of a subcutaneous pellet on concentrations of lipids and lipoproteins, particularly high density lipoproteins and its subfractions were determined in three young women with premature menopause. Plasma cholesterol, low density lipoprotein and very low density lipoprotein and very low density lipoprotein levels decreased following oestrogen implantation. High density lipoproteins and in particular subfraction 2 (density cut 1.063-1.125 gm/ml) and subfraction 3 (density cut 1.125-1.21 gm/ml) increased profoundly but there was a slight fall in the HDL 2/HDL 3 cholesterol ratio. The HDL/LDL cholesterol ratio increased from 0.21 to 0.46. A decrease in the urinary FSH levels paralleled these changes in the lipoprotein concentrations. Oestrogen administered in this form, unlike other oestrogen or mixed oestrogen-progestogen compounds is a definite modifier of arteriosclerotic risk, and as such could be given therapeutically in menopausal hypercholesterolemic females.     

The pathophysiology of cholesterol metabolism in man

Summary The concentration of low density lipoprotein in human plasma depends on the balance between its rates of synthesis and catabolism. Although both processes appear to be independently regulated they occur side by side in the liver and may be linked via the activity of the high affinity low density lipoprotein receptor on hepatocyte membranes. Dietary changes such as cholesterol feeding or variation in fat content can promote synthesis of the lipoprotein without changing catabolism while other interventions (e.g. sequestrant resin therapy) have the opposite effect. These different responses may be explained on the basis of compartmentalisation of regulatory sterol pools in the liver cell.Abbreviations apo apolipoprotein - FH familial hypercholesterolaemia - HDL high density lipoproteins (d=1.063–1.21 kg/l) - HMG CoA reductase 3-hydroxy-3-methylglutaryl Coenzyme A reductase - IDL intermediate density lipoproteins (d=1.006–1.019 kg/l) - LDL low density lipoproteins (d=1.019–1.063 kg/l) - VLDL very low density lipoproteins (d<1.006 kg/l)     

Supraphysiological concentrations of estradiol in menopausal women given repeated implant therapy do not adversely affect lipid profiles

BACKGROUND: The effects of oral estrogen therapy (ERT) on lipids and metabolic parameters are well known, in contrast to the effects of subcutaneously administered estrogen, particularly high concentrations of estrogen. We examined metabolic parameters in cohorts of women with and without subcutaneous estrogen therapy with concomitant supra-normal concentrations of estradiol (SE). METHODS: Lipids and lipoprotein concentrations, low density lipid (LDL) subfractions, and activity of hepatic lipase (HL) were assessed in 30 menopausal women with SE and 19 control subjects not using ERT, matched for body mass index and age. RESULTS: Waist-hip ratio (WHR) and fasting insulin (FI) concentrations were lower in the SE group compared with the women not on ERT (P < 0.05). The concentrations of triglyceride and high density lipid (HDL) cholesterol were similar (P > 0.1), whereas total cholesterol (P < 0.05), LDL cholesterol (P < 0.05), and HL activity (P < 0.01) were lower in the SE group. Concentrations of the large, buoyant LDL I subfraction were significantly lower in the SE group (P < 0.05), but there was no difference in LDL III concentrations. CONCLUSIONS: Women with SE have similar triglyceride and HDL cholesterol levels but lower LDL cholesterol concentrations compared with post-menopausal women not taking ERT. The observations that the SE group showed reduced fasting insulin and WHR suggest that supra-normal circulating concentrations of estradiol, delivered subcutaneously, may beneficially influence insulin metabolism.     

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     

A first British case of fish-eye disease presenting at age 75 years: a double heterozygote for defined and new mutations affecting LCAT structure and expression.

Fish-eye disease is a familial syndrome with corneal opacification, major high density lipoprotein (HDL) deficiency in plasma, significant cholesterol esterification in plasma on non-HDL lipoproteins, generally without premature coronary disease. This first British male case from unrelated British parents had infarcts when aged 49 and 73 years but was asymptomatic at age 81 years, with plasma cholesterol 4.3-7.1 mmol/litre, triglycerides 1.8-2.2 mmol/litre, HDL cholesterol < 0.1 mmol/litre, apolipoprotein A-I < 0.16 g/litre, lipoprotein(a) 0.61 g/litre. Cholesterol esterification was impaired using HDL-3 and A-I proteoliposomes but not using VLDL/IDL/LDL. The findings are those of LCAT deficiency with the classic fish-eye disease defect. Most of the 22 reported cases were homozygous or heterozygous for a Thr-Ile mutation at codon 123 of the lecithin:cholesterol acyltransferase (LCAT) gene. This patient was a double heterozygote for this mutation and a second new incompletely defined mutation affecting LCAT expression as defined by reduced mass and activity in plasma.     

Stimulating effect of intermediate-density lipoproteins (IDL) from hyperlipemic plasma on hepatic lipase

Summary The main lipoprotein density classes, namely very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), high-density lipoproteins₂ (HDL₂) and HDL₃ were investigated with respect to their influence on hepatic lipase (HTGL) activity in vitro.Lipoproteins from pooled normal plasma (NP) and from pooled hyperlipemic plasma (HP) were prepared by means of sequential ultracentrifugation. Hepatic lipase was determined radioenzymatically after preincubation with protamine sulfate. It could be demonstrated that IDL from HP were able to stimulate HTGL activity by approximately 100% above the baseline value. HDL₃ from both NP and HP revealed an inhibiting effect on HTGL activity. VLDL, LDL, and HDL₂ exhibited no significant effect on HTGL activity.It is speculated that HTGL could possibly represent a second pathophysiological pathway for the catabolism of IDL in hyperlipemia but this presumption is supported by only a few investigations in vivo.

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Abbreviations HDL₂ High-density lipoproteins₂ - HDL₃ High-density lipoproteins₃ - HP Hyperlipemic plasma pool - HTGL Hepatic lipase - IDL Intermediate-density lipoproteins - LDL Low-density lipoproteins - NP Normal plasma pool - VLDL Very low-density lipoproteins     

Serum lipids and lipoproteins during malaria infection

Total serum cholesterol and lipoproteins levels were determined in a selected group of healthy and Plasmodium falciparum infected Cameroonians. There was a significant difference (P less than 0.05) in the level of the cholesterol between normal individuals (1.61 +/- 0.60 g1-1) and patients (1.23 +/- 0.37 g1-1). The mean values +/- SD of HDL cholesterol were (0.62 +/- 0.25 g1-1) and (0.46 +/- 0.36 g1-1) for controls and malaria infected subjects respectively. The LDL cholesterol concentration was (0.77 +/- 0.85 g1-1) in patients compared to (0.99 +/- 0.33 g1-1) for controls. There was a significant difference between the apolipoprotein B concentration in the sera of non infected (1.03 +/- 0.50 g1-1) and infected subjects (1.64 +/- 0.50 g1-1) (P less than 0.05). A decrease of apolipoprotein A was observed in the sera of patients (1.36 +/- 0.60 g1-1) compared to controls (1.70 +/- 0.34 g1-1). These results suggest a possible atherogenic risk during persistent malaria infection.     

The influence of simvastatin alone or in combination with gemfibrozil on plasma lipids and lipoproteins in patients with type III hyperlipoproteinemia

Summary Nineteen adult patients with type III hyperlipoproteinemia (HLP) and homozygosity for apolipoprotein (apo) E2 were treated with the 3-hydroxy-3-methyl glutaryl coenzyme A (HMG CoA) reductase inhibitor simvastatin (20 or 40 mg per day) alone or in combination with the fibrate derivative gemfibrozil (450 mg per day) during a 30-week outpatient study. With the 20-mg dose (n = 19) the mean plasma cholesterol level decreased from 13.24±8.04 8.04 at baseline to 8.04±4.19 mmol/l (mean reduction 39.3%; P<0.05), and the mean plasma triglyceride level decreased from 13.47±19.22 to 7.84±7.71 mmol/l (–41.8%; NS); this was due to a decrease in very low density lipoprotein (VLDL) cholesterol from 8.95±8.64 to 4.94±4.24mmo1/l (–44.8%; NS), a decrease in low density lipoprotein (LDL) cholesterol from 3.54±0.93to 2.25 ± 0.59 mmol/l (–36.5%; P<0.01), and an increase in high density lipoprotein (HDL) cholesterol from 0.72±0.28 to 0.85±0.34 (+18.1%; NS). Thirteen patients were treated with 40 mg simvastatin per day. Under this regimen there was a further significant decrease in LDL cholesterol from 2.33±0.62 to 1.81±0.49 mmol/l (–22.3%; P<0.01). In six patients who remained hyperlipidemic on monotherapy combination drug therapy with simvastatin (40 mg per day) and gemfibrozil (450 mg per day) was given. Compared to simvastatin alone the addition of gemfibrozil further lowered plasma concentrations of total cholesterol by 14.9%, VLDL cholesterol by 23.5%, and triglycerides by 17.1%, although this was not statistically significant. No patient was discontinued from single or combination drug therapy, and no severe clinical or biochemical side effects were observed. The results of this study demonstrate the usefulness of simvastatin in the therapy of type III HLP and indicate that in individual patients who remain hyperlipidemic on monotherapy combination drug therapy with both of these drugs is effective in further reducing plasma concentrations of total cholesterol, VLDL cholesterol, and triglycerides. Although no patient in this investigation developed myopathy or rhabdomyolysis, combined fibrate-HMG CoA reductase inhibitor treatment should be considered only for severe forms of hyperlipidemia and for patients who do not respond sufficiently to mon-therapy of any of these drugs.Abbreviations Apo Apolipoprotein - CPK creatine phosphokinase - GGT gamma-glutamyl transpeptidase - HDL high density lipoproteins - HLP hyperlipoproteinemia - HMG CoA 3-hydroxy-3-methyl glutaryl coenzyme A - IDL intermediate density lipoproteins - LDL low density lipoproteins - TG triglycerides - VLDL very low density lipoproteins     

Treatment of coronary heart disease by diet and exercise: Fasting and diurnal lipoproteins

Summary The effects of a combined exercise and low-fat dientary regimen were studied in 11 patients with angiographically documented coronary heart disease (cholesterol 233 mg/dl, triglycerides 158 mg/dl) and 13 comparable patients (cholesterol 224 mg/dl, triglycerides 174 mg/dl) on usual care. During one year, fasting serum lipoproteins were lowered to ideal levels in the intervention group (cholesterol 191 mg/dl, triglycerides 100 mg/dl, LDL-cholesterol 121 mg/dl). There was no change of triglycerides and cholesterol on usual care while LDL-cholesterol rose significantly. Neither regimen had any effect on HDL-cholesterol. Diurnal triglycerides as a presumptive measure of IDL in the intervention group were diminished by 39%. The study demonstrates the feasibility of a diet and exercise regimen to normalize midly elevated plasma lipid levels and thus to possibly affect the course of coronary heart disease without drugs.Abbreviations Chol cholesterol - TG triglycerides - HDL high density lipoproteins - LDL low density lipoproteins - LP(a) lipoprotein (a) - P/S polyunsaturated to saturated fatty acid ratio - Int. Intervention group - C Control group Supported by Bundesministerium für Forschung und Technologie     

Disturbance of apolipoprotein B100 containing lipoprotein metabolism in severe hyperlipidemic and lipodystrophic HIV patients on combined antiretroviral therapy: evidences of insulin resistance effect

The aim was to study the mechanisms involved in the dyslipidemia associated with lipodystrophy in HIV infected patients on antiretroviral therapy (ART). We investigated the in vivo kinetics of apolipoprotein B100 (apoB) containing lipoproteins using a 14 h primed constant infusion of [5,5,5, (2)H(3)] leucine and compartmental modelling in normolipidemic without lipodystrophy (7 patients, NLD) or dyslipidemic with lipodystrophy (7 patients, LD) treated with ART. Subjects in group LD showed higher plasma triglycerides (5.73+/-3.58 vs 1.29+/-0.54 g/L, p<0.005), total cholesterol (2.98+/-0.95 vs 1.74+/-0.26 g/L, p<0.05), apoB (1.49+/-1.11 vs 0.51+/-0.11 g/L, p<0.005) and apolipoprotein CIII in apoB containing lipoproteins (117.7+/-42.2 vs 22.6+/-23.9 g/L, p<0.005). LD subjects exhibited an insulin resistant as observed by higher HOMA (3.44+/-1.62 vs 1.60+/-0.61, p<0.05). They exhibited an increase in VLDL (1.24+/-0.33 vs 0.80+/-0.21 mg/kg/h, p<0.05), decrease in IDL (0.20+/-0.10 vs 0.48+/-0.24 mg/kg/h, p<0.05) and no difference in LDL (0.38+/-0.19 vs 0.45+/-0.25 mg/kg/h) production rate. LD subject also showed a dramatic decrease in transformation of VLDL to IDL (0.013+/-0.010 vs 0.258+/-0.206 h(-1), p<0.005) and IDL to LDL (0.088+/-0.093 vs 0.366+/-0.189 h(-1), p<0.05) and a decrease in fractional catabolic rate (FCR) of VLDL (0.199+/-0.132 vs 0.555+/-0.398 h(-1), p<0.05), IDL (0.110+/-0.08 vs 0.523+/-0.275 h(-1), p<0.05) and LDL (0.010+/-0.005 vs 0.025+/-0.014 h(-1), p<0.05). These disturbances, overproduction and an overall delayed catabolism of apoB, are similar to those observed using the same protocol in insulin resistant subjects. Our study suggests that metabolic disturbance of apoB100 observed in lipodystrophic HIV in combined antiretroviral therapy are consecutive to insulin resistance induced by the treatment.     

Variability in the response of different male subjects to the effect of marathon running on the increase in plasma high density lipoprotein

Summary The acute effects of running a 42.2 km marathon race on the concentration and composition of the plasma lipoproteins were studied in 56 men of varying fitness, training experience, age and physical characteristics. There was no change in the mean concentration of total serum cholesterol, but a 10.9% increase (P<0.001) in the mean concentrations of high-density lipoprotein cholesterol (HDL-TC), representing an 11.1% increase (P<0.001) in the cholesteryl ester (CE) and 9.9% increase (P<0.001) in the unesterified cholesterol (UC) moieties of HDL. The ratio of total serum cholesterol to HDL-TC decreased significantly (P<0.001) during the exercise. Changes in lipoprotein concentrations during the marathon varied considerably between individual subjects, with a small proportion of subjects exhibiting relatively large increases or decreases in HDL-TC, HDL-CE and HDL-UC. Small sub-populations of runners were identified who showed abnormally large decreases in HDL-UC and abnormally small increases in HDL-CE relative to HDL-UC. A correlation (P<0.05) was found between the average weekly mileage of training and the increase in HDL-TC, whilst faster runners (finishing time <3 h; n=13) had a significantly greater (P<0.02) increase in HDL-TC than slower runners (>4 h; n=14). The observed alterations in the lipoproteins are consistent with increased rates of lipolysis of triacylglycerol-rich lipoproteins and of cholesterol esterification during the marathon and suggest that the effect of exercise on the activities of the enzymes that catalyse these processes may vary considerably between different subjects and may be modulated by training and other factors.Abbreviations VLDL very low density lipoproteins - LDL low density lipoproteins - HDL high density lipoproteins - HDL-TC high-density lipoprotein-total cholesterol - HDL-CE cholesteryl ester - HDL-UC unesterified cholesterol