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The effect of omega-3 fatty acids on the atherogenic lipoprotein phenotype in patients with nephrotic range proteinuria.
Bell, S, Cooney, J, Packard, CJ, Caslake, MJ, Deighan, CJ
Clinical nephrology. 2012;(6):445-53
Abstract
AIMS: Patients with nephrotic range proteinuria are known to have an increased risk of cardiovascular disease partly due to possessing the atherogenic lipoprotein phenotype. The aim of this study was to examine the effect of high dose omega-3 fatty acids on atherogenic triglyceride rich lipoproteins in patients with nephrotic range proteinuria, comparing their effect on lipoprotein profiles in age and sex matched controls. METHODS 17 patients with nephrotic range proteinuria and 17 age and sex matched controls were studied. Fasting lipids and lipoproteins were measured before and after 8 weeks treatment with 4 g daily of omega-3 fatty acids (Omacor®). RESULTS In patients with proteinuria treatment reduced plasma triglyceride by a mean of 0.45 mmol/l (95%CI 0.16 - 0.74, p = 0.005) and plasma very low density lipoprotein cholesterol by a mean of 0.38 (95%CI 0.01 - 0.75, p = 0.04). LDL III concentration fell from 178.8 mg/dl (61.6 - 231.0) to 96.1 mg/dl (49.3 - 204.5), p = 0.05. In patients treatment altered the LDL profile so that LDLIII which was the major subfraction present at baseline was reduced from 49.9% to 29.8% (p = 0.01). Remnant lipoproteins (RLP) also fell with a mean reduction of 3.5 mg/dl in RLP-Cholesterol (95%CI 0.1 - 6.9, p = 0.05) and 12.4 mg/dl in RLP-triglyceride (95%CI 2.6 - 22.2, p = 0.03). There was however a 0.6 mmol/l rise in LDL-C (p = 0.06) in the patients. Treatment did not alter HDL-C. CONCLUSION In patients with nephrotic range proteinuria, omega-3 fatty acids reduced triglyceride rich lipoproteins, LDL III and remnant lipoproteins. A tendency to an increase in LDL-C was observed but this was offset by an alteration in the distribution of the LDL profile towards lighter, larger LDL particles. We propose that treatment with omega-3 fatty acids in conjunction with a statin may be the ideal therapy in these patients.
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Reduction of serum lipids by soy protein and soluble fiber is not associated with the ABCG5/G8, apolipoprotein E, and apolipoprotein A1 polymorphisms in a group of hyperlipidemic Mexican subjects.
Torres, N, Guevara-Cruz, M, Granados, J, Vargas-Alarcón, G, González-Palacios, B, Ramos-Barragan, VE, Quiroz-Olguín, G, Flores-Islas, IM, Tovar, AR
Nutrition research (New York, N.Y.). 2009;(10):728-35
Abstract
Several studies have evaluated the effect of soy protein or soluble fiber on serum cholesterol in hypercholesterolemic subjects, with different results. We hypothesized that this response is associated with the presence of polymorphisms in genes encoding proteins involved in lipoprotein metabolism or reverse cholesterol transport. Thus, the aims of the present work were to study the effectiveness of a dietary portfolio consisting of a combination of soy protein and soluble fiber integrated in a low saturated fat (LSF) diet on blood lipids in a Mexican group with hyperlipidemia and to determine the association between responsiveness to the diet and the frequency of apolipoprotein (Apo) E and ApoA1 and ABCG5/8 polymorphisms. Forty-three hyperlipidemic subjects (20 men and 23 women) were given an LSF diet for 1 month, followed by an LSF diet that included 25 g of soy protein and 15 g of soluble fiber daily for 2 months. After the 3-month dietary intervention, serum total cholesterol (TC) significantly decreased by 20.6%, and serum triglycerides (TGs) decreased by 40.4%. Fifty-one percent of the subjects had a reduction more than 20% in serum TC, and 77% of the subjects had a reduction more than 20% in serum TG (hyperresponders). Approximately 14% of the hypercholesterolemic subjects had the ABCG8 (52 G/C) polymorphism, 65% had the ABCG5 (1950 C/G and G/G) polymorphism, 53.5% had the ApoA1 (-75 G/A and A/A) polymorphism, and 23.3% had the ApoE (3/4) polymorphism. Independently of genotype, the combination of cholesterol-lowering foods in an LSF diet significantly reduced serum TC and TG in Mexican hypercholesterolemic subjects.
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Fenofibrate and rosiglitazone improve quality of lipoproteins in patients with type 2 diabetes mellitus.
Vrablík, M, Dobiásová, M, Stulc, T, Kasalová, Z, Dolezalová, R, Prázný, M, Fait, T, Ceska, R
Neuro endocrinology letters. 2008;(1):146-50
Abstract
BACKGROUND Particle size distribution in both HDL and LDL is reflected in the fractional esterification rate of cholesterol by lecithin cholesterol acyltransferase (LCAT) in plasma depleted of apoB containing lipoproteins (FER(HDL)). We studied FER(HDL) in a group of patients with type 2 diabetes and determined the impact of two different PPAR agonists (fenofibrate and rosiglitazone) on this marker of lipoprotein particle quality. PATIENTS AND METHODS 66 patients with type 2 diabetes (26 women) and 32 control subjects (19 women) were included in the study. 33 patients received fenofibrate and 33 rosiglitazone as add on therapy. Average duration of treatment was 4 months. Plasma lipoprotein glucose levels were determined using an automated analyzer (COBAS Mira, Roche). LDL cholesterol concentrations were calculated by Friedewald formula. FER(HDL) was determined by a radioassay after precipitating apo-B containing particles of plasma. The assays were performed at baseline and at the end of each treatment. SPSS base program was used for statistical evaluation. RESULTS Both fenofibrate and rosiglitazone resulted in a significant decrease of FER(HDL) (24.62 +/- 11.27%/h vs. 19.93 +/- 10.34%/h; 20.0 +/- 6.1%/h vs. 15.8 +/- 5.8%/h, p < 0.001). Rosiglitazone was significantly more effective in FER(HDL) lowering than fenofibrate (p < 0,02) CONCLUSIONS Both fenofibrate and rosiglitazone improve FER(HDL) in patients with type 2 diabetes. The effect is more pronounced for rosiglitazone. Qualitative change of plasma lipoproteins reflected by FER(HDL) can contribute to antiatherogenic action of PPAR agonists. On contrary, changes of lipoprotein composition induced by PPAR agonists cannot explain adverse cardiovascular effects observed in some large clinical trials with PPAR agonists.
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Atypical antipsychotic usage-related higher serum leptin levels and disabled lipid profiles in euthymic bipolar patients.
Gergerlioglu, HS, Savas, HA, Celik, A, Savas, E, Yumru, M, Tarakcioglu, M, Gergerlioglu, N, Atmaca, M
Neuropsychobiology. 2006;(2):108-12
Abstract
Atypical antipsychotics (AA)-induced weight gain is associated with increased leptin levels. AA have been increasingly used in the treatment of bipolar disorders. This cross-sectional study aimed to evaluate the association between serum leptin and lipid profiles considering the drug treatments in euthymic bipolar outpatients. Leptin and lipid profiles were compared, and no differences were noted in leptin, cholesterol, and low-density lipoprotein levels among the patients and controls. Glucose, very-low-density lipoprotein, and triglyceride levels in patients were higher than in controls, while high-density lipoprotein levels were low. Patients were divided into three groups according to their type of drug usage: AA users, AA + mood stabilizer users, and mood stabilizer users. Each group of patients was compared with a healthy control group for mentioned biochemical parameters. Lipid profiles were disordered by using both AA and mood stabilizers, but higher leptin levels are associated with AA usage. However, leptin does not seem to be responsible for dyslipidemia caused by AA or mood stabilizers in euthymic bipolar patients.
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Lipids, lipoproteins, apolipoproteins, selected trace elements and minerals in the serum of children on valproic acid monotherapy.
Karikas, GA, Schulpis, KH, Bartzeliotou, A, Karakonstantakis, T, Georgala, S, Kanavaki, I, Demetriou, E, Papassotiriou, I
Basic & clinical pharmacology & toxicology. 2006;(6):599-603
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Abstract
We evaluated the serum levels of lipids, lipoproteins, apolipoproteins, along with a number of minerals and trace elements such as Ca, Mg, Cu and Zn in a group of children after 6 months of valproic acid monotherapy. Thirty patients with seizures, mean age, 9.8+/-2.6 years and 79 healthy children (controls), mean age, 10.9+/-3.2 years, formed the two styd groups. The patient group was treated with valproic acid (27.9+/-14.8 mg/kg/24 hr). Patients underwent clinical and laboratory evaluations including liver function tests, NH3, lipid, mineral and selected trace element levels before and after six months on valproic acid treatment, whereas controls only one evaluation. Liver function data and NH3 levels were found to be elevated in the group of patients, whereas albumin level was reduced. Triglycerides, total cholesterol, HDL-C, apolipoprotein (ApoA)-1, Apo B and Ca concentrations were found relative to control values, LDL-C, VLDL-C, Mg, Cu, Zn, were measured significantly altered (P<0.0001) compared to controls. The ratios ApoA-1/ApoB, HDL-C/ApoA-1, LDL-C/Apo B, which were closely related to the size of LDL particles, where correlated with Zn/Cu (P<0.001). Serum lipid profile, especially LDL size, indirectly evaluated for the first time and metal levels were found to be significantly changed, after six months on valproic acid monotherapy, suggesting a possible risk of developing coronary heart disease. Since valproic acid is a long-term treatment, it could be recommended that the incorporation of measurements of lipids, lipoproteins, apolipoproteins and trace elements in the "follow up" laboratory testing could be a preventive measure.
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Plasma lipoproteins and apolipoproteins as predictors of cardiovascular risk and treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).
Packard, CJ, Ford, I, Robertson, M, Shepherd, J, Blauw, GJ, Murphy, MB, Bollen, EL, Buckley, BM, Cobbe, SM, Gaw, A, et al
Circulation. 2005;(20):3058-65
Abstract
BACKGROUND Statins are important in vascular disease prevention in the elderly. However, the best method of selecting older patients for treatment is uncertain. We assessed the role of plasma lipoproteins as predictors of risk and of treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). METHOD AND RESULTS The association of LDLc and HDLc with risk was examined in the 5804 70- to 82-year-old subjects of PROSPER. Baseline LDLc showed no relation to risk of the primary end point in the placebo group (P=0.27), nor did on-treatment LDLc in the pravastatin group (P=0.12). HDLc was inversely associated with risk in subjects on placebo (P=0.0019) but not in those on pravastatin (P=0.24). Risk reduction on pravastatin treatment was unrelated to baseline LDLc (P=0.38) but exhibited a significant interaction with HDLc (P=0.012). Subjects in the lowest 2 quintiles of HDLc (<1.15 mmol/L) had a risk reduction of 33% (hazard ratio, 0.67; 95% confidence limits, 0.55, 0.81; P<0.0001), whereas those with higher HDLc showed no benefit (RR, 1.06; 95% confidence limits, 0.88, 1.27; P=0.53). During follow-up, there was no relation between achieved level of LDLc or HDLc and risk. However, the change in the LDLc/HDLc ratio on statin treatment appeared to account for the effects of therapy. CONCLUSIONS In people >70 years old, HDLc appears to be a key predictor of risk and of treatment benefit. Findings in PROSPER suggest that statin therapy could usefully be targeted to those with HDLc <1.15 mmol/L or an LDLc/HDLc ratio >3.3.
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Overweight and effect of hormone replacement therapy on lipid profiles in postmenopausal women.
Ko, HS, Kim, CJ, Ryu, WS
The Korean journal of internal medicine. 2005;(1):33-9
Abstract
BACKGROUND Many experimental and observational studies have suggested that hormone replacement therapy (HRT) in postmenopausal women is cardioprotective. However, the results of randomized controlled trials have been discouraging. We attempted to evaluate the influence of overweight, a frequent risk factor for coronary artery disease, on the lipid-modifying effects of HRT. METHODS A total of 345 postmenopausal women were divided into 2 groups according to body mass index (BMI): the control group; BMI <25 Kg/m2 (n=248) and the overweight group; BMI > or =25 Kg/m2 (n=97). All women received either 0.625 mg conjugated equine estrogen (CEE)(n=139), CEE plus 5 mg medroxyprogesterone acetate (MPA)(n=97) or CEE plus 10 mg MPA (n=109). Lipid profiles were measured before and 12 months after HRT. RESULTS In both the control and overweight groups, HRT reduced low density lipoprotein cholesterol (LDL-C) (p = 0.000 and p = 0.000 respectively) and lipoprotein (a) [Lp(a)] levels (p = 0.000 and p = 0.000 respectively) and raised high density lipoprotein cholesterol (HDL-C) levels (p = 0.000 and p = 0.002 respectively). However, the elevation of the HDL-C level was higher in the control group than in overweight group (17.5% vs. 10.4%, p = 0.015), and this was significant after adjusting for changes in body weights (p = 0.016). There were no differences in the reduction of LDL-C (p = 0.20) and Lp(a) (p = 0.09) levels between the two groups. CONCLUSION HRT had less favorable effects on HDL-C levels in overweight postmenopausal women than in women with normal body weight. This finding may be partially associated with no cardioprotective effect of HRT in postmenopausal patients at a high risk due to multiple risk factors including obesity.
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Effects of pravastatin on lipoproteins and endothelial function in patients receiving human immunodeficiency virus protease inhibitors.
Stein, JH, Merwood, MA, Bellehumeur, JL, Aeschlimann, SE, Korcarz, CE, Underbakke, GL, Mays, ME, Sosman, JM
American heart journal. 2004;(4):E18
Abstract
BACKGROUND Although recommended as initial therapy for patients with dyslipidemia who are taking human immunodeficiency virus protease inhibitors (HIV PIs), the effects of pravastatin on lipoproteins and arterial reactivity have not been elucidated. The purpose of this study was to determine the effects of pravastatin on lipoprotein subfractions and endothelial function in patients with dyslipidemia who are receiving HIV PIs. METHODS This was a placebo-controlled, double-blind, crossover study comparing pravastatin (40 mg) to placebo in 20 patients who were taking HIV PIs. Lipoprotein subfractions were measured with nuclear magnetic resonance spectroscopic analysis. Flow-mediated vasodilation (FMD) of the brachial artery was evaluated with high-resolution ultrasound scanning. RESULTS At baseline, subjects had an increased concentration of low-density lipoprotein (LDL) particles (1756 +/- 180 nmol/L), which tended to be small (19.9 +/- 0.2 nm), a low concentration of large high-density lipoproteins (HDL; 0.94 +/- 0.07 mmol/L), and an increased concentration of large very low-density lipoproteins (VLDL; 1.90 +/- 0.58 mmol/L). FMD was impaired (4.5% +/- 1.1%). Compared with placebo, pravastatin resulted in a 20.8% reduction in LDL particles (P =.030), a 26.7% reduction in small LDL (P =.100), and a 44.9% reduction in small VLDL (P =.023). Total and non-HDL cholesterol levels decreased by 18.3% (P <.001) and 21.7% (P <.001), respectively. FMD tended to increase in patients receiving pravastatin (0.7% +/- 0.6%); however, the difference between treatment phases was not statistically significant (P =.080). CONCLUSIONS This is the first double-blind, placebo-controlled study of the effects of statin therapy on lipids, lipoprotein subfractions, and endothelial function in patients taking HIV PIs. Pravastatin reduced concentrations of atherogenic lipoproteins, particularly those most associated with future coronary events.
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Hyperlipoproteinemia impairs endothelium-dependent vasodilation.
Kraml, P, Syrovátka, P, Stípek, S, Fialová, L, Koprivová, H, Potocková, J, Andel, M
Physiological research. 2004;(5):471-80
Abstract
Atherogenic lipoproteins can cause endothelial dysfunction in the initial stage of atherogenesis. In our study we examined 134 patients with defined hyperlipoproteinemia (non-HDL cholesterol>4.1 mmol/l or triglycerides>2.5 mmol/l or taking any of lipid lowering drugs)--94 men and 40 women. The subgroup of controls of comparable age contained 54 normolipidemic individuals--30 men and 24 women. Patients with hyperlipoproteinemia revealed significantly lower ability of endothelium-dependent flow-mediated vasodilation (EDV) measured on brachial artery (4.13+/-3.07 vs. 5.41+/-3.82 %; p=0.032) and higher carotid intima media thickness than normolipidemic controls (0.68+/-0.22 vs. 0.58+/-0.15 mm; p=0.005). In regression analysis, EDV correlated significantly with plasma concentrations of oxLDL (p<0.05) HDL-cholesterol (p<0.05), Apo A1 (p<0.05), ATI (p<0.01) and non-HDL cholesterol (p<0.05). Patients with hyperlipoproteinemia showed higher plasma levels of oxLDL (65.77+/-9.54 vs. 56.49+/-7.80 U/l; p=0.015), malondialdehyde (0.89+/-0.09 vs. 0.73+/-0.08 micromol/l; p=0.010) and nitrites/nitrates (20.42+/-4.88 vs. 16.37+/-4.44 micromol/l; p=0.018) indicating possible higher long-term oxidative stress in these patients.
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Association of lipoproteins with cytokines and cytokine receptors in heart failure patients. Differences between ischaemic versus idiopathic cardiomyopathy.
Conraads, VM, Bosmans, JM, Schuerwegh, AJ, De Clerck, LS, Bridts, CH, Wuyts, FL, Stevens, WJ, Vrints, CJ
European heart journal. 2003;(24):2221-6
Abstract
AIMS: The observation that low total cholesterol predicted poor survival in patients with chronic heart failure, has questioned the beneficial effect of lipid-lowering in this population. This study investigated the relation between lipoprotein concentrations and the levels of interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and the soluble TNF-alpha receptors in patients with chronic heart failure due to coronary artery disease (CAD) or idiopathic dilated cardiomyopathy (IDCM). METHODS AND RESULTS Seventy-one patients with chronic heart failure due to CAD (n=36) or IDCM (n=35) were enrolled. Plasma concentrations of lipoproteins, IL-6, TNF-alpha, soluble TNF-alpha receptor 1 (sTNFR1) and 2 (sTNFR2) were measured. Total cholesterol/HDL-cholesterol (CHOL/HDL) correlated with levels of TNF-alpha (r=0.24, P=0.035), sTNFR1 (r=0.32, P=0.008) and sTNFR2 (r=0.37, P=0.002). In the CAD group, CHOL/HDL and triglycerides (TG) correlated with sTNFR2 (r=0.48, P=0.005 for CHOL/HDL, r=0.40, P=0.015 for TG). No relation was found between lipoproteins and cytokines or sTNF-alpha receptors for IDCM patients (P>0.1). CONCLUSIONS An atherogenic lipid profile favoured the inflammatory process in patients with heart failure due to CAD. No relation between lipoproteins and cytokines was detected in case of IDCM.