Pravastatin treatment of very low density, intermediate density and low density lipoproteins in hypercholesterolemia and combined hyperlipidemia secondary to the nephrotic syndrome

BACKGROUND/AIMS: In the current study pravastatin was used in nephrotic syndrome patients with hypercholesterolemia and combined hyperlipidemia to test whether the drug decreases production of LDL and reduces levels of VLDL and IDL. METHODS: Thirteen patients (7 with high LDL alone and 6 with high VLDL, IDL and LDL) were randomized in a placebo-controlled study that had a crossover design. Patients were treated 8 weeks with pravastatin (40 mg/day) (or placebo) and switched to the corresponding placebo/drug for another 8 weeks. During each phase of the trial, patients had measurement of plasma levels of lipoprotein lipids, and turnover rates of autologous LDL apo B. RESULTS: Pravastatin increased LDL clearance by 16.7% and reduced total cholesterol content per LDL particle in patients with hypercholesterolemia. In combined hyperlipidemia, LDL clearance increased by 19% and there was no significant change in the production of LDL-apo B. Levels of VLDL+IDL apo B were not reduced significantly, while the total cholesterol content of these particles was reduced by 31.7%. CONCLUSION: Pravastatin effectively reduced LDL levels in both types of dyslipidemia by increasing LDL clearance. Treatment had no effect on production of LDL or on levels of VLDL+IDL-apo B. Thus, pravastatin increases LDL clearance. Statins do not seem to affect production rates of apo B-containing lipoproteins. Treatment of combined hyperlipidemia may require pravastatin and an added drug targeted to normalize levels of VLDL and IDL.     

Hypertriglyceridemia: danger for the arteries

AN INDEPENDENT RISK FACTOR: Although debate continues on the epidemiological impact, all surveys report that elevated serum triglyceride is an important risk factor in one-way analysis. More recent case-control studies in patients with premature coronary artery disease have shown that total triglyceride and VLDL levels discriminate better between subjects with and without coronary artery disease. Angiographic studies demonstrate that elevated serum triglyceride is found in coronary artery disease patients and that elevated VLDL or IDL is associated with severity. This relationship is persistently found when the serum cholesterol is taken into consideration but is no longer significant in most of the multivariate analyses. A recent meta-analysis is however in favor of an independent role for triglycerides, particularly in women. Two prospective studies published in 1998 confirmed that hypertriglyceridemia is an independent risk factor. VARIABLE IMPACT: Hypertriglyceridemia is a heterogeneous anomaly, not only due to different underlying pathophysiological mechanisms, but also in terms of cardiovascular risk. In familial hypertriglyceridemia, cardiovascular risk is apparently only moderately affected. Inversely, in combined familial hypertriglyceridemia and hyperapobetalipoproteinemia, the risk of premature cardiovascular disease is increased. ATHEROGENIC EFFECT: Unlike large VLDL rich in triglycerides, small VLDL rich in cholesterol ester have a strong atherogenic potential. Likewise, remnants are potentially atherogenic due to their relatively high cholesterol ester component and their accumulation on the arterial wall (Zilversmit postprandial atherogenesis theory). INCREASED RISK: The triglyceride-related risk is partly the consequence of frequently associated changes in lipoprotein distribution (lower HDL cholesterol, principal consequence of hypertriglyceridemia, elevation of small dense more readily oxidizable LDL) and hemostasis disorders (increased factor VIIc and PAI-1). In addition, hypertriglyceridemia is often found with other cardiovascular risk factors, particularly it readily occurs in insulin resistance syndromes.     

Significant Changes in the Lipid-Lipoprotein Status of Premenopausal Morbidly Obese Females following Gastric Bypass Surgery

The morbidly obese premenopausal female may be more dyslipoproteinemic and at greater risk for developing coronary heart disease than her lean or less seriously obese counterparts. The purpose of the present study was to examine the effects of weight loss with Roux-en-Y gastric bypass surgery on the lipid-lipoprotein status of morbidly obese, premenopausal females. Anthropometrics and blood samples for lipid-lipoprotein analyses were obtained before surgery and 6 - 12 months post-operatively. Following surgery, patients lost 30% of their initial body weight, along with a 40% decline (p < 0.01) in total triglyceride and a 20% decrease (p < 0.01) in total cholesterol. Levels of cholesterol in the high density lipoprotein (HDL) fraction were unaffected by weight loss, but there was a significant (p < 0.05) increase in the proportion of HDL in its more buoyant and anti-atherogenic form, i.e. HDL-L. The apolipoprotein B-containing lipoproteins, very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL), were reduced up to 70% following surgery. There were no significant changes in VLDL or IDL particle composition, i.e. cholesterol/triglyceride, cholesterol/protein, but there was a significant (p < 0.01) increase in the ratio of cholesterol/apolipoprotein B in LDL, suggesting a shift from the small, dense atherogenic LDL to a larger, less atherogenic particle. We conclude that weight loss following gastric bypass surgery markedly improves the lipid-lipoprotein status of morbidly obese premenopausal females and, thereby, significantly reduces the risk of coronary disease.     

Impact of ezetimibe on cholesterol subfractions in dyslipidemic cardiac transplant recipients receiving statin therapy

Abstract: Background: Ezetimibe decreases cholesterol in cardiac transplant recipients intolerant to statins therapy. The effects of ezetimibe in addition to statins therapy and its relationship with the magnitude of dyslipidemia and statins utilization have not been studied in cardiac transplant recipients. Methods: The design of this investigation was a retrospective case control study. Twenty‐two patients receiving the combination of therapy of statins plus ezetimibe were compared with 43 patients treated with statins only. The endpoints were assessed after three months of follow‐up. Results: The addition of ezetimibe decreased low density lipoprotein‐cholesterol by 25% compared with a 4% increase in patients receiving statins only. The impact of ezetimibe was similar regardless of the magnitude of dyslipidemia or statins dosage. Ezetimibe increase high density lipoprotein (HDL)‐cholesterol only in patients with baseline HDL‐cholesterol above 1.3 mM/L (p < 0.05). There was an asymptomatic, but significant increase in creatinine kinase level [+31.4 ± 8.1 (ezetimibe) vs. + 1.5 ± 5.0 mM/L (placebo); p = 0.005]. Conclusion: Ezetimibe therapy provides a significant reduction in most cholesterol subfractions regardless of the magnitude of dyslipidemia and statins dosage.     

The atherogenic lipoprotein profile associated with obesity and insulin resistance is largely attributable to intra-abdominal fat

Obesity and insulin resistance are both associated with an atherogenic lipoprotein profile. We examined the effect of insulin sensitivity and central adiposity on lipoproteins in 196 individuals (75 men and 121 women) with an average age of 52.7 years. Subjects were subdivided into three groups based on BMI and their insulin sensitivity index (S(I)): lean insulin sensitive (n = 65), lean insulin resistant (n = 73), and obese insulin resistant (n = 58). This categorization revealed that both obesity and insulin resistance determined the lipoprotein profile. In addition, the insulin-resistant groups had increased central adiposity. Increasing intra-abdominal fat (IAF) area, quantified by computed tomography scan and decreasing S(I), were important determinants of an atherogenic profile, marked by increased triglycerides, LDL cholesterol, and apolipoprotein B and decreased HDL cholesterol and LDL buoyancy (Rf). Density gradient ultracentrifugation (DGUC) revealed that in subjects who had more IAF and were more insulin resistant, the cholesterol content was increased in VLDL, intermediate-density lipoprotein (IDL), and dense LDL fractions whereas it was reduced in HDL fractions. Multiple linear regression analysis of the relation between the cholesterol content of each DGUC fraction as the dependent variable and IAF and S(I) as independent variables revealed that the cholesterol concentration in the fractions corresponding to VLDL, IDL, dense LDL, and HDL was associated with IAF, and that S(I) additionally contributed independently to VLDL, but not to IDL, LDL, or HDL. Thus an atherogenic lipoprotein profile appears to be the result primarily of an increase in IAF, perhaps via insulin resistance.     

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.     

Echolucent,rupture-prone carotid plaques associated with elevated triglyceride-rich lipoproteins,particularly in women

BACKGROUND: We tested whether fasting and postprandial triglyceride-rich lipoprotein elevations are gender specific (1) in patients with carotid artery stenosis >or=50% vs controls, and (2) in patients with echolucent, rupture-prone plaques compared with controls. METHODS AND RESULTS: We studied 66 controls and 323 patients with carotid artery stenosis >or=50%, of which 160 had echolucent plaques. Participants underwent a fat-tolerance test and carotid artery plaque evaluation with use of high-resolution B-mode ultrasound and computerized image analysis. By comparison, female cases with carotid stenosis >or=50% had higher fasting and postprandial triglyceride levels than did controls; however, this difference was not observed between male cases and controls. Fasting and postprandial very-low-density lipoprotein (VLDL) and intermediate density liprotein (IDL) cholesterol levels were elevated; low density lipoprotein (LDL) cholesterol level was unchanged, and high density lipoprotein (HDL) cholesterol level was reduced in both female and male cases vs controls. Fasting and postprandial triglyceride levels were elevated in women with echolucent plaques vs controls, but not in women with echo-rich plaques, or in men with echolucent or echo-rich plaques. Fasting and postprandial VLDL and IDL cholesterol levels were elevated, LDL cholesterol level was unchanged, and HDL cholesterol level was reduced in both female and male patients with echolucent plaques vs controls. CONCLUSIONS: Fasting and postprandial triglyceride-rich lipoproteins (but not LDLs) are elevated in patients with carotid artery stenosis of >or=50% compared with controls, and particularly identify echolucent, rupture-prone carotid plaques. These observations are more pronounced in women than in men.     

Managing metabolic complications of peritoneal dialysis

AIMS: The purposes of this paper are: to report our experience employing a comprehensive, multifaceted treatment program to improve the metabolic disturbances of dyslipidemia, hyperglycemia and weight gain observed in our peritoneal dialysis patients, and by post-hoc analysis to demonstrate how the routine clinical lipid profile can be manipulated arithmetically to estimate levels of atherogenic low-density lipids and thereby achieve a more sophisticated clinical analysis of dyslipidemia and its response to therapy. METHODS: Data are reported for 56 patients who were stable on peritoneal dialysis for at least 6 months and who had metabolic data available prior to beginning peritoneal dialysis. Metabolic complications of peritoneal dialysis were treated by a comprehensive strategy involving diet, glycemic control and lipid-lowering medications with an emphasis on weight control and exercise. From the measured lipid profile (total cholesterol (TC), high-density lipoprotein (HDL) and triglyceride (TG)), levels of atherogenic low-density lipids (low-density lipoprotein (LDL), non-HDL, very-low-density lipoprotein (VLDL) and intermediate-low-density lipoprotein (IDL) were calculated. RESULTS: Before initiation of peritoneal dialysis therapy, the most common lipid abnormalities were low levels of HDL (59%) and elevated levels of triglyceride (41%) with infrequent elevations of total cholesterol (9%) and low-density lipoprotein (23%). After initiation of peritoneal dialysis therapy, all lipid levels, except HDL, increased significantly, and hyperlipidemia, hyperglycemia and obesity, singly or in combination, occurred in 84% of patients. With treatment, elevated lipid levels decreased significantly with reversal of the adverse cardiovascular risk profile of lipids that developed during peritoneal dialysis therapy, and HDL levels increased significantly. On peritoneal dialysis therapy, all diabetic patients required insulin, and glycemic control was achieved in most patients (79%). Excessive weight gain (10-24% body weight) occurred in 20% of peritoneal dialysis patients. Diabetic patients had a higher incidence of being overweight and obese. Post-hoc analysis revealed that levels of VLDL and IDL frequently were elevated both before (57-61%) and during (68-84%) peritoneal dialysis and that target levels of these atherogenic low-density lipoproteins infrequently (22-26%) were achieved. CONCLUSIONS: The metabolic complications of peritoneal dialysis are responsive to a comprehensive treatment strategy. Controlling weight gain on peritoneal dialysis therapy maybe a difficult challenge for some patients, particularly those who are diabetic. Patients with renal failure and on dialysis, especially peritoneal dialysis, frequently have elevated levels of the atherogenic lipoproteins fragments VLDL and IDL. Future clinical trials should focus on the efficacy and safety of aggressive therapy to achieve target levels of these atherogenic lipids.     

Growth, serum lipoproteins and apoproteins in infants with congenital nephrosis.

Retarded growth and extremely high cholesterol levels have been reported in infants with congenital nephrotic syndrome of the Finnish type (CNF). In an attempt to normalize growth and lipid disturbances the high-calorie diet (130 kcal/kg/d) containing protein 4 g/kg/d and supplemented with unsaturated fatty acids (mean P/S-ratio 1.40) was given to ten infants with CNF from birth. Growth, lipoprotein and apoprotein concentrations were measured. All patients exhibited normal growth, which allows renal transplantation, the only life-saving treatment in CNF, already at an early age. In spite of the diet lipid profiles at 3 and 9 months revealed marked elevation of triglyceride in all lipoproteins, especially in VLDL fraction, compared to controls. The abnormalities increased significantly with time (p for VLDL-TG 0.04). The elevation of serum cholesterol was mainly attributable to the increase of cholesterol in triglyceride-rich particles (chylomicrons, VLDL, IDL). Analysis of VLDL, LDL and HDL revealed significant triglyceride enrichment and cholesterol deficiency in all lipoproteins. The concentrations of the low-molecular weight apoproteins A-I and A-II were significantly decreased, but the concentration of high-molecular apo B was high. Urinary analysis revealed progression and decreasing selectivity of proteinuria with time. Thus the mechanisms leading to lipid abnormalities in CNF are multiple including stimulated hepatic lipoprotein synthesis, impaired conversion of VLDL and IDL to LDL, compositional changes, urinary loss of low-molecular apoproteins and presumably reduced LPL activity. The abnormalities indicate an increased risk of arteriosclerosis in CNF patients.     

Impaired metabolism of high density lipoprotein in uremic patients.

We measured lipoproteins, apolipoproteins, lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), lecithin: cholesterol acyltransferase (LCAT) and parameters of calcium metabolism to evaluate the roles of these enzymes and hypertriglyceridemia for impaired high-density lipoprotein (HDL) metabolism in chronic renal failure, and to examine the impact of altered calcium homeostasis on the lipoprotein-regulating enzymes. The subjects were 25 healthy volunteers and 66 uremic patients, 24 treated with hemodialysis (HD) and 42 with continuous ambulatory peritoneal dialysis (CAPD). Lipoprotein analysis revealed: (1) reduction in HDL cholesterol especially in HDL2 subfraction; (2) increase in HDL triglyceride; and (3) decreased ratio of HDL2 cholesterol to HDL3 cholesterol in both HD and CAPD patients. Simple regression analysis showed: (1) a positive correlation between VLDL triglyceride and triglyceride/cholesterol ratio of HDL; (2) positive correlations of LPL level in post-heparin plasma to cholesterol concentrations in HDL2, HDL3 and total HDL, and to apolipoproteins A-I and A-II; and (3) inverse correlations of HTGL to HDL2 cholesterol and to the ratio of HDL2 cholesterol/HDL3 cholesterol. Multiple regression analysis of HDL cholesterol indicated positive association with LPL and inverse correlation with VLDL triglyceride. Four variables including LPL, HTGL, LCAT and VLDL triglyceride explained 51.5% of the variation of HDL cholesterol. HDL2 cholesterol was associated positively with LPL and negatively with VLDL triglyceride in the model. HDL3 cholesterol was associated positively with LPL, HTGL and LCAT and inversely with VLDL triglyceride. Stepwise multiple regression analysis indicated that independent predictors of HTGL were gender, parathyroid hormone levels by a mid-portion assay, ionized calcium and age, and that those of LCAT were ionized calcium and age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dialysis removes apolipoprotein C-I, improving very low-density lipoprotein clearance

Chronic kidney disease (CKD) is associated with dyslipidemia, characterized by increased levels of triglyceride-rich lipoproteins (TRLPs), including very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), with no change or a reduction in low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) levels. Serum triglycerides and IDL are risk factors for vascular disease in dialysis patients, whereas LDL is not. The principal cause of the increase in TRLPs is decreased removal, not increased synthesis. The clearance defect arises from a reduction in specific lipoprotein receptors, decreases in the activity of lipases, and increased levels of low-molecular weight apolipoproteins that inhibit the interaction between TRLPs and both the receptors and the lipases that catabolize them. VLDL from dialysis patients is structurally abnormal and is not metabolized at a normal rate by lipoprotein lipase (LPL).     

Prevention of obesity-linked renal disease: age-dependent effects of dietary food restriction

BACKGROUND: Hyperphagic obese Zucker rats develop glomerular injury and die of renal disease, an outcome prevented by food restriction at an early age. We examined the effects of food restriction imposed at different ages on systemic, renal hemodynamic, and hormonal changes to gain insight into the mechanisms of obesity-linked glomerular injury. METHODS: At 6 weeks of age obese Zucker rats were either fed ad libitum or were restricted in food intake at various ages (6, 12, 26, or 50 weeks) to that consumed by lean Zucker rats (14 g/day). Every four weeks 24-hour urine collections, blood pressure, and venous blood samples were obtained until the end of study (60 weeks). RESULTS: Food restriction at 6 or 12 weeks of age prevented glomerular injury and hypertrophy and delayed the development of hypertension, hypercholesterolemia, and hyperinsulinemia. Food restriction at 26 weeks of age reduced proteinuria, while restriction at 50 weeks prevented further increases in proteinuria without altering pre-existing hypercholesterolemia, hypertension, or hyperinsulinemia. Hypertriglyceridemia and glomerular hyperfiltration in the obese animals were reversed at any age by food restriction. Plasma leptin levels were elevated in all obese groups. CONCLUSIONS: (1) Early food restriction provided the greatest metabolic and renal benefits; (2) glomerular injury correlated with hyperphagia-induced hyperfiltration and hypertriglyceridemia and both were prevented by food restriction; (3) hypercholesterolemia was due to an increase in LDL and/or VLDL cholesterol; and (4) leptin does not directly contribute to glomerular injury in the obese Zucker rat.     

Kinetics of peritoneal protein loss during CAPD: II. Lipoprotein leakage and its impact on plasma lipid levels

We quantified the plasma levels and peritoneal loss of lipids and lipoproteins, and studied the composition of plasma and effluent lipoproteins in 16 patients on CAPD (5 females and 11 males, 18 to 76 years old). Five patients were studied prospectively (at 0, 1, 3 and 6 months) and 11 patients at 6 to 58 months on CAPD (N = 30). Elevated levels of plasma VLDL and reduced levels of plasma HDL were maintained in these patients throughout 58 months of CAPD, whereas the initially increased LDL levels showed a tendency towards normalization. All plasma lipoproteins (VLDL, IDL, LDL and HDL) were present in the peritoneal effluent. The lipoproteins isolated from plasma and peritoneal fluid shared a similar lipid and apolipoprotein composition. The peritoneal transport characteristics of plasma lipoproteins were similar to other plasma macromolecules. Their clearance correlated with their molecular mass, plasma concentration and dwell time, but was not affected by duration of CAPD treatment. The plasma lipid and lipoprotein levels were unaffected by the rate of glucose absorption. The peritoneal protein clearance correlated positively with plasma levels of triglyceride and LDL, and negatively with plasma HDL. An inverse correlation was observed also between plasma levels of HDL and its peritoneal clearance (r = -0.393, P less than 0.025, N = 30). The continuous peritoneal loss of HDL and the hypertriglyceridemia were found to contribute most to the persistent low plasma levels of HDL in CAPD patients, and thus may lead to the accelerated atherosclerosis observed in these patients.     

The Efficacy and Safety of Ezetimibe for Treatment of Dyslipidemia After Heart Transplantation

Introduction

Statins, although the treatment of choice for dyslipidemia after heart transplantation (HT), are not always well tolerated or effective. In such cases, administration of ezetimibe may be useful.

Aim

The aim of this study was to assess the efficacy and safety of ezetimibe, with or without statins, after HT.

Method

Thirty-six HT patients, 97% of whom were males of overall mean age of 57 ± 13 years, were all unable to reach target lipid levels with statins alone and/or were intolerant of statins. They were prescribed ezetimibe, with or without a statin. Efficacy and safety were evaluated after 1, 3, 6, and 12 months.

Results

Thirty-four patients were evaluated at 1 month and 12 months. Ezetimibe was prescribed to 27 patients (75%) because of statin inefficacy, and to 9 patients (25%) because of statin intolerance, manifested by myalgia in 4 cases (11%), hepatotoxicity in 2 cases (6%), and rhabdomyolysis in 3 cases (8%). Lipid levels (mg/dL; baseline vs 1 year) were as follows: cholesterol, 235 ± 49 versus 167 ± 32 (P = .013); LDL cholesterol, 137 ± 47 versus 89 ± 29 (P = .001); HDL cholesterol, 54 ± 13 versus 51 ± 10 (P = .235); and triglycerides, 243 ± 187 versus 143 ± 72 (P = .022). There were no cases of liver toxicity, renal dysfunction, or significant alteration of immunosuppressive pharmacokinetics. Ezetimibe was withdrawn from 2 patients because of hand edema or asymptomatic recurrence of rhabdomyolysis first caused by statins.

Conclusions

With or without a statin, ezetimibe was generally well tolerated, reducing total cholesterol, LDL cholesterol, and triglyceride levels with no long-term alteration of HDL cholesterol levels. CPK surveillance is recommended because of a slight continued risk of adverse effects. Further studies should evaluate the benefit for survival.     

Ezetimibe treatment in hypercholesterolemic kidney transplant patients is safe and effective and reduces the decline of renal allograft function: a pilot study.

BACKGROUND: Ezetimibe has shown efficacy in the therapy of hypercholesterolemia in renal transplant patients. This is the first study investigating the effect of ezetimibe on renal function in kidney transplant recipients. METHODS: Fifty-six patients with statin-resistant hypercholesterolemia (total cholesterol >200 mg/dl) after renal transplantation received additional ezetimibe therapy (10 mg/day) for 12 months. A group receiving statin therapy (n=28) served as controls in this prospective study. RESULTS: Total cholesterol and LDL cholesterol concentrations decreased significantly in the ezetimibe-treated patients but remained stable in the control group (delta total cholesterol: -24+/-49 mg/dl vs 19+/-49 mg/dl, P<0.01; delta LDL: -30+/-39 mg/dl vs -3+/-31 mg/dl, P<0.01). Mean creatinine clearance remained stable in ezetimibe-treated patients but decreased significantly in control group (delta Cockcroft-Gault: 0.9+/-7.3 ml/min vs - 4.8+/-12.8 ml/min, P=0.025; delta Modification of Diet in Renal Disease: -0.4+/-6.2 ml/min/1.73 m(2) vs 4.7+/-8.8 ml/min/1.73 m(2), P=0.033). CONCLUSIONS: The data of our prospective case-control study suggest that ezetimibe appears to ameliorate the decline of renal function after renal transplantation.     

Evolution of Lipid Profiles after Bariatric Surgery

Background  

The most commonly encountered dyslipidemia in obese individuals is characterized by a cluster of interrelated plasma lipid and lipoprotein abnormalities including hypertriglyceridemia, low HDL cholesterol values, and increased small, dense LDL cholesterol particles. The aim of this study was to assess the changes in lipid profiles at baseline (pre-operatively) and at follow-up (6, 12, and 18 months) after a laparoscopic Roux-en-Y gastric bypass (LRYGBP). A retrospective observational study was performed involving all patients who consecutively underwent a LRYGBP between January 1, 2007 and December 31, 2009. Fasting lipids sub-fractions (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) were measured and HOMA-IR calculated pre-operatively and at follow-up post-LRYGBP. Pearson’s correlation coefficients were used to assess the relationship between excess weight loss (EWL) and lipid sub-fractions. ANOVA was used to assess the differences between each lipid sub-fraction at various time-points.     

Dyslipidemia and renal disease: pathogenesis and clinical consequences

Patients with chronic renal disease suffer from a secondary form of complex dyslipidemia. The most important abnormalities are an increase in serum triglyceride levels (elevated VLDL-remnants/IDL), small LDL particles and a low HDL cholesterol level. The highly atherogenic LDL subclass, namely LDL-6 or small dense LDL, accumulates preferentially in hypertriglyceridemic diabetic patients with nephropathy or on hemodialysis treatment. All these lipoprotein particles contain apolipoprotein B, thus the complex disorder can be summarized as an elevation of triglyceride-rich apolipoprotein B-containing complex lipoprotein particles. Growing evidence suggests that all of the components of this type of dyslipidemia are independently atherogenic. These particles, specifically the apolipoprotein B moiety, are predominantly prone to modification such as oxidation and glycosilation, which contributes to impaired clearance by the LDL receptor. These complex alterations in lipoprotein composition not only passively accompany chronic renal disease but on the contrary also promote its progression and the development of atherosclerosis. Therefore, renal patients with dyslipidemia should be subjected to lipid-lowering therapy. The effectiveness of lipid lowering on the reduction of cardiovascular endpoints or the progression of renal disease is under investigation or remains to be studied.     

Serum Lipid Profile in Iranian Fat‐tailed Sheep in Late Pregnancy,at Parturition and During the Post‐parturition Period

Blood samples were obtained from 12 Iranian fat‐tailed sheep during 7 weeks pre‐partum, at parturition and 7 weeks post‐partum. The lipids measured were cholesterol, triglyceride, total lipid, high‐density lipoprotein (HDL)‐cholesterol, low‐density lipoprotein (LDL)‐cholesterol, and very low‐density lipoprotein (VLDL)‐cholesterol. The concentrations of cholesterol, triglyceride, HDL‐cholesterol and VLDL‐cholesterol during the 7 weeks pre‐partum, at parturition and the 7 weeks post‐partum were significantly different (P < 0.05). One week before parturition, the concentrations of cholesterol, triglyceride, HDL‐cholesterol and VLDL‐cholesterol were higher (P < 0.05) than at other periods. The lowest concentrations of these parameters were observed 2–3 weeks after parturition. In this study, significant positive correlations were observed between the time of sampling (pre‐partum, parturition and post‐partum) and serum cholesterol (r=0.22; P < 0.01) and HDL‐cholesterol (r=0.25; P < 0.01).     

HMG-CoA reductase, cholesterol 7alpha-hydroxylase, LDL receptor, SR-B1, and ACAT in diet-induced syndrome X

BACKGROUND: Long-term consumption of Western diets can lead to acquired syndrome X, which presents with obesity, insulin resistance, hypertension, hyperlipidemia, and risk of atherosclerotic cardiovascular disease. While plasma lipid abnormalities in syndrome X have been well characterized, their molecular basis remains unclear. This study explored potential mechanisms of hypercholesterolemia in diet-induced syndrome X. METHODS: Female Fischer rats were fed a high-fat, refined-carbohydrate (sucrose) diet (HFS) or standard rat chow (low-fat, complex carbohydrate, LFCC) for 20 months. Plasma lipids and hepatic tissue mRNA, protein, and/or activities of the key enzymes and receptors involved in cholesterol metabolism were determined. RESULTS: The HFS group exhibited hypertension, hyperlipidemia, insulin resistance, obesity, significant down-regulation of hepatic cholesterol 7alpha-hydroxylase (the rate-limiting step in cholesterol catabolism) and low-density lipoprotein (LDL) receptor (LDL-R, the primary pathway of LDL clearance). In contrast, hepatic tissue acyl-coenzyme A:cholesterol acyltransferase (ACAT-2, the primary enzyme involved in intracellular esterification of cholesterol) and scavenger-receptor class B, type 1 (SR-B1 or HDL receptor) were up-regulated. While 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA expression was increased, its protein abundance and activity were unchanged, and HMG-CoA reductase-to-cholesterol 7alpha-hydroxylase ratio was increased in HFS-fed animals. CONCLUSION: Hypercholesterolemia in diet-induced syndrome X is associated with depressed cholesterol 7alpha-hydroxylase, diminished LDL-R, elevated ACAT, and increased HMG-CoA reductase-to-cholesterol 7alpha-hydroxylase ratio. These findings point to impaired hepatic catabolism and uptake of cholesterol and inappropriate cholesterol production capacity as the underlying causes of hypercholesterolemia in rats with diet-induced syndrome X.