The Sirt1 activator SRT3025 provides atheroprotection in Apoe−/− mice by reducing hepatic Pcsk9 secretion and enhancing Ldlr expression

PubMed Central

Miranda, Melroy X.; van Tits, Lambertus J.; Lohmann, Christine; Arsiwala, Tasneem; Winnik, Stephan; Tailleux, Anne; Stein, Sokrates; Gomes, Ana P.; Suri, Vipin; Ellis, James L.; Lutz, Thomas A.; Hottiger, Michael O.; Sinclair, David A.; Auwerx, Johan; Schoonjans, Kristina; Staels, Bart; Lüscher, Thomas F.; Matter, Christian M.

2015-01-01

Aims The deacetylase sirtuin 1 (Sirt1) exerts beneficial effects on lipid metabolism, but its roles in plasma LDL-cholesterol regulation and atherosclerosis are controversial. Thus, we applied the pharmacological Sirt1 activator SRT3025 in a mouse model of atherosclerosis and in hepatocyte culture. Methods and results Apolipoprotein E-deficient (Apoe−/−) mice were fed a high-cholesterol diet (1.25% w/w) supplemented with SRT3025 (3.18 g kg−1 diet) for 12 weeks. In vitro, the drug activated wild-type Sirt1 protein, but not the activation-resistant Sirt1 mutant; in vivo, it increased deacetylation of hepatic p65 and skeletal muscle Foxo1. SRT3025 treatment decreased plasma levels of LDL-cholesterol and total cholesterol and reduced atherosclerosis. Drug treatment did not change mRNA expression of hepatic LDL receptor (Ldlr) and proprotein convertase subtilisin/kexin type 9 (Pcsk9), but increased their protein expression indicating post-translational effects. Consistent with hepatocyte Ldlr and Pcsk9 accumulation, we found reduced plasma levels of Pcsk9 after pharmacological Sirt1 activation. In vitro administration of SRT3025 to cultured AML12 hepatocytes attenuated Pcsk9 secretion and its binding to Ldlr, thereby reducing Pcsk9-mediated Ldlr degradation and increasing Ldlr expression and LDL uptake. Co-administration of exogenous Pcsk9 with SRT3025 blunted these effects. Sirt1 activation with SRT3025 in Ldlr−/− mice reduced neither plasma Pcsk9, nor LDL-cholesterol levels, nor atherosclerosis. Conclusion We identify reduction in Pcsk9 secretion as a novel effect of Sirt1 activity and uncover Ldlr as a prerequisite for Sirt1-mediated atheroprotection in mice. Pharmacological activation of Sirt1 appears promising to be tested in patients for its effects on plasma Pcsk9, LDL-cholesterol, and atherosclerosis. PMID:24603306

Balancing Low-density Lipoprotein Cholesterol Reduction and Hepatotoxicity With Lomitapide Mesylate and Mipomersen in Patients With Homozygous Familial Hypercholesterolemia.

PubMed

Won, Jane I; Zhang, Jun; Tecson, Kristen M; McCullough, Peter A

2017-01-01

Homozygous familial hypercholesterolemia (HoFH) is an autosomal codominant disorder manifested by high concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol, and premature cardiovascular disease. Despite conventional lipid-lowering therapy, LDL cholesterol levels remain elevated in patients with HoFH; these patients are considered to be at high risk for cardiovascular events. In 2012-2013, two drugs with novel mechanisms of action were approved by the US Food and Drug Administration for the treatment of HoFH: lomitapide mesylate and mipomersen. Both of these treatments reduce total cholesterol, LDL cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein a, and triglyceride levels. This review describes the clinical tradeoffs in efficacy and hepatotoxicity of these drugs in two cases of HoFH.

Macrophage heterogeneity and cholesterol homeostasis: classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL.

PubMed

Chu, Eugene M; Tai, Daven C; Beer, Jennifer L; Hill, John S

2013-02-01

Macrophages are centrally involved during atherosclerosis development and are the predominant cell type that accumulates cholesterol in the plaque. Macrophages however, are heterogeneous in nature reflecting a variety of microenvironments and different phenotypes may be more prone to contribute towards atherosclerosis progression. Using primary human monocyte-derived macrophages, we sought to evaluate one aspect of atherogenic potential of different macrophage phenotypes by determining their propensity to associate with and accumulate oxidized low density lipoprotein (oxLDL). Classically-activated macrophages treated simultaneously with interferon γ (IFNγ) and tumor necrosis factor α (TNFα) associated with less oxLDL and accumulated less cholesterol compared to untreated controls. The combined treatment of IFNγ and TNFα reduced the mRNA expression of CD36 and the expression of both cell surface CD36 and macrophage scavenger receptor 1 (MSR1) protein. Under oxLDL loaded conditions, IFNγ and TNFα did not reduce macrophage protein expression of the transcription factor peroxisome proliferator-actived receptor γ (PPARγ) which is known to positively regulate CD36 expression. However, macrophages treated with IFNγ attenuated the ability of the PPARγ-specific agonist rosiglitazone from upregulating cell surface CD36 protein expression. Our results demonstrate that the observed reduction of cholesterol accumulation in macrophages treated with IFNγ and TNFα following oxLDL treatment was due at least in part to reduced cell surface CD36 and MSR1 protein expression. Copyright © 2012 Elsevier B.V. All rights reserved.

Lomitapide

MedlinePlus

... is used along with diet changes (restriction of cholesterol and fat intake) and other treatments to reduce the amount of low-density lipoprotein (LDL) cholesterol ('bad cholesterol'), total cholesterol, and other fatty substances ...

LDL-cholesterol-lowering effect of a dietary supplement with plant extracts in subjects with moderate hypercholesterolemia.

PubMed

Ogier, Nicolas; Amiot, Marie-Josèphe; Georgé, Stéphane; Maillot, Matthieu; Mallmann, Cécilia; Maraninchi, Marie; Morange, Sophie; Lescuyer, Jean-François; Peltier, Sébastien L; Cardinault, Nicolas

2013-03-01

Red yeast rice (RYR), sugar cane-derived policosanols (SCdP) and artichoke leaf extracts (ALEs) are currently incorporated alone or in combination into dietary supplements for their potential low-density-lipoprotein cholesterol (LDL-cholesterol)-lowering effects. Yet, there is no information supporting the efficacy of this association on the reduction in LDL-cholesterol. The main objective of this study was to investigate the effects of a new dietary supplement (DS) with RYR, SCdP and ALEs on LDL-cholesterol. In a double-blind, randomized, parallel controlled study, 39 subjects from 21 to 55 years with moderate hypercholesterolemia without drug treatment were assigned to 2 groups and then consumed either a DS containing RYR, SCdP and ALEs or a placebo over a 16-week period. Plasma concentrations of lipids [LDL-cholesterol, total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-cholesterol), triacylglycerols (TG)] and plasma levels of vitamins C and E, total polyphenols and malondialdehyde were determined at baseline and after 4, 8, 12 and 16 weeks. LDL-cholesterol and TC were reduced by, respectively, 21.4 % (95 % CI, -13.3 to -24.9 %, p < 0.001) and 14.1 % (95 % CI, -10.1 to -18.0 %, p < 0.001) at week 16 in the DS group compared with baseline. Similar results were obtained at weeks 4, 8 and 12. TG decreased by 12.2 % after 16 weeks in the DS group (95 % CI: -24.4 to -0.1 %, p < 0.05). For the vitamin E/TC ratio, a difference was observed between groups at week 16 (p < 0.05). Other parameters were not modified. Daily consumption of this new DS decreased LDL-cholesterol and TC and is therefore an interesting, convenient aid in managing mild to moderate hypercholesterolemia.

Proprotein convertase subtilisin/kexin type 9 inhibition: a new therapeutic mechanism for reducing cardiovascular disease risk.

PubMed

Bergeron, Nathalie; Phan, Binh An P; Ding, Yunchen; Fong, Aleyna; Krauss, Ronald M

2015-10-27

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the regulation of cholesterol homeostasis. By binding to hepatic low-density lipoprotein (LDL) receptors and promoting their lysosomal degradation, PCSK9 reduces LDL uptake, leading to an increase in LDL cholesterol concentrations. Gain-of-function mutations in PCSK9 associated with high LDL cholesterol and premature cardiovascular disease have been causally implicated in the pathophysiology of autosomal-dominant familial hypercholesterolemia. In contrast, the more commonly expressed loss-of-function mutations in PCSK9 are associated with reduced LDL cholesterol and cardiovascular disease risk. The development of therapeutic approaches that inhibit PCSK9 function has therefore attracted considerable attention from clinicians and the pharmaceutical industry for the management of hypercholesterolemia and its associated cardiovascular disease risk. This review summarizes the effects of PCSK9 on hepatic and intestinal lipid metabolism and the more recently explored functions of PCSK9 in extrahepatic tissues. Therapeutic approaches that prevent interaction of PCSK9 with hepatic LDL receptors (monoclonal antibodies, mimetic peptides), inhibit PCSK9 synthesis in the endoplasmic reticulum (antisense oligonucleotides, siRNAs), and interfere with PCSK9 function (small molecules) are also described. Finally, clinical trials testing the safety and efficacy of monoclonal antibodies to PCSK9 are reviewed. These have shown dose-dependent decreases in LDL cholesterol (44%-65%), apolipoprotein B (48%-59%), and lipoprotein(a) (27%-50%) without major adverse effects in various high-risk patient categories, including those with statin intolerance. Initial reports from 2 of these trials have indicated the expected reduction in cardiovascular events. Hence, inhibition of PCSK9 holds considerable promise as a therapeutic option for decreasing cardiovascular disease risk. © 2015 American Heart Association, Inc.

Addition of Garlic Extract in Ration to Reduce Cholesterol Level of Broiler

NASA Astrophysics Data System (ADS)

Utami, M. M. D.; Pantaya, D.; Agus, A.

2018-01-01

The purpose of this research is to know the effect of garlic extract (GE) in reducing cholesterol level of broiler chicken by analyzing cholesterol level of broiler chicken blood. Two hundred one day broiler age were used in this study for 35 days. The chickens were randomly divided into four treatments, each treatment consist of five replications and each repetition consist of ten chickens. This research is used completely randomized design, such as: T0: 0% EBP, T1: 2%, T2: 4% and T3: 6%. Furthermore, at age 35 days each chicken was taken blood to be analyzed cholesterol levels, low density lipoprotein (LDL), high density lipoprotein (HDL) and calculated the ratio of LDL and HDL levels. The data obtained were analyzed using software from Statistical Product and Service Solution (SPSS 16.0). The results of significant analysis continued by Duncan’s New Multiple Range Test. Addition of GE from the 2% level decreases (P <0.05) of LDL and total cholesterol, and increases HDL and HDL-LDL ratio. The conclusions is obtained garlic extract plays an important role in lowering cholesterol levels of broiler meat.

Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease.

PubMed

Vega, Gloria Lena; Weiner, Myron F; Lipton, Anne M; Von Bergmann, Klaus; Lutjohann, Dieter; Moore, Carol; Svetlik, Doris

2003-04-01

The statin treatment of dyslipidemia is associated with a reduced risk of development of Alzheimer disease (AD). The effect may be mediated by a reduction in cholesterol biosynthesis in the brain, by lowering levels of apolipoprotein E (apo E)-containing lipoproteins, or by pleitropic effects such as reduction in beta-amyloid production. In the brain, cholesterol from damaged or dying neurons is converted to 24S-hydroxycholesterol by cholesterol 24-hydroxylase (CYP46). The oxysterol is subsequently transferred across the blood-brain barrier, transported to the liver by low-density lipoproteins (LDLs), and excreted as bile acids. Most of plasma 24S-hydroxycholesterol is derived from brain cholesterol; consequently, plasma levels of the oxysterol reflect brain cholesterol catabolism. To examine the effect of 3 statins and a nonstatin hypolipidemic agent on plasma levels of 24S-hydroxycholesterol and apo E in patients with AD. The study had a sequential parallel design. It was open-labeled and involved lipoprotein and 24S-hydroxycholesterol evaluations at baseline and at 6 weeks of treatment with 40 mg of lovastatin, simvastatin, or pravastatin sodium per day, or 1 g of extended-release niacin per day. Blood samples were drawn after a 12-hour fast for measurement of plasma sterols, oxysterols, lipoprotein cholesterol, and levels of apo E, plasma transaminases, and glucose. Measurements were made at baseline and during treatment. Statin treatment reduced levels of plasma lathosterol by 49.5%, 24S-hydroxycholesterol by 21.4%, LDL cholesterol by 34.9%, and total cholesterol by 25%. The ratios of lathosterol-campesterol and 24S-hydroxycholesterol-LDL cholesterol were reduced significantly, but the ratio of 24S-hydroxycholesterol-total cholesterol was unchanged. Extended-release niacin also significantly reduced levels of 24S-hydroxycholesterol by 10% and LDL cholesterol by 18.1%. None of the agents lowered plasma concentration of apo E. Statins lowered levels of plasma 24S-hydroxycholesterol without affecting levels of apo E. The LDL lowering was more pronounced than 24S-hydroxycholesterol reductions. The effect of statins on LDL partially explains the reduction of plasma oxysterol level.

LDL-C levels in older people: Cholesterol homeostasis and the free radical theory of ageing converge.

PubMed

Mc Auley, Mark T; Mooney, Kathleen M

2017-07-01

The cardiovascular disease (CVD) risk factor, low density lipoprotein cholesterol (LDL-C) increases with age, up until the midpoint of life in males and females. However, LDL-C can decrease with age in older men and women. Intriguingly, a recent systematic review also revealed an inverse association between LDL-C levels and cardiovascular mortality in older people; low levels of LDL-C were associated with reduced risk of mortality. Such findings are puzzling and require a biological explanation. In this paper a hypothesis is proposed to explain these observations. We hypothesize that the free radical theory of ageing (FRTA) together with disrupted cholesterol homeostasis can account for these observations. Based on this hypothesis, dysregulated hepatic cholesterol homeostasis in older people is characterised by two distinct metabolic states. The first state accounts for an older person who has elevated plasma LDL-C. This state is underpinned by the FRTA which suggests there is a decrease in cellular antioxidant capacity with age. This deficiency enables hepatic reactive oxidative species (ROS) to induce the total activation of HMG-CoA reductase, the key rate limiting enzyme in cholesterol biosynthesis. An increase in cholesterol synthesis elicits a corresponding rise in LDL-C, due to the downregulation of LDL receptor synthesis, and increased production of very low density lipoprotein cholesterol (VLDL-C). In the second state of dysregulation, ROS also trigger the total activation of HMG-CoA reductase. However, due to an age associated decrease in the activity of cholesterol-esterifying enzyme, acyl CoA: cholesterol acyltransferase, there is restricted conversion of excess free cholesterol (FC) to cholesterol esters. Consequently, the secretion of VLDL-C drops, and there is a corresponding decrease in LDL-C. As intracellular levels of FC accumulate, this state progresses to a pathophysiological condition akin to nonalcoholic fatty liver disease. It is our conjecture this deleterious state has the potential to account for the inverse association between LDL-C level and CVD risk observed in older people. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intercorrelations of lipoprotein subfractions and their covariation with lifestyle factors in healthy men.

PubMed

Parlesak, Alexandr; Eckoldt, Joachim; Winkler, Karl; Bode, Christian J; Schäfer, Christian

2014-05-01

So far, little is known about the effect of nutrition and lifestyle on the composition of circulating lipoprotein subfractions. In the current study, we measured the correlations among physical activity, nutrient intake, smoking, body-mass index (BMI), and age with the concentration of triglycerides, cholesterol, phospholipids, and apolipoproteins (ApoA1, ApoA2 and ApoB) in subfractions of LDL and HDL in 265 healthy working men. Concentrations of cholesterol, phospholipids, and ApoB in small, dense atherogenic LDL particles (sdLDL) correlated negatively (p<0.001) with those of cholesterol, phospholipids, and ApoA1 in HDL2, respectively. Age correlated positively with sdLDL while increasing BMI correlated with an atherogenic shift of cholesterol, phospholipids, and ApoB from large, buoyant LDL (lbLDL) to sdLDL and decreasing concentrations of HDL2 constituents. Physical activity and alcohol intake correlated negatively with sdLDL constituents and positively with HDL2 components. Consumption of monounsaturated fatty acids (MUFA) correlated with a lower ratio of sdLDL to HDL2 cholesterol. A favorable lipoprotein subfraction profile linked to a reduced risk of cardiovascular disease in men was associated with physical activity, moderate alcohol consumption, and dietary intake of MUFA, which might be exploited in future interventions for prevention of age- and BMI-associated atherogenic shifts of lipoprotein subfractions.

Intercorrelations of lipoprotein subfractions and their covariation with lifestyle factors in healthy men

PubMed Central

Parlesak, Alexandr; Eckoldt, Joachim; Winkler, Karl; Bode, Christian J; Schäfer, Christian

2014-01-01

So far, little is known about the effect of nutrition and lifestyle on the composition of circulating lipoprotein subfractions. In the current study, we measured the correlations among physical activity, nutrient intake, smoking, body-mass index (BMI), and age with the concentration of triglycerides, cholesterol, phospholipids, and apolipoproteins (ApoA1, ApoA2 and ApoB) in subfractions of LDL and HDL in 265 healthy working men. Concentrations of cholesterol, phospholipids, and ApoB in small, dense atherogenic LDL particles (sdLDL) correlated negatively (p<0.001) with those of cholesterol, phospholipids, and ApoA1 in HDL2, respectively. Age correlated positively with sdLDL while increasing BMI correlated with an atherogenic shift of cholesterol, phospholipids, and ApoB from large, buoyant LDL (lbLDL) to sdLDL and decreasing concentrations of HDL2 constituents. Physical activity and alcohol intake correlated negatively with sdLDL constituents and positively with HDL2 components. Consumption of monounsaturated fatty acids (MUFA) correlated with a lower ratio of sdLDL to HDL2 cholesterol. A favorable lipoprotein subfraction profile linked to a reduced risk of cardiovascular disease in men was associated with physical activity, moderate alcohol consumption, and dietary intake of MUFA, which might be exploited in future interventions for prevention of age- and BMI-associated atherogenic shifts of lipoprotein subfractions. PMID:24895480

Low-carbohydrate diets reduce lipid accumulation and arterial inflammation in guinea pigs fed a high-cholesterol diet.

PubMed

Leite, Jose O; DeOgburn, Ryan; Ratliff, Joseph; Su, Randy; Smyth, Joan A; Volek, Jeff S; McGrane, Mary M; Dardik, Alan; Fernandez, Maria Luz

2010-04-01

Low-carbohydrate diets (LCD) efficiently induce weight loss and favorably affect plasma lipids, however, the effect of LCD on atherosclerosis is still argued. To evaluate the effect of LCD on the prevention of atherosclerosis. Twenty guinea pigs were fed either a LCD or a low-fat diet (LFD) in combination with high-cholesterol (0.25g/100g) for 12 weeks. The percentage energy of macronutrient distribution was 10:65:25 for carbohydrate:fat:protein for the LCD, and 55:20:25 for the LFD. Plasma lipids were measured using colorimetric assays. Plasma and aortic oxidized (oxLDL) were quantified using ELISA methods. Inflammatory cytokines were measured in aortic homogenates using an immunoassay. H&E stained sections of aortic sinus and Schultz stained sections of carotid arteries were examined. LDL cholesterol was lower in the LCD compared to the LFD group (71.9+/-34.8 vs. 81.7+/-26.9mg/dL; p=0.039). Aortic cholesterol was also lower in the LCD (4.98+/-1.3mg/g) compared to the LFD group (6.68+/-2.0mg/g); p<0.05. The Schultz staining method confirmed less aortic cholesterol accumulation in the LCD group. Plasma oxLDL did not differ between groups, however, aortic oxLDL was 61% lower in the LCD compared to the LFD group (p=0.045). There was a positive correlation (r=0.63, p=0.03) between oxLDL and cholesterol concentration in the aorta of LFD group, which was not observed in LCD group (r=-0.05, p=0.96). Inflammatory markers were reduced in guinea pigs from the LCD group (p<0.05) and they were correlated with the decreases in oxLDL in aorta. These results suggest that LCD not only decreases lipid deposition, but also prevents the accumulation of oxLDL and reduces inflammatory cytokines within the arterial wall and may prevent atherosclerosis. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Beneficial effects of virgin coconut oil on lipid parameters and in vitro LDL oxidation.

PubMed

Nevin, K G; Rajamohan, T

2004-09-01

The present study was conducted to investigate the effect of consumption of virgin coconut oil (VCO) on various lipid parameters in comparison with copra oil (CO). In addition, the preventive effect of polyphenol fraction (PF) from test oils on copper induced oxidation of LDL and carbonyl formation was also studied. After 45 days of oil feeding to Sprague-Dawley rats, several lipid parameters and lipoprotein levels were determined. PF was isolated from the oils and its effect on in vitro LDL oxidation was assessed. VCO obtained by wet process has a beneficial effect in lowering lipid components compared to CO. It reduced total cholesterol, triglycerides, phospholipids, LDL, and VLDL cholesterol levels and increased HDL cholesterol in serum and tissues. The PF of virgin coconut oil was also found to be capable of preventing in vitro LDL oxidation with reduced carbonyl formation. The results demonstrated the potential beneficiary effect of virgin coconut oil in lowering lipid levels in serum and tissues and LDL oxidation by physiological oxidants. This property of VCO may be attributed to the biologically active polyphenol components present in the oil.

Exchanging a few commercial, regularly consumed food items with improved fat quality reduces total cholesterol and LDL-cholesterol: a double-blind, randomised controlled trial.

PubMed

Ulven, Stine M; Leder, Lena; Elind, Elisabeth; Ottestad, Inger; Christensen, Jacob J; Telle-Hansen, Vibeke H; Skjetne, Anne J; Raael, Ellen; Sheikh, Navida A; Holck, Marianne; Torvik, Kristin; Lamglait, Amandine; Thyholt, Kari; Byfuglien, Marte G; Granlund, Linda; Andersen, Lene F; Holven, Kirsten B

2016-10-01

The healthy Nordic diet has been previously shown to have health beneficial effects among subjects at risk of CVD. However, the extent of food changes needed to achieve these effects is less explored. The aim of the present study was to investigate the effects of exchanging a few commercially available, regularly consumed key food items (e.g. spread on bread, fat for cooking, cheese, bread and cereals) with improved fat quality on total cholesterol, LDL-cholesterol and inflammatory markers in a double-blind randomised, controlled trial. In total, 115 moderately hypercholesterolaemic, non-statin-treated adults (25-70 years) were randomly assigned to an experimental diet group (Ex-diet group) or control diet group (C-diet group) for 8 weeks with commercially available food items with different fatty acid composition (replacing SFA with mostly n-6 PUFA). In the Ex-diet group, serum total cholesterol (P<0·001) and LDL-cholesterol (P<0·001) were reduced after 8 weeks, compared with the C-diet group. The difference in change between the two groups at the end of the study was -9 and -11 % in total cholesterol and LDL-cholesterol, respectively. No difference in change in plasma levels of inflammatory markers (high-sensitive C-reactive protein, IL-6, soluble TNF receptor 1 and interferon-γ) was observed between the groups. In conclusion, exchanging a few regularly consumed food items with improved fat quality reduces total cholesterol, with no negative effect on levels of inflammatory markers. This shows that an exchange of a few commercially available food items was easy and manageable and led to clinically relevant cholesterol reduction, potentially affecting future CVD risk.

Mitotic Spindle Defects and Chromosome Mis-Segregation Induced by LDL/Cholesterol—Implications for Niemann-Pick C1, Alzheimer’s Disease, and Atherosclerosis

PubMed Central

Granic, Antoneta; Potter, Huntington

2013-01-01

Elevated low-density lipoprotein (LDL)-cholesterol is a risk factor for both Alzheimer’s disease (AD) and Atherosclerosis (CVD), suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy–in neurons and other cells in AD and in smooth muscle cells in atherosclerotic plaques in CVD. Indeed, specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in AD brain, indicating that aneuploidy underlies AD neurodegeneration. Cell/mouse models of AD develop similar aneuploidy through amyloid-beta (Aß) inhibition of specific microtubule motors and consequent disruption of mitotic spindles. Here we tested the hypothesis that, like upregulated Aß, elevated LDL/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. Specifically we found that: 1) high dietary cholesterol induces aneuploidy in mice, satisfying the hypothesis’ first prediction, 2) Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans 3) oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL), induce chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors, indicating that LDL/cholesterol directly affects the cell cycle, 4) LDL-induced aneuploidy requires the LDL receptor, but not Aß, showing that LDL works differently than Aß, with the same end result, 5) cholesterol treatment disrupts the structure of the mitotic spindle, providing a cell biological mechanism for its aneugenic activity, and 6) ethanol or calcium chelation attenuates lipoprotein-induced chromosome mis-segregation, providing molecular insights into cholesterol’s aneugenic mechanism, specifically through its rigidifying effect on the cell membrane, and potentially explaining why ethanol consumption reduces the risk of developing atherosclerosis or AD. These results suggest a novel, cell cycle mechanism by which aberrant cholesterol homeostasis promotes neurodegeneration and atherosclerosis by disrupting chromosome segregation and potentially other aspects of microtubule physiology. PMID:23593294

Rosiglitazone increases LDL particle size and buoyancy and decreases C-reactive protein in patients with type 2 diabetes on statin therapy.

PubMed

Yu, Dahong; Murdoch, Susan J; Parikh, Shamik J; Marcovina, Santica M; Cobitz, Alexander; Chen, Hongzi; Brunzell, John D

2006-12-01

A substantial number of individuals with type 2 diabetes mellitus (T2DM) demonstrate a predominance of small dense low-density lipoprotein (sdLDL), which is associated with an increased risk of cardiovascular disease (CVD). In some cases, sdLDL persists after treatment with a statin to reduce levels of LDL. The effect of the addition of a thiazolidinedione, rosiglitazone (RSG) (4 mg/day or 8 mg/day) to statin therapy on LDL phenotype and C reactive protein (CRP) levels was investigated in a 12- week, placebo-controlled study of 72 T2DM patients who were well controlled and on a statin, but who had persistently predominant sdLDL. Addition of RSG 8 mg to statin therapy significantly increased LDL buoyancy (relative flotation +0.014, p = 0.003) and LDL particle size (+4.2A, p = 0.001) from baseline and relative to the change with placebo (+0.014 and +3.8A; p = 0.03 and p = 0.04, respectively), and was associated with a non-significant decrease in sdLDL. RSG 8 mg moderately, but significantly, increased total cholesterol (by 12.2%, p = 0.004), LDL-cholesterol (11.2%, p = 0.02) and intermediate-density lipoprotein (IDL)-cholesterol from baseline but did not increase total or LDL apolipoprotein B. RSG 4 mg and 8 mg significantly reduced CRP compared with placebo (-44.9% and -48.0%; p = 0.008 and p = 0.004, respectively), and significantly reduced insulin resistance and fasting plasma glucose from baseline. Addition of RSG to statin therapy may further reduce cardiovascular risk by improving the LDL phenotype, as well as reducing insulin resistance and CRP levels. However, the increase in IDL may be proatherogenic and must be considered when assessing the benefits of rosiglitazone.

Cinnamon improves glucose and lipids of people with type 2 diabetes.

PubMed

Khan, Alam; Safdar, Mahpara; Ali Khan, Mohammad Muzaffar; Khattak, Khan Nawaz; Anderson, Richard A

2003-12-01

The objective of this study was to determine whether cinnamon improves blood glucose, triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol levels in people with type 2 diabetes. A total of 60 people with type 2 diabetes, 30 men and 30 women aged 52.2 +/- 6.32 years, were divided randomly into six groups. Groups 1, 2, and 3 consumed 1, 3, or 6 g of cinnamon daily, respectively, and groups 4, 5, and 6 were given placebo capsules corresponding to the number of capsules consumed for the three levels of cinnamon. The cinnamon was consumed for 40 days followed by a 20-day washout period. After 40 days, all three levels of cinnamon reduced the mean fasting serum glucose (18-29%), triglyceride (23-30%), LDL cholesterol (7-27%), and total cholesterol (12-26%) levels; no significant changes were noted in the placebo groups. Changes in HDL cholesterol were not significant. The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.

PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates.

PubMed

Lindholm, Marie W; Elmén, Joacim; Fisker, Niels; Hansen, Henrik F; Persson, Robert; Møller, Marianne R; Rosenbohm, Christoph; Ørum, Henrik; Straarup, Ellen M; Koch, Troels

2012-02-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for the reduction of low-density lipoprotein cholesterol (LDL-C). PCSK9 increases the degradation of the LDL receptor, resulting in high LDL-C in individuals with high PCSK9 activity. Here, we show that two locked nucleic acid (LNA) antisense oligonucleotides targeting PCSK9 produce sustained reduction of LDL-C in nonhuman primates after a loading dose (20 mg/kg) and four weekly maintenance doses (5 mg/kg). PCSK9 messenger RNA (mRNA) and serum PCSK9 protein were reduced by 85% which resulted in a 50% reduction in circulating LDL-C. Serum total cholesterol (TC) levels were reduced to the same extent as LDL-C with no reduction in high-density lipoprotein levels, demonstrating a specific pharmacological effect on LDL-C. The reduction in hepatic PCSK9 mRNA correlated with liver LNA oligonucleotide content. This verified that anti-PCSK9 LNA oligonucleotides regulated LDL-C through an antisense mechanism. The compounds were well tolerated with no observed effects on toxicological parameters (liver and kidney histology, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine). The pharmacologic evidence and initial safety profile of the compounds used in this study indicate that LNA antisense oligonucleotides targeting PCSK9 provide a viable therapeutic strategy and are potential complements to statins in managing high LDL-C.

HDL (Good), LDL (Bad) Cholesterol and Triglycerides

MedlinePlus

... Thromboembolism Aortic Aneurysm More HDL (Good), LDL (Bad) Cholesterol and Triglycerides Updated:May 3,2018 Cholesterol isn’ ... be measured by a blood test. LDL (Bad) Cholesterol LDL cholesterol is called “bad” cholesterol. Think of ...

Mipomersen preferentially reduces small low-density lipoprotein particle number in patients with hypercholesterolemia.

PubMed

Santos, Raul D; Raal, Frederick J; Donovan, Joanne M; Cromwell, William C

2015-01-01

Because of variability in lipoprotein cholesterol content, low-density lipoprotein (LDL) cholesterol frequently underrepresents or overrepresents the number of LDL particles. Mipomersen is an antisense oligonucleotide that reduces hepatic production of apolipoprotein B-100, the sole apolipoprotein of LDL. To characterize the effects of mipomersen on lipoprotein particle numbers as well as subclass distribution using nuclear magnetic resonance (NMR) spectroscopy. We compared the tertiary results for the direct measurement of LDL particle numbers by NMR among 4 placebo-controlled, phase 3 studies of mipomersen that had similar study designs but different patient populations: homozygous familial hypercholesterolemia (HoFH), severe hypercholesterolemia, heterozygous familial hypercholesterolemia with established coronary artery disease, or hypercholesterolemia with high risk for coronary heart disease (HC-CHD). HoFH patients had the highest median total LDL particles at baseline compared with HC-CHD patients, who had the lowest. At baseline, the HoFH population uniquely had a greater mean percentage of large LDL particles (placebo, 60.2%; mipomersen, 54.9%) compared with small LDL particles (placebo, 33.1%; mipomersen, 38.9%). In all 4 studies, mipomersen was associated with greater reductions from baseline in the concentrations of small LDL particles compared with those of large LDL particles, and both total LDL particles and small LDL particles were statistically significantly reduced. Mipomersen consistently reduced all LDL particle numbers and preferentially reduced the concentration of small LDL particles in all 4 phase 3 studies. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

[ECS guidelines 2016 - dyslipidaemias].

PubMed

Sinning, D; Landmesser, U

2016-12-01

Dyslipidaemia is a major cause of atherosclerotic cardiovascular disease and its progression towards clinical complications, such as acute coronary syndromes and stroke. In August 2016 the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) issued new joint guidelines for the management of dyslipidaemias. In these new guidelines, the concept of treating patients to a risk-based low-density lipoprotein (LDL) cholesterol target is reinforced. The task force considers LDL cholesterol as the primary target for dyslipidaemia treatment, whereas high-density lipoprotein (HDL) cholesterol is not recommended as a treatment target (based on the failure of HDL cholesterol elevation treatment strategies to reduce cardiovascular risk in recent studies). In patients with a very high risk for cardiovascular events it is recommended to treat to an LDL cholesterol target of less than 70 mg/dl. Moreover, the new guidelines now additionally recommend a > 50% reduction of LDL cholesterol in patients with very high cardiovascular risk patients and baseline levels between 70 and 135 mg/dl as well as in patients with high cardiovascular risk and baseline LDL cholesterol levels between 100 and 200 mg/dl. Statins are recommended as first-line medicinal treatment and the LDL cholesterol goals given imply the more frequent use of maximum tolerated statin therapy, in particular for patients with very high cardiovascular risk. Treatment with ezetimibe in patients with substantially elevated LDL cholesterol levels despite maximum tolerated statin therapy has now received a stronger recommendation (currently IIa recommendation). The guidelines also now include the potential use of the novel proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and a recent ESC/EAS consensus document provides more detailed information on which patients can be considered for treatment with PCSK9 inhibitors, i. e. in particular patients with familial hypercholesterolemia and patients at very high cardiovascular risk who have markedly elevated LDL cholesterol levels despite maximum tolerated statin and ezetimibe therapy.

Whole Soy Flour Incorporated into a Muffin and Consumed at 2 Doses of Soy Protein Does Not Lower LDL Cholesterol in a Randomized, Double-Blind Controlled Trial of Hypercholesterolemic Adults12

PubMed Central

Padhi, Emily MT; Blewett, Heather J; Duncan, Alison M; Guzman, Randolph P; Hawke, Aileen; Seetharaman, Koushik; Tsao, Rong; Wolever, Thomas MS; Ramdath, D Dan

2015-01-01

Background: Soy protein may reduce coronary heart disease (CHD) risk by lowering LDL cholesterol, but few studies have assessed whether whole soy flour displays a similar effect. Objective: The aim of this study was to assess the dose effect of whole soy flour incorporated into muffins on plasma LDL cholesterol in hypercholesterolemic adults. Methods: Adults aged 30–70 y (n = 243) with elevated LDL cholesterol (≥3.0 and ≤5.0 mmol/L) were stratified by LDL cholesterol and randomly assigned to consume 2 soy muffins containing 25 g soy protein [high-dose soy (HDS)], 1 soy and 1 wheat muffin containing 12.5 g soy protein and 12.5 g whey protein [low-dose soy (LDS)], or 2 wheat muffins containing 25 g whey protein (control) daily for 6 wk while consuming a self-selected diet. Fasting blood samples were collected at weeks 0, 3, and 6 for analysis of plasma lipids [total, LDL, and HDL cholesterol and triglycerides (TGs)], glucose, insulin, C-reactive protein (CRP), and isoflavones. Blood pressures also were measured. Dietary intake was assessed at weeks 0 and 4 with the use of 3 d food records. Treatment effects were assessed with the use of intention-to-treat analysis with multiple imputation and LDL cholesterol as the primary outcome. Results: In total, 213 (87.6%) participants completed the trial. Participants were primarily Caucasian (83%) and mostly female (63%), with a mean ± SD body mass index (in kg/m2) of 28.0 ± 4.6 and systolic and diastolic blood pressures of 122 ± 16 and 77 ± 11 mm Hg, respectively. Despite a dose-dependent increase in plasma isoflavones (P < 0.001), neither HDS nor LDS had a significant effect on LDL cholesterol compared with control (mean ± SEM changes: control, −0.04 ± 0.05 mmol/L; HDS, 0.01 ± 0.05 mmol/L; and LDS, −0.04 ± 0.06 mmol/L). There were no significant treatment effects on total or HDL cholesterol, TGs, CRP, homeostatic model assessment of insulin resistance, blood pressure, or the Framingham 10-y CHD risk score. Conclusion: Consuming 12.5 or 25 g protein from defatted soy flour incorporated into muffins does not reduce LDL cholesterol or other CHD risk factors in hypercholesterolemic adults. This trial was registered at clinicaltrials.gov as NCT01547585. PMID:26446482

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9

PubMed Central

Fitzgerald, Kevin; White, Suellen; Borodovsky, Anna; Bettencourt, Brian R.; Strahs, Andrew; Clausen, Valerie; Wijngaard, Peter; Horton, Jay D.; Taubel, Jorg; Brooks, Ashley; Fernando, Chamikara; Kauffman, Robert S.; Kallend, David; Vaishnaw, Akshay; Simon, Amy

2018-01-01

BACKGROUND Inclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin–kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol. METHODS In this phase 1 trial, we randomly assigned healthy volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100, 300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose cohort included four to eight participants. Safety, the side-effect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipid variables) were evaluated. RESULTS The most common adverse events were cough, musculoskeletal pain, nasopharyngitis, headache, back pain, and diarrhea. All the adverse events were mild or moderate in severity. There were no serious adverse events or discontinuations due to adverse events. There was one grade 3 elevation in the γ-glutamyltransferase level, which was considered by the investigator to be related to statin therapy. In the single-dose phase, inclisiran doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.5% from baseline to day 84), and doses of 100 mg or more reduced the LDL cholesterol level (up to a least-squares mean reduction of 50.6% from baseline). Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the levels of PCSK9 (up to a least-squares mean reduction of 83.8% from baseline to day 84) and LDL cholesterol (up to a least-squares mean reduction of 59.7% from baseline to day 84). CONCLUSIONS In this phase 1 trial, no serious adverse events were observed with inclisiran. Doses of 300 mg or more (in single or multiple doses) significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months. (Funded by Alnylam Pharmaceuticals and the Medicines Company; ClinicalTrials.gov number, NCT02314442.) PMID:27959715

Usefulness of the LDL-C/apoB ratio in the overall evaluation of atherogenicity of lipid profile.

PubMed

Kaneva, Anastasiya M; Potolitsyna, Natalya N; Bojko, Evgeny R

2017-02-01

The ratio of low-density lipoprotein cholesterol to apolipoprotein-B (LDL-C/apoB) conventionally represents an alternative index of LDL particle size. This study was undertaken to determine the importance of LDL-C/apoB ratio in the overall evaluation of atherogenicity of lipid profile. The plasma levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) A-I, apoB and apoE were measured in 186 apparently healthy men using enzymatic and immunoturbidimetric methods. The subjects with low values of the LDL-C/apoB ratio, indicating a predominance of small dense LDL (sd-LDL) particles in plasma, were characterized by higher TG levels and lower apoE levels. Low levels of apoE are most likely a cause of reduced clearance of TG-rich lipoproteins, which promotes the formation of sd-LDL. Determination of the LDL-C/apoB ratio can be used for monitoring qualitative changes in lipid profile, in addition to traditional lipid variables indicating quantitative changes.

Reduced diabetic, hypertensive, and cholesterol medication use with walking.

PubMed

Williams, Paul T

2008-03-01

To assess the relationships of walking distance, frequency, and intensity to the prevalence of antidiabetic, antihypertensive, and LDL cholesterol-lowering medications use. Cross-sectional analyses of 32,683 female and 8112 male participants of the National Walkers' Health Study, of whom 2.8% and 7.4% reported antidiabetic, 14.3% and 29.0% reported antihypertensive, and 7.3% and 21.5% reported LDL cholesterol-lowering medication use, respectively. Weekly walking distance, longest walk, and walking intensity were inversely related to the prevalence of antidiabetic (males: P < 0.001, females: P < 0.0001), antihypertensive (males: P < 0.01, females: P < 0.0001), and LDL cholesterol-lowering medications (males: P < 0.01, females: P < 0.0001). Each medication remained significantly related to both walking intensity and longest weekly walk when adjusted for total weekly distance. Compared with men and women who walked at a speed of < 1.2 m.s, those who walked > 2.1 m.s had 48% and 52% lower odds for antihypertensive, 68% and 59% lower odds for antidiabetic, and 53% and 40% lower odds for LDL cholesterol-lowering medications, respectively, when adjusted for age, smoking, and diet. The longest usual weekly walk was a better discriminator of medication status than the total cumulative distance per week, particularly in men. These results are consistent with the hypothesis that antidiabetic, antihypertensive, and LDL cholesterol-lowering medication use may be reduced substantially by walking more intensely and farther each week, and by including longer walks.

Saturated fatty acids and risk of coronary heart disease: modulation by replacement nutrients.

PubMed

Siri-Tarino, Patty W; Sun, Qi; Hu, Frank B; Krauss, Ronald M

2010-11-01

Despite the well-established observation that substitution of saturated fats for carbohydrates or unsaturated fats increases low-density lipoprotein (LDL) cholesterol in humans and animal models, the relationship of saturated fat intake to risk for atherosclerotic cardiovascular disease in humans remains controversial. A critical question is what macronutrient should be used to replace saturated fat. Substituting polyunsaturated fat for saturated fat reduces LDL cholesterol and the total cholesterol to high-density lipoprotein cholesterol ratio. However, replacement of saturated fat by carbohydrates, particularly refined carbohydrates and added sugars, increases levels of triglyceride and small LDL particles and reduces high-density lipoprotein cholesterol, effects that are of particular concern in the context of the increased prevalence of obesity and insulin resistance. Epidemiologic studies and randomized clinical trials have provided consistent evidence that replacing saturated fat with polyunsaturated fat, but not carbohydrates, is beneficial for coronary heart disease. Therefore, dietary recommendations should emphasize substitution of polyunsaturated fat and minimally processed grains for saturated fat.

Role of dietary supplements in lowering low-density lipoprotein cholesterol: a review.

PubMed

Nijjar, Prabhjot S; Burke, Frances M; Bloesch, Annette; Rader, Daniel J

2010-01-01

Coronary heart disease (CHD) remains a major source of morbidity and mortality. As the epidemic of obesity, diabetes, and hypertension continues to grow among young adults, the population at risk for atherosclerotic CHD is ever increasing. More than a century of laboratory and human findings link cholesterol levels with a propensity to develop atherosclerosis. Low-density lipoprotein (LDL) is the major atherogenic lipoprotein, and numerous clinical trials have shown the efficacy of lowering LDL-cholesterol (LDL-C) for reducing CHD risk. New trial data have resulted in LDL-C goals being lowered over time and expansion of the population of patients that are candidates for LDL-lowering therapy to decrease their lifetime risk of CHD. Although statins are relatively safe and well tolerated, there are still significant numbers of patients who cannot tolerate them and many others who only require mild LDL-C reduction and prefer nonprescription alternatives to statin therapy. A number of dietary supplements and functional foods have been suggested to reduce LDL-C levels, but only a few have withstood the rigors of randomized controlled trials. Here we review the evidence in support of dietary supplements and their LDL-C-lowering effects. We also review supplements that, after initial excitement about their purported effect, were not found to lower LDL-C significantly. Copyright © 2010 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Cholesterol-lowering effect of non-viscous soluble dietary fiber Nutriose6 in moderately hypercholesterolemic hamsters.

PubMed

Juhel, Christine; Tosini, Fredéric; Steib, Marlène; Wils, Daniel; Guerin-Deremaux, Laetitia; Lairon, Denis; Cara, Louis

2011-03-01

NUTRIOSE6 is a new wheat starch-based low-digestible carbohydrate. This study investigated the effect of this soluble non-viscous fiber on cholesterol metabolism. Hamsters fed with 0.25% cholesterol-enriched diet (CHO) were given graded amounts of NUTRIOSE6, i.e., 0% (cellulose, CHO), 3% (N3), 6% (N6) or 9% (N9) (w:w). As compared to CHO diet, 9% NUTRIOSE6 significantly lowered plasma and LDL cholesterol by 14.5 and 23.8%, respectively. The LDL-cholesterol lowering effect was also significant with the 6% dose (-21.4%). NUTRIOSE6 diets prevented hepatic cholesterol accumulation (-10 to -20%) and significantly decreased bile cholesterol (-47 to -68%) and phospholipids (-30 to -45%) concentrations. The 9% NUTRIOSE6 diet significantly decreased the rate of dietary cholesterol absorption (-25%) and markedly stimulated faecal neutral sterol (+81%) and bile salts (+220%) excretion. No significant change in cholesterol 7-alpha-hydroxylase or LDL-receptor activities was observed whereas 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was reduced by 29%. Reduced cholesterol and bile salt absorptions and lowered cholesterol synthesis are likely mechanisms underlying the cholesterol lowering effect of NUTRIOSE6. Results suggest the use of NUTRIOSE6 as a new dietary cholesterol-lowering agent that should be tested in humans as treatment and evenly prevention of mild hypercholesterolemia.

Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance.

PubMed

Thompson, Paul D; MacDougall, Diane E; Newton, Roger S; Margulies, Janice R; Hanselman, Jeffrey C; Orloff, David G; McKenney, James M; Ballantyne, Christie M

2016-01-01

ETC-1002 is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia. To compare 2 doses of ETC-1002, alone or combined with ezetimibe 10 mg (EZE), vs EZE monotherapy for lowering low-density lipoprotein cholesterol (LDL-C). This phase 2b, multicenter, double-blind trial-evaluated hypercholesterolemic patients (LDL-C, 130 to 220 mg/dL) with (n = 177) or without (n = 171) muscle-related intolerance to ≥2 statins; 1 at lowest approved dose. Subjects were randomized to 12-week treatment with ETC-1002 120 mg or ETC-1002 180 mg alone, EZE alone, ETC-1002 120 mg plus EZE, or ETC-1002 180 mg plus EZE. EZE alone lowered LDL-C by 21%, whereas ETC-1002 monotherapy with 120 mg or 180 mg reduced LDL-C by 27% (P = .0008 vs EZE) and 30% (P < .0001 vs EZE), respectively. The combination of ETC-1002, 120 mg or 180 mg plus EZE reduced LDL-C by 43% and 48%, respectively (both P < .0001 vs EZE). ETC-1002 alone or combined with EZE also reduced non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, LDL particle number, and high-sensitivity C-reactive protein compared with EZE alone. Across all treatment groups, statin-intolerant patients reported more muscle-related adverse events than did statin-tolerant patients. ETC-1002 was safe and well tolerated, and rates of muscle-related adverse events were similar in all treatment groups. In patients with and without statin intolerance, daily treatment with ETC-1002 120 mg and 180 mg alone or with EZE reduced LDL-C more than EZE alone and had a similar tolerability profile (NCT01941836). Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Short-term treatment with a 2-carba analog of cyclic phosphatidic acid induces lowering of plasma cholesterol levels in ApoE-deficient mice.

PubMed

Tsukahara, Tamotsu; Haniu, Hisao; Matsuda, Yoshikazu; Murakmi-Murofushi, Kimiko

2016-04-22

Plasma cholesterol levels are associated with an increased risk of developing atherosclerosis. An elevated low-density lipoprotein cholesterol (LDL-C) level is a hallmark of hypercholesterolemia in metabolic syndrome. Our previous study suggested that when acetylated LDL (AC-LDL) was co-applied with a PPARγ agonist, rosiglitazone (ROSI), many oil red O-positive macrophages could be observed. However, addition of cyclic phosphatidic acid (cPA) to ROSI-stimulated macrophages completely abolished oil red O-stained cells, indicating that cPA inhibits PPARγ-regulated AC-LDL uptake. This study aimed to determine whether metabolically stabilized cPA, in the form of a carba-derivative of cPA (2ccPA), could reduce plasma cholesterol levels and affect the expression of genes related to atherosclerosis in apolipoprotein E-knockout (apoE(-/-)) mice. 2ccPA reduced LDL-C levels in these mice (n = 3) from 460 to 330 mg/ml, from 420 to 350 mg/ml, and 420 to 281 mg/ml under a western-type diet. 2ccPA also reduced expression of lipid metabolism-related genes, cytokines, and chemokines in ApoE-deficient mice on a high-fat diet. Taken together, these results suggest that 2ccPA governs anti-atherogenic activities in the carotid arteries of apoE-deficient mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of Ezetimibe Alone or in Addition to a Statin on Plasma PCSK9 Concentrations in Patients with Type 2 Diabetes and Hypercholesterolemia: A Pilot Study.

PubMed

Miyoshi, Toru; Nakamura, Keigo; Doi, Masayuki; Ito, Hiroshi

2015-06-01

The increase in proprotein convertase subtilisin/kexin type 9 (PCSK9) leads to low-density lipoprotein (LDL) receptor degradation. Statins significantly reduce LDL-cholesterol levels, but upregulate PCSK9. This study evaluated the effect of ezetimibe monotherapy or ezetimibe in combination with a statin on serum levels of PCSK9 in patients with type 2 diabetes and hypercholesterolemia. Ezetimibe treatment was given to ten patients with diabetes without statin therapy and ten patients with statin therapy. Plasma levels of PCSK9 were examined at baseline and 24 weeks after treatment. At baseline, PCSK9 concentrations in patients with statin therapy were significantly higher than those in patients without statin use and in control subjects [median (25th-75th percentile) 411 (272-467) and 382 (356-453) ng/mL, respectively, p < 0.01]. After ezetimibe treatment for 24 weeks, LDL-cholesterol, triglyceride and remnant-like lipoprotein cholesterol were significantly decreased in both groups. However, PCSK9 concentration did not change compared with baseline measurements in both groups. The percentage change in LDL-cholesterol after ezetimibe therapy for 24 weeks was not correlated with the percentage change in PCSK9 concentration. Ezetimibe may reduce LDL-cholesterol levels without affecting PCSK9 in patients with type 2 diabetes and hypercholesterolemia.

The effect of oat β-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for CVD risk reduction: a systematic review and meta-analysis of randomised-controlled trials.

PubMed

Ho, Hoang V T; Sievenpiper, John L; Zurbau, Andreea; Blanco Mejia, Sonia; Jovanovski, Elena; Au-Yeung, Fei; Jenkins, Alexandra L; Vuksan, Vladimir

2016-10-01

Oats are a rich source of β-glucan, a viscous, soluble fibre recognised for its cholesterol-lowering properties, and are associated with reduced risk of CVD. Our objective was to conduct a systematic review and meta-analysis of randomised-controlled trials (RCT) investigating the cholesterol-lowering potential of oat β-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for the risk reduction of CVD. MEDLINE, Embase, CINAHL and Cochrane CENTRAL were searched. We included RCT of ≥3 weeks of follow-up, assessing the effect of diets enriched with oat β-glucan compared with controlled diets on LDL-cholesterol, non-HDL-cholesterol or apoB. Two independent reviewers extracted data and assessed study quality and risk of bias. Data were pooled using the generic inverse-variance method with random effects models and expressed as mean differences with 95 % CI. Heterogeneity was assessed by the Cochran's Q statistic and quantified by the I 2-statistic. In total, fifty-eight trials (n 3974) were included. A median dose of 3·5 g/d of oat β-glucan significantly lowered LDL-cholesterol (-0·19; 95 % CI -0·23, -0·14 mmol/l, P<0·00001), non-HDL-cholesterol (-0·20; 95 % CI -0·26, -0·15 mmol/l, P<0·00001) and apoB (-0·03; 95 % CI -0·05, -0·02 g/l, P<0·0001) compared with control interventions. There was evidence for considerable unexplained heterogeneity in the analysis of LDL-cholesterol (I 2=79 %) and non-HDL-cholesterol (I 2=99 %). Pooled analyses showed that oat β-glucan has a lowering effect on LDL-cholesterol, non-HDL-cholesterol and apoB. Inclusion of oat-containing foods may be a strategy for achieving targets in CVD reduction.

Aronia berry polyphenol consumption reduces plasma total and low-density lipoprotein cholesterol in former smokers without lowering biomarkers of inflammation and oxidative stress: a randomized controlled trial.

PubMed

Xie, Liyang; Vance, Terrence; Kim, Bohkyung; Lee, Sang Gil; Caceres, Christian; Wang, Ying; Hubert, Patrice A; Lee, Ji-Young; Chun, Ock K; Bolling, Bradley W

2017-01-01

Former smokers are at increased risk for cardiovascular disease. We hypothesized that dietary aronia polyphenols would reduce biomarkers of cardiovascular disease risk, inflammation, and oxidative stress in former smokers. We also determined the extent these effects were associated with polyphenol bioavailability. A 12-week, randomized, placebo-controlled trial was conducted in 49 healthy adult former smokers (n = 24/placebo, n = 25/aronia) to evaluate if daily consumption of 500 mg aronia extract modulated plasma lipids, blood pressure, biomarkers of inflammation and oxidative stress, and lipid transport genes of peripheral blood mononuclear cells. The primary outcome was change in low-density lipoprotein cholesterol (LDL-C) from baseline, and multivariate correlation analysis was performed to determine if changes in lipids were associated with urinary polyphenol excretion. Aronia consumption reduced fasting plasma total cholesterol by 8% (P = .0140), LDL-C by 11% (P = .0285), and LDL receptor protein in peripheral blood mononuclear cells (P = .0036) at 12 weeks compared with the placebo group. Positive changes in the urinary polyphenol metabolites peonidin-3-O-galactoside, 3-(4-hydroxyphenyl) propionic acid, and unmetabolized anthocyanin cyanidin-3-O-galactoside were associated with lower plasma total cholesterol and LDL-C in the aronia group. Aronia consumption did not change blood pressure or biomarkers of inflammation and oxidative stress. Aronia polyphenols reduced total and LDL-C in former smokers but did not improve biomarkers of oxidative stress and chronic inflammation. The cholesterol-lowering activity of aronia extract was most closely associated with urinary levels of cyanidin-3-O-galactoside and peonidin-3-O-galactoside, its methylated metabolite. This trial was registered at ClinicalTrials.gov as NCT01541826. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of yogurt and bifidus yogurt fortified with skim milk powder, condensed whey and lactose-hydrolysed condensed whey on serum cholesterol and triacylglycerol levels in rats.

PubMed

Beena, A; Prasad, V

1997-08-01

The possible hypocholesterolaemic properties of milk and fermented milk products have been investigated in groups of albino rats given a basal diet, basal diet plus cholesterol, and basal diet plus cholesterol together with whole milk or standard or bifidus yogurt. The yogurts were fortified with skim milk powder, condensed whey or lactose-hydrolysed condensed whey. After 30 d, triacylglycerols, total cholesterol, HDL-cholesterol and LDL-cholesterol were measured in serum. Whole milk and ordinary yogurt had no hypocholesterolaemic effect, but standard yogurt containing lactose-hydrolysed condensed whey and all bifidus yogurts lowered serum cholesterol. In general, yogurts changed HDL-cholesterol little, but tended to raise triacylglycerols. There was marked lowering of LDL-cholesterol in rats given either type of yogurt fortified with whey proteins. This study has demonstrated in a rat model that bifidus yogurts and yogurts fortified with whey proteins can reduce total and LDL-cholesterol, and suggests that if they have the same effect in human subjects they have potential value in cholesterol-lowering diets.

A fibre cocktail of fenugreek, guar gum and wheat bran reduces oxidative modification of LDL induced by an atherogenic diet in rats.

PubMed

Venkatesan, Nandini; Devaraj, S Niranjali; Devaraj, H

2007-01-01

LDL (low-density lipoprotein) oxidation is a key trigger factor for the development of atherosclerosis. Relatively few studies exist on the impact of dietary fibre on LDL oxidation. This study was undertaken to evaluate the influence of a novel fibre mix of fenugreek seed powder, guar gum and wheat bran (Fibernat) on LDL oxidation induced by an atherogenic diet. Male Wistar albino rats were administered one of the following diets: (1) a control diet that was fibre-free (Group I); (2) an atherogenic diet containing 1.5% cholesterol and 0.1% cholic acid (Group II) or (3) an atherogenic diet supplemented with Fibernat (Group III). Peroxidative changes in low-density lipoprotein (LDL) and the oxidative susceptibility of LDL and the LDL + VLDL (very low-density lipoprotein) fraction were determined. As a corollary to the oxidative modification theory, the titer of autoantibodies to oxidised LDL (oxLDL) was determined at various time points of the study. In addition, plasma homocysteine (tHcy) and lipoprotein (Lp (a)), apolipoprotein (apoB), cholesterol, triglyceride, phospholipid and alpha-tocopherol content of LDL were determined. A decrease in malonaldehyde (MDA) content (p<0.05) and relative electrophoretic mobility (REM) of LDL was observed in the group III rats as compared to the group II rats. An increase in lag time to oxidation (p<0.01) and decrease in maximum oxidation (p<0.01) and oxidation rate (p<0.01) were observed in the LDL + VLDL fraction of group III rats. In group II rats, formation of autoantibodies to oxLDL occurred at an earlier time point and at levels greater than in the group III rats. Fibernat, had a sparing effect on LDL alpha-tocopherol, which was about 51% higher in the group III rats than in the group II rats; apo B content of LDL was reduced by 37.6% in group III rats. LDL of group III rats displayed a decrease in free and ester cholesterol (p<0.01) as compared to that of group II. A decrease in plasma homocysteine (p<0.01) and an increase in GSH (p<0.05) were also observed in group III rats when compared with that of group II. Fibernat administration appears to combat oxidative stress resulting in a trend to lower oxidative modification of LDL. In addition, the cholesterol and apo B content of LDL were reduced significantly with a sparing effect on LDL alpha-tocopherol. This novel fibre preparation could be an effective diet therapy and therefore needs further investigation.

Comparison of changes in lipid profile after bilio-intestinal bypass and gastric banding in patients with morbid obesity.

PubMed

Corradini, Stefano Ginanni; Eramo, Annarita; Lubrano, Carla; Spera, Giovanni; Cornoldi, Alessandra; Grossi, Antonio; Liguori, Francesca; Siciliano, Maria; Pisanelli, Massimo Codacci; Salen, Gerald; Batta, Ashok Kumir; Attili, Adolfo Francesco; Badiali, Marco

2005-03-01

The presence of hypercholesterolemia is currently not considered a selection criteria for performing gastric restrictive or diversionary bariatric surgery. We prospectively investigated the effects of the bilio-intestinal bypass (BI-bypass) with a wide cholecysto-jejunal anastomosis and of adjustable gastric banding (AGB) on blood lipid concentrations in obese patients. To clarify the mechanism of the hypocholesterolemic effect of the BI-bypass, daily fecal sterol excretion was measured by gas-liquid chromatography (GLC). At 1 year after BI-bypass compared to baseline, the hypercholesterolemic (n=18) and the normocholesterolemic (n=19) patients significantly reduced total (-38% and -27%, respectively), LDL (-47% and -24%, respectively) and HDL (-11% and -13%, respectively) cholesterol and total / HDL cholesterol ratio (-25% and -13%, respectively). At 1 year after AGB, the total / HDL cholesterol ratio was significantly decreased (-11%) compared to baseline in hypercholesterolemic (n=12) but not in normocholesterolemic (n=6) patients, while total and LDL cholesterol were not affected in both groups. At 3 years after BI-bypass compared to baseline, the hypercholesterolemic (n=9) and the normocholesterolemic (n=11) patients significantly reduced total (-43% and -28%, respectively) and LDL (-53% and -29%, respectively) cholesterol and total / HDL cholesterol ratio (-38% and -21%, respectively). The BI-bypass induced a significant (P <0.005; n=7) 6-fold increase in mean fecal cholesterol output. The BI-bypass but not the AGB leads to a persistent and marked beneficial effect on blood LDL cholesterol associated with an increased cholesterol fecal output. BI-bypass but not AGB is indicated in morbidly obese patients with hypercholesterolemia.

Evaluation of Antiatherogenic Properties of Ezetimibe Using 3H-Labeled Low-Density-Lipoprotein Cholesterol and 99mTc-cAbVCAM1-5 SPECT in ApoE-/- Mice Fed the Paigen Diet.

PubMed

Dumas, Laurent S; Briand, François; Clerc, Romain; Brousseau, Emmanuel; Montemagno, Christopher; Ahmadi, Mitra; Bacot, Sandrine; Soubies, Audrey; Perret, Pascale; Riou, Laurent M; Devoogdt, Nick; Lahoutte, Tony; Barone-Rochette, Gilles; Fagret, Daniel; Ghezzi, Catherine; Sulpice, Thierry; Broisat, Alexis

2017-07-01

The addition of ezetimibe, an intestinal cholesterol absorption inhibitor, to statin therapy has recently shown clinical benefits in the Improved Reduction of Outcomes: Vytorin Efficacy International Trial by reducing low-density-lipoprotein (LDL) cholesterol levels more than statin therapy alone. Here, we investigated the mechanisms by which inhibition of intestinal cholesterol absorption might contribute to the clinically observed reduction in cardiovascular events by evaluating its effect on inflammatory plaque development in apolipoprotein E -/- mice. Methods: Apolipoprotein E -/- mice were fed the Paigen diet (1.25% cholesterol, 0.5% cholic acid, and 15% fat) without or with ezetimibe (7 mg/kg/d) for 6 wk. In a first set of mice ( n = 15), we intravenously injected 3 H-cholesteryl oleate-labeled human LDL to test whether ezetimibe promotes LDL-derived cholesterol fecal excretion. In a second set ( n = 20), we used the imaging agent 99m Tc-cAbVCAM1-5 to evaluate expression of an inflammatory marker, vascular cell adhesion molecule 1 (VCAM-1), in atherosclerotic plaques. In a third set ( n = 21), we compared VCAM-1 expression with 99m Tc-cAbVCAM1-5 uptake in various tissues. Results: Mice treated with ezetimibe showed a 173% higher LDL-cholesteryl ester plasma disappearance rate ( P < 0.001 vs. control) after 3 H-cholesteryl oleate-labeled LDL injection. At 96 h after injection, the hepatic fraction of 3 H-tracer was 61% lower in mice treated with ezetimibe ( P < 0.001). Meanwhile, LDL-derived 3 H-cholesterol excretion in the feces was 107% higher ( P < 0.001). The antiatherogenic effect of ezetimibe monitored by 99m Tc-cAbVCAM1-5 SPECT showed a 49% reduction in aortic tracer uptake (percentage injected dose per cubic centimeter, 0.95 ± 0.04 vs. 1.87 ± 0.11; P < 0.01). In addition to hypercholesterolemia, the proinflammatory Paigen diet significantly increased VCAM-1 expression with respect to the control group in various tissues, including the aorta, and this expression correlated strongly with 99m Tc-cAbVCAM1-5 uptake ( r = 0.75; P < 0.05). Conclusion: Inhibition of intestinal cholesterol absorption with ezetimibe promotes antiatherosclerotic effects through increased LDL cholesterol catabolism and LDL-derived cholesterol fecal excretion and reduces inflamed atherosclerotic plaques. These mechanisms may contribute to the benefits of adding ezetimibe to a statin therapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Increased ability of LDL from normolipidemic type 2 diabetic women to generate peroxides.

PubMed

Guerci, B; Antebi, H; Meyer, L; Durlach, V; Ziegler, O; Nicolas, J P; Alcindor, L G; Drouin, P

1999-09-01

We assessed the ability of LDL from 30 type 1 diabetic patients (18 men, 12 women), 65 type 2 diabetic patients (35 men, 30 women), and 35 controls (19 men, 16 women) to generate peroxides. The men and women in the diabetic groups were studied separately and matched for age, body mass index, duration of diabetes, glycohemoglobin, and conventional lipid characteristics according to the presence or absence of hyperlipidemia. The ability of LDL to form peroxides was assessed by measuring the thiobarbituric acid-reactive substances corrected for LDL-cholesterol [ratio of malondialdehyde (MDA) to LDL-cholesterol]. LDL particle size was expressed as the ratio of LDL-cholesterol to apolipoprotein B (LDL-cholesterol/apoB). The MDA/LDL-cholesterol ratio was higher in type 1 and type 2 diabetic patients with hyperlipidemia than in controls. The MDA/LDL-cholesterol ratio was also higher in type 2 normolipidemic women than in controls (P <0.01). The LDL-cholesterol/apoB ratio was lower in type 2 diabetic women than in type 2 diabetic men (P <0.05). The MDA/LDL-cholesterol ratio was negatively correlated with the LDL-cholesterol/apoB ratio (r = -0.78, P <0.001) in hyperlipidemic type 1 (not type 2) diabetic patients. In normolipidemic type 2 diabetic patients, the MDA/LDL-cholesterol ratio was also negatively correlated with the LDL-cholesterol/apoB ratio (r = -0.75, P <0.001) because of the highly significant negative correlation in type 2 diabetic women (r = -0.89, P <0.01). LDL from well-controlled type 2 diabetic women is smaller and more prone to form peroxides. This could explain why diabetic women are at greater risk of cardiovascular disease.

PCSK9 inhibition: the dawn of a new age in cholesterol lowering?

PubMed

Preiss, David; Mafham, Marion

2017-03-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating enzyme of hepatic origin that plays a key role in LDL receptor turnover. Genetic studies have confirmed that individuals with gain-of-function PCSK9 mutations have increased PCSK9 activity, elevated LDL-cholesterol levels and a severe form of familial hypercholesterolaemia. Those with variants leading to reduced PCSK9 have lower LDL-cholesterol levels and a reduced risk of coronary heart disease, and this has led to the development of various strategies aimed at reducing circulating PCSK9. Monoclonal antibodies to PCSK9, given every 2-4 weeks by subcutaneous injection, have been shown to reduce LDL-cholesterol by 50-60% compared with placebo in individuals with and without diabetes. PCSK9 inhibition also reduces lipoprotein(a), an atherogenic lipid particle, by around 20-30%. Major cardiovascular outcome trials for two agents, evolocumab and alirocumab, are expected to report from 2017. These trials involve over 45,000 participants and are likely to include about 15,000 individuals with diabetes. PCSK9-binding adnectins have been employed as an alternative method of removing circulating PCSK9. Small interfering RNA targeting messenger RNA for PCSK9, which acts by reducing hepatic production of PCSK9, is also under investigation. These agents may only need to be given by subcutaneous injection once every 4-6 months. Ongoing trials will determine whether anti-PCSK9 antibody therapy safely reduces cardiovascular risk, although high cost may limit its use. Development of PCSK9-lowering technologies cheaper than monoclonal antibodies will be necessary for large numbers of individuals to benefit from this approach to lowering cholesterol.

Additional consumption of one egg per day increases serum lutein plus zeaxanthin concentration and lowers oxidized low-density lipoprotein in moderately hypercholesterolemic males.

PubMed

Kishimoto, Yoshimi; Taguchi, Chie; Saita, Emi; Suzuki-Sugihara, Norie; Nishiyama, Hiroshi; Wang, Wei; Masuda, Yasunobu; Kondo, Kazuo

2017-09-01

The egg is a nutrient-dense food and contains antioxidative carotenoids, lutein and zeaxanthin, but its impact on serum cholesterol levels has been a matter of concern, especially for individuals who have high serum cholesterol levels. We conducted this study to determine whether and how the daily additional consumption of one egg affects serum lipid profiles and parameters of LDL oxidation in moderately hypercholesterolemic males. Nineteen male Japanese adults (total cholesterol [TC]>5.2mmol/L) participated, consuming one soft boiled egg per day for 4weeks in addition to their habitual diet. Despite the significant increase in their intake of dietary cholesterol during the intervention period, the subjects' serum concentrations of TC and low-density lipoprotein cholesterol (LDL-C) did not increase. Their serum malondialdehyde modified low-density lipoprotein (MDA-LDL) concentrations were significantly decreased and their LDL oxidation lag times, reflecting the resistance of free-radical-induced LDL lipid peroxidation (ex vivo), was prolonged after 2 and 4weeks. At weeks 2 and 4, the subjects' serum lutein+zeaxanthin concentrations were significantly higher than their baseline values and showed both an inverse relation with MDA-LDL and a positive relationship with the LDL oxidation lag time. These data showed that in moderately hypercholesterolemic males, the additional consumption of one egg per day for 4weeks did not have adverse effects on serum TC or LDL-C, and it might reduce the susceptibility of LDL to oxidation through an increase in the serum lutein and zeaxanthin concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel nonstatin strategies to lower low-density lipoprotein cholesterol.

PubMed

Davidson, Michael H

2009-01-01

There remains an unmet need to reduce elevated low-density lipoprotein cholesterol (LDL-C) in patients who are maximized on current therapy or intolerant to statins. Several novel agents have been developed to lower LDL-C, either as monotherapy or in combination with statins. These novel therapies include squalene synthase inhibitors, microsomal triglyceride transfer protein inhibitors, and antisense apolipoprotein B. Although each of these novel therapies effectively lowers LDL-C, challenges remain in the clinical development to assess long-term safety.

The good and the bad: what researchers have learned about dietary cholesterol, lipid management and cardiovascular disease risk since the Harvard Egg Study.

PubMed

Constance, C

2009-10-01

The prevalence of cardiovascular diseases, while lower than it once was, remains a significant health consideration. To review the evolving evidence with respect to what role various factors play in the aetiology of coronary heart disease (CHD). While total cholesterol and low-density lipoprotein cholesterol (LDL-C) were previously believed to play central roles, it has now become clear that neither in isolation is highly significant. For example, some people with very high LDL-C levels do not develop CHD, while others with very low LDL-C levels do. Furthermore, there is a difference between dietary cholesterol and serum cholesterol. Dietary cholesterol, which is found in animal-based foods, raises blood cholesterol in only approximately one-third of people. Conversely, intake of saturated fatty acids and trans fatty acids can result in dyslipidaemia. Furthermore, obesity--particularly abdominal obesity--and metabolic syndrome both are strong independent risk factors for development of cardiovascular disease. Statin therapy and a diet comprising a portfolio of plant sterols and viscous fibres can both significantly reduce LDL-C levels and C-reactive protein. The latter is a key marker of inflammation and of elevated risk for cardiovascular disease.

Regulation of plasma cholesterol by hepatic low-density lipoprotein receptors.

PubMed

Kovanen, P T

1987-02-01

The endogenous lipoprotein system (very low-density lipoprotein [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL] cascade) holds the key to understanding the mechanisms by which hormones, diet, and drugs interact to regulate the plasma cholesterol level. Crucial components of this system are hepatic LDL receptors that mediate the uptake and degradation of plasma LDL. With experimental animals, it has been possible to demonstrate that hepatic LDL receptors are sensitive to hormonal, dietary, and pharmacologic manipulation. The decrease in number of hepatic LDL receptors in hypothyroidism or after cholesterol feeding leads to elevation of plasma LDL cholesterol levels. Conversely, the increase in number of hepatic LDL receptors results in lowering of plasma LDL cholesterol levels. This can be observed in hyperthyroidism, during administration of pharmacologic doses of 17 alpha-ethinyl estradiol, or during treatment with cholesterol-lowering drugs such as the bile acid-binding resins and cholesterol-synthesis inhibitors. Since cholesterol excretion from the body occurs via the liver, the increased efficiency of disposal of plasma cholesterol by increasing hepatic LDL receptors will ultimately lead to depletion of excessive body cholesterol. Pharmacologic regulation of hepatic LDL receptors should be a valuable tool in the prevention and therapy of atherosclerosis.

Diet rich in high glucoraphanin broccoli reduces plasma LDL cholesterol: Evidence from randomised controlled trials

PubMed Central

Armah, Charlotte N; Derdemezis, Christos; Traka, Maria H; Dainty, Jack R; Doleman, Joanne F; Saha, Shikha; Leung, Wing; Potter, John F; Lovegrove, Julie A; Mithen, Richard F

2015-01-01

Scope Cruciferous-rich diets have been associated with reduction in plasma LDL-cholesterol (LDL-C), which may be due to the action of isothiocyanates derived from glucosinolates that accumulate in these vegetables. This study tests the hypothesis that a diet rich in high glucoraphanin (HG) broccoli will reduce plasma LDL-C. Methods and results One hundred and thirty volunteers were recruited to two independent double-blind, randomly allocated parallel dietary intervention studies, and were assigned to consume either 400 g standard broccoli or 400 g HG broccoli per week for 12 weeks. Plasma lipids were quantified before and after the intervention. In study 1 (37 volunteers), the HG broccoli diet reduced plasma LDL-C by 7.1% (95% CI: –1.8%, –12.3%, p = 0.011), whereas standard broccoli reduced LDL-C by 1.8% (95% CI +3.9%, –7.5%, ns). In study 2 (93 volunteers), the HG broccoli diet resulted in a reduction of 5.1% (95% CI: –2.1%, –8.1%, p = 0.001), whereas standard broccoli reduced LDL-C by 2.5% (95% CI: +0.8%, –5.7%, ns). When data from the two studies were combined the reduction in LDL-C by the HG broccoli was significantly greater than standard broccoli (p = 0.031). Conclusion Evidence from two independent human studies indicates that consumption of high glucoraphanin broccoli significantly reduces plasma LDL-C. PMID:25851421

Diet rich in high glucoraphanin broccoli reduces plasma LDL cholesterol: Evidence from randomised controlled trials.

PubMed

Armah, Charlotte N; Derdemezis, Christos; Traka, Maria H; Dainty, Jack R; Doleman, Joanne F; Saha, Shikha; Leung, Wing; Potter, John F; Lovegrove, Julie A; Mithen, Richard F

2015-05-01

Cruciferous-rich diets have been associated with reduction in plasma LDL-cholesterol (LDL-C), which may be due to the action of isothiocyanates derived from glucosinolates that accumulate in these vegetables. This study tests the hypothesis that a diet rich in high glucoraphanin (HG) broccoli will reduce plasma LDL-C. One hundred and thirty volunteers were recruited to two independent double-blind, randomly allocated parallel dietary intervention studies, and were assigned to consume either 400 g standard broccoli or 400 g HG broccoli per week for 12 weeks. Plasma lipids were quantified before and after the intervention. In study 1 (37 volunteers), the HG broccoli diet reduced plasma LDL-C by 7.1% (95% CI: -1.8%, -12.3%, p = 0.011), whereas standard broccoli reduced LDL-C by 1.8% (95% CI +3.9%, -7.5%, ns). In study 2 (93 volunteers), the HG broccoli diet resulted in a reduction of 5.1% (95% CI: -2.1%, -8.1%, p = 0.001), whereas standard broccoli reduced LDL-C by 2.5% (95% CI: +0.8%, -5.7%, ns). When data from the two studies were combined the reduction in LDL-C by the HG broccoli was significantly greater than standard broccoli (p = 0.031). Evidence from two independent human studies indicates that consumption of high glucoraphanin broccoli significantly reduces plasma LDL-C. © 2015 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Water-soluble dietary fibers and cardiovascular disease.

PubMed

Theuwissen, Elke; Mensink, Ronald P

2008-05-23

One well-established way to reduce the risk of developing cardiovascular disease (CVD) is to lower serum LDL cholesterol levels by reducing saturated fat intake. However, the importance of other dietary approaches, such as increasing the intake of water-soluble dietary fibers is increasingly recognized. Well-controlled intervention studies have now shown that four major water-soluble fiber types-beta-glucan, psyllium, pectin and guar gum-effectively lower serum LDL cholesterol concentrations, without affecting HDL cholesterol or triacylglycerol concentrations. It is estimated that for each additional gram of water-soluble fiber in the diet serum total and LDL cholesterol concentrations decrease by -0.028 mmol/L and -0.029 mmol/L, respectively. Despite large differences in molecular structure, no major differences existed between the different types of water-soluble fiber, suggesting a common underlying mechanism. In this respect, it is most likely that water-soluble fibers lower the (re)absorption of in particular bile acids. As a result hepatic conversion of cholesterol into bile acids increases, which will ultimately lead to increased LDL uptake by the liver. Additionally, epidemiological studies suggest that a diet high in water-soluble fiber is inversely associated with the risk of CVD. These findings underlie current dietary recommendations to increase water-soluble fiber intake.

Quantitative and qualitative effects of rosuvastatin on LDL-cholesterol: what is the clinical significance?

PubMed

Rizzo, M; Berneis, K; Spinas, G A; Rini, G B; Kapur, N K

2009-03-01

Statins have emerged as the global leader in pharmacologic therapy for dyslipidaemia, and rosuvastatin has demonstrated clinical efficacy as well as safety in several clinical trials and postmarketing analyses. The present article reviewed the effects of rosuvastatin on the quantity and the quality of low-density lipoproteins (LDL). We searched for and reviewed all the available evidence in a systematic way. A literature search (by Medline and Scopus) was performed using the following headings: 'LDL-cholesterol', 'LDL size', 'LDL subclasses', 'small dense LDL', 'apolipoprotein B, apo B' and 'rosuvastatin' up to 11 November 2008. The authors also manually reviewed the references of selected articles for any pertinent material. Rosuvastatin reduces LDL-cholesterol levels to a greater extent than other statins and is able to modulate significantly LDL size and subclasses towards less atherogenic particles as well as the LDL particle number, as indirectly measured by the levels of apo B. The recent Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin study provides more evidence about the effectiveness of rosuvastatin therapy in reducing cardiovascular risk, even among persons who would not currently be considered for pharmacotherapy. Further insights on cardiovascular outcomes will be available by the on-going trials included in the GALAXY program that includes subjects with type-2 diabetes, haemodialysis recipients, patients with congestive heart failure and specific ethnic groups, such as African American, Hispanic and South Asian populations.

Corn oil intake favorably impacts lipoprotein cholesterol, apolipoprotein and lipoprotein particle levels compared with extra-virgin olive oil.

PubMed

Maki, K C; Lawless, A L; Kelley, K M; Kaden, V N; Geiger, C J; Palacios, O M; Dicklin, M R

2017-01-01

Corn oil (CO) and extra-virgin olive oil (EVOO) are rich sources of unsaturated fatty acids (UFA), but UFA profiles differ among oils, which may affect lipoprotein levels. The objective of this study was to assess the effects of CO versus EVOO intake on fasting lipoprotein and subfraction cholesterol levels, apolipoprotein (apo) A1, apo B, and low-density lipoprotein particle concentrations in men and women. As part of a weight maintenance diet, men and women were provided with food items prepared with 54 g per day of CO or EVOO (21-day treatment, 21-day washout) in a randomized, double-blind, controlled-feeding, crossover trial. Fasting lipoprotein cholesterol and related variables were determined with density gradient ultracentrifugation. Among the 54 completers, CO reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apo B and LDL particle concentration to a greater extent compared with EVOO intake. Changes in LDL-C and VLDL-C contributed to the larger reduction in non-HDL-C with CO compared with EVOO intake (-0.39 mmol/l vs -0.04 mmol/l; P<0.001). The larger reduction in LDL-C by CO intake was attributable to changes (P<0.05) caused by CO vs EVOO in large LDL 1+2 -C (-0.22 mmol/l) and intermediate-density lipoprotein cholesterol (-0.12 mmol/l). HDL-C responses did not differ between treatments, but apo A1 increased more with EVOO compared with CO intake (4.6  versus 0.7 mg/dl, respectively, P=0.016). CO intake reduced atherogenic lipoprotein cholesterol and particle concentrations to a larger extent than did EVOO, which may have implications for cardiovascular disease risk.

Complexity of mechanisms among human proprotein convertase subtilisin-kexin type 9 variants.

PubMed

Dron, Jacqueline S; Hegele, Robert A

2017-04-01

There are many reports of human variants in proprotein convertase subtilisin-kexin type 9 (PCSK9) that are either gain-of-function (GOF) or loss-of-function (LOF), with downstream effects on LDL cholesterol and cardiovascular disease (CVD) risk. However, data on particular mechanisms have only been minimally curated. GOF variants are individually ultrarare, affect all domains of the protein, act to reduce LDL receptor expression through several mechanisms, are a minor cause of familial hypercholesterolemia, have been reported mainly within families, have variable LDL cholesterol-raising effects, and are associated with increased CVD risk mainly through observational studies in families and small cohorts. In contrast, LOF variants can be either ultrarare mutations or relatively more common polymorphisms seen in populations, affect all domains of the protein, act to increase LDL receptor expression through several mechanisms, have variable LDL cholesterol-lowering effects, and have been associated with decreased CVD risk mainly through Mendelian randomization studies in epidemiologic populations. There is considerable complexity underlying the clinical concept of both LOF and GOF variants of PCSK9. But despite the underlying mechanistic heterogeneity, altered PCSK9 secretion or function is ultimately correlated with plasma LDL cholesterol level, which is also the driver of CVD outcomes.

Strategies for proprotein convertase subtilisin kexin 9 modulation: a perspective on recent patents.

PubMed

Abifadel, Marianne; Pakradouni, Jihane; Collin, Matthieu; Samson-Bouma, Marie-Elisabeth; Varret, Mathilde; Rabès, Jean-Pierre; Boileau, Catherine

2010-11-01

Proprotein convertase subtilisin kexin 9 (PCSK9) is a new actor discovered in 2003 that is implicated in autosomal dominant hypercholesterolemia, cholesterol homeostasis and coronary heart disease. It has been shown to degrade the low-density lipoprotein (LDL) receptor independently of its catalytic activity. Several pharmacological strategies to reduce PCSK9 are being thoroughly investigated. This article reviews all different strategies that are presently pursued to modulate the functional activity of PCSK9 which is a prime target for controlling LDL-cholesterol. It also provides a briefing of all the patents up to July 2010 from various organizations including pharmaceutical companies and academic institutions that have been submitted and/or approved. This review is addressed to researchers from academia and pharmaceutical companies who are engaged in PCSK9 research/cholesterol regulation and in the development of cholesterol lowering drugs. Readers will gain an up-to-date overview of the different strategies that have been investigated to reduce PCSK9 including antisense technology and specific antibodies. Clinical trials have been launched using RNA interference approaches to reduce PCSK9 expression or specific antibodies targeting and inhibiting PCSK9 interaction with the LDL receptor. They constitute very promising approaches to reducing cholesterol levels and coronary heart disease.

The effect of exercise on plasma lipids and LDL subclass metabolism in miniature swine.

PubMed

Stucchi, A F; Terpstra, A H; Foxall, T L; Nicolosi, R J; Smith, S C

1991-05-01

The effects of exercise on plasma lipids and lipoproteins, high density lipoprotein (HDL) subclass cholesterol levels, and low density lipoprotein (LDL) subclass composition and metabolism were studied in Yucatan miniature swine following 2 yr of training. The exercise protocol produced significant training effects. Post-heparin lipolytic activity was also significantly increased. Although plasma cholesterol and triglycerides did not differ significantly (P = 0.08) between the exercised and control groups, multivariate analysis indicated a strong association between lipoprotein lipase (LPL) and HDL2-C (P less than 0.0001). Although HDL-C levels rose only slightly (P less than 0.09) with exercise, a significant shift was noted in the distribution of cholesterol from the HDL3 to the HDL2 fractions, perhaps mediated by the substantial increase in LPL activity. Exercise had little effect on the chemical composition of the major lipoprotein classes; however, the triglyceride content of the lighter LDL1 subclass was significantly reduced. In the more dense LDL2 subclass, exercise resulted in a significant decrease in triglycerides concomitant with a significant increase in free cholesterol levels. In contrast with the small reductions in fractional catabolic rates (FCR) in either subclass, production rates of the exercised group were reduced, which accounted for the reduction in LDL subclass pool size. These data indicate that exercise produces subtle but significant changes in lipoprotein metabolism that have been previously associated with reduced risk of atherosclerosis.

PCSK9 inhibition in the management of familial hypercholesterolemia.

PubMed

Ogura, Masatsune

2018-01-01

Familial hypercholesterolemia (FH) is a frequent hereditary metabolic disease characterized by high serum low-density lipoprotein (LDL) cholesterol concentration and premature atherosclerotic cardiovascular disease (ASCVD). The discovery of the LDL receptor as one of the causative genes of FH enabled us to understand the pathophysiology of FH and paved the way for developing statins. Similar to LDL receptor, discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) also created an opportunity for developing its inhibitors. Since PCSK9 degrades LDL receptor protein, inhibiting PCSK9 will be an effective strategy. Evolocumab and alirocumab, anti-PCSK9 antibodies that inhibit binding between PCSK9 and LDL receptors, are now available in Japan. Adding an anti-PCSK9 antibody to standard therapy with statin alone or statin combined with ezetimibe further reduced serum LDL cholesterol levels by around 60% and they significantly decrease cardiovascular event incidence as compared with placebo. Additionally, the strong LDL cholesterol lowering effect of anti-PCSK9 antibody therapies has reportedly enabled the frequency of lipoprotein apheresis to be reduced or to be discontinued. As alternative strategies against PCSK9, antisense oligonucleotide agents that inhibit PCSK9 protein synthesis as well as a small interfering (or short interference) RNA (siRNA) for PCSK9 are also being developed. While relatively high cost can be given as a problem, PCSK9 inhibitors are able to reduce LDL cholesterol dramatically even in FH patients who could not achieve targets until now. To ensure that these drugs are given to the patients who really need them, it is necessary to raise the diagnosis rate and family screening has to be more actively conducted. Finally, it has been reported that PCSK9 is expressed not only in hepatocytes but also in other cells such as epithelial cells in small intestine and vascular smooth muscle cells in atherosclerotic plaque. Further research regarding extra-hepatic pathophysiology of PCSK9 is expected. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Natural honey lowers plasma glucose, C-reactive protein, homocysteine, and blood lipids in healthy, diabetic, and hyperlipidemic subjects: comparison with dextrose and sucrose.

PubMed

Al-Waili, Noori S

2004-01-01

This study included the following experiments: (1) effects of dextrose solution (250 mL of water containing 75 g of dextrose) or honey solution (250 mL of water containing 75 g of natural honey) on plasma glucose level (PGL), plasma insulin, and plasma C-peptide (eight subjects); (2) effects of dextrose, honey, or artificial honey (250 mL of water containing 35 g of dextrose and 40 g of fructose) on cholesterol and triglycerides (TG) (nine subjects); (3) effects of honey solution, administered for 15 days, on PGL, blood lipids, C-reactive protein (CRP), and homocysteine (eight subjects); (4) effects of honey or artificial honey on cholesterol and TG in six patients with hypercholesterolemia and five patients with hypertriglyceridemia; (5) effects of honey for 15 days on blood lipid and CRP in five patients with elevated cholesterol and CRP; (6) effects of 70 g of dextrose or 90 g of honey on PGL in seven patients with type 2 diabetes mellitus; and (7) effects of 30 g of sucrose or 30 g of honey on PGL, plasma insulin, and plasma C-peptide in five diabetic patients. In healthy subjects, dextrose elevated PGL at 1 (53%) and 2 (3%) hours, and decreased PGL after 3 hours (20%). Honey elevated PGL after 1 hour (14%) and decreased it after 3 hours (10%). Elevation of insulin and C-peptide was significantly higher after dextrose than after honey. Dextrose slightly reduced cholesterol and low-density lipoprotein-cholesterol (LDL-C) after 1 hour and significantly after 2 hours, and increased TG after 1, 2, and 3 hours. Artificial honey slightly decreased cholesterol and LDL-C and elevated TG. Honey reduced cholesterol, LDL-C, and TG and slightly elevated high-density lipoprotein-cholesterol (HDL-C). Honey consumed for 15 days decreased cholesterol (7%), LDL-C (1%), TG (2%), CRP (7%), homocysteine (6%), and PGL (6%), and increased HDL-C (2%). In patients with hypertriglyceridemia, artificial honey increased TG, while honey decreased TG. In patients with hyperlipidemia, artificial honey increased LDL-C, while honey decreased LDL-C. Honey decreased cholesterol (8%), LDL-C (11%), and CRP (75%) after 15 days. In diabetic patients, honey compared with dextrose caused a significantly lower rise of PGL. Elevation of PGL was greater after honey than after sucrose at 30 minutes, and was lower after honey than it was after sucrose at 60, 120, and 180 minutes. Honey caused greater elevation of insulin than sucrose did after 30, 120, and 180 minutes. Honey reduces blood lipids, homocysteine, and CRP in normal and hyperlipidemic subjects. Honey compared with dextrose and sucrose caused lower elevation of PGL in diabetics.

[Diet in disordered lipid metabolism. A culinary balance act].

PubMed

Richter, W O

2003-08-07

When LDL cholesterol is elevated, HDL cholesterol is low or triglycerides are raised, dietary changes form the basis of treatment. Such changes are most important in the case of hypertriglyceridemia. Some 3 to 4 hours after a meal, triglycerides increase to an extent determined by the composition of the meal. Hypertriglyceridemia cannot be successfully treated unless alcohol is banished and rapidly assimilatable carbohydrates are restricted. In patients with elevated LDL cholesterol, a change in eating habits can have an appreciable effect (on average 10-15%). Since this measure can save the use or reduce the dose of medications, its value is obvious, and it must not be neglected. The measures aimed at elevating HDL cholesterol have only a moderate effect, so that more importance should be attached to lowering the LDL fraction.

Dietary patterns associated with HbA1c and LDL cholesterol among individuals with type 1 diabetes in China

PubMed Central

Jaacks, Lindsay M.; Crandell, Jamie; Mendez, Michelle A.; Lamichhane, Archana P.; Liu, Wei; Ji, Linong; Du, Shufa; Rosamond, Wayne; Popkin, Barry M.; Mayer-Davis, Elizabeth J.

2015-01-01

Aims To identify dietary patterns that influence cardiometabolic risk among individuals with type 1 diabetes (T1D) in China. Methods Data are from a cross-sectional study of T1D in China (n=99). Dietary intake was assessed using three 24-hour recalls. Reduced rank regression was used to identify dietary patterns from a set of 20 food groups that maximized the explained variation in glycated hemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) cholesterol. Results Dietary pattern 1 was characterized by low intakes of wheat products and high-fat cakes, and high intakes of beans and pickled vegetables. Dietary pattern 2 was characterized by low intakes of high-fat cakes, nuts/seeds, fish/shellfish, and teas/coffee, and high intakes of rice and eggs. Participants in the highest tertile of dietary pattern 1 had significantly (p<0.05) higher HbA1c and LDL cholesterol compared to participants in the lowest tertile: mean difference in HbA1c was 1.0 percentage point (11mmol/mol) and in LDL cholesterol was 0.36 mmol/L after adjustment for age and household income. Dietary pattern 2 was not associated with HbA1c or LDL cholesterol. Conclusions We identified a dietary pattern that is significantly related to HbA1c and LDL cholesterol. These findings provide support for behavioral strategies to prevent complications in individuals with T1D in China. PMID:25630525

COMBINATION THERAPY EFFECTIVENESS OF EZETIMIBE AND ATORVASTATIN IN PATIENTS WITH ACUTE CORONARY SYNDROME.

PubMed

Japaridze, L; Sadunishvili, M; Megreladze, I

2016-03-01

Atorvastatin reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe (EZE) , a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. We conducted a 16-week one-center, prospective, randomized, and open-label clinical trial, involving 323 patients who had been hospitalized for an acute coronary syndrome within the preceding 14 days. They were received atorvastatin 20 mg during 28 days and after that 292 patients, who had LDL cholesterol levels≥1.81 mmol/L, were randomized to ezetimibe 10 mg/day co-administered with atorvastatin therapy (EZE+Statin) or doubling their current atorvastatin dose. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. At 16 weeks, the mean LDL cholesterol level during the study was 1.60 mmol per liter in the atorvastatine-ezetimibe group, as compared with 1.91 mmol per liter in the atorvastatin-monotherapy group (p<0.001). The Kaplan-Meier survival rate at 16 weeks were 88 .1 % in the atorvastatin-ezetimibe group and 77.0 % in the atorvastatin monotherapy group (absolute risk reduction, 11.1 percentage points; hazard ratio, 2.099 ; 95% confidence interval, 1.165 to 3.781; p=0.014). Patients receiving ezetimibe and statin were more likely to achieve target LDL-C after 16 weeks compared to patients doubling their statin dose. When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Ezetimibe/statin combination therapy was well tolerated among this patients, without safety concerns.

Selected Cardiovascular Risk Markers in Vegetarians and Subjects of General Population.

PubMed

Valachovičová, Martina; Príbojová, Jana; Urbánek, Vladimír; Bírošová, Lucia

2017-12-01

Besides genetic factors there are environmental effects including nutritional habits which can influence the risk of age-related diseases. The aim of the study was to assess the age dependence of selected cardiovascular risk markers in two groups of subjects with different nutritional pattern. In 470 long-term vegetarians and 478 subjects of general population the following indicators were measured: total cholesterol, HDL-cholesterol, triacylglycerol, glucose, insulin concentrations, LDL-cholesterol, atherogenic index and insulin resistance IR(HOMA) were also calculated in studied subjects. Obtained data were evaluated according to age decades. Vegetarian vs. non-vegetarian concentrations of total cholesterol, LDL-cholesterol, insulin, and values of atherogenic index and IR(HOMA) were significantly reduced in all age decades. Vegetarian vs. non-vegetarian triacalglycerol concentrations were significantly reduced from 4th–7th decade. Vegetarian average decade values of all lipid parameters were in reference range. In non-vegetarian group, the risk average values of total cholesterol (>5.2 mmol/l) were found from 5th–7th decade, LDL-cholesterol (>3.3 mmol/l) in 7th decade and atherogenic index (>4) in 6th–7th decade. In vegetarians vs. non-vegetarians were noted the average decade values for total cholesterol ranging from 4.01–4.59 vs. 4.48–5.67 mmol/l, for triacylglycerols 1.00–1.33 vs. 1.13–1.74 mmol/l, for LDL-cholesterol 2.03–2.58 vs. 2.43–3.49 mmol/l, for atherogenic index 2.72–3.31 vs. 3.05–4.21 and for IR(HOMA) 0.99–1.15 vs. 1.15–1.84. Our data show significantly reduced mean age decade values of lipid and non-lipid cardiovascular risk markers in all adult vegetarians. Smaller changes of markers between decades compared to non-vegetarians document a protective effect of vegetarian nutrition in prevention of cardiovascular disease. Copyright© by the National Institute of Public Health, Prague 2017

Psyllium husk fiber supplementation to the diets rich in soybean or coconut oil: hypocholesterolemic effect in healthy humans.

PubMed

Ganji, V; Kies, C V

1996-03-01

The objective of this study was to investigate the effect of psyllium husk fiber supplementation to the diets of soybean and coconut oil on serum lipids in normolipidemic humans. A 28-day study was divided into four 7-day experimental periods. Dietary periods were soybean oil (SO), soybean oil plus psyllium fiber (SO + PF), coconut oil (CO) and coconut oil plus psyllium fiber (CO + PF), and were arranged to a randomized cross over design. Ten subjects consumed controlled diet containing 30% fat calories (20% from test oils and 10% from controlled diet) and 20 g per day of psyllium during fiber supplementation periods. SO + PF diet significantly reduced serum cholesterol compared with SO diet (P < 0.001). CO + PF diet significantly reduced serum cholesterol compared with CO diet (P < 0.014). Hypocholesterolemic response was greater with SO + PF compared with CO + PF (0.36 mmol 1(-1) vs 0.31 mmol 1(-1)). Reductions in low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B were parallel to reductions of serum cholesterol. SO diet decreased, while CO diet increased serum cholesterol, LDL cholesterol and apo B. Very-low density lipoprotein cholesterol, high-density lipoprotein cholesterol and apo A-1 were unaffected by psyllium fiber and saturation of fat. Reduction of serum cholesterol was due to reduction of LDL cholesterol. Psyllium fiber supplementation lowered serum cholesterol regardless of saturation level of dietary fat.

Cashew consumption reduces total and LDL cholesterol: a randomized, crossover, controlled-feeding trial.

PubMed

Mah, Eunice; Schulz, Jacqueline A; Kaden, Valerie N; Lawless, Andrea L; Rotor, Jose; Mantilla, Libertie B; Liska, DeAnn J

2017-05-01

Background: Cashews are the third most-consumed tree nut in the United States and are abundant with monounsaturated fatty acids and polyunsaturated fatty acids, which are associated with reduced cardiovascular disease risk. Although a qualified Food and Drug Administration health claim exists for nuts and heart health, cashews have been exempt from its use because cashews exceed the disqualifying amount of saturated fatty acids. Approximately one-third of the saturated fat in cashews is stearic acid, which is relatively neutral on blood lipids, thereby suggesting that cashews could have effects that are similar to those of other nuts. However, clinical data on cashews and blood lipids have been limited. Objective: We investigated the effect of reasonable intakes of cashews on serum lipids in adults with or at risk of high LDL cholesterol. Design: In a randomized, crossover, isocaloric, controlled-feeding study, 51 men and women (aged 21-73 y) with a median LDL-cholesterol concentration of 159 mg/dL (95% CI: 146, 165 mg/dL) at screening consumed typical American diets with cashews (28-64 g/d; 50% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 32% of kilocalories from total fat) or potato chips (control; 54% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 29% of kilocalories from total fat) for 28 d with a ≥2-wk washout period. Results: Consumption of the cashew diet resulted in a significantly greater median change from baseline (compared with the control, all P < 0.05) in total cholesterol [-3.9% (95% CI: -9.3%, 1.7%) compared with 0.8% (95% CI: -1.5%, 4.5%), respectively], LDL cholesterol [-4.8% (95% CI: -12.6%, 3.1%) compared with 1.2% (95% CI: -2.3%, 7.8%), respectively], non-HDL cholesterol [-5.3% (95% CI: -8.6%, 2.1%) compared with 1.7% (95% CI: -0.9%, 5.6%), respectively], and the total-cholesterol:HDL-cholesterol ratio [-0.0% (95% CI: -4.3%, 4.8%) compared with 3.4% (95% CI: 0.6%, 5.2%), respectively]. There were no significant differences between diets for HDL cholesterol and triglyceride. Conclusions: In comparison with a control diet, the incorporation of cashews into typical American diets decreases total cholesterol and LDL cholesterol. Results from this study provide support that the daily consumption of cashews, when substituted for a high-carbohydrate snack, may be a simple dietary strategy to help manage total cholesterol and LDL cholesterol. This study was registered at clinicaltrials.gov as NCT02769741. © 2017 American Society for Nutrition.

Efficacy and safety of alirocumab in insulin‐treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: The ODYSSEY DM‐INSULIN randomized trial

PubMed Central

Cariou, Bertrand; Müller‐Wieland, Dirk; Colhoun, Helen M.; Del Prato, Stefano; Tinahones, Francisco J.; Ray, Kausik K.; Bujas‐Bobanovic, Maja; Domenger, Catherine; Mandel, Jonas; Samuel, Rita; Henry, Robert R.

2017-01-01

Aims To investigate the efficacy and safety of alirocumab in participants with type 2 (T2D) or type 1 diabetes (T1D) treated with insulin who have elevated LDL cholesterol levels despite maximally tolerated statin therapy. Methods Participants at high cardiovascular risk with T2D (n = 441) or T1D (n = 76) and LDL cholesterol levels ≥1.8 mmol/L (≥70 mg/dL) were randomized 2:1 to alirocumab:placebo administered subcutaneously every 2 weeks, for 24 weeks' double‐blind treatment. Alirocumab‐treated participants received 75 mg every 2 weeks, with blinded dose increase to 150 mg every 2 weeks at week 12 if week 8 LDL cholesterol levels were ≥1.8 mmol/L. Primary endpoints were percentage change in calculated LDL cholesterol from baseline to week 24, and safety assessments. Results Alirocumab reduced LDL cholesterol from baseline to week 24 by a mean ± standard error of 49.0% ± 2.7% and 47.8% ± 6.5% vs placebo (both P < .0001) in participants with T2D and T1D, respectively. Significant reductions were observed in non‐HDL cholesterol (P < .0001), apolipoprotein B (P < .0001) and lipoprotein (a) (P ≤ .0039). At week 24, 76.4% and 70.2% of the alirocumab group achieved LDL cholesterol <1.8 mmol/L in the T2D and T1D populations (P < .0001), respectively. Glycated haemoglobin and fasting plasma glucose levels remained stable for the study duration. Treatment‐emergent adverse events were observed in 64.5% of alirocumab‐ vs 64.1% of placebo‐treated individuals (overall population). Conclusions Alirocumab produced significant LDL cholesterol reductions in participants with insulin‐treated diabetes regardless of diabetes type, and was generally well tolerated. Concomitant administration of alirocumab and insulin did not raise any safety concerns (NCT02585778). PMID:28905478

Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.

PubMed

Cannon, Christopher P; Blazing, Michael A; Giugliano, Robert P; McCagg, Amy; White, Jennifer A; Theroux, Pierre; Darius, Harald; Lewis, Basil S; Ophuis, Ton Oude; Jukema, J Wouter; De Ferrari, Gaetano M; Ruzyllo, Witold; De Lucca, Paul; Im, KyungAh; Bohula, Erin A; Reist, Craig; Wiviott, Stephen D; Tershakovec, Andrew M; Musliner, Thomas A; Braunwald, Eugene; Califf, Robert M

2015-06-18

Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).

The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity, cholesterol esterification and the expression of low-density lipoprotein receptors in cultured monocyte-derived macrophages.

PubMed Central

Knight, B L; Patel, D D; Soutar, A K

1983-01-01

Human blood monocytes cultured in medium containing 20% whole serum showed the greatest activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and [14C]acetate incorporation into non-saponifiable lipids around the 7th day after seeding, the period of greatest growth. Although there was enough low-density lipoprotein (LDL) in the medium to saturate the LDL receptors that were expressed by normal cells at that time, HMG-CoA reductase activity and acetate incorporation were as high in normal cells as in cells from familial-hypercholesterolaemic (FH) patients. Both the addition of extra LDL, which interacted with the cells by non-saturable processes, and receptor-mediated uptake of acetylated LDL significantly reduced reductase activity and increased incorporation of [14C]oleate into cholesteryl esters in normal cells and cells from FH patients ('FH cells'), and reduced the expression of LDL receptors in normal cells. Pre-incubation for 20h in lipoprotein-deficient medium apparently increased the number of LDL receptors expressed by normal cells but reduced the activity of HMG-CoA reductase in both normal and FH cells. During subsequent incubations the same rate of degradation of acetylated LDL and of non-saturable degradation of LDL by FH cells was associated with the same reduction in HMG-CoA reductase activity, although LDL produced a much smaller stimulation of oleate incorporation into cholesteryl esters. In normal cells pre-incubated without lipoproteins, receptor-mediated uptake of LDL could abolish reductase activity and the expression of LDL receptors. The results suggested that in these cells, receptor-mediated uptake of LDL might have a greater effect on reductase activity and LDL receptors than the equivalent uptake of acetylated LDL. It is proposed that endogenous synthesis is an important source of cholesterol for growth of normal cells, and that the site at which cholesterol is deposited in the cells may determine the nature and extent of the metabolic events that follow. PMID:6305342

Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.

PubMed

Marshall, Stephanie M; Kelley, Kathryn L; Davis, Matthew A; Wilson, Martha D; McDaniel, Allison L; Lee, Richard G; Crooke, Rosanne M; Graham, Mark J; Rudel, Lawrence L; Brown, J Mark; Temel, Ryan E

2014-01-01

An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE) is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL) support TICE, antisense oligonucleotides (ASO) were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP), which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg) mice, which predominantly excrete cholesterol via TICE, and wild type (WT) littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG) and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE.

Effect of an indigenous herbal compound preparation 'Trikatu' on the lipid profiles of atherogenic diet and standard diet fed Rattus norvegicus.

PubMed

Sivakumar, Valsala; Sivakumar, S

2004-12-01

Combating heart disease is one of the challenging problems of biomedical science today. Towards this goal an indigenous preparation 'Trikatu' (a herbal combination containing Piper longum (fruit), Piper nigrum (fruit) and Zingiber officinale (rhizome) dry powder) was fed to normal and cholesterol fed male Rattus norvegicus to ascertain its efficacy as a hypolipidaemic agent. Its effects on body weight, blood and tissue (aortic, cardiac and hepatic) lipids--total, free and esterified cholesterol, low density lipoprotein(LDL) and high density lipoprotein(HDL) cholesterol, triglycerides and phospholipids--and the atherogenic index were measured. It was found that 'Trikatu' by virtue of its ability to reduce triglycerides and LDL cholesterol and to increase HDL cholesterol can reduce the risk of hyperlipidaemia and atherosclerosis. Hence 'Trikatu' can be used as a potent hypolipidaemic agent and it can reduce the atherosclerosis associated with a high fat diet. 2004 John Wiley & Sons, Ltd.

The LDL receptor.

PubMed

Goldstein, Joseph L; Brown, Michael S

2009-04-01

In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life.

Analysis of lipid profile and atherogenic index in hyperlipidemic rat (Rattus norvegicus Berkenhout, 1769) that given the methanolic extract of Parijoto (Medinilla speciosa)

NASA Astrophysics Data System (ADS)

Sa'adah, Noor Nailis; Purwani, Kristanti Indah; Nurhayati, Awik Puji Dyah; Ashuri, Nova Maulidina

2017-06-01

Diet of high lipids cause hyperlipidemia, which marked by an increase of total cholesterols, triglycerides, LDL-C, and decreasing of HDL-C. Hyperlipidemia lead the occurrence of atherosclerosis, one of factors that trigger cardiovascular disease, as hypertention; coronary heart and stroke. Parijoto (M. speciosa) is endemic plants in Asia with a distribution center in Malaysia, Indonesia and Philippines. Parijoto contain phytochemical components such as flavonoids, saponins and kardenolin. Flavonoid potensial as an antioxidants and can improve the hyperlipidemia condition. This study was aimed to determine lipid profiles and atherogenic index of hyperlipidemic Wistar rats (R. norvegicus Berkenhout, 1769) which given the methanolic extract of Parijoto (M. speciosa). The research was done with pre and post test randomized control group design. Rats were given a mixture of duck yolk and reused cooking oil (1:1) orally as much as 1% of body weight (BW) for 30 days. After hyperlipidemia achieved, rats were divided into 5 group: normal rats, hyperlipidemic rats, hyperlipidemic rats were given the methanolic extract of Parijoto (M. speciosa) 500 mg/kg, 1000 mg/kg, and 1500 mg/kg BW. Blood samples were collected when rats in hyperlipidemia conditions and after treatment with the methanolic extract of Parijoto (M. speciosa) for 30 days. The data of total cholesterol, HDL-Cholesterol, LDL-Cholesterol level, and atherogenic index were analyzed using ANOVA followed by Tukey test at 5% significance level. The result showed that giving of methanolic extract of Parijoto (M. speciosa) in hyperlipidemic rats reduced the total cholesterol, LDL-Cholesterol levels, and increased of HDL-cholesterol levels significantly (p<0.01), so atherogenic index reduced significantly too (p<0.01). Total cholesterol and LDL-Cholesterol levels were positively correlated with the atherogenic index, whereas HDL-cholesterol levels were negatively correlated with the atherogenic index.

SKI-II--a sphingosine kinase 1 inhibitor--exacerbates atherosclerosis in low-density lipoprotein receptor-deficient (LDL-R-/-) mice on high cholesterol diet.

PubMed

Potì, Francesco; Ceglarek, Uta; Burkhardt, Ralph; Simoni, Manuela; Nofer, Jerzy-Roch

2015-05-01

Sphingosine 1-phosphate (S1P) is a lysosphingolipid associated with high-density lipoproteins (HDL) that contributes to their anti-atherogenic potential. We investigated whether a reduction in S1P plasma levels affects atherosclerosis in low-density lipoprotein receptor deficient (LDL-R-/-) mice. LDL-R-/- mice on Western diet containing low (0.25% w/w) or high (1.25% w/w) cholesterol were treated for 16 weeks with SKI-II, a sphingosine kinase 1 inhibitor that significantly reduced plasma S1P levels. SKI-II treatment increased atherosclerotic lesions in the thoracic aorta in mice on high but not low cholesterol diet. This compound did not affect body weight, blood cell counts and plasma total and HDL cholesterol, but decreased triglycerides. In addition, mice on high cholesterol diet receiving SKI-II showed elevated levels of tumor necrosis factor-α and endothelial adhesion molecules (sICAM-1, sVCAM-1). Prolonged lowering of plasma S1P produces pro-atherogenic effects in LDL-R-/- mice that are evident under condition of pronounced hypercholesterolemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Diagnostic Yield of Sequencing Familial Hypercholesterolemia Genes in Severe Hypercholesterolemia

PubMed Central

Khera, Amit V.; Won, Hong-Hee; Peloso, Gina M.; Lawson, Kim S.; Bartz, Traci M.; Deng, Xuan; van Leeuwen, Elisabeth M.; Natarajan, Pradeep; Emdin, Connor A.; Bick, Alexander G.; Morrison, Alanna C.; Brody, Jennifer A.; Gupta, Namrata; Nomura, Akihiro; Kessler, Thorsten; Duga, Stefano; Bis, Joshua C.; van Duijn, Cornelia M.; Cupples, L. Adrienne; Psaty, Bruce; Rader, Daniel J.; Danesh, John; Schunkert, Heribert; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Lander, Eric; Wilson, James G.; Correa, Adolfo; Boerwinkle, Eric; Merlini, Piera Angelica; Ardissino, Diego; Saleheen, Danish; Gabriel, Stacey; Kathiresan, Sekar

2017-01-01

Background About 7% of US adults have severe hypercholesterolemia (untreated LDL cholesterol ≥190 mg/dl). Such high LDL levels may be due to familial hypercholesterolemia (FH), a condition caused by a single mutation in any of three genes. Lifelong elevations in LDL cholesterol in FH mutation carriers may confer CAD risk beyond that captured by a single LDL cholesterol measurement. Objectives Assess the prevalence of a FH mutation among those with severe hypercholesterolemia and determine whether CAD risk varies according to mutation status beyond the observed LDL cholesterol. Methods Three genes causative for FH (LDLR, APOB, PCSK9) were sequenced in 26,025 participants from 7 case-control studies (5,540 CAD cases, 8,577 CAD-free controls) and 5 prospective cohort studies (11,908 participants). FH mutations included loss-of-function variants in LDLR, missense mutations in LDLR predicted to be damaging, and variants linked to FH in ClinVar, a clinical genetics database. Results Among 8,577 CAD-free control participants, 430 had LDL cholesterol ≥190 mg/dl; of these, only eight (1.9%) carried a FH mutation. Similarly, among 11,908 participants from 5 prospective cohorts, 956 had LDL cholesterol ≥190 mg/dl and of these, only 16 (1.7%) carried a FH mutation. Within any stratum of observed LDL cholesterol, risk of CAD was higher among FH mutation carriers when compared with non-carriers. When compared to a reference group with LDL cholesterol <130 mg/dl and no mutation, participants with LDL cholesterol ≥190 mg/dl and no FH mutation had six-fold higher risk for CAD (OR 6.0; 95%CI 5.2–6.9) whereas those with LDL cholesterol ≥190 mg/dl as well as a FH mutation demonstrated twenty-two fold increased risk (OR 22.3; 95%CI 10.7–53.2). Conclusions Among individuals with LDL cholesterol ≥190 mg/dl, gene sequencing identified a FH mutation in <2%. However, for any given observed LDL cholesterol, FH mutation carriers are at substantially increased risk for CAD. PMID:27050191

Actinidia chinensis Planch root extract inhibits cholesterol metabolism in hepatocellular carcinoma through upregulation of PCSK9.

PubMed

He, Mingyan; Hou, Jiayun; Wang, Lingyan; Zheng, Minghuan; Fang, Tingting; Wang, Xiangdong; Xia, Jinglin

2017-06-27

Actinidia chinensis Planch root extract (acRoots) is a traditional Chinese medicine with anti-tumor efficacy. To investigate the mechanisms responsible for this activity, we examined the effects of acRoots on cholesterol metabolism in hepatocellular carcinoma (HCC). mRNA chip analysis was used to identify the metabolic genes regulated by acRoots. The effects of acRoots on cholesterol synthesis and uptake were evaluated by measuring intracellular cholesterol levels and 3,3'-dioctadecylindocarbocyanine-labeled low-density lipoprotein (Dil-LDL) uptake. Expression of metabolic genes was analyzed using quantitative reverse transcription PCR, western blotting, and flow cytometry. acRoots reduced the viability of LM3 and HepG2 cells at 5 mg/mL and HL-7702 cells at 30 mg/mL. Gene expression profiling revealed that treatment with acRoots altered expression of genes involved in immune responses, inflammation, proliferation, cell cycle control, and metabolism. We also confirmed that acRoots enhances expression of PCSK9, which is important for cholesterol metabolism. This resulted in decreased LDL receptor expression, inhibition of LDL uptake by LM3 cells, decreased total intracellular cholesterol, and reduced proliferation. These effects were promoted by PCSK9 overexpression and rescued by PCSK9 knockdown. Our data demonstrate that acRoots is a novel anti-tumor agent that inhibits cholesterol metabolism though a PCSK9-mediated signaling pathway.

A Mediterranean-style low-glycemic-load diet increases plasma carotenoids and decreases LDL oxidation in women with metabolic syndrome☆

PubMed Central

Barona, Jacqueline; Jones, Jennifer J.; Kopec, Rachel E.; Comperatore, Michael; Andersen, Catherine; Schwartz, Steven J.; Lerman, Robert H.; Fernandez, Maria Luz

2013-01-01

Thirty-five women with metabolic syndrome and high plasma low-density lipoprotein (LDL) cholesterol (≥100 mg/dl) participated in a dietary intervention consisting of a Mediterranean-style low-glycemic-load diet for 12 weeks. Participants were randomly allocated to consume diet only (n=15) or diet plus a medical food containing soy protein and plant sterols (n=20). Plasma concentrations of carotenoids, lipoprotein subfractions and oxidized LDL (OxLDL) were measured. Independent of treatment, women had a significant increase in plasma lutein (P<.0001) and β-carotene (P<.0001), while plasma lycopene was reduced (P<.05) after 12 weeks. Low-density lipoprotein cholesterol was reduced from 138±35 to 114±33 mg/dl (P<.0001). In addition, decreases were observed in the atherogenic subfractions: large very low-density lipoprotein (P<.05), small LDL (P<.00001) and medium high-density lipoprotein (P<.05). Oxidized LDL was significantly reduced by 12% in both groups (P<.01). Changes in OxLDL were inversely correlated with plasma lutein (r=−.478, P<.0001). The data indicate that women complied with the dietary regimen by increasing fruits and vegetable intake. Decreased consumption of high-glycemic foods frequently co-consumed with lycopene-rich tomato sauce such as pasta and pizza may be responsible for the lowering of this carotenoid in plasma after 12 weeks. These results also suggest that plasma lutein concentrations may protect against oxidative stress by reducing the concentrations of OxLDL. PMID:21775117

Rice Bran Extract Reduces the Risk of Atherosclerosis in Post-Menopausal Vietnamese Women.

PubMed

Nhung, Bui Thi; Tuyen, Le Danh; Linh, Vu Anh; Anh, Nguyen Do Van; Nga, Tran Thuy; Thuc, Vu Thi Minh; Yui, Kei; Ito, Yukihiko; Nakashima, Yuri; Yamamoto, Shigeru

2016-01-01

We investigated whether pre-germinated brown rice bran extract containing acylated steryl glucosides (PSG) reduces the risk of atherosclerosis in post-menopausal Vietnamese women. A total of 60 post-menopausal Vietnamese women (45-65 y old) with high LDL cholesterol levels (over 140 mg/dL) were randomly divided into PSG (n=30) and placebo (n=30) groups. The subjects in the PSG group were assigned a daily intake of 6 capsules containing 50 mg PSG, and the subjects in the placebo group were assigned a daily intake of 6 capsules containing corn oil for 6 mo. Before baseline and after month 2, month 4, and month 6 of the intervention, we conducted anthropometric measurements, blood biochemical examinations, a nutrition survey, and physical activity, flow-mediated dilation (FMD), and cardio-ankle vascular index (CAVI) measurements. Serum LDL cholesterol concentrations were significantly reduced from 163.6±25.3 (mg/dL) to 135.9±26.8 (mg/dL) compared to the placebo group (p<0.001). FMD values of the placebo group were significantly reduced from 6.6±5.1 (%) to 4.7±2.6 (%) compared to the PSG group (p<0.05). Tumor necrosis factor (TNF)-α concentrations in the PSG group were significantly reduced from 19.8±11 (pg/mL) to 10.6±5.5 (pg/mL) compared to the placebo group (p<0.05). The findings suggest that PSG may improve LDL cholesterol, TNF-α levels, and FMD values. PSG might be considered in reducing the risk of atherosclerosis in post-menopausal Vietnamese women with high LDL cholesterol.

Natural honey and cardiovascular risk factors; effects on blood glucose, cholesterol, triacylglycerole, CRP, and body weight compared with sucrose.

PubMed

Yaghoobi, N; Al-Waili, Noori; Ghayour-Mobarhan, M; Parizadeh, S M R; Abasalti, Z; Yaghoobi, Z; Yaghoobi, F; Esmaeili, H; Kazemi-Bajestani, S M R; Aghasizadeh, R; Saloom, Khelod Y; Ferns, G A A

2008-04-20

It has been found that honey ameliorates cardiovascular risk factors in healthy individuals and in patients with elevated risk factors. The present study investigated the effect of natural honey on total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triacylglycerole, C-reactive protein (CRP), fasting blood glucose (FBG), and body weight in overweight individuals. There were 55 patients, overweight or obese, who were randomly recruited into the study and assigned into two groups: control group (17 subjects) and experimental group (38 subjects). Patients in the control group received 70 g of sucrose daily for a maximum of 30 days and patients in the experimental group received 70 g of natural honey for the same period. In the control and experimental groups, body weight, body mass index, body fat weight, total cholesterol, LDL-C, HDL-C, triacylglycerole, FBG, and CRP were measured before treatment and at day 31 after the commencement of treatment. Results showed that honey caused a mild reduction in body weight (1.3%) and body fat (1.1%). Honey reduced total cholesterol (3%), LDL-C (5.8), triacylglycerole (11%), FBG (4.2%), and CRP (3.2%), and increased HDL-C (3.3%) in subjects with normal values, while in patients with elevated variables, honey caused reduction in total cholesterol by 3.3%, LDL-C by 4.3%, triacylglycerole by 19%, and CRP by 3.3% (p < 0.05). It is our conclusion that consumption of natural honey reduces cardiovascular risk factors, particularly in subjects with elevated risk factors, and it does not increase body weight in overweight or obese subjects.

Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review.

PubMed

Hunter, J Edward; Zhang, Jun; Kris-Etherton, Penny M

2010-01-01

High stearic acid (STA) soybean oil is a trans-free, oxidatively stable, non-LDL-cholesterol-raising oil that can be used to replace trans fatty acids (TFAs) in solid fat applications. The objective was to assess the cardiovascular health effects of dietary STA compared with those of trans, other saturated, and unsaturated fatty acids. We reviewed epidemiologic and clinical studies that evaluated the relation between STA and cardiovascular disease (CVD) risk factors, including plasma lipids and lipoproteins, hemostatic variables, and inflammatory markers. In comparison with other saturated fatty acids, STA lowered LDL cholesterol, was neutral with respect to HDL cholesterol, and directionally lowered the ratio of total to HDL cholesterol. STA tended to raise LDL cholesterol, lower HDL cholesterol, and increase the ratio of total to HDL cholesterol in comparison with unsaturated fatty acids. In 2 of 4 studies, high-STA diets increased lipoprotein(a) in comparison with diets high in saturated fatty acids. Three studies showed increased plasma fibrinogen when dietary STA exceeded 9% of energy (the current 90th percentile of intake is 3.5%). Replacing industrial TFAs with STA might increase STA intake from 3.0% (current) to approximately 4% of energy and from 4% to 5% of energy at the 90th percentile. One-to-one substitution of STA for TFAs showed a decrease or no effect on LDL cholesterol, an increase or no effect on HDL cholesterol, and a decrease in the ratio of total to HDL cholesterol. TFA intake should be reduced as much as possible because of its adverse effects on lipids and lipoproteins. The replacement of TFA with STA compared with other saturated fatty acids in foods that require solid fats beneficially affects LDL cholesterol, the primary target for CVD risk reduction; unsaturated fats are preferred for liquid fat applications. Research is needed to evaluate the effects of STA on emerging CVD risk markers such as fibrinogen and to understand the responses in different populations.

Meta-Analysis: Effects of Probiotic Supplementation on Lipid Profiles in Normal to Mildly Hypercholesterolemic Individuals.

PubMed

Shimizu, Mikiko; Hashiguchi, Masayuki; Shiga, Tsuyoshi; Tamura, Hiro-omi; Mochizuki, Mayumi

2015-01-01

Recent experimental and clinical studies have suggested that probiotic supplementation has beneficial effects on serum lipid profiles. However, there are conflicting results on the efficacy of probiotic preparations in reducing serum cholesterol. To evaluate the effects of probiotics on human serum lipid levels, we conducted a meta-analysis of interventional studies. Eligible reports were obtained by searches of electronic databases. We included randomized, controlled clinical trials comparing probiotic supplementation with placebo or no treatment (control). Statistical analysis was performed with Review Manager 5.3.3. Subanalyses were also performed. Eleven of 33 randomized clinical trials retrieved were eligible for inclusion in the meta-analysis. No participant had received any cholesterol-lowering agent. Probiotic interventions (including fermented milk products and probiotics) produced changes in total cholesterol (TC) (mean difference -0.17 mmol/L, 95% CI: -0.27 to -0.07 mmol/L) and low-density lipoprotein cholesterol (LDL-C) (mean difference -0.22 mmol/L, 95% CI: -0.30 to -0.13 mmol/L). High-density lipoprotein cholesterol and triglyceride levels did not differ significantly between probiotic and control groups. In subanalysis, long-term (> 4-week) probiotic intervention was statistically more effective in decreasing TC and LDL-C than short-term (≤ 4-week) intervention. The decreases in TC and LDL-C levels with probiotic intervention were greater in mildly hypercholesterolemic than in normocholesterolemic individuals. Both fermented milk product and probiotic preparations decreased TC and LDL-C levels. Gaio and the Lactobacillus acidophilus strain reduced TC and LDL-C levels to a greater extent than other bacterial strains. In conclusion, this meta-analysis showed that probiotic supplementation could be useful in the primary prevention of hypercholesterolemia and may lead to reductions in risk factors for cardiovascular disease.

Short-term ezetimibe is well tolerated and effective in combination with statin therapy to treat elevated LDL cholesterol in HIV-infected patients.

PubMed

Chow, Dominic; Chen, Huichao; Glesby, Marshall J; Busti, Anthony; Souza, Scott; Andersen, Janet; Kohrs, Sharon; Wu, Julia; Koletar, Susan L

2009-10-23

Ezetimibe inhibits intestinal absorption of cholesterol. Multicentered double-blind, randomized, placebo-controlled, crossover study to determine the short-term safety, efficacy, and tolerability of ezetimibe in combination with ongoing statin therapy in HIV-infected adults with elevated low-density lipoprotein cholesterol (LDL-C). Participants on stable HAART with fasting LDL-C at least 130 mg/dl and stable statin were randomized to ezetimibe 10 mg daily or placebo for 12 weeks followed by 4 weeks of washout and then 12 weeks with alternative study assignment. Percentage and absolute change in LDL-C (primary endpoint), total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), apolipoprotein B, and high sensitivity C-reactive protein were compared. Changes in clinical symptoms and safety laboratory measurements were assessed. Forty-four participants enrolled: 70% men, median age 49 years, 43% White/Non-Hispanic, median CD4 cell count 547 cells/microl, and 95% HIV RNA less than 50 copies/ml. Median (interquartile range) percentage change in LDL-C was -20.8% (-25.4, -10.7) with ezetimibe and -0.7% (-10.3,18.6) with placebo; the median within-participant effect of ezetimibe was -14.1% (-33.0, -5.0; P < 0.0001). Median difference in absolute LDL-C values between ezetimibe and placebo was -32 mg/dl (-58, -6, P < 0.0001). Significant differences in within-participant effect of ezetimibe were noted for total cholesterol -18.60% (-27.22, -11.67, P < 0.001), non-HDL-C -23.18% (-33.14, -14.36, P < 0.0001), and apolipoprotein B -8.73% (-18.75, 1.99, P = 0.02). No significant changes seen in HDL-C, triglyceride, or high sensitivity C-reactive protein. Ezetimibe was well tolerated. Adverse events were similar between phases. The present short-term study found adding ezetimibe to ongoing statin therapy was well tolerated and effective in reducing LDL-C, total cholesterol, non-HDL-C, and apolipoprotein B. Adding ezetimibe to statin therapy offers reasonable treatment option for HIV-infected patients with elevated LDL-C.

Apolipoprotein B antisense inhibition--update on mipomersen.

PubMed

Gebhard, Catherine; Huard, Gabriel; Kritikou, Ekaterini A; Tardif, Jean-Claude

2013-01-01

Dyslipidemia is one of the main risk factors leading to cardiovascular disease (CVD). The standard of therapy, administration of statins, in conjunction with lifestyle and habit changes, can improve high cholesterol levels in the majority of patients. However, some patients with familial hypercholesterolemia (FH) need low-density-lipoprotein cholesterol (LDL-C) apheresis, as the available medications fail to reduce LDL-C levels sufficiently even at maximum doses. Intense research on cholesterol reducing agents and rapid progress in drug design have yielded many approaches that reduce cholesterol absorption or inhibit its synthesis. Antisense oligonucleotides (ASOs) targeting the production of apolipoprotein B-100 (apoB-100), inhibitors of proprotein convertase subtilisin/kexin type 9, microsomal triglyceride transfer protein inhibitors, squalene synthase inhibitors, peroxisome proliferator-activated receptor agonists, and thyroid hormone receptor agonists are some of the evolving approaches for lipid-lowering therapies. We provide an overview of the apoB ASO approach and its potential role in the management of dyslipidemia. Mipomersen (ISIS-301012, KYNAMRO™) is a synthetic ASO targeting the mRNA of apoB-100, which is an essential component of LDL particles and related atherogenic lipoproteins. ASOs bind to target mRNAs and induce their degradation thereby resulting in reduced levels of the corresponding protein levels. Mipomersen has been investigated in different indications including homozygous and heterozygous FH, as well as in high-risk hypercholesterolemic patients. Recent phase II and III clinical studies have shown a 25-47% reduction in LDL-C levels in mipomersen-treated patients. If future studies continue to show such promising results, mipomersen would likely be a viable additional lipid-lowering therapy for high-risk populations.

Low-dose atorvastatin improves dyslipidemia and vascular function in patients with primary biliary cirrhosis after one year of treatment.

PubMed

Stojakovic, Tatjana; Claudel, Thierry; Putz-Bankuti, Csilla; Fauler, Günter; Scharnagl, Hubert; Wagner, Martin; Sourij, Harald; Stauber, Rudolf E; Winkler, Karl; März, Winfried; Wascher, Thomas C; Trauner, Michael

2010-03-01

Primary biliary cirrhosis (PBC) is frequently associated with hypercholesterolemia and with an increased cardiovascular morbidity and mortality. Statins lower serum cholesterol levels and may thus improve the cardiovascular risk in PBC patients. The aim of our study was to prospectively examine the efficacy of low-dose atorvastatin on cholestasis as well as cardiovascular risk markers such as dyslipidemia and vascular function in patients with PBC. Nineteen patients with early-stage (biopsy proven and AMA positive) PBC and low-density lipoprotein cholesterol (LDL-C) above 130mg/dL were included in this single-center study and treated with atorvastatin 10mg per day for one year. Concentrations of total cholesterol, LDL-C, LDL triglycerides, oxLDL, IgG and sVCAM-1 decreased significantly after 48 weeks of atorvastatin treatment. Flow-mediated dilation (FMD) of the brachial artery as an indicator of vascular function significantly increased, while carotid artery intima-media thickness and vascular wall stiffness did not progress under treatment. No statistical differences in liver enzymes were observed except a transient increase of alkaline phosphatase. Treatment with low-dose atorvastatin is safe in early-stage PBC, effectively reduces total cholesterol, LDL-C, LDL triglycerides, oxLDL and sVCAM-1 and improves vascular function as reflected by FMD, without affecting cholestasis progression. Therefore, statin therapy should be considered in PBC patients with additional risk factors for cardiovascular disease.

Effects of cumin extract on oxLDL, paraoxanase 1 activity, FBS, total cholesterol, triglycerides, HDL-C, LDL-C, Apo A1, and Apo B in in the patients with hypercholesterolemia

PubMed Central

Samani, Keihan Ghatreh; Farrokhi, Effat

2014-01-01

Objectives Paraoxanase 1 (PON1) plays a protective role against the oxidative modification of plasma lipoproteins and hydrolyzes lipid peroxides in human atherosclerotic lesions. Cumin is the dried seed of the herb Cuminumcyminum that is known as Zeera in Iran. Cumin seeds contain flavonoids which are now generally recognized to have antioxidant activity and improve the antioxidant system. So, they possibly modify PON1 activity and oxidized low density lipoprotein (oxLDL) level. The present study was aimed to evaluate the effects of cumin extract supplementation on oxLDL, paraoxanase 1 activity, FBS, total cholesterol, triglycerides, High density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B)in the patients with hypercholesterolemia. Methodology A fasting venous blood sample was obtained from the voluntary persons before and 45±3 days after taking cumin. Glucose, total cholesterol, and triglycerides were assayed using standard enzymatic procedures. HDL-Cand LDL-C were measured by direct method and ApoA1 and ApoB levels by immunoturbidimeteric methods. The levels of arylesterase and paraoxanase activities in the samples were measured by photometry methods and oxLDL by enzyme-linked immunosorbent assay (ELISA) method. 3 to 5 drops of cumin extract were added to the patient’s diet three times a day based on manufacturer’s instruction for 45±3 days. The biochemical parameters were compared before and after taking cumin. Data were analyzed using paired Student’s t-test in SPSS statistical software (version 11.5). Results The results demonstrated that there was a significant decrease in the level of oxLDL after receiving cumin. Paraoxonase and arylesterase activities increased in serum after taking cumin extract. Conclusion Based on the results, cumin reduces oxLDL level and increases both paraoxonase and arylesterase activity. PMID:24899878

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol.

PubMed

Ray, Kausik K; Landmesser, Ulf; Leiter, Lawrence A; Kallend, David; Dufour, Robert; Karakas, Mahir; Hall, Tim; Troquay, Roland P T; Turner, Traci; Visseren, Frank L J; Wijngaard, Peter; Wright, R Scott; Kastelein, John J P

2017-04-13

In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers. We conducted a phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial of inclisiran administered as a subcutaneous injection in patients at high risk for cardiovascular disease who had elevated LDL cholesterol levels. Patients were randomly assigned to receive a single dose of placebo or 200, 300, or 500 mg of inclisiran or two doses (at days 1 and 90) of placebo or 100, 200, or 300 mg of inclisiran. The primary end point was the change from baseline in LDL cholesterol level at 180 days. Safety data were available through day 210, and data on LDL cholesterol and proprotein convertase subtilisin-kexin type 9 (PCSK9) levels were available through day 240. A total of 501 patients underwent randomization. Patients who received inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels. At day 180, the least-squares mean reductions in LDL cholesterol levels were 27.9 to 41.9% after a single dose of inclisiran and 35.5 to 52.6% after two doses (P<0.001 for all comparisons vs. placebo). The two-dose 300-mg inclisiran regimen produced the greatest reduction in LDL cholesterol levels: 48% of the patients who received the regimen had an LDL cholesterol level below 50 mg per deciliter (1.3 mmol per liter) at day 180. At day 240, PCSK9 and LDL cholesterol levels remained significantly lower than at baseline in association with all inclisiran regimens. Serious adverse events occurred in 11% of the patients who received inclisiran and in 8% of the patients who received placebo. Injection-site reactions occurred in 5% of the patients who received injections of inclisiran. In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels. (Funded by the Medicines Company; ORION-1 ClinicalTrials.gov number, NCT02597127 .).

Non-high-density lipoprotein cholesterol vs low-density lipoprotein cholesterol as a risk factor for ischemic stroke: a result from the Kailuan study.

PubMed

Wu, Jianwei; Chen, Shengyun; Liu, Liping; Gao, Xiang; Zhou, Yong; Wang, Chunxue; Zhang, Qian; Wang, Anxin; Hussain, Mohammed; Sun, Baoying; Wu, Shouling; Zhao, Xingquan

2013-06-01

To compare the predictive value of serum low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol levels for ischemic stroke in the Chinese population. We performed a four-year cohort study of 95 778 men and women, aged 18-98 years, selected from the Kailuan study (2006-2007). Baseline LDL cholesterol levels were estimated using direct test method. Total cholesterol levels were estimated using endpoint test method. The predictive values of LDL cholesterol and non-HDL cholesterol for ischemic stroke were compared. During the follow-up period, there were 1153 incident cases of ischemic stroke. The hazard ratio (HR) for ischemic stroke in the top quintile of LDL cholesterol was the highest among five quintiles (HR: 1·25; 95% confidence interval (CI), 1·01-1·53). The HR in the top quintile of non-HDL cholesterol for ischemic stroke was also the highest among five quintiles (HR: 1·53; 95% CI, 1·24-1·88). Analysis of trends showed a significant positive relationship between ischemic stroke incidence and serum LDL cholesterol level, and non-HDL cholesterol level, respectively (both P < 0·05). The area under the curve of LDL cholesterol and non-HDL cholesterol for ischemic stroke was 0·51 and 0·56, respectively (P < 0·05 for the difference). Serum Non-HDL cholesterol level is a stronger predictor for the risk of ischemic stroke than serum LDL cholesterol level in the Chinese population.

[The real measurement of non-HDL-cholesterol: Atherogenic cholesterol].

PubMed

Millán, Jesús; Hernández-Mijares, Antonio; Ascaso, Juan F; Blasco, Mariano; Brea, Angel; Díaz, Ángel; González-Santos, Pedro; Mantilla, Teresa; Pedro-Botet, Juan; Pintó, Xavier

Lowe density lipoproteins (LDL) are the causal agent of cardiovascular diseases. In practice, we identify LDL with cholesterol transported in LDL (cLDL). So, cLDL has become the major target for cardiovascular prevention. Howewer, we have progressive evidences about the role of triglycerides rich lipoproteins, particularly those very low density lipoprotein (VLDL) in promotion and progression of atherosclerosis, that leads cholesterol in VLDL and its remanents as a potential therapeutic target. This feature is particularly important and of a great magnitude, in patients with hypertiglyceridemia. We can to considere, that the non-HDL cholesterol -cLDL+cVLDL+c-remmants+Lp(a)- is the real measurement of atherogenic cholesterol. In addition, non-HDL-cholesterol do not show any variations between postprandial states. In fact, non-HDL-cholesterol should be an excellent marker of atherogenic cholesterol, and an major therapeutic target in patients with atherogenic dyslipidaemia. According with different clinical trials and with the epidemiological and mendelian studies, in patients with high cardiovascular risk, optimal level of cLDL will be under 70mg/dl, and under 100 ng/dl for non-HDL-cholesterol; and in high risk patients, 100mg/dl and 130mg/dl, respectively. Copyright © 2016. Publicado por Elsevier España, S.L.U.

Cholesterol-lowering effects of modified animal fats in postmenopausal women.

PubMed

Labat, J B; Martini, M C; Carr, T P; Elhard, B M; Olson, B A; Bergmann, S D; Slavin, J L; Hayes, K C; Hassel, C A

1997-12-01

In an attempt to improve the nutritional value of animal fats (including milkfat and lard), two technological approaches (i.e., cholesterol removal by steam distillation and linoleic acid enrichment by addition of safflower oil) were tested for cholesterolemic effects in a cohort of 29 older women (age 68 +/- 7 years). Test fat sources were incorporated into crackers, cookies, cheese, ice cream, whipped topping, sour cream, baking shortening, and table spreads. Subjects were permanent residents of a convent where meals were prepared in a centralized kitchen, allowing test fats to be provided in daily food menu items. The foods containing test fats were introduced into three sequential dietary treatment periods, each lasting 4 weeks, in the following order: cholesterol-reduced animal fat (CRAF): fatty-acid modified, cholesterol-reduced animal fat (FAMCRAF); and-unaltered animal fat (AF). Subjects were offered menu items cafeteria style and encouraged to make food selections consistent with their habitual diets, which were recorded daily. Fasted blood lipid profiles determined at the end of each treatment period showed that FAMCRAF reduced mean plasma total cholesterol, LDL cholesterol, and apolipoprotein B concentrations relative to AF (p < 0.05). Mean HDL cholesterol concentrations were not influenced by diet. Relative to native products, animal fats modified by cholesterol removal and linoleic acid enrichment reduced plasma total and LDL cholesterol concentrations in a predictable manner similar to that based on studies of men.

Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes

PubMed Central

Kones, Richard

2013-01-01

Residual risk, the ongoing appreciable risk of major cardiovascular events (MCVE) in statin-treated patients who have achieved evidence-based lipid goals, remains a concern among cardiologists. Factors that contribute to this continuing risk are atherogenic non-low-density lipoprotein (LDL) particles and atherogenic processes unrelated to LDL cholesterol, including other risk factors, the inherent properties of statin drugs, and patient characteristics, ie, genetics and behaviors. In addition, providers, health care systems, the community, public policies, and the environment play a role. Major statin studies suggest an average 28% reduction in LDL cholesterol and a 31% reduction in relative risk, leaving a residual risk of about 69%. Incomplete reductions in risk, and failure to improve conditions that create risk, may result in ongoing progression of atherosclerosis, with new and recurring lesions in original and distant culprit sites, remodeling, arrhythmias, rehospitalizations, invasive procedures, and terminal disability. As a result, identification of additional agents to reduce residual risk, particularly administered together with statin drugs, has been an ongoing quest. The current model of atherosclerosis involves many steps during which disease may progress independently of guideline-defined elevations in LDL cholesterol. Differences in genetic responsiveness to statin therapy, differences in ability of the endothelium to regenerate and repair, and differences in susceptibility to nonlipid risk factors, such as tobacco smoking, hypertension, and molecular changes associated with obesity and diabetes, may all create residual risk. A large number of inflammatory and metabolic processes may also provide eventual therapeutic targets to lower residual risk. Classically, epidemiologic and other evidence suggested that raising high-density lipoprotein (HDL) cholesterol would be cardioprotective. When LDL cholesterol is aggressively lowered to targets, low HDL cholesterol levels are still inversely related to MCVE. The efflux capacity, or ability to relocate cholesterol out of macrophages, is believed to be a major antiatherogenic mechanism responsible for reduction in MCVE mediated in part by healthy HDL. HDL cholesterol is a complex molecule with antioxidative, anti-inflammatory, anti-thrombotic, antiplatelet, and vasodilatory properties, among which is protection of LDL from oxidation. HDL-associated paraoxonase-1 has a major effect on endothelial function. Further, HDL promotes endothelial repair and progenitor cell health, and supports production of nitric oxide. HDL from patients with cardiovascular disease, diabetes, and autoimmune disease may fail to protect or even become proinflammatory or pro-oxidant. Mendelian randomization and other clinical studies in which raising HDL cholesterol has not been beneficial suggest that high plasma levels do not necessarily reduce cardiovascular risk. These data, coupled with extensive preclinical information about the functional heterogeneity of HDL, challenge the “HDL hypothesis”, ie, raising HDL cholesterol per se will reduce MCVE. After the equivocal AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) study and withdrawal of two major cholesteryl ester transfer protein compounds, one for off-target adverse effects and the other for lack of efficacy, development continues for two other agents, ie, anacetrapib and evacetrapib, both of which lower LDL cholesterol substantially. The negative but controversial HPS2-THRIVE (the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) trial casts further doubt on the HDL cholesterol hypothesis. The growing impression that HDL functionality, rather than abundance, is clinically important is supported by experimental evidence highlighting the conditional pleiotropic actions of HDL. Non-HDL cholesterol reflects the cholesterol in all atherogenic particles containing apolipoprotein B, and has outperformed LDL cholesterol as a lipid marker of cardiovascular risk and future mortality. In addition to including a measure of residual risk, the advantages of using non-HDL cholesterol as a primary lipid target are now compelling. Reinterpretation of data from the Treating to New Targets study suggests that better control of smoking, body weight, hypertension, and diabetes will help lower residual risk. Although much improved, control of risk factors other than LDL cholesterol currently remains inadequate due to shortfalls in compliance with guidelines and poor patient adherence. More efficient and greater use of proven simple therapies, such as aspirin, beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, combined with statin therapy, may be more fruitful in improving outcomes than using other complex therapies. Comprehensive, intensive, multimechanistic, global, and national programs using primordial, primary, and secondary prevention to lower the total level of cardiovascular risk are necessary. PMID:24174878

Efficacy and safety of mipomersen sodium (Kynamro).

PubMed

Hovingh, Kees; Besseling, Joost; Kastelein, John

2013-07-01

Mipomersen is a first-in-class drug indicated as an adjunct to lipid-lowering medications and diet to reduce low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), total cholesterol (TC) and non-high density lipoprotein-cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). This article summarizes the efficacy and safety profile of mipomersen based on literature, public materials available from the Endocrinologic and Metabolic Drugs Advisory Committee meeting (FDA) in review of the New Drug Application (NDA 203568) and the recent product label. Patients suffering from HoFH are characterized by elevated levels of LDL-C and are, therefore, at severely increased risk for cardiovascular disease (CVD). Currently available lipid-lowering therapies (LLT), such as statins, have been shown to lower LDL-C levels and CVD risk. However, in patients suffering from HoFH, additional therapy is urgently needed to further decrease LDL-C levels and CVD risk. Mipomersen (Kynamro) has recently been approved by the FDA as a novel LLT modality in patients with HoFH. Mipomersen has been show to result in highly relevant absolute LDL-C reductions in HoFH patients, and given the undisputed causal relationship between LDL-C levels and CVD risk, this additional LDL-C lowering is expected to result in a robust CVD risk reduction.

Cameroonian professional soccer players and risk of atherosclerosis.

PubMed

Nansseu, Jobert Richie; Ama Moor, Vicky Jocelyne; Takam, Ruth Danielle M; Zing-Awona, Bertrand; Azabji-Kenfack, Marcel; Tankeu, Francine; Tchoula, Corinne M; Moukette, Bruno M; Ngogang, Jeanne Y

2017-06-02

Elevated titers of antibodies against oxidized low-density lipoproteins-cholesterol (ox-LDL-Ab) have been reported among professional athletes, paradoxically reflecting an increased risk of developing atherogenic and/or cardiovascular events. This study aimed to determine titers of ox-LDL-Ab in a group of Cameroonian professional soccer players, and evaluate their evolution during part of a competition season as well as the plasmatic antioxidant status to find out if this latter correlates with ox-LDL-Ab . We conducted a descriptive cohort study in 2012 including 18 healthy male soccer players. Three samplings were performed in March (T1), May (T2), and July 2012 (T3) to assess the lipid profile, titers of ox-LDL-Ab, and plasmatic concentrations of four antioxidants: the ferric reducing antioxidant power (FRAP), reduced glutathione (GSH), superoxide dismutase (SOD), and uric acid. Ages ranged from 16 to 28 years with a median (interquartile range) of 19.5 (19-23) years. Total cholesterol, high-density lipoproteins-cholesterol (HDL-C), low-density lipoproteins-cholesterol (LDL-C) and triglycerides varied within normal ranges throughout the three samplings. While total cholesterol and LDL-C titers increased significantly (p = 0.003 and p = 0.006, respectively), triglycerides and HDL-C values varied non-significantly throughout the measurements (p = 0.061 and p = 0.192, respectively). The median ox-LDL-Ab titers were respectively: 653.3 (468.2-838.8) mIU/ml at T1, 777.7 (553.7-1150.7) mIU/ml at T2, and 1037.7 (901.7-1481.5) mIU/ml at T3. Overall, ox-LDL-Ab titers increased significantly from T1 to T3 (p = 0.006). Concomitantly, uric acid and FRAP concentrations decreased significantly (p = 0.001 and p = 0.003, respectively); on the contrary, GSH and SOD values increased, but insignificantly (p = 0.115 and p = 0.110, respectively). There was a positive and significant correlation between ox-LDL-Ab and HDL-C (ρ = 0.519, p = 0.027), and between ox-LDL-Ab and SOD (ρ = 0.504, p = 0.033) at T2. Ox-LDL-Ab values were expected to increase with each new visit (β = 201.1; p = 0.041) and each IU/ml of SOD titers (β = 23.6; p = 0.019). These Cameroonian professional soccer players exhibited high levels of ox-LDL-Ab reflecting elevated levels of oxidatively-modified LDL-C particles with an increment over time, this being insufficiently counterbalanced by the antioxidant defense mechanisms. As a consequence, they may be at increased atherogenic and cardiovascular risks.

Bergamot Reduces Plasma Lipids, Atherogenic Small Dense LDL, and Subclinical Atherosclerosis in Subjects with Moderate Hypercholesterolemia: A 6 Months Prospective Study.

PubMed

Toth, Peter P; Patti, Angelo M; Nikolic, Dragana; Giglio, Rosaria V; Castellino, Giuseppa; Biancucci, Teresa; Geraci, Fabiana; David, Sabrina; Montalto, Giuseppe; Rizvi, Ali; Rizzo, Manfredi

2015-01-01

Some patients experience statin-induced side effects or prefer nutraceutical approaches for the treatment of dyslipidemia. This has led to a search for alternative therapeutic approaches for dyslipidemia management. In recent studies Citrus bergamia (known as Bergamot) juice was able to reduce serum levels of lipids. Such benefit may be attributed to high amounts of flavonoids contained in Bergamot fruit juice (neoeriocitrin, neohesperidin, naringin). The aim of the present study was to fully investigate the effects of a Bergamot extract on cardio-metabolic parameters, including plasma lipids, atherogenic lipoproteins and subclinical atherosclerosis. Eighty subjects (42 men and 38 women, mean age: 55 ± 13 years) with moderate hypercholesterolemia [e.g., with plasma LDL-cholesterol concentrations between 160 and 190 mg/dl (between 4.1 and 4.9 mmol/l)] were included. A Bergamot-derived extract (Bergavit R(®)) was given at a fixed dose daily (150 mg of flavonoids, with 16% of neoeriocitrin, 47% of neohesperidin and 37% of naringin) for 6 months. Lipoprotein subfractions were assessed by gel electrophoresis. With this methodology low density lipoprotein (LDL) subclasses are distributed as seven bands (LDL-1 and -2 as large LDL, and LDL-3 to -7 as atherogenic small, dense LDL). Subclinical atherosclerosis was assessed by carotid intima-media thickness (cIMT) using B-mode ultrasound. After 6 months, Bergavit R(®) reduced total cholesterol (from 6.6 ± 0.4 to 5.8 ± 1.1 mmol/l, p < 0.0001), triglycerides (from 1.8 ± 0.6 to 1.5 ± 0.9 mmol/l, p = 0.0020), and LDL-cholesterol (from 4.6 ± 0.2 to 3.7 ± 1.0 mmol/l, p < 0.0001), while HDL- cholesterol increased (from 1.3 ± 0.2 to 1.4 ± 0.4 mmol/l, p < 0.0007). In addition, a significant increase in LDL-1 (from 41.2 ± 0.2 to 49.6 ± 0.2%, p < 0.0001) was accompanied by decreased small, dense LDL-3, -4, and 5 particles (from 14.5 ± 0.1 to 9.0 ± 0.1% p < 0.0001; 3.2 ± 0.1 to 1.5 ± 0.1% p = 0.0053; 0.3 ± 0.0% to 0.1 ± 0.0% p = 0.0133, respectively). cIMT also decreased from 1.2 ± 0.4 to 0.9 ± 0.1 mm (p < 0.0001). This is the first study investigating the effects of Bergamot flavonoids supplementation on cardio-metabolic risk in dyslipidemic subjects. Bergavit R(®) (Bergamot juice extract) supplementation significantly reduced plasma lipids and improved the lipoprotein profile. cIMT was also reduced significantly over a relatively short time frame of 6 months.

Hypolipidemic effect of MeOH extract of Bambusae Caulis in Taeniam in hyperlipidemia induced by Triton WR-1339 and high cholesterol diet in rats.

PubMed

Ham, Inhye; Yang, Gabsik; Lee, Jaejun; Lee, Kyung-Jin; Choi, Ho-Young

2009-01-01

Hyperlipidemia has been implicated in atherosclerosis which is the leading cause of death among world population and resulting from lipid metabolic changes is a major cause of atherosclerosis. Bambusae Caulis in Taeniam belongs to Bambusaceae is the stem of Phyllostachys nigra (Lodd.) Munro var. henonis (Bean) Stapf of Phyllostachys bambusoides Siebold et Zuccarini, the perennial evergreen tree. The green middle layer of stem is dried in string-shape I shadow after the bark had been removed. In this study, the effects of middle layer of PN, PB, PP, and BCT on rat with hyperlipidemia, induced by Triton WR-1339 and high cholesterol diet were investigated. We measured plasma levels of triglyceride, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol as measure of its hyperlipidemic effects. As a result, all of the Bambusae Caulis in Taeniam was reduced total cholesterol, LDL. Inhibition rate on LDL-oxidation, hACAT-1, and hACAT-2 was increased dose-dependently. Therefore all of the Bambusae Caulis in Taeniam is a good candidate for the treatment on Triton WR-1339 and high cholesterol diet-induced blood circulatory disorders, obesity, and hyperlipidemia.

Proanthocyanidin-rich extract from grape seeds attenuates the development of aortic atherosclerosis in cholesterol-fed rabbits.

PubMed

Yamakoshi, J; Kataoka, S; Koga, T; Ariga, T

1999-01-01

The aim of this study was to evaluate the antiatherosclerotic effect of proanthocyanidin-rich extracts from grape seeds in cholesterol-fed rabbits. Proanthocyanidin-rich extracts (0.1% and 1% in diets [w/w]) did not appreciably affect the changes in serum lipid profile of cholesterol-fed rabbits. The level of cholesteryl ester hydroperoxides (ChE-OOH) induced by 2,2'-azobis(2-amidinopropane-dihydrochloride (AAPH) were lower in the plasma of rabbits fed proanthocyanidin-rich extract plus cholesterol than in the plasma of rabbits fed cholesterol alone, but not in the low-density lipoprotein (LDL). Aortic malondialdehyde (MDA) content decreased in rabbits fed proanthocyanidin-rich extract. Feeding proanthocyanidin-rich extracts (0.1 and 1% in the diet) to rabbits significantly reduced severe atherosclerosis in the aorta. Immunohistochemical analysis revealed a decrease in the number of oxidized LDL-positive macrophage-derived foam cells in atherosclerotic lesions in the aorta of rabbits fed proanthocyanidin-rich extract. When proanthocyanidin-rich extract was administered orally to rats, proanthocyanidin was detected in the plasma by Porters method but not in the lipoproteins (LDL plus VLDL). In an in vitro experiment using human plasma, proanthocyanidin-rich extract added to the plasma inhibited the oxidation of cholesteryl linoleate in LDL, but not in the LDL isolated after the plasma and the extract were incubated in advance. These results suggested that proanthocyanidins, the major polyphenols in red wine, might trap reactive oxygen species in aqueous series such as plasma and interstitial fluid of the arterial wall, thereby inhibiting oxidation of LDL and showing an antiatherosclerotic activity.

Effects of an anti-oxidative ACAT inhibitor on apoptosis/necrosis and cholesterol accumulation under oxidative stress in THP-1 cell-derived foam cells.

PubMed

Miike, Tomohiro; Shirahase, Hiroaki; Jino, Hiroshi; Kunishiro, Kazuyoshi; Kanda, Mamoru; Kurahashi, Kazuyoshi

2008-01-02

THP-1 cell-derived foam cells were exposed to oxidative stress through combined treatment with acetylated LDL (acLDL) and copper ions (Cu2+). The foam cells showed caspase-dependent apoptotic changes on exposure to oxidative stress for 6 h, and necrotic changes with the leakage of LDH after 24 h. KY-455, an anti-oxidative ACAT inhibitor, and ascorbic acid (VC) but not YM-750, an ACAT inhibitor, prevented apoptotic and necrotic changes. These preventive effects of KY-455 and VC were accompanied by the inhibition of lipid peroxidation in culture medium containing acLDL and Cu2+, suggesting the involvement of oxidized acLDL in apoptosis and necrosis. Foam cells accumulated esterified cholesterol (EC) for 24 h in the presence of acLDL without Cu2+, which was suppressed by KY-455 and YM-750. Foam cells showed necrotic changes and died in the presence of acLDL and Cu2+. KY-455 but not YM-750 prevented cell death and reduced the amount of EC accumulated. The foam cells treated with VC further accumulated EC without necrotic changes for 24 h even in the presence of acLDL and Cu2+. YM-750 as well as KY-455 inhibited lipid accumulation when co-incubated with VC in foam cells exposed to oxidative stress. It is concluded that an anti-oxidative ACAT inhibitor or the combination of an antioxidant and an ACAT inhibitor protects foam cells from oxidative stress and effectively reduces cholesterol levels, which would be a promising approach in anti-atherosclerotic therapy.

Familial Hypercholesterolemia

PubMed Central

Bouhairie, Victoria Enchia; Goldberg, Anne Carol

2015-01-01

Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen and LDL apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with FH. It is important to increase awareness of this disorder in physicians and patients in order to reduce the burden of this disorder. PMID:25939291

Effect of Euterpe oleracea Mart. (Açaí) Oil on Dyslipidemia Caused by Cocos nucifera L. Saturated Fat in Wistar Rats.

PubMed

Faria E Souza, Belmira S; Carvalho, Helison O; Taglialegna, Talisson; Barros, Albenise Santana A; da Cunha, Edilson Leal; Ferreira, Irlon Maciel; Keita, Hady; Navarrete, Andres; Carvalho, José Carlos Tavares

2017-09-01

Dyslipidemia is caused by disturbances in lipid metabolism that lead to chronic elevations of serum lipids, especially low-density lipoprotein (LDL)-cholesterol and triglycerides, increasing the risk of metabolic syndrome, obesity, diabetes, atherogenic processes, and cardiovascular diseases. The oil from the fruits of Euterpe oleracea (OFEO) is rich in unsaturated fatty acids with potential for treating alterations in lipid metabolism. In this study, we aimed to investigate the effect of OFEO on hyperlipidemia induced by Cocos nucifera L. saturated fat (GSC) in Wistar rats. Chromatographic profile showed that unsaturated fatty acids account for 66.08% in OFEO, predominately oleic acid (54.30%), and saturated fatty acids (palmitic acid 31.6%) account for 33.92%. GSC-induced dyslipidemia resulted in an increase in total cholesterol, LDL-cholesterol, triglycerides, glucose, and liver and abdominal fat, as well as atherogenic processes in the thoracic aorta. OFEO treatment did not reduce hypertriglyceridemia, but did reduce total cholesterol and LDL-cholesterol, thus contributing to the antiatherogenic action of OFEO. OFEO treatment inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats, as well as those who were treated with simvastatin. The results obtained suggest that OFEO has an antiatherogenic effect in a rat model of dyslipidemia.

Effect of Vaccinium bracteatum Thunb. leaves extract on blood glucose and plasma lipid levels in streptozotocin-induced diabetic mice.

PubMed

Wang, Li; Zhang, Xue Tong; Zhang, Hai Yan; Yao, Hui Yuan; Zhang, Hui

2010-08-09

To investigate the hypoglycemic effects of Vaccinium bracteatum Thunb. leaves (VBTL) extract in streptozotocin-induced diabetic mice. After administration of VBTL extract for 4 weeks, the body weight, organ weight, blood glucose (BG), insulin and plasma lipid levels of streptozotocin-induced diabetic mice were measured. Body weights of diabetic mice treated with VBTL extract were partly recovered. The BG levels of AEG (diabetic mice treated with VBTL aqueous extract) were reduced to 91.52 and 85.82% at week 2 and week 4, respectively (P<0.05), while those of EEG (diabetic mice treated with VBTL ethanolic extract) were reduced slightly (P>0.05). The insulin levels of AEG and EEG were obviously higher (P<0.05) than those of MC (diabetic mice in model control group). Comparing with MC, AEG and EEG had significantly lower (P<0.05) TC or TG levels and similar HDL-cholesterol or LDL-cholesterol levels. In comparison with non-diabetic control mice, AEG had similar plasma lipid levels except higher LDL-cholesterol level, while EEG had higher TC, TG and LDL-cholesterol levels and lower HDL-cholesterol levels. Both aqueous and ethanolic extract of VBTL possess a potential hypoglycemic effect in streptozotocin-induced diabetic mice. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Effect of mipomersen on LDL-cholesterol in patients with severe LDL-hypercholesterolaemia and atherosclerosis treated by lipoprotein apheresis (The MICA-Study).

PubMed

Waldmann, Elisa; Vogt, Anja; Crispin, Alexander; Altenhofer, Julia; Riks, Ina; Parhofer, Klaus G

2017-04-01

In this study, we evaluated the effect of mipomersen in patients with severe LDL-hypercholesterolaemia and atherosclerosis, treated by lipid lowering drugs and regular lipoprotein apheresis. This prospective, randomized, controlled phase II single center trial enrolled 15 patients (9 males, 6 females; 59 ± 9 y, BMI 27 ± 4 kg/m 2 ) with established atherosclerosis, LDL-cholesterol ≥130 mg/dL (3.4 mmol/L) despite maximal possible drug therapy, and fulfilling German criteria for regular lipoprotein apheresis. All patients were on stable lipid lowering drug therapy and regular apheresis for >3 months. Patients randomized to treatment (n = 11) self-injected mipomersen 200 mg sc weekly, at day 4 after apheresis, for 26 weeks. Patients randomized to control (n = 4) continued apheresis without injection. The primary endpoint was the change in pre-apheresis LDL-cholesterol. Of the patients randomized to mipomersen, 3 discontinued the drug early (<12 weeks therapy) for side effects. For these, another 3 were recruited and randomized. Further, 4 patients discontinued mipomersen between 12 and 26 weeks for side effects (moderate to severe injection site reactions n = 3 and elevated liver enzymes n = 1). In those treated for >12 weeks, mipomersen reduced pre-apheresis LDL-cholesterol significantly by 22.6 ± 17.0%, from a baseline of 4.8 ± 1.2 mmol/L to 3.7 ± 0.9 mmol/L, while there was no significant change in the control group (+1.6 ± 9.3%), with the difference between the groups being significant (p=0.02). Mipomersen also decreased pre-apheresis lipoprotein(a) (Lp(a)) concentration from a median baseline of 40.2 mg/dL (32.5,71) by 16% (-19.4,13.6), though without significance (p=0.21). Mipomersen reduces LDL-cholesterol (significantly) and Lp(a) (non-significantly) in patients on maximal lipid-lowering drug therapy and regular apheresis, but is often associated with side effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial.

PubMed

Fitzgerald, Kevin; Frank-Kamenetsky, Maria; Shulga-Morskaya, Svetlana; Liebow, Abigail; Bettencourt, Brian R; Sutherland, Jessica E; Hutabarat, Renta M; Clausen, Valerie A; Karsten, Verena; Cehelsky, Jeffrey; Nochur, Saraswathy V; Kotelianski, Victor; Horton, Jay; Mant, Timothy; Chiesa, Joseph; Ritter, James; Munisamy, Malathy; Vaishnaw, Akshay K; Gollob, Jared A; Simon, Amy

2014-01-04

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to LDL receptors, leading to their degradation. Genetics studies have shown that loss-of-function mutations in PCSK9 result in reduced plasma LDL cholesterol and decreased risk of coronary heart disease. We aimed to investigate the safety and efficacy of ALN-PCS, a small interfering RNA that inhibits PCSK9 synthesis, in healthy volunteers with raised cholesterol who were not on lipid-lowering treatment. We did a randomised, single-blind, placebo-controlled, phase 1 dose-escalation study in healthy adult volunteers with serum LDL cholesterol of 3·00 mmol/L or higher. Participants were randomly assigned in a 3:1 ratio by computer algorithm to receive one dose of intravenous ALN-PCS (with doses ranging from 0·015 to 0·400 mg/kg) or placebo. The primary endpoint was safety and tolerability of ALN-PCS. Secondary endpoints were the pharmacokinetic characteristics of ALN-PCS and its pharmacodynamic effects on PCSK9 and LDL cholesterol. Study participants were masked to treatment assignment. Analysis was per protocol and we used ANCOVA to analyse pharmacodynamic endpoint data. This trial is registered with ClinicalTrials.gov, number NCT01437059. Of 32 participants, 24 were randomly allocated to receive a single dose of ALN-PCS (0·015 mg/kg [n=3], 0·045 mg/kg [n=3], 0·090 mg/kg [n=3], 0·150 mg/kg [n=3], 0·250 mg/kg [n=6], or 0·400 mg/kg [n=6]) and eight to placebo. The proportions of patients affected by treatment-emergent adverse events were similar in the ALN-PCS and placebo groups (19 [79%] vs seven [88%]). ALN-PCS was rapidly distributed, with peak concentration and area under the curve (0 to last measurement) increasing in a roughly dose-proportional way across the dose range tested. In the group given 0·400 mg/kg of ALN-PCS, treatment resulted in a mean 70% reduction in circulating PCSK9 plasma protein (p<0·0001) and a mean 40% reduction in LDL cholesterol from baseline relative to placebo (p<0·0001). Our results suggest that inhibition of PCSK9 synthesis by RNA interference (RNAi) provides a potentially safe mechanism to reduce LDL cholesterol concentration in healthy individuals with raised cholesterol. These results support the further assessment of ALN-PCS in patients with hypercholesterolaemia, including those being treated with statins. This study is the first to show an RNAi drug being used to affect a clinically validated endpoint (ie, LDL cholesterol) in human beings. Alnylam Pharmaceuticals. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Rational therapy of patients with essential hypertension and abdominal obesity with concomitant subclinical hypothyroidism].

PubMed

Pligovka, V M

2014-11-01

It was determined the characteristics of lipid status of patients with essential hypertension, abdominal obesity with concomitant subclinical hypothyroidism--mostly increased levels of total and LDL cholesterol. In assessing the effectiveness of statin therapy in combination with levothyroxine replacement therapy compared with statin monotherapy, combination therapy showed the best result in terms of achievement of target levels of both total cholesterol and LDL. The obtained results allow us to recommend the use of combination therapy for patients with hypertension, abdominal obesity with concomitant subclinical hypothyroidism in order to achieve the target values of LDL and thus to reduce the cardiovascular risk of these patients.

Successful treatment of homozygous familial hypercholesterolemia using cascade filtration plasmapheresis.

PubMed

Kardaş, Fatih; Cetin, Aysun; Solmaz, Musa; Büyükoğlan, Rüksan; Kaynar, Leylagül; Kendirci, Mustafa; Eser, Bülent; Unal, Ali

2012-12-01

The aim of this study was to report the efficacy of low-density lipoprotein cholesterol (LDL-C) apheresisusing a cascade filtration system in pediatric patients with homozygous familial hypercholesterolemia (FH), and toclarify the associated adverse effects and difficulties. LDL-C apheresis using a cascade filtration system was performed in 3 pediatric patientswith homozygous FH; in total, 120 apheresis sessions were performed. Cascade filtration therapy significantly reduced the mean LDL-C values from 418 ± 62 mg/dL to 145 ± 43 mg/dL (p= 0.011). We observed an acute mean reduction in the plasma level of total cholesterol (57.9%), LDL-C (70.8%),and high-density lipoprotein cholesterol (HDL-C) (40.7%). Treatments were well tolerated. The most frequent clinicaladverse effects were hypotension in 3 sessions (2.5%), chills (1.7%) in 2 sessions, and nausea/vomiting in 3 sessions(2.5%). Our experience using the cascade filtration system with 3 patients included good clinical outcomes andlaboratory findings, safe usage, and minor adverse effects and technical problems. None declared.

High doses of garlic extract significantly attenuated the ratio of serum LDL to HDL level in rat-fed with hypercholesterolemia diet.

PubMed

Ebrahimi, Tahereh; Behdad, Behnoosh; Abbasi, Maryam Agha; Rabati, Rahman Ghaffarzadegan; Fayyaz, Amir Farshid; Behnod, Vahid; Asgari, Ali

2015-06-20

Hypercholesterolemia is associated with an increased risk of heart disease. In this study, we investigated the antihyperlipidemic effects of garlic (Allium sativum L.) in rat models of hypercholesterolemic. Wistar male rats were randomly divided into 4 diet groups with garlic supplementation. Male Wistar rats were fed by standard pellet diet (group I), standard diet supplemented with 4% garlic (group II), lipogenic diet (containing sunflower oil, cholesterol and ethanol) equivalent to 200 mg raw garlic/kg body weight (raw) (group III) and lipogenic diet equivalent to 400 mg raw garlic/kg body weight (raw) (group IV). Rats fed 400 g/kg garlic extract(GE), had a significantly lower concentration of serum low-density lipoprotein cholesterol (LDL-C) cholesterol and elevated HDL -C cholesterol at day 28 (P < 0.05).In addition,serum levels of LDL-C was lower in the III and IV group than those in the IV group (P < 0.001 for each). However, cholesterol efflux capacity was positively correlated with HDL cholesterol concentration (P < 0 · 0001). It was also directly correlated with garlic supplementation (P < 0 · 0001). Together Taken, the results are clearly indicative of the beneficial effects of garlic in reducing lateral side effects of hyperlipidemia. Our data demonstrate that GE has protective effects on HDL in rats with high LDL intake. Therefore, it could be used to remedy hypercholesterolemia with help reduce risk of coronary heart disease The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1834155749171141.

HDL: The "Good" Cholesterol

MedlinePlus

... and LDL (bad) cholesterol: HDL stands for high-density lipoproteins. It is called the "good" cholesterol because ... cholesterol from your body. LDL stands for low-density lipoproteins. It is called the "bad" cholesterol because ...

LDL: The "Bad" Cholesterol

MedlinePlus

... and HDL (good) cholesterol: LDL stands for low-density lipoproteins. It is called the "bad" cholesterol because ... cholesterol in your arteries. HDL stands for high-density lipoproteins. It is called the "good" cholesterol because ...

Synergetic cholesterol-lowering effects of main alkaloids from Rhizoma Coptidis in HepG2 cells and hypercholesterolemia hamsters.

PubMed

Kou, Shuming; Han, Bing; Wang, Yue; Huang, Tao; He, Kai; Han, Yulong; Zhou, Xia; Ye, Xiaoli; Li, Xuegang

2016-04-15

Hyperlipidemia contributes to the progression of cardiovascular diseases. Main alkaloids from Rhizoma Coptidis including berberine (BBR), coptisine (COP), palmatine (PAL), epiberberine (EPI) and jatrorrhizine (JAT), improved dyslipidemia in hypercholesterolemic hamsters to a different degree. In this study, HepG2 cells and hypercholesterolemic hamsters were used to investigate the synergetic cholesterol-lowering efficacy of these five main alkaloids. The cellular lipid and cholesterol accumulation and in HepG2 cells were evaluated by Oil Red O staining and HPLC analysis. LDL receptor, 3-Hydroxy-3-methylglutaryl CoA reductase (HMGCR) and cholesterol 7-alpha-hydroxylase (CYP7A1) that involving cholesterol metabolism in HepG2 cells were measured by qRT-PCR, western blot and immunofluorescence analysis. The serum profiles including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c), as well as TC and total bile acids (TBA) of feces in hypercholesterolemic hamsters were also measured. As compared to single alkaloids, the combination of five main alkaloids (COM) reduced the lipid and cholesterol accumulation in HepG2 cells more effectively and performed an advantageous effect on controlling TC, TG, LDL-c and HDL-c in hypercholesterolemic hamsters. More effective reduction of TBA and TC levels in feces of hamsters were achieved after the administration of COM. These effects were derived from the up-regulation of LDL receptor and CYP7A1, as well as HMGCR downregulation. Our results demonstrated that COM showed a synergetic cholesterol-lowering efficacy, which was better than single alkaloids and it might be considered as a potential therapy for hypercholesterolemia. Copyright © 2016 Elsevier Inc. All rights reserved.

HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial.

PubMed

Ridker, Paul M; Genest, Jacques; Boekholdt, S Matthijs; Libby, Peter; Gotto, Antonio M; Nordestgaard, Børge G; Mora, Samia; MacFadyen, Jean G; Glynn, Robert J; Kastelein, John J P

2010-07-31

HDL-cholesterol concentrations are inversely associated with occurrence of cardiovascular events. We addressed, using the JUPITER trial cohort, whether this association remains when LDL-cholesterol concentrations are reduced to the very low ranges with high-dose statin treatment. Participants in the randomised placebo-controlled JUPITER trial were adults without diabetes or previous cardiovascular disease, and had baseline concentrations of LDL cholesterol of less than 3.37 mmol/L and high-sensitivity C-reactive protein of 2 mg/L or more. Participants were randomly allocated by a computer-generated sequence to receive rosuvastatin 20 mg per day or placebo, with participants and adjudicators masked to treatment assignment. In the present analysis, we divided the participants into quartiles of HDL-cholesterol or apolipoprotein A1 and sought evidence of association between these quartiles and the JUPITER primary endpoint of first non-fatal myocardial infarction or stroke, hospitalisation for unstable angina, arterial revascularisation, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT00239681. For 17,802 patients in the JUPITER trial, rosuvastatin 20 mg per day reduced the incidence of the primary endpoint by 44% (p<0.0001). In 8901 (50%) patients given placebo (who had a median on-treatment LDL-cholesterol concentration of 2.80 mmol/L [IQR 2.43-3.24]), HDL-cholesterol concentrations were inversely related to vascular risk both at baseline (top quartile vs bottom quartile hazard ratio [HR] 0.54, 95% CI 0.35-0.83, p=0.0039) and on-treatment (0.55, 0.35-0.87, p=0.0047). By contrast, among the 8900 (50%) patients given rosuvastatin 20 mg (who had a median on-treatment LDL-cholesterol concentration of 1.42 mmol/L [IQR 1.14-1.86]), no significant relationships were noted between quartiles of HDL-cholesterol concentration and vascular risk either at baseline (1.12, 0.62-2.03, p=0.82) or on-treatment (1.03, 0.57-1.87, p=0.97). Our analyses for apolipoprotein A1 showed an equivalent strong relation to frequency of primary outcomes in the placebo group but little association in the rosuvastatin group. Although measurement of HDL-cholesterol concentration is useful as part of initial cardiovascular risk assessment, HDL-cholesterol concentrations are not predictive of residual vascular risk among patients treated with potent statin therapy who attain very low concentrations of LDL cholesterol. AstraZeneca. Copyright 2010 Elsevier Ltd. All rights reserved.

Acidic Polysaccharide Extracts from Gastrodia Rhizomes Suppress the Atherosclerosis Risk Index through Inhibition of the Serum Cholesterol Composition in Sprague Dawley Rats Fed a High-Fat Diet

PubMed Central

Kim, Kui-Jin; Lee, Ok-Hwan; Han, Chan-Kyu; Kim, Young-Chan; Hong, Hee-Do

2012-01-01

Obesity is associated with a broad spectrum of cardio-metabolic disturbances, including atherosclerosis and cardiovascular disease (CDV). A high-fat diet has been shown to cause an elevation of the plasma cholesterol levels in humans, and the control of serum cholesterol has been demonstrated to be important in the prevention of CVD and atherosclerosis. The aims of this study were to demonstrate that crude and acidic polysaccharide extracts from Gastrodia rhizomes suppress atherosclerosis through the regulation of serum lipids in Sprague Dawley (SD) rats fed a high-fat diet. We examined the concentrations of serum lipids, including total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, and low-density lipoproteins (LDL) cholesterol, in SD rats fed a high-fat diet and evaluated the atherogenic index. Here, we show that both crude and acidic polysaccharide extracts from Gastrodia rhizomes inhibited the total cholesterol and LDL levels. Moreover, there was a significantly suppressed atherosclerosis risk due to the acidic polysaccharide extract from Gastrodia rhizome. Taken together, our results suggested that acidic polysaccharide extracts from Gastrodia rhizomes might be beneficial for lowering the incidence of CVD and atherosclerosis by reducing the de novo synthesis of total cholesterol and the LDL levels. PMID:22408412

Acidic polysaccharide extracts from Gastrodia Rhizomes suppress the atherosclerosis risk index through inhibition of the serum cholesterol composition in Sprague Dawley rats fed a high-fat diet.

PubMed

Kim, Kui-Jin; Lee, Ok-Hwan; Han, Chan-Kyu; Kim, Young-Chan; Hong, Hee-Do

2012-01-01

Obesity is associated with a broad spectrum of cardio-metabolic disturbances, including atherosclerosis and cardiovascular disease (CDV). A high-fat diet has been shown to cause an elevation of the plasma cholesterol levels in humans, and the control of serum cholesterol has been demonstrated to be important in the prevention of CVD and atherosclerosis. The aims of this study were to demonstrate that crude and acidic polysaccharide extracts from Gastrodia rhizomes suppress atherosclerosis through the regulation of serum lipids in Sprague Dawley (SD) rats fed a high-fat diet. We examined the concentrations of serum lipids, including total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, and low-density lipoproteins (LDL) cholesterol, in SD rats fed a high-fat diet and evaluated the atherogenic index. Here, we show that both crude and acidic polysaccharide extracts from Gastrodia rhizomes inhibited the total cholesterol and LDL levels. Moreover, there was a significantly suppressed atherosclerosis risk due to the acidic polysaccharide extract from Gastrodia rhizome. Taken together, our results suggested that acidic polysaccharide extracts from Gastrodia rhizomes might be beneficial for lowering the incidence of CVD and atherosclerosis by reducing the de novo synthesis of total cholesterol and the LDL levels.

L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice.

PubMed

Aji, W; Ravalli, S; Szabolcs, M; Jiang, X C; Sciacca, R R; Michler, R E; Cannon, P J

1997-01-21

The potential antiatherosclerotic actions of NO were investigated in four groups of mice (n = 10 per group) lacking functional LDL receptor genes, an animal model of familial hypercholesterolemia. Group 1 was fed a regular chow diet. Groups 2 through 4 were fed a 1.25% high-cholesterol diet. In addition, group 3 received supplemental L-arginine and group 4 received L-arginine and N omega-nitro-L-arginine (L-NA), an inhibitor of NO synthase (NOS). Animals were killed at 6 months; aortas were stained with oil red O for planimetry and with antibodies against constitutive and inducible NOSs. Plasma cholesterol was markedly increased in the animals receiving the high-cholesterol diet. Xanthomas appeared in all mice fed the high-cholesterol diet alone but not in those receiving L-arginine. Aortic atherosclerosis was present in all mice on the high-cholesterol diet. The mean atherosclerotic lesion area was reduced significantly (P < .01) in the cholesterol-fed mice given L-arginine compared with those receiving the high-cholesterol diet alone. The mean atherosclerotic lesion area was significantly larger (P < .01) in cholesterol-fed mice receiving L-arginine + L-NA than in those on the high-cholesterol diet alone. Within the atherosclerotic plaques, endothelial cells immunoreacted for endothelial cell NOS; macrophages, foam cells, and smooth muscle cells immunostained strongly for inducible NOS and nitrotyrosine residues. The data indicate that L-arginine prevents xanthoma formation and reduces atherosclerosis in LDL receptor knockout mice fed a high-cholesterol diet. The abrogation of the beneficial effects of L-arginine by L-NA suggests that the antiatherosclerotic actions of L-arginine are mediated by NOS. The data suggest that L-arginine may be beneficial in familial hypercholesterolemia.

Mycoprotein reduces blood lipids in free-living subjects.

PubMed

Turnbull, W H; Leeds, A R; Edwards, D G

1992-02-01

Mycoprotein is a food produced by continuous fermentation of Fusarium graminearum (Schwabe). A previous metabolic study showed that mycoprotein decreased total and low-density-lipoprotein (LDL) cholesterol and increased high-density-lipoprotein (HDL) cholesterol. This study was undertaken to determine the effects of mycoprotein under free-living conditions. Two groups of subjects with slightly raised cholesterol concentrations participated in the 8-wk study. The experimental group was fed cookies containing mycoprotein and the control group was fed a nutrient-balanced cookie without mycoprotein. After 8 wk of treatment total cholesterol was reduced by 0.46 mmol/L in the control group and 0.95 mmol/L in the mycoprotein group, and LDL was reduced by 0.34 mmol/L in the control group and 0.84 mmol/L in the mycoprotein group. All analysis of variance differences were statistically significant. This study confirms the metabolic-study results and we are now relatively confident that mycoprotein exerts a beneficial effect on blood lipids.

Low daily dose of 3 mg monacolin K from RYR reduces the concentration of LDL-C in a randomized, placebo-controlled intervention.

PubMed

Heinz, Tina; Schuchardt, Jan Philipp; Möller, Katharina; Hadji, Peyman; Hahn, Andreas

2016-10-01

Hypercholesterolemia and elevated homocysteine concentrations are associated with cardiovascular risk. Previous studies have demonstrated a cholesterol-lowering effect of red yeast rice (RYR) supplements which contained 5 to 10 mg of monacolin K. We hypothesized that the intake of a low monacolin K dose may likewise reduce low-density lipoprotein-cholesterol (LDL-C) and other plasma lipids. In secondary analyses, we tested the homocysteine lowering effect of folic acid, which was also included in the study preparation. Therefore, we conducted a randomized, double-blind, and placebo-controlled intervention study. One hundred forty-two nonstatin-treated participants with hypercholesterolemia (LDL-C ≥ 4.14 ≤ 5.69 mmol/L) were randomized to the supplement group with RYR or the placebo group. Participants of the supplement group consumed 3 mg monacolin K and 200 μg folic acid per day. A significant (P < .001) reduction of LDL-C (-14.8%), total cholesterol (-11.2%), and homocysteine (-12.5%) was determined in the supplement group after 12 weeks. A total of 51% of the participants treated with RYR achieved the limit of LDL-C <4.14 mmol/L advised and 26% reached the threshold level of homocysteine <10 μmol/L. No significant changes were exhibited within the placebo group. Other parameters remained unchanged and no intolerances or serious adverse events were observed. In conclusion, we demonstrated that a low dose of daily 3 mg monacolin K from RYR reduces the concentration of LDL-C; a risk factor for cardiovascular diseases. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Emerging biologic therapies for hypercholesterolaemia.

PubMed

Pucci, Giacomo; Cicero, Arrigo F; Borghi, Claudio; Schillaci, Giuseppe

2017-09-01

LDL-cholesterol (LDL-C) is one of the most well-established risk factors for CV disease. Indeed, therapies that decrease LDL-C are proven to effectively reduce the risk of atherosclerotic CV disease. Monoclonal antibodies (mAbs) that target proprotein convertase subtilisin/kexin type 9 (PCSK9) have recently gained traction as a promising therapeutic strategy. Areas covered: In this review, the authors discuss the effectiveness of mAbs against PCSK9 in lowering low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipid fractions. The discontinuation in the development of bococizumab due to efficacy and safety concerns, and the initial promising data about inclisiran, a long-acting small inhibiting RNA molecule against PCSK9 synthesis, is also discussed. Expert opinion: Initial data about cardiovascular (CV) outcomes in large scale, long-term studies suggest a possible further therapeutic pathway for LDL-C reduction, and currently support the notion that further LDL-C reduction, obtained with PCSK9 inhibition on top of best available therapy, provides increased CV protection in subjects at very high CV risk. The development and marketing of mAbs against PCSK9 could help to redefine current therapeutic strategies aimed at reducing cardiovascular (CV) morbidity and risk, through the reduction of LDL-C concentrations. The cost-effectiveness of these emerging drugs is yet to be established.

Cholesterol-lowering properties of different pectin types in mildly hyper-cholesterolemic men and women.

PubMed

Brouns, F; Theuwissen, E; Adam, A; Bell, M; Berger, A; Mensink, R P

2012-05-01

Viscous fibers typically reduce total cholesterol (TC) by 3-7% in humans. The cholesterol-lowering properties of the viscous fiber pectin may depend on its physico-chemical properties (viscosity, molecular weight (MW) and degree of esterification (DE)), but these are not typically described in publications, nor required by European Food Safety Authority (EFSA) with respect to its generic pectin cholesterol-lowering claim. Here, different sources and types of well-characterized pectin were evaluated in humans. Cross-over studies were completed in mildly hyper-cholesterolemic persons receiving either 15 g/day pectin or cellulose with food for 4 weeks. Relative low-density lipoprotein (LDL) cholesterol (LDL-C) lowering was as follows: citrus pectin DE-70=apple pectin DE-70 (7-10% reduction versus control)>apple pectin DE-35=citrus pectin DE-35>OPF (orange pulp fiber) DE-70 and low-MW pectin DE-70>citrus DE-0. In a subsequent 3-week trial with 6 g/day pectin, citrus DE-70 and high MW pectin DE-70 reduced LDL-C 6-7% versus control (without changes in TC). In both studies, high DE and high MW were important for cholesterol lowering. Source may also be important as citrus and apple DE-70 pectin were more effective than OPF DE-70 pectin. Pectin did not affect inflammatory markers high-sensitivity C-reactive protein (hsCRP) nor plasma homocysteine. Pectin source and type (DE and MW) affect cholesterol lowering. The EFSA pectin cholesterol-lowering claim should require a minimum level of characterization, including DE and MW.

Gender difference of association between LDL cholesterol concentrations and mortality from coronary heart disease amongst Japanese: the Ibaraki Prefectural Health Study.

PubMed

Noda, H; Iso, H; Irie, F; Sairenchi, T; Ohtaka, E; Ohta, H

2010-06-01

The aim of this study was to examine whether LDL cholesterol raises the risk of coronary heart disease in a dose-response fashion in a population with low LDL-cholesterol levels. Population-based prospective cohort study in Japan. A total of 30,802 men and 60,417 women, aged 40 to 79 years with no history of stroke or coronary heart disease, completed a baseline risk factor survey in 1993. Systematic mortality surveillance was performed through 2003 and 539 coronary heart disease deaths were identified. The mean values for LDL-cholesterol were 110.5 mg dL(-1) (2.86 mmol L(-1)) for men and 123.9 mg dL(-1) (3.20 mmol L(-1)) for women. Men with LDL-cholesterol > or =140 mg dL(-1) (> or =3.62 mmol L(-1)) had two-fold higher age-adjusted risk of mortality from coronary heart disease than did those with LDL-cholesterol <80 mg dL(-1) (<2.06 mmol L(-1)), whereas no such association for women was found. The multivariable hazard ratio for the highest versus lowest categories of LDL-cholesterol was 2.06 (95 percent confidence interval: 1.34 to 3.17) for men and 1.16 (0.64 to 2.12) for women. Higher concentrations of LDL-cholesterol were associated with an increased risk of mortality from coronary heart disease for men, but not for women, in a low cholesterol population.

Familial Hypercholesterolemia.

PubMed

Bouhairie, Victoria Enchia; Goldberg, Anne Carol

2016-03-01

Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen, and low-density lipoprotein (LDL) apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with familial hypercholesterolemia. It is important to increase awareness of this disorder in physicians and patients to reduce the burden of this disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

Familial hypercholesterolemia.

PubMed

Bouhairie, Victoria Enchia; Goldberg, Anne Carol

2015-05-01

Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen, and low-density lipoprotein (LDL) apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with familial hypercholesterolemia. It is important to increase awareness of this disorder in physicians and patients to reduce the burden of this disorder. Copyright © 2015 Elsevier Inc. All rights reserved.

Ezetimibe Increases Endogenous Cholesterol Excretion in Humans

PubMed Central

Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

2017-01-01

Objective Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers LDL cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly-mixing endogenous cholesterol pool into the stool. Approach and Results In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with LDL cholesterol 100–200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/day or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d7 in a lipid emulsion and dietary cholesterol with cholesterol-d5 and sitostanol-d4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30 ± 4.3% (SE, P < 0.0001) and LDL cholesterol 19.8 ± 1.9% (P = 0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6 ± 12.2% (P < 0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7 ± 14.3% (P < 0.0001) while plasma cholesterol turnover rose 26.2 ± 3.6% (P = 0.0096). Fecal bile acids were unchanged. Conclusions Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly-mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. PMID:28279967

Rosuvastatin-Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study.

PubMed

Rollefstad, S; Ikdahl, E; Hisdal, J; Olsen, I C; Holme, I; Hammer, H B; Smerud, K T; Kitas, G D; Pedersen, T R; Kvien, T K; Semb, A G

2015-07-01

Patients with rheumatoid arthritis (RA) and carotid artery plaques have an increased risk of acute coronary syndromes. Statin treatment with the goal of achieving a low-density lipoprotein (LDL) cholesterol level of ≤1.8 mmoles/liter (≤70 mg/dl) is recommended for individuals in the general population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA-AS) study was to evaluate the effect of 18 months of intensive lipid-lowering treatment with rosuvastatin with regard to change in carotid plaque height. Eighty-six patients (60.5% of whom were female) with carotid plaques and inflammatory joint disease (55 with RA, 21 with AS, and 10 with psoriatic arthritis) were treated with rosuvastatin to obtain the LDL cholesterol goal. Carotid plaque height was evaluated by B-mode ultrasonography. The mean ± SD age of the patients was 60.8 ± 8.5 years, and the median compliance with rosuvastatin treatment was 97.9% (interquartile range [IQR] 96.0-99.4). At baseline, the median number and height of the carotid plaques were 1.0 (range 1-8) and 1.80 mm (IQR 1.60-2.10), respectively. The mean ± SD change in carotid plaque height after 18 months of treatment with rosuvastatin was -0.19 ± 0.35 mm (P < 0.0001). The mean ± SD baseline LDL cholesterol level was 4.0 ± 0.9 mmoles/liter (154.7 ± 34.8 mg/dl), and the mean reduction in the LDL cholesterol level was -2.3 mmoles/liter (95% confidence interval [95% CI] -2.48, -2.15) (-88.9 mg/dl [95% CI -95.9, -83.1]). The mean ± SD LDL cholesterol level during the 18 months of rosuvastatin treatment was 1.7 ± 0.4 mmoles/liter (area under the curve). After adjustment for age/sex/blood pressure, no linear relationship between a reduction in carotid plaque height and the level of LDL cholesterol exposure during the study period was observed. Attainment of the LDL cholesterol goal of ≤1.8 mmoles/liter (≤70 mg/dl) or the amount of change in the LDL cholesterol level during the study period did not influence the degree of carotid plaque height reduction. Intensive lipid-lowering treatment with rosuvastatin induced atherosclerotic regression and reduced the LDL cholesterol level significantly in patients with inflammatory joint disease. © 2015, American College of Rheumatology.

Cholesterol

MedlinePlus

... fried and processed foods. Eating these fats can raise your LDL (bad) cholesterol. Lack of physical activity, ... lowers HDL cholesterol, especially in women. It also raises your LDL cholesterol. Genetics may also cause people ...

Serum Lipid Levels in Patients with Eating Disorders.

PubMed

Nakai, Yoshikatsu; Noma, Shun'ichi; Fukusima, Mitsuo; Taniguchi, Ataru; Teramukai, Satoshi

2016-01-01

Objective To evaluate some risk factors for cardiovascular diseases in feeding and eating disorders, the degree of lipid abnormalities was investigated in a large Japanese cohort of different groups of feeding and eating disorders, according to the Japan Atherosclerosis Society Guidelines for the Prevention of Atherosclerotic Cardiovascular Diseases 2012 (JAS Guidelines 2012). Methods Participants in the current study included 732 women divided into four groups of feeding and eating disorders: anorexia nervosa, restricting type (AN-R); anorexia nervosa, binge-eating/purging type; bulimia nervosa (BN); and binge-eating disorder (BED). We measured the serum levels of total cholesterol, high-density-lipoprotein (HDL) cholesterol, and triglyceride in these participants. Low-density-lipoprotein (LDL) cholesterol and non-HDL cholesterol levels were also calculated. Results The concentrations of LDL cholesterol and non-HDL cholesterol were widely distributed in all groups. When the LDL cholesterol risk was defined as ≥120 mg/dL and the non-HDL cholesterol risk as ≥150 mg/dL, according to the JAS Guidelines 2012, the proportion of LDL cholesterol risk ranged from 29.6% (BN) to 38.6% (AN-R), and the proportion of non-HDL cholesterol risk ranged from 17.8% (BN) to 30.1% (BED). Conclusion The present findings suggest the existence of LDL cholesterol risk and non-HDL cholesterol risk in all groups of eating disorders. Given the chronicity of this condition, the development of elevated concentrations of LDL cholesterol and non-HDL cholesterol at an early age may increase the risk of cardiovascular diseases.

Effective reduction of LDL cholesterol by indigenous plant product.

PubMed

Bhardwaj, P K; Dasgupta, D J; Prashar, B S; Kaushal, S S

1994-03-01

A herbal powder containing guar gum, methi, tundika and meshasringi was administered to 30 control and 30 type 2 (non-insulin dependent) diabetes mellitus patients for a month. Total serum cholesterol and its fractions eg, high density lipoprotein, low density lipoproteins, very low density lipoproteins and serum triglyceride were determined before and after the trial period. Total and low density lipoprotein (LDL) cholesterols were reduced significantly after the therapy. There were no significant changes in high density lipoproteins (HDL), very low density lipoproteins (VLDL) or triglyceride levels. Side-effects eg, mild flatulence and looseness of bowel were noticed in less than 40% cases.

Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial.

PubMed

Raal, Frederick J; Santos, Raul D; Blom, Dirk J; Marais, A David; Charng, Min-Ji; Cromwell, William C; Lachmann, Robin H; Gaudet, Daniel; Tan, Ju L; Chasan-Taber, Scott; Tribble, Diane L; Flaim, Joann D; Crooke, Stanley T

2010-03-20

Homozygous familial hypercholesterolaemia is a rare genetic disorder in which both LDL-receptor alleles are defective, resulting in very high concentrations of LDL cholesterol in plasma and premature coronary artery disease. This study investigated whether an antisense inhibitor of apolipoprotein B synthesis, mipomersen, is effective and safe as an adjunctive agent to lower LDL cholesterol concentrations in patients with this disease. This randomised, double-blind, placebo-controlled, phase 3 study was undertaken in nine lipid clinics in seven countries. Patients aged 12 years and older with clinical diagnosis or genetic confirmation of homozygous familial hypercholesterolaemia, who were already receiving the maximum tolerated dose of a lipid-lowering drug, were randomly assigned to mipomersen 200 mg subcutaneously every week or placebo for 26 weeks. Randomisation was computer generated and stratified by weight (<50 kg vs >/=50 kg) in a centralised blocked randomisation, implemented with a computerised interactive voice response system. All clinical, medical, and pharmacy personnel, and patients were masked to treatment allocation. The primary endpoint was percentage change in LDL cholesterol concentration from baseline. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00607373. 34 patients were assigned to mipomersen and 17 to placebo; data for all patients were analysed. 45 patients completed the 26-week treatment period (28 mipomersen, 17 placebo). Mean concentrations of LDL cholesterol at baseline were 11.4 mmol/L (SD 3.6) in the mipomersen group and 10.4 mmol/L (3.7) in the placebo group. The mean percentage change in LDL cholesterol concentration was significantly greater with mipomersen (-24.7%, 95% CI -31.6 to -17.7) than with placebo (-3.3%, -12.1 to 5.5; p=0.0003). The most common adverse events were injection-site reactions (26 [76%] patients in mipomersen group vs four [24%] in placebo group). Four (12%) patients in the mipomersen group but none in the placebo group had increases in concentrations of alanine aminotransferase of three times or more the upper limit of normal. Inhibition of apolipoprotein B synthesis by mipomersen represents a novel, effective therapy to reduce LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia who are already receiving lipid-lowering drugs, including high-dose statins. ISIS Pharmaceuticals and Genzyme Corporation. Copyright 2010 Elsevier Ltd. All rights reserved.

New clinical perspectives of hypolipidemic drug therapy in severe hypercholesterolemia.

PubMed

Stefanutti, C; Morozzi, C; Di Giacomo, S

2012-01-01

Patients with homozygous familial hypercholesterolemia (HoFH) represent the most severe patients within the spectrum of dyslipidemias. Untreated Low-Density Lipoprotein Cholesterol (LDL-C) levels in these patients are usually in the range 500 to 1200 mg/dL. Moreover, these patients exhibit a scarce responsiveness or even non responsiveness to oral lipid lowering agents. Patients with heterozygous familial hypercholesterolemia (HetFH) tend to have untreated LDL-C levels of 250-500 mg/dL. Many of these patients are responsive to 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA-reductase) inhibitors (statins) and/or other specific drugs. Unfortunately, a significant subset of these patients (5-10%) have a severe and/or refractory form of HetFH and after current maximal oral therapy, they remain significantly far from treatment goals (The National Cholesterol Education Program (NCEP) ATPIII guidelines). This would be defined as LDL-C levels of ≥ 190 mg/dL - prior Coronary Heart Disease (CHD) or CHD equivalent - or ≥ 250 mg/dL (no prior CHD or CHD risk-equivalent). The only current therapy option for these patients is Low Density Lipoprotein-apheresis (LDL_a). While LDL_a is very effective in reducing LDL-C, many patients do not receive this extracorporeal therapy because of costs and limited availability of LDL_a centers. Recently, new potent lipid-lowering drugs have been developed and are currently under investigation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role controlling the levels of LDL-C. Studies have demonstrated that PCSK9 acts mainly by enhancing degradation of the Low-Density Lipoprotein receptor (LDLR) protein in the liver. Inactivation of PCSK9 in mice reduces plasma cholesterol levels. Since the loss of a functional PCSK9 in human is not associated with apparent deleterious effects, this protease is becoming an attractive target for lowering plasma LDL-C levels either alone or in combination with statins. Mipomersen, an apolipoprotein B (ApoB) synthesis inhibitor, for lowering of LDL-C showed to be an effective therapy to reduce LDL-C concentrations in patients with HoFH who are already receiving lipid-lowering drugs, including high-dose statins. Lomitapide is a potent inhibitor of microsomal triglyceride transfer protein and is highly efficacious in reducing LDL-C and triglycerides (TG). Lomitapide is currently being developed for patients with HoFH at doses up to 60 mg/d. These new powerful lipid-lowering drugs might be possibly superior than available hypolipidemic agents. Their mechanisms of action, effectiveness, safety, and indication in severe, genetically determined dyslipidemias, are reviewed.

Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia.

PubMed

Jenkins, David J A; Chiavaroli, Laura; Wong, Julia M W; Kendall, Cyril; Lewis, Gary F; Vidgen, Edward; Connelly, Philip W; Leiter, Lawrence A; Josse, Robert G; Lamarche, Benoît

2010-12-14

Higher intake of monounsaturated fat may raise high-density lipoprotein (HDL) cholesterol without raising low-density lipoprotein (LDL) cholesterol. We tested whether increasing the monounsaturated fat content of a diet proven effective for lowering LDL cholesterol (dietary portfolio) also modified other risk factors for cardiovascular disease, specifically by increasing HDL cholesterol, lowering serum triglyceride and further reducing the ratio of total to HDL cholesterol. Twenty-four patients with hyperlipidemia consumed a therapeutic diet very low in saturated fat for one month and were then randomly assigned to a dietary portfolio low or high in monounsaturated fatty acid for another month. We supplied participants' food for the two-month period. Calorie intake was based on Harris-Benedict estimates for energy requirements. For patients who consumed the dietary portfolio high in monounsaturated fat, HDL cholesterol rose, whereas for those consuming the dietary portfolio low in monounsaturated fat, HDL cholesterol did not change. The 12.5% treatment difference was significant (0.12 mmol/L, 95% confidence interval [CI] 0.05 to 0.21, p = 0.003). The ratio of total to HDL cholesterol was reduced by 6.5% with the diet high in monounsaturated fat relative to the diet low in monounsaturated fat (-0.28, 95% CI -0.59 to -0.04, p = 0.025). Patients consuming the diet high in monounsaturated fat also had significantly higher concentrations of apolipoprotein AI, and their C-reactive protein was significantly lower. No treatment differences were seen for triglycerides, other lipids or body weight, and mean weight loss was similar for the diets high in monounsaturated fat (-0.8 kg) and low in monounsaturated fat (-1.2 kg). Monounsaturated fat increased the effectiveness of a cholesterol-lowering dietary portfolio, despite statin-like reductions in LDL cholesterol. The potential benefits for cardiovascular risk were achieved through increases in HDL cholesterol, further reductions in the ratio of total to HDL cholesterol and reductions in C-reactive protein. (ClinicalTrials.gov trial register no. NCT00430430.).

Lower Squalene Epoxidase and Higher Scavenger Receptor Class B Type 1 Protein Levels Are Involved in Reduced Serum Cholesterol Levels in Stroke-Prone Spontaneously Hypertensive Rats.

PubMed

Michihara, Akihiro; Mido, Mayuko; Matsuoka, Hiroshi; Mizutani, Yurika

2015-01-01

A lower serum cholesterol level was recently shown to be one of the causes of stroke in an epidemiological study. Spontaneously hypertensive rats stroke-prone (SHRSP) have lower serum cholesterol levels than normotensive Wistar-Kyoto rats (WKY). To elucidate the mechanisms responsible for the lower serum cholesterol levels in SHRSP, we determined whether the amounts of cholesterol biosynthetic enzymes or the receptor and transporter involved in cholesterol uptake and efflux in the liver were altered in SHRSP. When the mRNA levels of seven cholesterol biosynthetic enzymes were measured using real-time polymerase chain reaction (PCR), farnesyl pyrophosphate synthase and squalene epoxidase (SQE) levels in the liver of SHRSP were significantly lower than those in WKY. SQE protein levels were significantly reduced in tissues other than the brain of SHRSP. No significant differences were observed in low-density lipoprotein (LDL) receptor (uptake of serum LDL-cholesterol) or ATP-binding cassette transporter A1 (efflux of cholesterol from the liver/formation of high-density lipoprotein (HDL)) protein levels in the liver and testis between SHRSP and WKY, whereas scavenger receptor class B type 1 (SRB1: uptake of serum HDL-cholesterol) protein levels were higher in the livers of SHRSP. These results indicated that the lower protein levels of SQE and higher protein levels of SRB1 in the liver were involved in the reduced serum cholesterol levels in SHRSP.

Whole-grain ready-to-eat oat cereal, as part of a dietary program for weight loss, reduces low-density lipoprotein cholesterol in adults with overweight and obesity more than a dietary program including low-fiber control foods.

PubMed

Maki, Kevin C; Beiseigel, Jeannemarie M; Jonnalagadda, Satya S; Gugger, Carolyn K; Reeves, Matthew S; Farmer, Mildred V; Kaden, Valerie N; Rains, Tia M

2010-02-01

Weight loss and consumption of viscous fibers both lower low-density lipoprotein (LDL) cholesterol levels. We evaluated whether or not a whole-grain, ready-to-eat (RTE) oat cereal containing viscous fiber, as part of a dietary program for weight loss, lowers LDL cholesterol levels and improves other cardiovascular disease risk markers more than a dietary program alone. Randomized, parallel-arm, controlled trial. Free-living, overweight and obese adults (N=204, body mass index 25 to 45) with baseline LDL cholesterol levels 130 to 200 mg/dL (3.4 to 5.2 mmol/L) were randomized; 144 were included in the main analysis of participants who completed the trial without significant protocol violations. Two portions per day of whole-grain RTE oat cereal (3 g/day oat b-glucan) or energy-matched low-fiber foods (control), as part of a reduced energy ( approximately 500 kcal/day deficit) dietary program that encouraged limiting consumption of foods high in energy and fat, portion control, and regular physical activity. Fasting lipoprotein levels, waist circumference, triceps skinfold thickness, and body weight were measured at baseline and weeks 4, 8, 10, and 12. LDL cholesterol level was reduced significantly more with whole-grain RTE oat cereal vs control (-8.7+/-1.0 vs -4.3+/-1.1%, P=0.005). Total cholesterol (-5.4+/-0.8 vs -2.9+/-0.9%, P=0.038) and non-high-density lipoprotein-cholesterol (-6.3+/-1.0 vs -3.3+/-1.1%, P=0.046) were also lowered significantly more with whole-grain RTE oat cereal, whereas high-density lipoprotein and triglyceride responses did not differ between groups. Weight loss was not different between groups (-2.2+/-0.3 vs -1.7+/-0.3 kg, P=0.325), but waist circumference decreased more (-3.3+/-0.4 vs -1.9+/-0.4 cm, P=0.012) with whole-grain RTE oat cereal. Larger reductions in LDL, total, and non-high-density lipoprotein cholesterol levels and waist circumference were evident as early as week 4 in the whole-grain RTE oat cereal group. Consumption of a whole-grain RTE oat cereal as part of a dietary program for weight loss had favorable effects on fasting lipid levels and waist circumference. Copyright 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

Effect of classic ketogenic diet treatment on lipoprotein subfractions in children and adolescents with refractory epilepsy.

PubMed

Azevedo de Lima, Patricia; Baldini Prudêncio, Mariana; Murakami, Daniela Kawamoto; Pereira de Brito Sampaio, Leticia; Figueiredo Neto, Antônio Martins; Teixeira Damasceno, Nágila Raquel

2017-01-01

The aim of this study was to evaluate the effects of the classic ketogenic diet (KD) on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions in children and adolescents with refractory epilepsy. This prospective study recruited children and adolescents of either sex, whose epilepsy was refractory to treatment with multiple drugs. To be included, the patient had to have an indication for treatment with the KD and be treated as an outpatient. At baseline and after 3 and 6 mo of the KD, lipid profile (total cholesterol [TC], triacylglycerols [TG], LDL cholesterol [LDL-C], and HDL cholesterol [HDL-C]), apolipoproteins (apoA-I and apoB), 10 subfractions of HDL, 7 subfractions of LDL, LDL phenotype, and LDL size were analyzed using the Lipoprint system. The lipid profile components (TC, TG, LDL-C, HDL-C, apoA-I, and apoB) increased during the 3-mo follow-up, and remained consistent after 6 mo of treatment. Similarly, non-HDL-C, TC/HDL-C, LDL-C/HDL-C, and apoB/apoA-I ratios, representing atherogenic particles, significantly increased. In contrast, qualitative lipoprotein characteristics progressively changed during the follow-up period. Small LDL subfractions increased, and this profile was related with reduced LDL size (27.3 nm to 26.7 nm). The LDL phenotype became worse; 52.1% of the patients had a non-A phenotype after 6 mo of the KD. Small HDL subfractions decreased only after 6 mo of the KD. KD treatment promotes negative changes in lipoprotein size and phenotype, contributing to atherogenic risk in these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Red grape seed extract improves lipid profiles and decreases oxidized low-density lipoprotein in patients with mild hyperlipidemia.

PubMed

Razavi, Seyed-Mostafa; Gholamin, Sharareh; Eskandari, Ali; Mohsenian, Nakta; Ghorbanihaghjo, Amir; Delazar, Abbas; Rashtchizadeh, Nadereh; Keshtkar-Jahromi, Maryam; Argani, Hassan

2013-03-01

Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (-10.68±26.76 mg/dL, P=.015), LDL cholesterol (-9.66±23.92 mg/dL, P=.014), and Ox-LDL (-5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals.

The effect of simvastatin, aspirin, and their combination in reduction of atheroma plaque

NASA Astrophysics Data System (ADS)

Kurniati, Neng Fisheri; Permatasari, Anita

2015-09-01

Atherosclerosis is one of the risk factors of cardiovascular disease. Atherosclerosis is a chronic inflammatory disease caused by high level of cholesterol especially low density lipoprotein (LDL) and accumulation of neutrophil and macrophage in the artery wall. Thickness of aortic wall is an early stage of atherosclerosis plaque formation. Identification of atherosclerosis plaque formation was done by measuring level of total cholesterol, triglycerides, HDL, LDL, interleukin-18 (IL-18), myeloperoxidase (MPO) and measuring the thickness of aortic wall. Atherosclerosis's model induced by high fat diet and CCT (cholesterol, cholic acid, and propyltiouracil) oral administration. Rats induced cholesterol divided into positive control, simvastatin 25 mg/kg bw, aspirin 20 mg/kg bw, and combination simvastatin 25 mg/kg and aspirin 20 mg/kg bw group for 3 weeks. In the third week, therapy was given to atherosclerosis's model. Then, in the fourth and fifth week, therapy was given but induction of high cholesterol was stopped due to the massive loss of body weight. Total cholesterol, triglycerides, HDL, LDL, MPO, and IL-18 measured by uv-vis spectrophotometry and ELISA. In the end of therapy, aorta's rats was isolated to identify the thickness of aorta wall. In the fourth week, after 1 week of treatment, only combination group showed significantly higher total cholesterol, LDL and MPO compared to positive control group. Level of triglycerides and HDL in all groups did not significantly differ compared to positive control group. After 2 weeks continuing drug treatment, the level of total cholesterol, MPO, and IL-18 were decreased in all groups, and aspirin group showed the lowest level. The level of triglycerides was decreased in simvastatin and aspirin group, and aspirin group showed the lowest. Only combination group showed the lowest level of LDL. Based on histopathology result, the thickness of aortic wall was reduced in all groups and aspirin group showed the lowest.

Bergamot Reduces Plasma Lipids, Atherogenic Small Dense LDL, and Subclinical Atherosclerosis in Subjects with Moderate Hypercholesterolemia: A 6 Months Prospective Study

PubMed Central

Toth, Peter P.; Patti, Angelo M.; Nikolic, Dragana; Giglio, Rosaria V.; Castellino, Giuseppa; Biancucci, Teresa; Geraci, Fabiana; David, Sabrina; Montalto, Giuseppe; Rizvi, Ali; Rizzo, Manfredi

2016-01-01

Background: Some patients experience statin-induced side effects or prefer nutraceutical approaches for the treatment of dyslipidemia. This has led to a search for alternative therapeutic approaches for dyslipidemia management. In recent studies Citrus bergamia (known as Bergamot) juice was able to reduce serum levels of lipids. Such benefit may be attributed to high amounts of flavonoids contained in Bergamot fruit juice (neoeriocitrin, neohesperidin, naringin). The aim of the present study was to fully investigate the effects of a Bergamot extract on cardio-metabolic parameters, including plasma lipids, atherogenic lipoproteins and subclinical atherosclerosis. Methods: Eighty subjects (42 men and 38 women, mean age: 55 ± 13 years) with moderate hypercholesterolemia [e.g., with plasma LDL-cholesterol concentrations between 160 and 190 mg/dl (between 4.1 and 4.9 mmol/l)] were included. A Bergamot-derived extract (Bergavit R®) was given at a fixed dose daily (150 mg of flavonoids, with 16% of neoeriocitrin, 47% of neohesperidin and 37% of naringin) for 6 months. Lipoprotein subfractions were assessed by gel electrophoresis. With this methodology low density lipoprotein (LDL) subclasses are distributed as seven bands (LDL-1 and -2 as large LDL, and LDL-3 to -7 as atherogenic small, dense LDL). Subclinical atherosclerosis was assessed by carotid intima-media thickness (cIMT) using B-mode ultrasound. Results: After 6 months, Bergavit R® reduced total cholesterol (from 6.6 ± 0.4 to 5.8 ± 1.1 mmol/l, p < 0.0001), triglycerides (from 1.8 ± 0.6 to 1.5 ± 0.9 mmol/l, p = 0.0020), and LDL-cholesterol (from 4.6 ± 0.2 to 3.7 ± 1.0 mmol/l, p < 0.0001), while HDL- cholesterol increased (from 1.3 ± 0.2 to 1.4 ± 0.4 mmol/l, p < 0.0007). In addition, a significant increase in LDL-1 (from 41.2 ± 0.2 to 49.6 ± 0.2%, p < 0.0001) was accompanied by decreased small, dense LDL-3, -4, and 5 particles (from 14.5 ± 0.1 to 9.0 ± 0.1% p < 0.0001; 3.2 ± 0.1 to 1.5 ± 0.1% p = 0.0053; 0.3 ± 0.0% to 0.1 ± 0.0% p = 0.0133, respectively). cIMT also decreased from 1.2 ± 0.4 to 0.9 ± 0.1 mm (p < 0.0001). Conclusion: This is the first study investigating the effects of Bergamot flavonoids supplementation on cardio-metabolic risk in dyslipidemic subjects. Bergavit R® (Bergamot juice extract) supplementation significantly reduced plasma lipids and improved the lipoprotein profile. cIMT was also reduced significantly over a relatively short time frame of 6 months. PMID:26779019

Hypocholesterolemic effect of stilbenes containing extract-fraction from Cajanus cajan L. on diet-induced hypercholesterolemia in mice.

PubMed

Luo, Qing-Feng; Sun, Lan; Si, Jian-Yong; Chen, Di-Hua

2008-11-01

Cajanus cajan (L) is a natural plant which contains a lot of potential active components. In the present study, we identified the effects of the stilbenes containing extract-fraction from Cajanus cajan L (sECC) on diet-induced (for 4 weeks) hypercholesterolemia in Kunming mice. All experimental mice were divided into 5 groups: control group, model group, sECC-treated with 200 or 100 mg/kg/day, and simvastatin group. The effects of sECC were investigated by monitoring serum and liver lipid profile (cholesterol homeostasis and triglyceride) as well as serum superoxide dismutase activity in those mice. To further explore the mechanism of sECC, hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase), cholesterol 7α-hydroxylase (CYP7A1), and low density lipoprotein receptor (LDL receptor) expressions in cholesterol homeostasis were analyzed by reverse transcription PCR. After 4 weeks pretreatment, compared with model group, the increased serum and hepatic total cholesterol were markedly attenuated by sECC (200 mg/kg) by 31.4% and 22.7% (p<0.01), respectively, the triglyceride levels of serum and liver were also lowered by 22.98% and 14.39%, respectively. At the same time, serum LDL cholesterol decreased by 52.8% (p<0.01) accompanied with the activities of serum superoxide dismutase increased by 20.98%. Atherogenic index and body weight were also reduced markedly. The mRNA expressions of HMG-CoA reductase, CYP7A1, and LDL-receptor were significantly enhanced in the mice administered with sECC (200 mg/kg/day), whereas those expressions were suppressed by the hypercholesterolemic diet. These data indicate that sECC reduces the atherogenic properties of dietary cholesterol in mice. Its hypocholesterolemic effect may involve enhancement of the hepatic LDL-receptor and cholesterol 7alpha-hydroxylase expression levels and bile acid synthesis.

Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11β-hydroxysteroid dehydrogenase type 1.

PubMed

Ledda, Angelo; González, Marina; Gulfo, José; Díaz Ludovico, Ivo; Ramella, Nahuel; Toledo, Juan; Garda, Horacio; Grasa, Mar; Esteve, Montserrat

2016-07-01

Data about glucocorticoids role in the development of atherosclerosis are controversial showing different effects in human than in experimental animal models. Atherosclerosis is the result of a chronic inflammatory response to an injured endothelium where an uncontrolled uptake of OxLDL by macrophages triggers the development of foam cells, the main component of fatty streaks in atherosclerotic plaque. There are few data about the direct effect of glucocorticoids in macrophages of atherosclerotic plaque. The aim of the study was to elucidate the role of glucocorticoids in the development of foam cells in atherosclerosis initiation. For this purpose we used THP1 cells differentiated to macrophages with phorbol esters and incubated with OxLDL alone or with cortisol or cortisone. THP1 cells were also incubated with cortisone plus an inhibitor of 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) activity to determine the role of this enzyme on glucocorticoid action in this process. Ours results showed that cortisol and cortisone decreased significantly the inflammation promoted by OxLDL, and also diminished the expression of genes involved in influx and efflux of cholesterol resulting in a reduced lipid accumulation. Likewise cortisol and cortisone decreased 11βHSD1 expression in THP1 cells. The presence of the inhibitor of 11βHSD1 abolished all the effects elicited by cortisone. Our results indicate a direct effect of glucocorticoids on macrophages braking atherosclerosis initiation, reducing pro-inflammatory markers and OxLDL uptake and cholesterol re-esterification, but also inhibiting cholesterol output. These effects appear to be mediated, at least in part, by 11βHSD1 activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Statins in hypercholesterolaemia: A dose-specific meta-analysis of lipid changes in randomised, double blind trials

PubMed Central

Edwards, Jayne E; Moore, R Andrew

2003-01-01

Background Statins alter lipid concentrations. This systematic review determined the efficacy of particular statins, in terms of their ability to alter cholesterol. Review methods PubMed, the Cochrane Library, references lists of reports, and reviews were searched (September 2001) for randomised, double blind trials of statins for cholesterol in trials of 12 weeks or longer. Mean change in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides was calculated using pooled data for particular statins, and for particular doses of a statin. Pre-planned sensitivity analyses were used to determine the effects of initial concentration of total cholesterol, study duration, the effects of major trials, and effects in placebo versus active controlled trials. Information was not collected on adverse events. Results Different statins at a range of doses reduced total cholesterol by 17–35% and LDL-cholesterol by 24–49% from baseline. Lower doses of statins generally produced less cholesterol lowering, though for most statins in trials of 12 weeks or longer there was at best only a weak relationship between dose and cholesterol reduction. Duration of treatment and baseline total cholesterol concentration did not alter the amount of the benefit attained. Conclusions Statins are effective medicines and confer benefit to patients in terms of primary and secondary prevention of coronary heart disease. Reductions in total cholesterol of 25% or more and LDL cholesterol of more than 30% were recorded for fixed doses of simvastatin 40 mg, atorvastatin 10 mg, and rosuvastatin 5 mg and 10 mg. PMID:14969594

Comparison of different statin therapy to change low-density lipoprotein cholesterol and high-density lipoprotein cholesterol level in Korean patients with and without diabetes.

PubMed

Khang, Ah Reum; Song, Young Shin; Kim, Kyoung Min; Moon, Jae Hoon; Lim, Soo; Park, Kyong Soo; Jang, Hak Chul; Choi, Sung Hee

2016-01-01

It is difficult to apply the proper intensity of statin for new treatment guidelines in clinical settings because of few data about the statin efficacy in Asians. We conducted a retrospective, observational study to estimate the percentage changes in lipid parameters and glucose induced by different statins. We analyzed 3854 patients including those with nondiabetes and diabetes treated at the outpatient clinic between 2003 and 2013 who were statin-naïve and maintained fixed-dose of statin for at least 18 months. Moderate- and low-intensity statin therapy was effective in reducing low-density lipoprotein cholesterol (LDL-C) to <100 mg/dL (70.3%, 83.0%, and 87.2% of diabetic patients in the low-, moderate-, and high-intensity therapy groups, respectively). The rapid decrease of LDL-C was observed in the first 8 months, and LDL-C-lowering effect was maintained throughout the observation period in even the low-intensity statin group. The effects of statins in elevating high-density lipoprotein cholesterol were similar in each statin groups, except the ezetimibe-simvastatin group (4.5 ± 2.1%) and high-dose atorvastatin groups (9.7 ± 3.3% and 8.7 ± 2.4% for 40 mg and 80 mg of atorvastatin/day, respectively). High-density lipoprotein cholesterol increased less and LDL-C decreased more in diabetes than in nondiabetes. There were no significant changes of fasting glucose after statin use in nondiabetic patients. Moderate- or low-intensity statin was effective enough in reaching National Cholesterol Education Program Adult Treatment Panel III LDL-C target goals in Koreans. Low-intensity statin showed around 30% LDL-C reduction from the baseline level in Koreans, which is comparable to moderate-intensity statin in new guideline. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

The effect of a very high daily plant stanol ester intake on serum lipids, carotenoids, and fat-soluble vitamins.

PubMed

Gylling, Helena; Hallikainen, Maarit; Nissinen, Markku J; Miettinen, Tatu A

2010-02-01

Intake of 2-3 g/d of plant stanols as esters lowers LDL cholesterol level, but there is no information about the efficacy and safety of a respective very high daily intake. We studied the effects of 8.8 g/d of plant stanols as esters on serum lipids and safety variables in subjects with mild to moderate hypercholesterolemia. In a randomized, double-blind, placebo-controlled study the intervention (n=25) and control (n=24) groups consumed spread and drink enriched or not with plant stanol esters for 10 weeks. Plant stanols reduced serum total and LDL cholesterol concentrations by 12.8 and 17.3% from baseline and by 12.0 and 17.1% from controls (P<0.01 for all). Liver enzymes, markers of hemolysis, and blood cells were unchanged. Serum vitamins A, D, and gamma-tocopherol concentrations, and the ratios of alpha-tocopherol to cholesterol were unchanged. Serum beta-carotene concentrations decreased significantly from baseline and were different from controls even when adjusted for cholesterol. Serum alpha-carotene concentration and alpha-carotene/cholesterol ratio were not different from controls. High intake of plant stanols reduced LDL cholesterol values without any other side effects than reduction of serum beta-carotene concentration. However, the end product, serum vitamin A levels, were unchanged. The results suggest that plant stanol ester intake can be increased to induce a greater cholesterol lowering effect. Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Meta-Analysis: Effects of Probiotic Supplementation on Lipid Profiles in Normal to Mildly Hypercholesterolemic Individuals

PubMed Central

Shimizu, Mikiko; Hashiguchi, Masayuki; Shiga, Tsuyoshi; Tamura, Hiro-omi; Mochizuki, Mayumi

2015-01-01

Introduction Recent experimental and clinical studies have suggested that probiotic supplementation has beneficial effects on serum lipid profiles. However, there are conflicting results on the efficacy of probiotic preparations in reducing serum cholesterol. Objective To evaluate the effects of probiotics on human serum lipid levels, we conducted a meta-analysis of interventional studies. Methods Eligible reports were obtained by searches of electronic databases. We included randomized, controlled clinical trials comparing probiotic supplementation with placebo or no treatment (control). Statistical analysis was performed with Review Manager 5.3.3. Subanalyses were also performed. Results Eleven of 33 randomized clinical trials retrieved were eligible for inclusion in the meta-analysis. No participant had received any cholesterol-lowering agent. Probiotic interventions (including fermented milk products and probiotics) produced changes in total cholesterol (TC) (mean difference –0.17 mmol/L, 95% CI: –0.27 to –0.07 mmol/L) and low-density lipoprotein cholesterol (LDL-C) (mean difference –0.22 mmol/L, 95% CI: –0.30 to –0.13 mmol/L). High-density lipoprotein cholesterol and triglyceride levels did not differ significantly between probiotic and control groups. In subanalysis, long-term (>4-week) probiotic intervention was statistically more effective in decreasing TC and LDL-C than short-term (≤4-week) intervention. The decreases in TC and LDL-C levels with probiotic intervention were greater in mildly hypercholesterolemic than in normocholesterolemic individuals. Both fermented milk product and probiotic preparations decreased TC and LDL-C levels. Gaio and the Lactobacillus acidophilus strain reduced TC and LDL-C levels to a greater extent than other bacterial strains. Conclusions In conclusion, this meta-analysis showed that probiotic supplementation could be useful in the primary prevention of hypercholesterolemia and may lead to reductions in risk factors for cardiovascular disease. PMID:26473340

Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.

PubMed

Robinson, Jennifer G; Farnier, Michel; Krempf, Michel; Bergeron, Jean; Luc, Gérald; Averna, Maurizio; Stroes, Erik S; Langslet, Gisle; Raal, Frederick J; El Shahawy, Mahfouz; Koren, Michael J; Lepor, Norman E; Lorenzato, Christelle; Pordy, Robert; Chaudhari, Umesh; Kastelein, John J P

2015-04-16

Alirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and efficacy. We conducted a randomized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy. Patients were randomly assigned in a 2:1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24. At week 24, the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points (P<0.001); the treatment effect remained consistent over a period of 78 weeks. The alirocumab group, as compared with the placebo group, had higher rates of injection-site reactions (5.9% vs. 4.2%), myalgia (5.4% vs. 2.9%), neurocognitive events (1.2% vs. 0.5%), and ophthalmologic events (2.9% vs. 1.9%). In a post hoc analysis, the rate of major adverse cardiovascular events (death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) was lower with alirocumab than with placebo (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31 to 0.90; nominal P=0.02). Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels. In a post hoc analysis, there was evidence of a reduction in the rate of cardiovascular events with alirocumab. (Funded by Sanofi and Regeneron Pharmaceuticals; ODYSSEY LONG TERM ClinicalTrials.gov number, NCT01507831.).

Effects of dietary fats on egg quality and lipid parameters in serum and yolks of Shan Partridge Duck.

PubMed

Du, Xue; Liu, Yali; Lu, Lizhi; Wang, Weiqun; Zeng, Tao; Tian, Yong; Xu, Xiaoqin; Shen, Jianliang; Niu, Dong; Lu, Yingru

2017-05-01

The effects of different dietary fats with variable levels of polyunsaturated fatty acids (PUFAs) on egg quality of Shan Partridge Duck, serum, and yolk lipid parameters were examined in this study. A flock of 585 optimal produced ducks were selected and diets enriched with 0.5%, 1%, or 2% fish oil (F)/flaxseed oil (FL)/rapeseed oil (R)/tallow (T) plus basal diet were supplied through a 28-d period. Supplemental fat source and fat level had no effects on egg qualities. Proportions of yolk total cholesterol (TC), saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) were reduced (P < 0.001), while polyunsaturated fatty acids (PUFAs), ω-6 polyunsaturated fatty acids (n-6 PUFAs), ω-3 polyunsaturated fatty acids (n-3 PUFAs), Docosahexaenoic Acid (DHA), and Eicosapentaenoic Acid (EPA) were increased by fish oil, flaxseed oil, or rapeseed oil. Effects of supplementation increasing DHA and EPA were detected in F, FL, and R. Compared with C, fish oil significantly increased low-density lipoprotein cholesterol (LDL-C) in serum, flaxseed oil significantly reduced TC and increased very low-density lipoprotein cholesterol (VLDL-C), rapeseed oil significantly reduced TC and LDL-C in serum and increased VLDL-C, tallow significantly increased LDL-C. It is concluded that unsaturated fatty acids rich diets (fish oil, flaxseed oil, and rapeseed oil) might increase yolk PUFAs, reduce yolk cholesterol, and change serum lipid parameters without evident effect on egg qualities. © 2016 Poultry Science Association Inc.

Mechanism of transfer of LDL-derived free cholesterol to HDL subfractions in human plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miida, T.; Fielding, C.J.; Fielding, P.E.

1990-11-01

The transfer of ({sup 3}H)cholesterol in low-density lipoprotein (LDL) to different high-density lipoprotein (HDL) species in native human plasma was determined by using nondenaturing two-dimensional electrophoresis. Transfer from LDL had a t{sub 1/2} at 37{degree}C of 51 {plus minus} 8 min and an activation energy of 18.0 kCal mol{sup {minus}1}. There was unexpected specificity among HDL species as acceptors of LDL-derived labeled cholesterol. The largest fraction of the major {alpha}-migrating class (HDL{sub 2b}) was the major initial acceptor of LDL-derived cholesterol. Kinetic analysis indicated a rapid secondary transfer from HDL{sub 2b} to smaller {alpha}HDL (particularly HDL{sub 3}) driven enzymatically bymore » the lecithin-cholesterol acyltransferase reaction. Rates of transfer among {alpha}HDL were most rapid from the largest {alpha}HDL fraction (HDL{sub 2b}), suggesting possible protein-mediated facilitation. Simultaneous measurements of the transport of LDL-derived and cell-derived isotopic cholesterol indicated that the former preferably utilized the {alpha}HDL pathyway, with little label in pre-{beta}HDL. The same experiments confirmed earlier data that cell-derived cholesterol is preferentially channeled through pre-{beta}HDL. The authors suggest that the functional heterogeneity of HDL demonstrated here includes the ability to independently process cell- and LDL-derived free cholesterol.« less

microRNA-150 inhibits the formation of macrophage foam cells through targeting adiponectin receptor 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jing; Zhang, Suhua, E-mail: drsuhuangzhang@qq.com

Transformation of macrophages into foam cells plays a critical role in the pathogenesis of atherosclerosis. The aim of this study was to determine the expression and biological roles of microRNA (miR)-150 in the formation of macrophage foam cells and to identify its functional target(s). Exposure to 50 μg/ml oxidized low-density lipoprotein (oxLDL) led to a significant upregulation of miR-150 in THP-1 macrophages. Overexpression of miR-150 inhibited oxLDL-induced lipid accumulation in THP-1 macrophages, while knockdown of miR-150 enhanced lipid accumulation. apoA-I- and HDL-mediated cholesterol efflux was increased by 66% and 43%, respectively, in miR-150-overexpressing macrophages relative to control cells. In contrast, downregulationmore » of miR-150 significantly reduced cholesterol efflux from oxLDL-laden macrophages. Bioinformatic analysis and luciferase reporter assay revealed adiponectin receptor 2 (AdipoR2) as a direct target of miR-150. Small interfering RNA-mediated downregulation of AdipoR2 phenocopied the effects of miR-150 overexpression, reducing lipid accumulation and facilitating cholesterol efflux in oxLDL-treated THP-1 macrophages. Knockdown of AdipoR2 induced the expression of proliferator-activated receptor gamma (PPARγ), liver X receptor alpha (LXRα), ABCA1, and ABCG1. Moreover, pharmacological inhibition of PPARγ or LXRα impaired AdipoR2 silencing-induced upregulation of ABCA1 and ABCG1. Taken together, our results indicate that miR-150 can attenuate oxLDL-induced lipid accumulation in macrophages via promotion of cholesterol efflux. The suppressive effects of miR-150 on macrophage foam cell formation are mediated through targeting of AdipoR2. Delivery of miR-150 may represent a potential approach to prevent macrophage foam cell formation in atherosclerosis. -- Highlights: •miR-150 inhibits macrophage foam cell formation. •miR-150 accelerates cholesterol efflux from oxLDL-laden macrophages. •miR-150 suppresses macrophage foam cell formation by targeting AdipoR2.« less

Does obesity lead to a specific lipid disorder? Analysis from the German/Austrian/Swiss APV registry.

PubMed

Holl, Reinhard W; Hoffmeister, Ulrike; Thamm, Michael; Stachow, Rainer; Keller, Klaus-Michael; L'Allemand, Dagmar; Widhalm, Kurt; Flechtner-Mors, Marion; Wiegand, Susanna

2011-09-01

Overweight and obese youth represent a challenge for the affected individual, the healthcare system as well as society as a whole. Increased long-term cardiovascular risk is one of the major consequences of early-onset obesity, affecting both life expectancy and quality of life. The aim of this report is to study the effects of age, gender and obesity category on the presence of individual components of dyslipidemia using normal-weight subjects from the population-based German KIGGS study including 17,641 randomly selected children and adolescents, aged 0-18 years (11,110 normal-weight subjects with lipid measurements) and the German-Austrian-Swiss APV registry, including 57,239 overweight or obese children, adolescents and young adults from 162 specialized obesity care centers (lipid measurements available in 29,711 subjects). Subjects were classified according to BMI category based on the age- and gender-adjusted BMI-z-scores as recommended by the AGA (German Pediatric Obesity working group). Cut-offs for dyslipidemia were based on the recommendations by the American Heart Association: total cholesterol: > 5.2 mmol/l, HDL-cholesterol < 0.9 mmol/l, LDL-cholesterol > 3.4 mmol/l, triglycerides > 1.7 mmol/l. Using SAS 9.2-software, hierarchic modeling with both linear and logistic regression analysis was applied. Within the group of normal-weight children, fasting triglycerides were elevated in 3.3%, LDL-cholesterol in 7.2% and HDL-cholesterol was reduced in 3.1%. With increasing BMI-category, the prevalence of hypertriglyceridemia and reduced HDL-cholesterol increased rapidly. A weaker relationship was present for LDL-cholesterol and total cholesterol. Among obese youth, 30.5% displayed any dyslipidemia, underlining the importance of adequate screening and intervention.

Simultaneous intake of beta-glucan and plant stanol esters affects lipid metabolism in slightly hypercholesterolemic subjects.

PubMed

Theuwissen, Elke; Mensink, Ronald P

2007-03-01

Intake of food products rich in water-soluble fiber beta-glucan and products enriched with plant stanol esters lower serum cholesterol. Combining 2 functional food ingredients into one food product may achieve additional reductions of serum cholesterol. Our objective was to investigate the effects of a simultaneous intake of beta-glucan plus plant stanol esters on lipid metabolism in mildly hypercholesterolemic volunteers. In a randomized, controlled, 3-period crossover study, 40 mildly hypercholesterolemic men and women received muesli in random order twice a day for 4 wk, which provided, in total, 5 g control fiber from wheat (control muesli), 5 g oat beta-glucan (beta-glucan muesli), or 5 g oat beta-glucan plus 1.5 g plant stanols (combination muesli). beta-Glucan muesli decreased serum LDL cholesterol by 5.0% compared with control muesli (P = 0.013). Combination muesli reduced LDL cholesterol by 9.6% compared with control muesli (P < 0.001), and by 4.4% compared with beta-glucan muesli (P = 0.036). Serum HDL cholesterol and triacylglycerol concentrations did not differ after the 3 treatments. Compared with control muesli, beta-glucan muesli increased bile acid synthesis (P = 0.043) and decreased cholesterol absorption (P = 0.011). Addition of plant stanols did not influence bile acid synthesis but decreased cholesterol absorption (P < 0.001) and raised cholesterol synthesis (P = 0.016) compared with control muesli, and the plant stanols decreased cholesterol absorption compared with beta-glucan muesli (P = 0.004). The combination muesli decreased serum concentrations of sitostanol compared with control muesli (P = 0.010). Plasma concentrations of lipid-soluble antioxidants did not differ after the 3 treatments. beta-Glucan muesli effectively lowered serum LDL cholesterol concentrations. The addition of plant stanol esters to beta-glucan-enriched muesli further lowered serum LDL cholesterol, although effects were slightly less than predicted.

Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels.

PubMed

Katan, Martijn B; Grundy, Scott M; Jones, Peter; Law, Malcolm; Miettinen, Tatu; Paoletti, Rodolfo

2003-08-01

Foods with plant stanol or sterol esters lower serum cholesterol levels. We summarize the deliberations of 32 experts on the efficacy and safety of sterols and stanols. A meta-analysis of 41 trials showed that intake of 2 g/d of stanols or sterols reduced low-density lipoprotein (LDL) by 10%; higher intakes added little. Efficacy is similar for sterols and stanols, but the food form may substantially affect LDL reduction. Effects are additive with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20%; adding sterols or stanols to statin medication is more effective than doubling the statin dose. A meta-analysis of 10 to 15 trials per vitamin showed that plasma levels of vitamins A and D are not affected by stanols or sterols. Alpha carotene, lycopene, and vitamin E levels remained stable relative to their carrier molecule, LDL. Beta carotene levels declined, but adverse health outcomes were not expected. Sterol-enriched foods increased plasma sterol levels, and workshop participants discussed whether this would increase risk, in view of the marked increase of atherosclerosis in patients with homozygous phytosterolemia. This risk is believed to be largely hypothetical, and any increase due to the small increase in plasma plant sterols may be more than offset by the decrease in plasma LDL. There are insufficient data to suggest that plant stanols or sterols either prevent or promote colon carcinogenesis. Safety of sterols and stanols is being monitored by follow-up of samples from the general population; however, the power of such studies to pick up infrequent increases in common diseases, if any exist, is limited. A trial with clinical outcomes probably would not answer remaining questions about infrequent adverse effects. Trials with surrogate end points such as intima-media thickness might corroborate the expected efficacy in reducing atherosclerosis. However, present evidence is sufficient to promote use of sterols and stanols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease.

An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk.

PubMed

Rodgers, Anthony; Patel, Anushka; Berwanger, Otavio; Bots, Michiel; Grimm, Richard; Grobbee, Diederick E; Jackson, Rod; Neal, Bruce; Neaton, Jim; Poulter, Neil; Rafter, Natasha; Raju, P Krishnam; Reddy, Srinath; Thom, Simon; Vander Hoorn, Stephen; Webster, Ruth

2011-01-01

There has been widespread interest in the potential of combination cardiovascular medications containing aspirin and agents to lower blood pressure and cholesterol ('polypills') to reduce cardiovascular disease. However, no reliable placebo-controlled data are available on both efficacy and tolerability. We conducted a randomised, double-blind placebo-controlled trial of a polypill (containing aspirin 75 mg, lisinopril 10 mg, hydrochlorothiazide 12.5 mg and simvastatin 20 mg) in 378 individuals without an indication for any component of the polypill, but who had an estimated 5-year cardiovascular disease risk over 7.5%. The primary outcomes were systolic blood pressure (SBP), LDL-cholesterol and tolerability (proportion discontinued randomised therapy) at 12 weeks follow-up. At baseline, mean BP was 134/81 mmHg and mean LDL-cholesterol was 3.7 mmol/L. Over 12 weeks, polypill treatment reduced SBP by 9.9 (95% CI: 7.7 to 12.1) mmHg and LDL-cholesterol by 0.8 (95% CI 0.6 to 0.9) mmol/L. The discontinuation rates in the polypill group compared to placebo were 23% vs 18% (RR 1.33, 95% CI 0.89 to 2.00, p = 0.2). There was an excess of side effects known to the component medicines (58% vs 42%, p = 0.001), which was mostly apparent within a few weeks, and usually did not warrant cessation of trial treatment. This polypill achieved sizeable reductions in SBP and LDL-cholesterol but caused side effects in about 1 in 6 people. The halving in predicted cardiovascular risk is moderately lower than previous estimates and the side effect rate is moderately higher. Nonetheless, substantial net benefits would be expected among patients at high risk. Australian New Zealand Clinical Trials Registry ACTRN12607000099426.

Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease.

PubMed

Sabatine, Marc S; Giugliano, Robert P; Keech, Anthony C; Honarpour, Narimon; Wiviott, Stephen D; Murphy, Sabina A; Kuder, Julia F; Wang, Huei; Liu, Thomas; Wasserman, Scott M; Sever, Peter S; Pedersen, Terje R

2017-05-04

Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P<0.001). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85; 95% confidence interval [CI], 0.79 to 0.92; P<0.001) and the key secondary end point (816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80; 95% CI, 0.73 to 0.88; P<0.001). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events), with the exception of injection-site reactions, which were more common with evolocumab (2.1% vs. 1.6%). In our trial, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular events. These findings show that patients with atherosclerotic cardiovascular disease benefit from lowering of LDL cholesterol levels below current targets. (Funded by Amgen; FOURIER ClinicalTrials.gov number, NCT01764633 .).

Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial.

PubMed

Giugliano, Robert P; Pedersen, Terje R; Park, Jeong-Gun; De Ferrari, Gaetano M; Gaciong, Zbigniew A; Ceska, Richard; Toth, Kalman; Gouni-Berthold, Ioanna; Lopez-Miranda, Jose; Schiele, François; Mach, François; Ott, Brian R; Kanevsky, Estella; Pineda, Armando Lira; Somaratne, Ransi; Wasserman, Scott M; Keech, Anthony C; Sever, Peter S; Sabatine, Marc S

2017-10-28

LDL cholesterol is a well established risk factor for atherosclerotic cardiovascular disease. How much one should or safely can lower this risk factor remains debated. We aimed to explore the relationship between progressively lower LDL-cholesterol concentrations achieved at 4 weeks and clinical efficacy and safety in the FOURIER trial of evolocumab, a monoclonal antibody to proprotein convertase subtilisin-kexin type 9 (PCSK9). In this prespecified secondary analysis of 25 982 patients from the randomised FOURIER trial, the relationship between achieved LDL-cholesterol concentration at 4 weeks and subsequent cardiovascular outcomes (primary endpoint was the composite of cardiovascular death, myocardial infarction, stroke, coronary revascularisation, or unstable angina; key secondary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke) and ten prespecified safety events of interest was examined over a median of 2·2 years of follow-up. We used multivariable modelling to adjust for baseline factors associated with achieved LDL cholesterol. This trial is registered with ClinicalTrials.gov, number NCT01764633. Between Feb 8, 2013, and June 5, 2015, 27 564 patients were randomly assigned a treatment in the FOURIER study. 1025 (4%) patients did not have an LDL cholesterol measured at 4 weeks and 557 (2%) had already had a primary endpoint event or one of the ten prespecified safety events before the week-4 visit. From the remaining 25 982 patients (94% of those randomly assigned) 13 013 were assigned evolocumab and 12 969 were assigned placebo. 2669 (10%) of 25 982 patients achieved LDL-cholesterol concentrations of less than 0·5 mmol/L, 8003 (31%) patients achieved concentrations between 0·5 and less than 1·3 mmol/L, 3444 (13%) patients achieved concentrations between 1·3 and less than 1·8 mmol/L, 7471 (29%) patients achieved concentrations between 1·8 to less than 2·6 mmol/L, and 4395 (17%) patients achieved concentrations of 2·6 mmol/L or higher. There was a highly significant monotonic relationship between low LDL-cholesterol concentrations and lower risk of the primary and secondary efficacy composite endpoints extending to the bottom first percentile (LDL-cholesterol concentrations of less than 0·2 mmol/L; p=0·0012 for the primary endpoint, p=0·0001 for the secondary endpoint). Conversely, no significant association was observed between achieved LDL cholesterol and safety outcomes, either for all serious adverse events or any of the other nine prespecified safety events. There was a monotonic relationship between achieved LDL cholesterol and major cardiovascular outcomes down to LDL-cholesterol concentrations of less than 0·2 mmol/L. Conversely, there were no safety concerns with very low LDL-cholesterol concentrations over a median of 2·2 years. These data support further LDL-cholesterol lowering in patients with cardiovascular disease to well below current recommendations. Amgen. Copyright © 2017 Elsevier Ltd. All rights reserved.

Full-length amyloid precursor protein regulates lipoprotein metabolism and amyloid-β clearance in human astrocytes.

PubMed

Fong, Lauren K; Yang, Max M; Dos Santos Chaves, Rodrigo; Reyna, Sol M; Langness, Vanessa F; Woodruff, Grace; Roberts, Elizabeth A; Young, Jessica E; Goldstein, Lawrence S B

2018-06-01

Mounting evidence suggests that alterations in cholesterol homeostasis are involved in Alzheimer's disease (AD) pathogenesis. Amyloid precursor protein (APP) or multiple fragments generated by proteolytic processing of APP have previously been implicated in the regulation of cholesterol metabolism. However, the physiological function of APP in regulating lipoprotein homeostasis in astrocytes, which are responsible for de novo cholesterol biosynthesis and regulation in the brain, remains unclear. To address this, here we used CRISPR/Cas9 genome editing to generate isogenic APP-knockout (KO) human induced pluripotent stem cells (hiPSCs) and differentiated them into human astrocytes. We found that APP-KO astrocytes have reduced cholesterol and elevated levels of sterol regulatory element-binding protein (SREBP) target gene transcripts and proteins, which were both downstream consequences of reduced lipoprotein endocytosis. To elucidate which APP fragments regulate cholesterol homeostasis and examine whether familial AD mutations in APP affect lipoprotein metabolism, we analyzed an isogenic allelic series harboring the APP Swedish and APP V717F variants. Only astrocytes homozygous for the APP Swedish (APP Swe/Swe ) mutation, which had reduced full-length APP (FL APP) due to increased β-secretase cleavage, recapitulated the APP-KO phenotypes. Astrocytic internalization of amyloid-β (Aβ), another ligand for low-density lipoprotein (LDL) receptors, was also impaired in APP-KO and APP Swe/Swe astrocytes. Finally, impairing cleavage of FL APP through β-secretase inhibition in APP Swe/Swe astrocytes reversed the LDL and Aβ endocytosis defects. In conclusion, FL APP is involved in the endocytosis of LDL receptor ligands and required for proper cholesterol homeostasis and Aβ clearance in human astrocytes. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Low-density lipoprotein cholesterol versus particle number in middle school children.

PubMed

Mietus-Snyder, Michele; Drews, Kimberly L; Otvos, James D; Willi, Steven M; Foster, Gary D; Jago, Russell; Buse, John B

2013-08-01

To characterize lipids and lipoproteins in a diverse school-based cohort and identify features associated with discordance between low-density lipoprotein cholesterol (LDL-C) and LDL particle (LDL-P). Sixth-grade children enrolled in the HEALTHY trial (n = 2384; mean age 11.3 ± 0.6 years; 54.2% female) were evaluated for standard lipids, lipoprotein particles measured by nuclear magnetic resonance, and homeostatic model of insulin resistance. Characteristics of subgroups with values of LDL-C and LDL-P discordant by >20 percentile units, an amount reasoned to be clinically significant, were compared. Four-hundred twenty-eight (18%) of children were in the LDL-P < LDL-C subgroup and 375 (16%) in the LDL-P > LDL-C subgroup. Those with LDL-P > LDL-C had significantly greater body mass index, waist circumference, homeostatic model of insulin resistance, triglycerides, systolic and diastolic blood pressure, and reflected a greater Hispanic ethnic composition but fewer of black race than both the concordant (LDL-P ≅ LDL-C) and opposite discordant (LDL-P < LDL-C) subgroups. There is as much lipoprotein cholesterol compositional heterogeneity in sixth graders as has been described in adults and a discordant atherogenic phenotype of LDL-P > LDL-C, common in obesity, is often missed when only LDL-C is considered. Conversely, many children with moderate-risk cholesterol measures (75th to 99th percentile) have a lower LDL-P burden. Copyright © 2013 Mosby, Inc. All rights reserved.

Estimation and correlation of stress and cholesterol levels in college teachers and housewives of Hyderabad-Pakistan.

PubMed

Wattoo, Feroza Hamid; Memon, Muhammad Saleh; Memon, Allah Nawaz; Wattoo, Muhammad Hamid Sarwar; Tirmizi, Syed Ahmed; Iqbal, Javed

2008-01-01

To evaluate environmental, psychological and physiological stresses in college teachers and housewives, and to correlate with their serum total cholesterol, HDL cholesterol, and LDL cholesterol, and triglyceride levels. This cohort study was performed at the Institute of Biochemistry, University of Sindh, Jamshoro, Pakistan during 2003-2005. Eighty females from middle socioeconomic groups, college teachers (40) and housewives (40) aged between 25-45 years participated in this study and subjects were selected from Hyderabad and its adjoining areas. Environmental, psychological and physiological stress levels were measured with Likert scale. Total cholesterol, LDL cholesterol and HDL cholesterol were measured by CHOD-PAP method and triglyceride levels were measured by GPO method. Housewives had high levels of total cholesterol, LDL cholesterol and triglyceride but low levels of HDL cholesterol were found in college teachers. Environmental, psychological and physiological stresses were significantly higher in housewives as compared to college teachers. Housewives were under more stress than college teachers. High levels of total cholesterol, LDL cholesterol and triglyceride but low levels of HDL cholesterol were found in housewives compared to college teachers.

A genetic variant in the LDLR promoter is responsible for part of the LDL-cholesterol variability in primary hypercholesterolemia

PubMed Central

2014-01-01

Background GWAS have consistently revealed that LDLR locus variability influences LDL-cholesterol in general population. Severe LDLR mutations are responsible for familial hypercholesterolemia (FH). However, most primary hypercholesterolemias are polygenic diseases. Although Cis-regulatory regions might be the cause of LDL-cholesterol variability; an extensive analysis of the LDLR distal promoter has not yet been performed. We hypothesized that genetic variants in this region are responsible for the LDLR association with LDL-cholesterol found in GWAS. Methods Four-hundred seventy-seven unrelated subjects with polygenic hypercholesterolemia (PH) and without causative FH-mutations and 525 normolipemic subjects were selected. A 3103 pb from LDLR (-625 to +2468) was sequenced in 125 subjects with PH. All subjects were genotyped for 4 SNPs (rs17242346, rs17242739, rs17248720 and rs17249120) predicted to be potentially involved in transcription regulation by in silico analysis. EMSA and luciferase assays were carried out for the rs17248720 variant. Multivariable linear regression analysis using LDL-cholesterol levels as the dependent variable were done in order to find out the variables that were independently associated with LDL-cholesterol. Results The sequencing of the 125 PH subjects did not show variants with minor allele frequency ≥ 10%. The T-allele from g.3131C > T (rs17248720) had frequencies of 9% (PH) and 16.4% (normolipemic), p < 0.00001. Studies of this variant with EMSA and luciferase assays showed a higher affinity for transcription factors and an increase of 2.5 times in LDLR transcriptional activity (T-allele vs C-allele). At multivariate analysis, this polymorphism with the lipoprotein(a) and age explained ≈ 10% of LDL-cholesterol variability. Conclusion Our results suggest that the T-allele at the g.3131 T > C SNP is associated with LDL-cholesterol levels, and explains part of the LDL-cholesterol variability. As a plausible cause, the T-allele produces an increase in LDLR transcriptional activity and lower LDL-cholesterol levels. PMID:24708769

Soy, soy phytoestrogens and cardiovascular disease.

PubMed

Clarkson, Thomas B

2002-03-01

Dietary soy protein has been shown to have several beneficial effects on cardiovascular health. The best-documented effect is on plasma lipid and lipoprotein concentrations, with reductions of approximately 10% in LDL cholesterol concentrations (somewhat greater for individuals with high pretreatment LDL cholesterol concentrations) and small increases in HDL cholesterol concentrations. Dietary soy protein improves flow-mediated arterial dilation of postmenopausal women but worsens that of men. Soy isoflavone extracts improve systemic arterial compliance, an indicator of atherosclerosis extent. Complete soy protein but not alcohol-washed soy protein reduces atherosclerosis of postmenopausal monkeys. No definite experimental evidence exists currently to establish that the cardiovascular benefits of soy protein are accounted for by its isoflavones.

EFFECT OF-GYMNEMA SYLVESTRE, CITRULLUS COLOCYNTHIS AND ARTEMISIA ABSINTHIUM ON BLOOD GLUCOSE AND LIPID PROFILE IN DIABETIC HUMAN.

PubMed

Li, Youshan; Zheng, Min; Zhai, Xing; Huang, Youliang; Khalid, Anwar; Malik, Aneela; Shah, Pervaiz; Karim, Sabiha; Azhar, Saira; Hou, Xiaobing

2015-01-01

The aim of this study was to manage diabetes with medicinal plants (Gymnema sylvestre, Artemisia absinthium and Citillus colocynthis) in human patients with type II diabetes. Thirty two patients of type II diabetes from both sexes of 30-60 years age were registered for this study and distributed them into four groups, each having 8 patients. Capsules of each, Gymnema sylvestre, Artemisia absinthium and Citrullus colocynthis were given to patients twice a day for 30 days in 1 g per day dosage and investigated for glucose, triglyceride (TGL) and cholesterol level. Gymnema sylvestre reduced 37% glucose, 5% TGL, 13% cholesterol and 19% low desity lipoproteins (LDL) level in diabetic individuals. Citrullus colocynth reduced glucose, cholesterol and TGL and HDL-cholesterol level by 35, 6, 6, and 5%, respectively. Artemisia absinthium reduced 3% high desity lipoproteins (HDL) and 6% LDL level. From results, it can be concluded that the powdered Gymnema sylvestre, Citrulus colocynthis, and Artemisia absinthium possess good anti-diabetic features, however these herbal products had no significant effect on lipid profiles of the diabetic human.

Clinical and pathophysiological evidence supporting the safety of extremely low LDL levels-The zero-LDL hypothesis.

PubMed

Masana, Luis; Girona, Josefa; Ibarretxe, Daiana; Rodríguez-Calvo, Ricardo; Rosales, Roser; Vallvé, Joan-Carles; Rodríguez-Borjabad, Cèlia; Guardiola, Montserrat; Rodríguez, Marina; Guaita-Esteruelas, Sandra; Oliva, Iris; Martínez-Micaelo, Neus; Heras, Mercedes; Ferré, Raimon; Ribalta, Josep; Plana, Núria

While the impact of very low concentrations of low-density lipoprotein cholesterol (LDL-C) on cardiovascular prevention is very reassuring, it is intriguing to know what effect these extremely low LDL-C concentrations have on lipid homoeostasis. The evidence supporting the safety of extremely low LDL levels comes from genetic studies and clinical drug trials. Individuals with lifelong low LDL levels due to mutations in genes associated with increased LDL-LDL receptor (LDLR) activity reveal no safety issues. Patients achieving extremely low LDL levels in the IMPROVE-IT and FOURIER, and the PROFICIO and ODYSSEY programs seem not to have an increased prevalence of adverse effects. The main concern regarding extremely low LDL-C plasma concentrations is the adequacy of the supply of cholesterol, and other molecules, to peripheral tissues. However, LDL proteomic and kinetic studies reaffirm that LDL is the final product of endogenous lipoprotein metabolism. Four of 5 LDL particles are cleared through the LDL-LDLR pathway in the liver. Given that mammalian cells have no enzymatic systems to degrade cholesterol, the LDL-LDLR pathway is the main mechanism for removal of cholesterol from the body. Our focus, therefore, is to review, from a physiological perspective, why such extremely low LDL-C concentrations do not appear to be detrimental. We suggest that extremely low LDL-C levels due to increased LDLR activity may be a surrogate of adequate LDL-LDLR pathway function. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy.

PubMed

McGowan, Mary P; Tardif, Jean-Claude; Ceska, Richard; Burgess, Lesley J; Soran, Handrean; Gouni-Berthold, Ioanna; Wagener, Gilbert; Chasan-Taber, Scott

2012-01-01

Mipomersen, an antisense oligonucleotide targeting apolipoprotein B synthesis, significantly reduces LDL-C and other atherogenic lipoproteins in familial hypercholesterolemia when added to ongoing maximally tolerated lipid-lowering therapy. Safety and efficacy of mipomersen in patients with severe hypercholesterolemia was evaluated. Randomized, double-blind, placebo-controlled, multicenter trial. Patients (n  = 58) were ≥18 years with LDL-C ≥7.8 mmol/L or LDL-C ≥5.1 mmol/L plus CHD disease, on maximally tolerated lipid-lowering therapy that excluded apheresis. Weekly subcutaneous injections of mipomersen 200 mg (n  = 39) or placebo (n  = 19) were added to lipid-lowering therapy for 26 weeks. percent reduction in LDL-C from baseline to 2 weeks after the last dose of treatment. Mipomersen (n = 27) reduced LDL-C by 36%, from a baseline of 7.2 mmol/L, for a mean absolute reduction of 2.6 mmol/L. Conversely, mean LDL-C increased 13% in placebo (n = 18) from a baseline of 6.5 mmol/L (mipomersen vs placebo p<0.001). Mipomersen produced statistically significant (p<0.001) reductions in apolipoprotein B and lipoprotein(a), with no change in high-density lipoprotein cholesterol. Mild-to-moderate injection site reactions were the most frequently reported adverse events with mipomersen. Mild-to-moderate flu-like symptoms were reported more often with mipomersen. Alanine transaminase increase, aspartate transaminase increase, and hepatic steatosis occurred in 21%, 13% and 13% of mipomersen treated patients, respectively. Adverse events by category for the placebo and mipomersen groups respectively were: total adverse events, 16(84.2%), 39(100%); serious adverse events, 0(0%), 6(15.4%); discontinuations due to adverse events, 1(5.3%), 8(20.5%) and cardiac adverse events, 1(5.3%), 5(12.8%). Mipomersen significantly reduced LDL-C, apolipoprotein B, total cholesterol and non-HDL-cholesterol, and lipoprotein(a). Mounting evidence suggests it may be a potential pharmacologic option for lowering LDL-C in patients with severe hypercholesterolemia not adequately controlled using existing therapies. Future studies will explore alternative dosing schedules aimed at minimizing side effects. ClinicalTrials.gov NCT00794664.

Fluid-Phase Pinocytosis of Native Low Density Lipoprotein Promotes Murine M-CSF Differentiated Macrophage Foam Cell Formation

PubMed Central

Xu, Qing; Bohnacker, Thomas; Wymann, Matthias P.; Kruth, Howard S.

2013-01-01

During atherosclerosis, low-density lipoprotein (LDL)-derived cholesterol accumulates in macrophages to form foam cells. Macrophage uptake of LDL promotes foam cell formation but the mechanism mediating this process is not clear. The present study investigates the mechanism of LDL uptake for macrophage colony-stimulating factor (M-CSF)-differentiated murine bone marrow-derived macrophages. LDL receptor-null (LDLR−/−) macrophages incubated with LDL showed non-saturable accumulation of cholesterol that did not down-regulate for the 24 h examined. Incubation of LDLR−/− macrophages with increasing concentrations of 125I-LDL showed non-saturable macrophage LDL uptake. A 20-fold excess of unlabeled LDL had no effect on 125I-LDL uptake by wild-type macrophages and genetic deletion of the macrophage scavenger receptors CD36 and SRA did not affect 125I-LDL uptake, showing that LDL uptake occurred by fluid-phase pinocytosis independently of receptors. Cholesterol accumulation was inhibited approximately 50% in wild-type and LDLR−/− mice treated with LY294002 or wortmannin, inhibitors of all classes of phosphoinositide 3-kinases (PI3K). Time-lapse, phase-contrast microscopy showed that macropinocytosis, an important fluid-phase uptake pathway in macrophages, was blocked almost completely by PI3K inhibition with wortmannin. Pharmacological inhibition of the class I PI3K isoforms alpha, beta, gamma or delta did not affect macrophage LDL-derived cholesterol accumulation or macropinocytosis. Furthermore, macrophages from mice expressing kinase-dead class I PI3K beta, gamma or delta isoforms showed no decrease in cholesterol accumulation or macropinocytosis when compared with wild-type macrophages. Thus, non-class I PI3K isoforms mediated macropinocytosis in these macrophages. Further characterization of the components necessary for LDL uptake, cholesterol accumulation, and macropinocytosis identified dynamin, microtubules, actin, and vacuolar type H(+)-ATPase as contributing to uptake. However, Pak1, Rac1, and Src-family kinases, which mediate fluid-phase pinocytosis in certain other cell types, were unnecessary. In conclusion, our findings provide evidence that targeting those components mediating macrophage macropinocytosis with inhibitors may be an effective strategy to limit macrophage accumulation of LDL-derived cholesterol in arteries. PMID:23536783

SIRT6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox-LDL condition.

PubMed

He, Jiangping; Zhang, Guangya; Pang, Qi; Yu, Cong; Xiong, Jie; Zhu, Jing; Chen, Fengling

2017-05-01

SIRT6 is a pivotal regulator of lipid metabolism. It is also closely connected to cardiovascular diseases, which are the main cause of death in diabetic patients. We observed a decrease in the expression of SIRT6 and key autophagy effectors (ATG5, LC3B, and LAMP1) in ox-LDL-induced foam cells, a special form of lipid-laden macrophages. In these cells, SIRT6 WT but not SIRT6 H133Y overexpression markedly reduced foam cell formation, as shown by Oil Red O staining, while inducing autophagy flux, as determined by both mRFP-GFP-LC3 labeling and transmission electron microscopy. Silencing the key autophagy initiation gene ATG5, reversed the autophagy-promoting effect of SIRT6 in ox-LDL-treated THP1 cells, as evidenced by an increase in foam cells. Cholesterol efflux assays indicated that SIRT6 overexpression in foam cells promoted cholesterol efflux, increased the levels of ABCA1 and ABCG1, and reduced miR-33 levels. By transfecting miR-33 into cells overexpressing SIRT6, we observed that reduced foam cell formation and autophagy flux induction were largely reversed. These data imply that SIRT6 plays an essential role in protecting against atherosclerosis by reducing foam cell formation through an autophagy-dependent pathway. © 2017 Federation of European Biochemical Societies.

Statins, fibrates, nicotinic acid, cholesterol absorption inhibitors, anion-exchange resins, omega-3 fatty acids: which drugs for which patients?

PubMed

Drexel, Heinz

2009-12-01

Classes of lipid lowering drugs differ strongly with respect to the types of lipids or lipoproteins they predominantly affect. Statins inhibit the de-novo synthesis of cholesterol. Consequently, the liver produces less VLDL, and the serum concentration primarily of LDL cholesterol (but, to a lesser extent, also of triglycerides) is lowered. Further, statins somewhat increase HDL cholesterol. There is abundant evidence that statins lower the rate of cardiovascular events. Cardiovascular risk reduction is the better, the lower the LDL cholesterol values achieved with statin therapy are. Some evidence is available that anion exchange resins which also decrease LDL cholesterol decrease vascular risk, too. This is not the case for the ezetimibe, which strongly lowers LDL cholesterol: its potential to decrease vascular risk remains to be proven. In contrast evidence for cardiovascular risk reduction through the mainly triglyceride lowering fibrates as well as for niacin is available. Niacin is the most potent HDL increasing drug currently available and besides increasing HDL cholesterol efficaciously lowers triglycerides and LDL cholesterol. Large ongoing trials address the decisive question whether treatment with fibrates and niacin provides additional cardiovascular risk reduction when given in addition to statin treatment.

The use of probiotic L. fermentum ME-3 containing Reg'Activ Cholesterol supplement for 4 weeks has a positive influence on blood lipoprotein profiles and inflammatory cytokines: an open-label preliminary study.

PubMed

Kullisaar, Tiiu; Zilmer, Kersti; Salum, Tiit; Rehema, Aune; Zilmer, Mihkel

2016-10-28

Cardiovascular diseases continue to be a challenge and burden to heath. The incidence of type 2 diabetes is increasing. Modifying the (common) risk factors of them is the key of longterm success. The aim of the study was to establish if the special composition of innovative food supplement Reg'Activ Cholesterol (RAC) has a positive influence to the human body cardiovascular-inflammatory and diabetic parameters. Forty-five clinically asymptomatic participants consumed an RAC containing an antioxidative and antiatherogenic probiotic Lactobacillus fermentum ME-3 (LFME-3) for 4 weeks. The parameters measured were total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, oxLDL, hsCRP, IL-6 and glycosylated haemoglobin (HbA1c%). The cardiovascular and diabetes risk profile of the participants improved significantly after 4 weeks of the intervention. The reduction of total cholesterol (from 6.5 ± 1.0 to 5.7 ± 0.9 mmol/l, p = 9.90806E-11) was on the account of LDL cholesterol as the HDL cholesterol level rose from 1.60 ± 0.31to 1.67 ± 0.34mml/l, p = 0.01. HbA1c% was reduced from 5.85 ± 0.28 to 5.66 ± 0.25 p = 4.64E-05 and oxLDL decreased from 84 ± 20 to 71 ± 15 U/l, p = 4.66292E-08. The consumption of RAC in clinically asymptomatic volunteers with borderline-high values of risk factors for cardiovascular disease (BMI, HbA1c%, LDL cholesterol) for 4 weeks had a positive effect on blood lipoprotein, oxidative stress and inflammatory profile. There are no human trials published before with RAC. The trial described here isa n open label pilot study within the framework of a larger special clinical trial ( ISRCTN55339917 ) [Accessed 20 Feb 2016].

Intracellular trafficking of the free cholesterol derived from LDL cholesteryl ester is defective in vivo in Niemann-Pick C disease: insights on normal metabolism of HDL and LDL gained from the NP-C mutation.

PubMed

Shamburek, R D; Pentchev, P G; Zech, L A; Blanchette-Mackie, J; Carstea, E D; VandenBroek, J M; Cooper, P S; Neufeld, E B; Phair, R D; Brewer, H B; Brady, R O; Schwartz, C C

1997-12-01

Niemann-Pick C disease (NP-C) is a rare inborn error of metabolism with hepatic involvement and neurological sequelae that usually manifest in childhood. Although in vitro studies have shown that the lysosomal distribution of LDL-derived cholesterol is defective in cultured cells of NP-C subjects, no unusual characteristics mark the plasma lipoprotein profiles. We set out to determine whether anomalies exist in vivo in the cellular distribution of newly synthesized, HDL-derived or LDL-derived cholesterol under physiologic conditions in NP-C subjects. Three affected and three normal male subjects were administered [14C]mevalonate as a tracer of newly synthesized cholesterol and [3H]cholesteryl linoleate in either HDL or LDL to trace the distribution of lipoprotein-derived free cholesterol. The rate of appearance of free [14C]- and free [3H]cholesterol in the plasma membrane was detected indirectly by monitoring their appearance in plasma and bile. The plasma disappearance of [3H]cholesteryl linoleate was slightly faster in NP-C subjects regardless of its lipoprotein origin. Appearance of free [14C] cholesterol ill the plasma (and in bile) was essentially identical in normal and affected individuals as was the initial appearance of free [3H]cholesterol derived from HDL, observed before extensive exchange occurred of the [3H]cholesteryl linoleate among lipoproteins. In contrast, the rate of appearance of LDL-derived free [3H]cholesterol in the plasma membrane of NP-C subjects, as detected in plasma and bile, was retarded to a similar extent that LDL cholesterol metabolism was defective in cultured fibroblasts of these affected subjects. These findings show that intracellular distribution of both newly synthesized and HDL-derived cholesterol are essentially unperturbed by the NP-C mutation, and therefore occur by lysosomal-independent paths. In contrast, in NP-C there is defective trafficking of LDL-derived cholesterol to the plasma membrane in vivo as well as in vitro. The in vivo assay of intracellular cholesterol distribution developed herein should prove useful to quickly evaluate therapeutic interventions for NP-C.

[New agents for hypercholesterolemia].

PubMed

Pintó, Xavier; García Gómez, María Carmen

2016-02-19

An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of cholesterol lowering medications or to patients' bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Fasting time and lipid parameters: association with hepatic steatosis — data from a random population sample

PubMed Central

2014-01-01

Background Current guidelines recommend measuring plasma lipids in fasting patients. Recent studies, however, suggest that variation in plasma lipid concentrations secondary to fasting time may be minimal. Objective of the present study was to investigate the impact of fasting time on plasma lipid concentrations (total cholesterol, HDL and LDL cholesterol, triglycerides). A second objective was to determine the effect of non-alcoholic fatty liver disease exerted on the above-mentioned lipid levels. Method Subjects participating in a population-based cross-sectional study (2,445 subjects; 51.7% females) were questioned at time of phlebotomy regarding duration of pre-phlebotomy fasting. Total cholesterol, LDL and HDL cholesterol, and triglycerides were determined and correlated with length of fasting. An upper abdominal ultrasonographic examination was performed and body-mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Subjects were divided into three groups based on their reported fasting periods of 1–4 h, 4–8 h and > 8 h. After application of the exclusion criteria, a total of 1,195 subjects (52.4% females) were included in the study collective. The Kruskal-Wallis test was used for continuous variables and the chi-square test for categorical variables. The effects of age, BMI, WHR, alcohol consumption, fasting time and hepatic steatosis on the respective lipid variables were analyzed using multivariate logistic regression. Results At multivariate analysis, fasting time was associated with elevated triglycerides (p = 0.0047 for 1–4 h and p = 0.0147 for 4–8 h among females; p < 0.0001 for 1–4 h and p = 0.0002 for 4–8 h among males) and reduced LDL cholesterol levels (p = 0.0003 for 1–4 h and p = 0.0327 for 4–8 h among males). Among males, hepatic steatosis represents an independent factor affecting elevated total cholesterol (p = 0.0278) and triglyceride concentrations (p = 0.0002). Conclusion Total and HDL cholesterol concentrations are subject to slight variations in relation to the duration of the pre-phlebotomy fasting period. LDL cholesterol and triglycerides exhibit highly significant variability; the greatest impact is seen with the triglycerides. Fasting time represents an independent factor for reduced LDL cholesterol and elevated triglyceride concentrations. There is a close association between elevated lipids and hepatic steatosis. PMID:24447492

Pharmacologic profile of the Adnectin BMS-962476, a small protein biologic alternative to PCSK9 antibodies for low-density lipoprotein lowering.

PubMed

Mitchell, Tracy; Chao, Ginger; Sitkoff, Doree; Lo, Fred; Monshizadegan, Hossain; Meyers, Daniel; Low, Simon; Russo, Katie; DiBella, Rose; Denhez, Fabienne; Gao, Mian; Myers, Joseph; Duke, Gerald; Witmer, Mark; Miao, Bowman; Ho, Siew P; Khan, Javed; Parker, Rex A

2014-08-01

Proprotein convertase subtilisin kexin-9 (PCSK9) is an important pharmacological target for decreasing low-density lipoprotein (LDL) in cardiovascular disease, although seemingly inaccessible to small molecule approaches. Compared with therapeutic IgG antibodies currently in development, targeting circulating PCSK9 with smaller molecular scaffolds could offer different profiles and reduced dose burdens. This inspired genesis of PCSK9-binding Adnectins, a protein family derived from human fibronectin-10th-type III-domain and engineered for high-affinity target binding. BMS-962476, an ∼11-kDa polypeptide conjugated to polyethylene glycol to enhance pharmacokinetics, binds with subnanomolar affinity to human. The X-ray cocrystal structure of PCSK9 with a progenitor Adnectin shows ∼910 Å(2) of PCSK9 surface covered next to the LDL receptor binding site, largely by residues of a single loop of the Adnectin. In hypercholesterolemic, overexpressing human PCSK9 transgenic mice, BMS-962476 rapidly lowered cholesterol and free PCSK9 levels. In genomic transgenic mice, BMS-962476 potently reduced free human PCSK9 (ED50 ∼0.01 mg/kg) followed by ∼2-fold increases in total PCSK9 before return to baseline. Treatment of cynomolgus monkeys with BMS-962476 rapidly suppressed free PCSK9 >99% and LDL-cholesterol ∼55% with subsequent 6-fold increase in total PCSK9, suggesting reduced clearance of circulating complex. Liver sterol response genes were consequently downregulated, following which LDL and total PCSK9 returned to baseline. These studies highlight the rapid dynamics of PCSK9 control over LDL and liver cholesterol metabolism and characterize BMS-962476 as a potent and efficacious PCSK9 inhibitor. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Identification of the Best Anthropometric Predictors of Serum High- and Low-Density Lipoproteins Using Machine Learning.

PubMed

Lee, Bum Ju; Kim, Jong Yeol

2015-09-01

Serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels are associated with risk factors for various diseases and are related to anthropometric measures. However, controversy remains regarding the best anthropometric indicators of the HDL and LDL cholesterol levels. The objectives of this study were to identify the best predictors of HDL and LDL cholesterol using statistical analyses and two machine learning algorithms and to compare the predictive power of combined anthropometric measures in Korean adults. A total of 13,014 subjects participated in this study. The anthropometric measures were assessed with binary logistic regression (LR) to evaluate statistically significant differences between the subjects with normal and high LDL cholesterol levels and between the subjects with normal and low HDL cholesterol levels. LR and the naive Bayes algorithm (NB), which provides more reasonable and reliable results, were used in the analyses of the predictive power of individual and combined measures. The best predictor of HDL was the rib to hip ratio (p =< 0.0001; odds ratio (OR) = 1.895; area under curve (AUC) = 0.681) in women and the waist to hip ratio (WHR) (p =< 0.0001; OR = 1.624; AUC = 0.633) in men. In women, the strongest indicator of LDL was age (p =< 0.0001; OR = 1.662; AUC by NB = 0.653 ; AUC by LR = 0.636). Among the anthropometric measures, the body mass index (BMI), WHR, forehead to waist ratio, forehead to rib ratio, and forehead to chest ratio were the strongest predictors of LDL; these measures had similar predictive powers. The strongest predictor in men was BMI (p =< 0.0001; OR = 1.369; AUC by NB = 0.594; AUC by LR = 0.595 ). The predictive power of almost all individual anthropometric measures was higher for HDL than for LDL, and the predictive power for both HDL and LDL in women was higher than for men. A combination of anthropometric measures slightly improved the predictive power for both HDL and LDL cholesterol. The best indicator for HDL and LDL might differ according to the type of cholesterol and the gender. In women, but not men, age was the variable that strongly predicted HDL and LDL cholesterol levels. Our findings provide new information for the development of better initial screening tools for HDL and LDL cholesterol.

VLDL Cholesterol

MedlinePlus

... it into your bloodstream. The VLDL particles carry triglycerides, another type of fat, to your tissues. VLDL ... LDL carries cholesterol to your tissues instead of triglycerides. VLDL and LDL are "bad" cholesterols because they ...

Complementary Cholesterol-Lowering Response of a Phytosterol/α-Lipoic Acid Combination in Obese Zucker Rats

PubMed Central

Rideout, Todd C.; Carrier, Bradley; Wen, Shin; Raslawsky, Amy; Browne, Richard W.; Harding, Scott V.

2015-01-01

To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (−55%) than either the PS (−24%) or the αLA (−25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (−47%) or in combination with PS (−54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21–22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone. PMID:25664679

The Effect of a Three-Week Adaptation to a Low Carbohydrate/High Fat Diet on Metabolism and Cognitive Performance

DTIC Science & Technology

1990-04-11

triglycerides , insulin, glucagon, cholesterol (total, high density lipoprotein ( HDL ), low density lipoprotein (LDL)I, cortisol, thyroid hormone...thyroid function, triglycerides , total cholesterol , high density lipoprotein cholesterol ( HDL ), low density lipoprotein cholesterol (LDL), ketone... density lipoprotein ( HDL ) fraction of cholesterol was

Blockade of cholesterol absorption by ezetimibe reveals a complex homeostatic network in enterocytes[S

PubMed Central

Engelking, Luke J.; McFarlane, Matthew R.; Li, Christina K.; Liang, Guosheng

2012-01-01

Enterocyte cholesterol homeostasis reflects aggregated rates of sterol synthesis, efflux, and uptake from plasma and gut lumen. Cholesterol synthesis and LDL uptake are coordinately regulated by sterol regulatory element-binding proteins (SREBP), whereas sterol efflux is regulated by liver X receptors (LXR). How these processes are coordinately regulated in enterocytes, the site of cholesterol absorption, is not well understood. Here, we treat mice with ezetimibe to investigate the effect of blocking cholesterol absorption on intestinal SREBPs, LXRs, and their effectors. Ezetimibe increased nuclear SREBP-2 8-fold. HMG-CoA reductase (HMGR) and LDL receptor (LDLR) mRNA levels increased less than 3-fold, whereas their protein levels increased 30- and 10-fold, respectively. Expression of inducible degrader of LDLR (IDOL), an LXR-regulated gene that degrades LDLRs, was reduced 50% by ezetimibe. Coadministration of ezetimibe with the LXR agonist T0901317 abolished the reduction in IDOL and prevented the increase in LDLR protein. Ezetimibe-stimulated LDLR expression was independent of proprotein convertase subtilisin/kexin type 9 (PSCK9), a protein that degrades LDLRs. To maintain cholesterol homeostasis in the face of ezetimibe, enterocytes boost LDL uptake by increasing LDLR number, and they boost sterol synthesis by increasing HMGR and other cholesterologenic genes. These studies reveal a hitherto undescribed homeostatic network in enterocytes triggered by blockade of cholesterol absorption. PMID:22523394

Cholesterol accumulation in tissues of the Niemann-pick type C mouse is determined by the rate of lipoprotein-cholesterol uptake through the coated-pit pathway in each organ.

PubMed

Xie, C; Turley, S D; Dietschy, J M

1999-10-12

Niemann-Pick type C (NPC) disease is associated with the accumulation of unesterified cholesterol in nearly all tissues and with progressive neurodegeneration. A murine model of this disease, the NPC mouse, was used to determine whether this sequestered cholesterol represented sterol carried in low density lipoprotein (LDL) and chylomicrons (CMs) taken up into the tissues through the coated-pit pathway. By 7 weeks of age, the sterol pool in the NPC mice had increased from 2,165 to 5,669 mg/kg body weight because of the daily sequestration of 67 mg of cholesterol per kg in the various organs. This was 7-fold greater than the rate of accumulation in control mice. The rate of LDL clearance in the NPC mouse was normal (523 ml/day per kg) and accounted for the uptake of 78 mg/day per kg of cholesterol in LDL whereas 8 mg/day per kg was taken up from CMs. Deletion of the LDL receptor in NPC mice altered the concentration of unesterified cholesterol in every organ in a manner consistent with the changes also observed in the rate of LDL cholesterol uptake in those tissues. Similarly, altering the flow of cholesterol to the liver through the CM pathway changed the concentration of unesterified cholesterol in that organ. Together, these observations strongly support the conclusion that, in NPC disease, it is cholesterol carried in LDL and CMs that is sequestered in the tissues and not sterol that is newly synthesized and carried in high density lipoprotein.

Sex Differences in the Impact of the Mediterranean Diet on LDL Particle Size Distribution and Oxidation.

PubMed

Bédard, Alexandra; Corneau, Louise; Lamarche, Benoît; Dodin, Sylvie; Lemieux, Simone

2015-05-15

Sex differences have been previously highlighted in the cardioprotective effects of the Mediterranean diet (MedDiet). The objective of this study was to investigate whether sex differences also exist with regard to LDL particle size distribution and oxidation. Participants were 37 men and 32 premenopausal women (24-53 years) with slightly elevated LDL-C concentrations (3.4-4.9 mmol/L) or total cholesterol/HDL-C ≥5.0. Variables were measured before and after a four-week isoenergetic MedDiet. Sex differences were found in response to the MedDiet for the proportion of medium LDL (255-260 Å) (p for sex-by-time interaction = 0.01) and small, dense LDL (sdLDL; <255 Å) (trend; p for sex-by-time interaction = 0.06), men experiencing an increase in the proportion of medium LDL with a concomitant reduction in the proportion of sdLDL, while an opposite trend was observed in women. A sex difference was also noted for estimated cholesterol concentrations among sdLDL (p for sex-by-time interaction = 0.03), with only men experiencing a reduction in response to the MedDiet. The MedDiet marginally reduced oxidized LDL (oxLDL) concentrations (p = 0.07), with no sex difference. Results suggest that short-term consumption of the MedDiet leads to a favorable redistribution of LDL subclasses from smaller to larger LDL only in men. These results highlight the importance of considering sex issues in cardiovascular benefits of the MedDiet.

Small dense low density lipoprotein cholesterol and coronary heart disease: results from the Framingham Offspring Study

USDA-ARS?s Scientific Manuscript database

We sought to establish reference values for a new direct assay for small dense LDL cholesterol (sdLDL-C) and to measure sdLDL-C concentrations in patients with established coronary heart disease (CHD) vs controls. Direct LDL-C and sdLDL-C were measured in samples from 3188 male and female participan...

Practical technique to quantify small, dense low-density lipoprotein cholesterol using dynamic light scattering

NASA Astrophysics Data System (ADS)

Trirongjitmoah, Suchin; Iinaga, Kazuya; Sakurai, Toshihiro; Chiba, Hitoshi; Sriyudthsak, Mana; Shimizu, Koichi

2016-04-01

Quantification of small, dense low-density lipoprotein (sdLDL) cholesterol is clinically significant. We propose a practical technique to estimate the amount of sdLDL cholesterol using dynamic light scattering (DLS). An analytical solution in a closed form has newly been obtained to estimate the weight fraction of one species of scatterers in the DLS measurement of two species of scatterers. Using this solution, we can quantify the sdLDL cholesterol amount from the amounts of the low-density lipoprotein cholesterol and the high-density lipoprotein (HDL) cholesterol, which are commonly obtained through clinical tests. The accuracy of the proposed technique was confirmed experimentally using latex spheres with known size distributions. The applicability of the proposed technique was examined using samples of human blood serum. The possibility of estimating the sdLDL amount using the HDL data was demonstrated. These results suggest that the quantitative estimation of sdLDL amounts using DLS is feasible for point-of-care testing in clinical practice.

[Blood lipids and adaptation to stress as risk factors for stroke prevention].

PubMed

Anders, I; Esterbauer, E; Fink, A; Ladurner, G; Huemer, M; Wranek, U

2000-01-01

Do stroke prevention patients with increased blood-fat-protein compounds (total cholesterol, HDL- and LDL cholesterol and triglyceride) have a different method of coping than patients with normal blood fat? 1159 stroke prevention patients participated in the following stroke risk investigations at this hospital: biographical and risk factor-orientated anamnesis, a neurological status investigation, a laboratory investigation, a sonographic investigation and a psychological investigation. The differences in the coping strategies of those patients with normal and those with higher blood-fat-protein compounds were investigated. Patients with higher total cholesterol showed significantly higher values in the avoidance of stress situations (sig. 0.041) and a stronger tendency towards escapist behaviour (sig. 0.05). Patients with normal HDL cholesterol values indicated a tendency (sig. 0.07) to higher values in positive self-instruction in comparison to patients with reduced HDL cholesterol values. Those prevention patients with higher LDL values showed a tendency (sig. 0.08) to higher values in the intake of narcotic substances (nicotine, alcohol, tranquillisers, pharmaceutical agents). Patients with increased triglyceride indicated significantly higher values in coping by compensation (eating, shopping, reward behaviour, watching TV; sig. 0.037) and the intake of narcotic substances (sig. 0.044). Prevention patients with higher total cholesterol, LDL/HDL, or triglyceride values showed significantly different coping strategies in comparison to those patients with normal values. Increased avoidance and escapism behaviour and also compensation and the abuse of narcotic substances could be seen in connection with an increase in the risk of a stroke. In contrast, a constructive coping strategy such as positive self-instruction could reduce the risk of a stroke, which goes along with normal HDL cholesterol.

Inhibitory effect of Piper betel leaf extracts on copper-mediated LDL oxidation and oxLDL-induced lipid accumulation via inducing reverse cholesterol transport in macrophages.

PubMed

Ma, Gwo-Chin; Wu, Pei-Fang; Tseng, Hsien-Chun; Chyau, Charng-Cherng; Lu, Hsiu-Chin; Chou, Fen-Pi

2013-12-15

Piper betel leaf (PBL) has the biological capabilities of detoxification and can work as an anti-inflammatory agent and an anti-oxidant. In this study, we evaluated the anti-oxidative activity of the extract of Piper betel leaves (PBLs) on the basis of Cu(2+)-mediated oxidation, and its ability to prevent foam cell formation in a model for oxidised low density lipoprotein (oxLDL)-induced lipid accumulation in macrophages. Our data demonstrated that PBLs were able to inhibit LDL oxidation in vitro and are able to reduce the lipid accumulation in macrophages. We showed the underlying mechanisms to be the following: PBLs up-regulated the protein levels of the class A and class B scavenger receptors, the membrane lipid transporter ABCA1, and its upstream regulator Liver X receptor (LXR) in the macrophages exposed to oxLDL. The results suggested that PBLs activated the reverse cholesterol transport mechanism to enhance the metabolism of the oxLDL that could prevent both lipid accumulation and foam cell formation and further minimise the possible damage of vessels caused by the oxLDL. Copyright © 2013 Elsevier Ltd. All rights reserved.

Low HDL and High LDL Serum Cholesterol Are Associated With Cerebral Amyloidosis

PubMed Central

Reed, Bruce; Villeneuve, Sylvia; Mack, Wendy; DeCarli, Charles; Chui, Helena C.; Jagust, William

2014-01-01

Importance Because deposition of cerebral beta amyloid (Aβ) appears to be a key initiating event in Alzheimer’s disease, factors associated with increased deposition are of great interest. Whether or not elevated serum cholesterol acts as such a factor is unknown. Objective To investigate the relationship between serum cholesterol levels and cerebral Aβ during life, early in the AD process. Design Cross sectional analysis of potential associations between contemporaneously measured total serum cholesterol, HDL cholesterol, LDL cholesterol and cerebral Aβ, measured using PIB PET. Setting Multi-site, university medical center based study of vascular contributions to dementia. Participants 74 persons, mean age 78, recruited via direct outreach in stroke clinics and community senior facilities following a protocol designed to obtain a cohort enriched for cerebrovascular disease and elevated vascular risk. Three cases had mild dementia. All others were clinically normal (33 cases) or had mild cognitive impairment (38 cases). Results Cerebral Aβ was quantified using a global PIB index, which averages PIB retention in cortical areas prone to amyloidosis. Statistical models that controlled for age and the apoE ε4 allele showed independent associations between LDL cholesterol, HDL cholesterol and PIB index. Higher LDL and lower HDL were both associated with higher PIB index. No association was found between total cholesterol and PIB index. No association was found between statin use and PIB index, nor did controlling for cholesterol treatment in the statistical models alter the basic findings. Conclusions and Relevance Elevated cerebral Aβ was associated with cholesterol fractions in a pattern analogous to that found in coronary artery disease. This finding, in living, non-demented humans, is consistent with prior autopsy reports, with epidemiological findings, and with both animal and in vitro work suggesting an important role for cholesterol in Aβ processing. Because cholesterol levels are modifiable, understanding their link to amyloid deposition could potentially and eventually have impact in retarding the pathological cascade of AD. These findings suggest that understanding the mechanisms through which serum lipids modulate Aβ could offer new approaches to slowing Aβ deposition and thus to reducing the incidence of AD. PMID:24378418

[Effect of raw and cooked nopal (Opuntia ficus indica) ingestion on growth and profile of total cholesterol, lipoproteins, and blood glucose in rats].

PubMed

Cárdenas Medellín, M L; Serna Saldívar, S O; Velazco de la Garza, J

1998-12-01

Two different concentrations (approx. 6 and 12%) and two presentations (raw and cooked) of dehydrated nopal were fed to laboratory rats and growth and serum total cholesterol, lipoprotein profile and glucose determined. Samples of raw and cooked nopal were chemically characterized for moisture, protein, ash, crude fiber, ether extract, total dietary fiber, reducing sugars, amino acids, minerals and gross energy. Cooking slightly affected some of the nutrients analyzed. After one month feeding, blood was withdrawn via intracardiac puncture and serum glucose, total cholesterol, HDL, LDL, and VLDL were determined. Rats fed 12% nopal had lower weight gains (P < 0.05) when compared with counterparts fed 6% nopal or the control diet. Consumption of nopal did not affect (P > 0.05) glucose, total cholesterol and HDL cholesterol levels. However, rats fed raw nopal at the 12% concentration level had a 34% reduction in LDL cholesterol levels; thus, it was concluded that raw nopal had a potentially beneficial effect for hypercholesterolemic individuals.

Mipomersen, an antisense apolipoprotein B synthesis inhibitor.

PubMed

Bell, Damon A; Hooper, Amanda J; Burnett, John R

2011-02-01

mipomersen is a second-generation antisense oligonucleotide (ASO) targeted to human apolipoprotein (apo) B-100, a large protein synthesized by the liver that plays a fundamental role in human lipoprotein metabolism. Mipomersen predominantly distributes to the liver and decreases the production of apoB-100, the primary structural protein of the atherogenic lipoproteins including low density lipoprotein (LDL), thereby reducing plasma LDL-cholesterol and apoB-100 concentrations. the mode of action, preclinical development and clinical trials of mipomersen, an antisense apoB synthesis inhibitor. The paper provides an understanding of the pharmacokinetic and pharmacodynamic characteristics of mipomersen and insight into its clinical efficacy and safety. In clinical trials, mipomersen produced dose-dependent and prolonged reductions in LDL-cholesterol and other apoB-containing lipoproteins, including lipoprotein (a) [Lp(a)] in healthy volunteers and in patients with mild to moderate hypercholesterolemia. Mipomersen has been shown to decrease apoB, LDL-cholesterol and Lp(a) in patients with heterozygous and homozygous familial hypercholesterolemia on maximally tolerated lipid-lowering therapy. mipomersen shows promise as an adjunctive agent by reducing apoB-containing lipoproteins in patients at high risk of atherosclerotic cardiovascular disease who are not at target or are intolerant of statins. Although the short-term efficacy and safety of mipomersen has been established, concern exists regarding the long-term potential for hepatic steatosis with this ASO.

Serum sterol responses to increasing plant sterol intake from natural foods in the Mediterranean diet.

PubMed

Escurriol, Verónica; Cofán, Montserrat; Serra, Mercè; Bulló, Mónica; Basora, Josep; Salas-Salvadó, Jordi; Corella, Dolores; Zazpe, Itziar; Martínez-González, Miguel A; Ruiz-Gutiérrez, Valentina; Estruch, Ramón; Ros, Emilio

2009-09-01

Phytosterols in natural foods are thought to inhibit cholesterol absorption. The Mediterranean diet is rich in phytosterol-containing plant foods. To assess whether increasing phytosterol intake from natural foods was associated with a cholesterol-lowering effect in a substudy of a randomized trial of nutritional intervention with Mediterranean diets for primary cardiovascular prevention (PREDIMED study). One hundred and six high cardiovascular risk subjects assigned to two Mediterranean diets supplemented with virgin olive oil (VOO) or nuts, which are phytosterol-rich foods, or advice on a low-fat diet. Outcomes were 1-year changes in nutrient intake and serum levels of lipids and non-cholesterol sterols. Average phytosterol intake increased by 76, 158 and 15 mg/day in participants assigned VOO, nuts and low-fat diets, respectively. Compared to participants in the low-fat diet group, changes in outcome variables were observed only in those in the Mediterranean diet with nuts group, with increases in intake of fibre, polyunsaturated fatty acids and phytosterols (P < 0.020, all) and significant (P < 0.05) reductions of LDL-cholesterol (0.27 mmol/l or 8.3%) and the LDL/HDL-cholesterol ratio (0.29 mmol/l or 11.5%). Variations in saturated fat, cholesterol or fibre intake were unrelated to LDL-cholesterol changes. In the whole group, changes in serum sitosterol-to-cholesterol, which reflect those of dietary phytosterol intake and absorption, correlated inversely to LDL-cholesterol changes (r = -0.256; P = 0.008). In multivariate analyses, baseline LDL-cholesterol, increases in serum sitosterol ratios and statin use were independently associated with LDL-cholesterol reductions. Small amounts of phytosterols in natural foods appear to be bioactive in cholesterol lowering.

BMI, body fat mass and plasma leptin level in relation to cardiovascular diseases risk factors among adolescents in Taitung.

PubMed

Wu, Ya-Ke; Chu, Nain-Feng; Huang, Ya-Hsien; Syu, Jhu-Ting; Chang, Jin-Biou

2016-01-01

To investigate the risk factors associated with cardiovascular diseases and its relation to BMI, body fat mass and plasma leptin level among adolescents in Taitung, Taiwan. A cross-sectional Taitung Children Heart Study for 500 young adolescents between ages 13 and 15 was conducted. Gender-specific regression models were used to determine the associations between BMI, percentage of body fat mass, plasma leptin level and seven CVDs risk factors (systolic and diastolic blood pressure, mean arterial pressure, triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol) before and after adjusting for weight status and age. After adjusting for weight status and age, BMI was positively associated with systolic BP, triglycerides, LDL-cholesterol levels but negatively associated with HDL-cholesterol level in boys while positively associated with systolic and diastolic BP, mean arterial pressure, and LDL-cholesterol level in girls. The percentage of body fat mass was positively associated with triglycerides, total cholesterol, and LDL-cholesterol in boys while positively associated with systolic BP, total cholesterol, and LDL-cholesterol in girls. Plasma leptin was positively associated with triglycerides, total cholesterol and LDL-cholesterol in boys but no statistically significant associations with CVDs risk factors in girls. A strong relationship between the percentage of body fat mass and plasma leptin appeared among all participants (r=0.59, p<0.01). BMI, body fat mass and plasma leptin level may be used to identify certain CVDs risk factors among Taitung adolescents. Future researches could consider measuring body fat mass in the relationship of CVDs risk factors instead of plasma leptin among young adolescents. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Effect of dietary cholesterol and plant sterol consumption on plasma lipid responsiveness and cholesterol trafficking in healthy individuals.

PubMed

Alphonse, Peter A S; Ramprasath, Vanu; Jones, Peter J H

2017-01-01

Dietary cholesterol and plant sterols differentially modulate cholesterol kinetics and circulating cholesterol. Understanding how healthy individuals with their inherent variabilities in cholesterol trafficking respond to such dietary sterols will aid in improving strategies for effective cholesterol lowering and alleviation of CVD risk. The objectives of this study were to assess plasma lipid responsiveness to dietary cholesterol v. plant sterol consumption, and to determine the response in rates of cholesterol absorption and synthesis to each sterol using stable isotope approaches in healthy individuals. A randomised, double-blinded, crossover, placebo-controlled clinical trial (n 49) with three treatment phases of 4-week duration were conducted in a Manitoba Hutterite population. During each phase, participants consumed one of the three treatments as a milkshake containing 600 mg/d dietary cholesterol, 2 g/d plant sterols or a control after breakfast meal. Plasma lipid profile was determined and cholesterol absorption and synthesis were measured by oral administration of [3, 4-13C] cholesterol and 2H-labelled water, respectively. Dietary cholesterol consumption increased total (0·16 (sem 0·06) mmol/l, P=0·0179) and HDL-cholesterol (0·08 (sem 0·03) mmol/l, P=0·0216) concentrations with no changes in cholesterol absorption or synthesis. Plant sterol consumption failed to reduce LDL-cholesterol concentrations despite showing a reduction (6 %, P=0·0004) in cholesterol absorption. An over-compensatory reciprocal increase in cholesterol synthesis (36 %, P=0·0026) corresponding to a small reduction in absorption was observed with plant sterol consumption, possibly resulting in reduced LDL-cholesterol lowering efficacy of plant sterols. These data suggest that inter-individual variability in cholesterol trafficking mechanisms may profoundly impact plasma lipid responses to dietary sterols in healthy individuals.

The effects of coffee consumption on serum lipids and lipoprotein in healthy individuals.

PubMed

Onuegbu, A J; Agbedana, E O

2001-01-01

The changes in total serum cholestrol, serum triglyceride, HDL-cholesterol and LDL-cholesterol after twenty eight (28) days of consumption of moderate quantity of a commercial coffee preparation (NESCAFE brand) were studied in 30 human subjects consisting of 20 male and 10 female healthy adults. Significant increases in the mean total serum cholesterol concentration (110.8-126.5 mg/100 mls) and LDL- cholesterol concentration (78.4-94.5 mg/100 ml) were observed in the subjects. No significant differences were obtained in the mean HDL cholesterol concentration and in the mean serum triglyceride levels. The differences observed in the mean total serum cholesterol, LDL cholesterol, HDL- cholesterol and triglyceride concentrations in the individual male and female groups studied were not statistically significant. The results from this study suggest that short-term consumption of coffee may increase the total serum cholesterol and LDL cholesterol levels. It is therefore possible that long-term consumption of coffee may lead to clinically significant alterations in serum lipid profile and could be important in the aetiology of atherosclerotic vascular diseases such as coronary heart disease.

Effect of soy-based breakfast cereal on blood lipids and oxidized low-density lipoprotein.

PubMed

Jenkins, D J; Kendall, C W; Vidgen, E; Vuksan, V; Jackson, C J; Augustin, L S; Lee, B; Garsetti, M; Agarwal, S; Rao, A V; Cagampang, G B; Fulgoni, V

2000-11-01

Consumption of soy protein may reduce the risk of cardiovascular disease both through reduction in serum lipids and by the antioxidant properties of protein-associated soy isoflavones. However, the effect that processing required for the manufacture of breakfast cereals may have on the lipid lowering and antioxidant activities of soy has not been studied. We have therefore assessed the health benefits of soy incorporation into breakfast cereals. Twenty-five hyperlipidemic men and women took soy (providing 36 g/d soy protein and 168 mg/d isoflavones) and control breakfast cereals, each for 3 weeks in a randomized crossover study with a 2-week washout period between treatments. Fasting blood samples were obtained pretreatment and at weeks 2 and 3 of each treatment. No significant difference was seen in serum lipids between treatments at week 3 apart from a 3.8% +/- 1.5% higher apolipoprotein A-1 level on control versus soy (P = .021). However, oxidized low-density lipoprotein (LDL) was reduced on the test compared with the control both as total dienes in LDL and as the ratio of conjugated dienes to cholesterol in the LDL fraction by 9.2% +/- 4.3% (P = .042) and 8.7% +/- 4.2% (P = .050), respectively. High isoflavone intakes in soy breakfast cereals may decrease the risk of cardiovascular disease by reducing oxidized LDL, while having no significant effect on the absolute concentration of LDL cholesterol.

Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia

PubMed Central

Jenkins, David J.A.; Chiavaroli, Laura; Wong, Julia M.W.; Kendall, Cyril; Lewis, Gary F.; Vidgen, Edward; Connelly, Philip W.; Leiter, Lawrence A.; Josse, Robert G.; Lamarche, Benoît

2010-01-01

Background Higher intake of monounsaturated fat may raise high-density lipoprotein (HDL) cholesterol without raising low-density lipoprotein (LDL) cholesterol. We tested whether increasing the monounsaturated fat content of a diet proven effective for lowering LDL cholesterol (dietary portfolio) also modified other risk factors for cardiovascular disease, specifically by increasing HDL cholesterol, lowering serum triglyceride and further reducing the ratio of total to HDL cholesterol. Methods Twenty-four patients with hyperlipidemia consumed a therapeutic diet very low in saturated fat for one month and were then randomly assigned to a dietary portfolio low or high in monounsaturated fatty acid for another month. We supplied participants’ food for the two-month period. Calorie intake was based on Harris–Benedict estimates for energy requirements. Results For patients who consumed the dietary portfolio high in monounsaturated fat, HDL cholesterol rose, whereas for those consuming the dietary portfolio low in monounsaturated fat, HDL cholesterol did not change. The 12.5% treatment difference was significant (0.12 mmol/L, 95% confidence interval [CI] 0.05 to 0.21, p = 0.003). The ratio of total to HDL cholesterol was reduced by 6.5% with the diet high in monounsaturated fat relative to the diet low in monounsaturated fat (−0.28, 95% CI −0.59 to −0.04, p = 0.025). Patients consuming the diet high in monounsaturated fat also had significantly higher concentrations of apolipoprotein AI, and their C-reactive protein was significantly lower. No treatment differences were seen for triglycerides, other lipids or body weight, and mean weight loss was similar for the diets high in monounsaturated fat (−0.8 kg) and low in monounsaturated fat (−1.2 kg). Interpretation Monounsaturated fat increased the effectiveness of a cholesterol-lowering dietary portfolio, despite statin-like reductions in LDL cholesterol. The potential benefits for cardiovascular risk were achieved through increases in HDL cholesterol, further reductions in the ratio of total to HDL cholesterol and reductions in C-reactive protein. (ClinicalTrials.gov trial register no. NCT00430430.) PMID:21041432

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects.

PubMed

Aptekmann, Nancy P; Cesar, Thais B

2013-08-06

This study investigated the hypothesis that long-term orange juice consumption (≥ 12 months) was associated with low risk factors for cardiovascular disease in adult men and women with normal and moderately high cholesterol blood levels. The sample consisted of 103 men (18-66 y) and 26 women (18-65 y); all were employees of an orange juice factory with daily access to free orange juice. The results showed that 41% of the individuals consumed 2 cups (480 mL) of orange juice per day for at least twelve months, while 59% of the volunteers are non-consumers of orange juice. Orange juice consumers with normal serum lipid levels had significantly lower total cholesterol (-11%, p <0.001), LDL-cholesterol (-18%, p < 0.001), apolipoprotein B (apo B) (-12%, p < 0.01) and LDL/HDL ratio (-12%, p < 0.04) in comparison to non-consumers, as did the consumers with moderate hypercholesterolemia: lower total cholesterol (-5%, p <0.02), LDL-cholesterol (-12%, p <0.03), apolipoprotein B (-12%, p <0.01) and LDL/HDL ratio (-16%, p <0.05) in comparison the non-consumers counterparts. Serum levels of homocysteine, HDL- cholesterol and apolipoprotein A-1, body composition and the dietary intake of food energy and macronutrients did not differ among orange juice consumers and non-consumers, but vitamin C and folate intake was higher in orange juice consumers. Long-term orange juice consumers had lower levels of total cholesterol, LDL-cholesterol, apo B and LDL/HDL ratio and an improvement of folate and vitamin C in their diet.

Long-term orange juice consumption is associated with low LDL-cholesterol and apolipoprotein B in normal and moderately hypercholesterolemic subjects

PubMed Central

2013-01-01

Background This study investigated the hypothesis that long-term orange juice consumption (≥ 12 months) was associated with low risk factors for cardiovascular disease in adult men and women with normal and moderately high cholesterol blood levels. Methods The sample consisted of 103 men (18–66 y) and 26 women (18–65 y); all were employees of an orange juice factory with daily access to free orange juice. The results showed that 41% of the individuals consumed 2 cups (480 mL) of orange juice per day for at least twelve months, while 59% of the volunteers are non-consumers of orange juice. Results Orange juice consumers with normal serum lipid levels had significantly lower total cholesterol (−11%, p <0.001), LDL-cholesterol (−18%, p < 0.001), apolipoprotein B (apo B) (−12%, p < 0.01) and LDL/HDL ratio (−12%, p < 0.04) in comparison to non-consumers, as did the consumers with moderate hypercholesterolemia: lower total cholesterol (−5%, p <0.02), LDL-cholesterol (−12%, p <0.03), apolipoprotein B (−12%, p <0.01) and LDL/HDL ratio (−16%, p <0.05) in comparison the non-consumers counterparts. Serum levels of homocysteine, HDL- cholesterol and apolipoprotein A-1, body composition and the dietary intake of food energy and macronutrients did not differ among orange juice consumers and non-consumers, but vitamin C and folate intake was higher in orange juice consumers. Conclusion Long-term orange juice consumers had lower levels of total cholesterol, LDL-cholesterol, apo B and LDL/HDL ratio and an improvement of folate and vitamin C in their diet. PMID:23919812

Effects of plant sterol esters in skimmed milk and vegetable-fat-enriched milk on serum lipids and non-cholesterol sterols in hypercholesterolaemic subjects: a randomised, placebo-controlled, crossover study.

PubMed

Casas-Agustench, Patricia; Serra, Mercè; Pérez-Heras, Ana; Cofán, Montserrat; Pintó, Xavier; Trautwein, Elke A; Ros, Emilio

2012-06-01

Plant sterol (PS)-supplemented foods are recommended to help in lowering serum LDL-cholesterol (LDL-C). Few studies have examined the efficacy of PS-enriched skimmed milk (SM) or semi-SM enriched with vegetable fat (PS-VFM). There is also insufficient information on factors predictive of LDL-C responses to PS. We examined the effects of PS-SM (0·1 % dairy fat) and PS-VFM (0·1 % dairy fat plus 1·5 % vegetable fat) on serum lipids and non-cholesterol sterols in hypercholesterolaemic individuals. In a placebo-controlled, crossover study, forty-three subjects with LDL-C>1300 mg/l were randomly assigned to three 4-week treatment periods: control SM, PS-SM and PS-VFM, with 500 ml milk with or without 3·4 g PS esters (2 g free PS). Serum concentrations of lipids and non-cholesterol sterols were measured. Compared to control, LDL-C decreased by 8·0 and 7·4 % (P < 0·015, both) in the PS-SM and PS-VFM periods, respectively. Serum lathosterol:cholesterol (C) ratios increased by 11-25 %, while sitosterol:C and campesterol:C ratios increased by 70-120 % with both the PS-fortified milk. Adjusted LDL-C reductions were variably enhanced in participants with basal low serum lathosterol/C or conversely high sitosterol/C and campesterol/C. Subjects with post-treatment serum PS:C ratios above the median showed mean LDL-C changes of - 5·9 to - 10·4 %, compared with 1·7 to - 2·9 % below the median. In conclusion, consumption of 2 g/d of PS as PS-SM and PS-VFM lowered LDL-C in hypercholesterolaemic subjects to a similar extent. Basal and post-treatment changes in markers of cholesterol metabolism indicating low cholesterol synthesis and high cholesterol absorption predicted improved LDL-C responses to PS.

Andrographolide Inhibits Oxidized LDL-Induced Cholesterol Accumulation and Foam Cell Formation in Macrophages.

PubMed

Lin, Hung-Chih; Lii, Chong-Kuei; Chen, Hui-Chun; Lin, Ai-Hsuan; Yang, Ya-Chen; Chen, Haw-Wen

2018-01-01

oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells. Transcription factor liver X receptor [Formula: see text] (LXR[Formula: see text] plays a key role in lipid metabolism and inflammation as well as in the regulation of ABCA1 and ABCG1 expression. Because of the contribution of inflammation to macrophage foam cell formation and the potent anti-inflammatory activity of andrographolide, we hypothesized that andrographolide might inhibit oxLDL-induced macrophage foam cell formation. The results showed that andrographolide reduced oxLDL-induced lipid accumulation in macrophage foam cells. Andrographolide decreased the mRNA and protein expression of CD36 by inducing the degradation of CD36 mRNA; however, andrographolide had no effect on SR-A expression. In contrast, andrographolide increased the mRNA and protein expression of ABCA1 and ABCG1, which were dependent on LXR[Formula: see text]. Andrographolide enhanced LXR[Formula: see text] nuclear translocation and DNA binding activity. Treatment with the LXR[Formula: see text] antagonist GGPP and transfection with LXR[Formula: see text] siRNA reversed the ability of andrographolide to stimulate ABCA1 and ABCG1 protein expression. In conclusion, inhibition of CD36-mediated oxLDL uptake and induction of ABCA1- and ABCG1-dependent cholesterol efflux are two working mechanisms by which andrographolide inhibits macrophage foam cell formation, which suggests that andrographolide could be a potential candidate to prevent atherosclerosis.

Trends in lipid profiles and descriptive characteristics of U.S. adults with and without diabetes and cholesterol-lowering medication use-National Health and Nutrition Examination Survey, 2003-2012, United States.

PubMed

Mercado, Carla I; Gregg, Edward; Gillespie, Cathleen; Loustalot, Fleetwood

2018-01-01

With a cholesterol-lowering focus for diabetic adults and in the age of polypharmacy, it is important to understand how lipid profile levels differ among those with and without diabetes. Investigate the means, differences, and trends in lipid profile measures [TC, total cholesterol; LDL-c, low-density lipoprotein; HDL-c, high-density lipoprotein; and TG, triglycerides] among US adults by diabetes status and cholesterol-lowering medication. Population number and proportion of adults aged ≥21 years with diabetes and taking cholesterol-lowering medication were estimated using data on 10,384 participants from NHANES 2003-2012. Age-standardized means, trends, and differences in lipid profile measures were estimated by diabetes status and cholesterol medication use. For trends and differences, linear regression analysis were used adjusted for age, gender, and race/ethnicity. Among diabetic adults, 52% were taking cholesterol-lowering medication compared to the 14% taking cholesterol-lowering medication without diabetes. Although diabetic adults had significantly lower TC and LDL-c levels than non-diabetic adults [% difference (95% confidence interval): TC = -5.2% (-6.8 --3.5), LDL-c = -8.0% (-10.4 --5.5)], the percent difference was greater among adults taking cholesterol medication [TC = -8.0% (-10.3 --5.7); LDL-c = -13.7% (-17.1 --10.2)] than adults not taking cholesterol medication [TC = -3.5% (-5.2 --1.6); LDL-c = -4.3% (-7.1 --1.5)] (interaction p-value: TC = <0.001; LDL-c = <0.001). From 2003-2012, mean TC and HDL-c significantly decreased among diabetic adults taking cholesterol medication [% difference per survey cycle (p-value for linear trend): TC = -2.3% (0.003) and HDL-c = -2.3% (0.033)]. Mean TC, HDL-c, and LDL-c levels did not significantly change from 2003 to 2012 in non-diabetic adults taking cholesterol medication or for adults not taking cholesterol medications. Diabetic adults were more likely to have lower lipid levels, except for triglyceride levels, than non-diabetic adults with profound differences when considering cholesterol medication use, possibly due to the positive effects from clinical diabetes management.

Cholesterol lipoproteins and prevalence of dyslipidemias in urban Asian Indians: A cross sectional study

PubMed Central

Guptha, Soneil; Gupta, Rajeev; Deedwania, Prakash; Bhansali, Anil; Maheshwari, Anuj; Gupta, Arvind; Gupta, Balkishan; Saboo, Banshi; Singh, Jitendra; Achari, Vijay; Sharma, Krishna Kumar

2014-01-01

Objective To determine levels of cholesterol lipoproteins and prevalence of dyslipidemias in urban Asian Indians. Methods Population based 6123 subjects (men 3388) were evaluated. Mean±1SD of various cholesterol lipoproteins (total, HDL, LDL and non-HDL cholesterol) and triglycerides were reported. Subjects were classified according to US National Cholesterol Education Program. Results Age-adjusted levels in men and women were cholesterol total 178.4 ± 39 and 184.6 ± 39, HDL 44.9 ± 11 and 51.1 ± 11, LDL 102.5 ± 33 and 106.2 ± 33, total:HDL 4.15 ± 1.2 and 3.79 ± 1.0 and triglycerides 162.5 ± 83 and 143.7 ± 83 mg/dl. Age-adjusted prevalence (%) in men and women, respectively were, total cholesterol ≥200 mg/dl 25.1 and 24.9, LDL cholesterol ≥130 mg/dl 16.3 and 15.1 and ≥100 mg/dl 49.5 and 49.7, HDL cholesterol <40/<50 mg/dl 33.6 and 52.8, total:HDL cholesterol ≥4.5 29.4 and 16.8, and triglycerides ≥150 mg/dl 42.1 and 32.9%. Cholesterol level was significantly greater in subjects with better socioeconomic status, body mass index and waist circumference while triglycerides were more among those with high socioeconomic status, fat intake, body mass index and waist circumference (p < 0.05). Hypercholesterolemia awareness (15.6%), treatment (7.2%) and control (4.1%) were low. Conclusions Mean cholesterol and LDL cholesterol are low and triglycerides were high in urban Asian Indians. Most prevalent dyslipidemias are borderline high LDL, low HDL and high triglycerides. Subjects with high socioeconomic status, high fat intake and greater adiposity have higher total and LDL cholesterol and triglyceride and lower HDL cholesterol. PMID:24973832

ERICA: prevalence of dyslipidemia in Brazilian adolescents

PubMed Central

Faria, José Rocha; Bento, Vivian Freitas Rezende; Baena, Cristina Pellegrino; Olandoski, Marcia; Gonçalves, Luis Gonzaga de Oliveira; Abreu, Gabriela de Azevedo; Kuschnir, Maria Cristina Caetano; Bloch, Katia Vergetti

2016-01-01

ABSTRACT OBJECTIVE To determine the distribution of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides in Brazilian adolescents, as well as the prevalence of altered levels of such parameters. METHODS Data from the Study of Cardiovascular Risks in Adolescents (ERICA) were used. This is a country-wide, school-based cross-sectional study that evaluated 12 to 17-year old adolescents living in cities with over 100,000 inhabitants. The average and distribution of plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were evaluated. Dyslipidemia was determined by levels of total cholesterol ≥ 170 mg/dl, LDL cholesterol ≥ 130 mg/dl, HDL cholesterol < 45 mg/dL, or triglycerides ≥ 130 mg/dl. The data were analyzed by gender, age, and regions in Brazil. RESULTS We evaluated 38,069 adolescents – 59.9% of females, and 54.2% between 15 and 17 years. The average values found were: total cholesterol = 148.1 mg/dl (95%CI 147.1-149.1), HDL cholesterol = 47.3 mg/dl (95%CI 46.7-47.9), LDL cholesterol = 85.3 mg/dl (95%CI 84.5-86.1), and triglycerides = 77.8 mg/dl (95%CI 76.5-79.2). The female adolescents had higher average levels of total cholesterol, LDL cholesterol, and HDL cholesterol, without differences in the levels of triglycerides. We did not observe any significant differences between the average values among 12 to 14 and 15- to 17-year old adolescents. The most prevalent lipid alterations were low HDL cholesterol (46.8% [95%CI 44.8-48.9]), hypercholesterolemia (20.1% [95%CI 19.0-21.3]), and hypertriglyceridemia (7.8% [95%CI 7.1-8.6]). High LDL cholesterol was found in 3.5% (95%CI 3.2-4.0) of the adolescents. Prevalence of low HDL cholesterol was higher in Brazil’s North and Northeast regions. CONCLUSIONS A significant proportion of Brazilian adolescents has alterations in their plasma lipids. The high prevalence of low HDL cholesterol and hypertriglyceridemia, especially in Brazil’s North and Northeast regions, must be analyzed in future studies, to support the creation of strategies for efficient interventions. PMID:26910544

Dietary Almonds Increase Serum HDL Cholesterol in Coronary Artery Disease Patients in a Randomized Controlled Trial.

PubMed

Jamshed, Humaira; Sultan, Fateh Ali Tipoo; Iqbal, Romaina; Gilani, Anwar Hassan

2015-10-01

More than one-half of coronary artery disease (CAD) patients have low HDL cholesterol despite having well-managed LDL cholesterol. Almond supplementation has not been shown to elevate circulating HDL cholesterol concentrations in clinical trials, perhaps because the baseline HDL cholesterol of trial subjects was not low. This clinical trial was designed to test the effect of almond supplementation on low HDL cholesterol in CAD patients. A total of 150 CAD patients (50 per group), with serum LDL cholesterol ≤100 mg/dL and HDL cholesterol ≤40 mg/dL in men and ≤50 mg/dL in women, were recruited from the Aga Khan University Hospital. After recording vital signs and completing a dietary and physical activity questionnaire, patients were randomly assigned to 1 of the following 3 groups: the no-intervention group (NI), the Pakistani almonds group (PA), and the American almonds group (AA). The respective almond varieties (10 g/d) were given to patients with instructions to soak them overnight, remove the skin, and eat them before breakfast. Blood samples for lipid profiling, body weight, and blood pressure were collected, and assessment of dietary patterns was done at baseline, week 6, and week 12. Almonds significantly increased HDL cholesterol. At weeks 6 and 12, HDL cholesterol was 12-14% and 14-16% higher, respectively, in the PA and AA than their respective baselines. In line with previous reports, serum concentrations of total cholesterol, triglycerides, LDL cholesterol, and VLDL cholesterol; total-to-HDL and LDL-to-HDL cholesterol ratios, and the atherogenic index were reduced in both the PA and AA at weeks 6 and 12 compared with baseline (P < 0.05). Effects on serum lipids did not differ between the 2 almond groups. Dietary patterns, body weight, and blood pressure did not change in any of the 3 groups during the trial. A low dose of almonds (10 g/d) consumed before breakfast can increase HDL cholesterol, in addition to improving other markers of abnormal lipid metabolism in CAD patients with low initial HDL cholesterol. This trial was registered at the Australian New Zealand Clinical Trial Registry as ACTRN12614000036617. © 2015 American Society for Nutrition.

MicroRNA modulation of lipid metabolism and oxidative stress in cardiometabolic diseases.

PubMed

Aranda, Juan F; Madrigal-Matute, Julio; Rotllan, Noemi; Fernández-Hernando, Carlos

2013-09-01

The regulation of the metabolism of cholesterol has been one of the most studied biological processes since its first isolation from gallstones in 1784. High levels of plasma low-density lipoprotein (LDL) cholesterol and reduced levels of plasma high-density lipoprotein (HDL) cholesterol are widely recognized as major risk factors of cardiovascular disease. An imbalance in the production of reactive oxygen species can oxidize LDL particles, increasing the levels of the highly proatherogenic oxidized LDL. Furthermore, under pathological scenarios, numerous molecules can function as pro-oxidants, such as iron or (high levels of) glucose. In addition to the classical mechanisms regulating lipid homeostasis, recent studies have demonstrated the important role of microRNAs (miRNAs) as regulators of lipoprotein metabolism, oxidative derivatives of lipoprotein, and redox balance. Here, we summarize recent findings in the field, highlighting the contributions of some miRNAs to lipid- and oxidative-associated pathologies. We also discuss how therapeutic intervention of miRNAs may be a promising strategy to decrease LDL, increase HDL, and ameliorate lipid- and oxidative-related disorders, including atherosclerosis, nonalcoholic fatty liver disease, and metabolic syndrome. © 2013 Elsevier Inc. All rights reserved.

Proprotein convertase subtilisin/kexin 9 inhibitors: an emerging lipid-lowering therapy?

PubMed

Dragan, Simona; Serban, Maria-Corina; Banach, Maciej

2015-03-01

Proprotein convertase subtilisin/kexin 9 (PCSK9) is part of the proteinase K subfamily of subtilases and plays a key role in lipid metabolism. It increases degradation of the low-density lipoprotein receptor (LDL-R), modulates cholesterol metabolism and transport, and contributes to the production of apolipoprotein B (apoB) in intestinal cells. Exogenous PCSK9 modifies the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and acyl coenzyme A:cholesterol acyltransferase and enhances secretion of chylomicrons by modulating production of lipids and apoB-48. Statins increase PCSK9 messenger RNA expression and attenuate the capacity to increase LDL-R levels. Therefore, the inhibition of PCSK9 in combination with statins provides a promising approach for lowering low-density lipoprotein cholesterol (LDL-C) concentrations. This review will address new therapeutic strategies targeting PCSK9, including monoclonal antibodies, antisense oligonucleotides, small interfering RNAs, and other small molecule inhibitors. Further studies are still needed to determine the efficacy and safety of the PCSK9 inhibitors not only to decrease LDL-C but also to investigate the potential underlying mechanisms involved and to test whether these compounds actually reduce cardiovascular end points and mortality. © The Author(s) 2014.

Effects of a new combination of nutraceuticals with Morus alba on lipid profile, insulin sensitivity and endotelial function in dyslipidemic subjects. A cross-over, randomized, double-blind trial.

PubMed

Trimarco, Valentina; Izzo, Raffaele; Stabile, Eugenio; Rozza, Francesco; Santoro, Mario; Manzi, Maria Virginia; Serino, Federica; Schiattarella, Gabriele Giacomo; Esposito, Giovanni; Trimarco, Bruno

2015-06-01

Nutraceuticals (NUT) are forms of compounds with biological activity commonly used to improve health in dosage largely exceeding those obtainable in food. We compared, in a double blind randomized cross-over trial, the effects of two NUT combinations on the control of glico-lipidic metabolism in patients with hypercholesterolemia not on statins. At study start patients were given dietary counseling and received placebo for 2 weeks. After this run-in period, patients were randomized: (1) Combination A [Policosanol, Red yeast rice (Monakolin K 3 mg), Berberine 500 mg, Astaxantine, Folic Acid and Coenzyme Q10] for 4 weeks followed by 4 weeks of Combination B [Red yeast rice (Monakolin K 3.3 mg), Berberine 531.25 mg and leaf extract of Morus alba]; (2) Combination B for 4 weeks followed by 4 weeks of Combination A. Combination B reduced LDL cholesterol below 130 mg/dl in 56.5 % of the patients, and Cambination A only in 21.7 % of them (p ≤ 0.027). Both treatments reduced plasma levels of triglycerides, total and LDL cholesterol and increased HDL cholesterol (all p < 0.03). Total and LDL cholesterol reduction was more pronounced in patients taking Combination B (p < 0.005). Combination B reduced also glycated hemoglobin, fasting glucose and insulin plasma levels as well as HOMA index (p < 0.005). An increased content of Berberin and Monacolin K and the addition of Morus alba extract improves the effect on plasma cholesterol and on glucose metabolism of the NUT Combination. These effects may allow the speculation of a more marked improvement in cardiovascular prognosis.

Can change in high-density lipoprotein cholesterol levels reduce cardiovascular risk?

PubMed

Dean, Bonnie B; Borenstein, Jeff E; Henning, James M; Knight, Kevin; Merz, C Noel Bairey

2004-06-01

The cardiovascular risk reduction observed in many trials of lipid-lowering agents is greater than expected on the basis of observed low-density lipoprotein cholesterol (LDL-C) level reductions. Our objective was to explore the degree to which high-density lipoprotein cholesterol (HDL-C) level changes explain cardiovascular risk reduction. A systematic review identified trials of lipid-lowering agents reporting changes in HDL-C and LDL-C levels and the incidence of coronary heart disease (CHD). The observed relative risk reduction (RRR) in CHD morbidity and mortality rates was calculated. The expected RRR, given the treatment effect on total cholesterol level, was calculated for each trial with logistic regression coefficients from observational studies. The difference between observed and expected RRR was plotted against the change in HDL-C level, and a least-squares regression line was calculated. Fifty-one trials were identified. Nineteen statin trials addressed the association of HDL-C with CHD. Limited numbers of trials of other therapies precluded additional analyses. Among statin trials, therapy reduced total cholesterol levels as much as 32% and LDL-C levels as much as 45%. HDL-C level increases were <10%. Treatment effect on HDL-C levels was not a significant linear predictor of the difference in observed and expected CHD mortality rates, although we observed a trend in this direction (P =.08). Similarly, HDL-C effect was not a significant linear predictor of the difference between observed and expected RRRs for CHD morbidity (P =.20). Although a linear trend toward greater risk reduction was observed with greater effects on HDL-C, differences were not statistically significant. The narrow range of HDL-C level increases in the statin trials likely reduced our ability to detect a beneficial HDL-C effect, if present.

Achieving low-density lipoprotein cholesterol goals in high-risk patients in managed care: comparison of rosuvastatin, atorvastatin, and simvastatin in the SOLAR trial.

PubMed

Insull, William; Ghali, Jalal K; Hassman, David R; Y As, Joseph W; Gandhi, Sanjay K; Miller, Elinor

2007-05-01

To evaluate attainment of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein cholesterol (LDL-C) goal of less than 100 mg/dL with statin treatments in managed care patients at high risk for coronary heart disease. In a randomized, open-label, multicenter trial (SOLAR [Satisfying Optimal LDL-C ATP III goals with Rosuvastatin]) performed at 145 US clinical centers from June 5, 2002 to July 12, 2004, high-risk men and women in a managed care population received typical starting doses of rosuvastatin (10 mg/d), atorvastatin (10 mg/d), or simvastatin (20 mg/d) for 6 weeks. Those who did not meet the LDL-C target of less than 100 mg/dL at 6 weeks had their dose titrated (doubled), and all patients were followed up for another 6 weeks. A total of 1632 patients were randomized to 1 of the 3 treatment regimens. After 6 weeks, 65% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 41% with atorvastatin and 39% with simvastatin (P<.001 vs rosuvastatin for both). After 12 weeks, 76% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 58% with atorvastatin and 53% with simvastatin (P<.001 vs rosuvastatin for both). Reductions in the LDL-C level, total cholesterol level, non-high-density lipoprotein cholesterol (non-HDL-C) level, and non-HDL-C/HDL-C ratio were significantly greater with rosuvastatin at both 6 and 12 weeks compared with the other statins. Adverse events were similar in type and frequency in all treatment groups, and only 3% of all patients discontinued treatment because of adverse events. No myopathy was observed, no clinically important impact on renal function was attributed to study medications, and clinically important increases in serum transaminases were rare. In a managed care population, 10 mg of rosuvastatin treatment resulted in more patients reaching the NCEP ATP III LDL-C goal compared with 10 mg of atorvastatin and 20 mg of simvastatin, potentially reducing the need for titration visits.

Emerging Treatments for Heterozygous and Homozygous Familial Hypercholesterolemia.

PubMed

Baum, Seth J; Soffer, Daniel; Barton Duell, P

Familial hypercholesterolemia (FH) is an autosomal co-dominant disorder marked by extremely high low-density lipoprotein (LDL) cholesterol levels and concomitant premature vascular disease. FH is caused by mutations that most commonly affect three genes integrally involved in the LDL receptor's ability to clear LDL particles from the circulation. Primary intervention efforts to lower LDL cholesterol have centered on therapies that upregulate the LDL receptor. Unfortunately, most patients are insufficiently responsive to traditional LDL-lowering medications. This article focuses primarily on the clinical management of homozygous FH.

Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an open-label, randomized clinical trial

PubMed Central

2012-01-01

Background Reducing low-density lipoprotein cholesterol (LDL-C) is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia. Methods This was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83) to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg) or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg) for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks. Results At 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026) and total cholesterol (20.8% vs 12.2%, p = 0.0003). Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6%) vs doubling statin (41.2%), but the difference was not statistically significant (p = 0.1675). The safety and tolerability profiles were similar between treatments. Conclusion Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT00652327 PMID:22621316

The reactivity of plasma phospholipids with lecithin:cholesterol acyltransferase is decreased in fish oil-fed monkeys.

PubMed

Parks, J S; Bullock, B C; Rudel, L L

1989-02-15

The size of low density lipoproteins (LDL) is strongly correlated with LDL cholesteryl ester (CE) content and coronary artery atherosclerosis in monkeys fed cholesterol and saturated fat. African green monkeys fed 11% (weight) fish oil diets have smaller LDL and less CE per LDL particle than lard-fed animals. We hypothesized that this might be due to a lower plasma lecithin:cholesterol acyltransferase (LCAT) activity in fish oil-fed animals. Using recombinant particles made of egg yolk lecithin-[14C]cholesterol-apoA-I as exogenous substrate, we found no difference in plasma LCAT activity (27 versus 28 nmol CE formed per h/ml) of fish oil- versus lard-fed animals, respectively; furthermore, no diet-induced difference in immunodetectable LCAT was found. However, plasma phospholipids from fish oil-fed animals were over 4-fold enriched in n-3 fatty acids in the sn-2 position compared to those of lard-fed animals. Additionally, the proportion of n-3 fatty acid-containing CE products formed by LCAT, relative to the available n-3 fatty acid in the sn-2 position of phospholipids, was less than one-tenth of that for linoleic acid. The overall rate of LCAT-catalyzed CE formation with phospholipid substrates from fish oil-fed animals was lower (5-50%) than with phospholipid substrates from lard-fed animals. These data show that n-3 fatty acids in phospholipids are not readily utilized by LCAT for formation of CE; rather, LCAT preferentially utilizes linoleic acid for CE formation. The amount of linoleic acid in the sn-2 position of plasma phospholipids is reduced and replaced with n-3 fatty acids in fish oil-fed animals. As a result, LCAT-catalyzed plasma CE formation in vivo is likely reduced in fish oil-fed animals contributing to the decreased cholesteryl ester content and smaller size of LDL particles in the animals of this diet group.

Effect of Low-Density Lipoprotein Cholesterol Lowering by Ezetimibe/Simvastatin on Outcome Incidence: Overview, Meta-Analyses, and Meta-Regression Analyses of Randomized Trials.

PubMed

Thomopoulos, Costas; Skalis, George; Michalopoulou, Helena; Tsioufis, Costas; Makris, Thomas

2015-12-01

This analysis investigated the extent of different outcome reductions from low-density lipoprotein cholesterol (LDL-C) lowering following ezetimibe/simvastatin treatment and the proportionality of outcome to LDL-C reductions. The authors searched PubMed between 1997 and mid-June 2015 (any language) and the Cochrane Library to identify all randomized controlled trials comparing ezetimibe/simvastatin with placebo or less intensive LDL-C lowering. Risk ratios (RR) and 95% confidence intervals (CIs), standardized to 20 mg/dL LDL-C reduction, were calculated for 5 primary outcomes (fatal and nonfatal) and 4 secondary outcomes (non-cardiovascular [CV] death, cancer, myopathy, and hepatopathy). Five ezetimibe/simvastatin RCTs (30 051 individuals) were eligible, 2 comparing ezetimibe/simvastatin vs placebo and 3 vs less intensive treatment. Outcomes reduced almost to the same extent were stroke (RR: -13%, 95% CI: -21% to -3%), coronary heart disease (CHD; RR: -12%, 95% CI: -19% to -5%), and composite of stroke and CHD (RR: -14%, 95% CI: -20% to -8%). Absolute risk reductions: 5 strokes, 10 CHD events, and 16 stroke and CHD events prevented for every 1000 patients treated for 5 years. Residual risk was almost 7× higher than absolute risk reduction for all the above outcomes. All death outcomes were not reduced, and secondary outcomes did not differ between groups. Logarithmic risk ratios were not associated with LDL-C lowering. Our meta-analysis provides evidence that, in patients with different CV disease burden, major CV events are safely reduced by LDL-C lowering with ezetimibe/simvastatin, while raising the hypothesis that the extent of LDL-C lowering might not be accompanied by incremental clinical-event reduction. © 2015 Wiley Periodicals, Inc.

Comparison of cardiovascular protective effects of tropical seaweeds, Kappaphycus alvarezii, Caulerpa lentillifera, and Sargassum polycystum, on high-cholesterol/high-fat diet in rats.

PubMed

Matanjun, Patricia; Mohamed, Suhaila; Muhammad, Kharidah; Mustapha, Noordin Mohamed

2010-08-01

This study was designed to investigate the comparative in vivo cardiovascular protective effects of red, green, and brown tropical seaweeds, namely, Kappaphycus alvarezii (or Eucheuma cottonii), Caulerpa lentillifera, and Sargassum polycystum, in rats fed on high-cholesterol/high-fat (HCF) diets. Male Sprague-Dawley rats (weighing 260-300 g) on the HCF diet had significantly increased body weight, plasma total cholesterol (TC), plasma low-density lipoprotein cholesterol (LDL-C), plasma triglycerides (TG), lipid peroxidation, and erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase levels after 16 weeks. Supplementing 5% seaweeds to HCF diet significantly reduced plasma TC (-11.4% to -18.5%), LDL-C (-22% to -49.3%), and TG (-33.7% to -36.1%) levels and significantly increased HDL-C levels (16.3-55%). Among the seaweeds, S. polycystum showed the best anti-obesity and blood GSH-Px properties, K. alvarezii showed the best antihyperlipemic and in vivo antioxidation effects, and C. lentillifera was most effective at reducing plasma TC. All seaweeds significantly reduced body weight gain, erythrocyte GSH-Px, and plasma lipid peroxidation of HCF diet rats towards the values of normal rats.

Sex Differences in the Impact of the Mediterranean Diet on LDL Particle Size Distribution and Oxidation

PubMed Central

Bédard, Alexandra; Corneau, Louise; Lamarche, Benoît; Dodin, Sylvie; Lemieux, Simone

2015-01-01

Sex differences have been previously highlighted in the cardioprotective effects of the Mediterranean diet (MedDiet). The objective of this study was to investigate whether sex differences also exist with regard to LDL particle size distribution and oxidation. Participants were 37 men and 32 premenopausal women (24–53 years) with slightly elevated LDL-C concentrations (3.4–4.9 mmol/L) or total cholesterol/HDL-C ≥5.0. Variables were measured before and after a four-week isoenergetic MedDiet. Sex differences were found in response to the MedDiet for the proportion of medium LDL (255–260 Å) (p for sex-by-time interaction = 0.01) and small, dense LDL (sdLDL; <255 Å) (trend; p for sex-by-time interaction = 0.06), men experiencing an increase in the proportion of medium LDL with a concomitant reduction in the proportion of sdLDL, while an opposite trend was observed in women. A sex difference was also noted for estimated cholesterol concentrations among sdLDL (p for sex-by-time interaction = 0.03), with only men experiencing a reduction in response to the MedDiet. The MedDiet marginally reduced oxidized LDL (oxLDL) concentrations (p = 0.07), with no sex difference. Results suggest that short-termconsumption of the MedDiet leads to a favorable redistribution of LDL subclasses from smaller to larger LDL only in men. These results highlight the importance of considering sex issues in cardiovascular benefits of the MedDiet. PMID:25988764

Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study

PubMed Central

2013-01-01

Background Assessment of cardiovascular disease (CVD) risk factors can predict clinical manifestations of atherosclerosis in adulthood. In this pilot study with hypercholesterolemic children and adolescents, we investigated the effects of a combination of plant sterols, fish oil and B vitamins on the levels of four independent risk factors for CVD; LDL-cholesterol, triacylglycerols, C-reactive protein and homocysteine. Methods Twenty five participants (mean age 16 y, BMI 23 kg/m2) received daily for a period of 16 weeks an emulsified preparation comprising plant sterols esters (1300 mg), fish oil (providing 1000 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)) and vitamins B12 (50 μg), B6 (2.5 mg), folic acid (800 μg) and coenzyme Q10 (3 mg). Atherogenic and inflammatory risk factors, plasma lipophilic vitamins, provitamins and fatty acids were measured at baseline, week 8 and 16. Results The serum total cholesterol, LDL- cholesterol, VLDL-cholesterol, subfractions LDL-2, IDL-1, IDL-2 and plasma homocysteine levels were significantly reduced at the end of the intervention period (p<0.05). The triacylglycerols levels decreased by 17.6%, but did not reach significance. No significant changes in high sensitivity C-reactive protein, HDL-cholesterol and apolipoprotein A-1 were observed during the study period. After standardisation for LDL cholesterol, there were no significant changes in the levels of plasma γ-tocopherol, β-carotene and retinol, except for reduction in α-tocopherol levels. The plasma levels of n-3 fatty acids increased significantly with the dietary supplementation (p<0.05). Conclusions Daily intake of a combination of plant sterols, fish oil and B vitamins may modulate the lipid profile of hypercholesterolemic children and adolescents. Trial registration Current Controlled Trials ISRCTN89549017 PMID:23297818

Comparison of human plasma low- and high-density lipoproteins as substrates for lecithin: cholesterol acyltransferase.

PubMed

Barter, P J; Hopkins, G J; Gorjatschko, L

1984-01-17

A recent observation that lecithin: cholesterol acyltransferase (EC 2.3.1.43) interacts with both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) in human plasma is in apparent conflict with an earlier finding that the purified enzyme, while highly reactive with isolated HDL, was only minimally reactive with LDL. There is evidence, however, that lecithin: cholesterol acyltransferase may exist physiologically as a component of a complex with other proteins and that studies with the isolated enzyme may therefore provide misleading results. Consequently, interactions of the enzyme with isolated human lipoproteins have been re-examined in incubations containing lecithin: cholesterol acyltransferase as a component of human lipoprotein-free plasma in which a physiologically active complex of the enzyme with other proteins may have been preserved. In this system there was a ready esterification of the free cholesterol associated with both LDL and HDL-subfraction 3 (HDL3) in reactions that obeyed typical enzyme-saturation kinetics. For a given preparation of lipoprotein-free plasma the Vmax values with LDL and with HDL3 were virtually identical. The apparent Km for free cholesterol associated with HDL3 was 5.6 X 10(-5) M, while for that associated with LDL it was 4.1 X 10(-4) M. This implied that, in terms of free cholesterol concentration, the affinity of HDL3 for lecithin: cholesterol acyltransferase was about 7-times greater than that of LDL. When expressed in terms of lipoprotein particle concentration, however, it was apparent that the affinity of LDL for the enzyme was considerably greater than that of HDL3. When the lipoprotein fractions were equated in terms of lipoprotein surface area, the apparent affinities of the two fractions for the enzyme were found to be comparable.

Elevated serum uric acid increases risks for developing high LDL cholesterol and hypertriglyceridemia: A five-year cohort study in Japan.

PubMed

Kuwabara, Masanari; Borghi, Claudio; Cicero, Arrigo F G; Hisatome, Ichiro; Niwa, Koichiro; Ohno, Minoru; Johnson, Richard J; Lanaspa, Miguel A

2018-06-15

High serum uric acid (SUA) is associated with the dyslipidemia, but whether hyperuricemia predicts an increase in serum low-density lipoprotein (LDL) cholesterol is unknown. This study is to evaluate whether an elevated SUA predicts the development of high LDL cholesterol as well as hypertriglyceridemia. This is a retrospective 5-year cohort study of 6476 healthy Japanese adults (age, 45.7 ± 10.1 years; 2.243 men) who underwent health examinations at 2004 and were reevaluated in 2009 at St. Luke's International Hospital, Tokyo, Japan. Subjects were included if at their baseline examination they did not have hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, or if they were on medication for hyperuricemia and/or gout. The analysis was adjusted for age, body mass index (BMI), smoking and drinking habits, baseline estimated glomerular filtration rate (eGFR), baseline SUA and SUA change over the 5 years. High baseline SUA was an independent risk for developing high LDL cholesterol both in men (OR: 1.159 per 1 mg/dL increase, 95% CI:1.009-1.331) and women (OR: 1.215, 95% CI:1.061-1.390). Other risk factors included a higher baseline LDL cholesterol, higher BMI, and higher baseline eGFR (the latter two in women only). Increased SUA over 5 years were also independent risks for developing high LDL cholesterol and hypertriglyceridemia, but not for low high-density lipoprotein (HDL) cholesterol. This is the first study to report that an elevated SUA increases the risk for developing high LDL cholesterol, as well as hypertriglyceridemia. This may shed light into the role of SUA in cardiovascular disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels.

PubMed Central

Horton, J D; Cuthbert, J A; Spady, D K

1993-01-01

The concentration of LDL in plasma is strongly influenced by the amount and the type of lipid in the diet. Recent studies in the hamster have shown that dietary fatty acids differentially affect circulating LDL levels primarily by altering receptor-dependent LDL uptake in the liver. To investigate the mechanistic basis of this effect, rates of receptor-dependent LDL transport in the liver were correlated with LDL receptor protein and mRNA levels in hamsters fed safflower oil or coconut oil and varying amounts of cholesterol. Hepatic LDL receptor activity was significantly lower in animals fed coconut oil than in animals fed safflower oil at all levels of cholesterol intake (26, 53, and 61% lower at cholesterol intakes of 0, 0.06, and 0.12%, respectively). These fatty acid-induced changes in hepatic LDL receptor activity were accompanied by parallel changes in hepatic LDL receptor protein and mRNA levels, suggesting that dietary fatty acids regulate the LDL receptor pathway largely at the mRNA level. Images PMID:8349814

Relationship between Icodextrin use and decreased level of small low-density lipoprotein cholesterol fractioned by high-performance gel permeation chromatography

PubMed Central

2013-01-01

Background Because of the absorption of glucose in peritoneal dialysis (PD) solution, PD patients show an atherogenic lipid profile, which is predictive of poor survival in PD patients. Lipoprotein subclasses consist of a continuous spectrum of particles of different sizes and densities (fraction). In this study, we investigated the lipoprotein fractions in PD patients with controlled serum low-density lipoprotein (LDL) cholesterol level, and evaluated the effects of icodextrin on lipid metabolism. Methods Forty-nine PD patients were enrolled in this cross-sectional study in Japan. The proportions of cholesterol levels to total cholesterol level (cholesterol proportion) in 20 lipoprotein fractions were measured using an improved method of high-performance gel permeation chromatography (HPGPC). Results Twenty-six patients used icodextrin. Although no significant differences in cholesterol levels in LDL and high-density lipoprotein (HDL) were observed between the patients using icodextrin (icodextrin group) and control groups, HPGPC showed that the icodextrin group had significantly lower cholesterol proportions in the small LDL (t-test, p=0.053) and very small LDL (p=0.019), and significantly higher cholesterol proportions in the very large HDL and large HDL than the control group (p=0.037; p=0.066, respectively). Multivariate analysis adjusted for patient characteristics and statin use showed that icodextrin use was negatively associated with the cholesterol proportions in the small LDL (p=0.037) and very small LDL (p=0.026), and positively with those in the very large HDL (p=0.040), large HDL (p=0.047), and medium HDL (p=0.009). Conclusions HPGPC showed the relationship between icodextrin use and the cholesterol proportions in lipoprotein fractions in PD patients. These results suggest that icodextrin may improve atherogenic lipid profiles in a manner different from statin. PMID:24161017

Comparison of a dietary portfolio diet of cholesterol-lowering foods and a statin on LDL particle size phenotype in hypercholesterolaemic participants.

PubMed

Gigleux, Iris; Jenkins, David J A; Kendall, Cyril W C; Marchie, Augustine; Faulkner, Dorothea A; Wong, Julia M W; de Souza, Russell; Emam, Azadeh; Parker, Tina L; Trautwein, Elke A; Lapsley, Karen G; Connelly, Philip W; Lamarche, Benoît

2007-12-01

The effect of diet v. statins on LDL particle size as a risk factor for CVD has not been examined. We compared, in the same subjects, the impact of a dietary portfolio of cholesterol-lowering foods and a statin on LDL size electrophoretic characteristics. Thirty-four hyperlipidaemic subjects completed three 1-month treatments as outpatients in random order: a very-low saturated fat diet (control); the same diet with 20 mg lovastatin; a dietary portfolio high in plant sterols (1 g/4200 kJ), soya proteins (21.4 g/4200 kJ), soluble fibres (9.8 g/4200 kJ) and almonds (14 g/4200 kJ). LDL electrophoretic characteristics were measured by non-denaturing polyacrylamide gradient gel electrophoresis of fasting plasma at 0, 2 and 4 weeks of each treatment. The reductions in plasma LDL-cholesterol levels with the dietary portfolio and with statins were comparable and were largely attributable to reductions in the estimated concentration of cholesterol within the smallest subclass of LDL (portfolio - 0.69 (se 0.10) mmol/l, statin - 0.99 (se 0.10) mmol/l). These were significantly greater (P < 0.01) than changes observed after the control diet ( - 0.17 (se 0.08) mmol/l). Finally, baseline C-reactive protein levels were a significant predictor of the LDL size responsiveness to the dietary portfolio but not to the other treatments. The dietary portfolio, like the statin treatment, had only minor effects on several features of the LDL size phenotype, but the pronounced reduction in cholesterol levels within the small LDL fraction may provide additional cardiovascular benefit over the traditional low-fat diet of National Cholesterol Education Program Step II.

Screening and advanced lipid phenotyping in familial hypercholesterolemia: The Very Large Database of Lipids Study-17 (VLDL-17).

PubMed

Miller, P Elliott; Martin, Seth S; Toth, Peter P; Santos, Raul D; Blaha, Michael J; Nasir, Khurram; Virani, Salim S; Post, Wendy S; Blumenthal, Roger S; Jones, Steven R

2015-01-01

Familial hypercholesterolemia (FH) is an autosomal dominant dyslipidemia characterized by defective low-density lipoprotein (LDL) clearance. The aim of this study was to compare Friedewald-estimated LDL cholesterol (LDL-C) to biologic LDL-C in individuals screening positive for FH and then further characterize FH phenotypes. We studied 1,320,581 individuals from the Very Large Database of Lipids, referred from 2009 to 2011 for Vertical Auto Profile ultracentrifugation testing. Friedewald LDL-C was defined as the cholesterol content of LDL-C, intermediate-density lipoprotein cholesterol, and lipoprotein(a) cholesterol (Lp(a)-C), with LDL-C representing biologic LDL-C. Using Friedewald LDL-C, we phenotypically categorized patients by the National Lipid Association guideline age-based screening thresholds for FH. In those meeting criteria, we categorized patients using population percentile-equivalent biologic LDL-C cutpoints and explored Lp(a)-C and remnant lipoprotein cholesterol (RLP-C) levels. Overall, 3829 patients met phenotypic criteria for FH by Friedewald LDL-C screening (FH+). Of those screening FH+, 78.8% were above and 21.2% were below the population percentile-equivalent biologic LDL-C. The mean difference in Friedewald biologic LDL-C percentiles was -0.01 (standard deviation, 0.17) for those above, and 1.92 (standard deviation, 9.16) for those below, respectively. Over 1 of 3 were found to have an elevated Lp(a)-C and over 50% had RLP-C greater than 95th percentile of the entire VLDL population. Of those who screened FH+, Friedewald and biologic LDL-C levels were closely correlated. Large proportions of the FH+ group had excess levels of Lp(a)-C and RLP-C. Future studies are warranted to study these mixed phenotypic groups and determine the role for further risk stratification and treatment algorithms. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Ergonovine-induced changes of coronary artery diameter in patients with nonsignificant coronary artery stenosis : relation with lipid profile.

PubMed

Nedeljkovic, Milan A; Ostojic, Miodrag C; Beleslin, Branko D; Nedeljkovic, Ivana; Milic, Natasa; Vukcevic, Vladan; Stojkovic, Sinisa; Saponjski, Jovica; Orlic, Dejan; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Giga, Vojislav; Petrasinovic, Zorica; Arandjelovic, Aleksandra; Beleslin, Biljana; Kanjuh, Vladimir

2007-06-01

Serum cholesterol is positively associated with the risk of developing coronary heart disease. The aim of this study was to determine the relation between response of coronary arteries to ergonovine provocation and lipid profile in patients with nonsignificant coronary artery disease. 105 patients (46 male, 59 female, mean age 52 +/- 8 years) with chest pain syndrome and nonsignificant coronary artery stenosis (< 50% diameter stenosis) were analyzed. Ergonovine test was performed at the end of diagnostic catheterization. Coronary spasm was defined as total or near total obstruction of the coronary artery. By quantitative coronary arteriography, changes of minimal luminal diameter (MLD) during ergonovine provocation were evaluated. Total cholesterol, LDL and HDL cholesterol, and triglycerides were measured. There was a significant negative correlation between resting MLD and LDL cholesterol (r = -0.215; p = 0.034), and a significant positive correlation between MLD decrease provoked by ergonovine and total cholesterol (r = 0.275; p = 0.006), as well as LDL cholesterol (r = 0.284; p = 0.004), but not for HDL cholesterol and triglycerides (p = NS [not significant]). In patients with nonsignificant coronary artery stenosis evaluated by ergonovine provocation, there was not only a significant negative correlation between MLD and LDL cholesterol, but also a positive correlation between coronary vasoconstriction induced by ergonovine provocation and both total and LDL cholesterol.

Hypocholesterolemic effects of low calorie structured lipids on rats and rabbits fed on normal and atherogenic diet.

PubMed

Kanjilal, Sanjit; Kaki, Shiva Shanker; Rao, Bhamidipati V S K; Sugasini, Dhavamani; Rao, Yalagala Poornachandra; Prasad, Rachapudi B N; Lokesh, Belur R

2013-01-01

The hypocholesterolemic effects of two low calorie structured lipids (SL1 and SL2) containing essential fatty acids, prepared by lipase catalysed interesterification of ethyl behenate respectively with sunflower and soybean oils were studied in rats and rabbits. The feeding experiment conducted on rats as well as rabbits, fed on normal and atherogenic diet containing 10% of SL1 and SL2 (experimental) and sunflower oil (control) indicated no adverse effects on growth and food intake. However, the structured lipids beneficially lowered serum and liver lipids, particularly cholesterol, LDL cholesterol, triglycerides and also maintains the essential fatty acid status in serum and liver. The lipid deposition observed in the arteries of rabbits fed on atherogenic diets was significantly reduced when structured lipids were included in the diet. These observations coincided with reduced levels of serum cholesterol particularly LDL cholesterol observed in experimental groups. Therefore the structured lipids, designed to have low calorific value also beneficially lower serum lipids and lipid deposition in animals fed on atherogenic diets. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effect of maximal oxygen uptake and different forms of physical training on serum lipoproteins.

PubMed

Schnabel, A; Kindermann, W

1982-01-01

260 well trained male sportsmen between 17 and 30 years of age participating in a variety of events were examined for total serum cholesterol and lipoprotein cholesterol and compared with 37 moderately active leisure-time sportsmen and 20 sedentary controls of similar ages and sex. Lipoprotein cholesterol distribution was determined by quantitative electrophoresis. Mean HDL-cholesterol increased progressively from the mean of the sedentary control to the mean of the long-distance runners, indicating a graded effect of physical activity on HDL-cholesterol. In all sporting groups mean LDL-cholesterol tended to be lower than in the controls, no association between LDL-cholesterol and form of training being apparent. Except for the long-distance runners, all sporting groups tended to be lower in total cholesterol than the controls. The HDL-/total cholesterol and LDL/HDL ratios yielded a better discrimination between the physically active and inactive than the HDL-cholesterol alone. Significant positive correlations with maximal oxygen uptake and roentgenologically determined heart volume were found for HDL-cholesterol and HDL-/total cholesterol, and negative ones for LDL/HDL. Differences in the regressions among subsets made up of sporting groups under different physical demands suggest a positive relationship between lipoprotein distribution and the magnitude of the trained muscle mass.

Association of dietary nutrients with blood lipids and blood pressure in 18 countries: a cross-sectional analysis from the PURE study.

PubMed

Mente, Andrew; Dehghan, Mahshid; Rangarajan, Sumathy; McQueen, Matthew; Dagenais, Gilles; Wielgosz, Andreas; Lear, Scott; Li, Wei; Chen, Hui; Yi, Sun; Wang, Yang; Diaz, Rafael; Avezum, Alvaro; Lopez-Jaramillo, Patricio; Seron, Pamela; Kumar, Rajesh; Gupta, Rajeev; Mohan, Viswanathan; Swaminathan, Sumathi; Kutty, Raman; Zatonska, Katarzyna; Iqbal, Romaina; Yusuf, Rita; Mohammadifard, Noushin; Khatib, Rasha; Nasir, Nafiza Mat; Ismail, Noorhassim; Oguz, Aytekin; Rosengren, Annika; Yusufali, Afzalhussein; Wentzel-Viljoen, Edelweiss; Puoane, Thandi; Chifamba, Jephat; Teo, Koon; Anand, Sonia S; Yusuf, Salim

2017-10-01

The relation between dietary nutrients and cardiovascular disease risk markers in many regions worldwide is unknown. In this study, we investigated the effect of dietary nutrients on blood lipids and blood pressure, two of the most important risk factors for cardiovascular disease, in low-income, middle-income, and high-income countries. We studied 125 287 participants from 18 countries in North America, South America, Europe, Africa, and Asia in the Prospective Urban Rural Epidemiology (PURE) study. Habitual food intake was measured with validated food frequency questionnaires. We assessed the associations between nutrients (total fats, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, carbohydrates, protein, and dietary cholesterol) and cardiovascular disease risk markers using multilevel modelling. The effect of isocaloric replacement of saturated fatty acids with other fats and carbohydrates was determined overall and by levels of intakes by use of nutrient density models. We did simulation modelling in which we assumed that the effects of saturated fatty acids on cardiovascular disease events was solely related to their association through an individual risk marker, and then compared these simulated risk marker-based estimates with directly observed associations of saturated fatty acids with cardiovascular disease events. Participants were enrolled into the study from Jan 1, 2003, to March 31, 2013. Intake of total fat and each type of fat was associated with higher concentrations of total cholesterol and LDL cholesterol, but also with higher HDL cholesterol and apolipoprotein A1 (ApoA1), and lower triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein B (ApoB) to ApoA1 (all p trend <0·0001). Higher carbohydrate intake was associated with lower total cholesterol, LDL cholesterol, and ApoB, but also with lower HDL cholesterol and ApoA1, and higher triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ApoB-to-ApoA1 ratio (all p trend <0·0001, apart from ApoB [p trend =0·0014]). Higher intakes of total fat, saturated fatty acids, and carbohydrates were associated with higher blood pressure, whereas higher protein intake was associated with lower blood pressure. Replacement of saturated fatty acids with carbohydrates was associated with the most adverse effects on lipids, whereas replacement of saturated fatty acids with unsaturated fats improved some risk markers (LDL cholesterol and blood pressure), but seemed to worsen others (HDL cholesterol and triglycerides). The observed associations between saturated fatty acids and cardiovascular disease events were approximated by the simulated associations mediated through the effects on the ApoB-to-ApoA1 ratio, but not with other lipid markers including LDL cholesterol. Our data are at odds with current recommendations to reduce total fat and saturated fats. Reducing saturated fatty acid intake and replacing it with carbohydrate has an adverse effect on blood lipids. Substituting saturated fatty acids with unsaturated fats might improve some risk markers, but might worsen others. Simulations suggest that ApoB-to-ApoA1 ratio probably provides the best overall indication of the effect of saturated fatty acids on cardiovascular disease risk among the markers tested. Focusing on a single lipid marker such as LDL cholesterol alone does not capture the net clinical effects of nutrients on cardiovascular risk. Full funding sources listed at the end of the paper (see Acknowledgments). Copyright © 2017 Elsevier Ltd. All rights reserved.

Parent-child genetic testing for familial hypercholesterolaemia in an Australian context.

PubMed

Pang, Jing; Martin, Andrew C; Bates, Timothy R; Hooper, Amanda J; Bell, Damon A; Burnett, John R; Norman, Richard; Watts, Gerald F

2018-04-06

The aim of this study was to evaluate the clinical outcome of parent-child testing for familial hypercholesterolaemia (FH) employing genetic testing and the likely additional cost of treating each child. Parent-child testing for gene variants causative of FH was carried out according to Australian guidelines. The number of new cases detected, the low-density lipoprotein (LDL)-cholesterol that best predicted a mutation and the proportional reduction in LDL-cholesterol following statin treatment was evaluated. Treatment costs were calculated as the cost per mmol/L reduction in LDL-cholesterol. A total of 126 adult patients, known to have a pathogenic mutation causative of FH, and their children were studied. From 244 children identified, 148 (60.7%) were genetically screened; 84 children were identified as mutative positive (M+) and 64 as mutative negative. Six of the M+ children were already on statin treatment; 40 were subsequently treated with low-dose statins, with LDL-cholesterol falling significantly by 38% (P < 0.001). The estimated cost per mmol/L reduction of LDL-cholesterol of a child receiving statins from ages 10 to 18 years is AU$1361, which can potentially be cost-effective. An LDL-cholesterol threshold of 3.5 mmol/L had a sensitivity of 92.8% and specificity of 96.6% for the detection of a mutation. Genetic testing of children of affected parents with FH is an effective means of detecting new cases of FH. Cascade testing can enable early statin therapy with significant reductions in LDL-cholesterol concentration. © 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

High-oleic canola oil consumption enriches LDL particle cholesteryl oleate content and reduces LDL proteoglycan binding in humans

PubMed Central

Jones, Peter J. H.; MacKay, Dylan. S.; Senanayake, Vijitha K.; Pu, Shuaihua; Jenkins, David J. A.; Connelly, Philip W.; Lamarche, Benoît; Couture, Patrick; Kris-Etherton, Penny M.; West, Sheila G.; Liu, Xiaoran; Fleming, Jennifer A.; Hantgan, Roy R.; Rudel, Lawrence L.

2015-01-01

Oleic acid consumption is considered cardio-protective according to studies conducted examining effects of the Mediterranean diet. However, animal models have shown that oleic acid consumption increases LDL particle cholesteryl oleate content which is associated with increased LDL-proteoglycan binding and atherosclerosis. The objective was to examine effects of varying oleic, linoleic and docosahexaenoic acid consumption on human LDL-proteoglycan binding in a non-random subset of the Canola Oil Multi-center Intervention Trial (COMIT) participants. COMIT employed a randomized, double-blind, five-period, cross-over trial design. Three of the treatment oil diets; 1) a blend of corn/safflower oil (25:75); 2) high oleic canola oil; and 3) DHA-enriched high oleic canola oil were selected for analysis of LDL-proteoglycan binding in 50 participants exhibiting good compliance. LDL particles were isolated from frozen plasma by gel filtration chromatography and LDL cholesteryl esters quantified by mass-spectrometry. LDL-proteoglycan binding was assessed using surface plasmon resonance. LDL particle cholesterol ester fatty acid composition was sensitive to the treatment fatty acid compositions, with the main fatty acids in the treatments increasing in the LDL cholesterol esters. The corn/safflower oil and high-oleic canola oil diets lowered LDL-proteoglycan binding relative to their baseline values (p=0.0005 and p=0.0012, respectively). At endpoint, high-oleic canola oil feeding resulted in lower LDL-proteoglycan binding than corn/safflower oil (p=0.0243) and DHA-enriched high oleic canola oil (p=0.0249), although high-oleic canola oil had the lowest binding at baseline (p=0.0344). Our findings suggest that high-oleic canola oil consumption in humans increases cholesteryl oleate percentage in LDL, but in a manner not associated with a rise in LDL-proteoglycan binding. PMID:25528432

Mechanisms of foam cell formation in atherosclerosis.

PubMed

Chistiakov, Dimitry A; Melnichenko, Alexandra A; Myasoedova, Veronika A; Grechko, Andrey V; Orekhov, Alexander N

2017-11-01

Low-density lipoprotein (LDL) and cholesterol homeostasis in the peripheral blood is maintained by specialized cells, such as macrophages. Macrophages express a variety of scavenger receptors (SR) that interact with lipoproteins, including SR-A1, CD36, and lectin-like oxLDL receptor-1 (LOX-1). These cells also have several cholesterol transporters, including ATP-binding cassette transporter ABCA1, ABCG1, and SR-BI, that are involved in reverse cholesterol transport. Lipids internalized by phagocytosis are transported to late endosomes/lysosomes, where lysosomal acid lipase (LAL) digests cholesteryl esters releasing free cholesterol. Free cholesterol in turn is processed by acetyl-CoA acetyltransferase (ACAT1), an enzyme that transforms cholesterol to cholesteryl esters. The endoplasmic reticulum serves as a depot for maintaining newly synthesized cholesteryl esters that can be processed by neutral cholesterol ester hydrolase (NCEH), which generates free cholesterol that can exit via cholesterol transporters. In atherosclerosis, pro-inflammatory stimuli upregulate expression of scavenger receptors, especially LOX-1, and downregulate expression of cholesterol transporters. ACAT1 is also increased, while NCEH expression is reduced. This results in deposition of free and esterified cholesterol in macrophages and generation of foam cells. Moreover, other cell types, such as endothelial (ECs) and vascular smooth muscle cells (VSMCs), can also become foam cells. In this review, we discuss known pathways of foam cell formation in atherosclerosis.

Randomized, Placebo-Controlled Trial of Mipomersen in Patients with Severe Hypercholesterolemia Receiving Maximally Tolerated Lipid-Lowering Therapy

PubMed Central

McGowan, Mary P.; Tardif, Jean-Claude; Ceska, Richard; Burgess, Lesley J.; Soran, Handrean; Gouni-Berthold, Ioanna; Wagener, Gilbert; Chasan-Taber, Scott

2012-01-01

Objectives Mipomersen, an antisense oligonucleotide targeting apolipoprotein B synthesis, significantly reduces LDL-C and other atherogenic lipoproteins in familial hypercholesterolemia when added to ongoing maximally tolerated lipid-lowering therapy. Safety and efficacy of mipomersen in patients with severe hypercholesterolemia was evaluated. Methods and Results Randomized, double-blind, placebo-controlled, multicenter trial. Patients (n  = 58) were ≥18 years with LDL-C ≥7.8 mmol/L or LDL-C ≥5.1 mmol/L plus CHD disease, on maximally tolerated lipid-lowering therapy that excluded apheresis. Weekly subcutaneous injections of mipomersen 200 mg (n  = 39) or placebo (n  = 19) were added to lipid-lowering therapy for 26 weeks. Main outcome: percent reduction in LDL-C from baseline to 2 weeks after the last dose of treatment. Mipomersen (n = 27) reduced LDL-C by 36%, from a baseline of 7.2 mmol/L, for a mean absolute reduction of 2.6 mmol/L. Conversely, mean LDL-C increased 13% in placebo (n = 18) from a baseline of 6.5 mmol/L (mipomersen vs placebo p<0.001). Mipomersen produced statistically significant (p<0.001) reductions in apolipoprotein B and lipoprotein(a), with no change in high-density lipoprotein cholesterol. Mild-to-moderate injection site reactions were the most frequently reported adverse events with mipomersen. Mild-to-moderate flu-like symptoms were reported more often with mipomersen. Alanine transaminase increase, aspartate transaminase increase, and hepatic steatosis occurred in 21%, 13% and 13% of mipomersen treated patients, respectively. Adverse events by category for the placebo and mipomersen groups respectively were: total adverse events, 16(84.2%), 39(100%); serious adverse events, 0(0%), 6(15.4%); discontinuations due to adverse events, 1(5.3%), 8(20.5%) and cardiac adverse events, 1(5.3%), 5(12.8%). Conclusion Mipomersen significantly reduced LDL-C, apolipoprotein B, total cholesterol and non-HDL-cholesterol, and lipoprotein(a). Mounting evidence suggests it may be a potential pharmacologic option for lowering LDL-C in patients with severe hypercholesterolemia not adequately controlled using existing therapies. Future studies will explore alternative dosing schedules aimed at minimizing side effects. Trial Registration ClinicalTrials.gov NCT00794664. PMID:23152839

Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study).

PubMed

Bang, Casper N; Greve, Anders M; La Cour, Morten; Boman, Kurt; Gohlke-Bärwolf, Christa; Ray, Simon; Pedersen, Terje; Rossebø, Anne; Okin, Peter M; Devereux, Richard B; Wachtell, Kristian

2015-12-15

Recent American College of Cardiology/American Heart Association guidelines on statin initiation on the basis of total atherosclerotic cardiovascular disease risk argue that the preventive effect of statins on cardiovascular events outweigh the side effects, although this is controversial. Studies indicate a possible effect of statin therapy on reducing risk of lens opacities. However, the results are conflicting. The Simvastatin and Ezetimibe in Aortic Stenosis study (NCT00092677) enrolled 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease, or other serious co-morbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg ezetimibe versus placebo. The primary end point in this substudy was incident cataract. Univariate and multivariate Cox models were used to analyze: (1) if the active treatment reduced the risk of the primary end point and (2) if time-varying low-density lipoproteins (LDL) cholesterol lowering (annually assessed) was associated with less incident cataract per se. During an average follow-up of 4.3 years, 65 patients (3.5%) developed cataract. Mean age at baseline was 68 years and 39% were women. In Cox multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion, randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower risk of incident cataract development. This effect should perhaps be considered in the risk-benefit ratio of statin treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

High-intensity statin therapy and regression of coronary atherosclerosis in patients with diabetes mellitus.

PubMed

Athyros, Vasilios G; Katsiki, Niki; Karagiannis, Asterios; Mikhailidis, Dimitri P

2015-01-01

Recommended low-density lipoprotein cholesterol (LDL-C) levels for patients with documented cardiovascular disease (CVD) are <100mg/dL (2.6mmol/l) with further reduction to <70mg/dL (1.8mmol/l) for higher-risk patients. High-intensity statin treatment may halt the progression as well as stabilize and induce regression of coronary atheromatous plaques while lowering CVD event rates. Diabetes mellitus (DM) is a major negative determinant of coronary artery plaque regression during statin therapy. However, regression of coronary atherosclerosis in DM patients is feasible to the same degree as in those without DM when very low LDL-C values (<70mg/dL; 1.8mmol/l) are achieved with high intensity statin treatment. The recent 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults suggest to abandon specific LDL-C treatment targets. This strategy may deprive high risk patients, such as those with DM, from very high intensity statin treatment or drug combinations aiming to achieve very low LDL-C levels in order to reduce clinical events. Copyright © 2015 Elsevier Inc. All rights reserved.

Preparative Production of Acetylcholinesterase and Paraoxonase in Procaryotic and Eucaryotic Expression in Systems

DTIC Science & Technology

2006-01-01

HDL, ’good cholesterol ’) and are involved in the prevention of atherosclerosis . We describe the first crystal structure of a PON family member, a... atherosclerosis and to OP poisoning3. In vitro assays show that PON1 and PON3 inhibit lipid oxidation in LDL (“bad cholesterol ”), thus reducing levels of...PON3, which share ~60% sequence identity with PON1. PON1 and PON3 reside in the cholesterol -carrying HDL (“good cholesterol ”) particles, whereas

Effect of Leptin Replacement on PCSK9 in ob/ob Mice and Female Lipodystrophic Patients.

PubMed

Levenson, Amy E; Haas, Mary E; Miao, Ji; Brown, Rebecca J; de Ferranti, Sarah D; Muniyappa, Ranganath; Biddinger, Sudha B

2016-04-01

Leptin treatment has beneficial effects on plasma lipids in patients with lipodystrophy, but the underlying mechanism is unknown. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases low-density lipoprotein (LDL) clearance, promotes hypercholesterolemia, and has recently emerged as a novel therapeutic target. To determine the effect of leptin on PCSK9, we treated male and female ob/ob mice with leptin for 4 days via sc osmotic pumps (∼24 μg/d). Leptin reduced body weight and food intake in all mice, but the effects of leptin on plasma PCSK9 and lipids differed markedly between the sexes. In male mice, leptin suppressed PCSK9 but had no effect on plasma triglycerides or cholesterol. In female mice, leptin suppressed plasma triglycerides and cholesterol but had no effect on plasma PCSK9. In parallel, we treated female lipodystrophic patients (8 females, ages 5-23 y) with sc metreleptin injections (∼4.4 mg/d) for 4-6 months. In this case, leptin reduced plasma PCSK9 by 26% (298 ± 109 vs 221 ± 102 ng/mL; n = 8; P = .008), and the change in PCSK9 was correlated with a decrease in LDL cholesterol (r(2) = 0.564, P = .03). In summary, in leptin-deficient ob/ob mice, the effects of leptin on PCSK9 and plasma lipids appeared to be independent of one another and strongly modified by sex. On the other hand, in lipodystrophic females, leptin treatment reduced plasma PCSK9 in parallel with LDL cholesterol.

Effect of Leptin Replacement on PCSK9 in ob/ob Mice and Female Lipodystrophic Patients

PubMed Central

Levenson, Amy E.; Haas, Mary E.; Miao, Ji; Brown, Rebecca J.; de Ferranti, Sarah D.; Muniyappa, Ranganath

2016-01-01

Leptin treatment has beneficial effects on plasma lipids in patients with lipodystrophy, but the underlying mechanism is unknown. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases low-density lipoprotein (LDL) clearance, promotes hypercholesterolemia, and has recently emerged as a novel therapeutic target. To determine the effect of leptin on PCSK9, we treated male and female ob/ob mice with leptin for 4 days via sc osmotic pumps (∼24 μg/d). Leptin reduced body weight and food intake in all mice, but the effects of leptin on plasma PCSK9 and lipids differed markedly between the sexes. In male mice, leptin suppressed PCSK9 but had no effect on plasma triglycerides or cholesterol. In female mice, leptin suppressed plasma triglycerides and cholesterol but had no effect on plasma PCSK9. In parallel, we treated female lipodystrophic patients (8 females, ages 5–23 y) with sc metreleptin injections (∼4.4 mg/d) for 4–6 months. In this case, leptin reduced plasma PCSK9 by 26% (298 ± 109 vs 221 ± 102 ng/mL; n = 8; P = .008), and the change in PCSK9 was correlated with a decrease in LDL cholesterol (r2 = 0.564, P = .03). In summary, in leptin-deficient ob/ob mice, the effects of leptin on PCSK9 and plasma lipids appeared to be independent of one another and strongly modified by sex. On the other hand, in lipodystrophic females, leptin treatment reduced plasma PCSK9 in parallel with LDL cholesterol. PMID:26824363

Potential role of lycopene in targeting proprotein convertase subtilisin/kexin type-9 to combat hypercholesterolemia.

PubMed

Sultan Alvi, Sahir; Ansari, Irfan A; Khan, Imran; Iqbal, Johar; Khan, M Salman

2017-07-01

Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a serine protease of the proprotien convertase (PC) family that has profound effects on plasma low density lipoprotein cholesterol (LDL-C) levels, the major risk factor for coronary heart disease (CHD), through its ability to mediate LDL receptor (LDL-R) protein degradation and reduced recycling to the surface of hepatocytes. Thus, the current study was premeditated not only to evaluate the role of lycopene in targeting the inhibition of PCSK-9 via modulation of genes involved in cholesterol homeostasis in HFD rats but also to examine a correlation between HFD induced inflammatory cascades and subsequent regulation of PCSK-9 expression. Besides the effect of lycopene on hepatic PCSK-9 gene expression, PPI studies for PCSK-9-Lycopene complex and EGF-A of LDL-R were also performed via molecular informatics approach to assess the dual mode of action of lycopene in LDL-R recycling and increased removal of circulatory LDL-C. We for the first time deciphered that lycopene treatment significantly down-regulates the expression of hepatic PCSK-9 and HMGR, whereas, hepatic LDL-R expression was significantly up-regulated. Furthermore, lycopene ameliorated inflammation stimulated expression of PCSK-9 via suppressing the expression of inflammatory markers. The results from our molecular informatics studies confirmed that lycopene, while occupying the active site of PCSK-9 crystal structure, reduces the affinity of PCSK-9 to complex with EGF-A of LDL-R, whereas, atorvastatin makes PCSK-9-EGF-A complex formation more feasible than both of PCSK-9-EGF-A alone and Lycopene-PCSK-9-EGF-A complex. Based on above results, it can be concluded that lycopene exhibits potent hypolipidemic activities via molecular mechanisms that are either identical (HMGR inhibition) or distinct from that of statins (down-regulation of PCSK-9 mRNA synthesis). To the best of our knowledge, this is the first report that lycopene has this specific biological property. Being a natural, safer and alternative therapeutic agent, lycopene could be used as a complete regulator of cholesterol homeostasis and ASCVD. Copyright © 2017 Elsevier Inc. All rights reserved.

A systematic review and meta-analysis of randomized controlled trials of the effect of konjac glucomannan, a viscous soluble fiber, on LDL cholesterol and the new lipid targets non-HDL cholesterol and apolipoprotein B.

PubMed

Ho, Hoang Vi Thanh; Jovanovski, Elena; Zurbau, Andreea; Blanco Mejia, Sonia; Sievenpiper, John L; Au-Yeung, Fei; Jenkins, Alexandra L; Duvnjak, Lea; Leiter, Lawrence; Vuksan, Vladimir

2017-05-01

Background: Evidence from randomized controlled trials (RCTs) suggests the consumption of konjac glucomannan (KJM), a viscous soluble fiber, for improving LDL-cholesterol concentrations. It has also been suggested that the cholesterol-lowering potential of KJM may be greater than that of other fibers. However, trials have been relatively scarce and limited in sample size and duration, and the effect estimates have been inconsistent. The effect of KJM on new lipid targets of cardiovascular disease (CVD) risk is also unknown. Objective: This systematic review and meta-analysis aimed to assess the effect of KJM on LDL cholesterol, non-HDL cholesterol, and apolipoprotein B. Design: Medline, Embase, CINAHL, and the Cochrane Central databases were searched. We included RCTs with a follow-up of ≥3 wk that assessed the effect of KJM on LDL cholesterol, non-HDL cholesterol, or apolipoprotein B. Data were pooled by using the generic inverse-variance method with random-effects models and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I 2 statistic. Results: Twelve studies ( n = 370), 8 in adults and 4 in children, met the inclusion criteria. KJM significantly lowered LDL cholesterol (MD: -0.35 mmol/L; 95% CI: -0.46, -0.25 mmol/L) and non-HDL cholesterol (MD: -0.32 mmol/L; 95% CI: -0.46, -0.19 mmol/L). Data from 6 trials suggested no impact of KJM on apolipoprotein B. Conclusions: Our findings support the intake of ∼3 g KJM/d for reductions in LDL cholesterol and non-HDL cholesterol of 10% and 7%, respectively. The information may be of interest to health agencies in crafting future dietary recommendations related to reduction in CVD risk. This study was registered at clinicaltrials.gov as NCT02068248. © 2017 American Society for Nutrition.

Influence of specific mutations at the LDL-receptor gene locus on the response to simvastatin therapy in Afrikaner patients with heterozygous familial hypercholesterolaemia.

PubMed

Jeenah, M; September, W; Graadt van Roggen, F; de Villiers, W; Seftel, H; Marais, D

1993-01-04

Simvastatin, an inhibitor of HMG CoA reductase, lowers the plasma total cholesterol and LDL-cholesterol concentration in familial hypercholesterolemic patients. The efficacy of the drug shows considerable inter-individual variation, however. In this study we have assessed the influence of certain LDL-receptor gene mutations on this variation. A group of 20 male and female heterozygotic familial hypercholesterolemic patients, all Afrikaners and each bearing one of two different LDL receptor gene mutations, FH Afrikaner-1 (FH1) and FH Afrikaner-2 (FH2), was treated with simvastatin (40 mg once daily) for 18 months. The average reduction in total plasma cholesterol was 35.3% in the case of the FH2 men but only 23.2% in that of the FH1 men (P = 0.005); the reduction in LDL cholesterol concentrations was also greater in the FH2 group (39% as opposed to 27.1%, P = 0.02). The better response of the FH2 group was also evident when men and women were considered together. Female FH1 patients responded better to simvastatin treatment, however, than did males with the same gene defect. Mutations at the LDL-receptor locus may thus play a significant role in the variable efficacy of the drug. The particular mutations in the males of this group may have contributed up to 35% of the variance in total cholesterol response and 29% of the variance in LDL-cholesterol response to simvastatin treatment.

Combined effect of Lactobacillus acidophilus and β-cyclodextrin on serum cholesterol in pigs.

PubMed

Alonso, L; Fontecha, J; Cuesta, P

2016-01-14

A total of twenty-four Yorkshire gilt pigs of 6-7 weeks of age were used in a 2×2 factorial experiment to determine the individual and combined effects of the inclusion of two dietary factors (cholesterol rich, 3% β-cyclodextrin (BCD) and Lactobacillus acidophilus cultures) on total cholesterol and LDL-cholesterol levels in blood serum. Pigs were assigned randomly to treatment groups (n 6). Total serum cholesterol concentrations decreased after 3 weeks in all the experimental treatment groups, including diets with BCD, L. acidophilus or both. Similar trends were observed for serum LDL-cholesterol concentrations among the experimental treatments. No statistically significant differences from the control group were observed in either total serum cholesterol or LDL-cholesterol concentrations (P<0·05) for each of the individual treatment groups: BCD or L. acidophilus. However, significant differences in total serum cholesterol concentrations were observed when comparing the combined treatment group (BCD and L. acidophilus) with the control group, which consisted of a basal diet and sterile milk. The combined treatment group exhibited 17·9% lower total serum cholesterol concentration after 3 weeks. Similar significant differences were observed when comparing the combined effect experimental group with the control group after 3 weeks. The combined treatment group exhibited 27·9% lower serum LDL-cholesterol concentrations.

Cost-effectiveness of extended-release niacin/laropiprant added to a stable simvastatin dose in secondary prevention patients not at cholesterol goal in Germany.

PubMed

Michailov, Galin V; Davies, Glenn M; Krobot, Karl J

2012-06-01

Coronary heart disease (CHD) remains the leading cause of death in Germany despite statin use to reduce low-density lipoprotein cholesterol (LDL-C) levels; improving lipids beyond LDL-C may further reduce cardiovascular risk. A fixed-dose combination of extended-release niacin (ERN) with laropiprant (LRPT) provides comprehensive lipid management. We adapted a decision-analytic model to evaluate the economic value (incremental cost-effectiveness ratio [ICER] in terms of costs per life-years gained [LYG]) of ERN/LRPT 2 g over a lifetime in secondary prevention patients in a German setting. Two scenarios were modelled: (1) ERN/LRPT 2 g added to simvastatin 40 mg in patients not at LDL-C goal with simvastatin 40 mg; (2) adding ERN/LRPT 2 g compared with titration to simvastatin 40 mg in patients not at LDL-C goal with simvastatin 20 mg. In both scenarios, adding ERN/LRPT was cost-effective relative to simvastatin monotherapy at a commonly accepted threshold of €30,000 per LYG; ICERs for ERN/LRPT were €13,331 per LYG in scenario 1 and €17,684 per LYG in scenario 2. Subgroup analyses showed that ERN/LRPT was cost-effective in patients with or without diabetes, patients aged ≤ 65 or >65 years and patients with low baseline high-density lipoprotein cholesterol levels; ICERs ranged from €10,342 to €15,579 in scenario 1, and from €14,081 to €20,462 in scenario 2. In conclusion, comprehensive lipid management with ERN/LRPT 2 g is cost-effective in secondary prevention patients in Germany who have not achieved LDL-C goal with simvastatin monotherapy.

Design and Rationale of the LAPLACE-TIMI 57 Trial: A Phase II, Double-Blind, Placebo-Controlled Study of the Efficacy and Tolerability of a Monoclonal Antibody Inhibitor of PCSK9 in Subjects With Hypercholesterolemia on Background Statin Therapy

PubMed Central

Kohli, Payal; Desai, Nihar R.; Giugliano, Robert P.; Kim, Jae B.; Somaratne, Ransi; Huang, Fannie; Knusel, Beat; McDonald, Shannon; Abrahamsen, Timothy; Wasserman, Scott M.; Scott, Robert; Sabatine, Marc S.

2013-01-01

Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone for the prevention of atherosclerotic heart disease, improving clinical outcomes and reducing vascular mortality in patients with hypercholesterolemia. The clinical benefits of LDL-C reduction appear to extend even to patients starting with LDL-C as low as 60–80 mg/dL prior to initiating therapy. Statins are the first-line agents for treating hypercholesterolemia and are effective in reducing LDL-C, but many patients are unable to achieve their optimal lipid targets despite intensive statin therapy. Therefore, there has been a strong impetus for the development of novel pharmacologic agents designed to lower LDL-C further in patients already on statin therapy. Genetic mutations resulting in altered cholesterol homeostasis provide valuable information regarding novel approaches for treating hypercholesterolemia. To that end, mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) were linked to altered levels of LDL-C, illustrating this protein’s role in lipid metabolism. PCSK9 promotes degradation of the LDL receptor, preventing its transport back to the cell surface and thereby increasing circulating LDL-C. Conversely, inhibition of PCSK9 can profoundly decrease circulating LDL-C, and thus is an attractive new target for LDL-C–lowering therapy. AMG 145 is a fully human monoclonal immunoglobulin G2 antibody that binds specifically to human PCSK9 and inhibits its interaction with the low-density lipoprotein receptor. In this manuscript, we describe the rationale and design of LDL-C Assessment with PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy–Thrombolysis In Myocardial Infarction 57 (LAPLACE-TIMI 57; NCT01380730), a 12-week, randomized, double-blind, dose-ranging, placebo-controlled study designed to assess the safety and efficacy of AMG 145 when added to statin therapy in patients with hypercholesterolemia. PMID:22714699

Impact of oxLDL on Cholesterol-Rich Membrane Rafts

PubMed Central

Levitan, Irena; Shentu, Tzu-Pin

2011-01-01

Numerous studies have demonstrated that cholesterol-rich membrane rafts play critical roles in multiple cellular functions. However, the impact of the lipoproteins on the structure, integrity and cholesterol composition of these domains is not well understood. This paper focuses on oxidized low-density lipoproteins (oxLDLs) that are strongly implicated in the development of the cardiovascular disease and whose impact on membrane cholesterol and on membrane rafts has been highly controversial. More specifically, we discuss three major criteria for the impact of oxLDL on membrane rafts: distribution of different membrane raft markers, changes in membrane cholesterol composition, and changes in lipid packing of different membrane domains. We also propose a model to reconcile the controversy regarding the relationship between oxLDL, membrane cholesterol, and the integrity of cholesterol-rich membrane domains. PMID:21490811

Novel treatment options for the management of heterozygous familial hypercholesterolemia.

PubMed

Polychronopoulos, Georgios; Tziomalos, Konstantinos

2017-12-01

Even though statins represent the mainstay of treatment of heterozygous familial hypercholesterolemia (FH), their low-density lipoprotein cholesterol (LDL-C) lowering efficacy is finite and most patients with FH will not achieve LDL-C targets with statin monotherapy. Addition of ezetimibe with or without bile acid sequestrants will also not lead to treatment goals in many of these patients, particularly in those with established cardiovascular disease. In this selected subgroup of the FH population, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide substantial reductions in LDL-C levels, reduce cardiovascular morbidity and appear to be safe. Mipomersen, an antisense single-strand oligonucleotide that inhibits the production of apoB by binding to the mRNA that encodes the synthesis of apoB, and lomitapide, an inhibitor of microsomal triglyceride transfer protein, also reduce LDL-C levels but are currently indicated only for the management of homozygous FH. Areas covered: In the present review, the role of PCSK9 inhibitors, mipomersen and lomitapide in the management of FH is briefly discussed. Other LDL-C-lowering agents under evaluation include inclisiran, a small interference RNA molecule that induces long-term inhibition of PSCK9 synthesis, anacetrapib, a cholesterol ester-transfer protein inhibitor, ETC-1002 (bempedoic acid), an inhibitor of adenosine triphosphate citrate lyase, and gemcabene, which reduces hepatic apolipoprotein C-III mRNA. The safety and efficacy of these agents are also reviewed. Expert Commentary: Even though several novel treatment options for heterozygous FH are under development, it remains to be shown whether these treatments will also reduce cardiovascular morbidity in these high-risk patients.

LDL-cholesterol and insulin are independently associated with body mass index in adult cystic fibrosis patients.

PubMed

Coderre, Lise; Fadainia, Christophe; Belson, Linda; Belisle, Virginie; Ziai, Sophie; Maillhot, Geneviève; Berthiaume, Yves; Rabasa-Lhoret, Rémi

2012-09-01

The median life expectancy of cystic fibrosis (CF) patients has increased dramatically over the last few years and we now observe a subset of patients with a body mass index (BMI) exceeding 25 kg/m(2). The aim of this study was to characterize these individuals and to identify factors associated with higher BMI. This is a cross sectional study including 187 adult CF subjects. Percent predicted forced expiratory volume in 1s (%FEV(1)), blood lipid profiles as well as fasting glucose and insulin levels were evaluated. Subjects also had an oral glucose tolerance test (OGTT) and the area under the curve (AUC) for glucose and insulin was calculated. CF subjects were then stratified according to the following BMI categories: underweight: BMI≤18.5 kg/m(2); normal weight: 18.5 kg/m(2)

Control of hyperglycaemia and hyperlipidaemia by plant product.

PubMed

Bhardwaj, P K; Dasgupta, D J; Prashar, B S; Kaushal, S S

1994-01-01

A herbal powder consisting of Guargum, Methi, Tundika and Meshasringi was administered to thirty control and thirty NIDDM patients twice daily before principal meals for four weeks. Oral GTT showed improvement in both control and patient groups. Serum total and LDL cholesterol also fell significantly in both the groups after the trial period. Test meal of the herbal powder with D-Xylose excretion was otherwise normal. Follow up for upto two years did not reveal any long term side effect of the powder. This powder, therefore, can be effectively used to reduce postprandial blood glucose and LDL cholesterol in NIDDM patients as a long term measure.

Cholesterol Absorption and Synthesis in Vegetarians and Omnivores.

PubMed

Lütjohann, Dieter; Meyer, Sven; von Bergmann, Klaus; Stellaard, Frans

2018-03-01

Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Statin action enriches HDL3 in polyunsaturated phospholipids and plasmalogens and reduces LDL-derived phospholipid hydroperoxides in atherogenic mixed dyslipidemia

PubMed Central

Tan, Ricardo; Giral, Philippe; Robillard, Paul; Kontush, Anatol; Chapman, M. John

2016-01-01

Atherogenic mixed dyslipidemia associates with oxidative stress and defective HDL antioxidative function in metabolic syndrome (MetS). The impact of statin treatment on the capacity of HDL to inactivate LDL-derived, redox-active phospholipid hydroperoxides (PCOOHs) in MetS is indeterminate. Insulin-resistant, hypertriglyceridemic, hypertensive, obese males were treated with pitavastatin (4 mg/day) for 180 days, resulting in marked reduction in plasma TGs (−41%) and LDL-cholesterol (−38%), with minor effects on HDL-cholesterol and apoAI. Native plasma LDL (baseline vs. 180 days) was oxidized by aqueous free radicals under mild conditions in vitro either alone or in the presence of the corresponding pre- or poststatin HDL2 or HDL3 at authentic plasma mass ratios. Lipidomic analyses revealed that statin treatment i) reduced the content of oxidizable polyunsaturated phosphatidylcholine (PUPC) species containing DHA and linoleic acid in LDL; ii) preferentially increased the content of PUPC species containing arachidonic acid (AA) in small, dense HDL3; iii) induced significant elevation in the content of phosphatidylcholine and phosphatidylethanolamine (PE) plasmalogens containing AA and DHA in HDL3; and iv) induced formation of HDL3 particles with increased capacity to inactivate PCOOH with formation of redox-inactive phospholipid hydroxide. Statin action attenuated LDL oxidability Concomitantly, the capacity of HDL3 to inactivate redox-active PCOOH was enhanced relative to HDL2, consistent with preferential enrichment of PE plasmalogens and PUPC in HDL3. PMID:27581680

Lipid accumulation in smooth muscle cells under LDL loading is independent of LDL receptor pathway and enhanced by hypoxic conditions.

PubMed

Wada, Youichiro; Sugiyama, Akira; Yamamoto, Takashi; Naito, Makoto; Noguchi, Noriko; Yokoyama, Shinji; Tsujita, Maki; Kawabe, Yoshiki; Kobayashi, Mika; Izumi, Akashi; Kohro, Takahide; Tanaka, Toshiya; Taniguchi, Hirokazu; Koyama, Hidenori; Hirano, Ken-ichi; Yamashita, Shizuya; Matsuzawa, Yuji; Niki, Etsuo; Hamakubo, Takao; Kodama, Tatsuhiko

2002-10-01

The effect of a variety of hypoxic conditions on lipid accumulation in smooth muscle cells (SMCs) was studied in an arterial wall coculture and monocultivation model. Low density lipoprotein (LDL) was loaded under various levels of oxygen tension. Oil red O staining of rabbit and human SMCs revealed that lipid accumulation was greater under lower oxygen tension. Cholesterol esters were shown to accumulate in an oxygen tension-dependent manner by high-performance liquid chromatographic analysis. Autoradiograms using radiolabeled LDL indicated that LDL uptake was more pronounced under hypoxia. This result holds in the case of LDL receptor-deficient rabbit SMCs. However, cholesterol biosynthesis and cellular cholesterol release were unaffected by oxygen tension. Hypoxia significantly increases LDL uptake and enhances lipid accumulation in arterial SMCs, exclusive of LDL receptor activity. Although the molecular mechanism is not clear, the model is useful for studying lipid accumulation in arterial wall cells and the difficult-to-elucidate events in the initial stage of atherogenesis.

Radioiodinated cholesteryl ester analogs as residualizing tracers of lipoproteins disposition

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeForge, L.E.

1989-01-01

Due to the importance of low density lipoprotein (LDL) in lipid metabolism and atherosclerosis, efforts were made to incorporate {sup 125}I-cholesteryl iopanoate ({sup 125}I-CI), a residualizing cholesteryl ester (CE) analog, into the lipid core of LDL. This preparation is potentially useful as a scintigraphically detectable tracer of LDL uptake into atheroma and tissues such as the adrenal and liver. Initial studies using a cholesterol-fed rabbit model of atherosclerosis validated the use of {sup 125}I-CI as a tracer of CE deposition. However, scintigraphy revealed considerable nonspecific {sup 125}I-CI uptake due to tissue cholesterol loading. An alternative animal model was the guineamore » pig, which responds moderately to cholesterol feeding and carries the plasma cholesterol predominantly as LDL. Dietary fat and cholesterol, coupled with chronic aortic injury caused by an indwelling catheter, resulted in lipid containing, smooth muscle cell proliferative lesions in many animals. However, further studies are necessary to fully characterize this model. In additional studies, in vitro methods for incorporating {sup 125}I-CI into LDL were examined. These included a reconstitution procedure described by Krieger et al. and a procedure involving incubation of detergent (Tween 20)-solubilized {sup 125}I-CI with plasma. Although both LDL preparations were taken up normally by cultured fibroblasts, the plasma clearance rate of reconstituted LDL was markedly abnormal in guinea pigs. In contrast, LDL labeled by the detergent method cleared from the plasma identically to a radioiodinated LDL control. Therefore, this latter procedure was also used to incorporate two novel radioiodinated cholesteryl ether analogs {sup 125}I-CI cholesteryl m-iodobenzyl ether ({sup 125}I-CIDE) and {sup 125}I-cholesteryl 12-(miodophenyl)dodecyl ether ({sup 125}I-CIDE) into LDL.« less

Surrogate Lipid Markers for Small Dense Low-Density Lipoprotein Particles in Overweight Youth

PubMed Central

Burns, Stephen F.; Lee, So Jung; Arslanian, Silva A.

2013-01-01

Objectives To determine if the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL) and non–HDL cholesterol concentration could identify youth with small dense low-density lipoprotein (LDL). Study design One hundred forty-one (75 black and 66 white) overweight adolescents (9 to <18 years) had a fasting measurement of plasma lipids and LDL particle concentrations and size. Receiver operating characteristic curves were used to indicate the ability of different TG/HDL ratios and non–HDL cholesterol concentrations to identify overweight youth with atherogenic LDL concentration and size. Results Youth with a TG/HDL ratio of ≥3 vs <3 had higher concentrations of small dense LDL (1279.5 ± 60.1 vs 841.8 ± 24.2 nmol/L, P < .001) and smaller LDL particle size (20.3 ± 0.1 vs 21.2 ± 0.1 nm, P < .001). In receiver operating characteristic analyses a TG/HDL cut-point of 3 best predicted LDL concentration in white youth, and 2.5 in black youth. Non-HDL cholesterol cut-point of 120 mg/dL and 145 mg/dL predicted LDL particle concentration in white and in black youth, respectively. TG/HDL ratio with body mass index or waist circumference explained 71% and 79% of the variance, respectively, in total small LDL. Conclusions TG/HDL ratio and non-HDL cholesterol can identify overweight youth with atherogenic LDL particles. These easily obtained clinical lipid markers, in combination with body mass index and waist circumference, could be cost effective, in observational or interventional studies, for screening and follow-up of youth at heightened risk for atherogenic LDL. PMID:22809659

Surrogate lipid markers for small dense low-density lipoprotein particles in overweight youth.

PubMed

Burns, Stephen F; Lee, So Jung; Arslanian, Silva A

2012-12-01

To determine if the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL) and non-HDL cholesterol concentration could identify youth with small dense low-density lipoprotein (LDL). One hundred forty-one (75 black and 66 white) overweight adolescents (9 to <18 years) had a fasting measurement of plasma lipids and LDL particle concentrations and size. Receiver operating characteristic curves were used to indicate the ability of different TG/HDL ratios and non-HDL cholesterol concentrations to identify overweight youth with atherogenic LDL concentration and size. Youth with a TG/HDL ratio of ≥3 vs <3 had higher concentrations of small dense LDL (1279.5 ± 60.1 vs 841.8 ± 24.2 nmol/L, P < .001) and smaller LDL particle size (20.3 ± 0.1 vs 21.2 ± 0.1 nm, P < .001). In receiver operating characteristic analyses a TG/HDL cut-point of 3 best predicted LDL concentration in white youth, and 2.5 in black youth. Non-HDL cholesterol cut-point of 120 mg/dL and 145 mg/dL predicted LDL particle concentration in white and in black youth, respectively. TG/HDL ratio with body mass index or waist circumference explained 71% and 79% of the variance, respectively, in total small LDL. TG/HDL ratio and non-HDL cholesterol can identify overweight youth with atherogenic LDL particles. These easily obtained clinical lipid markers, in combination with body mass index and waist circumference, could be cost effective, in observational or interventional studies, for screening and follow-up of youth at heightened risk for atherogenic LDL. Copyright © 2012 Mosby, Inc. All rights reserved.

Comparison of effectiveness of rosuvastatin versus atorvastatin on the achievement of combined C-reactive protein (<2 mg/L) and low-density lipoprotein cholesterol (< 70 mg/dl) targets in patients with type 2 diabetes mellitus (from the ANDROMEDA study).

PubMed

Betteridge, D John; Gibson, J Martin; Sager, Philip T

2007-10-15

Decreasing C-reactive protein (CRP) in addition to decreasing low-density lipoprotein (LDL) cholesterol may further decrease coronary heart disease risk. The effects of rosuvastatin compared with atorvastatin in achieving a combined target of LDL cholesterol <70 mg/dl and CRP <2 mg/L in 509 patients with type 2 diabetes mellitus was evaluated. CRP decreased significantly versus baseline in both treatment groups. Significantly more patients treated with rosuvastatin achieved the combined end point of LDL cholesterol <70 mg/dl and CRP <2 mg/L compared with atorvastatin by the end of the study period (58% vs 37%; p <0.001 vs atorvastatin). In conclusion, CRP was effectively decreased in patients with type 2 diabetes receiving rosuvastatin or atorvastatin, whereas rosuvastatin decreased LDL cholesterol significantly more than atorvastatin.

Bergamot polyphenolic fraction enhances rosuvastatin-induced effect on LDL-cholesterol, LOX-1 expression and protein kinase B phosphorylation in patients with hyperlipidemia.

PubMed

Gliozzi, Micaela; Walker, Ross; Muscoli, Saverio; Vitale, Cristiana; Gratteri, Santo; Carresi, Cristina; Musolino, Vincenzo; Russo, Vanessa; Janda, Elzbieta; Ragusa, Salvatore; Aloe, Antonio; Palma, Ernesto; Muscoli, Carolina; Romeo, Franco; Mollace, Vincenzo

2013-12-10

Statins are the most commonly prescribed drugs to reduce cardiometabolic risk. Besides the well-known efficacy of such compounds in both preventing and treating cardiometabolic disorders, some patients experience statin-induced side effects. We hypothesize that the use of natural bergamot-derived polyphenols may allow patients undergoing statin treatment to reduce effective doses while achieving target lipid values. The aim of the present study is to investigate the occurrence of an enhanced effect of bergamot-derived polyphenolic fraction (BPF) on rosuvastatin-induced hypolipidemic and vasoprotective response in patients with mixed hyperlipidemia. A prospective, open-label, parallel group, placebo-controlled study on 77 patients with elevated serum LDL-C and triglycerides was designed. Patients were randomly assigned to a control group receiving placebo (n=15), two groups receiving orally administered rosuvastatin (10 and 20mg/daily for 30 days; n=16 for each group), a group receiving BPF alone orally (1000 mg/daily for 30 days; n=15) and a group receiving BPF (1000 mg/daily given orally) plus rosuvastatin (10mg/daily for 30 days; n=15). Both doses of rosuvastatin and BPF reduced total cholesterol, LDL-C, the LDL-C/HDL-C ratio and urinary mevalonate in hyperlipidemic patients, compared to control group. The cholesterol lowering effect was accompanied by reductions of malondialdehyde, oxyLDL receptor LOX-1 and phosphoPKB, which are all biomarkers of oxidative vascular damage, in peripheral polymorphonuclear cells. Addition of BPF to rosuvastatin significantly enhanced rosuvastatin-induced effect on serum lipemic profile compared to rosuvastatin alone. This lipid-lowering effect was associated with significant reductions of biomarkers used for detecting oxidative vascular damage, suggesting a multi-action enhanced potential for BPF in patients on statin therapy. © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

Effects of simvastatin and ezetimibe in lowering low-density lipoprotein cholesterol in subjects with type 1 and type 2 diabetes mellitus.

PubMed

Ciriacks, Kevin; Coly, Gerard; Krishnaswami, Shanthi; Patel, Shailendra B; Kidambi, Srividya

2015-03-01

Statins are used to lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels among patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). However, there are no studies of statin efficacy among T1DM patients. T1DM patients have higher gut cholesterol absorption than synthesis; hence cholesterol absorption inhibitors such as ezetimibe may also be effective in T1DM. Here, we compare the effects of simvastatin and ezetimibe among subjects with T1DM and T2DM. Subjects with T1DM (n=20, 45% female) or T2DM (n=27, 56% female) were assigned to alternating therapy with simvastatin (40 mg) or ezetimibe (10 mg) for 6 weeks in a crossover design. Among T2DM subjects, simvastatin lowered TC and LDL-C from the baseline (-25±4% and -40±5%, respectively, P<0.001), whereas ezetimibe was not as effective (-2±4% and -3±5%, respectively). Among T1DM subjects, both statin and ezetimibe showed significant decreases in TC and LDL-C from baseline, although ezetimibe lowered LDL-C much more than simvastatin (-32±12 (P<0.001) and -19±5% (P<0.01), respectively). Effect of simvastatin on LDL-C was much lower among T1DM subjects compared to T2DM subjects (P=0.02). This study shows that the cholesterol synthesis inhibitor simvastatin was less effective in lowering LDL-C in T1DM than T2DM subjects, whereas the cholesterol absorption inhibitor ezetimibe was at least as effective in lowering LDL-C as simvastatin among T1DM subjects.

Combined training (strength plus aerobic) potentiates a reduction in body fat but only functional training reduced low-density lipoprotein cholesterol in postmenopausal women with a similar training load.

PubMed

Rossi, Fabrício Eduardo; Fortaleza, Ana Claudia S; Neves, Lucas M; Diniz, Tiego A; de Castro, Marcela R; Buonani, Camila; Mota, Jorge; Freitas, Ismael F

2017-06-01

The aim of this study was to compare the effects of combined (CT; strength plus aerobic) and functional training (FT) on the body composition and metabolic profile with a similar training load in postmenopausal women. The participants were divided into three groups: CT (n=20), FT (n=17), and control group (CG, n=15). The trunk FM, fat mass (FM), percentage of FM (FM%), and fat-free mass were estimated by dual-energy X-ray absorptiometry. The metabolic profile, glucose, triacylglycerol, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-c) were assessed. There were main effects of time in trunk fat, FM, and FM% ( P <0.05). There were statistically significant interaction for FM ( P =0.015), FM% ( P =0.017) with lower values for CT group. For LDL-c, there was significant interaction ( P =0.002) with greater values for FT group in relation to CG and CT. Furthermore, when performed the post hoc test on the "mean absolute differences" (Δ), it can observed statistically significant difference between FT, CT, and CG (-13.0±16.5 mg/dL vs. 4.8±18.4 mg/dL vs. 9.2±18.8 mg/dL, P <0.05). In conclusion, when training loads are equivalent CT potentiated a reduction in FM and FM%, however, only FT reduced LDL-c in postmenopausal women.

The Comparison of Gemfibrozil and Lovastatin Therapy in Patients with High LDL and Low HDL Cholesterol Levels

DTIC Science & Technology

1990-08-01

cholesterol with same method as for TC; however, precision of the HDL measurements were (±SD) ±1.5 mg/dl. Triglycerides ( TG ) were...placebo lipid levels (TC and TG levels), lipoprotein cholesterol levels (LDL, VLDL, and HDL cholesterol levels), and the cholesterol ratios between... high density lipoprotein cholesterol in the serum and risk of mortality: evidence of a threshold effect. Br Med J. 1985; 290:1239-43. 7. Gordon

The importance of blood lipids in the association between BMI and blood pressure among Chinese overweight and obese children.

PubMed

Zou, Zhi-Yong; Yang, Yi-de; Wang, Shuo; Dong, Bin; Li, Xiao-Hui; Ma, Jun

2016-07-01

We aimed to examine the contribution of blood lipids to the association between BMI and blood pressure (BP) in children with overweight and obesity. Data were collected in elementary and high schools of Chaoyang District, Beijing, China in 2012. Participants' weight, height, BP and fasting plasma lipid profile were measured by standard protocols. Mediation analysis was used to examine the mediation role of blood lipids on the relation between BMI and BP, with age included as a covariate. We found that in boys 8·29 % (mediation effect=0·106, P=0·012) of the association between BMI and systolic BP was mediated through TAG. TAG mediated 12·53 % (mediation effect=0·093, P=0·018) and LDL-cholesterol mediated 7·75 % (mediation effect=0·57, P=0·046) of the association between BMI and diastolic BP was mediated by TAG and LDL-cholesterol, respectively. However, blood lipids did not show the mediation effect in girls. Our findings suggested that there was a sex difference in the contribution of blood lipids to the association between BMI and BP. Controlling TAG or LDL-cholesterol may be beneficial for reducing the risk of the BMI-related high BP in overweight boys; however, this outcome is not the case when controlling TAG or LDL-cholesterol in girls. This study may provide clues to explore the underlying mechanism of the association between obesity and hypertension.

Metabolomics reveals the sex-specific effects of the SORT1 low-density lipoprotein cholesterol locus in healthy young adults.

PubMed

Klein, Matthias S; Connors, Kimberly E; Shearer, Jane; Vogel, Hans J; Hittel, Dustin S

2014-11-07

Metabolite profiles of individuals possessing either the cardiovascular risk or protective variants of the low-density lipoprotein cholesterol (LDL-C) associated 1p13.3 locus of the SORT1 gene (rs646776) were analyzed. Serum metabolites and lipids were assessed using LC-MS-based metabolomics in a healthy young population (n = 138: 95 males, 43 females). Although no significant differences were observed in the combined cohort, divergent sex effects were identified. Females carrying the protective allele showed increased phosphatidylcholines, very long chain fatty acids (>C20), and unsaturated fatty acids. Unsaturated fatty acids are considered to be protective against cardiovascular disease. In contrast, males carrying the protective allele exhibited decreased long-chain fatty acids (≤C20) and sphingomyelins, which is similarly considered to decrease cardiovascular disease risk. No significant changes in clinically assessed lipids such as LDL-C, high-density lipoprotein (HDL-C), total cholesterol, or triglycerides were observed in females, whereas only LDL-C was significantly changed in males. This indicates that, apart from reducing LDL-C, other mechanisms may contribute to the protective effect of the SORT1 locus. Thus, the analysis of metabolic biomarkers might reveal early disease development that may be overlooked by relying on standard clinical parameters.

Effect of 8 Weeks Soccer Training on Health and Physical Performance in Untrained Women.

PubMed

Ortiz, Jaelson G; da Silva, Juliano F; Carminatti, Lorival J; Guglielmo, Luiz G A; Diefenthaeler, Fernando

2018-03-01

This study aims to analyze the physiological, neuromuscular, and biochemical responses in untrained women after eight weeks of regular participation in small-sided soccer games compared to aerobic training. Twenty-seven healthy untrained women were divided into two groups [soccer group (SG = 17) and running group (RG = 10)]. Both groups trained three times per week for eight weeks. The variables measured in this study were maximal oxygen uptake (VO 2 max), relative velocity at VO 2 max (vVO 2 max), peak velocity, relative intensity at lactate threshold (vLT), relative intensity at onset of blood lactate accumulation (vOBLA), peak force, total cholesterol, HDL, LDL, triglycerides, and cholesterol ratio (LDL/HDL). VO 2 max, vLT, and vOBLA increased significantly in both groups (12.8 and 16.7%, 11.1 and 15.3%, 11.6 and 19.8%, in SG and RG respectively). However, knee extensors peak isometric strength and triglyceride levels, total cholesterol, LDL, and HDL did not differ after eight weeks of training in both groups. On the other hand, the LDL/HDL ratio significantly reduced in both groups. In conclusion, eight weeks of regular participation in small-sided soccer games was sufficient to increase aerobic performance and promote health benefits related to similar aerobic training in untrained adult women.

Mipomersen sodium: a new option for the treatment of familial hypercholesterolemia.

PubMed

Haddley, K

2011-12-01

In collaboration with Genzyme, Isis Pharmaceuticals has developed mipomersen sodium (ISIS-310312), a synthetic second-generation 20-base phosphorothioate antisense oligonucleotide (ASO) that targets messenger RNA encoding apolipoprotein B-100 (Apo B-100). Elevated cholesterol levels, in particular low-density lipoprotein cholesterol (LDL-C) which contains a single apolipoprotein B (ApoB) molecule, have been directly correlated with the incidence of cardiovascular events. Preclinical investigations in transgenic mice have demonstrated that lowering LDL-C or ApoB can reduce aortic plaque formation associated with atherosclerosis. Mipomersen pharmacokinetics showed a wide and rapid tissue distribution and a slow prolonged elimination phase of several days in a range of species. Mipomersen displayed dose-dependent efficacy in lowering LDL-C, ApoB, triglycerides, total cholesterol and other low-density lipoproteins in healthy volunteers with mild hyperlipidemia. Similar decreases were observed in patients on stable lipid-lowering therapy for familial hypercholesterolemia with baseline LDL-C levels declining towards clinically desirable concentrations of 70 mg/dL. The efficacy of mipomersen in treating patients with severe heterozygous or homozygous familial hypercholesterolemia with cardiovascular complications has been recently assessed. There have been no serious adverse events noted with treatment and mipomersen can be administered in combination with other lipid-lowering therapies. One concern noted was an elevation in liver transaminase concentrations, although these increases were reversible.

Elevated levels of serum cholesterol are associated with better performance on tasks of episodic memory.

PubMed

Leritz, Elizabeth C; McGlinchey, Regina E; Salat, David H; Milberg, William P

2016-04-01

We examined how serum cholesterol, an established risk factor for cerebrovascular disease (CVD), relates to cognitive function in healthy middle-older aged individuals with no neurologic or CVD history. A complete lipid panel was obtained from a cohort of one hundred twenty individuals, ages 43-85, who also underwent a comprehensive neuropsychological examination. In order to reduce the number of variables and empirically identify broad cognitive domains, scores from neuropsychological tests were submitted into a factor analysis. This analysis revealed three explainable factors: Memory, Executive Function and Memory/Language. Three separate hierarchical multiple regression analyses were conducted using individual cholesterol metrics (total cholesterol, low density lipoprotein; LDL, high density lipoprotein; HDL, and triglycerides), as well as age, education, medication status (lipid lowering agents), ApoE status, and additional risk factors for CVD to predict neuropsychological function. The Memory Factor was predicted by a combination of age, LDL, and triglyceride levels; both age and triglycerides were negatively associated with factor score, while LDL levels revealed a positive relationship. Both the Executive and Memory/Language factor were only explained by education, whereby more years were associated with better performance. These results provide evidence that individual cholesterol lipoproteins and triglycerides may differentially impact cognitive function, over and above other common CVD risk factors and ApoE status. Our findings demonstrate the importance of consideration of vascular risk factors, such as cholesterol, in studies of cognitive aging.

Streptococcal serum opacity factor promotes cholesterol ester metabolism and bile acid secretion in vitro and in vivo.

PubMed

Gillard, Baiba K; Rodriguez, Perla J; Fields, David W; Raya, Joe L; Lagor, William R; Rosales, Corina; Courtney, Harry S; Gotto, Antonio M; Pownall, Henry J

2016-03-01

Plasma high density lipoprotein-cholesterol (HDL-C) concentrations negatively correlate with atherosclerotic cardiovascular disease. HDL is thought to have several atheroprotective functions, which are likely distinct from the epidemiological inverse relationship between HDL-C levels and risk. Specifically, strategies that reduce HDL-C while promoting reverse cholesterol transport (RCT) may have therapeutic value. The major product of the serum opacity factor (SOF) reaction versus HDL is a cholesteryl ester (CE)-rich microemulsion (CERM), which contains apo E and the CE of ~400,000 HDL particles. Huh7 hepatocytes take up CE faster when delivered as CERM than as HDL, in part via the LDL-receptor (LDLR). Here we compared the final RCT step, hepatic uptake and subsequent intracellular processing to cholesterol and bile salts for radiolabeled HDL-, CERM- and LDL-CE by Huh7 cells and in vivo in C57BL/6J mice. In Huh7 cells, uptake from LDL was greater than from CERM (2-4X) and HDL (5-10X). Halftimes for [(14)C]CE hydrolysis were 3.0±0.2, 4.4±0.6 and 5.4±0.7h respectively for HDL, CERM and LDL-CE. The fraction of sterols secreted as bile acids was ~50% by 8h for all three particles. HDL, CERM and LDL-CE metabolism in mice showed efficient plasma clearance of CERM-CE, liver uptake and metabolism, and secretion as bile acids into the gall bladder. This work supports the therapeutic potential of the SOF reaction, which diverts HDL-CE to the LDLR, thereby increasing hepatic CE uptake, and sterol disposal as bile acids. Copyright © 2015 Elsevier B.V. All rights reserved.

Association between lipid levels and major adverse cardiovascular events in rheumatoid arthritis compared to non-rheumatoid arthritis patients.

PubMed

Liao, Katherine P; Liu, Jun; Lu, Bing; Solomon, Daniel H; Kim, Seoyoung C

2015-05-01

Lower levels of low-density lipoprotein (LDL) cholesterol may be associated with increased cardiovascular (CV) risk in rheumatoid arthritis (RA). This study was undertaken to determine whether the complex relationship between levels of LDL and high-density lipoprotein (HDL) cholesterol and CV risk is different in RA patients as compared to non-RA controls. Using data from a US health insurance plan (2003-2012), we conducted a cohort study that included patients with RA and non-RA control subjects matched with regard to age, sex, and index date. The nonlinearity of associations between lipid levels and incidence of major adverse CV events (MACE) was tested. We used multivariable Cox proportional hazards regression models to examine for an interaction between lipid levels and RA status in relation to the risk of MACE, after adjustment for CV risk factors. In total, 16,085 RA patients and 48,499 non-RA controls were studied. The mean age was 52.6 years and 78.6% were women. The relationship between LDL cholesterol levels and incidence of MACE was nonlinear and similar between RA patients and non-RA controls (P for interaction = 0.72). No significant increase in CV risk was observed between the lowest quintile of LDL cholesterol levels (≤91.0 mg/dl) and the second, third, or fourth quintiles, whereas the highest quintile (>190.0 mg/dl) conveyed a 40% increase in risk of MACE (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.17-1.68). The relationship between HDL cholesterol levels and incidence of MACE was also nonlinear and similar between RA patients and non-RA controls (P for interaction = 0.39). Compared to the lowest quintile of HDL cholesterol levels, each successive quintile was associated with a reduced risk of MACE (HR 0.45, 95% CI 0.48-0.72 for lowest quintile [≤43.0 mg/dl] versus highest quintile [>71.0 mg/dl]). The complex relationship between LDL cholesterol levels, HDL cholesterol levels, and risk of MACE was nonlinear in RA patients and also not statistically significantly different from that in an age- and sex-matched non-RA cohort. © 2015, American College of Rheumatology.

Novel Approaches for the Treatment of Familial Hypercholesterolemia.

PubMed

Bonanni, L; Cutolo, A; Dalla Vestra, M

2016-11-01

Familial hypercholesterolemia (FH) is an autosomal disorder characterized by increased levels of total cholesterol and low density lipoprotein (LDL) cholesterol.The extent of underdiagnosis and undertreatment of individuals with FH is largely unknown.The LDL-lowering capacity of statins in combination with other lipid-lowering drugs is maximally around 50-60%. FH patients have a strongly elevated LDL-C and in most cases maximal current treatment is not sufficient to reach the desired LDL targets.Therefore, FH patients have a large residual cardiovascular risk despite the use of statins and there is a medical need for new additional drugs to further lower LDL-C in patients with FH to improve their prognosis.PCSK9 inhibitors have shown great efficacy in lowering lipids with very few side effects. No synergism between statins and PCSK9 inhibition was observed in many trials, allowing clinicians to select a statin dose before considering the initiation of PCSK9-inhibitor therapy.In patients with FH, who are at risk for markedly accelerated atherosclerosis and premature cardiovascular death, also treatment with lomitapide or mipomersen has the potential to reduce the risk of atherosclerotic cardiovascular disease and premature mortality.These new drugs will be probably reserved for the most severely affected FH patients and could help clinicians to reduce their residual cardiovascular risk. © Georg Thieme Verlag KG Stuttgart · New York.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez-Acebes, Sara; CIBER de Fisiopatologia de la Obesidad y Nutricion; Cueva, Paloma de la

We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5 {mu}M lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition ofmore » mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.« less

Lysosomes are involved in induction of steroidogenic acute regulatory protein (StAR) gene expression and progesterone synthesis through low-density lipoprotein in cultured bovine granulosa cells.

PubMed

Zhang, Jin-You; Wu, Yi; Zhao, Shuan; Liu, Zhen-Xing; Zeng, Shen-Ming; Zhang, Gui-Xue

2015-09-15

Progesterone is an important steroid hormone in the regulation of the bovine estrous cycle. The steroidogenic acute regulatory protein (StAR) is an indispensable component for transporting cholesterol to the inner mitochondrial membrane, which is one of the rate-limiting steps for progesterone synthesis. Low-density lipoprotein (LDL) supplies cholesterol precursors for progesterone formation, and the lysosomal degradation pathway of LDL is essential for progesterone biosynthesis in granulosa cells after ovulation. However, it is currently unknown how LDL and lysosomes coordinate the expression of the StAR gene and progesterone production in bovine granulosa cells. Here, we investigated the role of lysosomes in LDL-treated bovine granulosa cells. Our results reported that LDL induced expression of StAR messenger RNA and protein as well as expression of cholesterol side-chain cleavage cytochrome P-450 (CYP11A1) messenger RNA and progesterone production in cultured bovine granulosa cells. The number of lysosomes in the granulosa cells was also significantly increased by LDL; whereas the lysosomal inhibitor, chloroquine, strikingly abolished these LDL-induced effects. Our results indicate that LDL promotes StAR expression, synthesis of progesterone, and formation of lysosomes in bovine granulosa cells, and lysosomes participate in the process by releasing free cholesterol from hydrolyzed LDL. Copyright © 2015 Elsevier Inc. All rights reserved.

Cross-sectional study on the relationship between the Mediterranean Diet Score and blood lipids.

PubMed

Mertens, Evelien; Mullie, Patrick; Deforche, Benedicte; Lefevre, Johan; Charlier, Ruben; Huybrechts, Inge; Clarys, Peter

2014-09-04

Blood lipids are cardiovascular health indicators. High LDL cholesterol values and/or high total cholesterol (TC)/HDL cholesterol ratios are positively related with cardiovascular mortality. Evidence suggests that a Mediterranean diet can reduce the incidence of cardiovascular diseases. Adherence to the Mediterranean diet is often measured by the Mediterranean Diet Score (MDS). However, the association between the Mediterranean diet and blood lipid profiles seems still inconclusive. The aim of this study was to investigate the relationship between the MDS, its different components and blood lipid profiles. A sample of 506 women and 707 men (aged 18-75 years) was recruited. Three-day diet records were used to calculate the MDS. Blood samples were analyzed for serum TC, LDL and HDL cholesterol. ANOVA was used to analyze blood lipids across the MDS tertiles. A multivariate linear regression analysis was performed to investigate the associations between the MDS, its components and blood lipids, adjusted for several confounders. All analyses were stratified by gender. Few gender-specific associations were found between the MDS, its components and blood lipids. Only in men, the total MDS was negatively related with LDL cholesterol and the ratio TC/HDL cholesterol while positively with HDL cholesterol. In women, respectively two (MUFA/SFA and cereals) and in men three (fruits & nuts, meat and alcohol) of the nine MDS components were related with blood lipids. Analyses investigating the relationship between the MDS, its components and blood lipid profiles indicate only limited influence of the Mediterranean diet on blood lipids. More associations were detected in men compared to women.

21-Methylpyrenyl-cholesterol stably and specifically associates with lipoprotein peripheral hemi-membrane: A new labelling tool

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaibelet, Gérald; CEA, SB2SM and UMR8221 CNRS, IBiTec-Saclay, Gif-sur-Yvette; Tercé, François

Highlights: •21-Methylpyrenyl-cholesterol specifically and stably associates to lipoproteins. •It is not esterified by LCAT, and thus reliably labels their peripheral hemi-membrane. •HDL vs. LDL are well distinguishable by various fluorescent labelling characteristics. •LDL peripheral hemi-membrane harbors cholesterol-rich ordered lipid (micro)domains. •Cultured cells can be stained by such labelled lipoproteins-mediated delivery. -- Abstract: Lipoproteins are important biological components. However, they have few convenient fluorescent labelling probes currently reported, and their physiological reliability can be questioned. We compared the association of two fluorescent cholesterol derivatives, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), to serum lipoproteins and to purified HDL and LDL. Both lipoproteins couldmore » be stably labelled by Pyr-met-Chol, but virtually not by NBD-Chol. At variance with NBD-Chol, LCAT did not esterify Pyr-met-Chol. The labelling characteristics of lipoproteins by Pyr-met-Chol were well distinguishable between HDL and LDL, regarding dializability, associated probe amount and labelling kinetics. We took benefit of the pyrene labelling to approach the structural organization of LDL peripheral hemi-membrane, since Pyr-met-Chol-labelled LDL, but not HDL, presented a fluorescence emission of pyrene excimers, indicating that the probe was present in an ordered lipid micro-environment. Since the peripheral membrane of LDL contains more sphingomyelin (SM) than HDL, this excimer formation was consistent with the existence of cholesterol- and SM-enriched lipid microdomains in LDL, as already suggested in model membranes of similar composition and reminiscent to the well-described “lipid rafts” in bilayer membranes. Finally, we showed that Pyr-met-Chol could stain cultured PC-3 cells via lipoprotein-mediated delivery, with a staining pattern well different to that observed with NBD-Chol non-specifically delivered to the cells.« less

Association of lifestyle with serum lipid levels: a study of middle-aged Japanese men.

PubMed

Nakanishi, N; Tatara, K; Nakamura, K; Suzuki, K

2000-07-01

Cross-sectional associations between lifestyle and serum lipid levels were examined in 1591 Japanese male office workers aged 35 to 59 years in Osaka, Japan. From multiple linear regression analyses, significant correlates with low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and Log triglyceride levels and the ratio of LDL cholesterol to HDL cholesterol were, in the order of relative importance: BMI, alcohol intake (negative) and age for LDL cholesterol level; BMI (negative), cigarette smoking (negative), alcohol intake, consideration for nutritional balance, hours of brisk walking, hours of walking at an ordinary pace and physical exercise for HDL cholesterol level; BMI, cigarette smoking, consideration for nutritional balance (negative), hours of work (negative), alcohol intake and coffee drinking (negative) for Log triglyceride level; and BMI, alcohol intake (negative), cigarette smoking, consideration for nutritional balance (negative), age, hours of brisk walking (negative) and the frequency of snack intake between meals for the ratio of LDL cholesterol to HDL cholesterol. Our data suggest that obesity, cigarette smoking and snack intake between meals are atherogenic whereas alcohol consumption, consideration for nutritional balance and walking long hours, especially at a brisk pace, are anti-atherogenic in middle-aged Japanese men.

Utilization of lipid-modifying therapy and low-density lipoprotein cholesterol goal attainment in patients at high and very-high cardiovascular risk: Real-world evidence from Germany.

PubMed

März, Winfried; Dippel, Franz-Werner; Theobald, Karlheinz; Gorcyca, Katherine; Iorga, Şerban R; Ansell, David

2018-01-01

Elevated low-density lipoprotein cholesterol (LDL-C) is a causal risk factor for cardiovascular (CV) events. European guidelines recommend reducing LDL-C as the primary lipid target to reduce CV risk, using lifestyle modifications and lipid-lowering therapy (LLT). Many European patients do not achieve guideline-recommended LDL-C levels. The present database analysis aimed to assess LLT treatment patterns and LDL-C threshold attainment in Germany in a large, real-world cohort of patients. Patients from the Cegedim Longitudinal Practice Database in Germany who met selection criteria were included: (a) LDL-C measurement in 2013; (b) ≥20 years of age; (c) high or very-high CV risk conditions: recent acute coronary syndrome (ACS), other coronary heart disease (CHD), ischemic stroke, peripheral arterial disease (PAD) (atherosclerotic cardiovascular disease [ASCVD]) or diabetes mellitus (DM) (non-ASCVD). LDL-C threshold attainment was assessed based on LDL-C targets from 2011 European guidelines. 42,767 patients met the inclusion criteria; 35% received current statin treatment, and 30% achieved guideline-recommended LDL-C targets. Attainment of LDL-C goals among ASCVD hierarchical categories was 46.7% for recent ACS, 35.8% for ischemic stroke, 34.9% for other CHD, and 26.9% for PAD. Among patients in the non-ASCVD group with DM, 23.6% achieved LDL-C goals. Similar results were observed when patients were grouped by prevalence (patients assigned to every risk group for which they qualified). In this high/very-high CV risk population in Germany, statin utilization was low; suggesting that LLTs are not prescribed as per European guidelines. These results highlight the need to increase LLT use among high-risk patients. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of intensive atorvastatin and rosuvastatin treatment on apolipoprotein B-48 and remnant lipoprotein cholesterol levels

USDA-ARS?s Scientific Manuscript database

Atorvastatin and rosuvastatin at maximal doses are both highly effective in lowering low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels. Rosuvastatin has been shown to be more effective than atorvastatin in lowering LDL-C, small dense LDL-C and in raising high-density lipoprote...

Lipoprotein degradation and cholesterol esterification in primary cell cultures of rabbit atherosclerotic lesions.

PubMed Central

Jaakkola, O.; Nikkari, T.

1990-01-01

Lipoprotein metabolism and cholesterol accumulation in atherosclerotic lesions was studied using enzymatically isolated primary cell cultures from aortas of rabbits made atherosclerotic by cholesterol feeding. The cultures consisted of macrophages and smooth muscle cells, thus resembling, in composition, fatty streak lesions. The mean (+/- SD) cholesteryl ester content of the dispersed cells was 1059 +/- 445 micrograms/mg cell protein, but it declined steeply during 1 week in primary culture. The uptake of low-density lipoprotein (LDL), beta-migrating very low-density lipoprotein (beta-VLDL), and acetylated LDL (acetyl-LDL), labeled with 125I or with the fluorescent probe 1,1'-dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine (DiI), was studied in 2-day-old primary cultures. DiI-acetyl-LDL was avidly taken up by the macrophages and, to a lesser extent, by some smooth muscle cells. The uptake of DiI-beta-VLDL by the macrophages was weaker and less homogeneous than that of DiI-acetyl-LDL. The degradation rates of 125I-labeled beta-VLDL, LDL and acetyl-LDL were 135 +/- 54, 195 +/- 20, and 697 +/- 14 ng/mg cell protein/8 hours, respectively. Incubation with unlabeled acetyl-LDL enhanced the incorporation of [3H]oleate into cholesteryl esters and increased the cellular cholesteryl ester content. These results suggest that arterial macrophages and, to some extent, smooth muscle cells from cholesterol-fed rabbits actively metabolize acetyl-LDL and are thus capable of accumulating cholesteryl esters by uptake of modified forms of LDL. Images Figure 2 PMID:2201201

Combined Effects of Rosuvastatin and Exercise on Gene Expression of Key Molecules Involved in Cholesterol Metabolism in Ovariectomized Rats

PubMed Central

Ngo Sock, Emilienne Tudor; Mayer, Gaétan; Lavoie, Jean-Marc

2016-01-01

The purpose of this study was to investigate the effects of three weeks of rosuvastatin (Ros) treatment alone and in combination with voluntary training (Tr) on expression of genes involved in cholesterol metabolism (LDLR, PCSK9, LRP-1, SREBP-2, IDOL, ACAT-2 and HMGCR) in the liver of eight week-old ovariectomized (Ovx) rats. Sprague Dawley rats were Ovx or sham-operated (Sham) and kept sedentary for 8 weeks under a standard diet. Thereafter, rats were transferred for three weeks in running wheel cages for Tr or kept sedentary (Sed) with or without Ros treatment (5mg/kg/day). Six groups were formed: Sham-Sed treated with saline (Sal) or Ros (Sham-Sed-Sal; Sham-Sed-Ros), Ovx-Sed treated with Sal or Ros (Ovx-Sed-Sal; Ovx-Sed-Ros), Ovx trained treated with Sal or Ros (Ovx-Tr-Sal; Ovx-Tr-Ros). Ovx-Sed-Sal rats depicted higher (P < 0.05) body weight, plasma total cholesterol (TC) and LDL-C, and liver TC content compared to Sham-Sed-Sal rats. In contrast, mRNA levels of liver PCSK9, LDLR, LRP-1 as well as plasma PCSK9 concentrations and protein levels of LRP-1 were reduced (P < 0.01) in Ovx-Sed-Sal compared to Sham-Sed-Sal rats. However, protein levels of LDLR increased (P < 0.05) in Ovx-Sed-Sal compared to Sham-Sed-Sal rats. Treatment of Ovx rats with Ros increased (P < 0.05) mRNA and protein levels of LRP-1 and PCSK9 but not mRNA levels of LDLR, while its protein abundance was reduced at the level of Sham rats. As a result, plasma LDL-C was not reduced. Exercise alone did not affect the expression of any of these markers in Ovx rats. Overall, Ros treatment corrected Ovx-induced decrease in gene expression of markers of cholesterol metabolism in liver of Ovx rats, but without reducing plasma LDL-C concentrations. Increased plasma PCSK9 levels could be responsible for the reduction of liver LDLR protein abundance and the absence of reduction of plasma LDL-C after Ros treatment. PMID:27442011

Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels

USDA-ARS?s Scientific Manuscript database

Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipo...

Nutraceuticals in the management of patients with statin-associated muscle symptoms, with a note on real-world experience.

PubMed

Ward, Natalie C; Pang, Jing; Ryan, Jacqueline D M; Watts, Gerald F

2018-01-01

There is considerable evidence for the role of low-density lipoprotein cholesterol (LDL-C) in the development of atherosclerotic cardiovascular disease. Although statin therapy remains the most frequency prescribed medication to reduce LDL-C and lower risk of cardiovascular disease, a considerable number of patients develop muscle-related side affects. This review summarizes recent literature supporting the role of nutraceuticals as LDL-C-lowering therapy in statin-intolerant patients, with evidence from our own clinical practices. © 2018 Wiley Periodicals, Inc.

Prevention of oxLDL uptake leads to decreased atherosclerosis in hematopoietic NPC1-deficient Ldlr-/- mice.

PubMed

Jeurissen, Mike L J; Walenbergh, Sofie M A; Houben, Tom; Gijbels, Marion J J; Li, Jieyi; Hendrikx, Tim; Oligschlaeger, Yvonne; van Gorp, Patrick J; Binder, Christoph J; Donners, Marjo M P C; Shiri-Sverdlov, Ronit

2016-12-01

Atherosclerosis is a chronic inflammatory disease of medium and large vessels and is typically characterized by the predominant accumulation of low-density lipoprotein (LDL)-cholesterol inside macrophages that reside in the vessel walls. Previous studies clearly demonstrated an association specifically between the oxidized type of LDL (oxLDL) and atherosclerotic lesion formation. Further observations revealed that these atherosclerotic lesions displayed enlarged, lipid-loaded lysosomes. By increasing natural antibodies against oxLDL, pneumococcal vaccination has been shown to reduce atherosclerosis in LDL receptor knockout (Ldlr -/- ) mice. Relevantly, loss of the lysosomal membrane protein Niemann-Pick Type C1 (NPC1) led to lysosomal accumulation of various lipids and promoted atherosclerosis. Yet, the importance of lysosomal oxLDL accumulation inside macrophages, compared to non-modified LDL, in atherosclerosis has never been established. By transplanting NPC1 bone marrow into lethally irradiated Ldlr -/- mice, a hematopoietic mouse model for lysosomal cholesterol accumulation was created. Through injections with heat-inactivated pneumococci, we aimed to demonstrate the specific contribution of lysosomal oxLDL accumulation inside macrophages in atherosclerosis development. While there were no differences in plaque morphology, a reduction in plaque size and plaque inflammation was found in immunized NPC1 mut -transplanted mice, compared to non-immunized NPC1 mut -transplanted mice. Lysosomal oxLDL accumulation within macrophages contributes to murine atherosclerosis. Future intervention strategies should focus specifically on preventing oxLDL, unlike non-modified LDL, from being internalized into lysosomes. Such an intervention can have an additive effect to current existing treatments against atherosclerosis. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

[Lipid control in secondary prevention: multicenter observational study in primary care].

PubMed

Brotons, C; Maiques, A; Mostaza, J; Pintó, X; Vilaseca, J

2004-06-30

To assess the implementation of pharmacological and non-pharmacological treatment in coronary patients followed in primary care. Observational prospective study of 6 months of follow-up. Primary care centers all over Spain. Men and women, between 18 and 75 years old, diagnosed in the last 3 years of myocardial infarction, stable angina, and unstable angina, with cholesterol levels higher than the lipid therapeutical goal recommended by the Guía de Prevención Cardiovascular del Programa de Actividades y de Promoción de la Salud de la Sociedad Española de Medicina de Familia y Comunitaria. Patients were recruited between february of 1998 and july of 1999, and were followed for 6 months. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, weight, height, body mass index, systolic and diastolic blood pressure (SBP and DBP). 4464 patients were included, mean age of 59 years (range, 20-96), 60% men. At 6 months, 66% of the patients had a cholesterol level higher than 200 mg/dL, 55% had LDL-C higher than 130 mg/dL, and 11% had triglycerides higher than 190 mg/dL. At 6 months a reduction of 70 mg/dL of total cholesterol, of 52 mg/dL of triglycerides, and of 51 mg/dL of LDL-C, and an increase of 4 mg/dL of HDL-Cholesterol was observed. Also, SBP and DBP were reduced 5 mm Hg and 3 mm Hg. Although a clear improved was observed in the control of lipids and other risk factors, there is still a considerable potential to raise standards in secondary prevention of coronary patients followed in primary care concerning control of cardiovascular risk factors, particularly total cholesterol and lipid fractions.

A dietary portfolio approach to cholesterol reduction: combined effects of plant sterols, vegetable proteins, and viscous fibers in hypercholesterolemia.

PubMed

Jenkins, David J A; Kendall, Cyril W C; Faulkner, Dorothea; Vidgen, Edward; Trautwein, Elke A; Parker, Tina L; Marchie, Augustine; Koumbridis, George; Lapsley, Karen G; Josse, Robert G; Leiter, Lawrence A; Connelly, Philip W

2002-12-01

Plant sterols, soy proteins, and viscous fibers are advised for cholesterol reduction but their combined effect has never been tested. We therefore assessed their combined effect on blood lipids in hyperlipidemic subjects who were already consuming a low-saturated fat, low-cholesterol diet before starting the study. The test (combination) diet was 1 month in duration and was very low in saturated fat and high in plant sterols (1 g/1,000 kcal), soy protein (23 g/1,000 kcal), and viscous fibers (9 g/1,000 kcal) obtained from foods available in supermarkets and health food stores. One subject also completed 2 further diet periods: a low-fat control diet and a control diet plus 20 mg/d lovastatin. Fasting blood lipids, blood pressure, and body weight were measured prior to and at weekly intervals during the study. The combination diet was rated as acceptable and very filling. The diet reduced low-density lipoprotein (LDL)-cholesterol by 29.0% +/- 2.7% (P <.001) and the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol by 26.5% +/- 3.4% (P <.001). Near maximal reductions were seen by week 2. In the subject who took Mevacor and control diets each for 4 weeks, the reduction in LDL:HDL-cholesterol on Mevacor was similar to the combination diet. We conclude that acceptable diets of foods from supermarkets and health food stores that contain recognized cholesterol-lowering dietary components in combination (a dietary portfolio) may be as effective as the starting dose of older first-line drugs in managing hypercholesterolemia. Copyright 2002, Elsevier Science (USA). All rights reserved.

Usefulness of non-fasting lipid parameters in children.

PubMed

Kubo, Toshihide; Takahashi, Kyohei; Furujo, Mahoko; Hyodo, Yuki; Tsuchiya, Hiroki; Hattori, Mariko; Fujinaga, Shoko; Urayama, Kenji

2017-01-01

This study assessed whether non-fasting lipid markers could be substituted for fasting markers in screening for dyslipidemia, whether direct measurement of non-fasting low-density lipoprotein cholesterol [LDL-C (D)] could be substituted for the calculation of fasting LDL-C [LDL-C (F)], and the utility of measuring non-high-density lipoprotein cholesterol (non-HDL-C). In 33 children, the lipid profile was measured in the non-fasting and fasting states within 24 h. Correlations were examined between non-fasting LDL-C (D) or non-HDL-C levels and fasting LDL-C (F) levels. Non-fasting triglyceride (TG), total cholesterol (TC), HDL-C, LDL-C (D), and non-HDL-C levels were all significantly higher than the fasting levels, but the mean difference was within 10% (except for TG). Non-fasting LDL-C (D) and non-HDL-C levels were strongly correlated with the fasting LDL-C (F) levels. In conclusion, except for TG, non-fasting lipid parameters are useful when screening children for dyslipidemia. Direct measurement of non-fasting LDL-C and calculation of non-fasting non-HDL-C could replace the calculation of fasting LDL-C because of convenience.

Eating Patterns and Health Outcomes in Patients With Type 2 Diabetes.

PubMed

Aguiar Sarmento, Roberta; Peçanha Antonio, Juliana; Lamas de Miranda, Ingrid; Bellicanta Nicoletto, Bruna; Carnevale de Almeida, Jussara

2018-01-01

To evaluate the relationship between eating patterns and therapeutic target's achieving in patients with type 2 diabetes. In this cross-sectional study, patients underwent clinical, laboratory, and nutritional evaluations. Dietary intake was assessed by a quantitative food frequency questionnaire and eating patterns identified by cluster analysis. The therapeutic targets were as follows: blood pressure, <140/90 mm Hg; BMI, <25 kg/m 2 (<27 kg/m 2 for elderly); waist circumference, <94 cm for men and <80 cm for women; fasting plasma glucose, <130 mg/dL; HbA1c, <7%; triglycerides, <150 mg/dL; HDL-cholesterol, >40 mg/dL for men and >50 mg/dL for women; LDL-cholesterol, <100 mg/dL. One hundred ninety seven patients were studied. We identified two eating patterns: "unhealthy" (n = 100)-high consumption of refined carbohydrates, ultra-processed foods, sweets and desserts ( P < 0.05); and "healthy" (n = 97)-high intake of whole carbohydrates, dairy, white meat, fish, fruits and vegetables ( P < 0.05). The healthy group more frequently achieved therapeutic targets for fasting plasma glucose, HbA1c, and LDL-cholesterol than the unhealthy group. Poisson regression confirmed the association of healthy eating pattern with attaining the therapeutic target for fasting plasma glucose [PR, 1.59 (95% CI, 1.01 to 2.34); P = 0.018], HbA1c [PR, 2.09 (95% CI, 1.17 to 3.74); P = 0.013], and LDL-cholesterol [PR, 1.37 (95% CI, 1.01 to 1.86); P = 0.042]. A healthy eating pattern, including the frequent intake of whole carbohydrates, dairy, white meat, fish, fruits, and vegetables, is associated with reduced fasting plasma glucose, HbA1c, and LDL cholesterol levels in patients with type 2 diabetes.

Low dose chromium-polynicotinate or policosanol is effective in hypercholesterolemic children only in combination with glucomannan.

PubMed

Martino, Francesco; Puddu, Paolo Emilio; Pannarale, Giuseppe; Colantoni, Chiara; Martino, Eliana; Niglio, Tarcisio; Zanoni, Cristina; Barillà, Francesco

2013-05-01

A low-fat, fiber-rich diet is the first step in the management for hypercholesterolemic children. Glucomannan (GM) is a natural fiber that has been demonstrated to lower total and LDL-cholesterol. The use of high-dose chromium-polynicotinate (CP) and policosanol (PC) has also shown cholesterol-lowering benefits. We aimed at investigating the effects of low-dose CP or PC and their GM combination in hypercholesterolemic children. A double-blind trial was conducted in 120 children (60 M, 60 F, 9 ± 4 years, median 9.6 years, range: 3-16 years) randomly assigned to 5 neutraceutical and 1 placebo (only resistant starch) 8-week treatment groups. Fasting blood glucose (FBG), total cholesterol (CholT), triglycerides (TG), HDL and LDL cholesterol were considered. GM combination of low-dose CP or PC reduced CholT and LDL without changing HDL, TG and FBG. The highest post-treatment changes were seen after GM combination with CP (CholT 85 ± 3% and LDL 85 ± 5%, of pretreatment) which was significantly (p < 0.01) less than with low-dose CP or PC and starch. When GM was associated with starch, there was no lipid lowering effect, which was an unexpected finding as compared to previous data with GM and no starch. No adverse effects were reported. This is the first report to show the cholesterol-lowering efficacy of GM combined treatment with low-dose CP or PC. Further studies are needed to investigate the best combinations and doses of nutraceutics to be added to the standard GM treatment. The potential negative association of GM and nutraceutics with starch is clearly shown. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia.

PubMed

Akdim, Fatima; Visser, Maartje E; Tribble, Diane L; Baker, Brenda F; Stroes, Erik S G; Yu, Rosie; Flaim, Joann D; Su, John; Stein, Evan A; Kastelein, John J P

2010-05-15

A randomized, double-blind, placebo-controlled, dose-escalation study was conducted to examine the efficacy and safety of mipomersen (ISIS 301012), an antisense inhibitor of apolipoprotein B, when added to conventional lipid-lowering therapy for patients with heterozygous familial hypercholesterolemia. A total of 44 patients were enrolled and were separated into 4 cohorts, with doses ranging from 50 to 300 mg (4:1 active treatment/placebo ratio). Patients received 8 doses subcutaneously during a 6-week treatment period. Patients assigned to the 300-mg dose continued for an additional 7 weeks with once-per-week dosing. The primary efficacy end point was the percentage of change from baseline to week 7 in low-density lipoprotein (LDL) cholesterol. Safety was assessed using the laboratory test results and according to the incidence, severity, and relation of adverse events to drug dose. Mipomersen produced significant reductions in LDL cholesterol and other atherogenic apolipoprotein B-containing lipoproteins. After 6 weeks of treatment, the LDL cholesterol level was reduced by 21% from baseline in the 200-mg/week dose group (p <0.05) and 34% from baseline in the 300-mg/week dose group (p <0.01), with a concomitant reduction in apolipoprotein B of 23% (p <0.05) and 33% (p <0.01), respectively. Injection site reactions were the most common adverse event. Elevations in liver transaminase levels (> or =3 times the upper limit of normal) occurred in 4 (11%) of 36 patients assigned to active treatment; 3 of these patients were in the highest dose group. In conclusion, mipomersen has an incremental LDL cholesterol lowering effect when added to conventional lipid-lowering therapy. Copyright 2010 Elsevier Inc. All rights reserved.

Effects of ezetimibe added to statin therapy on markers of cholesterol absorption and synthesis and LDL-C lowering in hyperlipidemic patients

PubMed Central

Thongtang, Nuntakorn; Lin, Jianxin; Schaefer, Ernst J.; Lowe, Robert S.; Tomassini, Joanne E.; Shah, Arvind K.; Tershakovec, Andrew M.

2013-01-01

Objective Statins inhibit cholesterol synthesis but can upregulate cholesterol absorption, with higher doses producing larger effects. Ezetimibe inhibits cholesterol absorption but also upregulates synthesis. We tested whether ezetimibe added to ongoing statin therapy would be most effective in lowering LDL-cholesterol (LDL-C) in subjects on high-potency statins and whether these effects would be related to alterations in cholesterol absorption (β-sitosterol) and synthesis (lathosterol) markers. Methods Hypercholesterolemic subjects (n=874) on statins received ezetimibe 10 mg/day. Plasma lipids, lathosterol, and β-sitosterol were measured at baseline and on treatment. Subjects were divided into low- (n=133), medium- (n=582), and high- (n=159) statin potency groups defined by predicted LDL-C–lowering effects of each ongoing statin type and dose (reductions of ~20-30%, ~31-45%, or ~46-55%, respectively). Results The high-potency group had significantly lower baseline lathosterol (1.93 vs. 2.58 vs. 3.17 μmol/l; p <0.001) and higher baseline β-sitosterol values (6.21 vs. 4.58 vs. 4.51 μmol/l, p <0.001) than medium-/low-potency groups. Ezetimibe treatment in the high-potency group produced significantly greater reductions from baseline in LDL-C than medium-/low-potency groups (−29.1% vs. −25.0% vs. −22.7%; p <0.001) when evaluating unadjusted data. These effects and group differences were significantly (p <0.05) related to greater β-sitosterol reductions and smaller lathosterol increases. However, LDL-C reduction differences between groups were no longer significant after controlling for placebo effects, due mainly to modest LDL-C lowering by placebo in the high-potency group. Conclusion Patients on high-potency statins have the lowest levels of cholesterol synthesis markers and the highest levels of cholesterol absorption markers at baseline, and the greatest reduction in absorption markers and the smallest increases in synthesis markers with ezetimibe addition. Therefore, such patients may be good candidates for ezetimibe therapy if additional LDL-C lowering is needed. PMID:23040830

Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease.

PubMed

Gylling, Helena; Plat, Jogchum; Turley, Stephen; Ginsberg, Henry N; Ellegård, Lars; Jessup, Wendy; Jones, Peter J; Lütjohann, Dieter; Maerz, Winfried; Masana, Luis; Silbernagel, Günther; Staels, Bart; Borén, Jan; Catapano, Alberico L; De Backer, Guy; Deanfield, John; Descamps, Olivier S; Kovanen, Petri T; Riccardi, Gabriele; Tokgözoglu, Lale; Chapman, M John

2014-02-01

This EAS Consensus Panel critically appraised evidence relevant to the benefit to risk relationship of functional foods with added plant sterols and/or plant stanols, as components of a healthy lifestyle, to reduce plasma low-density lipoprotein-cholesterol (LDL-C) levels, and thereby lower cardiovascular risk. Plant sterols/stanols (when taken at 2 g/day) cause significant inhibition of cholesterol absorption and lower LDL-C levels by between 8 and 10%. The relative proportions of cholesterol versus sterol/stanol levels are similar in both plasma and tissue, with levels of sterols/stanols being 500-/10,000-fold lower than those of cholesterol, suggesting they are handled similarly to cholesterol in most cells. Despite possible atherogenicity of marked elevations in circulating levels of plant sterols/stanols, protective effects have been observed in some animal models of atherosclerosis. Higher plasma levels of plant sterols/stanols associated with intakes of 2 g/day in man have not been linked to adverse effects on health in long-term human studies. Importantly, at this dose, plant sterol/stanol-mediated LDL-C lowering is additive to that of statins in dyslipidaemic subjects, equivalent to doubling the dose of statin. The reported 6-9% lowering of plasma triglyceride by 2 g/day in hypertriglyceridaemic patients warrants further evaluation. Based on LDL-C lowering and the absence of adverse signals, this EAS Consensus Panel concludes that functional foods with plant sterols/stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant, 3) and in adults and children (>6 years) with familial hypercholesterolaemia, in line with current guidance. However, it must be acknowledged that there are no randomised, controlled clinical trial data with hard end-points to establish clinical benefit from the use of plant sterols or plant stanols. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Differences in hypolipidaemic effects of two statins on Hep G2 cells or human hepatocytes in primary culture.

PubMed Central

Clerc, T.; Sbarra, V.; Domingo, N.; Rault, J. P.; Diaconescu, N.; Moutardier, V.; Hasselot, N.; Lafont, H.; Jadot, G.; Laruelle, C.; Chanussot, F.

1996-01-01

1. The objective of this study was to compare in cultured human hepatocytes or Hep G2 cells, changes in the fate of unesterified low density lipoprotein (LDL)-cholesterol induced by crilvastatin, a new cholesterol lowering drug and a reference statin, simvastatin. 2. The experiments were carried out for 20 h, each well contained 4.2 x 10(5)/cm2 Hep G2 cells or 0.5 x 10(5)/Cm2 human hepatocytes, 130 microM ursodeoxycholate, 0.68 microCi or 1.59 microCi unesterified human [14C]-LDL-cholesterol, crilvastatin or simvastatin at 0 or 50 microM (both cell types) or 300 microM (Hep-G2 cells). Incubation with the two drugs resulted in increased amounts of unesterified [14C]-LDL-cholesterol taken by the two cell types, compared to control. 3. Crilvastatin 50 microM led to significantly higher quantities of [14C]-glyco-tauro-conjugated bile salts, compared to simvastatin. Statins reduced the apo B100 level secreted by the two cell types (simvastatin) or human hepatocytes (crilvastatin). Crilvastatin enhanced both the level of apo A1 secreted by the Hep G2 cells and the level of APF, a high density lipoprotein (HDL) and biliary apoprotein. 4. Crilvastatin not only acts by stimulating LDL-cholesterol uptake by hepatocytes, but also by enhancing the catabolism of LDL-cholesterol in bile salts and probably by stimulating HDL and/or bile component secretion. Such a mechanism was not previously described for HMG CoA reductase inhibitors. Our results on APF show that this apoprotein could be considered also as an indicator of changes in bile and/or HDL compartments. 5. The human hepatocyte model appeared to be a suitable and relevant model in the pharmacological-metabolic experiments carried out in this study. It led to more consistent data than those obtained with Hep G2 cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8842455

The comparison of the effects of standard 20 mg atorvastatin daily and 20 mg atorvastatin every other day on serum LDL-cholesterol and high sensitive C-reactive protein levels.

PubMed

Keleş, Telat; Akar Bayram, Nihal; Kayhan, Tuğba; Canbay, Alper; Sahin, Deniz; Durmaz, Tahir; Ozdemir, Ozcan; Aydoğdu, Sinan; Diker, Erdem

2008-12-01

In this study, we aimed at comparing the effects of standard once daily 20 mg atorvastatin treatment with that of atorvastatin 20 mg administered every other day on serum lipids and high sensitive C-reactive protein (hs-CRP) levels. Sixty-one patients with serum total cholesterol levels of above 200 mg/dl and low density lipoprotein (LDL)--cholesterol levels of above 130 mg/dl were included in this prospective, randomized study. The patients were randomized into daily treatment of 20 mg atorvastatin (standard treatment) and 20 mg atorvastatin every other day (every other day treatment) groups. Before the treatment and at each visit, serum lipids and hs-CRP levels of all the patients were measured. Statistical analyses were performed Chi-square, unpaired t and two-way repeated measurements ANOVA tests. In the every other day treatment group, there was a 36.1% reduction in LDL-cholesterol levels by the end of first month (p<0.01). At the end of three months there was further decrease of 10.2% in LDL-cholesterol levels when compared to 1 month levels (p>0.05). The LDL cholesterol levels of the group receiving 20 mg atorvastatin every day was reduced by %41 by the end of 1 month (p<0.01). At the end of three months, the difference between the changes in the all lipid parameters of the two groups was not found to be of statistical significance. In the group receiving the medication every other day, there was a 21% decrease in hs-CRP levels compared to the basal measurements at the end of first month (p<0.05). In the group, receiving the medication every day the decrease in hs-CRP levels at the end of one month was more striking (37%, p<0.05). However, the effects of both treatment arms on hs-CRP levels, did not differ significantly (p>0.05). Alternate-day dosing of atorvastatin causes a significant lipid-lowering and antiinflammatory effects similar to that of daily administration and yet may provide some cost savings.

Nonlinear Associations between Plasma Cholesterol Levels and Neuropsychological Function

PubMed Central

Wendell, Carrington R.; Zonderman, Alan B.; Katzel, Leslie I.; Rosenberger, William F.; Plamadeala, Victoria V.; Hosey, Megan M.; Waldstein, Shari R.

2016-01-01

Objective Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Method Participants were 190 older adults (53% men, ages 54–83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed/dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as <70 vs. 70+) as an effect modifier. Results A significant quadratic effect of total cholesterol2 × age was identified for Logical Memory II (b=−.0013, p=.039), such that the 70+ group performed best at high and low levels of total cholesterol than at mid-range total cholesterol (U-shaped), and the <70 group performed worse at high and low levels of total cholesterol than at mid-range total cholesterol (inverted U-shape). Similarly, significant U- and J-shaped effects of LDL cholesterol2 × age were identified for Visual Reproduction II (b=−.0020, p=.026) and log of Trails B (b=.0001, p=.044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Conclusions Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. PMID:27280580

Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols.

PubMed

Maki, K C; Geohas, J G; Dicklin, M R; Huebner, M; Udani, J K

2015-08-01

This randomized, double-blind, placebo-controlled multi-center trial investigated the lipid-altering effects of a medical food (PDL-0101) providing 1.8 g/d eicosapentaenoic acid; 12 mg/d astaxanthin, a marine algae-derived carotenoid; and 100 mg/d tocopherol-free gamma/delta tocotrienols enriched with geranylgeraniol, extracted from annatto, on triacylglycerols (TAG), other lipoprotein lipids, and oxidized low-density lipoprotein (LDL) in 102 subjects with TAG 150-499 mg/dL (1.69-5.63 mmol/L) and LDL cholesterol (LDL-C) ≥70 mg/dL (1.81 mmol/L). Compared to placebo, after eight weeks of treatment, PDL-0101 significantly reduced median TAG (-9.5% vs. 10.6%, p<0.001), while not significantly altering mean LDL-C (-3.0% vs. -8.0% for PDL-0101 and placebo, respectively, p=0.071), mean high-density lipoprotein cholesterol (~3% decrease in both groups, p=0.732), or median oxidized LDL concentrations (5% vs. -5% for PDL-0101 and placebo, respectively, p=0.112). These results demonstrate that PDL-0101 is an effective medical food for the management of elevated TAG. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association of blood polychlorinated biphenyls and cholesterol levels among Canadian Inuit.

PubMed

Singh, Kavita; Chan, Hing Man

2018-01-01

It has generally been thought that Inuit populations have low risk of cardiovascular disease due to high consumption of omega-3 fatty acids found in traditional marine-based diets. However, results of recent surveys showed that Inuit populations are experiencing increasing rates of cardiovascular disease and related risk factors. The purpose of this study was to investigate if blood polychlorinated biphenyls (PCBs) are associated with high cholesterol and related parameters in Canadian Inuit, known risk factors for cardiovascular disease. The Adult Inuit Health Survey (IHS, 2007-2008) included 2595 Inuit participants from three regions of the Canadian Arctic, of which 2191 could be classified as with or without high cholesterol. The high cholesterol outcome was defined by LDL-C > 3.36mmol/L or taking medication(s) that reduce cholesterol, and was examined in adjusted logistic regression models with individual blood levels of PCB congeners, sum of dioxin-like PCBs (∑DL-PCBs), or sum of non-dioxin-like PCBs (∑NDL-PCBs). Statistically significant covariates for high cholesterol were ranked in importance according to the proportion of the model log likelihood explained. Continuous clinical parameters of total cholesterol, triglycerides, LDL-C, and HDL-C were examined in multiple linear regression models with ∑DL-PCBs or ∑NDL-PCBs. A total of 719 participants had high cholesterol (32.8%). PCBs were associated with increased risk of high cholesterol, and higher levels of serum triglycerides, total cholesterol, and LDL-C. No association was observed between PCBs and serum HDL-C. With respect to other statistically significant covariates for high cholesterol, the log likelihood ranking of PCBs generally fell between body mass index (BMI) and age. Further work is needed to corroborate the associations observed with PCBs and lipids in Canadian Inuit and to examine if they are causal in the direction anticipated. Copyright © 2017 Elsevier Inc. All rights reserved.

CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL.

PubMed

Bartuzi, Paulina; Billadeau, Daniel D; Favier, Robert; Rong, Shunxing; Dekker, Daphne; Fedoseienko, Alina; Fieten, Hille; Wijers, Melinde; Levels, Johannes H; Huijkman, Nicolette; Kloosterhuis, Niels; van der Molen, Henk; Brufau, Gemma; Groen, Albert K; Elliott, Alison M; Kuivenhoven, Jan Albert; Plecko, Barbara; Grangl, Gernot; McGaughran, Julie; Horton, Jay D; Burstein, Ezra; Hofker, Marten H; van de Sluis, Bart

2016-03-11

The low-density lipoprotein receptor (LDLR) plays a pivotal role in clearing atherogenic circulating low-density lipoprotein (LDL) cholesterol. Here we show that the COMMD/CCDC22/CCDC93 (CCC) and the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complexes are both crucial for endosomal sorting of LDLR and for its function. We find that patients with X-linked intellectual disability caused by mutations in CCDC22 are hypercholesterolaemic, and that COMMD1-deficient dogs and liver-specific Commd1 knockout mice have elevated plasma LDL cholesterol levels. Furthermore, Commd1 depletion results in mislocalization of LDLR, accompanied by decreased LDL uptake. Increased total plasma cholesterol levels are also seen in hepatic COMMD9-deficient mice. Inactivation of the CCC-associated WASH complex causes LDLR mislocalization, increased lysosomal degradation of LDLR and impaired LDL uptake. Furthermore, a mutation in the WASH component KIAA0196 (strumpellin) is associated with hypercholesterolaemia in humans. Altogether, this study provides valuable insights into the mechanisms regulating cholesterol homeostasis and LDLR trafficking.

The potential of mipomersen, an ApoB synthesis inhibitor, to reduce necessity for LDL-apheresis in patients with heterozygous familial hypercholesterolemia and coronary artery disease.

PubMed

Vogt, Anja; Parhofer, Klaus G

2013-04-01

LDL-apheresis is a treatment option for familial hypercholesterolemia (FH) with country-specific thresholds for LDL-cholesterol (LDL-C) for initiation. Apheresis also reduces lipoprotein(a) [Lp(a)] and may be used to lower Lp(a) in high-risk patients. Mipomersen, an apolipoproteinB-synthesis-inhibitor, reduces LDL-C and Lp(a). We hypothesized that mipomersen may prevent the necessity for apheresis by reducing the both below thresholds. Data from a study in 123 patients with heterozygous FH and coronary artery disease on maximally tolerated lipid-lowering therapy were used to evaluate in what percentage adding mipomersen resulted in lipid-levels below apheresis-thresholds. Different thresholds were tested: LDL-C ≥ 2.59 mmol/l, ≥ 3.36 mmol/l, ≥ 4.14 mmol/l, Lp(a) ≥ 60 mg/dl. Mipomersen decreased LDL-C by 28% (baseline 153 mg/dl), Lp(a) by 21% (baseline 45 mg/dl) (placebo no effect). Mipomersen reduced the percentage of patients with LDL-C ≥ 4.14 mmol/l from 39 to 2%, with LDL ≥ 3.36 mmol/l from 62 to 16%, with LDL ≥ 2.59 mmol/l from 98 to 54%, and with Lp(a) ≥ 60 mg/dl from 39 to 23%. When added to maximally tolerated lipid-lowering therapy, mipomersen may reduce the necessity for apheresis in many of these patients. In Germany, the threshold for apheresis for LDL typically is 2.59 mmol/l, for Lp(a) 60 mg/dl. Almost 50% of the patients could avoid apheresis with the addition of mipomersen. Further studies are warranted to evaluate whether patients who qualify for apheresis could be adequately controlled with mipomersen.

Protective effect of ascorbic acid on netilmicin-induced lipid profile and peroxidation parameters in rabbit blood plasma.

PubMed

Devbhuti, Pritesh; Sikdar, Debasis; Saha, Achintya; Sengupta, Chandana

2011-01-01

A drug may cause alteration in blood-lipid profile and induce lipid peroxidation phenomena on administration in the body. Antioxidant may play beneficial role to control the negative alteration in lipid profile and lipid peroxidation. In view of this context, the present in vivo study was carried out to evaluate the role of ascorbic acid as antioxidant on netilmicin-induced alteration of blood lipid profile and peroxidation parameters. Rabbits were used as experimental animals and blood was collected to estimate blood-lipid profiles, such as total cholesterol (TCh), high density lipoprotein cholesterol (HDL-Ch), low density lipoprotein cholesterol (LDL-Ch), very low density lipoprotein cholesterol (VLDL-Ch), triglycerides (Tg), phospholipids (PL), and total lipids (TL), as well as peroxidation parameters, such as malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), reduced glutathione (GSH) and nitric oxide (NO). The results revealed that netilmicin caused significant enhancement of MDA, HNE, TCh, LDL-Ch, VLDL-Ch, Tg levels and reduction in GSH, NO, HDL-Ch, PL, TL levels. On co-administration, ascorbic acid was found to be effective in reducing netilmicin-induced negative alterations of the above parameters.

Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study.

PubMed

Jamnagerwalla, Juzar; Howard, Lauren E; Allott, Emma H; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freeman, Michael R; Freedland, Stephen J

2017-12-27

Epidemiologic evidence for a serum cholesterol-prostate cancer link is mixed. Prostate-specific antigen (PSA) is positively correlated with cholesterol, potentially increasing PSA-driven biopsy recommendations in men with high cholesterol, though biopsy compliance may be lower in men with comorbid conditions. These potential biases may affect PSA-driven biopsy rates and subsequent prostate cancer detection in men with high serum cholesterol. Our objective was to test the association between serum cholesterol and prostate cancer risk in men receiving PSA independent, study-mandated prostate biopsies. We conducted a post hoc analysis of data from 4974 non-statin users in REDUCE, a randomized trial in men with elevated PSA and a negative baseline biopsy. Men underwent 2- and 4-year trial-mandated prostate biopsies. Associations between baseline serum levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and prostate cancer risk, overall and by Gleason grade (<7 vs. ≥7), were examined using multivariable logistic regression. High total serum cholesterol was associated with an increased risk of high-grade prostate cancer diagnosis (OR per 10 mg/dL 1.05; 95% CI 1.00-1.09; p = 0.048), but cholesterol was unrelated to either overall or low-grade prostate cancer risk (p-values >0.185). There was no association between serum LDL and overall, low- or high-grade prostate cancer risk (p-values >0.137). In contrast, elevated serum HDL was associated with increased risk of both overall (OR per 10 mg/dL 1.08; 95% CI 1.01-1.16; p = 0.033) and high-grade prostate cancer (OR per 10 mg/dL 1.14; 95% CI 1.01-1.28; p = 0.034). In REDUCE, where all men received PSA independent, trial-mandated biopsies thus ensuring complete prostate cancer ascertainment, high total serum cholesterol and high HDL were associated with increased risk of high-grade prostate cancer, supporting a cholesterol-prostate cancer link.

Does a lack of physical activity explain the rheumatoid arthritis lipid profile?

PubMed

AbouAssi, Hiba; Connelly, Margery A; Bateman, Lori A; Tune, K Noelle; Huebner, Janet L; Kraus, Virginia B; Winegar, Deborah A; Otvos, James D; Kraus, William E; Huffman, Kim M

2017-02-10

In rheumatoid arthritis (RA), cardiovascular risk is associated with paradoxical reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C). Concentrations of small LDL (LDL-P) and HDL (HDL-P) particles are also reduced with increased inflammation and disease activity in RA patients. Here we sought to identify which measure(s) of inflammation, disease activity and cardiometabolic risk contribute most to the RA-associated lipoprotein profile. NMR lipoprotein measurements were obtained for individuals with RA (n = 50) and age-, gender-, and body mass index (BMI)-matched controls (n = 39). Groups were compared using 39 matched pairs with 11 additional subjects used in RA only analyses. Among RA patients, relationships were determined for lipoprotein parameters with measures of disease activity, disability, pain, inflammation, body composition, insulin sensitivity and exercise. Percentage of time spent in basal activity (<1 metabolic equivalent) and exercise (≥3 metabolic equivalents) were objectively-determined. Subjects with RA had fewer total and small LDL-P as well as larger LDL and HDL size (P < 0.05). Among RA patients, pain and disability were associated with fewer small HDL-P (P < 0.05), while interleukin (IL)-6, IL-18, and TNF-α were associated with LDL size (P < 0.05). BMI, waist circumference, abdominal visceral adiposity and insulin resistance were associated with more total and small LDL-P, fewer large HDL-P, and a reduction in HDL size (P < 0.05). Most similar to the RA lipoprotein profile, more basal activity (minimal physical activity) and less exercise time were associated with fewer small LDL-P and total and small HDL-P (P < 0.05). The RA-associated lipoprotein profile is associated with a lack of physical activity. As this was a cross-sectional investigation and not an intervention and was performed from 2008-13, this study was not registered in clinicaltrials.gov.

Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor.

PubMed

Chechi, Kanta; McGuire, John J; Cheema, Sukhinder K

2009-04-01

We have previously shown that a maternal high-fat diet, rich in saturated fatty acids (SFA), alters the lipid metabolism of their adult offspring. The present study was designed to investigate 1) whether alterations in hepatic LDL-receptor (LDL-r) expression may serve as a potential mechanism of developmental programming behind the altered lipid metabolism of the offspring, 2) whether altered lipid metabolism leads to aortic vascular dysfunction in the offspring, 3) whether deleterious effects of SFA exposure preweaning are influenced by postweaning diet, and 4) whether gender-specific programming effects are observed. Female C57Bl/6 mice were fed a high-SFA diet or regular chow during gestation and lactation while their pups, both male and female, received either SFA or a chow diet after weaning. Male offspring obtained from mothers fed an SFA diet and those who continued on chow postweaning had higher plasma triglycerides and total cholesterol, whereas female offspring had higher plasma total and LDL cholesterol levels, lower hepatic LDL-r mRNA expression, and reduced aortic contractile responses compared with the offspring that were fed chow throughout the study. A comparison of the postweaning diet revealed significantly lower hepatic LDL-r expression along with significantly higher plasma LDL-cholesterol concentration in the female offspring that were obtained from mothers fed an SFA diet and who continued on an SFA diet postweaning, compared with the female offspring that were obtained from mothers fed an SFA diet but who continued on chow postweaning. In conclusion, we report a novel observation of hepatic LDL-r-mediated programming of altered lipid metabolism, along with aortic vascular dysfunction, in the female offspring of mothers fed a high-SFA diet. Male offspring only exhibited dyslipidemia, suggesting gender-mediated programming. This study further highlighted the role of postweaning diets in overriding the effects of maternal programming.

High susceptibility to fatty liver disease in two-pore channel 2-deficient mice.

PubMed

Grimm, Christian; Holdt, Lesca M; Chen, Cheng-Chang; Hassan, Sami; Müller, Christoph; Jörs, Simone; Cuny, Hartmut; Kissing, Sandra; Schröder, Bernd; Butz, Elisabeth; Northoff, Bernd; Castonguay, Jan; Luber, Christian A; Moser, Markus; Spahn, Saskia; Lüllmann-Rauch, Renate; Fendel, Christina; Klugbauer, Norbert; Griesbeck, Oliver; Haas, Albert; Mann, Matthias; Bracher, Franz; Teupser, Daniel; Saftig, Paul; Biel, Martin; Wahl-Schott, Christian

2014-08-21

Endolysosomal organelles play a key role in trafficking, breakdown and receptor-mediated recycling of different macromolecules such as low-density lipoprotein (LDL)-cholesterol, epithelial growth factor (EGF) or transferrin. Here we examine the role of two-pore channel (TPC) 2, an endolysosomal cation channel, in these processes. Embryonic mouse fibroblasts and hepatocytes lacking TPC2 display a profound impairment of LDL-cholesterol and EGF/EGF-receptor trafficking. Mechanistically, both defects can be attributed to a dysfunction of the endolysosomal degradation pathway most likely on the level of late endosome to lysosome fusion. Importantly, endolysosomal acidification or lysosomal enzyme function are normal in TPC2-deficient cells. TPC2-deficient mice are highly susceptible to hepatic cholesterol overload and liver damage consistent with non-alcoholic fatty liver hepatitis. These findings indicate reduced metabolic reserve of hepatic cholesterol handling. Our results suggest that TPC2 plays a crucial role in trafficking in the endolysosomal degradation pathway and, thus, is potentially involved in the homoeostatic control of many macromolecules and cell metabolites.

A pilot study on the effect of Catha edulis Frosk., (Celastraceae) on metabolic syndrome in WOKW rats.

PubMed

Mahmood, Samira Abdulla; Lindequist, Ulrike

2008-04-10

This study investigated the effect of Catha edulis (khat) on some important parameters of the metabolic syndrome in Wistar Ottawa Karlsburg W (WOKW) rat. The animals were fed with the standard chow containing 5% air dried pulverized khat leaves for 14 days; followed by the standard chow for 16 days. The khat leaves were sorted into green (khat light; KL) and crimson (khat dark; KD) leaves. The control rats were fed on standard chow. Blood glucose (G), serum insulin, serum leptin and serum lipids (triglycerides, total cholesterol, HDL-, LDL-, and VLDL cholesterol) were determined. Feeding with khat leaves reduced the body weight and the triglyceride level of the animals. The effect of KD on these parameters was stronger than that of KL. KD lowered the blood glucose concentration and the leptin content whereas KL was inactive. The khat intake had no significant influence on serum insulin, total serum cholesterol, HDL-, LDL- and VLDL-cholesterol.

Noni juice improves serum lipid profiles and other risk markers in cigarette smokers.

PubMed

Wang, Mian-Ying; Peng, Lin; Weidenbacher-Hoper, Vicki; Deng, Shixin; Anderson, Gary; West, Brett J

2012-01-01

Cigarette smoke-induced oxidative stress leads to dyslipidemia and systemic inflammation. Morinda citrifolia (noni) fruit juice has been found previously to have a significant antioxidant activity. One hundred thirty-two adult heavy smokers completed a randomized, double blind, placebo-controlled clinical trial designed to investigate the effect of noni juice on serum cholesterol, triglyceride, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), high-sensitivity C-reactive protein (hs-CRP), and homocysteine. Volunteers drank noni juice or a fruit juice placebo daily for one month. Drinking 29.5 mL to 188 mL of noni juice per day significantly reduced cholesterol levels, triglycerides, and hs-CRP. Decreases in LDL and homocysteine, as well increases in HDL, were also observed among noni juice drinkers. The placebo, which was devoid of iridoid glycosides, did not significantly influence blood lipid profiles or hs-CRP. Noni juice was able to mitigate cigarette smoke-induced dyslipidemia, an activity associated with the presence of iridoids.

Noni Juice Improves Serum Lipid Profiles and Other Risk Markers in Cigarette Smokers

PubMed Central

Wang, Mian-Ying; Peng, Lin; Weidenbacher-Hoper, Vicki; Deng, Shixin; Anderson, Gary; West, Brett J.

2012-01-01

Cigarette smoke-induced oxidative stress leads to dyslipidemia and systemic inflammation. Morinda citrifolia (noni) fruit juice has been found previously to have a significant antioxidant activity. One hundred thirty-two adult heavy smokers completed a randomized, double blind, placebo-controlled clinical trial designed to investigate the effect of noni juice on serum cholesterol, triglyceride, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), high-sensitivity C-reactive protein (hs-CRP), and homocysteine. Volunteers drank noni juice or a fruit juice placebo daily for one month. Drinking 29.5 mL to 188 mL of noni juice per day significantly reduced cholesterol levels, triglycerides, and hs-CRP. Decreases in LDL and homocysteine, as well increases in HDL, were also observed among noni juice drinkers. The placebo, which was devoid of iridoid glycosides, did not significantly influence blood lipid profiles or hs-CRP. Noni juice was able to mitigate cigarette smoke-induced dyslipidemia, an activity associated with the presence of iridoids. PMID:23097636

Hypolipidemic effect of arborium plus in experimentally induced hypercholestermic rabbits.

PubMed

Murty, Devarakonda; Rajesh, Enjamoori; Raghava, Doonaboina; Raghavan, Tangaraj Vijaya; Surulivel, Mukanthan Karupiah Munirajan

2010-06-01

Hypercholesteremia is one of the risk factors for coronary artery disease. The present study highlights the efficacy of the ayurvedic herbal formulation Arborium Plus [Hyppophae ramnoides L. fruit juice (S) and Rhododendron arboreum Sm. Linn flower juice (R) in a 1:4 ratio] on triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), atherogenic index (AI), high-density lipoprotein (HDL), and high-sensitivity c-reactive protein (hs CRP) in experimentally induced hypercholesterolemic rabbits. Four groups of rabbits were subjected to different treatments for 8 weeks: control group, CHOL group (1% w/w cholesterol for 8 weeks), S+R group (1% w/w cholesterol and Arborium Plus for 8 weeks), and A group (1% w/w cholesterol and atorvastatin for 8 weeks). The results showed significant increases in TG, TC, LDL, AI, and hs CRP in hypercholesterolemic rabbits which was significantly reduced in Arborium Plus-treated hypercholesterolemic rabbits. The data demonstrated that the Arborium Plus formulation was associated with hypolipidemic effects in experimentally induced hypercholesterolemic rabbits.

Lipid effects of peroxisome proliferator-activated receptor-δ agonist GW501516 in subjects with low high-density lipoprotein cholesterol: characteristics of metabolic syndrome.

PubMed

Olson, Eric J; Pearce, Gregory L; Jones, Nigel P; Sprecher, Dennis L

2012-09-01

Peroxisome proliferator-activated receptor-δ-induced upregulation in skeletal muscle fatty acid oxidation would predict the modulation of lipid/lipoproteins. GW501516 (2.5, 5.0, or 10.0 mg) or placebo was given for 12 weeks to patients (n=268) with high-density lipoprotein (HDL) cholesterol <1.16 mmol/L. Fasting lipids/apolipoproteins (apos), insulin, glucose, and free fatty acid were measured; changes from baseline were calculated and assessed. A second smaller exploratory study (n=37) in a similar population was conducted using a sequence of 5 and 10 mg dosing for the assessment of lipoprotein particle concentration. GW501516 demonstrated HDL cholesterol increases up to 16.9% (10 mg) and apoA-I increases up to 6.6%. Reductions were observed in low-density lipoprotein (LDL) cholesterol (-7.3%), triglycerides (-16.9%), apoB (-14.9%), and free fatty acids (-19.4%). The exploratory study showed significant reductions in the concentration of very LDL (-19%), intermediate-density lipoprotein (-52%), and LDL (-14%, predominantly a reduction in small particles), whereas the number of HDL particles increased (+10%; predominantly medium and large HDL). GW501516 produced significant changes in HDL cholesterol, LDL cholesterol, apoA1, and apoB. Fewer very LDL and larger LDL support a transition toward less atherogenic lipoprotein profiles. These data are consistent with peroxisome proliferator-activated receptor-δ being a potentially important target for providing cardiovascular protection in metabolic syndrome-like patients.

Effect of obstructive sleep apnea hypopnea syndrome on lipid profile: a meta-regression analysis.

PubMed

Nadeem, Rashid; Singh, Mukesh; Nida, Mahwish; Waheed, Irfan; Khan, Adnan; Ahmed, Saeed; Naseem, Jawed; Champeau, Daniel

2014-05-15

Obstructive sleep apnea (OSA) is associated with obesity, metabolic syndrome, and dyslipidemia, which may be related to decrease androgen levels found in OSA patients. Dyslipidemia may contribute to atherosclerosis leading to increasing risk of heart disease. Systematic review was conducted using PubMed and Cochrane library by utilizing different combinations of key words; sleep apnea, obstructive sleep apnea, serum lipids, dyslipidemia, cholesterol, total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), and triglyceride (TG). Inclusion criteria were: English articles, and studies with adult population in 2 groups of patients (patients with OSA and without OSA). A total 96 studies were reviewed for inclusion, with 25 studies pooled for analysis. Sixty-four studies were pooled for analysis; since some studies have more than one dataset, there were 107 datasets with 18,116 patients pooled for meta-analysis. All studies measured serum lipids. Total cholesterol pooled standardized difference in means was 0.267 (p = 0.001). LDL cholesterol pooled standardized difference in means was 0.296 (p = 0.001). HDL cholesterol pooled standardized difference in means was -0.433 (p = 0.001). Triglyceride pooled standardized difference in means was 0.603 (p = 0.001). Meta-regression for age, BMI, and AHI showed that age has significant effect for TC, LDL, and HDL. BMI had significant effect for LDL and HDL, while AHI had significant effect for LDL and TG. Patients with OSA appear to have increased dyslipidemia (high total cholesterol, LDL, TG, and low HDL).

G-protein estrogen receptor as a regulator of low-density lipoprotein cholesterol metabolism: cellular and population genetic studies.

PubMed

Hussain, Yasin; Ding, Qingming; Connelly, Philip W; Brunt, J Howard; Ban, Matthew R; McIntyre, Adam D; Huff, Murray W; Gros, Robert; Hegele, Robert A; Feldman, Ross D

2015-01-01

Estrogen deficiency is linked with increased low-density lipoprotein (LDL) cholesterol. The hormone receptor mediating this effect is unknown. G-protein estrogen receptor (GPER) is a recently recognized G-protein-coupled receptor that is activated by estrogens. We recently identified a common hypofunctional missense variant of GPER, namely P16L. However, the role of GPER in LDL metabolism is unknown. Therefore, we examined the association of the P16L genotype with plasma LDL cholesterol level. Furthermore, we studied the role of GPER in regulating expression of the LDL receptor and proprotein convertase subtilisin kexin type 9. Our discovery cohort was a genetically isolated population of Northern European descent, and our validation cohort consisted of normal, healthy women aged 18 to 56 years from London, Ontario. In addition, we examined the effect of GPER on the regulation of proprotein convertase subtilisin kexin type 9 and LDL receptor expression by the treatment with the GPER agonist, G1. In the discovery cohort, GPER P16L genotype was associated with a significant increase in LDL cholesterol (mean±SEM): 3.18±0.05, 3.25±0.08, and 4.25±0.33 mmol/L, respectively, in subjects with CC (homozygous for P16), CT (heterozygotes), and TT (homozygous for L16) genotypes (P<0.05). In the validation cohort (n=339), the GPER P16L genotype was associated with a similar increase in LDL cholesterol: 2.17±0.05, 2.34±0.06, and 2.42±0.16 mmol/L, respectively, in subjects with CC, CT, and TT genotypes (P<0.05). In the human hepatic carcinoma cell line, the GPER agonist, G1, mediated a concentration-dependent increase in LDL receptor expression, blocked by either pretreatment with the GPER antagonist G15 or by shRNA-mediated GPER downregulation. G1 also mediated a GPER- and concentration-dependent decrease in proprotein convertase subtilisin kexin type 9 expression. GPER activation upregulates LDL receptor expression, probably at least, in part, via proprotein convertase subtilisin kexin type 9 downregulation. Furthermore, humans carrying the hypofunctional P16L genetic variant of GPER have increased plasma LDL cholesterol. In aggregate, these data suggest an important role of GPER in the regulation of LDL receptor expression and consequently LDL metabolism. © 2014 American Heart Association, Inc.

A comparative systematic review of Yasmin (drospirenone pill) versus standard treatment options for symptoms of polycystic ovary syndrome.

PubMed

Li, Jing; Ren, Jing; Sun, Wenxia

2017-03-01

To systematically review the impact of Yasmin (drospirenone pill) compares with other standard treatments for symptoms of Polycystic Ovary Syndrome (PCOS). The relevant studies of the randomized controlled trials in women with PCOS treated with drospirenone were retrieved and the systematic evaluation was conducted. Eighteen articles were included. Compared with drospirenone (DRSP) monotherapy, DRSP plus metformin was better in reducing body mass index (BMI), luteinizing hormone (LH) and low-density lipoprotein cholesterol (LDL-C). Compared with metformin, DRSP was better in modulating serum total testosterone (T), sex hormone-binding globulin (SHBG), follicle stimulating hormone (FSH) and free androgen index (FAI), while metformin was more effective in reducing BMI, total cholesterol (TC), LDL-C and Triglyceride (TG). DRSP was superior to cyproterone acetate (CPA) in reducing TC and homeostasis model assessment of insulin resistance (HOMA-IR). DRSP shows better effect in modulating LDL-C and high-density lipoprotein cholesterol (HDL-C) compared with desogestrel (DSG). The available data suggested that DRSP was effective in modulating hormones, insulin and lipid metabolism in women with PCOS. Compared with commonly used drugs for symptoms of PCOS as CPA and DSG, DRSP shows identical or better effect in improving symptoms and protect cardiovascular system. For the PCOS patients with IR, obesity or high LH/FSH ratio, DRSP combines with metformin maybe more effective than use DRSP alone. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans.

PubMed

Wan, Y; Vinson, J A; Etherton, T D; Proch, J; Lazarus, S A; Kris-Etherton, P M

2001-11-01

Flavonoids are polyphenolic compounds of plant origin with antioxidant effects. Flavonoids inhibit LDL oxidation and reduce thrombotic tendency in vitro. Little is known about how cocoa powder and dark chocolate, rich sources of polyphenols, affect these cardiovascular disease risk factors. We evaluated the effects of a diet high in cocoa powder and dark chocolate (CP-DC diet) on LDL oxidative susceptibility, serum total antioxidant capacity, and urinary prostaglandin concentrations. We conducted a randomized, 2-period, crossover study in 23 healthy subjects fed 2 diets: an average American diet (AAD) controlled for fiber, caffeine, and theobromine and an AAD supplemented with 22 g cocoa powder and 16 g dark chocolate (CP-DC diet), providing approximately 466 mg procyanidins/d. LDL oxidation lag time was approximately 8% greater (P = 0.01) after the CP-DC diet than after the AAD. Serum total antioxidant capacity measured by oxygen radical absorbance capacity was approximately 4% greater (P = 0.04) after the CP-DC diet than after the AAD and was positively correlated with LDL oxidation lag time (r = 0.32, P = 0.03). HDL cholesterol was 4% greater after the CP-DC diet (P = 0.02) than after the AAD; however, LDL-HDL ratios were not significantly different. Twenty-four-hour urinary excretion of thromboxane B(2) and 6-keto-prostaglandin F(1)(alpha) and the ratio of the 2 compounds were not significantly different between the 2 diets. Cocoa powder and dark chocolate may favorably affect cardiovascular disease risk status by modestly reducing LDL oxidation susceptibility, increasing serum total antioxidant capacity and HDL-cholesterol concentrations, and not adversely affecting prostaglandins.

Beta-glucan- or rice bran-enriched foods: a comparative crossover clinical trial on lipidic pattern in mildly hypercholesterolemic men.

PubMed

Rondanelli, M; Opizzi, A; Monteferrario, F; Klersy, C; Cazzola, R; Cestaro, B

2011-07-01

There has been growing interest in using dietary intervention to improve the lipid profile. This work aims at analyzing the effects and the comparison of the enrichment of a diet with beta-glucans or rice bran in mildly hypercholesterolemic men. The subjects initially consumed a 3-week Step 1 American Heart Association diet with rice bran-enriched foods. After this adaptation period, volunteers were randomly assigned to follow a crossover, controlled trial that consisted of two treatment with beta-glucan- or rice bran-enriched foods, each of 4 weeks, with a 3-week wash-out, like the adaptation period, between periods. Fasted blood samples were collected on days 0, 21, 49, 70 and 98 in both study arms for measuring low-density lipoprotein (LDL)-cholesterol (primary outcome), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, apolipoprotein (apo) A-I, apo B and glucose levels. Twenty-four men (mean age: 50.3±5.3, mean body mass index: 24.9±1.9) completed the 14-week trial. Subjects in the 3-week adaptation period experienced significant reductions in the mean level of LDL cholesterol, total cholesterol, total cholesterol/HDL cholesterol, LDL cholesterol/HDL cholesterol, apo A-I, apo A-I/apo B and glucose. During the intervention diet periods, a difference was found between treatment groups for the mean change in LDL (0.21 (95% confidence interval (CI): 0.02-0.40), P=0.033) and total cholesterol (0.34 (95% CI: 0.20-0.47), P<0.001). Other parameters evaluated were not significantly affected by the diet consumed. The results of the present crossover clinical trial showed that beta-glucan-enriched foods are more effective in lowering serum LDL levels, compared with rice bran-enriched foods.

The association between dietary cholesterol intake and subclinical atherosclerosis in Korean adults: The Kangbuk Samsung Health Study.

PubMed

Rhee, Eun-Jung; Ryu, Seungho; Lee, Jong-Young; Lee, Sung Ho; Cheong, EunSun; Park, Se Eun; Park, Cheol-Young; Won, Yu Sam; Kim, Joon Mo; Cho, Dong-Sik; Chung, Hye-Kyung; Sung, Ki Chul

The Scientific Report of the Dietary Guidelines Advisory Committee (2015) concluded that restriction of dietary cholesterol is unnecessary in most adults for the prevention of cardiovascular disease. We aimed to assess the risk for subclinical atherosclerosis according to coronary artery calcium score (CACS), based on dietary cholesterol intake in apparently healthy Korean adults. This was a cross-sectional study performed in 30,068 participants (mean age 40.8 years; 84.5% men) in a health screening program in Korea. The data were collected from 2001 to 2013 and analyzed in 2015. Total energy intake and dietary cholesterol intake were assessed with a food frequency questionnaire. The participants were stratified according to quartile of dietary cholesterol intake. CACS was measured by multi-detector computed tomography. Lipid profiles were measured, and the participants were divided into 6 groups according to low-density lipoprotein cholesterol (LDL-C) level: <70, 70 to 99, 100 to 129, 130 to 159, 160 to 189, and ≥190 mg/dL. The presence of coronary artery calcification was defined as CACS>0. Dietary cholesterol intake did not correlate with mean value of serum LDL-C level. For both genders, the odds ratio for coronary artery calcification was not significantly greater with greater amounts of dietary cholesterol (as assessed by quartile). The risk for coronary artery calcification was not higher in subjects with LDL-C 70-129 mg/dL compared with those with LDL-C < 70 mg/dL; however, the risk was significantly greater in subjects with LDL-C ≥ 130 mg/dL compared with those with LDL-C < 70 mg/dL. Dietary cholesterol intake did not have an association with LDL-C level or with risk for coronary artery calcification in apparently healthy Korean adults. The results have to be translated with consideration of limitation of population-based studies. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

A Spectrum of PCSK9 Alleles Contributes to Plasma Levels of Low-Density Lipoprotein Cholesterol

PubMed Central

Kotowski, Ingrid K.; Pertsemlidis, Alexander; Luke, Amy; Cooper, Richard S.; Vega, Gloria L.; Cohen, Jonathan C.; Hobbs, Helen H.

2006-01-01

Selected missense mutations in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) cause autosomal dominant hypercholesterolemia, whereas nonsense mutations in the same gene are associated with low plasma levels of low-density lipoprotein cholesterol (LDL-C). Here, DNA sequencing and chip-based oligonucleotide hybridization were used to determine whether other sequence variations in PCSK9 contribute to differences in LDL-C levels. The coding regions of PCSK9 were sequenced in the blacks and whites from the Dallas Heart Study (n=3,543) who had the lowest (<5th percentile) and highest (>95th percentile) plasma levels of LDL-C. Of the 17 missense variants identified, 3 (R46L, L253F, and A443T) were significantly and reproducibly associated with lower plasma levels of LDL-C (reductions ranging from 3.5% to 30%). None of the low–LDL-C variants were associated with increased hepatic triglyceride content, as measured by proton magnetic resonance spectroscopy. This finding is most consistent with the reduction in LDL-C being caused primarily by accelerating LDL clearance, rather than by reduced lipoprotein production. Association studies with 93 noncoding single-nucleotide polymorphisms (SNPs) at the PCSK9 locus identified 3 SNPs associated with modest differences in plasma LDL-C levels. Thus, a spectrum of sequence variations ranging in frequency (from 0.2% to 34%) and magnitude of effect (from a 3% increase to a 49% decrease) contribute to interindividual differences in LDL-C levels. These findings reveal that PCSK9 activity is a major determinant of plasma levels of LDL-C in humans and make it an attractive therapeutic target for LDL-C lowering. PMID:16465619

Oxidized LDL lipids increase β-amyloid production by SH-SY5Y cells through glutathione depletion and lipid raft formation

PubMed Central

Dias, Irundika H.K.; Mistry, Jayna; Fell, Shaun; Reis, Ana; Spickett, Corinne M.; Polidori, Maria C.; Lip, Gregory Y.H.; Griffiths, Helen R.

2014-01-01

Elevated total cholesterol in midlife has been associated with increased risk of dementia in later life. We have previously shown that low-density lipoprotein (LDL) is more oxidized in the plasma of dementia patients, although total cholesterol levels are not different from those of age-matched controls. β-Amyloid (Aβ) peptide, which accumulates in Alzheimer disease (AD), arises from the initial cleavage of amyloid precursor protein by β-secretase-1 (BACE1). BACE1 activity is regulated by membrane lipids and raft formation. Given the evidence for altered lipid metabolism in AD, we have investigated a mechanism for enhanced Aβ production by SH-SY5Y neuronal-like cells exposed to oxidized LDL (oxLDL). The viability of SH-SY5Y cells exposed to 4 μg oxLDL and 25 µM 27-hydroxycholesterol (27OH-C) was decreased significantly. Lipids, but not proteins, extracted from oxLDL were more cytotoxic than oxLDL. In parallel, the ratio of reduced glutathione (GSH) to oxidized glutathione was decreased at sublethal concentrations of lipids extracted from native and oxLDL. GSH loss was associated with an increase in acid sphingomyelinase (ASMase) activity and lipid raft formation, which could be inhibited by the ASMase inhibitor desipramine. 27OH-C and total lipids from LDL and oxLDL independently increased Aβ production by SH-SY5Y cells, and Aβ accumulation could be inhibited by desipramine and by N-acetylcysteine. These data suggest a mechanism whereby oxLDL lipids and 27OH-C can drive Aβ production by GSH depletion, ASMase-driven membrane remodeling, and BACE1 activation in neuronal cells. PMID:25048970

Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD.

PubMed

Funamoto, Masafumi; Sunagawa, Yoichi; Katanasaka, Yasufumi; Miyazaki, Yusuke; Imaizumi, Atsushi; Kakeya, Hideaki; Yamakage, Hajime; Satoh-Asahara, Noriko; Komiyama, Maki; Wada, Hiromichi; Hasegawa, Koji; Morimoto, Tatsuya

2016-01-01

COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin-low-density lipoprotein (AT-LDL) complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin(®), a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD. This is a randomized, double-blind, parallel-group study. Subjects with stages I-II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin(®) or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated. There were no differences between the Theracurmin(®) and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure and hemoglobin A1c and LDL-cholesterol, triglyceride, or high-density lipoprotein-cholesterol levels after treatment were similar for the two groups. However, the percent change in the AT-LDL level was significantly (P=0.020) lower in the Theracurmin(®) group compared with the placebo group. Theracurmin(®) reduced levels of atherosclerotic AT-LDL, which may lead to the prevention of future cardiovascular events in mild COPD subjects.

Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice

PubMed Central

Ai, Ding; Chen, Chiyuan; Han, Seongah; Ganda, Anjali; Murphy, Andrew J.; Haeusler, Rebecca; Thorp, Edward; Accili, Domenico; Horton, Jay D.; Tall, Alan R.

2012-01-01

Individuals with type 2 diabetes have an increased risk of atherosclerosis. One factor underlying this is dyslipidemia, which in hyperinsulinemic subjects with early type 2 diabetes is typically characterized by increased VLDL secretion but normal LDL cholesterol levels, possibly reflecting enhanced catabolism of LDL via hepatic LDLRs. Recent studies have also suggested that hepatic insulin signaling sustains LDLR levels. We therefore sought to elucidate the mechanisms linking hepatic insulin signaling to regulation of LDLR levels. In WT mice, insulin receptor knockdown by shRNA resulted in decreased hepatic mTORC1 signaling and LDLR protein levels. It also led to increased expression of PCSK9, a known post-transcriptional regulator of LDLR expression. Administration of the mTORC1 inhibitor rapamycin caused increased expression of PCSK9, decreased levels of hepatic LDLR protein, and increased levels of VLDL/LDL cholesterol in WT but not Pcsk9–/– mice. Conversely, mice with increased hepatic mTORC1 activity exhibited decreased expression of PCSK9 and increased levels of hepatic LDLR protein levels. Pcsk9 is regulated by the transcription factor HNF1α, and our further detailed analyses suggest that increased mTORC1 activity leads to activation of PKCδ, reduced activity of HNF4α and HNF1α, decreased PCSK9 expression, and ultimately increased hepatic LDLR protein levels, which result in decreased circulating LDL levels. We therefore suggest that PCSK9 inhibition could be an effective way to reduce the adverse side effect of increased LDL levels that is observed in transplant patients taking rapamycin as immunosuppressive therapy. PMID:22426206

Elevated Levels of LDL-C are Associated With ApoE4 but Not With the rs688 Polymorphism in the LDLR Gene.

PubMed

Cahua-Pablo, Gabriel; Cruz, Miguel; Moral-Hernández, Oscar Del; Leyva-Vázquez, Marco A; Antúnez-Ortiz, Diana L; Cahua-Pablo, José A; Alarcón-Romero, Luz Del Carmen; Ortuño-Pineda, Carlos; Moreno-Godínez, Ma Elena; Hernández-Sotelo, Daniel; Flores-Alfaro, Eugenia

2016-07-01

Apolipoprotein E (ApoE) 4 isoform has been associated with elevated levels of cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGs), meanwhile several polymorphisms in the LDL receptor (LDLR) gene have been associated with increased levels of total cholesterol and LDL-C. We studied 400 women from Southwest Mexico. Anthropometric features and biochemical profile were evaluated, and genotyping of single nucleotide polymorphisms rs429358 and rs7412 in the APOE gene and rs688 in the LDLR gene was determined by TaqMan assays. We found significant association between LDL-C (odds ratio [OR] = 3.3, 95% confidence interval [CI]: 1.9-5.7) and marginal association with TG (OR = 1.7, 95% CI: 1.0-2.9) of atherogenic risk in women carriers of the ApoE4 isoform compared to ApoE3. The TT genotype of rs688 in the LDLR gene was not found to be associated with elevated levels of total cholesterol or LDL-C. Our results show that carrier women of the ApoE4 isoform are more likely to have elevated levels of LDL-C and therefore increased risk of developing atherosclerosis. © The Author(s) 2015.

Effects of obeticholic acid on lipoprotein metabolism in healthy volunteers.

PubMed

Pencek, R; Marmon, T; Roth, J D; Liberman, A; Hooshmand-Rad, R; Young, M A

2016-09-01

The bile acid analogue obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist in development for treatment of several chronic liver diseases. FXR activation regulates lipoprotein homeostasis. The effects of OCA on cholesterol and lipoprotein metabolism in healthy individuals were assessed. Two phase I studies were conducted to evaluate the effects of repeated oral doses of 5, 10 or 25 mg OCA on lipid variables after 14 or 20 days of consecutive administration in 68 healthy adults. Changes in HDL and LDL cholesterol levels were examined, in addition to nuclear magnetic resonance analysis of particle sizes and sub-fraction concentrations. OCA elicited changes in circulating cholesterol and particle size of LDL and HDL. OCA decreased HDL cholesterol and increased LDL cholesterol, independently of dose. HDL particle concentrations declined as a result of a reduction in medium and small HDL. Total LDL particle concentrations increased because of an increase in large LDL particles. Changes in lipoprotein metabolism attributable to OCA in healthy individuals were found to be consistent with previously reported changes in patients receiving OCA with non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. © 2016 John Wiley & Sons Ltd.

High-oleic canola oil consumption enriches LDL particle cholesteryl oleate content and reduces LDL proteoglycan binding in humans.

PubMed

Jones, Peter J H; MacKay, Dylan S; Senanayake, Vijitha K; Pu, Shuaihua; Jenkins, David J A; Connelly, Philip W; Lamarche, Benoît; Couture, Patrick; Kris-Etherton, Penny M; West, Sheila G; Liu, Xiaoran; Fleming, Jennifer A; Hantgan, Roy R; Rudel, Lawrence L

2015-02-01

Oleic acid consumption is considered cardio-protective according to studies conducted examining effects of the Mediterranean diet. However, animal models have shown that oleic acid consumption increases LDL particle cholesteryl oleate content which is associated with increased LDL-proteoglycan binding and atherosclerosis. The objective was to examine effects of varying oleic, linoleic and docosahexaenoic acid consumption on human LDL-proteoglycan binding in a non-random subset of the Canola Oil Multi-center Intervention Trial (COMIT) participants. COMIT employed a randomized, double-blind, five-period, cross-over trial design. Three of the treatment oil diets: 1) a blend of corn/safflower oil (25:75); 2) high oleic canola oil; and 3) DHA-enriched high oleic canola oil were selected for analysis of LDL-proteoglycan binding in 50 participants exhibiting good compliance. LDL particles were isolated from frozen plasma by gel filtration chromatography and LDL cholesteryl esters quantified by mass-spectrometry. LDL-proteoglycan binding was assessed using surface plasmon resonance. LDL particle cholesterol ester fatty acid composition was sensitive to the treatment fatty acid compositions, with the main fatty acids in the treatments increasing in the LDL cholesterol esters. The corn/safflower oil and high-oleic canola oil diets lowered LDL-proteoglycan binding relative to their baseline values (p = 0.0005 and p = 0.0012, respectively). At endpoint, high-oleic canola oil feeding resulted in lower LDL-proteoglycan binding than corn/safflower oil (p = 0.0243) and DHA-enriched high oleic canola oil (p = 0.0249), although high-oleic canola oil had the lowest binding at baseline (p = 0.0344). Our findings suggest that high-oleic canola oil consumption in humans increases cholesteryl oleate percentage in LDL, but in a manner not associated with a rise in LDL-proteoglycan binding. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Portfolio Dietary Pattern and Cardiovascular Disease: A Systematic Review and Meta-Analysis of Controlled Trials.

PubMed

Chiavaroli, Laura; Nishi, Stephanie K; Khan, Tauseef A; Braunstein, Catherine R; Glenn, Andrea J; Mejia, Sonia Blanco; Rahelić, Dario; Kahleová, Hana; Salas-Salvadó, Jordi; Jenkins, David J A; Kendall, Cyril W C; Sievenpiper, John L

2018-05-25

The evidence for the Portfolio dietary pattern, a plant-based dietary pattern that combines recognized cholesterol-lowering foods (nuts, plant protein, viscous fibre, plant sterols), has not been summarized. To update the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of controlled trials using GRADE of the effect of the Portfolio dietary pattern on the primary therapeutic lipid target for cardiovascular disease prevention, low-density lipoprotein cholesterol (LDL-C), and other established cardiometabolic risk factors. We searched MEDLINE, EMBASE, and The Cochrane Library through April 19, 2018. We included controlled trials ≥ 3-weeks assessing the effect of the Portfolio dietary pattern on cardiometabolic risk factors compared with an energy-matched control diet free of Portfolio dietary pattern components. Two independent reviewers extracted data and assessed risk of bias. The primary outcome was LDL-C. Data were pooled using the generic inverse-variance method and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q statistic) and quantified (I 2 -statistic). GRADE assessed the certainty of the evidence. Eligibility criteria were met by 7 trial comparisons in 439 participants with hyperlipidemia, in which the Portfolio dietary pattern was given on a background of a National Cholesterol Education Program (NCEP) Step II diet. The combination of a portfolio dietary pattern and NCEP Step II diet significantly reduced the primary outcome LDL-C by ~17% (MD, -0.73mmol/L, [95% CI, -0.89 to -0.56 mmol/L]) as well as non-high-density lipoprotein cholesterol, apolipoprotein B, total cholesterol, triglycerides, systolic and diastolic blood pressure, C-reactive protein, and estimated 10-year coronary heart disease (CHD) risk, compared with an NCEP Step 2 diet alone (P<0.05). There was no effect on high-density lipoprotein cholesterol or body weight. The certainty of the evidence was high for LDL-cholesterol and most lipid outcomes and moderate for all others outcomes. Current evidence demonstrates that the Portfolio dietary pattern leads to clinically meaningful improvements in LDL-C as well as other established cardiometabolic risk factors and estimated 10-year CHD risk. Copyright © 2018. Published by Elsevier Inc.

Lipid profiles and determinants of total cholesterol and hypercholesterolaemia among 25–74 year-old urban and rural citizens of the Yangon Region, Myanmar: a cross-sectional study

PubMed Central

Htet, Aung Soe; Aung, Wai Phyo; Moe Myint, Aye Nyein; Aye, Win Thuzar; Wai, Myint Myint; Nu, Than Than; Hla, Ei Mon; Soe, Pyone Pyone; Tun, Nan Wut Yi; Angela, Naw; Khaing, Mya Mya; Htoo, Aung Kyaw; Tun, Soe; Thitsar, Pai; Lwin, Theeoo; Wai, San San; Aung, Thi Thi; Thant, Khin Aye; Aung Po, Wai Wai; Gauzam, Seng Taung; Naing, Tun Tun; Tun, Thet Min; Myint, Khin San; Oo, Kyi Kyi; Mang, Nang Kee Myu; Naing, Soe Moe; Zaw, Ko Ko; Bjertness, Marius Bergsmark; Sherpa, Lhamo Yangchen; Oo, Win Myint; Stigum, Hein; Bjertness, Espen

2017-01-01

Objective The first is to estimate the prevalence of dyslipidaemia (hypercholesterolaemia, hypertriglyceridaemia, high low-density lipoprotein (LDL) level and low high-density lipoprotein (HDL) level), as well as the mean levels of total cholesterol, triglyceride, LDL and HDL, in the urban and rural Yangon Region, Myanmar. The second is to investigate the association between urban-rural location and total cholesterol. Design Two cross-sectional studies using the WHO STEPS methodology. Setting Both the urban and rural areas of the Yangon Region, Myanmar. Participants A total of 1370 men and women aged 25–74 years participated based on a multistage cluster sampling. Physically and mentally ill people, monks, nuns, soldiers and institutionalised people were excluded. Results Compared with rural counterparts, urban dwellers had a significantly higher age-standardised prevalence of hypercholesterolaemia (50.7% vs 41.6%; p=0.042) and a low HDL level (60.6% vs 44.4%; p=0.001). No urban-rural differences were found in the prevalence of hypertriglyceridaemia and high LDL. Men had a higher age-standardised prevalence of hypertriglyceridaemia than women (25.1% vs 14.8%; p<0.001), while the opposite pattern was found in the prevalence of a high LDL (11.3% vs 16.3%; p=0.018) and low HDL level (35.3% vs 70.1%; p<0.001). Compared with rural inhabitants, urban dwellers had higher age-standardised mean levels of total cholesterol (5.31 mmol/L, SE: 0.044 vs 5.05 mmol/L, 0.068; p=0.009), triglyceride (1.65 mmol/L, 0.049 vs 1.38 mmol/L, 0.078; p=0.017), LDL (3.44 mmol/L, 0.019 vs 3.16 mmol/L, 0.058; p=0.001) and lower age-standardised mean levels of HDL (1.11 mmol/L, 0.010 vs 1.25 mmol/L, 0.012; p<0.001). In linear regression, the total cholesterol was significantly associated with an urban location among men, but not among women. Conclusion The mean level of total cholesterol and the prevalence of hypercholesterolaemia were alarmingly high in men and women in both the urban and rural areas of Yangon Region, Myanmar. Preventive measures to reduce cholesterol levels in the population are therefore needed. PMID:29146640

Therapeutic effect of probiotic dahi on plasma, aortic, and hepatic lipid profile of hypercholesterolemic rats.

PubMed

Mohania, Dheeraj; Kansal, Vinod Kumar; Shah, Dilip; Nagpal, Ravinder; Kumar, Manoj; Gautam, Sanjeev Kumar; Singh, Birbal; Behare, Pradip Vishnu

2013-09-01

This study examined the effects of probiotic dahi prepared by Lactobacillus plantarum Lp9 and dahi culture in buffalo milk on lowering cholesterol in rats fed a hypercholesterolemic basal diet. Male Wistar rats were divided into 3 groups and fed with probiotic dahi, dahi, or buffalo milk for 120 days. Following the consumption of supplements (probiotic dahi, dahi or buffalo milk), the animals were fed a basal hypercholesterolemic diet. Plasma total cholesterol and triglycerides (TAGs) were decreased by 35% and 72% in rats fed with probiotic dahi group, while cholesterol levels increased by 70% and TAGs increased by 97% in buffalo milk and 59% in dahi fed groups. Supplementation of probiotic dahi further lowered plasma low-density lipoprotein (LDL) + very-low-density lipoprotein (VLDL)- cholesterol by 59%, while it elevated plasma high-density lipoprotein (HDL)-cholesterol by 116%. As a result, atherogenic index, the ratio of HDL to LDL + VLDL was markedly improved. Deposition of cholesterol and TAGs in liver and aorta were significantly reduced in rats fed with probiotic dahi. These observations suggest that probiotic dahi may have therapeutic potential to decrease plasma, hepatic and aortic lipid profile, and attenuate diet-induced hypercholesterolemia.

Similar cholesterol-lowering properties of rice bran oil, with varied gamma-oryzanol, in mildly hypercholesterolemic men.

PubMed

Berger, Alvin; Rein, Dietrich; Schäfer, Angela; Monnard, Irina; Gremaud, Gérard; Lambelet, Pierre; Bertoli, Constantin

2005-03-01

The cholesterol lowering properties of rice bran oil (RBO) containing differing amounts of non-saponifiable components have not been studied in humans, to our knowledge. To evaluate cholesterol lowering effects of RBO, with low and high amounts of gamma-oryzanol (ferulated plant sterols) in mildly hypercholesterolemic men. Mildly hypercholesterolemic men, 38-64 y, starting cholesterol 4.9-8.4 mmol/l (n = 30), consumed 50 g/d peanut oil (PNO) in vehicles for 2 wks during a run-in period, then, without wash-out, were randomly equilibrated (based on initial level of cholesterol) into two groups to consume 50 g/d RBO low (0.05 g/d) or high (0.8 g/d) gamma-oryzanol for 4 wks, in a randomized, controlled, parallel design study. Subjects were free-living and consumed habitual diets with some restrictions. Plasma concentrations of total, LDL-,HDL-cholesterol and triacylglycerol were measured at base line and after 2, 4, and 6 wks. The two RBO types were not significantly different with respect to effects on various cholesterol parameters, at 2 and 4 wks, including total cholesterol, LDL-, HDL- and LDL/HDL cholesterol ratio. Low and high gamma-oryzanolcontaining RBO feeding for 4 wks lowered total plasma cholesterol (6.3 %), LDL-C (10.5 %) and the LDL-C/HDL-C ratio (18.9 %). RBO supplementation at ca. 50% total fat intake improved lipoprotein pattern in mildly hypercholesterolemic men. Methylated sterols in gamma-oryzanol are thought to be largely ineffective at inhibiting dietary cholesterol absorption, but could enhance cholesterol-lowering ability of 4-desmethylsterols. Assuming all ferulated sterols become de-ferulated in the gut, low and high gamma-oryzanolcontaining RBOs provided intestinal loads of 453 and 740 mg/d free 4-desmethylsterols, respectively. This intestinal load of 453-740 mg/d of efficacious free plant sterol equivalents had identical effects on lipoproteins.

A new rapid method to measure human platelet cholesterol: a pilot study.

PubMed

Jagroop, I Anita; Persaud, Jahm Want; Mikhailidis, Dimitri P

2011-01-01

Platelet cholesterol (PC) could be used to assess "tissue" cholesterol of patients with vascular disease. However, the methods available so far to measure PC involve a complex extraction process. We developed a rapid method to measure PC and assessed its correlation with serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C ratio, triglycerides (TG), and non-HDL-C. We assessed repeatability (20 times, 3 participants) and reproducibility (8 times, 2 participants). A group of 47 healthy participants was studied. Blood was collected to analyze serum TC, LDL-C, HDL-C, and TG. Citrated blood was used to prepare a platelet pellet. A "clear soup" was produced (by disrupting this pellet using freeze-thaw and sonication cycles) and used to measure PC. Repeatability of PC showed a coefficient of variation (CV) of 4.8%. The reproducibility of PC over a period of 2 months was CV 7.5% and 8.1% (8 measurements for 2 participants). The PC of participants with serum LDL-C >2.6 mmol/L (treatment goal recommended by the National Cholesterol Education Program Adult Treatment Panel III) was 377 ± 120 μmol/10(12) platelets (n = 25). There was a significant correlation (Spearman, correlation coefficient) of PC (n = 25) with serum LDL-C (r(s) = 0.45, P = .02), LDL-C/HDL-C (r(s) = 0.45, P = .02), TG (r(s) = 0.43, P = .03), and non-HDL-C (r(s) = 0.53, P = .007). This technique of measuring PC has the advantage of being reproducible, fast, and simpler than previous methods. Thus, it may be useful for multiple sampling when investigating changes in PC in hypercholesterolemic patients. More extensive evaluation is necessary.

Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial.

PubMed

Puska, P; Korpelainen, V; Høie, L H; Skovlund, E; Lahti, T; Smerud, K T

2002-04-01

To study whether Abacor, a product based on isolated soy protein with high and standardised levels of isoflavones and cotyledon soy fibres, was more effective in lowering total and LDL cholesterol than placebo. Randomised, placebo-controlled, double-blind, parallel group, single centre study. Primary care in Joensuu, North Karelia, Finland. Subjects were screened from the patient database of the health centre; 30 were randomised to the Abacor group and 30 subjects to placebo. Eight subjects were withdrawn, six from the active group, two from the placebo group. The preparations were given as two daily liquid supplements in addition to the subjects' regular diets for 6 weeks. Abacor showed a statistically significant lipid-lowering effect as compared to placebo, although an unexpected reduction was seen in the placebo group. The estimated difference between active treatment and placebo was 0.25 mmol/l (95% CI 0.01, 0.50; P=0.049) for total cholesterol, corresponding to reductions of 8.3 and 5.1%, respectively. The difference in reduction of LDL-cholesterol was 0.27 mmol/l (95% CI 0.06, 0.49; P=0.014) and corresponded to a reduction of 13.2% in the active treatment group, and 8.0% in the placebo group. Abacor showed a rapid onset of effect, as compared with placebo. During a wash-out period of 4 weeks after treatment, the subjects returned to pre-treatment cholesterol levels. Added to a regular diet, Abacor significantly reduced LDL-cholesterol and total cholesterol. These beneficial effects occurred within 6 weeks of treatment.

CE: Triglycerides: Do They Matter?

PubMed

Scordo, Kristine; Pickett, Kim Anne

2017-01-01

: Since the introduction of HMG-CoA reductase inhibitors, also known as statins, as an adjunct to diet in the treatment of hyperlipidemia and the greater emphasis placed on reducing low-density lipoprotein (LDL) cholesterol levels in the prevention of atherosclerosis and cardiovascular disease (CVD), there has been less focus on the value of lowering serum triglyceride levels. Many patients are aware of their "good" and "bad" cholesterol levels, but they may not be aware of their triglyceride level or of the association between high triglycerides and the development of CVD. In recent years, however, in light of the increasing incidences of obesity, insulin resistance, and type 2 diabetes, lowering triglyceride levels has gained renewed interest. In addition to the focus on lowering LDL cholesterol levels in CVD prevention, clinicians need to be aware of the role of triglycerides-their contribution to CVD, and the causes and treatment of hypertriglyceridemia.

Nonlinear associations between plasma cholesterol levels and neuropsychological function.

PubMed

Wendell, Carrington R; Zonderman, Alan B; Katzel, Leslie I; Rosenberger, William F; Plamadeala, Victoria V; Hosey, Megan M; Waldstein, Shari R

2016-11-01

Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as <70 vs. 70+) as an effect modifier. A significant quadratic effect of Total Cholesterol² × Age was identified for Logical Memory II ( b = -.0013, p = .039), such that the 70+ group performed best at high and low levels of total cholesterol than at midrange total cholesterol (U-shaped) and the <70 group performed worse at high and low levels of total cholesterol than at midrange total cholesterol (inverted U shape). Similarly, significant U- and J-shaped effects of LDL Cholesterol² × Age were identified for Visual Reproduction II ( b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis.

PubMed

Wolk, Robert; Armstrong, Ehrin J; Hansen, Peter R; Thiers, Bruce; Lan, Shuping; Tallman, Anna M; Kaur, Mandeep; Tatulych, Svitlana

Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional lipid parameters and CV risk markers in patients with psoriasis from a phase III study, OPT Pivotal 1. Patients with psoriasis were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo BID. Serum samples were collected at baseline, week 4, and week 16. Analyses included serum cholesterol levels, triglycerides, lipoproteins, lipid particles, lipid-related parameters/CV risk markers, and high-density lipoprotein (HDL) function analyses. At week 16, small concurrent increases in mean low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels were observed with tofacitinib; total cholesterol/HDL-C ratio did not change. There was no significant change in the number of small dense LDL particles, which are considered to be more atherogenic than large particles, and oxidized LDL did not increase. Paraoxonase 1 activity, linked to HDL antioxidant capacity, increased, and HDL-associated serum amyloid A, which reduces the anti-atherogenic potential of HDL, decreased. HDL capacity to promote cholesterol efflux from macrophages did not change. Lecithin-cholesterol acyltransferase activity, which is associated with reverse cholesterol transport, increased. Markers of systemic inflammation, serum amyloid A and C-reactive protein, decreased with tofacitinib. While small increases in lipid levels are observed with tofacitinib treatment in patients with psoriasis, effects on selected lipid-related parameters and other circulating CV risk biomarkers are not suggestive of an increased CV risk [NCT01276639]. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe).

PubMed

Kim, Kyung-Jin; Kim, Sang-Hyun; Yoon, Young Won; Rha, Seung-Woon; Hong, Soon-Jun; Kwak, Choong-Hwan; Kim, Weon; Nam, Chang-Wook; Rhee, Moo-Yong; Park, Tae-Ho; Hong, Taek-Jong; Park, Sungha; Ahn, Youngkeun; Lee, Namho; Jeon, Hui-Kyung; Jeon, Dong-Woon; Han, Kyoo-Rok; Moon, Keon-Woong; Chae, In-Ho; Kim, Hyo-Soo

2016-10-01

We aimed to compare the effects of fixed-dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS). This multicenter eight-week randomized double-blind phase III study evaluated the safety and efficacy of fixed-dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid-lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily). Fixed-dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed-dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non-DM or non-MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non-DM or MetS vs non-MetS patients. Fixed-dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS. © 2016 The Authors Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.

Comprehensive Evaluation of the Association of APOE Genetic Variation with Plasma Lipoprotein Traits in U.S. Whites and African Blacks

PubMed Central

Radwan, Zaheda H.; Wang, Xingbin; Waqar, Fahad; Pirim, Dilek; Niemsiri, Vipavee; Hokanson, John E.; Hamman, Richard F.; Bunker, Clareann H.; Barmada, M. Michael; Demirci, F. Yesim; Kamboh, M. Ilyas

2014-01-01

Although common APOE genetic variation has a major influence on plasma LDL-cholesterol, its role in affecting HDL-cholesterol and triglycerides is not well established. Recent genome-wide association studies suggest that APOE also affects plasma variation in HDL-cholesterol and triglycerides. It is thus important to resequence the APOE gene to identify both common and uncommon variants that affect plasma lipid profile. Here, we have sequenced the APOE gene in 190 subjects with extreme HDL-cholesterol levels selected from two well-defined epidemiological samples of U.S. non-Hispanic Whites (NHWs) and African Blacks followed by genotyping of identified variants in the entire datasets (623 NHWs, 788 African Blacks) and association analyses with major lipid traits. We identified a total of 40 sequence variants, of which 10 are novel. A total of 32 variants, including common tagSNPs (≥5% frequency) and all uncommon variants (<5% frequency) were successfully genotyped and considered for genotype-phenotype associations. Other than the established associations of APOE*2 and APOE*4 with LDL-cholesterol, we have identified additional independent associations with LDL-cholesterol. We have also identified multiple associations of uncommon and common APOE variants with HDL-cholesterol and triglycerides. Our comprehensive sequencing and genotype-phenotype analyses indicate that APOE genetic variation impacts HDL-cholesterol and triglycerides in addition to affecting LDL-cholesterol. PMID:25502880

Small dense low density lipoprotein-cholesterol and cholesterol ratios to predict arterial stiffness progression in normotensive subjects over a 5-year period.

PubMed

Li, Gang; Wu, Hui-Kun; Wu, Xiao-Wei; Cao, Zhe; Tu, Yuan-Chao; Ma, Yi; Wang, Wei-Qing; Cheng, Jian; Zhou, Zi-Hua

2018-02-12

Small dense low density lipoprotein-cholesterol (sdLDL-C), cholesterol ratios and carotid-femoral pulse wave velocity (cf-PWV) impart risk for all-cause morbidity and mortality independently of conventional cardiovascular disease (CVD) risk factors. This study was designed to identify feasible indicators for predicting arterial stiffness progression. We followed up 816 normotensive participants without diabetes or CVD for nearly 5.0 years. Cholesterol parameters, ratios and other clinical and laboratory data were collected at baseline. cf-PWV were measured at baseline and the end of follow-up. PWV progression subjects had higher levels of PWV parameters, sdLDL-C and TG/HDL-C ratio. sdLDL-C and TG/HDL-C were significantly correlated with all PWV parameters. Multiple regression models showed that sdLDL-C was closely associated with follow-up PWV (β = 0.222, p < 0.001) and △PWV (β = 0.275, p < 0.001). TG/HDL-C was only one cholesterol ratios that associated with all PWV parameters. sdLDL-C (OR = 2.070, 95%CI: 1.162 to 3.688, p = 0.014) and TG/HDL-C (OR = 1.355, 95%CI: 1.136 to 1.617, p = 0.001) could significantly determine the progression of PWV after correction for covariates. High sd-LDL-C quantiles subjects were more likely to develop arterial stiffness progression than low quantiles (Tertiles 3 vs Tertiles1, RR = 2.867, 95%CI: 1.106 to 7.434, p = 0.03). We founded that sdLDL-C and TG/HDL-C ratio can independently predict arterial stiffness progression in normotensive subjects, and high level sdLDL-C and TG/HDL-C ratio were associated with a higher risk of arterial stiffness.

Evaluation of lipid profile in adolescents during long-term use of combined oral hormonal contraceptives.

PubMed

Guazzelli, Christina Aparecida Falbo; Lindsey, Prescilla Chow; de Araújo, Fabio Fernando; Barbieri, Márcia; Petta, Carlos Alberto; Aldrighi, Jose Mendes

2005-02-01

The study evaluated the effects of the long-term use of a combined oral hormonal contraceptive containing 30 microg ethinyl estradiol and 75 microg gestodene in adolescents. Thirty-three volunteers, aged from 14 to 19 years, who used the oral contraceptive for three consecutive years, were studied. Evaluation of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides was made before use and after 1, 2 and 3 years. During the 3-year study period, total cholesterol, HDL-C, LDL-C and triglyceride levels were significantly higher than previous measurements, but average values did not exceed the normal range. Compared to the first year, the second- and third-year cholesterol, HDL-C, LDL-C and triglyceride levels were not significantly different.

Comparison of the impact of SFAs from cheese and butter on cardiometabolic risk factors: a randomized controlled trial.

PubMed

Brassard, Didier; Tessier-Grenier, Maude; Allaire, Janie; Rajendiran, Ethendhar; She, Yongbo; Ramprasath, Vanu; Gigleux, Iris; Talbot, Denis; Levy, Emile; Tremblay, Angelo; Jones, Peter Jh; Couture, Patrick; Lamarche, Benoît

2017-04-01

Background: Controversies persist concerning the association between intake of dietary saturated fatty acids (SFAs) and cardiovascular disease risk. Objective: We compared the impact of consuming equal amounts of SFAs from cheese and butter on cardiometabolic risk factors. Design: In a multicenter, crossover, randomized controlled trial, 92 men and women with abdominal obesity and relatively low HDL-cholesterol concentrations were assigned to sequences of 5 predetermined isoenergetic diets of 4 wk each separated by 4-wk washouts: 2 diets rich in SFAs (12.4-12.6% of calories) from either cheese or butter; a monounsaturated fatty acid (MUFA)-rich diet (SFAs: 5.8%, MUFAs: 19.6%); a polyunsaturated fatty acid (PUFA)-rich diet (SFAs: 5.8%, PUFAs: 11.5%); and a low-fat, high-carbohydrate diet (fat: 25%, SFAs: 5.8%). Results: Serum HDL-cholesterol concentrations were similar after the cheese and butter diets but were significantly higher than after the carbohydrate diet (+3.8% and +4.7%, respectively; P < 0.05 for both). LDL-cholesterol concentrations after the cheese diet were lower than after the butter diet (-3.3%, P < 0.05) but were higher than after the carbohydrate (+2.6%), MUFA (+5.3%), and PUFA (+12.3%) diets ( P < 0.05 for all). LDL-cholesterol concentrations after the butter diet also increased significantly (from +6.1% to +16.2%, P < 0.05) compared with the carbohydrate, MUFA, and PUFA diets. The LDL-cholesterol response to treatment was significantly modified by baseline values ( P -interaction = 0.02), with the increase in LDL cholesterol being significantly greater with butter than with cheese only among individuals with high baseline LDL-cholesterol concentrations. There was no significant difference between all diets on inflammation markers, blood pressure, and insulin-glucose homeostasis. Conclusions: The results of our study suggest that the consumption of SFAs from cheese and butter has similar effects on HDL cholesterol but differentially modifies LDL-cholesterol concentrations compared with the effects of carbohydrates, MUFAs, and PUFAs, particularly in individuals with high LDL cholesterol. In contrast, SFAs from either cheese or butter have no significant effects on several other nonlipid cardiometabolic risk factors. This trial was registered at clinicaltrials.gov as NCT02106208. © 2017 American Society for Nutrition.

Effect of VCO and olive oil on HDL, LDL, and cholesterol level of hyperglycemic Rattus Rattus Norvegicus

NASA Astrophysics Data System (ADS)

Yusuf Wachidah Yuiwarti, Enny; Rini Saraswati, Tyas; Kusdiyantini, Endang

2018-05-01

Virgin coconut oil (VCO) and olive oil are edible oil containing an antioxidant that can prevent free radicals in Rattus rattus norvegicus hypoglycemic due to the damage of pancreatic beta cell after alloxan injection. Virgin coconut oil and olive oil are fatty acids when being consumed will affect lipid metabolism particularly HDL, LDL and cholesterol in serum. This research aims to determine the effect of VCO and Olive oil on cholesterol levels in hyperglycemic rats. Research materials were twenty male Rattus rattus norvegicus. Randomized Factorial Design was used in four treatment groups including P1(control), P2 (mice injected with alloxan), P3 (mice injected with alloxan plus 0.1 ml/BW of each VCO and vitamin E) and P4 (mice injected with alloxan plus 0.1 ml/BW of each olive oil and vitamin E. Each treatment was replicated 5 times. Feed and water were provided adlibitum for four weeks. The result showed that there was no significant difference in the level of HDL serum across the treatments, but P4 had a significantly higher LDL than the other treatments. Moreover, total cholesterol was significantly increased in P4 compared to the other groups. It can be concluded that olive oil could increase the level of cholesterol and LDL in serum, while VCO did not increase the level of cholesterol and LDL so VCO more potential to maintain cholesterol in hyperglycemic Rattus rattus norvegicus.

Saturated fat, carbohydrate, and cardiovascular disease.

PubMed

Siri-Tarino, Patty W; Sun, Qi; Hu, Frank B; Krauss, Ronald M

2010-03-01

A focus of dietary recommendations for cardiovascular disease (CVD) prevention and treatment has been a reduction in saturated fat intake, primarily as a means of lowering LDL-cholesterol concentrations. However, the evidence that supports a reduction in saturated fat intake must be evaluated in the context of replacement by other macronutrients. Clinical trials that replaced saturated fat with polyunsaturated fat have generally shown a reduction in CVD events, although several studies showed no effects. An independent association of saturated fat intake with CVD risk has not been consistently shown in prospective epidemiologic studies, although some have provided evidence of an increased risk in young individuals and in women. Replacement of saturated fat by polyunsaturated or monounsaturated fat lowers both LDL and HDL cholesterol. However, replacement with a higher carbohydrate intake, particularly refined carbohydrate, can exacerbate the atherogenic dyslipidemia associated with insulin resistance and obesity that includes increased triglycerides, small LDL particles, and reduced HDL cholesterol. In summary, although substitution of dietary polyunsaturated fat for saturated fat has been shown to lower CVD risk, there are few epidemiologic or clinical trial data to support a benefit of replacing saturated fat with carbohydrate. Furthermore, particularly given the differential effects of dietary saturated fats and carbohydrates on concentrations of larger and smaller LDL particles, respectively, dietary efforts to improve the increasing burden of CVD risk associated with atherogenic dyslipidemia should primarily emphasize the limitation of refined carbohydrate intakes and a reduction in excess adiposity.

Intake of 3 Eggs per Day When Compared to a Choline Bitartrate Supplement, Downregulates Cholesterol Synthesis without Changing the LDL/HDL Ratio.

PubMed

Lemos, Bruno S; Medina-Vera, Isabel; Blesso, Christopher N; Fernandez, Maria Luz

2018-02-24

Cardiovascular disease (CVD) risk is associated with high concentrations of low-density lipoprotein cholesterol (LDL-C). The impact of dietary cholesterol on plasma lipid concentrations still remains a concern. The effects of egg intake in comparison to choline bitartrate supplement was studied in a young, healthy population. Thirty participants were enrolled for a 13-week intervention. After a 2-week run-in period, subjects were randomized to consume either 3 eggs/day or a choline bitartrate supplement (~400 mg choline for both treatments) for 4-weeks each. After a 3-week washout period, they were allocated to the alternate treatment. Dietary records, plasma lipids, apolipoproteins (apo) concentrations, and peripheral blood mononuclear cell expression of regulatory genes for cholesterol homeostasis were assessed at the end of each intervention. Dietary intakes of saturated and monounsaturated fat were higher with the consumption of eggs compared to the choline period. In addition, higher plasma concentrations of total cholesterol (7.5%), high density lipoprotein cholesterol (HDL-C) (5%) and LDL-C (8.1%) were observed with egg consumption ( p < 0.01), while no change was seen in LDL-C/HDL-C ratio, a key marker of heart disease risk. Compared to choline supplementation, intake of eggs resulted in higher concentrations of plasma apoA-I (8%) and apoE (17%) with no changes in apoB. Sterol regulatory element-binding protein 2 and 3-hydroxy-3-methylglutaryl-CoA reductase expression were lower with egg consumption by 18% and 31%, respectively ( p < 0.05), suggesting a compensation to the increased dietary cholesterol load. Therefore, dietary cholesterol from eggs appears to regulate endogenous synthesis of cholesterol in such a way that the LDL-C/HDL-C ratio is maintained.

Intake of 3 Eggs per Day When Compared to a Choline Bitartrate Supplement, Downregulates Cholesterol Synthesis without Changing the LDL/HDL Ratio

PubMed Central

Lemos, Bruno S

2018-01-01

Cardiovascular disease (CVD) risk is associated with high concentrations of low-density lipoprotein cholesterol (LDL-C). The impact of dietary cholesterol on plasma lipid concentrations still remains a concern. The effects of egg intake in comparison to choline bitartrate supplement was studied in a young, healthy population. Thirty participants were enrolled for a 13-week intervention. After a 2-week run-in period, subjects were randomized to consume either 3 eggs/day or a choline bitartrate supplement (~400 mg choline for both treatments) for 4-weeks each. After a 3-week washout period, they were allocated to the alternate treatment. Dietary records, plasma lipids, apolipoproteins (apo) concentrations, and peripheral blood mononuclear cell expression of regulatory genes for cholesterol homeostasis were assessed at the end of each intervention. Dietary intakes of saturated and monounsaturated fat were higher with the consumption of eggs compared to the choline period. In addition, higher plasma concentrations of total cholesterol (7.5%), high density lipoprotein cholesterol (HDL-C) (5%) and LDL-C (8.1%) were observed with egg consumption (p < 0.01), while no change was seen in LDL-C/HDL-C ratio, a key marker of heart disease risk. Compared to choline supplementation, intake of eggs resulted in higher concentrations of plasma apoA-I (8%) and apoE (17%) with no changes in apoB. Sterol regulatory element-binding protein 2 and 3-hydroxy-3-methylglutaryl-CoA reductase expression were lower with egg consumption by 18% and 31%, respectively (p < 0.05), suggesting a compensation to the increased dietary cholesterol load. Therefore, dietary cholesterol from eggs appears to regulate endogenous synthesis of cholesterol in such a way that the LDL-C/HDL-C ratio is maintained. PMID:29495288

[Minimal effective dose on serum cholesterol concentration and the safety evaluation of dressing containing plant sterol in Japanese subjects].

PubMed

Kurokawa, Masanori; Masuda, Yasunobu; Noda, Mitsuhiro; Marushima, Ranko; Usuda, Mika; Takeda, Sayaka; Hasegawa, Mineo; Homma, Yasuhiko; Sugano, Michihiro

2008-01-01

We examined the minimal effective dose on serum cholesterol concentration and the safety of dressing containing plant sterol in humans. EXP.1: Sixty-eight healthy Japanese males (total cholesterol (TC) > or = 170 mg/dL) were randomly divided into four groups, and were given 0, 400, 800 or 1200 mg/day of plant sterol in 15 g dressing for 4 weeks followed by the washout period of 4 weeks. Although there were no significant differences in serum TC and low-density lipoprotein cholesterol (LDL-C) concentrations among all groups after feeding plant sterol for 4 weeks, in 36 subjects with TC > or = 220 mg/dL, serum LDL-C concentration tended to reduce when received 800 or 1200 mg of plant sterol, and the difference between 0 and 1200 mg groups was statistically significant. The difference between 0 and 800 mg groups was near significant (p=0.053). Intake of 400 mg of plant sterol did not change serum LDL-C concentration. EXP.2: Twenty-one healthy Japanese subjects (TC > or = 180 mg/dL, 10 men, 11 women) were given 2400 mg/day of plant sterol in 45 g dressing for 4 weeks. Clinical data were all remained normal. These results indicated that minimal effective dose of the plant sterol on serum cholesterol concentration in healthy male subjects is around 800 mg/day, and intake of 2400 mg/day of plant sterol is regarded to be safe.

New compounds able to control hepatic cholesterol metabolism: Is it possible to avoid statin treatment in aged people?

PubMed Central

Trapani, Laura; Segatto, Marco; Pallottini, Valentina

2013-01-01

Aging is characterized by the loss of homeostasis that leads to changes in the biochemical composition of tissues, reduced ability to respond adaptively to environmental stimuli, and increased susceptibility and vulnerability to diseases including coronary artery diseases, carotid artery disease and brain vessel disease. Hypercholesterolemia is one of the primary risk factors for these pathologies, whose incidence is highly related to aging. Almost 25% of men and 42% of women older than 65 years have a serum total cholesterol level greater than 240 mg/dL. The mechanisms behind this age-related increase in plasma cholesterol are still incompletely understood, thus, the control of plasma cholesterol content in aged people is more challenging than in adults. In this review the different pharmacological approaches to reduce plasma cholesterol levels, particularly in aged people, will be discussed. In brief, current therapies are mostly based on the prescription of statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) that are pretty effective but that exert several side effects. More attention should be given to potential drug interactions, potential age-related changes in drug pharmacokinetics, adverse effects such as myopathy and competing risks when statins are prescribed to old patients. In combination or in alternative to statin therapy, other agents might be required to reduce low density lipoprotein (LDL) cholesterol levels. Among the available drugs, the most commonly prescribed are those addressed to reduce cholesterol absorption, to modulate lipoprotein lipase activity and bile acid sequestrants: even these pharmacological interventions are not exempt from side effects. The use of antioxidants or organoselenium compounds and the discovery of new proteins able to modulate exclusively LDL receptor recycling such as Proprotein convertase subtilisin kexin 9 and SEC24 offer new pharmacological approaches to selectively reduce the main causes of dyslipidemia. PMID:24432184

The effect of chronic consumption of red wine on cardiovascular disease risk factors in postmenopausal women.

PubMed

Naissides, Mary; Mamo, John C L; James, Anthony P; Pal, Sebely

2006-04-01

Moderate red wine has been shown to reduce cardiovascular disease (CVD) risk, however the effects on certain CVD risk factors are unclear. In this study we have investigated the effects of dealcoholised red wine (DRW) and full-complement red wine (RW) on several cardiovascular risk factors in mildly hypercholesterolaemic postmenopausal women. To elucidate whether the chronic consumption of red wine polyphenols improves risk factors associated with CVD in hypercholesterolaemic postmenopausal women. Forty-five hypercholesterolaemic postmenopausal women were randomly assigned to consume 400 mL/day of either water, DRW or RW for 6 weeks following a 4-week washout. Fasting measures of lipids, lipoproteins, insulin and glucose were taken at 0 and 6 weeks. DRW consumption had no effect of fasting concentrations of lipids, lipoproteins, insulin and glucose. However, chronic consumption of RW significantly reduced fasting LDL cholesterol concentrations by 8% and increased HDL cholesterol concentrations by 17% in hypercholesterolaemic postmenopausal women. Collectively, regular consumption of full-complement red wine reduces CVD risk by improving fasting lipid levels in hypercholesterolaemic postmenopausal women. This study uniquely demonstrated the LDL cholesterol-lowering effects of red wine in individuals at high CVD risk, which has not previously been shown.

Exchanging partially hydrogenated fat for palmitic acid in the diet increases LDL-cholesterol and endogenous cholesterol synthesis in normocholesterolemic women.

PubMed

Sundram, Kalyana; French, Margaret A; Clandinin, M Thomas

2003-08-01

Partial hydrogenation of oil results in fats containing unusual isomeric fatty acids characterized by cis and trans configurations. Hydrogenated fats containing trans fatty acids increase plasma total cholesterol (TC) and LDL-cholesterol while depressing HDL-cholesterol levels. Identifying the content of trans fatty acids by food labeling is overshadowed by a reluctance of health authorities to label saturates and trans fatty acids separately. Thus, it is pertinent to compare the effects of trans to saturated fatty acids using stable isotope methodology to establish if the mechanism of increase in TC and LDL-cholesterol is due to the increase in the rate of endogenous synthesis of cholesterol. Ten healthy normocholesterolemic female subjects consumed each of two diets containing approximately 30% of energy as fat for a fourweek period. One diet was high in palmitic acid (10.6% of energy) from palm olein and the other diet exchanged 5.6% of energy as partially hydrogenated fat for palmitic acid. This fat blend resulted in monounsaturated fatty acids decreasing by 4.9 % and polyunsaturated fats increasing by 2.7%. The hydrogenated fat diet treatment provided 3.1% of energy as elaidic acid. For each dietary treatment, the fractional synthesis rates for cholesterol were measured using deuterium-labeling procedures and blood samples were obtained for blood lipid and lipoprotein measurements. Subjects exhibited a higher total cholesterol and LDL-cholesterol level when consuming the diet containing trans fatty acids while also depressing the HDL-cholesterol level. Consuming the partially hydrogenated fat diet treatment increased the fractional synthesis rate of free cholesterol. Consumption of hydrogenated fats containing trans fatty acids in comparison to a mixtur e of palmitic and oleic acids increase plasma cholesterol levels apparently by increasing endogenous synthesis of cholesterol.

Cheese intake in large amounts lowers LDL-cholesterol concentrations compared with butter intake of equal fat content.

PubMed

Hjerpsted, Julie; Leedo, Eva; Tholstrup, Tine

2011-12-01

Despite its high content of saturated fatty acids, cheese does not seem to increase plasma total and LDL-cholesterol concentrations when compared with an equivalent intake of fat from butter. This effect may be due to the high calcium content of cheese, which results in a higher excretion of fecal fat. The objective was to compare the effects of diets of equal fat content rich in either hard cheese or butter or a habitual diet on blood pressure and fasting serum blood lipids, C-reactive protein, glucose, and insulin. We also examined whether fecal fat excretion differs with the consumption of cheese or butter. The study was a randomized dietary intervention consisting of two 6-wk crossover periods and a 14-d run-in period during which the subjects consumed their habitual diet. The study included 49 men and women who replaced part of their habitual dietary fat intake with 13% of energy from cheese or butter. After 6 wk, the cheese intervention resulted in lower serum total, LDL-, and HDL-cholesterol concentrations and higher glucose concentrations than did the butter intervention. Cheese intake did not increase serum total or LDL-cholesterol concentrations compared with the run-in period, during which total fat and saturated fat intakes were lower. Fecal fat excretion did not differ between the cheese and butter periods. Cheese lowers LDL cholesterol when compared with butter intake of equal fat content and does not increase LDL cholesterol compared with a habitual diet. This trial is registered at clinicaltrials.gov as NCT01140165.

The food matrix and sterol characteristics affect the plasma cholesterol lowering of phytosterol/phytostanol.

PubMed

Cusack, Laura Kells; Fernandez, Maria Luz; Volek, Jeff S

2013-11-01

Foods with added phytosterols/phytostanols (PS) are recommended to lower LDL cholesterol (LDL-c) concentrations. Manufacturers have incorporated PS into a variety of common foods. Understanding the cholesterol-lowering impact of the food matrix and the PS characteristics would maximize their success and increase the benefit to consumers. This review systematically examines whether the PS characteristics and the fatty acid composition of foods with added PS affects serum LDL-c. A total of 33 studies published between the years 1998 and 2011 inclusive of 66 individual primary variables (strata) were evaluated. The functional food matrices included margarine, mayonnaise, yogurt, milk, cheese, meat, grain, juice, and chocolate. Consistently, ≥10% reductions in LDL-c were reported when the characteristics of the food matrix included poly- and monounsaturated fatty acids known to lower LDL-c. Also, >10% mean reductions in LDL-c were reported when β-sitostanol and campestanol as well as stanol esters were used. These characteristics allow both low-fat and high-fat foods to successfully incorporate PS and significantly lower LDL-c.

Unesterified plant sterols and stanols do not affect LDL electrophoretic characteristics in hypercholesterolemic subjects.

PubMed

Charest, Amélie; Desroches, Sophie; Vanstone, Catherine A; Jones, Peter J H; Lamarche, Benoît

2004-03-01

The extent to which sterols and stanols modulate LDL particle size is unknown. We examined the effects of supplementation with unesterified plant sterols and stanols on several LDL electrophoretic characteristics. Healthy hypercholesterolemic subjects (n = 14) consumed each of four experimental diets contained plant sterols (S), plant stanols (SN), a 50:50 mixture of sterols and stanols (SSN), or cornstarch (control) in a randomized crossover design. The butter component of the diet was blended with unesterified sterols and stanols at a dose of 1.8 g/d. The LDL particles were characterized by polyacrylamide gradient gel electrophoresis of whole plasma. LDL cholesterol (LDL-C) concentrations decreased by 8.8, 13.6, and 13.1% in the S, SN, and SSN groups, respectively (P < 0.01) with a significant increase of 4.3% in the control group. None of the treatments with sterols and stanols induced significant changes in LDL peak particle diameter or in the cholesterol levels of the small LDL subfraction (<25.5 nm). The reduction in plasma LDL-C levels with SN consumption was due mainly to a decrease (P < 0.05) in the concentration of cholesterol in the large subfraction (>26.0 nm). The significant reduction in plasma LDL-C concentrations by sterol and stanol consumption in subjects was not paralleled by any beneficial changes in LDL electrophoretic characteristics.

The relationship between job stress and dyslipidemia.

PubMed

Catalina-Romero, C; Calvo, E; Sánchez-Chaparro, M A; Valdivielso, P; Sainz, J C; Cabrera, M; González-Quintela, A; Román, J

2013-03-01

To investigate whether there is an association between job stress, lipid profile and dyslipidemia diagnosis. This study used a questionnaire to evaluate job stress and lifestyle variables in 91,593 workers undergoing periodic checkups. Serum lipid levels were measured in all cases. The prevalence of job stress was 8.7% (95% CI, 8.5-8.8%). In bivariate analyses, job stress was significantly associated with previous dyslipidemia diagnosis (p < 0.001), lipid-lowering therapy (p < 0.001), and altered total-cholesterol (p = 0.001), HDL-cholesterol (p < 0.001) and LDL-cholesterol levels (p = 0.025). After adjusting for potential confounding variables, job stress was still associated with current dyslipidemia diagnosis (OR = 1.10; 95% CI, 1.04-1.17), high LDL-cholesterol (OR = 1.14; 95% CI, 1.05-1.23), low HDL-cholesterol (OR 1.08; 95% CI, 1.01-1.15), high total cholesterol/HDL-cholesterol ratio (OR 1.13; 95% CI, 1.05-1.23) and high LDL-cholesterol/HDL-cholesterol ratio (OR 1.11; 95% CI, 1.04-1.19). These results support the hypothesis of an association between job stress and lipid disturbances.

Knee osteoarthritis, dyslipidemia syndrome and exercise.

PubMed

Păstrăiguş, Carmen; Ancuţa, Codrina; Miu, Smaranda; Ancuţa, E; Chirieac, Rodica

2012-01-01

The aim of our study was to evaluate the influence of aerobic training on the dyslipedemia in patients with knee osteoarthritis (KOA). Prospective observational six-month study performed on 40 patients with KOA, fulfilling the inclusion criteria, classified according to their participation in specific aerobic training program (30 minutes/day, 5 days/ week) in two subgroups. A standard evaluation protocol was followed assessing lipid parameters (total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol levels) at baseline, three and six months. Statistical analysis was performed in SPSS 16.0, p < 0.05. Subgroup analysis has demonstrated a statistical significant improvement in plasma lipids levels in all patients performing regular aerobic training (cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol) (p < 0.05). Although the difference reported for total cholesterol, triglycerides and LDL-cholesterol after six months between subgroups was not significant (p > 0.05), the mean level of HDL-cholesterol was significantly higher in patients performing aerobic training, reaching the cardio-vascular protective levels. Regular aerobic exercise has a positive effect on plasma lipoprotein concentrations; further research is needed for the assessment of long-term effects of physical exercises for both KOA and lipid pattern.

Dietary fats do not contribute to hyperlipidemia in children and adolescents with type 1 diabetes.

PubMed

Wiltshire, Esko J; Hirte, Craig; Couper, Jennifer J

2003-05-01

To determine the relative influence of diet, metabolic control, and familial factors on lipids in children with type 1 diabetes and control subjects. We assessed fasting serum cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, lipoprotein(a), apolipoprotein (apo)-A1, and apoB in 79 children and adolescents with type 1 diabetes and 61 age- and sex-matched control subjects, together with dietary intakes using a quantitative food frequency questionnaire. Total cholesterol, LDL cholesterol, apoB, HDL cholesterol, and apoA1 were significantly higher in children with diabetes. Children with diabetes had higher percentage energy intake from complex carbohydrates (P = 0.001) and fiber intake (P = 0.02), and they had lower intake of refined sugar (P < 0.001) and percentage energy from saturated fat (P = 0.045) than control subjects. Total cholesterol (beta = 0.43, P < 0.001), LDL cholesterol (beta = 0.4, P < 0.001), and apoB (beta = 0.32, P = 0.006) correlated independently with HbA(1c) but not dietary intake. HDL cholesterol (beta = 0.24, P = 0.05) and apoA1 (beta = 0.32, P = 0.004) correlated independently with HbA(1c), and HDL cholesterol (beta = -0.34, P = 0.009) correlated with percentage energy intake from complex carbohydrates. Triglycerides correlated independently with percentage energy intake from complex carbohydrates (beta = 0.33, P = 0.01) and insulin dose (beta = 0.26, P = 0.04). Subjects with diabetes and elevated LDL (>3.35 mmol/l, >130 mg/dl), for whom dietary therapy would be recommended, had significantly higher HbA(1c) (P = 0.007), but they had higher intake of complex carbohydrates than subjects with LDL cholesterol <3.35 mmol/l. Lipid abnormalities remain common in children and adolescents with type 1 diabetes who adhere to current dietary recommendations, and they relate to metabolic control but not dietary intake.

CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL

PubMed Central

Bartuzi, Paulina; Billadeau, Daniel D.; Favier, Robert; Rong, Shunxing; Dekker, Daphne; Fedoseienko, Alina; Fieten, Hille; Wijers, Melinde; Levels, Johannes H.; Huijkman, Nicolette; Kloosterhuis, Niels; van der Molen, Henk; Brufau, Gemma; Groen, Albert K.; Elliott, Alison M.; Kuivenhoven, Jan Albert; Plecko, Barbara; Grangl, Gernot; McGaughran, Julie; Horton, Jay D.; Burstein, Ezra; Hofker, Marten H.; van de Sluis, Bart

2016-01-01

The low-density lipoprotein receptor (LDLR) plays a pivotal role in clearing atherogenic circulating low-density lipoprotein (LDL) cholesterol. Here we show that the COMMD/CCDC22/CCDC93 (CCC) and the Wiskott–Aldrich syndrome protein and SCAR homologue (WASH) complexes are both crucial for endosomal sorting of LDLR and for its function. We find that patients with X-linked intellectual disability caused by mutations in CCDC22 are hypercholesterolaemic, and that COMMD1-deficient dogs and liver-specific Commd1 knockout mice have elevated plasma LDL cholesterol levels. Furthermore, Commd1 depletion results in mislocalization of LDLR, accompanied by decreased LDL uptake. Increased total plasma cholesterol levels are also seen in hepatic COMMD9-deficient mice. Inactivation of the CCC-associated WASH complex causes LDLR mislocalization, increased lysosomal degradation of LDLR and impaired LDL uptake. Furthermore, a mutation in the WASH component KIAA0196 (strumpellin) is associated with hypercholesterolaemia in humans. Altogether, this study provides valuable insights into the mechanisms regulating cholesterol homeostasis and LDLR trafficking. PMID:26965651

Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study

PubMed Central

2013-01-01

Background Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. ANCHOR was a 12-week, phase 3 study that evaluated the efficacy and safety of IPE in patients (N = 702) with residual high fasting TG levels (≥200 and <500 mg/dL) despite having optimized low-density lipoprotein cholesterol (LDL-C) levels (≥40 and <100 mg/dL) on statin therapy. Among patients randomized to IPE (4 g/day or 2 g/day) or placebo, 514 (73%) had diabetes mellitus. Methods A post hoc subgroup analysis of the ANCHOR study was conducted to assess the effects of IPE on median placebo-adjusted percent change from baseline in efficacy end point parameters in 3 subgroups: total (all subjects with diabetes—overall median baseline glycosylated hemoglobin A1c [A1c] = 6.8%), better-controlled diabetes (below median baseline A1c), and less-controlled diabetes (above median baseline A1c). Results Baseline efficacy parameters were similar among all groups except high-sensitivity C-reactive protein (hsCRP), which was higher in the total and less-controlled diabetes groups. Compared with placebo, IPE 4 g/day significantly reduced TG, non-high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol (VLDL-C), lipoprotein-associated phospholipase A2, apolipoprotein B (Apo B), total cholesterol, high-density lipoprotein cholesterol, VLDL-TG, oxidized LDL, and remnant-like particle cholesterol in all 3 diabetes groups, LDL-C in the total diabetes group, and hsCRP in the total and less-controlled diabetes groups. Decreases in hsCRP and Apo B were much greater in patients with less-controlled diabetes. There were no significant increases in fasting plasma glucose, A1c, insulin, or homeostasis model assessment-estimated insulin resistance in any group. Conclusion IPE 4 g/day significantly improved lipid and lipid-related parameters without worsening glycemic control in patients with diabetes and mixed dyslipidemia, with possibly greater effects among those with less-controlled diabetes. Trial registration Clinicaltrials.gov Identifier NCT01047501 PMID:23835245

Cholesterol - what to ask your doctor

MedlinePlus

... your doctor; What to ask your doctor about cholesterol ... What is my cholesterol level? What should my cholesterol level be? What are HDL ("good") cholesterol and LDL ("bad") cholesterol? Does my cholesterol ...

Efficacy and tolerability of two different formulations of atorvastatin in Korean patients with hypercholesterolemia: a multicenter, prospective, randomized clinical trial.

PubMed

Lee, Ju-Hee; Kim, Sang-Hyun; Choi, Dong-Ju; Tahk, Seung-Jea; Yoon, Jung-Han; Choi, Si Wan; Hong, Taek-Jong; Kim, Hyo-Soo

2017-01-01

This study was designed to compare the efficacy and tolerability of the generic formulation (Atorva ® ) and the reference formulation (Lipitor ® ) of atorvastatin, both at a dosage of 20 mg once daily. This study was a prospective open-label, randomized controlled study. Hypercholesterolemic patients who had not achieved low-density lipoprotein (LDL) cholesterol goals according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guideline were randomized to generic formulation or reference formulation of atorvastatin. The primary end point was the percent change of blood LDL cholesterol at 8 weeks from the baseline. The secondary end points included the percent changes of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA1) levels, the percent changes of ApoB/ApoA1 and total cholesterol/HDL cholesterol ratios, and the change in high-sensitivity C-reactive protein (hsCRP) levels. The LDL cholesterol goal achievement rate according to the NCEP-ATP III guideline was also evaluated. Three hundred and seventy-six patients were randomized, and 346 patients (176 in the generic group and 170 in the reference group) completed the study. After the 8 weeks of treatment, LDL cholesterol level was significantly decreased in both the groups, and the decrement was comparable between the two groups (-43.9%±15.3% in the generic group, -43.3%±17.0% in the reference group, P =0.705). The percent changes of total cholesterol, HDL cholesterol, TG, ApoB, ApoA1, ApoB/ApoA1 ratio, total cholesterol/HDL cholesterol ratio, and hsCRP showed insignificant difference between the two groups. However, LDL cholesterol goal achievement rate was significantly higher in the generic group compared to the reference group (90.6% vs 83.0%, P =0.039) in per-protocol analysis. Adverse event rate was comparable between the two groups (12.0% vs 13.7%, P =0.804). The generic formulation of atorvastatin 20 mg was not inferior to the reference formulation of atorvastatin 20 mg in the management of hypercholesterolemia.

Efficacy and tolerability of two different formulations of atorvastatin in Korean patients with hypercholesterolemia: a multicenter, prospective, randomized clinical trial

PubMed Central

Lee, Ju-Hee; Kim, Sang-Hyun; Choi, Dong-Ju; Tahk, Seung-Jea; Yoon, Jung-Han; Choi, Si Wan; Hong, Taek-Jong; Kim, Hyo-Soo

2017-01-01

Purpose This study was designed to compare the efficacy and tolerability of the generic formulation (Atorva®) and the reference formulation (Lipitor®) of atorvastatin, both at a dosage of 20 mg once daily. Methods This study was a prospective open-label, randomized controlled study. Hypercholesterolemic patients who had not achieved low-density lipoprotein (LDL) cholesterol goals according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guideline were randomized to generic formulation or reference formulation of atorvastatin. The primary end point was the percent change of blood LDL cholesterol at 8 weeks from the baseline. The secondary end points included the percent changes of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA1) levels, the percent changes of ApoB/ApoA1 and total cholesterol/HDL cholesterol ratios, and the change in high-sensitivity C-reactive protein (hsCRP) levels. The LDL cholesterol goal achievement rate according to the NCEP-ATP III guideline was also evaluated. Results Three hundred and seventy-six patients were randomized, and 346 patients (176 in the generic group and 170 in the reference group) completed the study. After the 8 weeks of treatment, LDL cholesterol level was significantly decreased in both the groups, and the decrement was comparable between the two groups (−43.9%±15.3% in the generic group, −43.3%±17.0% in the reference group, P=0.705). The percent changes of total cholesterol, HDL cholesterol, TG, ApoB, ApoA1, ApoB/ApoA1 ratio, total cholesterol/HDL cholesterol ratio, and hsCRP showed insignificant difference between the two groups. However, LDL cholesterol goal achievement rate was significantly higher in the generic group compared to the reference group (90.6% vs 83.0%, P=0.039) in per-protocol analysis. Adverse event rate was comparable between the two groups (12.0% vs 13.7%, P=0.804). Conclusion The generic formulation of atorvastatin 20 mg was not inferior to the reference formulation of atorvastatin 20 mg in the management of hypercholesterolemia. PMID:28814835

Argan oil reduces, in rats, the high fat diet-induced metabolic effects of obesity.

PubMed

Sour, S; Belarbi, M; Sari, N; Benammar, C H; Baghdad, C H; Visioli, F

2015-04-01

Obesity is a multi-factorial disorder which is of worldwide concern. In addition to calorie control, some specific dietary components might help resolving some of the complication of obesity, by providing antioxidant and anti-inflammatory activities. We investigated the effect of argan oil supplementation on plasma lipid profile and oxidant-antioxidant status of rats with high-fat diet (HFD)-induced obesity compared with rats fed a normal diet (ND). We used an animal model of high fat diet-induced obesity to study the metabolic effects of argan oil and we measured several markers lipid and redox statuses. Consumption of a high-fat diet led to an increase in serum total cholesterol (TC), LDL-cholesterol (LDL-C), and triacylglycerols (TAG) concentrations; however, argan oil blunted the increases of TC, LDL-C and TG, glucose, and insulin. Plasma total antioxidant capacity, erythrocyte catalase and superoxide dismutase activities were lower, whereas plasma hydroperoxide, thiobarbituric acid-reacting substances, and susceptibility of LDL to copper-induced oxidation were higher in obese rats compared with normal rats. Administration of argan oil ameliorated all these indices of redox status. Proper diet and lifestyle should be foremost implemented to reduce the lipoprotein metabolism and oxidant/antioxidant status alterations brought about by obesity. In addition, argan oil reduces the metabolic effects of obesity and its use might be promoted within the context of a balanced diet. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of a moderate fat diet with and without avocados on lipoprotein particle number, size and subclasses in overweight and obese adults: a randomized, controlled trial.

PubMed

Wang, Li; Bordi, Peter L; Fleming, Jennifer A; Hill, Alison M; Kris-Etherton, Penny M

2015-01-07

Avocados are a nutrient-dense source of monounsaturated fatty acids (MUFA) that can be used to replace saturated fatty acids (SFA) in a diet to lower low density lipoprotein cholesterol (LDL-C). Well-controlled studies are lacking on the effect of avocado consumption on cardiovascular disease (CVD) risk factors. A randomized, crossover, controlled feeding trial was conducted with 45 overweight or obese participants with baseline LDL-C in the 25th to 90th percentile. Three cholesterol-lowering diets (6% to 7% SFA) were fed (5 weeks each): a lower-fat diet (LF: 24% fat); 2 moderate-fat diets (34% fat) provided similar foods and were matched for macronutrients and fatty acids: the avocado diet (AV) included one fresh Hass avocado (136 g) per day, and the moderate-fat diet (MF) mainly used high oleic acid oils to match the fatty acid content of one avocado. Compared with baseline, the reduction in LDL-C and non-high-density lipoprotein (HDL) cholesterol on the AV diet (-13.5 mg/dL, -14.6 mg/dL) was greater (P<0.05) than the MF (-8.3 mg/dL, -8.7 mg/dL) and LF (-7.4 mg/dL, -4.8 mg/dL) diets. Furthermore, only the AV diet significantly decreased LDL particle number (LDL-P, -80.1 nmol/L, P=0.0001), small dense LDL cholesterol (LDL(3+4), -4.1 mg/dL, P=0.04), and the ratio of LDL/HDL (-6.6%, P<0.0001) from baseline. Inclusion of one avocado per day as part of a moderate-fat, cholesterol-lowering diet has additional LDL-C, LDL-P, and non-HDL-C lowering effects, especially for small, dense LDL. Our results demonstrate that avocados have beneficial effects on cardio-metabolic risk factors that extend beyond their heart-healthy fatty acid profile. http://www.clinicaltrials.gov. Unique identifier: NCT01235832. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Experimental support for the effects of a probiotic/digestive enzyme supplement on serum cholesterol concentrations and the intestinal microbiome.

PubMed

Ichim, Thomas E; Patel, Amit N; Shafer, Kim A

2016-06-22

Elevated levels of blood cholesterol are associated with cardiovascular disease, a leading cause of morbidity and mortality worldwide. Current therapies for addressing elevated blood cholesterol can be inadequate, ineffective or associated with side effects; therefore, the search for additional therapies is ongoing. This study evaluated Daily Body Restore (DBR), a proprietary blend of 9 probiotic organisms of the genera Lactobacillus and Bifidobacterium, and 10 digestive enzymes, for its effects on cholesterol metabolism using an in vitro system and a mouse model. We used a murine model of hypercholesterolemia induced by a high fat diet to evaluate the effects of DBR on blood cholesterol concentrations. Hypercholesterolemic mice were supplemented with DBR in their drinking water for 8 weeks and compared to control mice given low fat diets or unsupplemented high fat diets. To evaluate the effects of DBR on the activity of gut microbiota in vitro, the Shime(®) system consisting of sequential colon reactors was supplemented with DBR for analysis of short chain fatty acid production. Analysis of hypercholesterolemic mice after 4 and 8 weeks of DBR supplementation revealed significant decreases in blood concentrations of low-density lipoprotein (LDL) and increases in high-density lipoprotein (HDL) while triglyceride concentrations were unaltered. Specifically, after 4 weeks of DBR supplementation, there was a 47 % decrease in LDL and a 32 % increase in HDL in peripheral blood compared to unsupplemented, high fat diet-fed mice. After 8 weeks of DBR treatment, LDL concentrations were dramatically reduced by 78 % and HDL was increased by 52 % relative to control mice. Addition of DBR to the Shime(®) system led to significantly increased production of propionate in colon reactors, indicative of microbial production of short chain fatty acids known to inhibit cholesterol synthesis. DBR, a probiotic and digestive enzyme supplement, lowered harmful LDL and increased HDL levels in a mouse model and also exerted in vitro effects consistent with cholesterol-lowering activity. Given the magnitude of the effects of DBR, these findings are promising for clinical implementation of DBR for treating hypercholesterolemia.

Garlic powder intake and cardiovascular risk factors: a meta-analysis of randomized controlled clinical trials

PubMed Central

Kwak, Jin Sook; Kim, Ji Yeon; Paek, Ju Eun; Lee, You Jin; Kim, Haeng-Ran; Park, Dong-Sik

2014-01-01

BACKGROUND/OBJECTIVES Although preclinical studies suggest that garlic has potential preventive effects on cardiovascular disease (CVD) risk factors, clinical trials and reports from systematic reviews or meta-analyses present inconsistent results. The contradiction might be attributed to variations in the manufacturing process that can markedly influence the composition of garlic products. To investigate this issue further, we performed a meta-analysis of the effects of garlic powder on CVD risk factors. MATERIALS/METHODS We searched PubMed, Cochrane, Science Direct and EMBASE through May 2014. A random-effects meta-analysis was performed on 22 trials reporting total cholesterol (TC), 17 trials reporting LDL cholesterol (LDL-C), 18 trials reporting HDL cholesterol (HDL-C), 4 trials reporting fasting blood glucose (FBG), 9 trials reporting systolic blood pressure (SBP) and 10 trials reporting diastolic blood pressure (DBP). RESULTS The overall garlic powder intake significantly reduced blood TC and LDL-C by -0.41 mmol/L (95% confidence interval [CI], -0.69, -0.12) (-15.83 mg/dL [95% CI, -26.64, -4.63]) and -0.21 mmol/L (95% CI, -0.40, -0.03) (-8.11 mg/dL [95% CI, -15.44, -1.16]), respectively. The mean difference in the reduction of FBG levels was -0.96 mmol/L (95% CI, -1.91, -0.01) (-17.30 mg/dL [95% CI, -34.41, -0.18]). Evidence for SBP and DBP reduction in the garlic supplementation group was also demonstrated by decreases of -4.34 mmHg (95% CI, -8.38, -0.29) and -2.36 mmHg (95% CI, -4.56, -0.15), respectively. CONCLUSIONS This meta-analysis provides consistent evidence that garlic powder intake reduces the CVD risk factors of TC, LDL-C, FBG and BP. PMID:25489404

Garlic powder intake and cardiovascular risk factors: a meta-analysis of randomized controlled clinical trials.

PubMed

Kwak, Jin Sook; Kim, Ji Yeon; Paek, Ju Eun; Lee, You Jin; Kim, Haeng-Ran; Park, Dong-Sik; Kwon, Oran

2014-12-01

Although preclinical studies suggest that garlic has potential preventive effects on cardiovascular disease (CVD) risk factors, clinical trials and reports from systematic reviews or meta-analyses present inconsistent results. The contradiction might be attributed to variations in the manufacturing process that can markedly influence the composition of garlic products. To investigate this issue further, we performed a meta-analysis of the effects of garlic powder on CVD risk factors. We searched PubMed, Cochrane, Science Direct and EMBASE through May 2014. A random-effects meta-analysis was performed on 22 trials reporting total cholesterol (TC), 17 trials reporting LDL cholesterol (LDL-C), 18 trials reporting HDL cholesterol (HDL-C), 4 trials reporting fasting blood glucose (FBG), 9 trials reporting systolic blood pressure (SBP) and 10 trials reporting diastolic blood pressure (DBP). The overall garlic powder intake significantly reduced blood TC and LDL-C by -0.41 mmol/L (95% confidence interval [CI], -0.69, -0.12) (-15.83 mg/dL [95% CI, -26.64, -4.63]) and -0.21 mmol/L (95% CI, -0.40, -0.03) (-8.11 mg/dL [95% CI, -15.44, -1.16]), respectively. The mean difference in the reduction of FBG levels was -0.96 mmol/L (95% CI, -1.91, -0.01) (-17.30 mg/dL [95% CI, -34.41, -0.18]). Evidence for SBP and DBP reduction in the garlic supplementation group was also demonstrated by decreases of -4.34 mmHg (95% CI, -8.38, -0.29) and -2.36 mmHg (95% CI, -4.56, -0.15), respectively. This meta-analysis provides consistent evidence that garlic powder intake reduces the CVD risk factors of TC, LDL-C, FBG and BP.

A randomized controlled trial of the effects of aerobic dance training on blood lipids among individuals with hypertension on a thiazide.

PubMed

Maruf, Fatai A; Akinpelu, Aderonke O; Salako, Babatunde L

2014-12-01

Hypertension is associated with dyslipidemia. Thiazides adversely affect serum lipid levels in hypertensives. There is currently a dearth of information on benefits of aerobic exercise training on serum lipid levels in individuals on thiazides and this study aimed at bridging this gap in knowledge. This randomized-controlled trial involved 120 newly-diagnosed adults with essential hypertension (≥65 years). They were treated with 50 mg of hydrochlorothiazide + 5 mg of hydrochloride amiloride and 5 or 10 mg of amlodipine for 4-6 weeks before they were randomly assigned into exercise group (EG) and control croup (CG). Only EG underwent 12-week aerobic dance training at 50-70 % of heart rate reserve three times per week. Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglyceride and total cholesterol were measured and recorded at baseline and post-study. Eighty-eight (45 in EG and 43 in CG) of 120 participants randomly assigned to groups completed the study. Systolic (p = 0.370) and diastolic (p = 0.771) blood pressures (BP) were similar between the two groups at baseline. Systolic (p < 0.001) and diastolic (p < 0.001) BPs reduced significantly in exercise and control groups. LDL-C (from 120.10 ± 33.41 to 110.50 ± 31.68 mg/dl; p = 0.037) and triglyceride (from 117.49 ± 45.12 to 100.63 ± 35.42 mg/dl; p = 0.002) decreased in EG post-study but no significant between-group differences were observed. Although, LDL-C and triglyceride are reduced after aerobic dance training, they were not any more than without it. Aerobic dance training has favorable effects on LDL-C, triglyceride, and systolic and diastolic BP in individuals with hypertension on a thiazide.

Low-density lipoprotein cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidaemia: the HIJ-PROPER study, a prospective, open-label, randomized trial.

PubMed

Hagiwara, Nobuhisa; Kawada-Watanabe, Erisa; Koyanagi, Ryo; Arashi, Hiroyuki; Yamaguchi, Junichi; Nakao, Koichi; Tobaru, Tetsuya; Tanaka, Hiroyuki; Oka, Toshiaki; Endoh, Yasuhiro; Saito, Katsumi; Uchida, Tatsuro; Matsui, Kunihiko; Ogawa, Hiroshi

2017-08-01

To elucidate the effects of intensive LDL-C lowering treatment with a standard dose of statin and ezetimibe in patients with dyslipidaemia and high risk of coronary events, targeting LDL-C less than 70 mg/dL (1.8 mmol/L), compared with standard LDL-C lowering lipid monotherapy targeting less than 100 mg/dL (2.6 mmol/L). The HIJ-PROPER study is a prospective, randomized, open-label trial to assess whether intensive LDL-C lowering with standard-dose pitavastatin plus ezetimibe reduces cardiovascular events more than standard LDL-C lowering with pitavastatin monotherapy in patients with acute coronary syndrome (ACS) and dyslipidaemia. Patients were randomized to intensive lowering (target LDL-C < 70 mg/dL [1.8 mmol/L]; pitavastatin plus ezetimibe) or standard lowering (target LDL-C 90 mg/dL to 100 mg/dL [2.3-2.6 mmol/L]; pitavastatin monotherapy). The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischaemia-driven revascularization. Between January 2010 and April 2013, 1734 patients were enroled at 19 hospitals in Japan. Patients were followed for at least 36 months. Median follow-up was 3.86 years. Mean follow-up LDL-C was 65.1 mg/dL (1.68 mmol/L) for pitavastatin plus ezetimibe and 84.6 mg/dL (2.19 mmol/L) for pitavastatin monotherapy. LDL-C lowering with statin plus ezetimibe did not reduce primary endpoint occurrence in comparison with standard statin monotherapy (283/864, 32.8% vs. 316/857, 36.9%; HR 0.89, 95% CI 0.76-1.04, P = 0.152). In, ACS patients with higher cholesterol absorption, represented by elevated pre-treatment sitosterol, was associated with significantly lower incidence of the primary endpoint in the statin plus ezetimibe group (HR 0.71, 95% CI 0.56-0.91). Although intensive lowering with standard pitavastatin plus ezetimibe showed no more cardiovascular benefit than standard pitavastatin monotherapy in ACS patients with dyslipidaemia, statin plus ezetimibe may be more effective than statin monotherapy in patients with higher cholesterol absorption; further confirmation is needed. UMIN000002742, registered as an International Standard Randomized Controlled Trial. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology

Effect of short-term low- and high-fat diets on low-density lipoprotein particle size in normolipidemic subjects.

PubMed

Guay, Valérie; Lamarche, Benoît; Charest, Amélie; Tremblay, André J; Couture, Patrick

2012-01-01

High-fat, low-carbohydrate diets have been shown to raise plasma cholesterol levels, an effect associated with the formation of large low-density lipoprotein (LDL) particles. However, the impact of dietary intervention on time-course changes in LDL particle size has not been investigated. To test whether a short-term dietary intervention affects LDL particle size, we conducted a randomized, double-blind, crossover study using an intensive dietary modification in 12 nonobese healthy men with normal plasma lipid profile. Participants were subjected to 2 isocaloric 3-day diets: high-fat diet (37% energy from fat and 50% from carbohydrates) and low-fat diet (25% energy from fat and 62% from carbohydrates). Plasma lipid levels and LDL particle size were assessed on fasting blood samples after 3 days of feeding on each diet. The LDL particles were characterized by polyacrylamide gradient gel electrophoresis. Compared with the low-fat diet, plasma cholesterol, LDL cholesterol, and high-density lipoprotein cholesterol were significantly increased (4.45 vs 4.78 mmol/L, P = .04; 2.48 vs 2.90 mmol/L, P = .005; and 1.29 vs 1.41 mmol/L, P = .005, respectively) following the 3-day high-fat diet. Plasma triglycerides and fasting apolipoprotein B-48 levels were significantly decreased after the high-fat diet compared with the low-fat diet (1.48 vs 1.01 mmol/L, P = .0003 and 9.6 vs 5.5 mg/L, P = .008, respectively). The high-fat diet was also associated with a significant increase in LDL particle size (255.0 vs 255.9 Å;P = .01) and a significant decrease in the proportion of small LDL particle (<255.0 Å) (50.7% vs 44.6%, P = .01). As compared with a low-fat diet, the cholesterol-raising effect of a high-fat diet is associated with the formation of large LDL particles after only 3 days of feeding. Copyright © 2012 Elsevier Inc. All rights reserved.

Esculeogenin A, a new tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting ACAT.

PubMed

Fujiwara, Yukio; Kiyota, Naoko; Hori, Masaharu; Matsushita, Sayaka; Iijima, Yoko; Aoki, Koh; Shibata, Daisuke; Takeya, Motohiro; Ikeda, Tsuyoshi; Nohara, Toshihiro; Nagai, Ryoji

2007-11-01

We recently identified esculeoside A, a new spirosolane-type glycoside, with a content in tomatoes that is 4-fold higher than that of lycopene. In the present study, we examined the effects of esculeoside A and esculeogenin A, a new aglycon of esculeoside A, on foam cell formation in vitro and atherogenesis in apoE-deficient mice. Esculeogenin A significantly inhibited the accumulation of cholesterol ester (CE) induced by acetylated low density lipoprotein (acetyl-LDL) in human monocyte-derived macrophages (HMDM) in a dose-dependent manner without inhibiting triglyceride accumulation, however, it did not inhibit the association of acetyl-LDL to the cells. Esculeogenin A also inhibited CE formation in Chinese hamster ovary cells overexpressing acyl-coenzymeA (CoA): cholesterol acyl-transferase (ACAT)-1 or ACAT-2, suggesting that esculeogenin A suppresses the activity of both ACAT-1 and ACAT-2. Furthermore, esculeogenin A prevented the expression of ACAT-1 protein, whereas that of SR-A and SR-BI was not suppressed. Oral administration of esculeoside A to apoE-deficient mice significantly reduced the levels of serum cholesterol, triglycerides, LDL-cholesterol, and the areas of atherosclerotic lesions without any detectable side effects. Our study provides the first evidence that purified esculeogenin A significantly suppresses the activity of ACAT protein and leads to reduction of atherogenesis.

Common low-density lipoprotein receptor p.G116S variant has a large effect on plasma low-density lipoprotein cholesterol in circumpolar inuit populations.

PubMed

Dubé, Joseph B; Wang, Jian; Cao, Henian; McIntyre, Adam D; Johansen, Christopher T; Hopkins, Scarlett E; Stringer, Randa; Hosseinzadeh, Siyavash; Kennedy, Brooke A; Ban, Matthew R; Young, T Kue; Connelly, Philip W; Dewailly, Eric; Bjerregaard, Peter; Boyer, Bert B; Hegele, Robert A

2015-02-01

Inuit are considered to be vulnerable to cardiovascular disease because their lifestyles are becoming more Westernized. During sequence analysis of Inuit individuals at extremes of lipid traits, we identified 2 nonsynonymous variants in low-density lipoprotein receptor (LDLR), namely p.G116S and p.R730W. Genotyping these variants in 3324 Inuit from Alaska, Canada, and Greenland showed they were common, with allele frequencies 10% to 15%. Only p.G116S was associated with dyslipidemia: the increase in LDL cholesterol was 0.54 mmol/L (20.9 mg/dL) per allele (P=5.6×10(-49)), which was >3× larger than the largest effect sizes seen with other common variants in other populations. Carriers of p.G116S had a 3.02-fold increased risk of hypercholesterolemia (95% confidence interval, 2.34-3.90; P=1.7×10(-17)), but did not have classical familial hypercholesterolemia. In vitro, p.G116S showed 60% reduced ligand-binding activity compared with wild-type receptor. In contrast, p.R730W was associated with neither LDL cholesterol level nor altered in vitro activity. LDLR p.G116S is thus unique: a common dysfunctional variant in Inuit whose large effect on LDL cholesterol may have public health implications. © 2014 American Heart Association, Inc.

Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

PubMed

Xu, Dan; Luo, Hanwen W; Hu, Wen; Hu, Shuwei W; Yuan, Chao; Wang, Guihua H; Zhang, Li; Yu, Hong; Magdalou, Jacques; Chen, Liaobin B; Wang, Hui

2018-05-02

Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20. Female rat offspring were euthanized at GD20 and postnatal wk 12; several adult rat offspring were additionally subjected to ice-water swimming stimulation to induce chronic stress prior to death. The effects of GCs on cholesterol metabolism and epigenetic regulation were verified using the L02 cell line. The results showed that PCE induced hypercholesterolemia in adult offspring, which manifested as significantly higher levels of serum total cholesterol and LDL cholesterol (LDL-C) as well as higher ratios of LDL-C/HDL cholesterol. We further found that the cholesterol levels were increased in fetal livers but were decreased in fetal blood, accompanied by increased maternal blood cholesterol levels and reduced placental cholesterol transport. Furthermore, analysis of PCE offspring in the uterus and in a postnatal basal/chronic stress state and the results of in vitro experiments showed that hepatic cholesterol metabolism underwent GC-dependent changes and was associated with cholesterol synthase via abnormalities in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) histone acetylation. We concluded that, to compensate for intrauterine placentally derived decreases in fetal blood cholesterol levels, high intrauterine GC levels activated fetal hepatic CCAAT enhancer binding protein α signaling and down-regulated Sirtuin1 expression, which mediated the high levels of histone acetylation ( via H3K9ac and H3K14ac) and expression of HMGCR. This GC-dependent cholesterol metabolism programming effect was sustained through adulthood, leading to the occurrence of hypercholesterolemia.-Xu, D., Luo, H. W., Hu, W., Hu, S. W., Yuan, C., Wang, G. H., Zhang, L., Yu, H., Magdalou, J., Chen, L. B., Wang, H. Intrauterine programming mechanism for hypercholesterolemia in prenatal caffeine-exposed female adult rat offspring.

Effect of soy protein foods on low-density lipoprotein oxidation and ex vivo sex hormone receptor activity--a controlled crossover trial.

PubMed

Jenkins, D J; Kendall, C W; Garsetti, M; Rosenberg-Zand, R S; Jackson, C J; Agarwal, S; Rao, A V; Diamandis, E P; Parker, T; Faulkner, D; Vuksan, V; Vidgen, E

2000-04-01

Plant-derived estrogen analogs (phytoestrogens) may confer significant health advantages including cholesterol reduction, antioxidant activity, and possibly a reduced cancer risk. However, the concern has also been raised that phytoestrogens may be endocrine disrupters and major health hazards. We therefore assessed the effects of soy foods as a rich source of isoflavonoid phytoestrogens on LDL oxidation and sex hormone receptor activity. Thirty-one hyperlipidemic subjects underwent two 1-month low-fat metabolic diets in a randomized crossover study. The major differences between the test and control diets were an increase in soy protein foods (33 g/d soy protein) providing 86 mg isoflavones/2,000 kcal/d and a doubling of the soluble fiber intake. Fasting blood samples were obtained at the start and at weeks 2 and 4, with 24-hour urine collections at the end of each phase. Soy foods increased urinary isoflavone excretion on the test diet versus the control (3.8+/-0.7 v 0.0+/-0.0 mg/d, P < .001). The test diet decreased both oxidized LDL measured as conjugated dienes in the LDL fraction (56+/-3 v 63+/-3 micromol/L, P < .001) and the ratio of conjugated dienes to LDL cholesterol (15.0+/-1.0 v 15.7+/-0.9, P = .032), even in subjects already using vitamin E supplements (400 to 800 mg/d). No significant difference was detected in ex vivo sex hormone activity between urine samples from the test and control periods. In conclusion, consumption of high-isoflavone foods was associated with reduced levels of circulating oxidized LDL even in subjects taking vitamin E, with no evidence of increased urinary estrogenic activity. Soy consumption may reduce cardiovascular disease risk without increasing the risk for hormone-dependent cancers.

Maternal-fetal cholesterol transport in the second half of mouse pregnancy does not involve LDL receptor-related protein 2.

PubMed

Zwier, M V; Baardman, M E; van Dijk, T H; Jurdzinski, A; Wisse, L J; Bloks, V W; Berger, R M F; DeRuiter, M C; Groen, A K; Plösch, T

2017-08-01

LDL receptor-related protein type 2 (LRP2) is highly expressed on both yolk sac and placenta. Mutations in the corresponding gene are associated with severe birth defects in humans, known as Donnai-Barrow syndrome. We here characterized the contribution of LRP2 and maternal plasma cholesterol availability to maternal-fetal cholesterol transport and fetal cholesterol levels in utero in mice. Lrp2 +/- mice were mated heterozygously to yield fetuses of all three genotypes. Half of the dams received a 0.5% probucol-enriched diet during gestation to decrease maternal HDL cholesterol. At E13.5, the dams received an injection of D7-labelled cholesterol and were provided with 1- 13 C acetate-supplemented drinking water. At E16.5, fetal tissues were collected and maternal cholesterol transport and fetal synthesis quantified by isotope enrichments in fetal tissues by GC-MS. The Lrp2 genotype did not influence maternal-fetal cholesterol transport and fetal cholesterol. However, lowering of maternal plasma cholesterol levels by probucol significantly reduced maternal-fetal cholesterol transport. In the fetal liver, this was associated with increased cholesterol synthesis rates. No indications were found for an interaction between the Lrp2 genotype and maternal probucol treatment. Maternal-fetal cholesterol transport and endogenous fetal cholesterol synthesis depend on maternal cholesterol concentrations but do not involve LRP2 in the second half of murine pregnancy. Our results suggest that the mouse fetus can compensate for decreased maternal cholesterol levels. It remains a relevant question how the delicate system of cholesterol transport and synthesis is regulated in the human fetus and placenta. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease.

PubMed

Stein, Evan A; Dufour, Robert; Gagne, Claude; Gaudet, Daniel; East, Cara; Donovan, Joanne M; Chin, Wai; Tribble, Diane L; McGowan, Mary

2012-11-06

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder leading to premature coronary artery disease. Despite statins and additional lipid-lowering therapies, many HeFH patients fail to achieve low-density lipoprotein cholesterol (LDL-C) goals. We evaluated mipomersen, an apolipoprotein B synthesis inhibitor, to further lower LDL-C in HeFH patients with coronary artery disease. This double-blind, placebo-controlled, phase 3 trial randomized patients with HeFH and coronary artery disease on maximally tolerated statin and LDL-C ≥2.6 mmol/L (≥100 mg/dL) to weekly subcutaneous mipomersen 200 mg or placebo (2:1) for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28. Safety assessments included adverse events, laboratory tests, and magnetic resonance imaging assessment of hepatic fat. Of 124 randomized patients (41 placebo, 83 mipomersen), 114 (41 placebo, 73 mipomersen) completed treatment. Mean (95% confidence interval) LDL-C decreased significantly with mipomersen (-28.0% [-34.0% to -22.1%] compared with 5.2% [-0.5% to 10.9%] increase with placebo; P<0.001). Mipomersen significantly reduced apolipoprotein B (-26.3%), total cholesterol (-19.4%), and lipoprotein(a) (-21.1%) compared with placebo (all P<0.001). No significant change occurred in high-density lipoprotein cholesterol. Adverse events included injection site reactions and influenza-like symptoms. Five mipomersen patients (6%) had 2 consecutive alanine aminotransferase values ≥3 times the upper limit of normal at least 7 days apart; none were associated with significant bilirubin increases. Hepatic fat content increased a median of 4.9% with mipomersen versus 0.4% with placebo (P<0.001). Mipomersen is an effective therapy to further reduce apolipoprotein B-containing lipoproteins, including LDL and lipoprotein(a), in HeFH patients with coronary artery disease on statins and other lipid-lowering therapy. The significance of hepatic fat and transaminase increases remains uncertain at this time. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00706849.

Dietary corn fractions reduce atherogenesis in low-density lipoprotein receptor knockout mice.

PubMed

Masisi, Kabo; Le, Khuong; Ghazzawi, Nora; Moghadasian, Mohammed H; Beta, Trust

2017-01-01

Accumulating evidence has suggested that intake of whole grains is a protective factor against pathogenesis of coronary artery disease. The exact mechanisms, however, are still not clearly understood. In this study, we hypothesized that adequate intake of corn fractions (aleurone, endosperm and germ) can modify lipid profiles in relation to atherosclerotic lesion development in low-density lipoprotein receptor knockout (LDLr-KO) mice. The purpose of the present study was to investigate the potential cardiovascular benefits of corn fractions in LDLr-KO mice through a number of biomarkers including lipid profile, and morphologic and morphometrical analysis of atherosclerotic lesions in aortic root. Four groups of male LDLr-KO mice were fed with the experimental diets supplemented with (3 treated) or without (control) 5% (wt/wt) of each of corn fractions for 10 weeks. All diets were supplemented with 0.06% (wt/wt) cholesterol. Compared with mice in the control group, atherosclerotic lesions in the aortic roots were significantly reduced (P=.003) in the mice that were fed diet supplemented with aleurone and germ fractions. This effect was associated with significant reductions in plasma total (P=.02) and LDL (P=.03) cholesterol levels, and an increase in fecal cholesterol excretion (P=.04). Furthermore, abdominal fat mass was significantly reduced by consumption of aleurone (P=.03). In summary, the consumption of aleurone and germ may help attenuate atherosclerosis by reducing plasma total and LDL cholesterol levels. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of the relationship between plasma lipids and abdominal aortic aneurysm: A Mendelian randomization study.

PubMed

Weng, Lu-Chen; Roetker, Nicholas S; Lutsey, Pamela L; Alonso, Alvaro; Guan, Weihua; Pankow, James S; Folsom, Aaron R; Steffen, Lyn M; Pankratz, Nathan; Tang, Weihong

2018-01-01

Studies have reported that higher circulating levels of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and lower of high-density lipoprotein (HDL) cholesterol may be associated with increased risk of abdominal aortic aneurysm (AAA). Whether dyslipidemia causes AAA is still unclear and is potentially testable using a Mendelian randomization (MR) approach. We investigated the associations between blood lipids and AAA using two-sample MR analysis with SNP-lipids association estimates from a published genome-wide association study of blood lipids (n = 188,577) and SNP-AAA association estimates from European Americans (EAs) of the Atherosclerosis Risk in Communities (ARIC) study (n = 8,793). We used inverse variance weighted (IVW) MR as the primary method and MR-Egger regression and weighted median MR estimation as sensitivity analyses. Over a median of 22.7 years of follow-up, 338 of 8,793 ARIC participants experienced incident clinical AAA. Using the IVW method, we observed positive associations of plasma LDL cholesterol and TC with the risk of AAA (odds ratio (OR) = 1.55, P = 0.02 for LDL cholesterol and OR = 1.61, P = 0.01 for TC per 1 standard deviation of lipid increment). Using the MR-Egger regression and weighted median methods, we were able to validate the association of AAA risk with TC, although the associations were less consistent for LDL cholesterol due to wider confidence intervals. Triglycerides and HDL cholesterol were not associated with AAA in any of the MR methods. Assuming instrumental variable assumptions are satisfied, our finding suggests that higher plasma TC and LDL cholesterol are causally associated with the increased risk of AAA in EAs.

Serum LDL cholesterol concentration and lipoprotein electrophoresis pattern in patients with small cell lung cancer.

PubMed

Siemianowicz, K; Gminski, J; Stajszczyk, M; Wojakowski, W; Goss, M; Machalski, M; Telega, A; Brulinski, K; Magiera-Molendowska, H

2000-01-01

Epidemiological studies show that people with low level of total cholesterol have a greater risk of death due to cancer, predominantly lung cancer. The aim of our study was to evaluate serum level of LDL cholesterol and lipoprotein electrophoresis pattern in patients with small cell lung cancer and their dependence on clinical stage of the neoplasm. The studied group consisted of 34 patients with newly diagnosed small cell lung cancer and 39 healthy controls. Fasting level of LDL cholesterol was analyzed and lipoprotein electrophoresis was performed. There were no statistically significant differences of evaluated serum lipid parameters between lung cancer patients and controls, and between the clinical stages of small cell lung cancer.

Efficacy and safety of coadministration of fenofibrate and ezetimibe compared with each as monotherapy in patients with type IIb dyslipidemia and features of the metabolic syndrome: a prospective, randomized, double-blind, three-parallel arm, multicenter, comparative study.

PubMed

Ansquer, Jean-Claude; Bekaert, Ivan; Guy, Martine; Hanefeld, Markolf; Simon, Alain

2009-01-01

Patients with type IIb, or mixed, dyslipidemia have high levels of low-density lipoprotein cholesterol (LDL-C) with predominance of small dense LDL particles, high levels of triglycerides (TG), and low levels of high-density lipoprotein cholesterol (HDL-C). Fenofibrate significantly reduces TG and, more moderately, LDL-C, increases HDL-C and produces a shift from small to large LDL particle size; the main effect of ezetimibe is a reduction in LDL-C levels. Combined treatment with fenofibrate and ezetimibe may correct all the abnormalities of type IIb dyslipidemia. To assess the efficacy and safety of coadministration of fenofibrate (NanoCrystal(R)) and ezetimibe in patients with type IIb dyslipidemia and the metabolic syndrome compared with administration of fenofibrate and ezetimibe alone (ClinicalTrials.gov Identifier: NCT00349284; Study ID: CLF178P 04 01). This was a prospective, randomized, double-blind, three-parallel arm, multicenter, comparative study. Sixty ambulatory patients (mean age 56 years; 50% women, 50% men) were treated in each group. For inclusion in the study, patients were required to have LDL-C >or=4.13 mmol/L (>or=160 mg/dL), TG >or=1.71 mmol/L and or=150 mg/dL and

Antioxidants and reduced functional capacity in the elderly: findings from the Nun Study.

PubMed

Snowdon, D A; Gross, M D; Butler, S M

1996-01-01

This study investigated the relationship of plasma antioxidants to reduced functional capacity in the elderly. A hallmark of reduced functional capacity in the elderly is dependence in self-care (i.e., requiring assistance with bathing, walking, dressing, standing, toileting, and feeding). This relationship was assessed in a cross-sectional study of 88 Catholic sisters (nuns). These 77- to 98-year-old women lived in the same building, ate food prepared in the same kitchen, and had all nursing services provided by the same staff. In 1993, ability to perform self-care was assessed, and blood was drawn to determine plasma carotenoids (lycopene, beta carotene, alpha carotene, zeaxanthin and lutein combined, and beta cryptoxanthin) and alpha tocopherol. Dependence in self-care had a strong negative association with lycopene, but was not clearly related to other carotenoids or alpha tocopherol. Results from age-adjusted least squares regression indicated that a 30 micrograms/dl decrease in lycopene was associated with 2.4 additional dependencies in self-care (95% confidence interval = 1.5, 3.3; p < .001). Lycopene's relationship to dependence was modified by plasma LDL-cholesterol, the predominant carrier of lycopene in the blood. Women with low lycopene and low LDL-cholesterol had 3.6 dependencies (95% confidence interval = 3.1, 4.2; p < .001), compared to 1.0 dependency (95% confidence interval = 0.3, 1.8) in those with high lycopene and low LDL-cholesterol. This is the first study to report an association between lycopene and functional status. This finding needs to be replicated in other human and animal studies before the association is accepted as real.

Plant sterols and stanols in the treatment of dyslipidemia: new insights into targets and mechanisms related to cardiovascular risk.

PubMed

Baumgartner, Sabine; Mensink, Ronald P; Plat, Jogchum

2011-01-01

Plant sterols and stanols are naturally occurring constituents of plants and as such normal components of our daily diet. The consumption of foods enriched in plant sterols and stanols may help to reduce low-density lipoprotein cholesterol (LDL-C) concentrations. Meta-analyses have shown that consuming approximately 2.5 g plant sterols or stanols per day lowers serum LDL-C concentrations up to 10%, with little additional benefit achieved at higher intakes. However, recent studies evaluating plant stanol intakes up to 9 g/d have indicated that LDL-C concentrations can be reduced up to 17%, which suggests that more pronounced reductions can be achieved at higher intakes. Studies describing effects of high plant sterol intakes on serum LDL-C concentrations are not consistent. Besides the effects of higher than advocated intakes on serum LDL-C concentrations, several topics will be discussed in this review. First, besides the well-characterized effect of plant sterols and stanols on serum LDL-C concentrations, evidence is now emerging of their effects on triacylglycerol metabolism, which makes them highly attractive for interventions in metabolic syndrome-like populations. Secondly, there is an ongoing debate whether increased plant sterol concentrations are associated with an increased cardiovascular disease risk or not. For this there are at least two possible explanations. First, the potential atherogenicity of increased plant sterol concentrations might be ascribed to the formation of plant sterol oxidation products (so-called oxyphytosterols) or secondly, elevated serum plant sterol concentrations should only be seen as surrogate markers for characterizing subjects with high intestinal cholesterol absorption. Finally, we discuss recent studies, which suggest that plant sterols and stanols can improve endothelial dysfunction in subjects at risk, although evidence is limited and more research is needed.

Intake of up to 3 Eggs/Day Increases HDL Cholesterol and Plasma Choline While Plasma Trimethylamine-N-oxide is Unchanged in a Healthy Population.

PubMed

DiMarco, Diana M; Missimer, Amanda; Murillo, Ana Gabriela; Lemos, Bruno S; Malysheva, Olga V; Caudill, Marie A; Blesso, Christopher N; Fernandez, Maria Luz

2017-03-01

Eggs are a source of cholesterol and choline and may impact plasma lipids and trimethylamine-N-oxide (TMAO) concentrations, which are biomarkers for cardiovascular disease (CVD) risk. Therefore, the effects of increasing egg intake (0, 1, 2, and 3 eggs/day) on these and other CVD risk biomarkers were evaluated in a young, healthy population. Thirty-eight subjects [19 men/19 women, 24.1 ± 2.2 years, body mass index (BMI) 24.3 ± 2.5 kg/m 2 ] participated in this 14-week crossover intervention. Participants underwent a 2-week washout with no egg consumption, followed by intake of 1, 2, and 3 eggs/day for 4 weeks each. Anthropometric data, blood pressure (BP), dietary records, and plasma biomarkers (lipids, glucose, choline, and TMAO) were measured during each intervention phase. BMI, waist circumference, systolic BP, plasma glucose, and plasma triacylglycerol did not change throughout the intervention. Diastolic BP decreased with egg intake (P < 0.05). Compared to 0 eggs/day, intake of 1 egg/day increased HDL cholesterol (HDL-c) (P < 0.05), and decreased LDL cholesterol (LDL-c) (P < 0.05) and the LDL-c/HDL-c ratio (P < 0.01). With intake of 2-3 eggs/day, these changes were maintained. Plasma choline increased dose-dependently with egg intake (P < 0.0001) while fasting plasma TMAO was unchanged. These results indicate that in a healthy population, consuming up to 3 eggs/day results in an overall beneficial effect on biomarkers associated with CVD risk, as documented by increased HDL-c, a reduced LDL-c/HDL-c ratio, and increased plasma choline in combination with no change in plasma LDL-c or TMAO concentrations.

Comparison of the low-density lipoprotein cholesterol target value and the preventive effect of statins in elderly patients and younger patients.

PubMed

Endo, Akihiro; Okada, Taiji; Pak, Misun; Kagawa, Yuzo; Ito, Shimpei; Sato, Hirotomo; Kageshima, Kenji; Yoshida, Yasuyuki; Tanabe, Kazuaki

2017-06-01

To assess whether the low-density lipoprotein cholesterol (LDL-C) target value and preventive effect of statins are different between elderly and younger patients. We investigated 304 patients with previous percutaneous coronary intervention who underwent coronary angiography from January 2007 to December 2016 for examination of recurrent ischemia beyond the early restenosis. Patients were classified into two groups: age ≥ 75 years (elderly group: n = 140) and < 75 years (younger group: n = 164). Relationships between the achieved LDL-C level, incidence of late coronary events, and the effectiveness of statins were evaluated. During follow-up, 179 patients underwent late coronary revascularization. Recurrent ischemia presenting as acute coronary syndrome (ACS) occurred in 83 cases. Kaplan-Meier curve analysis revealed that in the younger group, recurrent ACS was significantly lower in patients with LDL-C < 70 mg/dL than in those with LDL-C ranging from 70 to < 100 mg/dL ( P = 0.035); however, there was no difference between these in the elderly group ( P = 0.863). Instead, recurrent ACS was less frequent in patients with LDL-C ranging from 70 mg/dL to < 100 mg/dL than in those with LDL-C ≥ 100 mg/dL in the elderly group ( P = 0.033). Statin use was associated with decreased recurrent ACS ( P = 0.005); moreover, only using statins was an independent predictor in the elderly group (HR: 0.375; P = 0.007). Strict control of LDL-C to < 70 mg/dL was effective for reducing the incidence of recurrent ACS in younger patients. However, LDL-C < 100 mg/dL might be sufficient as the target value of LDL-C-lowering therapy for secondary prevention of ischemic events in Japanese elderly patients.

Acute sterol o-acyltransferase 2 (SOAT2) knockdown rapidly mobilizes hepatic cholesterol for fecal excretion.

PubMed

Marshall, Stephanie M; Gromovsky, Anthony D; Kelley, Kathryn L; Davis, Matthew A; Wilson, Martha D; Lee, Richard G; Crooke, Rosanne M; Graham, Mark J; Rudel, Lawrence L; Brown, J Mark; Temel, Ryan E

2014-01-01

The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE). We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD), the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ∼ 2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion.

Association of CETP Gene Variants With Risk for Vascular and Nonvascular Diseases Among Chinese Adults

PubMed Central

Bennett, Derrick A.; Holmes, Michael V.; Boxall, Ruth; Guo, Yu; Bian, Zheng; Yang, Ling; Sansome, Sam; Chen, Yiping; Du, Huaidong; Yu, Canqing; Hacker, Alex; Reilly, Dermot F.; Tan, Yunlong; Hill, Michael R.; Chen, Junshi; Peto, Richard; Shen, Hongbing; Collins, Rory; Clarke, Robert; Li, Liming; Walters, Robin G.; Chen, Zhengming

2017-01-01

Importance Increasing levels of high-density lipoprotein (HDL) cholesterol through pharmacologic inhibition of cholesteryl ester transfer protein (CETP) is a potentially important strategy for prevention and treatment of cardiovascular disease (CVD). Objective To use genetic variants in the CETP gene to assess potential risks and benefits of lifelong lower CETP activity on CVD and other outcomes. Design, Setting, and Participants This prospective biobank study included 151 217 individuals aged 30 to 79 years who were enrolled from 5 urban and 5 rural areas of China from June 25, 2004, through July 15, 2008. All participants had baseline genotype data, 17 854 of whom had lipid measurements and 4657 of whom had lipoprotein particle measurements. Median follow-up of 9.2 years (interquartile range, 8.2-10.1 years) was completed January 1, 2016, through linkage to health insurance records and death and disease registries. Exposures Five CETP variants, including an East Asian loss-of-function variant (rs2303790), combined in a genetic score weighted to associations with HDL cholesterol levels. Main Outcomes and Measures Baseline levels of lipids and lipoprotein particles, cardiovascular risk factors, incidence of carotid plaque and predefined major vascular and nonvascular diseases, and a phenome-wide range of diseases. Results Among the 151 217 individuals included in this study (58.4% women and 41.6% men), the mean (SD) age was 52.3 (10.9) years. Overall, the mean (SD) low-density lipoprotein (LDL) cholesterol level was 91 (27) mg/dL; HDL cholesterol level, 48 (12) mg/dL. CETP variants were strongly associated with higher concentrations of HDL cholesterol (eg, 6.1 [SE, 0.4] mg/dL per rs2303790-G allele; P = 9.4 × 10−47) but were not associated with lower LDL cholesterol levels. Within HDL particles, cholesterol esters were increased and triglycerides reduced, whereas within very low-density lipoprotein particles, cholesterol esters were reduced and triglycerides increased. When scaled to 10-mg/dL higher levels of HDL cholesterol, the CETP genetic score was not associated with occlusive CVD (18 550 events; odds ratio [OR], 0.98; 95% CI, 0.91-1.06), major coronary events (5767 events; OR, 1.08; 95% CI, 0.95-1.22), myocardial infarction (3118 events; OR, 1.14; 95% CI, 0.97-1.35), ischemic stroke (13 759 events; OR, 0.94; 95% CI, 0.86-1.02), intracerebral hemorrhage (6532 events; OR, 0.94; 95% CI, 0.83-1.06), or other vascular diseases or carotid plaque. Similarly, rs2303790 was not associated with any vascular diseases or plaque. No associations with nonvascular diseases were found other than an increased risk for eye diseases with rs2303790 (4090 events; OR, 1.43; 95% CI, 1.13-1.80; P = .003). Conclusions and Relevance CETP variants were associated with altered HDL metabolism but did not lower LDL cholesterol levels and had no significant association with risk for CVD. These results suggest that in the absence of reduced LDL cholesterol levels, increasing HDL cholesterol levels by inhibition of CETP may not confer significant benefits for CVD. PMID:29141072

Validation of the Martin Method for Estimating Low-Density Lipoprotein Cholesterol Levels in Korean Adults: Findings from the Korea National Health and Nutrition Examination Survey, 2009-2011

PubMed Central

Lee, Jongseok; Jang, Sungok; Son, Heejeong

2016-01-01

Despite the importance of accurate assessment for low-density lipoprotein cholesterol (LDL-C), the Friedewald formula has primarily been used as a cost-effective method to estimate LDL-C when triglycerides are less than 400 mg/dL. In a recent study, an alternative to the formula was proposed to improve estimation of LDL-C. We evaluated the performance of the novel method versus the Friedewald formula using a sample of 5,642 Korean adults with LDL-C measured by an enzymatic homogeneous assay (LDL-CD). Friedewald LDL-C (LDL-CF) was estimated using a fixed factor of 5 for the ratio of triglycerides to very-low-density lipoprotein cholesterol (TG:VLDL-C ratio). However, the novel LDL-C (LDL-CN) estimates were calculated using the N-strata-specific median TG:VLDL-C ratios, LDL-C5 and LDL-C25 from respective ratios derived from our data set, and LDL-C180 from the 180-cell table reported by the original study. Compared with LDL-CF, each LDL-CN estimate exhibited a significantly higher overall concordance in the NCEP-ATP III guideline classification with LDL-CD (p< 0.001 for each comparison). Overall concordance was 78.2% for LDL-CF, 81.6% for LDL-C5, 82.3% for LDL-C25, and 82.0% for LDL-C180. Compared to LDL-C5, LDL-C25 significantly but slightly improved overall concordance (p = 0.008). LDL-C25 and LDL-C180 provided almost the same overall concordance; however, LDL-C180 achieved superior improvement in classifying LDL-C < 70 mg/dL compared to the other estimates. In subjects with triglycerides of 200 to 399 mg/dL, each LDL-CN estimate showed a significantly higher concordance than that of LDL-CF (p< 0.001 for each comparison). The novel method offers a significant improvement in LDL-C estimation when compared with the Friedewald formula. However, it requires further modification and validation considering the racial differences as well as the specific character of the applied measuring method. PMID:26824910

Sebelipase alfa improves atherogenic biomarkers in adults and children with lysosomal acid lipase deficiency.

PubMed

Wilson, Don P; Friedman, Mark; Marulkar, Sachin; Hamby, Tyler; Bruckert, Eric

Measures of atherogenic cholesterol, with and without concomitant use of lipid-lowering medications (LLMs), are reported with up to 52 weeks of sebelipase alfa treatment in children and adults with lysosomal acid lipase deficiency (LAL-D) participating in the phase 3 Acid Lipase Replacement Investigating Safety and Efficacy study (NCT01757184). To examine the effects of sebelipase alfa on levels of atherogenic biomarkers in the Acid Lipase Replacement Investigating Safety and Efficacy study. Data were prospectively collected for LDL particle (LDL-P) number, LDL-C, HDL-C, apolipoprotein B (apoB), apolipoprotein A1 (apoA1), and LDL-P size. Differences at week 20 between the sebelipase alfa and placebo groups were assessed for the overall LAL-D cohort and for patients receiving and not receiving LLMs. Changes from baseline after up to 52 weeks of treatment were also calculated for the overall cohort and separately for patients receiving and not receiving LLMs. Baseline values for LDL-C, LDL-P number, and apoB were elevated while HDL-C and apoA1 were low. Treatment with sebelipase alfa for 20 weeks significantly improved atherogenic measures compared with placebo irrespective of LLM usage. The reduction in LDL-C with sebelipase alfa was associated with a reduction in the LDL-P number. Treatment for up to 52 weeks was associated with sustained improvements of LDL-P, LDL-C, HDL-C, apoB, and apoA1, regardless of LLM use. Patients with LAL-D have high atherogenic risk. It is essential to address the underlying LAL deficiency to restore cholesterol homeostasis in LAL-D patients, as treatment with sebelipase alfa improves atherogenic measures regardless of LLM use and for a sustained period. Sebelipase alfa appears to reduce LDL-C by decreasing the LDL-P number, suggesting improvement in cardiovascular disease risk in LAL-D patients. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Accumulation of cholesterol and increased demand for zinc in serum-deprived RPE cells

PubMed Central

Mishra, Sanghamitra; Peterson, Katherine; Yin, Lili; Berger, Alan; Fan, Jianguo

2016-01-01

Purpose Having observed that confluent ARPE-19 cells (derived from human RPE) survive well in high-glucose serum-free medium (SFM) without further feeding for several days, we investigated the expression profile of RPE cells under the same conditions. Methods Expression profiles were examined with microarray and quantitative PCR (qPCR) analyses, followed by western blot analysis of key regulated proteins. The effects of low-density lipoprotein (LDL) and zinc supplementation were examined with qPCR. Immunofluorescence was used to localize the LDL receptor and to examine LDL uptake. Cellular cholesterol levels were measured with filipin binding. Expression patterns in primary fetal RPE cells were compared using qPCR. Results Microarray analyses of gene expression in ARPE-19, confirmed with qPCR, showed upregulation of lipid and cholesterol biosynthesis pathways in SFM. At the protein level, the cholesterol synthesis control factor SRBEF2 was activated, and other key lipid synthesis proteins increased. Supplementation of SFM with LDL reversed the upregulation of lipid and cholesterol synthesis genes, but not of cholesterol transport genes. The LDL receptor relocated to the plasma membrane, and LDL uptake was activated by day 5–7 in SFM, suggesting increased demand for cholesterol. Confluent ARPE-19 cells in SFM accumulated intracellular cholesterol, compared with cells supplemented with serum, over 7 days. Over the same time course in SFM, the expression of metallothioneins decreased while the major zinc transporter was upregulated, consistent with a parallel increase in demand for zinc. Supplementation with zinc reversed expression changes for metallothionein genes, but not for other zinc-related genes. Similar patterns of regulation were also seen in primary fetal human RPE cells in SFM. Conclusions ARPE-19 cells respond to serum deprivation and starvation with upregulation of the lipid and cholesterol pathways, accumulation of intracellular cholesterol, and increased demand for zinc. Similar trends are seen in primary fetal RPE cells. Cholesterol accumulation basal to RPE is a prominent feature of age-related macular degeneration (AMD), while dietary zinc is protective. It is conceivable that accumulating defects in Bruch’s membrane and dysfunction of the choriocapillaris could impede transport between RPE and vasculature in AMD. Thus, this pattern of response to serum deprivation in RPE-derived cells may have relevance for some aspects of the progression of AMD. PMID:28003730

Preparation of a Homologous (Human) Intravenous Botulinal Immune Globulin.

DTIC Science & Technology

1983-05-01

lipoprotein ( HDL ) per ml of plasma to ŗ.06 mg/ml for beta- lipoprotein (LDL). Triglyceride and cholesterol levels were intermediate within this...OF LIPOPROTEIN DURING FRACTIONATION "( HDL ) (LDL) Triglyceride Cholesterol cxLipoprotein 8 LipoproteinSample mg/ml mg/ml mg/mi m/ml IVBG-l.A:"Plasma...plasminogen, prekallikrein, triglycerides , cholesterol , alpha- lipoprotein , beta- lipoprotein , clotting factors, fibrinogen and complement

Potential effects of reclassifying CKD as a coronary heart disease risk equivalent in the US population.

PubMed

Foster, Meredith C; Rawlings, Andreea M; Marrett, Elizabeth; Neff, David; Grams, Morgan E; Kasiske, Bertram L; Willis, Kerry; Inker, Lesley A; Coresh, Josef; Selvin, Elizabeth

2014-05-01

Persons with chronic kidney disease (CKD) are at high risk for cardiovascular disease events, but are not classified as such in current US cholesterol treatment guidelines. We examined potential effects of modified guidelines in which CKD was considered a "coronary heart disease (CHD) risk equivalent" for risk stratification. Nationally representative cross-sectional study. 4,823 adults 20 years or older from the 2007-2010 National Health and Nutrition Examination Survey. Cardiovascular risk stratification based on current US cholesterol treatment guidelines and 2 simulated scenarios in which CKD stages 3-5 or CKD stages 1-5 were considered a CHD risk equivalent. Proportion of persons with low-density lipoprotein (LDL) cholesterol at levels above treatment targets and above the threshold for lipid-lowering therapy initiation, based on current guidelines and the 2 simulated scenarios. Under current guidelines, 55.1 million adults in 2010 did not achieve the target LDL cholesterol goal. Of these, 25.2 million had sufficiently elevated levels to meet recommendations for initiating lipid-lowering therapy; 12.1 million were receiving this therapy but remained above goal. When CKD stages 3-5 were considered a CHD risk equivalent, 59.2 million persons were above target LDL cholesterol goals, with 28.5 million and 13.3 million meriting therapy initiation and intensification, respectively. When CKD stages 1-5 were considered a CHD risk equivalent, 65.2 million adults were above goal, with 33.9 million and 14.4 million meriting therapy initiation and intensification, respectively. CKD and LDL cholesterol defined using a single laboratory value. Many adults in the United States currently do not meet recommended goals for LDL cholesterol levels. Modifying the current cholesterol guidelines to include CKD as a CHD risk equivalent would lead to a substantial increase in both the number of persons with levels above LDL cholesterol treatment targets and those recommended to initiate lipid-lowering therapy. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The hypocholesterolemic effect of an antacid containing aluminum hydroxide.

PubMed

Sperber, A D; Henkin, Y; Zuili, I; Bearman, J E; Shany, S

1991-12-01

To evaluate the efficacy, safety, and hypocholesterolemic effect of an aluminum hydroxide-containing antacid in hypercholesterolemic individuals. A prospective, randomized, double-masked, placebo-controlled phase of 2 months' duration, followed by an open-design treatment phase of 2 months' duration and a washout phase of 2 months' duration. Family practice clinics of two rural communities (kibbutzim) in Israel. Fifty-six men and women with hypercholesterolemia (type IIa or IIb). Fifty individuals completed the study. After 2 months of dietary modification (low-fat, low-cholesterol diet), the participants were randomized into two matched groups. Group 1 (28 participants) was treated for 2 months with a chewable antacid tablet containing simethicone, magnesium hydroxide, and 113 mg of aluminum hydroxide per tablet, at a dose of two tablets four times daily. Group 2 (22 participants) was given a similar number of placebo tablets for 2 months. During the following 2 months, both groups received the antacid at the above dose. Lipoprotein levels were evaluated at baseline and every 2 months thereafter for 6 months. Compared with pretreatment levels, Group 1 experienced a decrease in low-density lipoprotein cholesterol (LDL-C) of 9.8% after 2 months (p less than 0.001) and 18.5% after 4 months (p less than 0.001). Compared with Group 2, the decrease in LDL-C in Group 1 was 6.2% at the end of the 2-month double-masked, placebo phase. Although the high-density lipoprotein cholesterol (HDL-C) was also reduced in Group 1 at the end of 4 months of therapy (10.2%), the HDL-C/LDL-C ratio increased by 13% during the same interval (p less than 0.05). The treatment was well tolerated, with minimal side effects. An aluminum hydroxide-containing antacid reduces LDL-C in hypercholesterolemic individuals. Although HDL-C was also reduced to a lesser extent, the overall atherogenic index was improved. Further studies should be conducted to evaluate the long-term safety and efficacy of antacids containing aluminum hydroxide in hypercholesterolemic patients.

Non-cholesterol sterols in serum and endarterectomized carotid arteries after a short-term plant stanol and sterol ester challenge.

PubMed

Miettinen, T A; Nissinen, M; Lepäntalo, M; Albäck, A; Railo, M; Vikatmaa, P; Kaste, M; Mustanoja, S; Gylling, H

2011-03-01

It is not known whether dietary intake of plant stanols or sterols changes the composition of arterial sterols. Therefore, we compared serum and carotid artery cholesterol and non-cholesterol sterols after plant stanol (staest) or sterol (steest) ester feeding in endarterectomized patients. Elderly statin-treated asymptomatic patients undergoing carotid endarterectomy were randomized double-blind to consume staest (n=11) or steest (n=11) spread (2 g of stanol or sterol/day) for four weeks preoperatively. Non-cholesterol sterols from serum and carotid artery tissue were analysed with gas-liquid chromatography. Staest spread lowered serum total (17.2%), VLDL, and LDL cholesterol and serum triglycerides, while steest spread lowered serum total (13.8%) and LDL cholesterol levels from baseline (p<0.05 for all). Serum cholestanol and avenasterol were decreased in both groups, but campesterol and sitosterol were decreased by staest and increased by steest from baseline (p<0.05 from baseline and between the groups). Serum sitostanol to cholesterol ratio was increased by staest, but in arterial tissue this ratio was similar in both groups. On staest, lathosterol, campesterol, and sitosterol, and on steest sitosterol and avenasterol correlated significantly between serum and arterial tissue. Cholesterol metabolism, eg. lathosterol/campesterol, suggested that plant sterols were reduced in serum and in arterial tissue during staest. The novel observations were that plant stanol ester consumption, in contrast to plant sterols, tended to reduce carotid artery plant sterols in statin-treated patients. Furthermore, despite increased serum sitostanol contents during plant stanol ester consumption, their arterial levels were unchanged suggesting that sitostanol is not taken up into the arterial wall. Copyright © 2009 Elsevier B.V. All rights reserved.

The influence of a high level of corn oil on rat serum lipoproteins.

PubMed

Narayan, K A; McMullen, J J; Butler, D P; Wakefield, T; Calhoun, W K

1976-01-01

Although the stated requirement for linoleic acid in humans is less than 2% of the dietary calories, recently there has been considerable emphasis on the necessity to substitute dietary polyunsaturates for saturates in order to reduce serum cholesterol levels. In this study we have sought to determine the nutritional consequences of feeding a very high level of linoleate to rats. Three groups of thirty adult animals each were fed a semipurified diet consisting by weight of casein 17%; mineral mixture 5.5%; vitamin mixture in glucose 2.2%; cellulose fiber 3.0%; and corn oil 0% (group A), 10% (group B) or 40% (group C), which was provided at the expense of glucose. At the end of four weeks on the diets, blood was obtained in the fasting state from 16 rats in each group. The serum was ultracentrifugally fractionated into six classes of lipoproteins and analyzed for lipid composition and protein content. Disc gel electrophoresis using lipid and protein stains established that the various lipoprotein subclasses were reasonably free of adjacent density fractions. Although the total serum cholesterol levels were practically the same in the three groups, the cholesterol moiety of the major low density lipoproteins, LDL2 (d 1.019-1.050), but not of very low density lipoproteins, VLDL (d 1.006) or low density lipoproteins, LDL1 (d 1.006-1.019), was substantially and very significantly increased in rats fed the high level of corn oil as compared to the other groups. The concentration of the very low density lipoproteins was significantly lower in group C than in the groups A and B. The LDL2 concentration but not that of LDL1 was significantly greater in group C as compared to group A. The cholesterol/total lipid ratio was significantly greater in both LDL2 and LDL1 but not in VLDL of group C as compared with group A. The serum high density lipoproteins were relatively less influenced by the ingestion of an excessive level of corn oil at this time period. The serum lipoprotein levels as well as their lipid composition were generally similar in groups A and B and suggested that a moderate level (5%) of dietary linoleate did not cause any untoward changes in rats. On the basis of current information on the metabolism of lipoproteins, it has been proposed that the increase in rat serum LDL2 of group C reflects the status of the liver and that a large portion of the cholesterol moiety of LDL2 is perhaps derived from the liver while the protein and phospholipid portions may represent remnants of VLDL catabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Polyphenol-Rich Bilberry Ameliorates Total Cholesterol and LDL-Cholesterol when Implemented in the Diet of Zucker Diabetic Fatty Rats

PubMed Central

Brader, Lea; Overgaard, Ann; Christensen, Lars P.; Jeppesen, Per B.; Hermansen, Kjeld

2013-01-01

BACKGROUND: Bilberries and blackcurrants are nutrient sources rich in bioactive components, including dietary fibers, polyphenols, and anthocyanins, which possess potent cardiovascular protective properties. Few studies investigating the cardio-protective effects of natural components have focused on whole bilberries or blackcurrants. OBJECTIVE: The aim of this trial was to investigate whether a diet enriched with bilberries or blackcurrants has beneficial effects on glucose metabolism, lipid profile, blood pressure, and expression of genes related to glucose and lipid metabolism. METHODS: Male Zucker Diabetic Fatty (ZDF) rats (n = 48) were randomly assigned to either a control, bilberry-enriched, blackcurrant-enriched, or fiber-enriched diet for 8 weeks ad libitum. Real-time quantitative PCR analysis was performed on liver, adipose, and muscle tissue. Berry polyphenol content was determined by HPLC and LC-MS analysis. RESULTS: Bilberry enrichment reduced total (-21%, p = 0.0132) and LDL-cholesterol (-60%, p = 0.0229) levels, but increased HDL-cholesterol to a lesser extent than in controls. This may partly be due to the altered hepatic liver X receptor-α expression (-24%, p < 0.001). Neither bilberries nor blackcurrants influenced glucose metabolism or blood pressure. Nevertheless, transcriptional analysis implied a better conservation of hepatic and adipocyte insulin sensitivity by bilberry enrichment. Anthocyanins constituted 91% and 87% of total polyphenol content in bilberries and blackcurrants, respectively. However, total anthocyanin content (3441 mg/100 g) was 4-fold higher in bilberries than in blackcurrants (871 mg/100 g). CONCLUSIONS: Bilberry consumption ameliorated total and LDL-cholesterol levels, but not HDL-cholesterol levels in ZDF rats. Neither bilberry nor blackcurrant enrichment delayed the development of diabetes or hypertension. Thus, in rats, bilberries may be valuable as a dietary preventive agent against hypercholesterolemia, probably by virtue of their high anthocyanin content. PMID:24841880

Dietary saturated fat intake and atherosclerotic vascular disease mortality in elderly women: a prospective cohort study.

PubMed

Blekkenhorst, Lauren C; Prince, Richard L; Hodgson, Jonathan M; Lim, Wai H; Zhu, Kun; Devine, Amanda; Thompson, Peter L; Lewis, Joshua R

2015-06-01

The reduction of saturated fatty acid (SFA) intake has been the basis of long-standing dietary recommendations. However, recent epidemiologic studies have reported conflicting evidence in the relation between SFA consumption and risk of atherosclerotic vascular disease (ASVD) mortality. We investigated the association of SFA intake with serum lipid profiles and ASVD mortality in a population-based 10-y cohort study. At baseline (1998) 1469 women living in Perth, Western Australia, with a mean ± SD age of 75.2 ± 2.7 y had SFA intake measured by using a validated food-frequency questionnaire. Outcome data were serum lipids at baseline and ASVD deaths over 10 y (13,649 person-years of follow-up), retrieved from the Western Australian Data Linkage System. Other risk factors for ASVD were assessed and adjusted for in multivariable analyses. ASVD deaths occurred in 9.1% (134) of participants. The highest quartile of SFA intake (>31.28 g/d) had an ~16% cumulative mortality risk compared with ~5% in the lowest quartile (<17.39 g/d) (HR: 3.07; 95% CI: 1.54, 6.11; P = 0.001). Baseline SFA intake was associated with baseline serum total and LDL cholesterol in multivariable-adjusted models (β: 0.199, SE: 0.056, P < 0.001 and β: 0.190, SE: 0.051, P < 0.001, respectively). However, baseline serum total and LDL cholesterol were not associated with ASVD mortality. High SFA intake was associated with the risk of ASVD mortality in this population of elderly women. Although there was a strong positive association between SFA intake and LDL cholesterol, LDL cholesterol was not associated with ASVD mortality in this cohort. Nevertheless, these data support dietary advice to reduce SFA intake. © 2015 American Society for Nutrition.

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study

PubMed Central

Yamashita, Shizuya; Nakaya, Noriaki; Sasaki, Jun; Kono, Suminori

2017-01-01

Aim: We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. Methods: The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. Results: A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean ± SD changes in LDL cholesterol were −24.2% ± 14.7% with combination therapy, −16.0% ± 16.0% with fenofibrate alone, and −17.4% ± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p < 0.01 for each). The corresponding values for triglycerides were −40.0% ± 29.5%, −40.1% ± 28.7%, and −3.4% ± 32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. Conclusion: The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia. PMID:27397061

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study.

PubMed

Oikawa, Shinichi; Yamashita, Shizuya; Nakaya, Noriaki; Sasaki, Jun; Kono, Suminori

2017-01-01

We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean±SD changes in LDL cholesterol were -24.2%±14.7% with combination therapy, -16.0%±16.0% with fenofibrate alone, and -17.4%± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p＜0.01 for each). The corresponding values for triglycerides were -40.0%±29.5%, -40.1%±28.7%, and -3.4%±32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia.

Characteristics and Health Benefit of Highly Marbled Wagyu and Hanwoo Beef

PubMed Central

Gotoh, Takafumi

2016-01-01

This review addresses the characteristics and health benefit of highly marbled Wagyu and Hanwoo beef. Marbling of Wagyu and Hanwoo beef has been increased in Japan and Korea to meet domestic consumer preferences. Wagyu and Hanwoo cattle have high potential of accumulating intramuscular fat (IMF) and producing highly marbled beef. The IMF content varies depending on the feeding of time, finishing diet, and breed type. IMF increases when feeding time is increased. The rate of IMF increase in grain-fed cattle is faster than that in pasture-fed cattle. Fatty acid composition are also different depending on breeds. Highly marbled Wagyu and Hanwoo beef have higher proportions of monounsaturated fatty acid (MUFA) due to higher concentrations of oleic acid. MUFAs have little effect on total cholesterol. They are heart-healthy dietary fat because they can lower low-density lipoprotein (LDL)-cholesterol while increasing high-density lipoprotein (HDL)-cholesterol. Clinical trials have indicated that highly marbled beef does not increase LDL-cholesterol. This review also emphasizes that high oleic acid beef such as Wagyu and Hanwoo beef might be able to reduce risk factors for cardiovascular disease. PMID:28115881

Low-density lipoprotein apheresis: an evidence-based analysis.

PubMed

2007-01-01

To assess the effectiveness and safety of low-density lipoprotein (LDL) apheresis performed with the heparin-induced extracorporeal LDL precipitation (HELP) system for the treatment of patients with refractory homozygous (HMZ) and heterozygous (HTZ) familial hypercholesterolemia (FH). BACKGROUND ON FAMILIAL HYPERCHOLESTEROLEMIA: Familial hypercholesterolemia is a genetic autosomal dominant disorder that is caused by several mutations in the LDL-receptor gene. The reduced number or absence of functional LDL receptors results in impaired hepatic clearance of circulating low-density lipoprotein cholesterol (LDL-C) particles, which results in extremely high levels of LDL-C in the bloodstream. Familial hypercholesterolemia is characterized by excess LDL-C deposits in tendons and arterial walls, early onset of atherosclerotic disease, and premature cardiac death. Familial hypercholesterolemia occurs in both HTZ and HMZ forms. Heterozygous FH is one of the most common monogenic metabolic disorders in the general population, occurring in approximately 1 in 500 individuals. Nevertheless, HTZ FH is largely undiagnosed and an accurate diagnosis occurs in only about 15% of affected patients in Canada. Thus, it is estimated that there are approximately 3,800 diagnosed and 21,680 undiagnosed cases of HTZ FH in Ontario. In HTZ FH patients, half of the LDL receptors do not work properly or are absent, resulting in plasma LDL-C levels 2- to 3-fold higher than normal (range 7-15mmol/L or 300-500mg/dL). Most HTZ FH patients are not diagnosed until middle age when either they or one of their siblings present with symptomatic coronary artery disease (CAD). Without lipid-lowering treatment, 50% of males die before the age of 50 and 25% of females die before the age of 60, from myocardial infarction or sudden death. In contrast to the HTZ form, HMZ FH is rare (occurring in 1 case per million persons) and more severe, with a 6- to 8-fold elevation in plasma LDL-C levels (range 15-25mmol/L or 500-1000mg/dL). Homozygous FH patients are typically diagnosed in infancy, usually due to the presence of cholesterol deposits in the skin and tendons. The main complication of HMZ FH is supravalvular aortic stenosis, which is caused by cholesterol deposits on the aortic valve and in the ascending aorta. The average life expectancy of affected individuals is 23 to 25 years. In Ontario, it is estimated that there are 13 to 15 cases of HMZ FH. An Ontario clinical expert confirmed that 9 HMZ FH patients have been identified to date. There are 2 accepted clinical diagnostic criterion for the diagnosis of FH: the Simon Broome FH Register criteria from the United Kingdom and the Dutch Lipid Network criteria from the Netherlands. The criterion supplement cholesterol levels with clinical history, physical signs and family history. DNA-based-mutation-screening methods permit a definitive diagnosis of HTZ FH to be made. However, given that there are over 1000 identified mutations in the LDL receptor gene and that the detection rates of current techniques are low, genetic testing becomes problematic in countries with high genetic heterogeneity, such as Canada. The primary aim of treatment in both HTZ and HMZ FH is to reduce plasma LDL-C levels in order to reduce the risk of developing atherosclerosis and CAD. The first line of treatment is dietary intervention, however it alone is rarely sufficient for the treatment of FH patients. Patients are frequently treated with lipid-lowering drugs such as resins, fibrates, niacin, statins and cholesterol absorption-inhibiting drugs (ezetimibe). Most HTZ FH patients require a combination of drugs to achieve or approach target cholesterol levels. A small number of HTZ FH patients are refractory to treatment or intolerant to lipid-lowering medication. According to clinical experts, the prevalence of refractory HTZ FH in Ontario is between 1 to 5%. Using the mean of 3%, it is estimated that there are approximately 765 refractory HTZ FH patients in Ontario, of which 115 are diagnosed and 650 are undiagnosed. Drug therapy is less effective in HMZ FH patients since the effects of the majority of cholesterol-lowering drugs are mediated by the upregulation of LDL receptors, which are often absent or function poorly in HMZ FH patients. Some HMZ FH patients may still benefit from drug therapy, however this rarely reduces LDL-C levels to targeted levels. EXISTING TECHNOLOGY: PLASMA EXCHANGE An option currently available in Ontario for FH patients who do not respond to standard diet and drug therapy is plasma exchange (PE). Patients are treated with this lifelong therapy on a weekly or biweekly basis with concomitant drug therapy. Plasma exchange is nonspecific and eliminates virtually all plasma proteins such as albumin, immunoglobulins, coagulation factors, fibrinolytic factors and HDL-C, in addition to acutely lowering LDL-C by about 50%. Blood is removed from the patient, plasma is isolated, discarded and replaced with a substitution fluid. The substitution fluid and the remaining cellular components of the blood are then returned to the patient. The major limitation of PE is its nonspecificity. The removal of HDL-C prevents successful vascular remodeling of the areas stenosed by atherosclerosis. In addition, there is an increased susceptibility to infections, and costs are incurred by the need for replacement fluid. Adverse events can be expected to occur in 12% of procedures. OTHER ALTERNATIVES: Surgical alternatives for FH patients include portocaval shunt, ileal bypass and liver transplantation. However, these are risky procedures and are associated with a high morbidity rate. Results with gene therapy are not convincing to date. LDL APHERESIS An alternative to PE is LDL apheresis. Unlike PE, LDL apheresis is a selective treatment that removes LDL-C and other atherogenic lipoproteins from the blood while minimally impacting other plasma components such as HDL-C, total serum protein, albumin and immunoglobulins. As with PE, FH patients require lifelong therapy with LDL apheresis on a weekly/biweekly basis with concomitant drug therapy. HEPARIN-INDUCED EXTRACORPOREAL LDL PRECIPITATION: Heparin-induced extracorporeal LDL precipitation (HELP) is one of the most widely used methods of LDL apheresis. It is a continuous closed-loop system that processes blood extracorporeally. It operates on the principle that at a low pH, LDL and lipoprotein (a) [Lp(a)] bind to heparin and fibrinogen to form a precipitate which is then removed by filtration. In general, the total duration of treatment is approximately 2 to 3 hours. Results from early trials indicate that LDL-C concentration is reduced by 65% to 70% immediately following treatment in both HMZ and HTZ FH and then rapidly begins to rise. Typically patients with HTZ FH are treated every 2 weeks while patients with HMZ FH require weekly therapy. Heparin-induced extracorporeal LDL precipitation also produces small transient decreases in HDL-C, however levels generally return to baseline within 2 days. After several months of therapy, long-term reductions in LDL-C and increases in HDL-C have been reported. In addition to having an impact on plasma cholesterol concentrations, HELP lowers plasma fibrinogen, a risk factor for atherosclerosis, and reduces concentrations of cellular adhesion molecules, which play a role in early atherogenesis. In comparison with PE, HELP LDL apheresis does not have major effects on essential plasma proteins and does not require replacement fluid, thus decreasing susceptibility to infections. One study noted that adverse events were documented in 2.9% of LDL apheresis treatments using the HELP system compared with 12% using PE. As per the manufacturer, patients must weigh at least 30kgs to be eligible for treatment with HELP. The H.E.L.P.® System (B.Braun Medizintechnologie GmbH, Germany) has been licensed by Health Canada since December 2000 as a Class 3 medical device (Licence # 26023) for performing LDL apheresis to acutely remove LDL from the plasma of 3 high-risk patient populations for whom diet has been ineffective and maximum drug therapy has either been ineffective or not tolerated. The 3 patient groups are as follows: Functional hypercholesterolemic homozygotes with LDL-C >500 mg/dL (>13mmol/L);Functional hypercholesterolemic heterozygotes with LDL-C >300 mg/dL (>7.8mmol/L);Functional hypercholesterolemic heterozygotes with LDL-C >200 mg/dL (>5.2mmol/L) and documented CADNo other LDL apheresis system is currently licensed in Canada. The Medical Advisory Secretariat systematically reviewed the literature to assess the effectiveness and safety of LDL apheresis performed with the HELP system for the treatment of patients with refractory HMZ and HTZ FH. A standard search methodology was used to retrieve international health technology assessments and English-language journal articles from selected databases. The GRADE approach was used to systematically and explicitly make judgments about the quality of evidence and strength of recommendations. The search identified 398 articles published from January 1, 1998 to May 30, 2007. Eight studies met the inclusion criteria. Five case series, 2 case series nested within comparative studies, and one retrospective review, were included in the analysis. A health technology assessment conducted by the Alberta Heritage Foundation for Medical Research, and a review by the United States Food and Drug Administration were also included. Large heterogeneity among the studies was observed. Studies varied in inclusion criteria, baseline patient characteristics and methodology. Overall, the mean acute relative decrease in LDL-C with HELP LDL apheresis ranged from 53 to 77%. The mean acute relative reductions ranged as follows: total cholesterol (TC) 47 to 64%, HDL-C +0. (ABSTRACT TRUNCATED)

LDL-cholesterol Predicts a First CHD Event in Senior Citizens, Especially So in Those With Elevated Lipoprotein(a): Dubbo Study of the Elderly.

PubMed

Simons, Leon A; Simons, Judith; Friedlander, Yechiel; McCallum, John

2018-03-01

The analysis was designed to explore the combined effects of LDL-cholesterol and lipoprotein(a) (Lp(a)) in predicting incident coronary heart disease (CHD) in senior citizens without prior CHD. This is a prospective cohort study in Dubbo NSW which has followed 2805 men and women 60 years and older for 16 years since 1988-1989. Subjects with prior CHD (n=607) were excluded from this analysis. Incident CHD events were identified by hospital record linkage. The contributions of LDL and Lp(a) to CHD events and their combined effects were evaluated in proportional hazards regression models. There were 689 CHD events over 16 years in a cohort of 2198 men and women without prior CHD. LDL-cholesterol (corrected for cholesterol content of Lp(a)) and Lp(a) modelled in quartile categories each independently predicted CHD, but exclusively in Quartile 4 (Q4) for each parameter. Using the combination of LDL Q1 and Lp(a) Q1 as a reference group, LDL Q4 (>4.90mmol/L) most clearly predicted CHD in combination with Lp(a) Q4 (>276mg/L), hazard ratio 1.95 (95%CI 1.31-2.90). The present findings may have important practical implications in clinical management. If Lp(a) is assessed in senior citizens without prior CHD and found to be genuinely low, elevated LDL-cholesterol may not require active intervention. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

A comparison of the effects of 2 doses of soy protein or casein on serum lipids, serum lipoproteins, and plasma total homocysteine in hypercholesterolemic subjects.

PubMed

Tonstad, Serena; Smerud, Knut; Høie, Lars

2002-07-01

Studies have shown that soy protein reduces some atherogenic lipid and lipoprotein concentrations, although lipoprotein(a) concentrations may be increased. The dose response of soy protein has not been established; neither has its effect on plasma total homocysteine. Our objective was to evaluate the effect of 2 doses of soy protein on lipid, lipoprotein, and homocysteine concentrations. Four to 24 wk after being instructed to consume a lipid-lowering diet, 130 men and women with LDL-cholesterol concentrations > or = 4 mmol/L were studied during a parallel group trial in which 4 interventions were assigned randomly. Thirty grams isolated soy protein (ISP) and 10 g cotyledon fiber or 50 g ISP and 16.6 g cotyledon fiber or equivalent doses of casein and cellulose were consumed daily as a beverage for 16 wk. When the 2 groups who consumed ISP were compared with the 2 groups who consumed casein, the differences in the net changes from baseline to week 16 in the concentrations of LDL cholesterol and plasma total homocysteine were -0.26 mmol/L (95% CI: -0.43, -0.09 mmol/L; P = 0.01) and -0.8 micromol/L (-1.4, -0.2 micromol/L; P = 0.005), respectively. The effect of the ISP dose was not significant. There were no significant differences between the 2 ISP and the 2 casein groups in changes in lipoprotein(a), HDL-cholesterol, or triacylglycerol concentrations. Adding 30-50 g soy protein/d to a lipid-lowering diet significantly reduced LDL-cholesterol concentrations without increasing lipoprotein(a) concentrations. Plasma total homocysteine concentrations also decreased, suggesting a novel, possibly antiatherosclerotic effect.

A Genomic DNA Reporter Screen Identifies Squalene Synthase Inhibitors That Act Cooperatively with Statins to Upregulate the Low-Density Lipoprotein Receptor

PubMed Central

Kerr, Alastair G.; Tam, Lawrence C. S.; Hale, Ashley B.; Cioroch, Milena; Douglas, Gillian; Agkatsev, Sarina; Hibbitt, Olivia; Mason, Joseph; Holt-Martyn, James; Bataille, Carole J. R.; Wynne, Graham M.; Channon, Keith M.; Russell, Angela J.

2017-01-01

Hypercholesterolemia remains one of the leading risk factors for the development of cardiovascular disease. Many large double-blind studies have demonstrated that lowering low-density lipoprotein (LDL) cholesterol using a statin can reduce the risk of having a cardiovascular event by approximately 30%. However, despite the success of statins, some patient populations are unable to lower their LDL cholesterol to meet the targeted lipid levels, due to compliance or potency issues. This is especially true for patients with heterozygous familial hypercholesterolemia who may require additional upregulation of the low-density lipoprotein receptor (LDLR) to reduce LDL cholesterol levels below those achievable with maximal dosing of statins. Here we identify a series of small molecules from a genomic DNA reporter screen that upregulate the LDLR in mouse and human liver cell lines at nanomolar potencies (EC50 = 39 nM). Structure-activity relationship studies carried out on the lead compound, OX03771 [(E)-N,N-dimethyl-3-(4-styrylphenoxy)propan-1-amine], led to the identification of compound OX03050 [(E)-3-(4-styrylphenoxy)propan-1-ol], which had similar potency (EC50 = 26 nM) but a much-improved pharmacokinetic profile and showed in vivo efficacy. Compounds OX03050 and OX03771 were found to inhibit squalene synthase, the first committed step in cholesterol biosynthesis. These squalene synthase inhibitors were shown to act cooperatively with statins to increase LDLR expression in vitro. Overall, we demonstrated here a novel series of small molecules with the potential to be further developed to treat patients either alone or in combination with statins. PMID:28360334

Adding MUFA to a dietary portfolio of cholesterol-lowering foods reduces apoAI fractional catabolic rate in subjects with dyslipidaemia.

PubMed

Labonté, Marie-Ève; Jenkins, David J A; Lewis, Gary F; Chiavaroli, Laura; Wong, Julia M W; Kendall, Cyril W C; Hogue, Jean-Charles; Couture, Patrick; Lamarche, Benoît

2013-08-28

The present randomised parallel study assessed the impact of adding MUFA to a dietary portfolio of cholesterol-lowering foods on the intravascular kinetics of apoAI- and apoB-containing lipoproteins in subjects with dyslipidaemia. A sample of sixteen men and postmenopausal women consumed a run-in stabilisation diet for 4 weeks. Subjects were then randomly assigned to an experimental dietary portfolio either high or low in MUFA for another 4 weeks. MUFA substituted 13·0% of total energy from carbohydrate (CHO) in the high-MUFA dietary portfolio. Lipoprotein kinetics were assessed after the run-in and portfolio diets using a primed, constant infusion of [2H3]leucine and multicompartmental modelling. The high-MUFA dietary portfolio resulted in higher apoAI pool size (PS) compared with the low-MUFA dietary portfolio (15·9% between-diet difference, P¼0·03). This difference appeared to be mainly attributable to a reduction in apoAI fractional catabolic rate (FCR) after the high-MUFA diet (25·6%, P¼0·02 v. pre-diet values), with no significant change in production rate. The high-MUFA dietary portfolio tended to reduce LDL apoB100 PS compared with the low-MUFA dietary portfolio (228·5% between-diet that adding MUFA to a dietary portfolio of cholesterol-lowering foods provides the added advantage of raising HDL primarily through a reduction in HDL clearance rate. Replacing CHO with MUFA in a dietary portfolio may also lead to reductions in LDL apoB100 concentrations primarily by increasing LDL clearance rate, thus potentiating further the well-known cholesterol-lowering effect of this diet.

Is High Serum LDL/HDL Cholesterol Ratio an Emerging Risk Factor for Sudden Cardiac Death? Findings from the KIHD Study.

PubMed

Kunutsor, Setor K; Zaccardi, Francesco; Karppi, Jouni; Kurl, Sudhir; Laukkanen, Jari A

2017-06-01

Low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c), which are components of total cholesterol, have each been suggested to be linked to the risk of sudden cardiac death (SCD). However, the relationship between LDL-c/HDL-c ratio and the risk of SCD has not been previously investigated. We aimed to assess the associations of LDL-c, HDL-c, and the ratio of LDL-c/HDL-c with the risk of SCD. Serum lipoprotein concentrations were assessed at baseline in the Finnish Kuopio Ischemic Heart Disease prospective cohort study of 2,616 men aged 42-61 years at recruitment. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed. During a median follow-up of 23.0 years, a total of 228 SCDs occurred. There was no significant evidence of an association of LDL-c or HDL-c with the risk of SCD. In analyses adjusted for age, examination year, body mass index, systolic blood pressure, smoking, alcohol consumption, physical activity, years of education, diabetes, previous myocardial infarction, family history of coronary heart disease, and serum high sensitivity C-reactive protein, there was approximately a two-fold increase in the risk of SCD (HR 1.94, 95% CI 1.21-3.11; p=0.006), comparing the top (＞4.22) versus bottom (≤2.30) quintile of serum LDL-c/HDL-c ratio. In this middle-aged male population, LDL-c or HDL-c was not associated with the risk of SCD. However, a high serum LDL-c/HDL-c ratio was found to be independently associated with an increased risk of SCD. Further research is warranted to understand the mechanistic pathways underlying this association.

Association between traditional cholesterol parameters, lipoprotein particle concentration, novel biomarkers and carotid plaques in retired National Football League players.

PubMed

Virani, Salim S; Pompeii, Lisa; Lincoln, Andrew E; Dunn, Reginald E; Tucker, Andrew M; Nambi, Vijay; Nasir, Khurram; Vogel, Robert A; Boone, Jeffrey L; Roberts, Arthur J; Ballantyne, Christie M

2012-06-01

We assessed whether low-density lipoprotein particle concentration (LDL-P) and high-sensitivity C-reactive protein [hs-CRP] can identify subclinical atherosclerosis better than traditional cholesterol parameters in retired National Football League (NFL) players. It is not known whether LDL-P and the biomarker hs-CRP can identify subclinical atherosclerosis better than low-density lipoprotein cholesterol (LDL-C) or non-high-density-lipoprotein cholesterol (non-HDL-C) in retired NFL players, given high prevalence of metabolic syndrome in these players. Carotid artery plaque screening was performed with traditional lipids, LDL-P, and hs-CRP in 996 retired players. Logistic regression analyses comparing highest with the lowest quartile were performed. Carotid artery plaques were seen in 41%. LDL-C (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.06-2.59), non-HDL-C (OR 1.67, 95% CI 1.04-2.67), and LDL-P (OR 2.21, 95% CI 1.35-3.62) were associated with plaques in adjusted models. Among 187 retired players with metabolic syndrome, LDL-C (OR 1.40, 95% CI 0.53-3.72) was not associated with carotid plaques, whereas LDL-P (OR 3.71, 95% CI 1.16-11.84) and non-HDL-C (OR 2.63, 95% CI 0.91-7.63, p=0.07; borderline significant) were associated with carotid plaques. hs-CRP (OR 1.13, 95% CI 0.71-1.79) was not associated with carotid plaques. Carotid artery plaques were common in retired NFL players and were strongly associated with LDL-P, especially among those with metabolic syndrome. hs-CRP was not associated with carotid plaques in this cohort. Published by Elsevier Ireland Ltd.

Can We Eliminate Low-Density Lipoprotein Cholesterol-Related Cardiovascular Events Through More Aggressive Primary Prevention Therapy?

PubMed

Mancini, G B John; Hegele, Robert A

2018-05-01

Intravascular levels of low-density lipoprotein cholesterol (LDL-C) at approximately ≤ 0.6 mmol/L are likely to minimize, and perhaps eliminate, LDL-C-related vascular toxicity while having no effect on essential, intracellular cholesterol homeostatic pathways, according to accumulated knowledge from basic science. Randomized clinical trials, observational reports, and Mendelian randomization trials are also forcing a reconsideration of what "normal" LDL-C means. Recent trials of secondary prevention have substantiated that such levels are safe and associated with a decreased risk of cardiovascular events (CVEs) compared with patients with higher levels of LDL-C. Similarly, treatment to this low range is associated with regression and stabilization of established atherosclerosis. Primary prevention trials also show that low levels of LDL-C are safe and associated with decreased risk of CVEs through cholesterol-lowering in adults with LDL-C ≥ 3.5 mmol/L or when levels are < 3.5 mmol/L in association with other cardiovascular risks. Although there are no randomized clinical outcome trials of familial hypercholesterolemia patients, such patients have very high, lifetime risk of CVE, and registry studies show that LDL-C reduction has nearly normalized their CVE rates. The possibility of familial hypercholesterolemia should be considered if LDL-C is > 4.5 and > 4.0 mmol/L at ages 18-39 years and younger than 18 years, respectively. On the basis of these convergent and internally consistent lines of evidence, in this article we speculate on a translational paradigm aimed at eliminating LDL-C-related CVEs through aggressive primary prevention strategies that are already proven and well accepted in principle. Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Lipid Profiles and APOE4 Allele Impact Midlife Cognitive Decline in HIV-Infected Men on Antiretroviral Therapy.

PubMed

Mukerji, Shibani S; Locascio, Joseph J; Misra, Vikas; Lorenz, David R; Holman, Alex; Dutta, Anupriya; Penugonda, Sudhir; Wolinsky, Steven M; Gabuzda, Dana

2016-10-15

Dyslipidemia and apolipoprotein E4 (APOE ϵ4) allele are risk factors for age-related cognitive decline, but how these risks are modified by human immunodeficiency virus (HIV) infection is unclear. In a longitudinal nested study from the Multicenter AIDS Cohort Study, 273 HIV type 1-infected (HIV(+)) men aged 50-65 years with baseline HIV RNA <400 copies/mL and on continuous antiretroviral therapy (ART) in ≥95% of follow-up visits were matched by sociodemographic variables to 516 HIV-uninfected (HIV(-)) controls. The association between lipid markers (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), APOE genotype, and cognitive decline in HIV infection was examined using mixed-effects models. The median baseline age of participants was 51, 81% were white, and 89% had education >12 years. HIV(+) men had similar baseline total cholesterol and LDL-C, but lower HDL-C and higher triglycerides than controls (P < .001). Higher total cholesterol and LDL-C were associated with faster rates of cognitive decline (P < .01), whereas higher HDL-C attenuated decline (P = .02) in HIV(+) men. In HIV(+) men with elevated cholesterol, statin use was associated with a slower estimated rate of decline (P = .02). APOE ϵ4 genotype accelerated cognitive decline in HIV(+) but not HIV(-) men (P = .01), with trajectories diverging from HIV(-) ε4 carriers after age 50. Total cholesterol levels did not modify the association of ϵ4 genotype with decline (P = .9). Elevated cholesterol and APOE ϵ4 genotype are independent risk factors for cognitive decline in ART-adherent HIV(+) men aged >50 years. Treatment of dyslipidemia may be an effective strategy to reduce cognitive decline in older HIV(+) individuals. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Hypoglycemic and hypolipidemic effects of Aronia melanocarpa fruit juice in streptozotocin-induced diabetic rats.

PubMed

Valcheva-Kuzmanova, S; Kuzmanov, K; Tancheva, S; Belcheva, A

2007-03-01

Aronia melanocarpa fruit juice (AMFJ) is rich in phenolic antioxidants, especially flavonoids from the anthocyanin subclass. The aim of the present study was to investigate the influence of AMFJ on plasma glucose and lipids in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (50 mg/kg). AMFJ was applied by gavage at doses of 10 and 20 ml/kg for 6 weeks to normal and diabetic rats. Streptozotocin caused a significant elevation of plasma glucose by 141% and of plasma triglycerides (TG) by 64% in comparison with normal control rats and induced statistically insignificant elevations of total cholesterol and LDL-cholesterol and a reduction of HDL-cholesterol. Applied to normal rats, AMFJ did not influence plasma glucose and lipid levels. Applied to diabetic rats, AMFJ (10 and 20 ml/kg) significantly reduced plasma glucose by 44% and 42% and TG by 35% and 39%, respectively, to levels that did not significantly differ from those of the normal control rats and counteracted the influence of streptozotocin on total cholesterol, LDL-cholesterol and HDL-cholesterol. In conclusion, AMFJ significantly decreased the streptozotocin-induced abnormalities in blood glucose and TG in diabetic rats and might be useful in prevention and control of diabetes mellitus and diabetes-associated complications. Copyright 2007 Prous Science.

Are your patients with risk of CVD getting the viscous soluble fiber they need?

PubMed

Shamliyan, Tatyana A; Jacobs, David R; Raatz, Susan K; Nordstrom, David L; Keenan, Joseph M

2006-09-01

A diet that includes 5 to 10 g/d of viscous soluble fiber reduces cardiovascular disease (CVD) events and death independent of baseline risk. Consuming foods rich in viscous soluble fiber reduces low-density lipoprotein cholesterol (LDL-C) blood levels 10% to 15% with expected reduction in CVD events by 10% to 15%. Routinely counsel adults at risk of CVD to promote a healthy diet: assess dietary fiber consumption; recommend specific foods rich in viscous soluble fiber; monitor LDL-C levels and encourage increased dietary fiber intake at follow-up visits; motivate patients to comply with recommendations.

Dietary carbohydrates and triacylglycerol metabolism.

PubMed

Roche, H M

1999-02-01

There is a growing body of scientific evidence which demonstrates that plasma triacylglycerol (TAG) concentration, especially in the postprandial state, is an important risk factor in relation to the development of CHD. Postprandial hypertriacylglycerolaemia is associated with a number of adverse metabolic risk factors, including the preponderance of small dense LDL, low HDL-cholesterol concentrations and elevated factor VII activity. Traditionally, a low-fat high-carbohydrate diet was used to prevent CHD because it effectively reduces plasma cholesterol concentrations, but this dietary regimen increases plasma TAG concentrations and reduces HDL-cholesterol concentrations. There is substantial epidemiological evidence which demonstrates that high plasma TAG and low plasma HDL concentrations are associated with an increased risk of CHD. Thus, there is reason for concern that the adverse effects of low-fat high-carbohydrate diets on TAG and HDL may counteract or negate the beneficial effect of reducing LDL-cholesterol concentrations. Although there have been no prospective studies to investigate whether reduced fat intake has an adverse effect on CHD, there is strong epidemiological evidence that reducing total fat intake is not protective against CHD. On the other hand, high-fat diets predispose to obesity, and central obesity adversely affects TAG metabolism. There is substantial evidence that in free-living situations low-fat high-carbohydrate diets lead to weight loss, which in turn will correct insulin resistance and plasma TAG metabolism. Clearly there is a need for prospective studies to resolve the issue as to whether low-fat high-carbohydrate diets play an adverse or beneficial role in relation to the development of CHD.

Diabetic dyslipidemia and exercise alter the plasma low-density lipoproteome in Yucatan pigs

PubMed Central

Richardson, Matthew R.; Lai, Xianyin; Dixon, Joseph L.; Sturek, Michael; Witzmann, Frank A.

2010-01-01

Although low-density lipoprotein (LDL) plays a predominant role in atherogenesis, the low-density lipoproteome has not been fully characterized. Moreover, alterations from a Western diet, diabetes, and physical inactivity on this proteome have yet to be determined. Accordingly, relative quantification was determined in LDL proteins from male Yucatan diabetic dyslipidemic (DD) swine in the early stages of atherosclerosis compared to healthy control (C) and non-diabetic hyperlipidemic (H) swine. Importantly, coronary vascular dysfunction was prevented by aerobic exercise training in these animals (DDX) without altering total LDL concentration. Using 2-DE, Western blot, label-free quantitative MS, and selected reaction monitoring, alterations in the abundance of apolipoproteins A-I, B, C-III, D, E, and J and noncovalently associated proteins were determined in LDL isolated using fast protein liquid chromatography. At least 28 unique proteins, many of which were novel, were identified with high confidence. An apolipoprotein E isoform demonstrated stronger correlation to disease (percent of coronary artery segments with intimal thickening) than some traditional risk factors (total cholesterol, LDL cholesterol, and LDL/HDL cholesterol). Taken together, this work identifies new possible biomarkers, potential therapeutic targets for atherosclerosis, and generates new hypotheses regarding the role of LDL in atherogenesis. PMID:19402046

Effect of cocoa bran on low-density lipoprotein oxidation and fecal bulking.

PubMed

Jenkins, D J; Kendall, C W; Vuksan, V; Vidgen, E; Wong, E; Augustin, L S; Fulgoni, V

Legumes have reported benefits in terms of reduced risk for coronary heart disease and of colonic health. A novel legume fiber, cocoa bran, also may have favorable health effects on serum lipid levels, low-density lipoprotein (LDL) cholesterol oxidation, and fecal bulk. Twenty-five healthy normolipidemic subjects (13 men and 12 women) (mean +/- SEM age, 37 +/- 2 years; mean +/- SEM body mass index [calculated as weight in kilograms divided by the square of height in meters], 24.6 +/- 0.7) ate cocoa-bran and chocolate-flavored low-fiber breakfast cereals for 2-week periods, with 2-week washout, in a double-blind crossover study. The cocoa-bran cereal provided 25.0 g/d of total dietary fiber (TDF). The low-fiber cereal (5.6 g/d TDF) was of similar appearance and energy value. Fasting blood samples were obtained at the start and end of each period, and 4-day fecal collections were made from days 11 through 14. High-density lipoprotein (HDL) cholesterol level was higher (7.6% +/- 2.9%; P =.02) and the LDL/HDL cholesterol ratio was lower (6.7% +/- 2.3%; P =.007) for cocoa-bran compared with low-fiber cereal at 2 weeks. No effect was seen on LDL cholesterol oxidation. Mean fecal output was significantly higher for cocoa-bran than for low-fiber cereal (56 +/- 14 g/d; P<.001) and equal to the increase seen in the same subjects with wheat fiber in a previous study. A chocolate-flavored cocoa-bran cereal increased fecal bulk similarly to wheat bran and was associated with a reduction in the LDL/HDL cholesterol ratio. In view of the low-fat, high-fiber nature of the material, these results suggest a possible role for this novel fiber source in the diets of normal, hyperlipidemic, and constipated subjects.

Effects of Different Types of Statins on Lipid Profile: A Perspective on Asians.

PubMed

Meor Anuar Shuhaili, Meor Fairuz Rizal; Samsudin, Intan Nureslyna; Stanslas, Johnson; Hasan, Shariful; Thambiah, Subashini C

2017-04-01

The present review aimed at reviewing the effects of different statins on lipid profile, particularly in Asians. PubMed searches were conducted using the keywords 'statin, effect, and lipid profile' from database inception through March 2016. In this review, 718 articles were retrieved from the primary search. After reviewing the titles, abstracts, and full texts, we found that 59 studies met our inclusion criteria. These also included subsequent reference searches of retrieved articles. CURVES study compared the effect on lipid profile between atorvastatin and other statins. This study demonstrated that low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were reduced more with atorvastatin compared to simvastatin, pravastatin, lovastatin, and fluvastatin. However, simvastatin provided a greater elevation of high-density lipoprotein cholesterol (HDL-C) compared to atorvastatin. The STELLAR trial was based on dose-to-dose comparisons between atorvastatin and rosuvastatin efficacy in reducing LDL-C. Te present study also revealed that as the doses of rosuvastatin, simvastatin, and pravastatin increased, HDL-C also increased, with rosuvastatin having the greatest effect. However, HDL-C levels decreased as the dose of atorvastatin increased. The DISCOVERY study involving the Asian population revealed that the percentage of patients achieving the European goals for LDL-C and TC at 12 weeks was higher in rosuvastatin group compared to atorvastatin group. The effects of statins on lipid profile are dose dependent. Most studies showed that rosuvastatin has the best effect on lipid profile. Prescribing lower doses of statins in Asians seems necessary.

Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials

PubMed Central

Ha, Vanessa; Sievenpiper, John L.; de Souza, Russell J.; Jayalath, Viranda H.; Mirrahimi, Arash; Agarwal, Arnav; Chiavaroli, Laura; Mejia, Sonia Blanco; Sacks, Frank M.; Di Buono, Marco; Bernstein, Adam M.; Leiter, Lawrence A.; Kris-Etherton, Penny M.; Vuksan, Vladimir; Bazinet, Richard P.; Josse, Robert G.; Beyene, Joseph; Kendall, Cyril W.C.; Jenkins, David J.A.

2014-01-01

Background: Evidence from controlled trials encourages the intake of dietary pulses (beans, chickpeas, lentils and peas) as a method of improving dyslipidemia, but heart health guidelines have stopped short of ascribing specific benefits to this type of intervention or have graded the beneficial evidence as low. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction. Methods: We searched electronic databases and bibliographies of selected trials for relevant articles published through Feb. 5, 2014. We included RCTs of at least 3 weeks’ duration that compared a diet emphasizing dietary pulse intake with an isocaloric diet that did not include dietary pulses. The lipid targets investigated were low-density lipoprotein (LDL) cholesterol, apolipoprotein B and non–high-density lipoprotein (non-HDL) cholesterol. We pooled data using a random-effects model. Results: We identified 26 RCTs (n = 1037) that satisfied the inclusion criteria. Diets emphasizing dietary pulse intake at a median dose of 130 g/d (about 1 serving daily) significantly lowered LDL cholesterol levels compared with the control diets (mean difference −0.17 mmol/L, 95% confidence interval −0.25 to −0.09 mmol/L). Treatment effects on apolipoprotein B and non-HDL cholesterol were not observed. Interpretation: Our findings suggest that dietary pulse intake significantly reduces LDL cholesterol levels. Trials of longer duration and higher quality are needed to verify these results. Trial registration: ClinicalTrials.gov, no. NCT01594567. PMID:24710915

Lipid modifying action of atorvastatin in comparison to combination of atorvastatin and nicotinic acid in patients with ischaemic heart disease.

PubMed

Santanu, Guha; Suhrita, Paul; Mookerjee, Soura; Tania, Kundu; Mita, Saha; Pramit, Ghosh; Sharmila, Guha; Miraj, Mandal; Debdutta, Majumder

2011-01-01

The current study is a prospective, randomized controlled study with two parallel treatment groups done to assess the tolerability and efficacy of a combination of atorvastatin (10 mg) and extended release nicotinic acid (1G) in comparison to atorvastatin (20 mg) alone in modulating the lipid profile in patients of Ischemic Heart Disease in our population. Patients were randomly allocated into two equal groups (n = 216) as per selection criteria. Group A received Atorvastatin 20 mg while Group B received combination of Atorvastatin -10 mg and extended release nicotinic acid (1G), both once daily at bed time, for a period of 24 weeks. Final end-of-study assessment and evaluation of tolerability and efficacy was done after 24 weeks. Comparison between the groups was performed with paired t-test. A p value < 0.05 was considered to be statistically significant. There was significant reduction in cholesterol, LDL & triglycerides in both the groups. Mean values of cholesterol and LDL were comparable in both groups where as there was increased reduction of triglycerides in Group B. Mean value of HDL cholesterol significantly increased only in group B thus the total cholesterol: HDL ratio was decreased more favorably. SGPT level was not significantly altered in either of the groups. In the Indian perspective, where HDL is low and the LDL values are not very high, a combination of low dose atorvastatin with nicotinic acid may influence the lipid profile more favorably and reduce the cholesterol/HDL ratio in comparison to atorvastatin alone and is also fairly well tolerated.

Lipoprotein Particle Concentrations May Explain the Absence of Coronary Protection in the Women's Health Initiative Hormone Trials

PubMed Central

Hsia, Judith; Otvos, James D.; Rossouw, Jacques E.; Wu, LieLing; Wassertheil-Smoller, Sylvia; Hendrix, Susan L.; Robinson, Jennifer G.; Lund, Bernedine; Kuller, Lewis H.

2009-01-01

Objective The Women's Health Initiative randomized hormone trials unexpectedly demonstrated an increase in early coronary events. In an effort to explain this finding, we examined lipoprotein particle concentrations and their interactions with hormone therapy in a case–control substudy. Methods and Results We randomized 16 608 postmenopausal women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10 739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo, and measured lipoprotein subclasses by nuclear magnetic resonance spectroscopy at baseline and year 1 in 354 women with early coronary events and matched controls. Postmenopausal hormone therapy raised high-density lipoprotein cholesterol and particle concentration and reduced low-density lipoprotein cholesterol (LDL-C; all P<0.001 versus placebo). In contrast, neither unopposed estrogen nor estrogen with progestin lowered low-density lipoprotein particle concentration (LDL-P). Conclusions Postmenopausal hormone therapy–induced reductions in LDL-C were not paralleled by favorable effects on LDL-P. This finding may account for the absence of coronary protection conferred by estrogen in the randomized hormone trials. PMID:18599797

Effect of Exercise Therapy on Lipid Parameters in Patients with End-Stage Renal Disease on Hemodialysis

PubMed Central

Gordon, Lorenzo; McGrowder, Donovan A; Pena, Yeiny T; Cabrera, Elsa; Lawrence-Wright, Marilyn

2012-01-01

Background: Dyslipidemia has been established as a well-known traditional risk factor for cardiovascular disease in chronic kidney disease patients. Aim: This study investigated the impact of Hatha yoga exercise on lipid parameters in patients with end-stage renal disease (ESRD) on hemodialysis. Materials and Methods: This prospective randomized study consisted of 33 ESRD patients in the Hatha yoga exercise group that was matched with 35 ESRD patients in the control group. Serum total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol were determined at baseline (0 month) and after 4 months. Results: Comparing values after 4 months versus baseline in the prehemodialysis Hatha yoga exercise group, there was found a significant decrease in total cholesterol from 5.126 ± 0.092 mmol/l to 4.891 ± 0.072 mmol/l (-4.58%; P = 0.0001), triglycerides from 2.699 ± 0.078 mmol/l to 2.530 ± 0.063 mmol/l (-6.26%; P = 0.0001), LDL-cholesterol from 2.729 ± 0.083 mmol/l to 2.420 ± 0.066 mmol/l (-11.32%; P = 0.0001), and total cholesterol/HDL-cholesterol ratio from 5.593 ± 0.119 mmol/l to 4.907 ± 0.116 mmol/l (-12.26%; P = 0.047). For patients in the Hatha yoga exercise group, 51.5% had normal total cholesterol at 0 month while 70.0% had normal total cholesterol (P < 0.05) after 4 four months and 54.5% of patients had normal LDL-cholesterol at 0 month while 84.9% had normal LDL-cholesterol after 4 months (P < 0.05). Conclusion: These findings suggest that Hatha yoga exercise has preventive and beneficial effects and may be a safe therapeutic modality in ESRD patients. PMID:22923917

Projected Real-World Effectiveness of Using Aggressive Low-Density Lipoprotein Cholesterol Targets Among Elderly Statin Users Following Acute Coronary Syndromes in Canada.

PubMed

Alter, David A; Tu, Jack V; Koh, Maria; Jackevicius, Cynthia A; Austin, Peter C; Rezai, Mohammad R; Bhatia, R Sacha; Johnston, Sharon; Udell, Jacob A; Ko, Dennis T

2018-05-12

The extent to which outcome benefits may be achieved through the implementation of aggressive low-density lipoprotein (LDL) cholesterol targets in real world settings remains unknown, especially among elderly statin users following acute coronary syndromes. A population-based cohort study consisting of 19 544 post-acute coronary syndrome statin-users aged ≥66 years between January 1, 2017 and March 31, 2014 was used to project the number of adverse outcome events (acute myocardial infarction or death from any cause) that could be prevented if all post-acute coronary syndrome elderly statin users were treated to 1 of 2 LDL cholesterol target levels (≤50 and ≤70 mg/dL). The number of preventable adverse outcomes was estimated by using model-based expected event probabilities as derived from Cox Proportional hazards models. In total, 61.6% and 25.5% of the elderly patients met LDL cholesterol targets of ≤70 and ≤50 mg/dL, respectively, based on current management. No more than 2.3 adverse events per 1000 elderly statin users (95% confidence interval: -0.7 to 5.4, P =0.62) could be prevented over 8.1 years if all patients were to be treated from current LDL cholesterol levels to either of the 2 LDL cholesterol targets of 70 or 50 mg/dL. The number of acute myocardial infarctions or death that could be prevented through the implementation of LDL cholesterol targets with statins is negligible among an elderly post-acute coronary syndrome population. Such findings may have implications for the applicability of newer agents, such as proprotein convertase subtilisin/kexin type-9- inhibitors. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Structure-function relationships in reconstituted HDL: Focus on antioxidative activity and cholesterol efflux capacity.

PubMed

Cukier, Alexandre M O; Therond, Patrice; Didichenko, Svetlana A; Guillas, Isabelle; Chapman, M John; Wright, Samuel D; Kontush, Anatol

2017-09-01

High-density lipoprotein (HDL) contains multiple components that endow it with biological activities. Apolipoprotein A-I (apoA-I) and surface phospholipids contribute to these activities; however, structure-function relationships in HDL particles remain incompletely characterised. Reconstituted HDLs (rHDLs) were prepared from apoA-I and soy phosphatidylcholine (PC) at molar ratios of 1:50, 1:100 and 1:150. Oxidative status of apoA-I was varied using controlled oxidation of Met112 residue. HDL-mediated inactivation of PC hydroperoxides (PCOOH) derived from mildly pre-oxidized low-density lipoprotein (LDL) was evaluated by HPLC with chemiluminescent detection in HDL+LDL mixtures and re-isolated LDL. Cellular cholesterol efflux was characterised in RAW264.7 macrophages. rHDL inactivated LDL-derived PCOOH in a dose- and time-dependent manner. The capacity of rHDL to both inactivate PCOOH and efflux cholesterol via ATP-binding cassette transporter A1 (ABCA1) increased with increasing apoA-I/PC ratio proportionally to the apoA-I content in rHDL. Controlled oxidation of apoA-I Met112 gradually decreased PCOOH-inactivating capacity of rHDL but increased ABCA1-mediated cellular cholesterol efflux. Increasing apoA-I content in rHDL enhanced its antioxidative activity towards oxidized LDL and cholesterol efflux capacity via ABCA1, whereas oxidation of apoA-I Met112 decreased the antioxidative activity but increased the cholesterol efflux. These findings provide important considerations in the design of future HDL therapeutics. Non-standard abbreviations and acronyms: AAPH, 2,2'-azobis(-amidinopropane) dihydrochloride; ABCA1, ATP-binding cassette transporter A1; apoA-I, apolipoprotein A-I; BHT, butylated hydroxytoluene; CV, cardiovascular; EDTA, ethylenediaminetetraacetic acid; HDL-C, high-density lipoprotein cholesterol; LOOH, lipid hydroperoxides; Met(O), methionine sulfoxide; Met112, methionine 112 residue; Met86, methionine 86 residue; oxLDL, oxidized low-density lipoprotein; PBS, phosphate-buffered saline; PC, phosphatidylcholine; PL, phospholipid; PCOOH, phosphatidylcholine hydroperoxide; PLOOH, phospholipid hydroperoxide. Copyright © 2017 Elsevier B.V. All rights reserved.

A randomized placebo-controlled pilot study of pravastatin as an adjunctive therapy in schizophrenia patients: effect on inflammation, psychopathology, cognition and lipid metabolism

PubMed Central

Vincenzi, Brenda; Stock, Shannon; Borba, Christina P.C.; Cleary, Sarah M.; Oppenheim, Claire E.; Petruzzi, Liana J.; Fan, Xiaoduo; Copeland, Paul M.; Freudenreich, Oliver; Cather, Corinne; Henderson, David C.

2015-01-01

Objective The aim of this study was to investigate the role of pravastatin, as an adjunctive therapy, on inflammatory markers, lipid and glucose metabolism, psychopathology, and cognition in subjects with schizophrenia and schizoaffective disorder. Methods Schizophrenia or schizoaffective subjects (N=60) were randomized to receive either a 12-week supply of pravastatin 40 mg/day or placebo treatment. Anthropometric measures, lipids and glucose metabolism, inflammatory markers, psychopathology and cognitive performance were assessed at baseline, 6 weeks and 12 weeks. Results Pravastatin use was associated with a significant decrease in total cholesterol, low density lipoprotein (LDL) cholesterol and LDL particle number levels, but was not associated with any significant changes in cognition or psychopathology in the participants, except a significant decrease in the Positive and Negative Syndrome Scale (PANSS) positive symptoms score from baseline to week 6. However, this decrease failed to remain significant at 12 weeks. Interestingly, triglycerides, LDLCholesterol, Total cholesterol, LDL particle number, small LDL particle number, large very low density lipoprotein (VLDL) particle number and c-reactive protein (CRP) followed a similar pattern at 6 and 12 weeks as psychopathology. Conclusions These results suggest that a randomized trial with a larger sample size and a higher dosage of pravastatin, and would be helpful in further evaluating the anti-inflammatory properties of pravastatin, its association with improvements in cognitive symptoms, and its potential to reduce positive and negative symptoms associated with schizophrenia or schizoaffective disorders. PMID:25261882

Effects of extended-release niacin with laropiprant in high-risk patients.

PubMed

Landray, Martin J; Haynes, Richard; Hopewell, Jemma C; Parish, Sarah; Aung, Theingi; Tomson, Joseph; Wallendszus, Karl; Craig, Martin; Jiang, Lixin; Collins, Rory; Armitage, Jane

2014-07-17

Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL) cholesterol level, but its clinical efficacy and safety are uncertain. After a prerandomization run-in phase to standardize the background statin-based LDL cholesterol-lowering therapy and to establish participants' ability to take extended-release niacin without clinically significant adverse effects, we randomly assigned 25,673 adults with vascular disease to receive 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily. The primary outcome was the first major vascular event (nonfatal myocardial infarction, death from coronary causes, stroke, or arterial revascularization). During a median follow-up period of 3.9 years, participants who were assigned to extended-release niacin-laropiprant had an LDL cholesterol level that was an average of 10 mg per deciliter (0.25 mmol per liter as measured in the central laboratory) lower and an HDL cholesterol level that was an average of 6 mg per deciliter (0.16 mmol per liter) higher than the levels in those assigned to placebo. Assignment to niacin-laropiprant, as compared with assignment to placebo, had no significant effect on the incidence of major vascular events (13.2% and 13.7% of participants with an event, respectively; rate ratio, 0.96; 95% confidence interval [CI], 0.90 to 1.03; P=0.29). Niacin-laropiprant was associated with an increased incidence of disturbances in diabetes control that were considered to be serious (absolute excess as compared with placebo, 3.7 percentage points; P<0.001) and with an increased incidence of diabetes diagnoses (absolute excess, 1.3 percentage points; P<0.001), as well as increases in serious adverse events associated with the gastrointestinal system (absolute excess, 1.0 percentage point; P<0.001), musculoskeletal system (absolute excess, 0.7 percentage points; P<0.001), skin (absolute excess, 0.3 percentage points; P=0.003), and unexpectedly, infection (absolute excess, 1.4 percentage points; P<0.001) and bleeding (absolute excess, 0.7 percentage points; P<0.001). Among participants with atherosclerotic vascular disease, the addition of extended-release niacin-laropiprant to statin-based LDL cholesterol-lowering therapy did not significantly reduce the risk of major vascular events but did increase the risk of serious adverse events. (Funded by Merck and others; HPS2-THRIVE ClinicalTrials.gov number, NCT00461630.).

Lipid profiles and determinants of total cholesterol and hypercholesterolaemia among 25-74 year-old urban and rural citizens of the Yangon Region, Myanmar: a cross-sectional study.

PubMed

Htet, Aung Soe; Kjøllesdal, Marte Karoline; Aung, Wai Phyo; Moe Myint, Aye Nyein; Aye, Win Thuzar; Wai, Myint Myint; Nu, Than Than; Hla, Ei Mon; Soe, Pyone Pyone; Tun, Nan Wut Yi; Angela, Naw; Khaing, Mya Mya; Htoo, Aung Kyaw; Tun, Soe; Thitsar, Pai; Lwin, Theeoo; Wai, San San; Aung, Thi Thi; Thant, Khin Aye; Aung Po, Wai Wai; Gauzam, Seng Taung; Naing, Tun Tun; Tun, Thet Min; Myint, Khin San; Oo, Kyi Kyi; Mang, Nang Kee Myu; Naing, Soe Moe; Zaw, Ko Ko; Bjertness, Marius Bergsmark; Sherpa, Lhamo Yangchen; Oo, Win Myint; Stigum, Hein; Bjertness, Espen

2017-11-15

The first is to estimate the prevalence of dyslipidaemia (hypercholesterolaemia, hypertriglyceridaemia, high low-density lipoprotein (LDL) level and low high-density lipoprotein (HDL) level), as well as the mean levels of total cholesterol, triglyceride, LDL and HDL, in the urban and rural Yangon Region, Myanmar. The second is to investigate the association between urban-rural location and total cholesterol. Two cross-sectional studies using the WHO STEPS methodology. Both the urban and rural areas of the Yangon Region, Myanmar. A total of 1370 men and women aged 25-74 years participated based on a multistage cluster sampling. Physically and mentally ill people, monks, nuns, soldiers and institutionalised people were excluded. Compared with rural counterparts, urban dwellers had a significantly higher age-standardised prevalence of hypercholesterolaemia (50.7% vs 41.6%; p=0.042) and a low HDL level (60.6% vs 44.4%; p=0.001). No urban-rural differences were found in the prevalence of hypertriglyceridaemia and high LDL. Men had a higher age-standardised prevalence of hypertriglyceridaemia than women (25.1% vs 14.8%; p<0.001), while the opposite pattern was found in the prevalence of a high LDL (11.3% vs 16.3%; p=0.018) and low HDL level (35.3% vs 70.1%; p<0.001).Compared with rural inhabitants, urban dwellers had higher age-standardised mean levels of total cholesterol (5.31 mmol/L, SE: 0.044 vs 5.05 mmol/L, 0.068; p=0.009), triglyceride (1.65 mmol/L, 0.049 vs 1.38 mmol/L, 0.078; p=0.017), LDL (3.44 mmol/L, 0.019 vs 3.16 mmol/L, 0.058; p=0.001) and lower age-standardised mean levels of HDL (1.11 mmol/L, 0.010 vs 1.25 mmol/L, 0.012; p<0.001). In linear regression, the total cholesterol was significantly associated with an urban location among men, but not among women. The mean level of total cholesterol and the prevalence of hypercholesterolaemia were alarmingly high in men and women in both the urban and rural areas of Yangon Region, Myanmar. Preventive measures to reduce cholesterol levels in the population are therefore needed. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pleiotropic Effects of Statins on the Cardiovascular System.

PubMed

Oesterle, Adam; Laufs, Ulrich; Liao, James K

2017-01-06

The statins have been used for 30 years to prevent coronary artery disease and stroke. Their primary mechanism of action is the lowering of serum cholesterol through inhibiting hepatic cholesterol biosynthesis thereby upregulating the hepatic low-density lipoprotein (LDL) receptors and increasing the clearance of LDL-cholesterol. Statins may exert cardiovascular protective effects that are independent of LDL-cholesterol lowering called pleiotropic effects. Because statins inhibit the production of isoprenoid intermediates in the cholesterol biosynthetic pathway, the post-translational prenylation of small GTP-binding proteins such as Rho and Rac, and their downstream effectors such as Rho kinase and nicotinamide adenine dinucleotide phosphate oxidases are also inhibited. In cell culture and animal studies, these effects alter the expression of endothelial nitric oxide synthase, the stability of atherosclerotic plaques, the production of proinflammatory cytokines and reactive oxygen species, the reactivity of platelets, and the development of cardiac hypertrophy and fibrosis. The relative contributions of statin pleiotropy to clinical outcomes, however, remain a matter of debate and are hard to quantify because the degree of isoprenoid inhibition by statins correlates to some extent with the amount of LDL-cholesterol reduction. This review examines some of the currently proposed molecular mechanisms for statin pleiotropy and discusses whether they could have any clinical relevance in cardiovascular disease. © 2017 American Heart Association, Inc.

Is splenectomy a dyslipidemic intervention? Experimental response of serum lipids to different diets and operations.

PubMed

Paulo, Danilo N S; Paulo, Isabel Cal; Morais, Alvaro A C; Kalil, Mitre; Guerra, Alvino J; Colnago, Geraldo L; Faintuch, Joel

2009-01-01

Spleen removal may be recommended during organ transplantation in ABO-incompatible recipients as well as for hypoperfusion of the grafted liver, besides conventional surgical indications, but elevation of serum lipids has been observed in certain contexts. Aiming to analyze the influence of two dietary regimens on lipid profile, an experimental study was conducted. Male Wistar rats (n = 86, 333.0 +/- 32.2 g) were divided in four groups: group 1: controls; group 2: sham operation; group 3: total splenectomy; group 4: subtotal splenectomy with upper pole preservation; subgroups A (cholesterol reducing chow) and B (cholesterol-rich mixture) were established, and diet was given during 90 days. Total cholesterol (Tchol), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and triglycerides were documented. After total splenectomy, hyperlipidemia ensued with cholesterol-reducing chow. Tchol, LDL, VLDL, triglycerides, and HDL changed from 56.4 +/- 9.2, 24.6 +/- 4.7, 9.7 +/- 2.2, 48.6 +/- 11.1, and 22.4 +/- 4.3 mg/dL to 66.9 +/- 11.4, 29.9 +/- 5.9, 10.9 +/- 2.3, 54.3 +/- 11.4, and 26.1 +/- 5.1 mg/dL, respectively. Upper pole preservation inhibited abnormalities of Tchol, HDL, VLDL, and triglycerides, and LDL decreased (23.6 +/- 4.9 vs. 22.1 +/- 5.1, P = 0.002). Higher concentrations were triggered by splenectomy and cholesterol-enriched diet (Tchol 59.4 +/- 10.1 vs. 83.9 +/- 14.3 mg/dL, P = 0.000), and upper-pole preservation diminished without abolishing hyperlipidemia (Tchol 55.9 +/- 10.0 vs. 62.3 +/- 7.8, P = 0.002). After splenectomy, hyperlipidemia occurred with both diets. Preservation of the upper pole tended to correct dyslipidemia in modality A and to attenuate it in subgroup B. (c) 2008 Wiley-Liss, Inc.

MicroRNA 302a is a novel modulator of cholesterol homeostasis and atherosclerosis

PubMed Central

Meiler, Svenja; Baumer, Yvonne; Toulmin, Emma; Seng, Kosal; Boisvert, William A.

2014-01-01

Objective Macrophage foam cell formation is a key feature of atherosclerosis. Recent studies have shown that specific microRNAs (miRs) are regulated in modified low-density lipoprotein (LDL)- treated macrophages, which can affect the cellular cholesterol homeostasis. Undertaking a genome-wide screen of microRNAs regulated in primary macrophages by modified LDL, miR-302a emerged as a potential candidate that may play a key role in macrophage cholesterol homeostasis. Approach and Results The objective of this study was to assess the involvement of miR-302a in macrophage lipid homeostasis and if it can influence circulating lipid levels and atherosclerotic development when it is inhibited in a murine atherosclerosis model. We found that transfection of primary macrophages with either miR-302a or anti-miR-302a regulated the expression of ATP-binding cassette (ABC) transporter ABCA1 mRNA and protein. Luciferase reporter assays showed that miR-302a repressed the 3′UTR activity of mouse Abca1 by 48% and human ABCA1 by 45%. Additionally, transfection of murine macrophages with miR-302a attenuated cholesterol efflux to apolipoprotein A-1 (apoA-1) by 38%. Long-term in vivo administration of anti-miR-302a to mice with LDL receptor deficiency (Ldlr−/−) fed an atherogenic diet led to an increase in ABCA1 in the liver and aorta as well as an increase in circulating plasma HDL levels by 35% compared with that of control mice. The anti-miR-302a-treated mice also displayed reduced atherosclerotic plaque size by approximately 25% as well as a more stable plaque morphology with reduced signs of inflammation. Conclusions These studies identify miR-302a as a novel modulator of cholesterol efflux and a potential therapeutic target for suppressing atherosclerosis. PMID:25524771

Ethnic differences in blood lipids and dietary intake between UK children of black African, black Caribbean, South Asian, and white European origin: the Child Heart and Health Study in England (CHASE).

PubMed

Donin, Angela S; Nightingale, Claire M; Owen, Christopher G; Rudnicka, Alicja R; McNamara, Mary C; Prynne, Celia J; Stephen, Alison M; Cook, Derek G; Whincup, Peter H

2010-10-01

Ischemic heart disease (IHD) rates are lower in UK black Africans and black Caribbeans and higher in South Asians when compared with white Europeans. Ethnic differences in lipid concentrations may play a part in these differences. The objective was to investigate blood lipid and dietary patterns in UK children from different ethnic groups. This was a cross-sectional study in 2026 UK children (including 285 black Africans, 188 black Caribbeans, 534 South Asians, and 512 white Europeans) attending primary schools in London, Birmingham, and Leicester. We measured fasting blood lipid concentrations and collected 24-h dietary recalls. In comparison with white Europeans, black African children had lower total cholesterol (-0.14 mmol/L; 95% CI: -0.25, -0.04 mmol/L), LDL-cholesterol (-0.10 mmol/L; 95% CI: -0.20, -0.01 mmol/L), and triglyceride concentrations (proportional difference: -0.11 mmol/L; 95% CI: -0.16, -0.06 mmol/L); HDL-cholesterol concentrations were similar. Lower saturated fat intakes (-1.4%; 95% CI: -1.9%, -0.9%) explained the differences between total and LDL cholesterol. Black Caribbean children had total, LDL-cholesterol, HDL-cholesterol, and triglyceride concentrations similar to those for white Europeans, with slightly lower saturated fat intakes. South Asian children had total and LDL-cholesterol concentrations similar to those for white Europeans, lower HDL-cholesterol concentrations (-0.7 mmol/L; 95% CI: -0.11, -0.03 mmol/L), and elevated triglyceride concentrations (proportional difference: 0.14 mmol/L; 95% CI: 0.09, 0.20 mmol/L); higher polyunsaturated and monounsaturated fat intakes did not explain these lipid differences. Only black African children had a blood lipid profile and associated dietary pattern likely to protect against future IHD. The loss of historically lower LDL-cholesterol concentrations among UK black Caribbeans and South Asians may have important adverse consequences for future IHD risk in these groups.

The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: baseline characteristics of study participants. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: impact on Global Health outcomes (AIM-HIGH) trial.

PubMed

2011-03-01

The study aims to report the baseline characteristics of the fully randomized AIM-HIGH study population. Residual risk persists despite aggressive low-density lipoprotein cholesterol (LDL-C) reduction in patients with atherosclerotic cardiovascular (CV) disease, many of whom have atherogenic dyslipidemia (low levels of high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, and small dense LDL particles). All study participants had established CV disease and atherogenic dyslipidemia. Participants received simvastatin (or simvastatin plus ezetimibe) at a dose sufficient to maintain LDL-C at 40 - 80 mg/dL (1.03-2.07 mmol/L) and were randomized to receive extended-release niacin or matching placebo. The primary end point is time to the first occurrence of coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome or symptom-driven coronary or cerebral revascularization with average follow-up of 4.1 years. Between 2006 and 2010, 8,162 individuals signed consent to be screened, 4,275 began study drug run-in, and 3,414 were randomized to treatment. Mean age at entry was 64 ± 9 years, 85% were men, and 92% were white. As expected, risk factors were prevalent with 34% having diabetes; 71%, hypertension; and 81%, metabolic syndrome. Most participants had coronary artery disease (92%), whereas 11% had peripheral arterial disease; and 12%, cerebrovascular disease. Previous coronary revascularization occurred in 82%, and 54% reported a prior myocardial infarction. Among participants on a statin at entry (94%), mean baseline LDL-C was 71 mg/dL (1.84 mmol/L); mean HDL-C, 34.9 mg/dL (0.90 mmol/L); and median triglycerides, 161 mg/dL (1.82 mmol/L). AIM-HIGH enrolled a high-risk group of patients with established atherosclerotic CV disease and atherogenic dyslipidemia. This study should determine whether there is incremental clinical benefit of niacin in reducing cardiovascular events in patients who have attained optimal on-treatment levels of LDL-C with a statin. Copyright © 2011 Mosby, Inc. All rights reserved.

Plant Sterols as Dietary Adjuvants in the Reduction of Cardiovascular Risk: Theory and Evidence

PubMed Central

Patch, Craig S; Tapsell, Linda C; Williams, Peter G; Gordon, Michelle

2006-01-01

Plant sterol-enriched foods are an effective dietary adjuvant in reducing cardiovascular risk by lowering total cholesterol and low density lipoprotein-cholesterol (LDL-C) in serum by up to ∼15%. The mechanism of action of plant sterols is different from those of 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) and thus their effect is additive. Combining plant sterols with other dietary components known to reduce cholesterol in a portfolio approach has proven to be most effective for reduction of hypercholesterolemia and provide an alternative treatment option for clinicians. Plant sterol-enriched foods provides clinicians with a relatively cheap, safe, and effective way to help patients manage their cardiovascular risk. PMID:17319460

Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia – Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR)

PubMed Central

Clearfield, Michael B; Amerena, John; Bassand, Jean-Pierre; García, Hugo R Hernández; Miller, Sam S; Sosef, Froukje FM; Palmer, Michael K; Bryzinski, Brian S

2006-01-01

Background Many patients at high risk of cardiovascular disease do not achieve recommended low-density lipoprotein cholesterol (LDL-C) goals. This study compared the efficacy and safety of low doses of rosuvastatin (10 mg) and atorvastatin (20 mg) in high-risk patients with hypercholesterolemia. Methods A total of 996 patients with hypercholesterolemia (LDL-C ≥ 3.4 and < 5.7 mmol/L [130 and 220 mg/dL]) and coronary heart disease (CHD), atherosclerosis, or a CHD-risk equivalent were randomized to once-daily rosuvastatin 10 mg or atorvastatin 20 mg. The primary endpoint was the percentage change from baseline in LDL-C levels at 6 weeks. Secondary endpoints included LDL-C goal achievement (National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] goal < 100 mg/dL; 2003 European goal < 2.5 mmol/L for patients with atherosclerotic disease, type 2 diabetes, or at high risk of cardiovascular events, as assessed by a Systematic COronary Risk Evaluation (SCORE) risk ≥ 5% or 3.0 mmol/L for all other patients), changes in other lipids and lipoproteins, cost-effectiveness, and safety. Results Rosuvastatin 10 mg reduced LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs. 42.7%, p < 0.05). Significantly more patients achieved NCEP ATP III and 2003 European LDL-C goals with rosuvastatin 10 mg compared with atorvastatin 20 mg (68.8% vs. 62.5%, p < 0.05; 68.0% vs. 63.3%, p < 0.05, respectively). High-density lipoprotein cholesterol was increased significantly with rosuvastatin 10 mg versus atorvastatin 20 mg (6.4% vs. 3.1%, p < 0.001). Lipid ratios and levels of apolipoprotein A-I also improved more with rosuvastatin 10 mg than with atorvastatin 20 mg. The use of rosuvastatin 10 mg was also cost-effective compared with atorvastatin 20 mg in both a US and a UK setting. Both treatments were well tolerated, with a similar incidence of adverse events (rosuvastatin 10 mg, 27.5%; atorvastatin 20 mg, 26.1%). No cases of rhabdomyolysis, liver, or renal insufficiency were recorded. Conclusion In high-risk patients with hypercholesterolemia, rosuvastatin 10 mg was more efficacious than atorvastatin 20 mg at reducing LDL-C, enabling LDL-C goal achievement and improving other lipid parameters. Both treatments were well tolerated. PMID:17184550

Effect of the Probiotic Saccharomyces boulardii on Cholesterol and Lipoprotein Particles in Hypercholesterolemic Adults: A Single-Arm, Open-Label Pilot Study.

PubMed

Ryan, Jennifer Joan; Hanes, Douglas Allen; Schafer, Morgan Beth; Mikolai, Jeremy; Zwickey, Heather

2015-05-01

Elevated blood cholesterol levels are a major risk factor for coronary artery disease, the leading cause of death worldwide. Probiotics have been investigated as potential cholesterol-lowering therapies, but no previous studies have assessed the effect of the probiotic yeast Saccharomyces boulardii on cholesterol levels in human volunteers. The objective of this study was to examine the effect of S. boulardii on serum cholesterol and lipoprotein particles in hypercholesterolemic adults. This study was a single-arm, open-label pilot study. Twelve hypercholesterolemic participants were recruited into the study; one dropped out. Participants took 5.6×10(10) colony forming unit (CFU) encapsulated S. boulardii (Saccharomyces cerevisiae var. boulardii CNCM I-1079) twice daily for an 8-week period. Fasting concentrations of cholesterol (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], and triglycerides), lipoprotein particles (very-low-density lipoprotein-particle [VLDL-P], remnant lipoprotein particle [RLP-P], total LDL-P, LDL III-P, LDL IV-P, total HDL-P, and HDL 2b-P), and additional cardiovascular biomarkers (apo B-100, lipoprotein [a], high-sensitivity C-reactive protein, homocysteine, fibrinogen, and insulin) were measured at baseline, after 4 weeks, and after 8 weeks. Remnant lipoprotein particles decreased by 15.5% (p=0.03) over the 8-week period. The remaining outcome measures were not significantly altered. In this pilot study, 8 weeks of daily supplementation with S. boulardii lowered remnant lipoprotein, a predictive biomarker and potential therapeutic target in the treatment and prevention of coronary artery disease.

Higher HDL cholesterol is associated with better cognitive function: the Maine-Syracuse study.

PubMed

Crichton, Georgina E; Elias, Merrill F; Davey, Adam; Sullivan, Kevin J; Robbins, Michael A

2014-11-01

Few studies have examined associations between different subcategories of cholesterol and cognitive function. We examined relationships between total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride levels and cognitive performance in the Maine-Syracuse Longitudinal Study, a community-based study of cardiovascular risk factors. Cross-sectional analyses were undertaken on data from 540 participants, aged 60 to 98 years, free of dementia and stroke. TC, HDL, LDL, and triglyceride levels were obtained. Cognitive function was assessed using a thorough neuropsychological test battery, including domains of cognitive function indexed by multiple cognitive tests. The cognitive outcomes studied were as follows: Visual-Spatial Memory and Organization, Verbal and Working Memory, Scanning and Tracking, Abstract Reasoning, a Global Composite score, and the Mini-Mental State Examination (MMSE). Significant positive associations were observed between HDL-cholesterol and the Global Composite score, Working Memory, and the MMSE after adjustment for demographic and cardiovascular risk factors. Participants with desirable levels of HDL (≥60 mg/dL) had the highest scores on all cognitive outcomes. There were no significant associations observed between TC, LDL, or triglyceride concentrations and cognition. In older individuals, HDL-cholesterol was related to a composite of Working Memory tests and for general measures of cognitive ability when adjusted for cardiovascular variables. We speculate that persons over 60 are survivors and thus less likely to show cognitive deficit in relation to TC, LDL-cholesterol, and triglycerides. Longitudinal studies are needed to examine relations between specific cognitive abilities and the different subcategories of cholesterol.

LDL apheresis in the treatment of familial hypercholesterolemia: experience of Hospital Santo António, Porto.

PubMed

Palma, Isabel; Caldas, Ana Rita; Palma, Isabel Mangas; Queirós, José Alexandre; Madureira, Anselmo; Oliveira, José Carlos; Palma, Paulo; Correia, Carlos; Ramos, Maria Helena

2015-03-01

High plasma levels of low-density lipoprotein (LDL) cholesterol are a risk factor for the development of premature atherosclerosis. Direct adsorption of lipoproteins (DALI) is an apheresis technique by which LDL cholesterol is selectively removed from whole blood. The present study describes our experience with DALI LDL apheresis in severely hypercholesterolemic patients. Three hypercholesterolemic patients suffering from atherosclerotic complications were treated fortnightly by DALI apheresis, in a total of 308 sessions between December 2008 and January 2013. All patients were on the highest tolerated dose of statins and other lipid-lowering drugs. The sessions were essentially uneventful, adverse events being recorded in only 3.6% of them. A mean 63.3% acute reduction in LDL cholesterol was obtained. DALI apheresis proved to be a simple, safe and efficient method of lipid apheresis in hypercholesterolemic patients refractory to conservative lipid-lowering therapy. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

[Homozygous familial hypercholesterolemia].

PubMed

Kayikçioğlu, Meral

2014-10-01

Familial hypercholesterolemia (FH) is caused by genetic deficiency of LDL receptors leading to extremely high cholesterol levels and atherosclerosis at early ages. For the prevention of early atherosclerotic cardiovascular events, effective reduction of LDL-cholesterol is necessary from the early ages. However, particularly in homozygous patients, it's almost impossible to achieve target LDL-cholesterol levels with antilipid agents including statin agents, due to the severe LDL receptor dysfunction. LDL apheresis is an effective treatment modality in severe AH patients. However, the invasive, chronic time consuming nature of this treatment decreases the compliance of these patients. Moreover, atherosclerosis progress in 25% of the patients undergoing regular and effective apheresis even though since early ages. Clinical data also indicate that there is still an unmet medical need for new effective treatments for AH patients. This review will address new therapeutic strategies targeting Apolipoprotein (Apo) B including MTTP inhibitor Lomitapideand oligonucleotide Mipomersen. As both agents are targeted against ApoB, they are expected to be effective even in receptor negative homozygous AH patients.

A Selective and Regenerable Surface Based on β-Cyclodextrin for Low-Density Lipoprotein Adsorption.

PubMed

Fang, Fei; Huang, Xiao-Jun; Guo, Yi Zong; Hong, Xiao; Wu, Hui Min; Liu, Rong; Chen, Da Jing

2018-06-20

Cyclodextrins (CDs) are a family of cyclic oligosaccharides and its unique hydrophilic outer surface and lipophilic central cavity facilitate the formation of inclusion complexes with various biomolecules, such as cholesterol and phospholipids, via multi-interactions. Low-density lipoprotein (LDL) is the main carrier of cholesterol in bloodstream and is associated with the progression of atherosclerosis. The surface of LDL is composed of a shell of phospholipids monolayer containing most of the free unesterified cholesterol, as well as the single copy of apolipoprotein B-100. Till date, various LDL adsorbents have been fabricated to interact with the biomolecules on LDL surface. Owing to its elegant structure, CD is considered to be a promising choice for preparation of more economical and effective LDL-adsorbing materials. Therefore, in this study, interaction between β-CD and LDL in solution was investigated by dynamic light scattering, circular dichroism, and ultraviolet spectroscopy. Further, a supramolecular surface based on β-CD was simply prepared by self-assembled monolayer on gold surface. The effect of hydrogen bond and the cavity of β-CD on the interaction between β-CD and LDL was particularly explored by surface plasmon resonance (SPR) analysis. The SPR results showed that such β-CD-modified surface exhibited good selectivity and could be largely regenerated by sodium dodecyl sulfate wash. This study may extend the understanding of the interaction between LDL and LDL adsorbent, or the design and development of more efficient and lower cost LDL adsorbents in the future.

Pitavastatin

MedlinePlus

... fatty substances such as low-density lipoprotein (LDL) cholesterol ('bad cholesterol') in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol ('good cholesterol'). Pitavastatin is in a class of ...

LDL-cholesterol reduction in patients with hypercholesterolemia by modulation of adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase.

PubMed

Filippov, Sergey; Pinkosky, Stephen L; Newton, Roger S

2014-08-01

To review the profile of ETC-1002, as shown in preclinical and clinical studies, including LDL-cholesterol (LDL-C)-lowering activity and beneficial effects on other cardiometabolic risk markers as they relate to the inhibition of adenosine triphosphate-citrate lyase and the activation of adenosine monophosphate-activated protein kinase. ETC-1002 is an adenosine triphosphate-citrate lyase inhibitor/adenosine monophosphate-activated protein kinase activator currently in Phase 2b clinical development. In seven Phase 1 and Phase 2a clinical studies, ETC-1002 dosed once daily for 2-12 weeks has lowered LDL-C and reduced high-sensitivity C-reactive protein by up to 40%, with neutral to positive effects on glucose levels, blood pressure, and body weight. Importantly, use of ETC-1002 in statin-intolerant patients has shown statin-like lowering of LDL-C without the muscle pain and weakness responsible for discontinuation of statin use by many patients. ETC-1002 has also been shown to produce an incremental benefit, lowering LDL-C as an add-on therapy to a low-dose statin. In over 300 individuals in studies of up to 12 weeks, ETC-1002 has been well tolerated with no serious adverse effects. Because adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase play central roles in regulating lipid and glucose metabolism, pharmacological modulation of these two enzymes could provide an important therapeutic alternative for statin-intolerant patients with hypercholesterolemia.

Novel treatments for familial hypercholesterolemia: pharmacogenetics at work.

PubMed

Marbach, Jeffrey A; McKeon, Jessica L; Ross, Joyce L; Duffy, Danielle

2014-09-01

The familial hypercholesterolemias (FHs) are inherited disorders of lipoprotein metabolism that are among the most prevalent genetically inherited disorders. Various genetic mutations ultimately lead to greatly increased low-density lipoprotein-cholesterol (LDL-C) levels over a lifetime. Consequently, patients with FH develop coronary artery disease at significantly earlier ages and at a greater frequency than the general population. Current therapies revolve around aggressive lifestyle modifications, cholesterol-lowering medications, and in some cases LDL apheresis. Despite maximal medical therapy, LDL-C is not sufficiently reduced in some patients, and they remain at a substantially increased risk of coronary heart disease. Recent advances in genetic-based pharmacology have enabled the development of three novel classes of medications for FH. Two of those compounds, mipomersen and lomitapide, result in decreased LDL-C production and were approved by the Food and Drug Administration in the past 18 months for treatment of homozygous FH. Mipomersen is an antisense oligonucleotide that inhibits the translation of apolipoprotein B-100, and lomitapide is an inhibitor of the microsomal triglyceride transfer protein, which prevents the incorporation of triglycerides into lipoproteins. A third class of drugs, the proprotein convertase subtilisin/kexin type 9 inhibitors, is still in development, although studies in patients with heterozygous or receptor-defective homozygous FH have demonstrated substantial reductions in LDL-C by decreasing the degradation of LDL receptors. Development of these novel treatments for hypercholesterolemia resulted from the application of known genetic mutations and is the focus of this review. © 2014 Pharmacotherapy Publications, Inc.

Effects of Apple Consumption on Lipid Profile of Hyperlipidemic and Overweight Men

PubMed Central

Vafa, Mohammad Reza; Haghighatjoo, Elham; Shidfar, Farzad; Afshari, Shirin; Gohari, Mahmood Reza; Ziaee, Amir

2011-01-01

Objectives: Fruits and vegetables may be beneficial on lipid profile of hyperlipidemic subjects. The present study was aimed to verify the effect of golden delicious apple on Lipid Profile in hyperlipidemic and overweight men. Methods: Forty six hyperlipidemic and overweight men were randomly divided into two groups. Intervention group received 300g golden delicious apple per day for 8 weeks. Control group had the regular dietary regimen for the same period of time. Blood samples were analyzed for serum triglycerides (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), very low density lipoprotein-cholesterol (VLDL), apolipoprotein B (Apo B), lipoprotein a (Lp a) and LDL/HDL ratio at baseline and after intervention. Results: Total polyphenols and fibers were 485 mg/kg and 4.03 g/100g in fresh apple respectively. After 8 weeks, significant statistical differences were observed considering the TG and VLDL levels between two groups, but no significant differences were observed regarding TC, LDL-C, HDL-C, Apo (B), Lp (a) and LDL/HDL ratio. Conclusions: Consumption of Golden delicious apple may be increased serum TG and VLDL in hyperlipidemic and overweight men. We need more studies to assay the effect of apple consumption on serum TC, LDL-C, HDL-C, Apo (B), Lp (a) and LDL/HDL ratio. PMID:21603015

Sea buckthorn seed oil protects against the oxidative stress produced by thermally oxidized lipids.

PubMed

Zeb, Alam; Ullah, Sana

2015-11-01

Thermally oxidized vegetable ghee was fed to the rabbits for 14 days with specific doses of sea buckthorn seed oil (SO). The ghee and SO were characterized for quality parameters and fatty acid composition using GC-MS. Rabbits serum lipid profile, hematology and histology were investigated. Major fatty acids were palmitic acid (44%) and oleic acid (46%) in ghee, while SO contains oleic acid (56.4%) and linoleic acid (18.7%). Results showed that oxidized vegetable ghee increases the serum total cholesterol, LDL-cholesterols, triglycerides and decrease the serum glucose. Oxidized ghee produced toxic effects in the liver and hematological parameters. Sea buckthorn oil supplementation significantly lowered the serum LDL-cholesterols, triglycerides and increased serum glucose and body weight of the animals. Sea buckthorn oil was found to reduce the toxic effects and degenerative changes in the liver and thus provides protection against the thermally oxidized lipids induced oxidative stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

Drugs targeting high-density lipoprotein cholesterol for coronary artery disease management.

PubMed

Katz, Pamela M; Leiter, Lawrence A

2012-01-01

Many patients remain at high risk for future cardiovascular events despite levels of low-density lipoprotein cholesterol (LDL-C) at, or below, target while taking statin therapy. Much effort is therefore being focused on strategies to reduce this residual risk. High-density lipoprotein cholesterol (HDL-C) is a strong, independent, inverse predictor of coronary heart disease risk and is therefore an attractive therapeutic target. Currently available agents that raise HDL-C have only modest effects and there is limited evidence of additional cardiovascular risk reduction on top of background statin therapy associated with their use. It was hoped that the use of cholesteryl ester transfer protein (CETP) inhibitors would provide additional benefit, but the results of clinical outcome studies to date have been disappointing. The results of ongoing trials with other CETP inhibitors that raise HDL-C to a greater degree and also lower LDL-C, as well as with other emerging therapies are awaited. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

A new pure ω-3 eicosapentaenoic acid ethyl ester (AMR101) for the management of hypertriglyceridemia: the MARINE trial.

PubMed

Jacobson, Terry A

2012-06-01

ω-3 fatty acids reduce triglyceride (TG) levels, but corresponding increases in low-density lipoprotein cholesterol (LDL-C) levels may compromise achievement of lipid goals in patients with elevated cardiovascular risk. AMR101 is an investigational agent containing ≥96% of pure icosapent ethyl (the ethyl ester of eicosapentaenoic acid). The Phase III Multi-Center, Placebo-Controlled, Randomized, Double-Blind, 12-Week Study with an Open-Label Extension (MARINE) investigated the efficacy and safety of AMR101 in 229 patients with very high TG levels (≥500 mg/dl). AMR101 4 g/day significantly reduced median placebo-adjusted TG levels from baseline by 33.1% (p < 0.0001), and AMR101 2 g/day reduced TG levels by 19.7% (p = 0.0051). Changes in LDL-C were minimal and nonsignificant. AMR101 may offer substantial TG lowering without increases in LDL-C levels.

Hydroxychloroquine reduces low-density lipoprotein cholesterol levels in systemic lupus erythematosus: a longitudinal evaluation of the lipid-lowering effect.

PubMed

Cairoli, E; Rebella, M; Danese, N; Garra, V; Borba, E F

2012-10-01

The influence of antimalarials on lipids in systemic lupus erythematosus (SLE) has been identified in several studies but not in many prospective cohorts. The aim of this study was to longitudinally determine the effect of antimalarials on the lipoprotein profile in SLE. Fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein cholesterol (LDL) plasma levels were determined at entry and after 3 months of hydroxychloroquine (HCQ) treatment in a longitudinal evaluation of 24 patients with SLE. a significant decrease in TC (198 ± 33.7 vs. 183 ± 30.3 mg/dl, p = 0.023) and LDL levels (117 ± 31.3 vs. 101 ± 26.2 mg/dl, p = 0.023) were detected after the 3 months of HCQ therapy. The reduction of 7.6% in TC (p = 0.055) and 13.7% in LDL levels (p = 0.036) determined a significant decrease in the frequency of dyslipidemia (26% vs. 12.5%, p = 0.013) after HCQ therapy. This longitudinal study demonstrated the beneficial effect of antimalarials on lipids in SLE since this therapy induced a reduction of atherogenic lipoproteins.

Association between berries intake and cardiovascular diseases risk factors: a systematic review with meta-analysis and trial sequential analysis of randomized controlled trials.

PubMed

Luís, Ângelo; Domingues, Fernanda; Pereira, Luísa

2018-02-21

The main goal of this work was to clarify the effects of the consumption of berries on cardiovascular disease (CVD) risk factors by performing a systematic review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, followed by a meta-analysis and a trial sequential analysis (TSA) of randomized controlled trials (RCTs). The electronic search was conducted in PubMed, Scopus, SciELO, Web of Science and Cochrane Library between April and June 2016. To be included, RCTs had to report 1 or more of the following outcomes: total cholesterol (TC), HDL-cholesterol (HDL), LDL-cholesterol (LDL), triglycerides (TG), blood pressure (BP), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM), intercellular adhesion molecule-1 (ICAM), glucose, insulin, apolipoprotein A-I (Apo A-I) or apolipoprotein B (Apo B). It was observed that the intake of berries reduces TC, LDL, TG, and BP while increasing the level of HDL, suggesting a beneficial effect on the control of CVDs' risk factors. Thus, the intake of berries as nutraceuticals or functional foods could be suggested for the prevention and control of CVDs.

Superiority of dietary safflower oil over olive oil in lowering serum cholesterol and increasing hepatic mRnas for the LDL receptor and cholesterol 7alpha-hydroxylase in exogenously hypercholesterolemic (exHC) rats.

PubMed

Sato, M; Yoshida, S; Nagao, K; Imaizumi, K

2000-06-01

The exogenously hypercholesterolemic (ExHC) rat is a strain segregated from SD rats with a high response to dietary cholesterol. To understand the underlying mechanism(s) for this hypercholesterolemia, the interactive effects of dietary fatty acid and the susceptibility of rats to dietary cholesterol on the serum cholesterol concentration and hepatic mRNA abundance of the low-density lipoprotein (LDL) receptor, cholesterol 7alpha-hydroxylase (7alpha-hydroxylase) and 3-hydroxyl-3methylglutaryl (HMG) CoA reductase were examined. Both strains were fed on a diet supplemented with 10% each of olive, safflower or coconut oil with or without the addition of 1% cholesterol for one week. The ExHC rats fed on olive, safflower and coconut oil in combination with cholesterol respectively resulted in a 3.5-, 2.0- and 2.1-fold higher serum cholesterol concentration than that in the animals fed on the corresponding dietary fats without any supplementation of cholesterol (p < 0.01 by dietary cholesterol or type of fat). The dietary cholesterol dependent-elevation of serum cholesterol in the SD rats was less than 1.5-fold (p<0.01) and there was no dietary fat effect. The ExHC rats fed on the safflower oil-containing diet supplemented with cholesterol resulted in a higher mRNA abundance of the LDL receptor and 7alpha-hydroxylase than in the corresponding fat-fed rats without cholesterol (p<0.05). There was no dietary cholesterol-dependent change of mRNA abundance in either strain fed on olive or coconut oil, except for a decreased abundance of HMG CoA reductase mRNA in the olive oil-fed ExHC rats and coconut oil-fed Sprague-Dawley (SD) rats (p<0.05). These results indicate that the hepatic mRNA abundance of the LDL receptor and of 7alpha-hydroxylase depended on the dietary combination of cholesterol and a fatty acid and suggest that a linoleic acid-rich diet may alleviate exogenous hypercholesterolemia by activating the process involved in the hepatic uptake and biliary excretion of serum cholesterol.

Butter vs. Margarine: Which Is Better for My Heart?

MedlinePlus

... is made from vegetable oils, so it contains unsaturated "good" fats — polyunsaturated and monounsaturated fats. These types of fats help reduce low-density lipoprotein (LDL), or "bad," cholesterol when substituted for saturated fat. Butter, on the other hand, is made ...

Differential reactivities of four homogeneous assays for LDL-cholesterol in serum to intermediate-density lipoproteins and small dense LDL: comparisons with the Friedewald equation.

PubMed

Yamashita, Shizuya; Kawase, Ryota; Nakaoka, Hajime; Nakatani, Kazuhiro; Inagaki, Miwako; Yuasa-Kawase, Miyako; Tsubakio-Yamamoto, Kazumi; Sandoval, Jose C; Masuda, Daisaku; Ohama, Tohru; Nakagawa-Toyama, Yumiko; Matsuyama, Akifumi; Nishida, Makoto; Ishigami, Masato

2009-12-01

In routine clinical laboratory testing and numerous epidemiological studies, LDL-cholesterol (LDL-C) has been estimated commonly using the Friedewald equation. We investigated the relationship between the Friedewald equation and 4 homogeneous assays for LDL-C. LDL-C was determined by 4 homogeneous assays [liquid selective detergent method: LDL-C (L), selective solubilization method: LDL-C (S), elimination method: LDL-C (E), and enzyme selective protecting method: LDL-C (P)]. Samples with discrepancies between the Friedewald equation and the 4 homogeneous assays for LDL-C were subjected to polyacrylamide gel electrophoresis and the beta-quantification method. The correlations between the Friedewald equation and the 4 homogeneous LDL-C assays were as follows: LDL-C (L) (r=0.962), LDL-C (S) (r=0.986), LDL-C (E) (r=0.946) and LDL-C (P) (r=0.963). Discrepancies were observed in sera from type III hyperlipoproteinemia patients and in sera containing large amounts of midband and small dense LDL on polyacrylamide gel electrophoresis. LDL-C (S) was most strongly correlated with the beta-quantification method even in sera from patients with type III hyperlipoproteinemia. Of the 4 homogeneous assays for LDL-C, LDL-C (S) exhibited the closest correlation with the Friedewald equation and the beta-quantification method, thus reflecting the current clinical databases for coronary heart disease.

Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins.

PubMed

Furtado, Jeremy D; Wedel, Mark K; Sacks, Frank M

2012-04-01

Mipomersen, an antisense oligonucleotide that reduces hepatic production of apoB, has been shown in phase 2 studies to decrease plasma apoB, LDL cholesterol (LDL-C), and triglycerides. ApoC-III inhibits VLDL and LDL clearance, and it stimulates inflammatory responses in vascular cells. Concentrations of VLDL or LDL with apoC-III independently predict cardiovascular disease. We performed an exploratory posthoc analysis on a subset of hypercholesterolemic subjects obtained from a randomized controlled dose-ranging phase 2 study of mipomersen receiving 100, 200, or 300 mg/wk, or placebo for 13 wk (n = 8 each). ApoC-III-containing lipoproteins were isolated by immuno-affinity chromatography and ultracentrifugation. Mipomersen 200 and 300 mg/wk reduced total apoC-III from baseline by 6 mg/dl (38-42%) compared with placebo group (P < 0.01), and it reduced apoC-III in both apoB lipoproteins and HDL. Mipomersen 100, 200, and 300 mg doses reduced apoB concentration of LDL with apoC-III (27%, 38%, and 46%; P < 0.05). Mipomersen reduced apoC-III concentration in HDL. The drug had no effect on apoE concentration in total plasma and in apoB lipoproteins. In summary, antisense inhibition of apoB synthesis reduced plasma concentrations of apoC-III and apoC-III-containing lipoproteins. Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease (CHD) in epidemiologic studies independent of traditional risk factors.

Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins

PubMed Central

Furtado, Jeremy D.; Wedel, Mark K.; Sacks, Frank M.

2012-01-01

Mipomersen, an antisense oligonucleotide that reduces hepatic production of apoB, has been shown in phase 2 studies to decrease plasma apoB, LDL cholesterol (LDL-C), and triglycerides. ApoC-III inhibits VLDL and LDL clearance, and it stimulates inflammatory responses in vascular cells. Concentrations of VLDL or LDL with apoC-III independently predict cardiovascular disease. We performed an exploratory posthoc analysis on a subset of hypercholesterolemic subjects obtained from a randomized controlled dose-ranging phase 2 study of mipomersen receiving 100, 200, or 300 mg/wk, or placebo for 13 wk (n = 8 each). ApoC-III–containing lipoproteins were isolated by immuno-affinity chromatography and ultracentrifugation. Mipomersen 200 and 300 mg/wk reduced total apoC-III from baseline by 6 mg/dl (38–42%) compared with placebo group (P < 0.01), and it reduced apoC-III in both apoB lipoproteins and HDL. Mipomersen 100, 200, and 300 mg doses reduced apoB concentration of LDL with apoC-III (27%, 38%, and 46%; P < 0.05). Mipomersen reduced apoC-III concentration in HDL. The drug had no effect on apoE concentration in total plasma and in apoB lipoproteins. In summary, antisense inhibition of apoB synthesis reduced plasma concentrations of apoC-III and apoC-III–containing lipoproteins. Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease (CHD) in epidemiologic studies independent of traditional risk factors. PMID:22301884

Fluvastatin

MedlinePlus

... fatty substances such as low-density lipoprotein (LDL) cholesterol ('bad cholesterol') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol ('good cholesterol') in the blood. Fluvastatin may also ...

Simvastatin

MedlinePlus

... fatty substances such as low-density lipoprotein (LDL) cholesterol (''bad cholesterol'') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol (''good cholesterol'') in the blood. Simvastatin may also ...

Pravastatin

MedlinePlus

... fatty substances such as low-density lipoprotein (LDL) cholesterol ('bad cholesterol') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol ('good cholesterol') in the blood. Pravastatin is in ...

The effect of essential oils of dietary wormwood (Artemisia princeps), with and without added vitamin E, on oxidative stress and some genes involved in cholesterol metabolism.

PubMed

Chung, Mi Ja; Kang, Ah-Young; Park, Sung-Ok; Park, Kuen-Woo; Jun, Hee-Jin; Lee, Sung-Joon

2007-08-01

Wormwood (Artemisia princeps) due to the abundance of antioxidant in its essential oils (EO), has been used as a traditional drug and health food in Korea. Oxidative stress plays an important role in the etiology of atherosclerosis thus antioxidative chemicals improves hepatic lipid metabolism partly by reducing oxysterol formation. The antioxidant activity was assessed using two methods, human low-density lipoprotein (LDL) oxidation and the anti-DPPH free radical assays. It was found that the antioxidant activity of EO with vitamin E higher than EO alone. To study mechanisms accounting for the antiatherosclerotic properties of this wormwood EO, we examined the expression of key genes in cholesterol metabolism such as the LDL receptor, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and sterol regulatory element binding proteins. The induction was increased up to twofold at 0.05 mg/mL of EO treatment in HepG2 cells for 24h. When EO (0.2 mg/mL) was co-incubated with vitamin E, interestingly, the LDL receptor was dramatically induced by 5-6-folds. HMG-CoA reductase did not change. However, treatment with the higher concentration resulted in cytotoxicity. Our data suggest that wormwood EO with vitamin E may be anti-atherogenic due to their inhibition of LDL oxidation and upregulation of the LDL receptor.

Equol status and blood lipid profile in hyperlipidemia after consumption of diets containing soy foods.

PubMed

Wong, Julia M W; Kendall, Cyril W C; Marchie, Augustine; Liu, Zhen; Vidgen, Ed; Holmes, Candice; Jackson, Chung-Ja; Josse, Robert G; Pencharz, Paul B; Rao, A Venketeshwer; Vuksan, Vladimir; Singer, William; Jenkins, David J A

2012-03-01

Recent analyses have challenged the effectiveness of soy foods as part of a cardiovascular risk reduction diet. The objective of the study was to show whether equol status determines the effectiveness of soy foods to lower LDL cholesterol and to raise HDL cholesterol. Eighty-five hypercholesterolemic men and postmenopausal women (42 men, 43 women) participated in 1 of 3 studies that represented a range of soy interventions and that followed the same general protocol at a Canadian university hospital research center. Soy foods were provided for 1 mo at doses of 30-52 g/d for the 3 studies as follows: 1) soy foods with either high-normal (73 mg/d) or low (10 mg/d) isoflavones, 2) soy foods with or without a prebiotic to enhance colonic fermentation (10 g polyfructans/d), or 3) soy foods with a low-carbohydrate diet (26% carbohydrate). Studies 1 and 2 were randomized controlled crossover trials, and study 3 was a parallel study. The separation of the group into equol producers (n = 30) and nonproducers (n = 55) showed similar reductions from baseline in LDL cholesterol (-9.3 ± 2.5% and -11.1 ± 1.6%, respectively; P = 0.834), with preservation of HDL cholesterol and apolipoprotein A-I only in equol producers compared with reductions in nonproducers (HDL cholesterol: +0.9 ± 2.7% compared with -4.3 ± 1.1%, P = 0.006; apolipoprotein A-I: -1.0 ± 1.1% compared with -4.7 ± 1.0%; P = 0.011). The amount of urinary equol excreted did not relate to the changes in blood lipids. Soy foods reduced serum LDL cholesterol equally in both equol producers and nonproducers. However, in equol producers, ~35% of our study population, soy consumption had the added cardiovascular benefit of maintaining higher HDL-cholesterol concentrations than those seen in equol nonproducers. This trial was registered at clinicaltrials.gov as NCT00877825 (study 1), NCT00516594 (study 2), and NCT00256516 (study 3).

No additional cholesterol-lowering effect observed in the combined treatment of red yeast rice and Lactobacillus casei in hyperlipidemic patients: A double-blind randomized controlled clinical trial.

PubMed

Lee, Chien-Ying; Yu, Min-Chien; Perng, Wu-Tsun; Lin, Chun-Che; Lee, Ming-Yung; Chang, Ya-Lan; Lai, Ya-Yun; Lee, Yi-Ching; Kuan, Yu-Hsiang; Wei, James Cheng-Chung; Shih, Hung-Che

2017-08-01

To observe the effect of combining red yeast rice and Lactobacillus casei (L. casei) in lowering cholesterol in patients with primary hyperlipidemia, the later has also been shown to remove cholesterol in in vitro studies. A double-blind clinical trial was conducted to evaluate the cholesterol-lowering effect of the combination of red yeast rice and L. casei. Sixty patients with primary hyperlipidemia were recruited and randomized equally to either the treatment group (red yeast rice + L. casei) or the control group (red yeast rice + placebo). One red yeast rice capsule and two L. casei capsules were taken twice a day. The treatment lasted for 8 weeks, with an extended follow-up period of 4 weeks. The primary endpoint was a difference of serum low-density lipoprotein cholesterol (LDL-C) level at week 8. At week 8, the LDL-C serum level in both groups was lower than that at baseline, with a decrease of 33.85±26.66 mg/dL in the treatment group and 38.11±30.90 mg/dL in the control group; however, there was no statistical difference between the two groups (P>0.05). The total cholesterol was also lower than the baseline in both groups, yet without a statistical difference between the two groups. The only statistically signifificant difference between the two groups was the average diastolic pressure at week 12, which dropped by 2.67 mm Hg in the treatment group and increased by 4.43 mm Hg in the placebo group (P<0.05). The antihypertensive activity may be associated with L. casei. Red yeast rice can signifificantly reduce LDL-C, total cholesterol and triglyceride. The combination of red yeast rice and L. casei did not have an additional effect on lipid profifiles.

The small dense LDL particle/large buoyant LDL particle ratio is associated with glucose metabolic status in pregnancy.

PubMed

Chen, Yanmin; Du, Mengkai; Xu, Jianyun; Chen, Danqing

2017-12-14

The lipoprotein subfraction particle profile can be used to improve clinical assessments of cardiovascular disease risk and contribute to early detection of atherogenic dyslipidemia. Lipid alterations in gestational diabetes have been extensively studied, but the results have been inconsistent. Here, we investigated serum lipoprotein subfraction particle levels and their association with glucose metabolic status in pregnancy. Twenty-eight pregnant women with gestational diabetes and 56 pregnant women with normal glucose tolerance matched for body mass index were enrolled in this study. We assessed fasting serum lipid concentrations and lipoprotein subfraction particle levels in participants between 24 and 28 weeks of gestation. The level of low-density lipoprotein (LDL) cholesterol was significantly lower in women with gestational diabetes than in those with normal glucose tolerance, but the triglyceride and high-density lipoprotein (HDL) cholesterol levels of the two groups were similar. Lipoprotein particle analysis showed that very-low-density lipoprotein (VLDL) particle number and the small dense LDL particle/large buoyant LDL particle (sdLDL-P/lbLDL-P) ratio were significantly higher in women with gestational diabetes than in those with normal glucose tolerance (P = 0.013 and P = 0.015, respectively). In multivariate analysis, fasting glucose was independently and positively associated with sdLDL-P/lbLDL-P ratio even after adjustment for maternal age, gestational weight gain, BMI and LDL cholesterol (standardized Beta = 0.214, P = 0.029). The sdLDL-P/lbLDL-P ratio is higher in GDM compared with non-diabetic pregnant women, and positively and independently associated with fasting glucose in pregnant women.

Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

PubMed Central

Postmus, Iris; Trompet, Stella; Deshmukh, Harshal A.; Barnes, Michael R.; Li, Xiaohui; Warren, Helen R.; Chasman, Daniel I.; Zhou, Kaixin; Arsenault, Benoit J.; Donnelly, Louise A.; Wiggins, Kerri L.; Avery, Christy L.; Griffin, Paula; Feng, QiPing; Taylor, Kent D.; Li, Guo; Evans, Daniel S.; Smith, Albert V.; de Keyser, Catherine E.; Johnson, Andrew D.; de Craen, Anton J. M.; Stott, David J.; Buckley, Brendan M.; Ford, Ian; Westendorp, Rudi G. J.; Eline Slagboom, P.; Sattar, Naveed; Munroe, Patricia B.; Sever, Peter; Poulter, Neil; Stanton, Alice; Shields, Denis C.; O’Brien, Eoin; Shaw-Hawkins, Sue; Ida Chen, Y.-D.; Nickerson, Deborah A.; Smith, Joshua D.; Pierre Dubé, Marie; Matthijs Boekholdt, S.; Kees Hovingh, G.; Kastelein, John J. P.; McKeigue, Paul M.; Betteridge, John; Neil, Andrew; Durrington, Paul N.; Doney, Alex; Carr, Fiona; Morris, Andrew; McCarthy, Mark I.; Groop, Leif; Ahlqvist, Emma; Bis, Joshua C.; Rice, Kenneth; Smith, Nicholas L.; Lumley, Thomas; Whitsel, Eric A.; Stürmer, Til; Boerwinkle, Eric; Ngwa, Julius S.; O’Donnell, Christopher J.; Vasan, Ramachandran S.; Wei, Wei-Qi; Wilke, Russell A.; Liu, Ching-Ti; Sun, Fangui; Guo, Xiuqing; Heckbert, Susan R; Post, Wendy; Sotoodehnia, Nona; Arnold, Alice M.; Stafford, Jeanette M.; Ding, Jingzhong; Herrington, David M.; Kritchevsky, Stephen B.; Eiriksdottir, Gudny; Launer, Leonore J.; Harris, Tamara B.; Chu, Audrey Y.; Giulianini, Franco; MacFadyen, Jean G.; Barratt, Bryan J.; Nyberg, Fredrik; Stricker, Bruno H.; Uitterlinden, André G.; Hofman, Albert; Rivadeneira, Fernando; Emilsson, Valur; Franco, Oscar H.; Ridker, Paul M.; Gudnason, Vilmundur; Liu, Yongmei; Denny, Joshua C.; Ballantyne, Christie M.; Rotter, Jerome I.; Adrienne Cupples, L.; Psaty, Bruce M.; Palmer, Colin N. A.; Tardif, Jean-Claude; Colhoun, Helen M.; Hitman, Graham; Krauss, Ronald M.; Wouter Jukema, J; Caulfield, Mark J.; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C. A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G.; Blackwell, Jenefer M.; Brown, Matthew A.; Corvin, Aiden; McCarthy, Mark I.; Spencer, Chris C. A.

2014-01-01

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response. PMID:25350695

What Are High Blood Cholesterol and Triglycerides?

MedlinePlus

ANSWERS by heart Lifestyle + Risk Reduction Cholesterol What Are High Blood Cholesterol and Triglycerides? Cholesterol travels to the body’s cells through the bloodstream by way of lipoproteins (LDL and ...

Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds.

PubMed

Ramprasath, Vanu R; Jenkins, David J A; Lamarche, Benoit; Kendall, Cyril W C; Faulkner, Dorothea; Cermakova, Luba; Couture, Patrick; Ireland, Chris; Abdulnour, Shahad; Patel, Darshna; Bashyam, Balachandran; Srichaikul, Korbua; de Souza, Russell J; Vidgen, Edward; Josse, Robert G; Leiter, Lawrence A; Connelly, Philip W; Frohlich, Jiri; Jones, Peter J H

2014-10-18

Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption. The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins. Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months. No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased β-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted β-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; β-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; β-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and β-sitosterol concentrations were negatively correlated (p < 0.001) with total and LDL-C levels. Results demonstrate that consuming a portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction. clinicaltrials.gov Identifier: NCT00438425.

The effects of treatment on lipoprotein subfractions evaluated by polyacrylamide gel electrophoresis in patients with autoimmune hypothyroidism and hyperthyroidism.

PubMed

Minarikova, Zuzana; Gaspar, Ludovit; Kruzliak, Peter; Celecová, Zuzana; Oravec, Stanislav

2014-10-10

Atherogenic dyslipoproteinemia is one of the most important risk factor for atherosclerotic changes development. Hypothyroidism is one of the most common causes of secondary dyslipidemias which results from reduced LDL clearance and therefore raised levels of LDL and apoB. Association between small dense LDL (sdLDL) presentation and thyroid status has been examinated using polyacrylamide gel electrophoresis for lipoprotein subfractions evaluation. 40 patients with diagnosed autoimmune hypothyroidism and 30 patients with autoimmune hyperthyroidism were treated with thyroxine replacement or thyreo-suppressive treatment. In both groups lipid profiles, LDL subractions, apolipoproteins (apoA1, apoB), apoA1/apoB ratio and atherogenic index of plazma (AIP) were examined before treatment and in state of euthyreosis. Thyroxine replacement therapy significantly reduced levels of total cholesterol (TC), LDL, triglycerides (TG) and also decreased levels of sdLDL (8,55±11,671 vs 0,83±1,693mg/dl; p<0,001), apoB and AIP. For estimation of atherogenic lipoprotein profile existence an AIP evaluation seems to be better than apoB measurement because of the more evident relationship with sdLDL (r=0,538; p<0,01). Thyreo-suppressive therapy significantly increased levels of TC, LDL, TG and apoB. The sdLDL was not found in hyperthyroid patients. Atherogenic lipoprotein profile was present in 52.5% of hypothyroid subjects, which is higher prevalence than in normal, age-related population. Substitution treatment leads to an improvement of the lipid levels, TG, apoB, AIP and LDL subclasses. It significantly changed the presentation of sdLDL - we noticed shift to large, less atherogenic LDL particles. Significantly positive correlation between sdLDL and TAG; sdLDL and VLDL alerts to hypertriglyceridemia as a major cardiovascular risk factor.

Athletes with higher VO2max present reduced oxLDL after a marathon race

PubMed Central

Bachi, André L L; Sierra, Ana Paula R; Rios, Francisco J O; Gonçalves, Danieli A; Ghorayeb, Nabil; Abud, Ronaldo L; Victorino, Angélica B; dos Santos, Juliana M B; Kiss, Maria Augusta D P; Pithon-Curi, Tania C; Vaisberg, Mauro

2015-01-01

Background During a session of prolonged and exhaustive exercise, such as a marathon race, large quantities of free radicals are produced and can oxidise (ox) several molecules, such as low-density lipoprotein (LDL). To prevent oxidative damage, athletes present higher antioxidant levels. However, the effect of marathon running on the natural IgM or IgG anti-oxLDL autoantibodies is not understood. Thus, we investigated the effect of a marathon race on oxidative stress and the mechanisms of control of this stress. Methods Blood samples of 20 marathon runners were collected 24 hours before, immediately and 72 hours after a marathon race to evaluate: plasma lipid profile; serum levels of oxLDL and anti-oxLDL autoantibodies (IgM and IgG isotype) and total antioxidant capacity (TAC). Maximum oxygen uptake (VO2max) was also determined. Results Immediately after the race, oxLDL and TAC levels decreased in comparison to the basal levels; however, the IgM or IgG anti-oxLDL levels remain unchanged. Whereas no differences were observed in the IgM or IgG anti-oxLDL levels 72h after the marathon, the oxLDL and TAC levels returned to the basal values. Significant positive correlations were observed between oxLDL and LDL-cholesterol before, and 72h after the marathon. Significant negative correlations were observed between oxLDL and VO2max immediately after the marathon and 72 h later, as well as between oxLDL and TAC 72 h after the race. Conclusions Athletes with a higher VO2max and total antioxidant activity presented reduced LDL oxidation. The levels of IgM or IgG anti-oxLDL autoantibodies were not affected by running the marathon. PMID:27900109

Regulation of hepatic 7 alpha-hydroxylase expression by dietary psyllium in the hamster.

PubMed Central

Horton, J D; Cuthbert, J A; Spady, D K

1994-01-01

Soluble fiber consistently lowers plasma total and low density lipoprotein (LDL)-cholesterol concentrations in humans and various animal models including the hamster; however, the mechanism of this effect remains incompletely defined. We performed studies to determine the activity of dietary psyllium on hepatic 7 alpha-hydroxylase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase and LDL receptor expression in the hamster. In animals fed a cholesterol-free semisynthetic diet containing 7.5% cellulose (avicel) as a fiber source, substitution of psyllium for avicel increased hepatic 7 alpha-hydroxylase activity and mRNA levels by 3-4-fold. Comparable effects on 7 alpha-hydroxylase expression were observed with 1% cholestyramine. Psyllium also increased hepatic 7 alpha-hydroxylase activity and mRNA in animals fed a diet enriched with cholesterol and triglyceride. Activation of 7 alpha-hydroxylase was associated with an increase in hepatic cholesterol synthesis that was apparently not fully compensatory since the cholesterol content of the liver declined. Although dietary psyllium did not increase hepatic LDL receptor expression in animals fed the cholesterol-free, very-low-fat diet, it did increase (or at least restore) receptor expression that had been downregulated by dietary cholesterol and triglyceride. Thus, 7.5% dietary psyllium produced effects on hepatic 7 alpha-hydroxylase and LDL metabolism that were similar to those of 1% cholestyramine. Induction of hepatic 7 alpha-hydroxylase activity by dietary psyllium may account, in large part, for the hypocholesterolemic effect of this soluble fiber. Images PMID:8182140

The composition and metabolism of large and small LDL

USDA-ARS?s Scientific Manuscript database

Decreased size and increased density of LDL have been associated with increased coronary heart disease (CHD) risk. Elevated plasma concentrations of small dense LDL (sdLDL) correlate with high plasma triglycerides and low HDL cholesterol levels. This review highlights recent findings about the met...

[Dyslipidemia in schoolchildren with a history of a high birth weight].

PubMed

Rodríguez Vargas, Nuris; Martínez Pérez, Tania P; Martínez García, Rolando; Garriga Reyes, Mailin; Ortega Soto, Manuel; Rojas, Teresa

2014-01-01

The process of atherosclerosis begins at early ages and is closely related to plasma lipid levels, specifically, an increase in low density lipoprotein (LDL), very low density lipoprotein (VLDL), and a decrease in high density lipoprotein (HDL). To determine if high birth weight, or macrosomia, is of predictive value for dyslipidemia in school children. A descriptive study with a case control design was conducted on two groups of children; one group of 140 children with a history of macrosomia, and another group of 100 children with normal weight at birth, born between January 1992 and December 1995. The aim was the early identification of atherosclerotic risk factors in school children with high weight at birth. Anthropometric variables and lipid profile were studied (cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, and triglycerides). There were significant differences between the mean weights of the two groups. There were no significant statistical differences between the two groups in the cholesterol levels (93.57% normal and 6.43% abnormal in the study group, and 90.00% normal and 10.00% abnormal in the control group), or in the values of HDL cholesterol. LDL cholesterol was abnormal in more children in the control group, and abnormal values of triglycerides were observed in 14.00% of cases in the study group 0.00% in the control group. High birth weight is not a predictive factor for hypercholesterolemia or HDL and LDL-cholesterol esters, but is positive for triglycerides in our study. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

ABCG1-mediated generation of extracellular cholesterol microdomains[S

PubMed Central

Freeman, Sebastian R.; Jin, Xueting; Anzinger, Joshua J.; Xu, Qing; Purushothaman, Sonya; Fessler, Michael B.; Addadi, Lia; Kruth, Howard S.

2014-01-01

Previous studies have demonstrated that the ATP-binding cassette transporters (ABC)A1 and ABCG1 function in many aspects of cholesterol efflux from macrophages. In this current study, we continued our investigation of extracellular cholesterol microdomains that form during enrichment of macrophages with cholesterol. Human monocyte-derived macrophages and mouse bone marrow-derived macrophages, differentiated with macrophage colony-stimulating factor (M-CSF) or granulocyte macrophage colony-stimulation factor (GM-CSF), were incubated with acetylated LDL (AcLDL) to allow for cholesterol enrichment and processing. We utilized an anti-cholesterol microdomain monoclonal antibody to reveal pools of unesterified cholesterol, which were found both in the extracellular matrix and associated with the cell surface, that we show function in reverse cholesterol transport. Coincubation of AcLDL with 50 μg/ml apoA-I eliminated all extracellular and cell surface-associated cholesterol microdomains, while coincubation with the same concentration of HDL only removed extracellular matrix-associated cholesterol microdomains. Only at an HDL concentration of 200 µg/ml did HDL eliminate the cholesterol microdomains that were cell-surface associated. The deposition of cholesterol microdomains was inhibited by probucol, but it was increased by the liver X receptor (LXR) agonist TO901317, which upregulates ABCA1 and ABCG1. Extracellular cholesterol microdomains did not develop when ABCG1-deficient mouse bone marrow-derived macrophages were enriched with cholesterol. Our findings show that generation of extracellular cholesterol microdomains is mediated by ABCG1 and that reverse cholesterol transport occurs not only at the cell surface but also within the extracellular space. PMID:24212237

Trans fatty acids and cholesterol levels: an evidence map of the available science

USDA-ARS?s Scientific Manuscript database

High intakes of industrial trans fatty acids (iTFA) increase circulating low density lipoprotein cholesterol (LDL-C) levels, which has implicated iTFA in coronary heart disease (CHD) risk. Published data on iTFA and LDL-C, however, represent higher intake levels than the U.S. population currently co...

Clinical characteristics and evaluation of LDL-cholesterol treatment of the Spanish Familial Hypercholesterolemia Longitudinal Cohort Study (SAFEHEART)

USDA-ARS?s Scientific Manuscript database

Familial hypercholesterolemia (FH) patients are at high risk for premature coronary heart disease (CHD). Despite the use of statins, most patients do not achieve an optimal LDL-cholesterol goal. The aims of this study are to describe baseline characteristics and to evaluate Lipid Lowering Therapy (L...

[Factors affecting the control of blood pressure and lipid levels in patients with cardiovascular disease: the PREseAP Study].

PubMed

Orozco-Beltrán, Domingo; Brotons, Carlos; Moral, Irene; Soriano, Nuria; Del Valle, María A; Rodríguez, Ana I; Pepió, Josep M; Pastor, Ana

2008-03-01

The aim of this observational study was to identify factors influencing the control of blood pressure (i.e., <140/90 mmHg, or <130/80 mmHg in diabetic patients) and low-density lipoprotein (LDL) cholesterol level (<100 mg/dL) in 1223 patients with cardiovascular disease. Overall, 70.2% of patients were men, and their mean age was 66.4 years. Blood pressure was poorly controlled in 50.9% (95% confidence interval [CI], 46.9%-54.8%) and the LDL cholesterol level was poorly controlled in 60.1% (95% CI, 56.3%-63.9%). Determinants of poor blood pressure control were diabetes, hypertension, no previous diagnosis of heart failure, previous diagnosis of peripheral artery disease or stroke, obesity, and no lipid-lowering treatment. Determinants of poor LDL cholesterol control were no lipid-lowering treatment, no previous diagnosis of ischemic heart disease, no antihypertensive treatment, and dyslipidemia. The factors affecting blood pressure control were different from those affecting LDL cholesterol control, an observation that should be taken into account when implementing treatment recommendations for achieving therapeutic objectives in secondary prevention.

Mangifera indica L. extract (Vimang®) reduces plasma and liver cholesterol and leucocyte oxidative stress in hypercholesterolemic LDL receptor deficient mice.

PubMed

Dorighello, Gabriel G; Inada, Natália M; Paim, Bruno A; Pardo-Andreu, Gilberto L; Vercesi, Anibal E; Oliveira, Helena C F

2018-06-01

Cardiovascular diseases are major causes of death worldwide. Beyond the classical cholesterol risk factor, other conditions such as oxidative stress are well documented to promote atherosclerosis. The Mangifera indica L. extract (Vimang®) was reported to present antioxidant and hypocholesterolemic properties. Thus, here we evaluate the effects of Vimang treatment on risk factors of the atherosclerosis prone model of familial hypercholesterolemia, the LDL receptor knockout mice. Mice were treated with Vimang during 2 weeks and were fed a cholesterol-enriched diet during the second week. The Vimang treated mice presented significantly reduced levels of plasma (15%) and liver (20%) cholesterol, increased plasma total antioxidant capacity (10%) and decreased reactive oxygen species (ROS) production by spleen mononuclear cells (50%), P < 0.05 for all. In spite of these benefits, the average size of aortic atherosclerotic lesions stablished in this short experimental period did not change significantly in Vimang treated mice. Therefore, in this study we demonstrated that Vimang has protective effects on systemic and tissue-specific risk factors, but it is not sufficient to promote a reduction in the initial steps of atherosclerosis development. In addition, we disclosed a new antioxidant target of Vimang, the spleen mononuclear cells that might be relevant for more advanced stages of atherosclerosis. © 2018 International Federation for Cell Biology.

The hypocholesterolemic activity of açaí (Euterpe oleracea Mart.) is mediated by the enhanced expression of the ATP-binding cassette, subfamily G transporters 5 and 8 and low-density lipoprotein receptor genes in the rat.

PubMed

de Souza, Melina Oliveira; Souza E Silva, Lorena; de Brito Magalhães, Cíntia Lopes; de Figueiredo, Bianca Barros; Costa, Daniela Caldeira; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia

2012-12-01

Previous studies have demonstrated that the ingestion of açaí pulp can improve serum lipid profile in various animal models; therefore, we hypothesized that açaí pulp (Euterpe oleracea Mart.) may modulate the expression of the genes involved in cholesterol homeostasis in the liver and increase fecal excretion, thus reducing serum cholesterol. To test this hypothesis, we analyzed the expression of 7α-hydroxylase and ATP-binding cassette, subfamily G transporters (ABCG5 and ABCG8), which are genes involved with the secretion of cholesterol in the rat. We also evaluated the expression of sterol regulatory element-binding protein 2, 3-hydroxy-3-methylglutaryl CoA reductase, low-density lipoprotein receptor (LDL-R), and apolipoprotein B100, which are involved in cholesterol biosynthesis. Female Fischer rats were divided into 4 groups: the C group, which was fed a standard AIN-93 M diet; the CA group, which was fed a standard diet supplemented with 2% açaí pulp; the H group, which was fed a hypercholesterolemic diet (25% soy oil and 1% cholesterol); and the HA group, which was fed a hypercholesterolemic diet supplemented with 2% açaí pulp. At the end of the experimental period, the rats were euthanized, and their blood and livers were collected. The HA group exhibited a significant decrease in serum total cholesterol, low-density lipoprotein cholesterol, and atherogenic index and also had increased high-density lipoprotein cholesterol and cholesterol excretion in feces compared with the H group. In addition, the expression of the LDL-R, ABCG5, and ABCG8 genes was significantly increased by the presence of açaí pulp. These results suggest that açaí pulp promotes a hypocholesterolemic effect in a rat model of dietary-induced hypercholesterolemia through an increase in the expression of ATP-binding cassette, subfamily G transporters, and LDL-R genes. Copyright © 2012 Elsevier Inc. All rights reserved.

Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice.

PubMed

Graham, Mark J; Lemonidis, Kristina M; Whipple, Charles P; Subramaniam, Amuthakannan; Monia, Brett P; Crooke, Stanley T; Crooke, Rosanne M

2007-04-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a member of a family of proteases that is thought to promote the degradation of the low density lipoprotein receptor (LDLR) through an as yet undefined mechanism. We developed second generation antisense oligonucleotide (ASO) inhibitors targeting murine PCSK9 to determine their potential as lipid-lowering agents. Administration of a PCSK9 ASO to high fat-fed mice for 6 weeks reduced total cholesterol and LDL by 53% and 38%, respectively. Moreover, inhibition of PCSK9 expression resulted in a 2-fold increase in hepatic LDLR protein levels. This phenotype closely resembles that reported previously in Pcsk9-deficient mice. The absence of cholesterol lowering in Ldlr-deficient mice effectively demonstrated a critical role for this receptor in mediating the lipid-lowering effects of PCSK9 inhibition. Antisense inhibition of PCSK9 is an attractive and novel therapeutic approach for treating hypercholesterolemia in human.

First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro.

PubMed

Canfrán-Duque, Alberto; Barrio, Luis C; Lerma, Milagros; de la Peña, Gema; Serna, Jorge; Pastor, Oscar; Lasunción, Miguel A; Busto, Rebeca

2016-03-18

First- and second-generation antipsychotics (FGAs and SGAs, respectively), have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL)-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanineperchlorate (DiI)-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2) and LBPA (lysobisphosphatidic acid), which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1) and coatomer subunit β (β-COP) were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes' internal milieu induced by haloperidol affects lysosomal functionality.

Current and future pharmacologic options for the management of patients unable to achieve low-density lipoprotein-cholesterol goals with statins.

PubMed

El Harchaoui, Karim; Akdim, Fatima; Stroes, Erik S G; Trip, Mieke D; Kastelein, John J P

2008-01-01

Low-density lipoprotein-cholesterol (LDL-C) lowering is the mainstay of the current treatment guidelines in the management of cardiovascular risk. HMG-CoA reductase inhibitors (statins) are currently the most effective LDL-C-lowering drugs. However, a substantial number of patients do not reach treatment targets with statins. Therefore, an unmet medical need exists for lipid-lowering drugs with novel mechanisms of action to reach the recommended cholesterol target levels, either by monotherapy or combination therapy. Upregulation of the LDL receptor with squalene synthase inhibitors has shown promising results in animal studies but the clinical development of the lead compound lapaquistat (TAK-475) has recently been discontinued. Ezetimibe combined with statins allowed significantly more patients to reach their LDL-C targets. Other inhibitors of intestinal cholesterol absorption such as disodium ascorbyl phytostanol phosphate (FM-VP4) and bile acid transport inhibitors have shown positive results in early development trials, whereas the prospect of acyl coenzyme A: cholesterol acyltransferase inhibition in cardiovascular prevention is dire. Selective inhibition of messenger RNA (mRNA) by antisense oligonucleotides is a new approach to modify cholesterol levels. The inhibition of apolipoprotein B mRNA is in advanced development and mipomersen sodium (ISIS 301012) has shown striking results in phase II studies both as monotherapy as well as in combination with statins.

Does non-alcoholic fatty liver impair alterations of plasma lipoproteins and associated factors in metabolic syndrome?

PubMed

Lucero, Diego; Zago, Valeria; López, Graciela I; Graffigna, Mabel; López, Gustavo H; Fainboim, Hugo; Miksztowicz, Verónica; Gómez Rosso, Leonardo; Belli, Susana; Levalle, Oscar; Berg, Gabriela; Brites, Fernando; Wikinski, Regina; Schreier, Laura

2011-03-18

Hepatic steatosis (HS) is closely associated to metabolic syndrome (MS). Both, VLDL-triglyceride oversecretion and intrahepatic deposits, can take place. We evaluated VLDL characteristics, CETP, hepatic lipase (HL), IDL and small dense LDL (sdLDL), in patients with HS associated to MS. We studied 3 groups matched by age and sex: 25 MS patients with HS (diagnosed by ultrasonography), 25 MS patients without HS and 25 healthy controls. Main measurements were: lipid profile, free fatty acids, VLDL composition, VLDL size by HPLC, CETP and HL activities, IDL-cholesterol and sdLDL-cholesterol. Patients with HS presented higher triglyceride levels, HOMA-IR and free fatty acids, VLDL mass and VLDL-apoB (p<0.05). No differences in VLDL composition were observed. MS groups presented higher proportion of large VLDL than controls (p<0.05). HS group showed higher CETP than controls (p=0.01) and almost higher than MS without HS (p=0.06). CETP correlated with VLDL-cholesterol content, r=0.48, p<0.005. The increase in sdLDL-cholesterol correlated with CETP (r=0.47) and HL (r=0.56), independent of insulin resistance (p<0.003). Despite intrahepatic fat, patients with HS secreted higher number of VLDL particles. CETP would have a remodeling action on VLDL in circulation, enriching it in cholesterol and also favoring, together with HL, the formation of sdLDL. Copyright © 2010 Elsevier B.V. All rights reserved.

Guar gum effects on food intake, blood serum lipids and glucose levels of Wistar rats.

PubMed

Frias, A C; Sgarbieri, V C

1998-01-01

The effects of guar gum derived from the endosperm of Cyamopsis tetragonoloba (75% soluble fiber, 7.6% insoluble fiber, 2.16% crude protein, 0.78% total lipids, 0.54% ash and 9.55% moisture) on food intake, levels of blood serum cholesterol, triacylglycerols, glucose and LDL and HDL-cholesterol were studied. The effects of guar gum on indices of protein absorption and utilization were also investigated. Diets containing 0%, 10% and 20% (w/w) guar gum or 10% and 20% cellulose powder (reference) were fed to normal rats for 60 days. The rats fed the guar gum diets showed significantly (p < or = 0.05) lower levels of blood serum cholesterol, triacylglycerols, reduced food intake and body weight gain. Furthermore, a concomitant increase in HDL-cholesterol with a substantial elevation of the HDL/LDL cholesterol ratio were noted. Guar gum decreased blood serum glucose only during the first month of the experiment, and no changes in the indices of protein absorption and utilization were found. The guar gum caused a 10% increase in the small intestine length and a 25% retardation in the intestinal transit. The results of this research suggested that guar gum could potentially be effective in the treatment of hypercholesterolemia and obesity in humans.

A randomized, placebo-controlled, crossover study of an herbal preparation containing Vernonia cinerea in the treatment of type 2 diabetes.

PubMed

Bin Sayeed, Muhammad Shahdaat; Mostofa, A G M; Ferdous, F M Touhidul Islam; Islam, Md Siddiqul

2013-09-01

A randomized, single-center, double-blind, crossover clinical trial investigated the effects of an herbal preparation containing Vernonia cinerea in patients with type 2 diabetes mellitus. 48 patients with type 2 diabetes mellitus for longer than 6 months were divided into two groups matched for demographic and paraclinical variables. One group received a standard preparation of V. cinerea for 3 months, followed by placebo for another 3 months, and the other group received treatment in the reverse order. All patients received detailed advice on diet, exercise, and lifestyle modification. Glucose level was documented every 2 weeks, and hemoglobin A1c, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, and creatinine levels were determined at recruitment, 3 months, and study completion at 6 months. Glucose, hemoglobin A1c, cholesterol, LDL cholesterol, and triglyceride levels decreased significantly in both groups. No significant differences were seen in aspartate aminotransferase, alanine aminotransferase, or creatinine levels, indicating that use of the herbal preparation had no adverse effect on liver or renal function. Herbal treatment with V. cinerea has a beneficial effect on reducing the glycemic state in patients with type 2 diabetes.

Superior short-term cholesterol control and achievement of the adult treatment panel III low-density lipoprotein goals with initiation of statin therapy by the time of hospital discharge following acute myocardial infarction.

PubMed

Bybee, Kevin A; Powell, Brian D; Williams, Brent A; Murphy, Joseph G; Kopecky, Stephen L; Wright, R Scott

2004-03-15

In a community-based population, we compared serum cholesterol concentrations following hospital discharge after acute myocardial infarction based on statin therapy at the time of hospital discharge. At the time of follow-up cholesterol measurement, patients discharged from the hospital on a statin had lower mean low-density lipoprotein (LDL) (106.4 vs 116.7 mg/dl, p <0.01) and total cholesterol (182.2 vs 193.6 mg/dl, p <0.01) concentrations, larger absolute reductions in LDL (-24.7 vs -4.7 mg/dl, p <0.01) and total cholesterol (-24.2 vs -0.1 mg/dl, p <0.01) from pre-myocardial infarction levels, and superior attainment of the Adult Treatment Panel III LDL goal of <100 mg/dl at the time of follow-up compared with patients who were discharged without a statin (49% vs 33%; adjusted odds ratio 2.56; p <0.01).

Metabolic profiles and lipoprotein lipid concentrations in non-obese and obese patients with polycystic ovarian disease.

PubMed

Mahabeer, S; Naidoo, C; Norman, R J; Jialal, I; Reddi, K; Joubert, S M

1990-10-01

Clinical parameters, androgen status and lipoprotein lipid profiles were assessed in 10 non-obese and 10 obese patients with polycystic ovarian disease (PCOD) and reference subjects matched for age, height and weight. Both obese and non-obese women with PCOD had significantly higher androgen levels when compared to the reference groups. When comparison of lipoprotein lipid profiles were made between groups, non-obese women with PCOD had significantly higher total cholesterol, triglycerides and LDL-cholesterol levels than non-obese reference subjects. Obese PCOD women manifested significantly higher total cholesterol, LDL-cholesterol, cholesterol/HDL, and LDL/HDL values than did obese reference subjects. Correlations between serum androgens and lipoprotein lipid concentrations in PCOD and normal women were unhelpful. Both non-obese and obese patients with PCOD had significantly higher systolic and diastolic blood pressures (BPs) than the reference groups. Thus, both non-obese and obese women with PCOD manifest hyperandrogenaemia which may result in a male pattern of lipoprotein lipid concentrations.

Bile acid sequestrants for cholesterol

MedlinePlus

... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

Genome-wide screen for modulation of hepatic apolipoprotein A-I (ApoA-I) secretion.

PubMed

Miles, Rebecca R; Perry, William; Haas, Joseph V; Mosior, Marian K; N'Cho, Mathias; Wang, Jian W J; Yu, Peng; Calley, John; Yue, Yong; Carter, Quincy; Han, Bomie; Foxworthy, Patricia; Kowala, Mark C; Ryan, Timothy P; Solenberg, Patricia J; Michael, Laura F

2013-03-01

Control of plasma cholesterol levels is a major therapeutic strategy for management of coronary artery disease (CAD). Although reducing LDL cholesterol (LDL-c) levels decreases morbidity and mortality, this therapeutic intervention only translates into a 25-40% reduction in cardiovascular events. Epidemiological studies have shown that a high LDL-c level is not the only risk factor for CAD; low HDL cholesterol (HDL-c) is an independent risk factor for CAD. Apolipoprotein A-I (ApoA-I) is the major protein component of HDL-c that mediates reverse cholesterol transport from tissues to the liver for excretion. Therefore, increasing ApoA-I levels is an attractive strategy for HDL-c elevation. Using genome-wide siRNA screening, targets that regulate hepatocyte ApoA-I secretion were identified through transfection of 21,789 siRNAs into hepatocytes whereby cell supernatants were assayed for ApoA-I. Approximately 800 genes were identified and triaged using a convergence of information, including genetic associations with HDL-c levels, tissue-specific gene expression, druggability assessments, and pathway analysis. Fifty-nine genes were selected for reconfirmation; 40 genes were confirmed. Here we describe the siRNA screening strategy, assay implementation and validation, data triaging, and example genes of interest. The genes of interest include known and novel genes encoding secreted enzymes, proteases, G-protein-coupled receptors, metabolic enzymes, ion transporters, and proteins of unknown function. Repression of farnesyltransferase (FNTA) by siRNA and the enzyme inhibitor manumycin A caused elevation of ApoA-I secretion from hepatocytes and from transgenic mice expressing hApoA-I and cholesterol ester transfer protein transgenes. In total, this work underscores the power of functional genetic assessment to identify new therapeutic targets.

Effects of butter naturally enriched with conjugated linoleic acid and vaccenic acid on blood lipids and LDL particle size in growing pigs

PubMed Central

Haug, Anna; Sjøgren, Per; Hølland, Nina; Müller, Hanne; Kjos, Nils P; Taugbøl, Ole; Fjerdingby, Nina; Biong, Anne S; Selmer-Olsen, Eirik; Harstad, Odd M

2008-01-01

Background Cow milk is a natural source of the cis 9, trans 11 isomer of conjugated linoleic acid (c9,t11-CLA) and trans vaccenic acid (VA). These fatty acids may be considered as functional foods, and the concentration in milk can be increased by e.g. sunflower oil supplementation to the dairy cow feed. The objective of this study was to compare the effects of regular butter with a special butter naturally enriched in c9,t11-CLA and VA on plasma lipids in female growing pigs. The experimental period lasted for three weeks and the two diets provided daily either 5.0 g c9,t11-CLA plus 15.1 g VA or 1.3 g c9,t11-CLA plus 3.6 g VA. Results The serum concentrations of c9,t11-CLA, VA and alpha-linolenic acid were increased and myristic (14:0) and palmitic acid (16:0) were reduced in the pigs fed the CLA+VA-rich butter-diet compared to regular butter, but no differences in plasma concentrations of triacylglycerol, cholesterol, HDL-cholesterol, LDL-cholesterol, LDL particle size distribution or total cholesterol/HDL cholesterol were observed among the two dietary treatment groups. Conclusion Growing pigs fed diets containing butter naturally enriched in about 20 g c9,t11-CLA plus VA daily for three weeks, had increased serum concentrations of alpha-linolenic acid and decreased myristic and palmitic acid compared to pigs fed regular butter, implying a potential benefit of the CLA+VA butter on serum fatty acid composition. Butter enriched in CLA+VA does not appear to have significant effect on the plasma lipoprotein profile in pigs. PMID:18759970

Effects of butter naturally enriched with conjugated linoleic acid and vaccenic acid on blood lipids and LDL particle size in growing pigs.

PubMed

Haug, Anna; Sjøgren, Per; Hølland, Nina; Müller, Hanne; Kjos, Nils P; Taugbøl, Ole; Fjerdingby, Nina; Biong, Anne S; Selmer-Olsen, Eirik; Harstad, Odd M

2008-08-29

Cow milk is a natural source of the cis 9, trans 11 isomer of conjugated linoleic acid (c9,t11-CLA) and trans vaccenic acid (VA). These fatty acids may be considered as functional foods, and the concentration in milk can be increased by e.g. sunflower oil supplementation to the dairy cow feed. The objective of this study was to compare the effects of regular butter with a special butter naturally enriched in c9,t11-CLA and VA on plasma lipids in female growing pigs. The experimental period lasted for three weeks and the two diets provided daily either 5.0 g c9,t11-CLA plus 15.1 g VA or 1.3 g c9,t11-CLA plus 3.6 g VA. The serum concentrations of c9,t11-CLA, VA and alpha-linolenic acid were increased and myristic (14:0) and palmitic acid (16:0) were reduced in the pigs fed the CLA+VA-rich butter-diet compared to regular butter, but no differences in plasma concentrations of triacylglycerol, cholesterol, HDL-cholesterol, LDL-cholesterol, LDL particle size distribution or total cholesterol/HDL cholesterol were observed among the two dietary treatment groups. Growing pigs fed diets containing butter naturally enriched in about 20 g c9,t11-CLA plus VA daily for three weeks, had increased serum concentrations of alpha-linolenic acid and decreased myristic and palmitic acid compared to pigs fed regular butter, implying a potential benefit of the CLA+VA butter on serum fatty acid composition. Butter enriched in CLA+VA does not appear to have significant effect on the plasma lipoprotein profile in pigs.

A crossover study of rosuvastatin and pitavastatin in patients with type 2 diabetes.

PubMed

Yanagi, Kazunori; Monden, Tsuyoshi; Ikeda, Shiori; Matsumura, Mihoko; Kasai, Kikuo

2011-02-01

The effects of a low dose of rosuvastatin (ROS) and pitavastatin (PIT) on lipid profiles and inflammation markers were assessed in subjects with type 2 diabetes mellitus. A total of 90 Japanese type 2 diabetes patients with hyperlipidemia (low-density lipoprotein cholesterol [LDL-C] ≥140 mg/dL) were enrolled in this study. They were randomly assigned to four groups with open-label treatment with ROS (2.5 mg daily) or PIT (2 mg daily); two groups were sequentially treated with both drugs, with crossover of medication after 12 weeks, and the other two groups underwent treatment with either ROS or PIT for 24 weeks. The primary endpoints were the percentage changes in LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglyceride, and the LDL-C/HDL-C ratio. Both ROS and PIT lowered LDL-C and triglyceride, and increased HDL-C. In particular, significantly greater reduction in LDL-C was seen with ROS (-44.1%) than with PIT (-36.9%, P<0.01) in the crossover group from ROS to PIT, and the same result was detected in the crossover group from PIT (-34.8%) to ROS (-44.7%). The ratio of LDL-C/HDL-C was significantly reduced with ROS treatment (from 3.45 to 1.85) compared with that with PIT (from 3.45 to 2.22, P<0.01). Both ROS and PIT lowered plasma levels of high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-alpha, and plasminogen activator inhibitor-1 (PAI-1). In addition, the hsCRP level with the administration of ROS was significantly improved compared with the administration of PIT. There was no significant correlation between changes in LDL-C and hsCRP, TNF-alpha, and PAI-1 levels. ROS and PIT did not have an adverse effect on glycemic control in type 2 diabetes patients. Therapy with both statins improved lipid profiles and reduced proinflammatory responses; however, 2.5 mg of ROS have a potent LDL-C-lowering and hsCRP-lowering effect compared with 2 mg of PIT in patients with diabetes.

Effect of ezetimibe add-on therapy over 52 weeks extension analysis of prospective randomized trial (RESEARCH study) in type 2 diabetes subjects.

PubMed

Sakamoto, Kentaro; Kawamura, Mitsunobu; Watanabe, Takayuki; Ashidate, Keiko; Kohro, Takahide; Tanaka, Akira; Mori, Yasumichi; Tagami, Motoki; Hirano, Tsutomu; Yamazaki, Tsutomu; Shiba, Teruo

2017-06-24

Lowering cholesterol levels decreases the risk of atherosclerotic diseases. Effective ways to stably reduce LDL-C level are warranted in type 2 diabetic patients, a high-risk population for CVD, with various anti-diabetic therapeutic background. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles. We evaluated long-term ezetimibe add-on therapy in T2DM patients with hypercholesterolemia. In a randomized, multicenter, open-label, prospective study, a total of 109 T2DM patients not attaining LDL-C target value despite first-line dose statin (10 mg of atorvastatin or 1 mg of pitavastatin) therapy in Japan were recruited. We investigated the difference in cholesterol lowering effect between ezetimibe (10 mg) add-on statin (EAT) group and double-dose statin (DST) group. Changes of parameters related to atherosclerotic event risks were assessed. The reduction of LDL-C was larger in the EAT group (28.3%) than in the DST group (9.2%) at 52 weeks as well as the primary endpoint of 12 weeks. EAT achieved significant lower levels of TC and apo B, respectively. Both treatments attained significant reduction in sd-LDL-C or hsCRP on this long-term basis. Notably, sd-LDL-C in EAT reduced as low as 36.1 ± 14.9 mg/dl to reach near the threshold (35.0 mg/dl) for atherosclerosis with significantly higher achievement rate (55.6%) than DST treatment. Simultaneously, hsCRP reduction by EAT attained as low value as 0.52 ± 0.43 mg/l. In the present 52-week long-term period, ezetimibe add-on therapy showed a robust advantage in lowering LDL-C and in attaining target LDL-C values compared with the doubling of statin dose. Moreover, it's meaningful that sd-LDL, powerfully atherogenic lipoprotein, exhibited prominent decrease consistently prominently by ezetimibe add-on therapy. DM patients with hypercholesterolemia are at high risk for CAD, and adding ezetimibe onto usual-dose statin treatment in Japan has been suggested as the first-line therapy for those DM patients who failed to attain the target LDL-C value (UMIN000002593).

Vitamin D Levels and Lipid Response to Atorvastatin

PubMed Central

Pérez-Castrillón, José Luis; Abad Manteca, Laura; Vega, Gemma; del Pino Montes, Javier; de Luis, Daniel; Dueňas Laita, Antonio

2010-01-01

Adequate vitamin D levels are necessary for good vascular health. 1,25-dihydroxycholecalciferol activates CYP3A4, an enzyme of the cytochrome P450 system, which metabolizes atorvastatin to its main metabolites. The objective of this study was to evaluate the response of cholesterol and triglycerides to atorvastatin according to vitamin D levels. Sixty-three patients with acute myocardial infarction treated with low and high doses of atorvastatin were included. Levels of total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol were measured at baseline and at 12 months of follow-up. Baseline levels of 25-hydroxyvitamin D (25-OHD) were classified as deficient (<30 nmol/L), insufficient (30–50 nmol/L), and normal (>50 nmol/L). In patients with 25-OHD <30 nmol/L, there were no significant changes in levels of total cholesterol (173 ± 47 mg/dL versus 164 ± 51 mg/dL), triglycerides (151 ± 49 mg/dL versus 177 ± 94 mg/dL), and LDL cholesterol (111 ± 48 mg/dL versus 92 45 ± mg/dL); whereas patients with insufficient (30–50 nmol/L) and normal vitamin D (>50 nmol/L) had a good response to atorvastatin. We suggest that vitamin D concentrations >30 nmol/L may be required for atorvastatin to reduce lipid levels in patients with acute myocardial infarction. PMID:20016682

Rationale and Design of the PROSPECTIVE Trial: Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Prior Coronary Heart Disease.

PubMed

Yamashita, Shizuya; Masuda, Daisaku; Ohama, Tohru; Arai, Hidenori; Bujo, Hideaki; Kagimura, Tatsuo; Kita, Toru; Matsuzaki, Masunori; Saito, Yasushi; Fukushima, Masanori; Matsuzawa, Yuji

2016-06-01

Reduction of serum LDL-cholesterol by statins was shown to improve clinical outcomes in patients with coronary heart disease (CHD). Although intensive statin therapy significantly reduced cardiovascular risks, atherosclerotic cardiovascular events have not been completely prevented. Therefore, effective pharmacologic therapy is necessary to improve "residual risks" in combination with statins. Probucol has a potent antioxidative effect, inhibits the oxidation of LDL, and reduces xanthomas. Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Prior Coronary Heart Disease (PROSPECTIVE) is a multicenter, randomized, prospective study designed to test the hypothesis that the addition of probucol to other lipid-lowering drugs will prevent cerebro- and cardiovascular events in patients with prior coronary events and high LDL cholesterol levels. The study will recruit approximately 860 patients with a prior CHD and dyslipidemia with LDL-C level ≥140 mg/dl without any medication and those treated with any lipid-lowering drugs with LDL-C level ≥100 mg/dl. Lipid-lowering agents are continuously administered during the study period in control group, and probucol (500 mg/day, 250 mg twice daily) is added to lipid-lowering therapy in the test group. The efficacy and safety of probucol with regard to the prevention of cerebro- and cardiovascular events and the intima-media thickness of carotid arteries as a surrogate marker will be evaluated. PROSPECTIVE will determine whether the addition of probucol to other lipid-lowering drugs improves cerebro- and cardiovascular outcomes in patients with prior coronary heart disease. Furthermore, the safety of a long-term treatment with probucol will be clarified.

Total, LDL, and HDL cholesterol decrease with age in older men and women. The Rancho Bernardo Study 1984-1994.

PubMed

Ferrara, A; Barrett-Connor, E; Shan, J

1997-07-01

The purpose of the present study was to study the effects of age, weight change, and covariates on lipid and lipoprotein levels cross-sectionally and prospectively in an elderly population. A community-based sample of 1041 men and 1303 women aged 50 to 93 years was studied cross-sectionally in 1984 to 1987, with follow-up of 372 men and 545 women 8 years later. In the cross-sectional study, levels of total cholesterol (TC) and LDL cholesterol (LDL-C) decreased and levels of HDL cholesterol (HDLC) increased with age in men (all P < .001) but not in women. In the prospective study, TC, LDL-C, and HDL-C levels all decreased in both men and women, in all age groups (50 to 64 years, 65 to 74 years, and > or = 75 years) and in all weight change groups (> 2.5-kg loss, change within 2.5 kg, and > 2.5-kg gain) and in all waist girth change groups, for an overall decrement of approximately 1% per year. In multiple linear regression models, change in weight was the most important independent and consistent predictor of changes in TC, LDL-C, and HDL-C. Similar results were obtained in analyses excluding subjects taking lipid-lowering drugs or estrogen and in analyses adjusted for changes in cigarette smoking, alcohol intake, physical activity, medication use, and incident myocardial infarction, cancer, or diabetes. Cross-sectional decrements in TC and LDL-C with age in men are not explained by survivor bias because they are also observed prospectively. Although weight change was the most important explanatory variable, TC, LDL-C, and HDL-C levels also decreased in those who lost or gained weight. Age was not an independent predictor of change. Other prospective studies are recommended to better define the causes and consequences of cholesterol and lipoprotein changes in old age.

Smoking-induced alterations in platelet membrane fluidity and Na(+)/K(+)-ATPase activity in chronic cigarette smokers.

PubMed

Padmavathi, Pannuru; Reddy, Vaddi Damodara; Maturu, Paramahamsa; Varadacharyulu, Nallanchakravarthula

2010-06-30

Cigarette smoking is a recognized risk factor for cardiovascular diseases and has been implicated in the pathogenesis of atherosclerosis. Platelet adhesiveness and aggregation increases as a result of smoking. Cigarette smoking modifies haemostatic parameters via thrombosis with a consequently higher rate of cardiovascular events, but smoking-induced alterations of platelet membrane fluidity and other changes have not been studied. Thirty experimental and control subjects (mean age 35+/-8) were selected for the study. Experimental subjects had smoked 10+/-2 cigarettes per day for 7-10 years. The plasma lipid profile, platelet carbonyls, sulfhydryl groups, Na(+)/k(+)-ATPase activity, fluidity using a fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH), total cholesterol and phospholipids as well individual phospholipids were determined. Increases in the platelet membrane cholesterol phospholipid (C/P) ratio, phosphotidylethanolamine, phosphotidylserine with decreased phosphotidylcholine, Na(+)/k(+)-ATPase activity, fluidity and no significant change in phosphotidylinositol and sphingomylein, as well as increases in plasma total cholesterol, LDL-cholesterol, protein carbonyls with decreased HDL-cholesterol and sulfhydryl groups were observed in cigarette smokers. Platelet membrane total phospholipids were positively correlated with plasma LDL-cholesterol (r=0.568) and VLDL-cholesterol (r=0.614) in cigarette smokers. Increased plasma LDL-cholesterol, VLDL-cholesterol and total cholesterol might have resulted in the increased C/P ratio and decreased platelet membrane fluidity of cigarette smokers.

Paleolithic nutrition improves plasma lipid concentrations of hypercholesterolemic adults to a greater extent than traditional heart-healthy dietary recommendations.

PubMed

Pastore, Robert L; Brooks, Judith T; Carbone, John W

2015-06-01

Recent research suggests that traditional grain-based heart-healthy diet recommendations, which replace dietary saturated fat with carbohydrate and reduce total fat intake, may result in unfavorable plasma lipid ratios, with reduced high-density lipoprotein (HDL) and an elevation of low-density lipoprotein (LDL) and triacylglycerols (TG). The current study tested the hypothesis that a grain-free Paleolithic diet would induce weight loss and improve plasma total cholesterol, HDL, LDL, and TG concentrations in nondiabetic adults with hyperlipidemia to a greater extent than a grain-based heart-healthy diet, based on the recommendations of the American Heart Association. Twenty volunteers (10 male and 10 female) aged 40 to 62 years were selected based on diagnosis of hypercholesterolemia. Volunteers were not taking any cholesterol-lowering medications and adhered to a traditional heart-healthy diet for 4 months, followed by a Paleolithic diet for 4 months. Regression analysis was used to determine whether change in body weight contributed to observed changes in plasma lipid concentrations. Differences in dietary intakes and plasma lipid measures were assessed using repeated-measures analysis of variance. Four months of Paleolithic nutrition significantly lowered (P < .001) mean total cholesterol, LDL, and TG and increased (P < .001) HDL, independent of changes in body weight, relative to both baseline and the traditional heart-healthy diet. Paleolithic nutrition offers promising potential for nutritional management of hyperlipidemia in adults whose lipid profiles have not improved after following more traditional heart-healthy dietary recommendations. Copyright © 2015 Elsevier Inc. All rights reserved.

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia.

PubMed

Ferreira, António Miguel; Marques da Silva, Pedro

2017-06-01

Statin-ezetimibe combinations are a potentially advantageous therapeutic option for high-risk patients who need additional lowering of low-density lipoprotein cholesterol (LDL-C). These combinations may overcome some of the limitations of statin monotherapy by blocking both sources of cholesterol. Recently, a fixed-dose combination with atorvastatin, one of the most extensively studied statins, was approved and launched in several countries, including the USA. Depending on atorvastatin dose, this combination provides LDL-C reductions of 50-60%, triglyceride reductions of 30-40%, and high-density lipoprotein cholesterol (HDL-C) increases of 5-9%. Studies comparing the lipid-lowering efficacy of the atorvastatin-ezetimibe combination with the alternatives of statin dose titration or switching to a more potent statin consistently showed that combination therapy provided greater LDL-C reduction, translating into a greater proportion of patients achieving lipid goals. Simvastatin-ezetimibe combinations have been shown to reduce the incidence of major atherosclerotic events in several clinical settings to a magnitude that seems similar to that observed with statins for the same degree of absolute LDL-C lowering. The atorvastatin-ezetimibe combination has also been shown to induce the regression of coronary atherosclerosis measured by intravascular ultrasound in a significantly greater proportion of patients than atorvastatin alone. Atorvastatin-ezetimibe combinations are generally well tolerated. Previous concerns of a possible increase in the incidence of cancer with ezetimibe were dismissed in large trials with long follow-up periods. In this paper, we examine the rationale for an atorvastatin-ezetimibe combination, review the evidence supporting it, and discuss its potential role in the management of dyslipidemia.

Managing the residual cardiovascular disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: a clinical update.

PubMed

Reiner, Z

2013-09-01

Cardiovascular disease (CVD) is a significant cause of death in Europe. In addition to patients with proven CVD, those with type 2 diabetes (T2D) are at a particularly high-risk of CVD and associated mortality. Treatment for dyslipidaemia, a principal risk factor for CVD, remains a healthcare priority; evidence supports the reduction of low-density lipoprotein cholesterol (LDL-C) as the primary objective of dyslipidaemia management. While statins are the treatment of choice for lowering LDL-C in the majority of patients, including those with T2D, many patients retain a high CVD risk despite achieving the recommended LDL-C targets with statins. This 'residual risk' is mainly due to elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels. Following statin therapy optimisation additional pharmacotherapy should be considered as part of a multifaceted approach to risk reduction. Fibrates (especially fenofibrate) are the principal agents recommended for add-on therapy to treat elevated TG or low HDL-C levels. Currently, the strongest evidence of benefit is for the addition of fenofibrate to statin treatment in high-risk patients with T2D and dyslipidaemia. An alternative approach is the addition of agents to reduce LDL-C beyond the levels attainable with statin monotherapy. Here, addition of fibrates and niacin to statin therapy is discussed, and novel approaches being developed for HDL-C and TG management, including cholesteryl ester transfer protein inhibitors, Apo A-1 analogues, mipomersen, lomitapide and monoclonal antibodies against PCSK9, are reviewed. Copyright © 2013 Elsevier B.V. All rights reserved.

Physical Activity and Sedentary Behavior in Adolescents With Type 1 Diabetes

PubMed Central

Michaliszyn, Sara Fleet; Faulkner, Melissa Spezia

2014-01-01

The purpose of this study was to describe the associations between levels of physical activity measured by accelerometry and changes in fitness, body composition, lipids, and glucose control (i.e., glycosolated hemoglobin [A1C]) in a sample of 16 adolescents with type 1 diabetes participating in a personalized exercise program. More sedentary activity was associated with lower fitness and fat free mass and increased total cholesterol, low-density lipoprotein (LDL-c), and triglycerides (p < .05). Greater amounts of moderate to vigorous activity were associated with higher fitness and fat free mass, and decreased total cholesterol, LDL-c, triglycerides, and A1C (p < .05). Findings support the beneficial effects of increased moderate activity and decreased sedentary behavior to reduce cardiovascular risks and improve glucose control in adolescents with type 1 diabetes. PMID:20672318

Ocimum gratissmum aqueous extract reduces plasma lipid in hypercholesterol-fed hamsters

PubMed Central

Chao, Pei-Yu; Lin, James A.; Ting, Wei-Jen; Lee, Hsueh-Hui; Hsieh, Kuanghui; Chiu, Yung-Wei; Lai, Te-Jen; Hwang, Jin-Ming; Liu, Je-rYuh; Huang, Chih-Yang

2016-01-01

Objectives: Hyperlipidemia is a significant risk factor in the development of atherosclerosis and related diseases which are major health problem in many developed and developing countries that can lead to fatality due to the changes in lifestyle and dietary habits in this modern age. Methods: In the present study, the Ocimum gratissimum aqueous extract (OGE) was tested for the lowering effect on the serum lipid level of male hamsters on a high-fat (12%) and high-cholesterol (0.2%) diet (HFCD). Results: The results showed that the levels of serum high-density-lipoprotein-cholesterol (HDL-C) low-density-lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglycerols (TG) were increased in the HFCD group (113±11, 259±87, 629±175 and 625±262, respectively), as compared to the control normal diet group (51±8, 19±5, 77±16 and 101±44, respectively). When co-treated with various doses (10 and 20 mg/kg) of the OGE or rosuvastatin, the rats exhibited the restoration of normal serum LDL-C, TC, and TG levels. Conclusion: Therefore, we suggest that the Ocimum gratissimum aqueous extract may have the potential function of lowering serum lipid in rats. PMID:27877073

Inhibiting LDL glycation ameliorates increased cholesteryl ester synthesis in macrophages and hypercholesterolemia and aortic lipid peroxidation in streptozotocin diabetic rats

PubMed Central

Cohen, Margo P.; Shea, Elizabeth A.; Wu, Van-Yu

2009-01-01

Increased nonenzymatic glycation of apoB-containing lipoproteins impairs uptake and metabolism by the high affinity low density lipoprotein (LDL) receptor, and is one of the post-secretory modifications contributory to accelerated atherosclerosis in diabetes. The present study evaluated in vitro and in vivo effects of 2,2-chlorophenylaminophenylacetate (CAP22) to probe the influence of glycated lipoprotein on cholesterol homeostasis. This compound prevented the increased formation of glycated products in LDL incubated with 200 mM glucose and the increased cholesteryl ester synthesis in THP-1 macrophages induced by apoB-containing lipoproteins preincubated with high glucose concentration. The elevated circulating concentrations of glycated lipoprotein and cholesterol and higher vascular levels of lipid peroxidation products observed in streptozotocin diabetic rats compared to nondiabetic controls were significantly reduced in diabetic animals treated for six months with test compound. These results are the first to demonstrate that inhibiting nonenzymatic glycation of apoB-containing lipoproteins ameliorates abnormalities contributory to hypercholesterolemia and atherogenic risk in diabetes. PMID:19922964

Self-determination, smoking, diet and health.

PubMed

Williams, Geoffrey C; Minicucci, Daryl S; Kouides, Ruth W; Levesque, Chantal S; Chirkov, Valery I; Ryan, Richard M; Deci, Edward L

2002-10-01

A Clinical Trial will test (1) a Self-Determination Theory (SDT) model of maintained smoking cessation and diet improvement, and (2) an SDT intervention, relative to usual care, for facilitating maintained behavior change and decreasing depressive symptoms for those who quit smoking. SDT is the only empirically derived theory which emphasizes patient autonomy and has a validated measure for each of its constructs, and this is the first trial to evaluate an SDT intervention. Adult smokers will be stratified for whether they are at National Cholesterol Education Program (1996) recommended goal for low-density lipoprotein cholesterol (LDL-C). Those with elevated LDL-C will be studied for diet improvement as well as smoking cessation. Six-month interventions involve a behavior-change counselor using principles of SDT to facilitate autonomous motivation and perceived competence for healthier behaving. Cotinine-validated smoking cessation and LDL-C-validated dietary recall of reduced fat intake, as well as depressive symptoms, will be assessed at 6 and 18 months. Structural equation modeling will test the model for both behaviors within the intervention and usual-care conditions.

Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages.

PubMed

Lanuti, Mirko; Talamonti, Emanuela; Maccarrone, Mauro; Chiurchiù, Valerio

2015-01-01

The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer. However, its physiological role and underlying mechanism remain unclear. In the present work, we demonstrate for the first time its presence in human macrophages and its increased expression in ox-LDL-induced foam cells. In addition, pharmacological activation of GPR55 by its selective agonist O-1602 increased CD36- and SRB-I-mediated lipid accumulation and blocked cholesterol efflux by downregulating ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, as well as enhanced cytokine- and pro-metalloprotease-9 (pro-MMP-9)-induced proinflammatory responses in foam cells. Treatment with cannabidiol, a selective antagonist of GPR55, counteracted these pro-atherogenic and proinflammatory O-1602-mediated effects. Our data suggest that GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases.

Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages

PubMed Central

Lanuti, Mirko; Talamonti, Emanuela; Maccarrone, Mauro; Chiurchiù, Valerio

2015-01-01

The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer. However, its physiological role and underlying mechanism remain unclear. In the present work, we demonstrate for the first time its presence in human macrophages and its increased expression in ox-LDL-induced foam cells. In addition, pharmacological activation of GPR55 by its selective agonist O-1602 increased CD36- and SRB-I-mediated lipid accumulation and blocked cholesterol efflux by downregulating ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, as well as enhanced cytokine- and pro-metalloprotease-9 (pro-MMP-9)-induced proinflammatory responses in foam cells. Treatment with cannabidiol, a selective antagonist of GPR55, counteracted these pro-atherogenic and proinflammatory O-1602-mediated effects. Our data suggest that GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases. PMID:25970609

Liver heparan sulfate proteoglycans mediate clearance of triglyceride-rich lipoproteins independently of LDL receptor family members

PubMed Central

MacArthur, Jennifer M.; Bishop, Joseph R.; Stanford, Kristin I.; Wang, Lianchun; Bensadoun, André; Witztum, Joseph L.; Esko, Jeffrey D.

2007-01-01

We examined the role of hepatic heparan sulfate in triglyceride-rich lipoprotein metabolism by inactivating the biosynthetic gene GlcNAc N-deacetylase/N-sulfotransferase 1 (Ndst1) in hepatocytes using the Cre-loxP system, which resulted in an approximately 50% reduction in sulfation of liver heparan sulfate. Mice were viable and healthy, but they accumulated triglyceride-rich lipoprotein particles containing apoB-100, apoB-48, apoE, and apoCI-IV. Compounding the mutation with LDL receptor deficiency caused enhanced accumulation of both cholesterol- and triglyceride-rich particles compared with mice lacking only LDL receptors, suggesting that heparan sulfate participates in the clearance of cholesterol-rich lipoproteins as well. Mutant mice synthesized VLDL normally but showed reduced plasma clearance of human VLDL and a corresponding reduction in hepatic VLDL uptake. Retinyl ester excursion studies revealed that clearance of intestinally derived lipoproteins also depended on hepatocyte heparan sulfate. These findings show that under normal physiological conditions, hepatic heparan sulfate proteoglycans play a crucial role in the clearance of both intestinally derived and hepatic lipoprotein particles. PMID:17200715

Atherogenic Lipoprotein Subfractions Determined by Ion Mobility and First Cardiovascular Events After Random Allocation to High-Intensity Statin or Placebo: The Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) Trial.

PubMed

Mora, Samia; Caulfield, Michael P; Wohlgemuth, Jay; Chen, Zhihong; Superko, H Robert; Rowland, Charles M; Glynn, Robert J; Ridker, Paul M; Krauss, Ronald M

2015-12-08

Cardiovascular disease (CVD) can occur in individuals with low low-density lipoprotein (LDL) cholesterol (LDL-C). We investigated whether detailed measures of LDL subfractions and other lipoproteins can be used to assess CVD risk in a population with both low LDL-C and high C-reactive protein who were randomized to high-intensity statin or placebo. In 11 186 Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) participants, we tested whether lipids, apolipoproteins, and ion mobility-measured particle concentrations at baseline and after random allocation to rosuvastatin 20 mg/d or placebo were associated with first CVD events (n=307) or CVD/all-cause death (n=522). In placebo-allocated participants, baseline LDL-C was not associated with CVD (adjusted hazard ratio [HR] per SD, 1.03; 95% confidence interval [CI], 0.88-1.21). In contrast, associations with CVD events were observed for baseline non-high-density lipoprotein (HDL) cholesterol (HR, 1.18; 95% CI, 1.01-1.38), apolipoprotein B (HR, 1.28; 95% CI, 1.11-1.48), and ion mobility-measured non-HDL particles (HR, 1.19; 95% CI, 1.05-1.35) and LDL particles (HR, 1.21; 95% CI, 1.07-1.37). Association with CVD events was also observed for several LDL and very-low-density lipoprotein subfractions but not for ion mobility-measured HDL subfractions. In statin-allocated participants, CVD events were associated with on-treatment LDL-C, non-HDL cholesterol, and apolipoprotein B; these were also associated with CVD/all-cause death, as were several LDL and very-low-density lipoprotein subfractions, albeit with a pattern of association that differed from the baseline risk. In JUPITER, baseline LDL-C was not associated with CVD events, in contrast with significant associations for non-HDL cholesterol and atherogenic particles: apolipoprotein B and ion mobility-measured non-HDL particles, LDL particles, and select subfractions of very-low-density lipoprotein particles and LDL particles. During high-intensity statin therapy, on-treatment levels of LDL-C and atherogenic particles were associated with residual risk of CVD/all-cause death. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681. © 2015 American Heart Association, Inc.

[Characteristics of fatty acid composition of phosphatidyl cholines and sphingomyelins of low-density lipoproteins in the plasma of native inhabitants of Chukotka].

PubMed

Gerasimova, E N; Levachev, M M; Perova, N V; Nikitin, Iu P; Ozerova, I N

1986-01-01

Contents of cholesterol, triglycerides, high density lipoproteins (HDL) cholesterol as well as phospholipid and fatty acid compositions of phosphatidyl cholines and sphingomyelins in low density lipoproteins (LDL) were studied in blood plasma of Chukot aborigenes--Eskimos as compared with Moscow inhabitants. In Eskimos content of HDL cholesterol was higher but concentration of cholesterol and triglycerides was lower in blood plasma. In LDL concentration of sphingomyelins was increased and fatty acid composition of phosphatidyl cholines and sphingomyelins was altered where amount of polyunsaturated fatty acids was elevated (20:5 + 22:5 + 22:6). The specific characteristics of the LDL phospholipids observed in Eskimos might be responsible for the higher liquid properties of the surface monolayer in the lipoproteins; this alteration might be important for the lipoprotein properties and transformation as well as for the properties of membrane-bound enzymes, for synthesis of thromboxane and prostacyclins.

Diet, atherosclerosis, and fish oil.

PubMed

Connor, W E; Connor, S L

1990-01-01

The principal goal of dietary prevention and treatment of atherosclerotic coronary heart disease is the achievement of physiological levels of the plasma total and LDL cholesterol, triglyceride, and VLDL. These goals have been well delineated by the National Cholesterol Education Program of the National Heart, Lung and Blood Institute and the American Heart Association. Dietary treatment is first accomplished by enhancing LDL receptor activity and at the same time depressing liver synthesis of cholesterol and triglyceride. Both dietary cholesterol and saturated fat decrease LDL receptor activity and inhibit the removal of LDL from the plasma by the liver. Saturated fat decreases LDL receptor activity, especially when cholesterol is concurrently present in the diet. The total amount of dietary fat is of importance also. The greater the flux of chylomicron remnants is into the liver, the greater is the influx of cholesterol ester. In addition, factors that affect VLDL and LDL synthesis could be important. These include excessive calories (obesity), which enhance triglyceride and VLDL and hence LDL synthesis. Weight loss and omega-3 fatty acids from fish oil depress synthesis of both VLDL and triglyceride in the liver. The optimal diet for the treatment of children and adults to prevent coronary disease has the following characteristics: cholesterol (100 mg/day), total fat (20% of calories, 6% saturated with the balance from omega-3 and omega-6 polyunsaturated and monounsaturated fat), carbohydrate (65% of calories, two thirds from starch including 11 to 15 gm of soluble fiber), and protein (15% of calories). This low-fat, high-carbohydrate diet can lower the plasma cholesterol 18% to 21%. This diet is also an antithrombotic diet, thrombosis being another major consideration in preventing coronary heart disease. Dietary therapy is the mainstay of the prevention and treatment of coronary heart disease through the control of plasma lipid and lipoprotein levels. The exact place of the omega-3 fatty acids from fish and fish oil remains to be defined. However, this much seems certain. Fish provides an excellent substitute for meat in the diet. Fish is lower in fat, especially saturated fat, and contains the omega-3 fatty acids. Fish oil may have promise as a therapeutic agent in certain hyperlipidemic states, especially the chylomicronemia of type V hyperlipidemia. Fish oil has logical and well-defined antithrombotic and anti-atherosclerotic activities since it depresses thromboxane A2 production and inhibits cellular proliferation responsible for the progression of atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Association of Low-Density Lipoprotein Cholesterol–Related Genetic Variants With Aortic Valve Calcium and Incident Aortic Stenosis

PubMed Central

Smith, J. Gustav; Luk, Kevin; Schulz, Christina-Alexandra; Engert, James C.; Do, Ron; Hindy, George; Rukh, Gull; Dufresne, Line; Almgren, Peter; Owens, David S.; Harris, Tamara B.; Peloso, Gina M.; Kerr, Kathleen F.; Wong, Quenna; Smith, Albert V.; Budoff, Matthew J.; Rotter, Jerome I.; Cupples, L. Adrienne; Rich, Stephen; Kathiresan, Sekar; Orho-Melander, Marju; Gudnason, Vilmundur; O’Donnell, Christopher J.; Post, Wendy S.; Thanassoulis, George

2014-01-01

IMPORTANCE Plasma low-density lipoprotein cholesterol (LDL-C) has been associated with aortic stenosis in observational studies; however, randomized trials with cholesterol-lowering therapies in individuals with established valve disease have failed to demonstrate reduced disease progression. OBJECTIVE To evaluate whether genetic data are consistent with an association between LDL-C, high-density lipoprotein cholesterol (HDL-C), or triglycerides (TG) and aortic valve disease. DESIGN, SETTING, AND PARTICIPANTS Using a Mendelian randomization study design, we evaluated whether weighted genetic risk scores (GRSs), a measure of the genetic predisposition to elevations in plasma lipids, constructed using single-nucleotide polymorphisms identified in genome-wide association studies for plasma lipids, were associated with aortic valve disease. We included community-based cohorts participating in the CHARGE consortium (n = 6942), including the Framingham Heart Study (cohort inception to last follow-up: 1971-2013; n = 1295), Multi-Ethnic Study of Atherosclerosis (2000-2012; n = 2527), Age Gene/Environment Study-Reykjavik (2000-2012; n = 3120), and the Malmö Diet and Cancer Study (MDCS, 1991-2010; n = 28 461). MAIN OUTCOMES AND MEASURES Aortic valve calcium quantified by computed tomography in CHARGE and incident aortic stenosis in the MDCS. RESULTS The prevalence of aortic valve calcium across the 3 CHARGE cohorts was 32% (n = 2245). In the MDCS, over a median follow-up time of 16.1 years, aortic stenosis developed in 17 per 1000 participants (n = 473) and aortic valve replacement for aortic stenosis occurred in 7 per 1000 (n = 205). Plasma LDL-C, but not HDL-C or TG, was significantly associated with incident aortic stenosis (hazard ratio [HR] per mmol/L, 1.28; 95% CI, 1.04-1.57; P = .02; aortic stenosis incidence: 1.3% and 2.4% in lowest and highest LDL-C quartiles, respectively). The LDL-C GRS, but not HDL-C or TG GRS, was significantly associated with presence of aortic valve calcium in CHARGE (odds ratio [OR] per GRS increment, 1.38; 95% CI, 1.09-1.74; P = .007) and with incident aortic stenosis in MDCS (HR per GRS increment, 2.78; 95% CI, 1.22-6.37; P = .02; aortic stenosis incidence: 1.9% and 2.6% in lowest and highest GRS quartiles, respectively). In sensitivity analyses excluding variants weakly associated with HDL-C or TG, the LDL-C GRS remained associated with aortic valve calcium (P = .03) and aortic stenosis (P = .009). In instrumental variable analysis, LDL-C was associated with an increase in the risk of incident aortic stenosis (HR per mmol/L, 1.51; 95% CI, 1.07-2.14; P = .02). CONCLUSIONS AND RELEVANCE Genetic predisposition to elevated LDL-C was associated with presence of aortic valve calcium and incidence of aortic stenosis, providing evidence supportive of a causal association between LDL-C and aortic valve disease. Whether earlier intervention to reduce LDL-C could prevent aortic valve disease merits further investigation. PMID:25344734

Effect of natural honey from Ilam and metformin for improving glycemic control in streptozotocin-induced diabetic rats

PubMed Central

Nasrolahi, Ozra; Heidari, Reza; Rahmani, Fatima; Farokhi, Farah

2012-01-01

Objective(s): Diabetes mellitus is a public health problem and one of the five leading causes of death globally. In the present study, the effect of Metformin with natural honey was investigated on glycemia in the Streptozotocin-induced diabetic rats. Materials and Methods: Thirty Wistar male rats were randomly divided into six groups including C: non diabetic rats received distilled water, CH: non diabetic rats received honey, CD: diabetic rats administered with distilled water, DM: Metformin treated diabetic rats, DH: honey treated diabetic rats, and DMH: diabetic rats treated with a combination of Metformin and natural honey. Diabetes was induced by a single dose of Streptozotocin (65 mg/kg; i.p.). The animals were treated by oral gavage once daily for four weeks. At the end of the treatment period, the animals were sacrificed and their blood samples collected. Amount of glucose, triglyceride (TG), total cholesterol (TC), HDL cholesterol, LDL cholesterol, VLDL cholesterol, total bilirubin, and albumin were determined in serum. Results: Group CD: showed hyperglycemia (252.2±4.1 mg/dl), while level of blood glucose was significantly (p<0.01) reduced in groups DH (124.2±2.7 mg/dl), DM (108.0±3.4 mg/dl), and DMH (115.4±2.1 mg/dl). Honey in combination with Metformin significantly (p<0.01) reduced level of bilirubin but Metformin alone did not reduce bilirubin. Honey alone and in combination with Metformin also significantly reduced triglycerides, total cholesterol, LDL, VLDL and increased HDL, but Metformin did not reduced triglycerides and increased HDL. Conclusion: The results of the present study demonstrated that consuming natural honey with Metformin improves glycemic control and is more useful than consuming Metformin alone. The higher therapeutic effect of Ilam honey on lipid abnormalities than Tualang honey was also evident. PMID:25050251

Hematopoietic Stem/Progenitor Cell Proliferation and Differentiation Is Differentially Regulated by High-Density and Low-Density Lipoproteins in Mice

PubMed Central

Feng, Yingmei; Schouteden, Sarah; Geenens, Rachel; Van Duppen, Vik; Herijgers, Paul; Holvoet, Paul; Van Veldhoven, Paul P.; Verfaillie, Catherine M.

2012-01-01

Rationale Hematopoietic stem/progenitor cells (HSPC) are responsible for maintaining the blood system as a result of their self-renewal and multilineage differentiation capacity. Recently, studies have suggested that HDL cholesterol may inhibit and impaired cholesterol efflux may increase HSPC proliferation and differentiation. Objectives We hypothesized that LDL may enhance HSPC proliferation and differentiation while HDL might have the opposing effect which might influence the size of the pool of inflammatory cells. Methods and Results HSPC number and function were studied in hypercholesterolemic LDL receptor knockout (LDLr−/−) mice on high fat diet. Hypercholesterolemia was associated with increased frequency of HSPC, monocytes and granulocytes in the peripheral blood (PB). In addition, an increased proportion of BM HSPC was in G2M of the cell cycle, and the percentage of HSPC and granulocyte-macrophage progenitors (GMP) increased in BM of LDLr−/− mice. When BM Lin-Sca-1+cKit+ (i.e. “LSK”) cells were cultured in the presence of LDL in vitro we also found enhanced differentiation towards monocytes and granulocytes. Furthermore, LDL promoted lineage negative (Lin−) cells motility. The modulation by LDL on HSPC differentiation into granulocytes and motility was inhibited by inhibiting ERK phosphorylation. By contrast, when mice were infused with human apoA-I (the major apolipoprotein of HDL) or reconstituted HDL (rHDL), the frequency and proliferation of HSPC was reduced in BM in vivo. HDL also reversed the LDL-induced monocyte and granulocyte differentiation in vitro. Conclusion Our data suggest that LDL and HDL have opposing effects on HSPC proliferation and differentiation. It will be of interest to determine if breakdown of HSPC homeostasis by hypercholesterolemia contributes to inflammation and atherosclerosis progression. PMID:23144813

Milk minerals modify the effect of fat intake on serum lipid profile: results from an animal and a human short-term study.

PubMed

Lorenzen, Janne K; Jensen, Søren K; Astrup, Arne

2014-04-28

Despite a high content of saturated fat, evidence from observational studies indicates that the consumption of dairy products may have a neutral effect or may be inversely associated with the risk of CVD. We aimed to examine whether milk minerals modify the effect of saturated fat on serum lipid profile. We present data from two studies. Study I had a randomised, blinded, parallel design (n 24 pigs) with a 10 d adaptation period during which a high-fat diet was fed to the pigs and a 14 d intervention period during which the same diet either enriched with milk minerals (MM group) or placebo (control group) was fed to the pigs. Study II had a randomised cross-over design (n 9 men) where the subjects were fed either a high-fat diet enriched with milk minerals (MM period) or a regular diet (control period). In both the studies, blood variables were measured before and after the intervention and faecal and urine samples were collected at the end of the dietary periods. The increase in plasma total cholesterol and LDL-cholesterol concentrations but not in HDL-cholesterol concentration was markedly lowered by milk minerals in both the studies. In the animal study, baseline adjusted total cholesterol and LDL-cholesterol concentrations in the MM group were 11% (P = 0.004) and 13% (P = 0.03) lower compared with those in the control group after the intervention. Similarly in the human study, baseline adjusted total cholesterol and LDL-cholesterol concentrations were 6% (P = 0.002) and 9% (P = 0.03) lower after the MM period compared with those in the control period. HDL-cholesterol concentration was not lowered by milk minerals. These short-term studies indicate that the addition of milk minerals to a high-fat diet to some extent attenuates the increase in total cholesterol and LDL-cholesterol concentrations, without affecting HDL-cholesterol concentration.

CHD risk equivalents and the metabolic syndrome. Trial evidence supports aggressive management.

PubMed

Thompson, Paul D

2003-08-01

Updated guidelines issued by the National Cholesterol Education Program's 2001 Adult Treatment Panel III (ATP III) reaffirm the importance of intensive management of low density lipoprotein cholesterol (LDL-C) in patients with established coronary heart disease (CHD). Clinical studies also show that diabetes, peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease are CHD risk equivalents that require intensive therapeutic lifestyle changes and drug therapy to prevent associated morbidity and mortality. Likewise, the metabolic syndrome is a secondary target of treatment. Drug therapy usually starts with an LDL-C-lowering agent, such as a statin. If LDL-C and non-high-density lipoprotein cholesterol goals are not achieved, statin therapy should be intensified or a fibrate or niacin should be added.

Can pleiotropic effects of eicosapentaenoic acid (EPA) impact residual cardiovascular risk?

PubMed

Nelson, John R; True, Wayne S; Le, Viet; Mason, R Preston

2017-11-01

Residual cardiovascular (CV) risk persists even in statin-treated patients with optimized low-density lipoprotein cholesterol (LDL-C) levels. Other pathways beyond cholesterol contribute to CV risk and the key to reducing residual risk may be addressing non-cholesterol risk factors through pleiotropic mechanisms. The purpose of this review is to examine the literature relating to the potential role of the omega-3 fatty acid eicosapentaenoic acid (EPA) in reducing residual CV risk. The literature shows that EPA can robustly lower plasma triglyceride (TG) levels without raising LDL-C levels and documents EPA to have a broad range of beneficial effects on the atherosclerotic pathway, including those on lipids, lipoproteins, inflammation, oxidation, phospholipid membranes, and the atherosclerotic plaque itself. Clinical imaging studies have consistently demonstrated that EPA decreases plaque vulnerability and prevents plaque progression. The evidence therefore points to a potential role for EPA to reduce residual CV risk. A large randomized study of statin-treated Japanese patients demonstrated that EPA ethyl ester reduced major coronary events by 19% (P = 0.011). However, while there has been significant benefit demonstrated in this and another Japanese CV outcomes study, the question as to whether EPA can play a role in reducing residual CV risk remains to be addressed in broader populations. The large, global, ongoing, randomized, placebo-controlled REDUCE-IT study of high-risk statin-treated patients with persistent hypertriglyceridemia is currently underway to investigate the potential of icosapent ethyl (high-purity prescription EPA ethyl ester) as an add-on therapy to reduce residual CV risk.

Effect of the combination of methyltestosterone and esterified estrogens compared with esterified estrogens alone on apolipoprotein CIII and other apolipoproteins in very low density, low density, and high density lipoproteins in surgically postmenopausal women.

PubMed

Chiuve, Stephanie E; Martin, Lisa A; Campos, Hannia; Sacks, Frank M

2004-05-01

Androgens are known to lower plasma triglycerides, an independent risk factor for coronary heart disease (CHD). Triglycerides are carried in plasma on very low density (VLDL) and low density (LDL) lipoprotein particles. Apolipoprotein CIII (apoCIII), a strong predictor of CHD, impairs the metabolism of VLDL and LDL, contributing to increased triglycerides. The objective of this study was to assess the effect of oral methyltestosterone (2.5 mg/d), added to esterified estrogens (1.25 mg/d), on concentrations of apolipoproteins and lipoproteins, specifically those containing apoCIII, compared with esterified estrogens alone in surgically postmenopausal women. The women in the methyltestosterone plus esterified estrogen group had significant decreases in total triglycerides, apoCI, apoCII, apoCIII, apoE, and high density lipoprotein (HDL) cholesterol compared with those in the esterified estrogen group. The decreases in apoCIII concentrations occurred in VLDL (62%; P = 0.02), LDL (35%; P = 0.001), and HDL (17%; P < 0.0001). There were also decreases in cholesterol and triglycerides concentrations of apoCIII containing LDL, and apoCI concentration of apoCIII containing VLDL. There was no effect on VLDL and LDL particles that did not contain apoCIII or on apoB concentrations. In conclusion, methyltestosterone, when administered to surgically postmenopausal women taking esterified estrogen, has a selective effect to reduce the apoCIII concentration in VLDL and LDL, a predictor of CHD. Methyltestosterone may lower plasma triglycerides through a reduction in apoCIII.

The babel of the ABCs: novel transporters involved in the regulation of sterol absorption and excretion.

PubMed

Ordovas, Jose M; Tai, E Shyong

2002-01-01

Hypercholesterolaemia is a major risk factor for coronary heart disease (CHD). Therefore, the reduction of low-density lipoprotein (LDL) cholesterol is one of the primary targets of the current recommendations to decrease CHD risk in the population. Whereas, the mechanisms involved in de novo cholesterol synthesis and its uptake by cells via the LDL receptor are well known, we still need better understanding about the mechanisms involved in intestinal cholesterol absorption and excretion. The recent discovery of ABCG5 and ABCG8 transporters will significantly improve our understanding of cholesterol trafficking and it will lead to better and new therapeutic strategies to maintain cholesterol homeostasis.

Effect of vildagliptin and pravastatin combination on cholesterol efflux in adipocytes.

PubMed

Mostafa, Ahmed M; Hamdy, Nadia M; Abdel-Rahman, Sherif Z; El-Mesallamy, Hala O

2016-07-01

Many reports suggested that some statins are almost ineffective in reducing triglycerides or enhancing HDL-C plasma levels, although statin treatment was still efficacious in reducing LDL-C. In diabetic dyslipidemic patients, it may therefore be necessary to use a combination therapy with other drugs to achieve either LDL-C- and triglyceride-lowering or HDL-C-enhancing goals. Such ineffectiveness of statins can be attributed to their effect on the liver X receptor (LXR) which regulates the expression of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1. A decrease in the expression of these transporters eventually leads to decreased cholesterol efflux from peripheral tissues leading to low levels of HDL-C. Although manipulating the LXR pathway may complement the effects of statins, LXR synthetic ligands as T091317 have shown significant hypertriglyceridemic action which limits their use. We recently found that the antidiabetic drug vildagliptin stimulates LXR expression leading to increased ABCB1/ABCG1 expression which improves cholesterol efflux from adipocytes. Therefore, a combination of vildagliptin and statin may provide a solution without the hypertriglyceridemic action observed with LXR agonist. We hypothesize that a combination of vildagliptin and pravastatin will improve cholesterol efflux in adipocytes. Statin-treated 3T3-L1 adipocytes were treated with vildagliptin, and the expression of LXR-ABCA1/ABCG1 cascade and the cholesterol efflux were then determined. Our data indicate that a combination of vildagliptin and pravastatin significantly induces the expression of LXR-ABCA1/ABCG1 cascade and improves cholesterol efflux (P > 0.05) in adipocytes. Our data may explain, at least in part, the improvement in HDL-C levels observed in patients receiving both medications. © 2016 IUBMB Life, 68(7):535-543, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Effect of Lactobacillus acidophilus NS1 on plasma cholesterol levels in diet-induced obese mice.

PubMed

Song, M; Park, S; Lee, H; Min, B; Jung, S; Park, S; Kim, E; Oh, S

2015-03-01

We investigated the probiotic properties of Lactobacillus acidophilus NS1, such as acid resistance, bile tolerance, adherence to HT-29 cells, and cholesterol assimilation activity. In an animal study, 7-wk-old male C57BL/6 mice were fed a normal diet, a high-fat diet (HFD), or an HFD with L. acidophilus NS1 (ca. 1.0×10(8) cfu/mL) for 10 wk. Total cholesterol and low-density lipoprotein (LDL) cholesterol levels were significantly lower in mice fed an HFD with L. acidophilus NS1 than in those fed an HFD only, whereas high-density lipoprotein cholesterol levels were similar between these 2 groups. To understand the mechanism of the cholesterol-lowering effect of L. acidophilus NS1 on the HFD-mediated increase in plasma cholesterol levels, we determined mRNA levels of genes involved in cholesterol homeostasis in the liver. Expression of sterol regulatory element-binding protein 2 (Srebp2) and LDL receptor (Ldlr) in the liver was dramatically reduced in mice fed a HFD compared with those fed a normal diet. When L. acidophilus NS1 was administered orally to HFD-fed mice, an HFD-induced suppression of Srebp2 and Ldlr expression in the liver was abolished. These results suggest that the oral administration of L. acidophilus NS1 to mice fed an HFD increased the expression of Srebp2 and Ldlr in the liver, which was inhibited by high fat intake, thus leading to a decrease in plasma cholesterol levels. Lactobacillus acidophilus NS1 could be a useful probiotic microorganism for cholesterol-lowering dairy products and the improvement of hyperlipidemia and hepatic lipid metabolism. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Antisense apolipoprotein B therapy: where do we stand?

PubMed

Akdim, Fatima; Stroes, Erik S G; Kastelein, John J P

2007-08-01

Antisense oligonucleotides are novel therapeutic agents that reduce the number of specific mRNAs available for translation of the encoded protein. ISIS 301012 is an antisense oligonucleotide developed to reduce the hepatic synthesis of apolipoprotein B-100. Apolipoprotein B-100 is made in the liver, and antisense oligonucleotides preferentially distribute to that organ, so antisense apolipoprotein B-100 may have potential as an efficacious lipid-lowering agent. Recently, in healthy volunteers and in mild dyslipidaemic patients, this strategy as monotherapy or in conjunction with statins has shown unparalleled efficacy in reducing apolipoprotein B-100 and LDL-cholesterol. Tolerance for this novel therapy is encouraging and safety concerns currently only relate to mild injection-site reactions and rare liver-function test abnormalities. It should be noted, however, that these safety results were obtained in relatively few individuals. ISIS 301012 has initially shown promising results in experimental animal models, and in clinical trials in humans. Besides the effect of reducing apolipoprotein B-100 and LDL-cholesterol, this compound also significantly lowers plasma triglycerides. Safety concerns related to the drug include increased liver-function tests. To date no evidence of hepatic steatosis has been reported. Nonetheless, clinical trials of longer duration are required to demonstrate further safety.

Impact of quality of dietary fat on serum cholesterol and coronary heart disease: focus on plant sterols and other non-glyceride components.

PubMed

Ghafoorunissa

2009-01-01

Elevated serum low density lipoprotein (LDL) cholesterol is a strong risk factor for coronary heart disease; dietary as well as therapeutic regimens target reduction of serum LDL cholesterol to decrease the morbidity and mortality of coronary heart disease. The fatty acid composition of dietary fat has a marked impact on serum LDL cholesterol and other risk factors of diet-related chronic diseases (metabolic syndrome, diabetes and coronary heart disease). Besides fatty acids, which constitute > 95% of their content, fats in foods contain other fat-soluble chemicals collectively called non-glyceride components. Sterols are a major part of the non-glyceride components of fats in plant foods and get concentrated in vegetable oils. Current evidence suggests that properly solubilized plant sterols or stanols incorporated in ester or free form in various food formulations effectively restrict the absorption of both dietary and biliary cholesterol causing 10%-14% reduction in serum LDL cholesterol in normal, hyperlipidaemic and diabetic subjects. The carotenoid-lowering effect of foods enriched with plant sterols can be corrected by increasing the intake of foods rich in carotenoids. The use of foods enriched with plant sterols as a part of a heart-healthy diet is recommended only after consulting a clinician. Recent studies strongly suggest that even smaller amounts of sterols available from natural plant foods and vegetable oils are important dietary components for lowering serum LDL cholesterol. Furthermore, some of the other non-glyceride components of food fats have one or more of the following functions-vitamin activity, serum LDL cholesterol-lowering and antioxidant activity. Since the hypocholesterolaemic and antioxidant effects ofa combination of the non-glyceride components may be more than their individual effects, increasing dietary plant sterols and non-glyceride components from natural plant foods and vegetable oils could provide an additional dietary means for prevention/correction of dyslipidaemia and increasing the antioxidant potential of human diets. The food-based dietary guidelines recommended to ensure an optimal fat quality in the diet of Indians provide high levels of natural plant sterols and other health-promoting non-glyceride components in addition to adequate absolute levels of individual fatty acids and their optimal balance. National policies to promote these dietary guidelines may contribute to the prevention of coronary heart disease and other diet-related chronic diseases.

Significance of platelet-activating factor acetylhydrolase in patients with non-insulin-dependent (type 2) diabetes mellitus.

PubMed

Serban, M; Tanaseanu, Cristina; Kosaka, T; Vidulescu, Cristina; Stoian, Irina; Marta, Daciana S; Tanaseanu, S; Moldoveanu, Elena

2002-01-01

Non-insulin dependent diabetes mellitus (NIDDM) represents an independent risk factor for cardiovascular diseases (CVD), being characterized by a continuous low-grade inflammation and endothelial activation state. Plasma platelet - activating factor - acetylhydrolases (PAF-AHs) are a subgroup of Ca(2+)-independent phospholipase A(2) family (also known as lipoprotein-associated phospholipases A(2)) that hydrolyze and inactivate the lipid mediator platelet-activating factor (PAF) and/or oxidized phospholipids. This enzyme is considered to play an important role in inflammatory diseases and atherosclerosis. The present study aims to investigate the relations between the levels of PAF-AH activity and LDL-cholesterol / HDL-cholesterol (LDL-ch / HDL-ch) ratio in NIDDM patients as compared to controls. serum PAF-AH activity was measured in 50 patients with dyslipidemia, in 50 NIDDM patients and in 50 controls (normal lipid and glucose levels). Total cholesterol, LDL-ch, HDL-ch, triglyceride and blood glucose were determined in all subjects. All NIDDM patients display hiperlipidemia, with increased LDL-ch and triglyceride levels. There is a significant correlation between LDL-ch levels (especially LDL-ch / HDL-ch ratio) and PAF-AH activity in dyslipidemic and NIDDM patients. Diabetic and dyslipidemic patients have an increased plasma PAF-AH activity correlated with their LDL-ch levels and mainly with LDL-ch / HDL-ch ratio. Plasma PAF-AH high levels appear to be important as a risk marker for endothelial dysfunction in patients with NIDDM.