Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1-mediated caveolin-1 downregulation in cultured vascular smooth muscle cells

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

Luo, Di-xian, E-mail: luodixian_2@163.com; Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan; First People's Hospital of Chenzhou City, Chenzhou 423000, Hunan

Research highlights: {yields} Vertical static pressure accelerates ox-LDL-induced cholesterol accumulation in cultured vascular smooth muscle cells. {yields} Static pressure induces SREBP-1 activation. {yields} Static pressure downregulates the expressions of caveolin-1 by activating SREBP-1. {yields} Static pressure also downregulates the transcription of ABCA1 by activating SREBP-1. {yields} Static pressure increases ox-LDL-induced cholesterol accumulation by SREBP-1-mediated caveolin-1 downregulation in vascular smooth muscle cells cultured in vitro. -- Abstract: Objective: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism. Methods: Rat-derived VSMC cell line A10 treated with 50 mg/L ox-LDL and different staticmore » pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure. Results: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 {+-} 2.8 mg/g, 31.8 {+-} 0.7 mg/g, 92.3 {+-} 2.1 mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 {+-} 9.4 mg/g, 235.9 {+-} 3.0 mg/g, 386.7 {+-} 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels

Nurse-coordinated care improves the achievement of LDL cholesterol targets through more intensive medication titration

PubMed Central

Snaterse, Marjolein; Jorstad, Harald T; Heiligenberg, Marlies; ter Riet, Gerben; Boekholdt, S Matthijs; Scholte op Reimer, Wilma; Peters, Ron J

2017-01-01

Background Nurse-coordinated care (NCC) improves the achievement of low-density lipoprotein-cholesterol (LDL-C) targets after an acute coronary syndrome (ACS). We hypothesised that NCC improves achievement of LDL-C targets through more intensive medication titration. Methods We used data from Randomised Evaluation of Secondary Prevention by Outpatient Nurse Specialists (RESPONSE), a multicentre randomised trial on the efficacy of NCC in 754 ACS patients. Follow-up data were collected at 6 and 12 months. To enable comparison between the various types and dosages of statins, we used the average lipid-lowering potency (ALLP, % LDL-C lowering) as an indicator of lipid-lowering medication intensity. Results Most patients in NCC intervention and usual care groups (96%) had started lipid-lowering therapy during the index hospitalisation. At 6 months, titration activities (up or down) were applied in 45% of NCC patients compared with 24% of patients receiving usual care (p<0.001), and a difference was also seen at 12 months follow-up (52% vs 34%, p<0.001). In patients not on LDL-C target at baseline, titration activities at 6 months were recorded in 63% and 30% of NCC and usual care patients respectively (p<0.001), with increased titration activities in both groups at 12 months (69% vs 43%, p<0.001). Conclusion NCC is associated with more frequent and intense lipid-lowering medication titration to reach LDL-C targets as compared with usual care alone. Further, merely starting the guideline-recommended dose is insufficient to reach the guideline-recommended LDL-C target level. Trial Registration number TC1290 (Netherlands). PMID:28761680

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)LDL-cholesterol as well as insulin AUC. Further analyses demonstrated that BMI correlated with %FEV(1), fasting insulin, insulin AUC, total cholesterol, LDL-cholesterol and the ratio of HDL-cholesterol to total cholesterol and that %FEV(1), insulin AUC and LDL-cholesterol were independent associated with BMI. Overweight CF subjects have higher fasting insulin and insulin AUC as well as total and LDL-cholesterol. Furthermore, we also demonstrated that LDL-cholesterol, insulin AUC are independently associated with BMI in a population of adult CF subjects. Copyright © 2012. Published by Elsevier B.V.

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

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

Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia

PubMed Central

Lee, Li-Chen; Wei, Li; Huang, Wen-Ching; Hsu, Yi-Ju; Chen, Yi-Ming; Huang, Chi-Chang

2015-01-01

Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia. PMID:26694461

Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia.

PubMed

Lee, Li-Chen; Wei, Li; Huang, Wen-Ching; Hsu, Yi-Ju; Chen, Yi-Ming; Huang, Chi-Chang

2015-12-17

Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia.

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

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.

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.

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.

Vegetarian diet and cholesterol and TAG levels by gender.

PubMed

Jian, Zhi-Hong; Chiang, Yi-Chen; Lung, Chia-Chi; Ho, Chien-Chang; Ko, Pei-Chieh; Ndi Nfor, Oswald; Chang, Hui-Chin; Liaw, Yi-Ching; Liang, Yu-Chiu; Liaw, Yung-Po

2015-03-01

The present study assessed the effects of vegetarian and omnivorous diets on HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), TAG and the ratio of HDL-C to total cholesterol (TC) by gender. HDL-C, LDL-C, TAG and HDL-C:TC were compared among three diet groups (vegan, ovo-lacto vegetarian and omnivorous). Multivariate linear regression analysis was performed to examine factors significantly and independently associated with vegetarian status and to estimate the β value of lipid profiles for the diet groups. Settings A cross-sectional study. Data were obtained from the Taiwanese Survey on the Prevalence of Hyperglycemia, Hyperlipidemia and Hypertension (TwSHHH). The study comprised included 3257 men and 3551 women. After adjusting for confounders, vegan and ovo-lacto vegetarian diets lowered LDL-C levels (β=-10.98, P=0.005 and β=-7.12, P=0.025, respectively) in men compared with omnivorous diet. There was a significant association between HDL-C and vegan diet (β=-6.53, P=0.004). In females, the β values of HDL-C, TAG and HDL-C:TC were -5.72 (P<0.0001), 16.51 (P=0.011) and -0.02 (P=0.012) for vegan diet, and -4.86 (P=0.002), 15.09 (P=0.008) and -0.01 (P=0.026) for ovo-lacto vegetarian diet, when compared with omnivorous diet. Vegan diet was associated with lower HDL-C concentrations in both males and females. Because the ovo-lacto vegetarian diet was effective in lowering LDL-C, it may be more appropriate for males.

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.

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.

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.

Mitotic spindle defects and chromosome mis-segregation induced by LDL/cholesterol-implications for Niemann-Pick C1, Alzheimer's disease, and atherosclerosis.

PubMed

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

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.

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.

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.

[LDL cholesterol lowering therapy: no target value but personalised treatment].

PubMed

Simoons, Maarten L; Deckers, Jaap W

2015-01-01

We previously recommended that LDL cholesterol lowering therapy be based on the risk for (recurrent) coronary events, rather than on arbitrary targets for serum LDL cholesterol concentration. We also recommended refraining from therapy with ezetimibe until its efficacy in preventing cardiovascular events had been documented. At the American Heart Association scientific sessions 2014 the results of the IMPROVE-IT study were reported. In this large, randomised trial, a modest benefit of the combination of simvastatin plus ezetimibe over simvastatin alone was reported after 7 years of treatment. The efficacy of such combination therapy was similar to the efficacy of high-dose statin therapy, while the combination therapy is much more expensive. Comparing the efficacy and costs of different preventive therapies, we recommend first prescribing aspirin and a moderate dose of statin, secondly an ACE inhibitor. A high-dose statin should be considered in high-risk patients. The combination of simvastatin and ezetimibe should be prescribed only in high-risk patients (e.g. diabetics after myocardial infarction) who do not tolerate high-dose statins.

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

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.

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.

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.

A promoter variant of the APOA5 gene increases atherogenic LDL levels and arterial stiffness in hypertriglyceridemic patients.

PubMed

Kim, Minjoo; Kim, Minkyung; Yoo, Hye Jin; Lee, Eunji; Chae, Jey Sook; Lee, Sang-Hyun; Lee, Jong Ho

2017-01-01

Hypertriglyceridemia is recognized as an independent risk factor for coronary artery disease. The apolipoprotein A5 gene (APOA5) is a key regulator of triglyceride levels. We aimed to evaluate the associations of single nucleotide polymorphisms (SNPs) in APOA5, including -1131T>C and c.553G>T, with hypertriglyceridemia, apoA5 concentrations, atherogenic LDL cholesterol levels, and arterial stiffness in hypertriglyceridemic patients. The study population included 599 hypertriglyceridemic patients (case) and 1,549 untreated normotriglyceridemic subjects (control). We genotyped two APOA5 variants, -1131T>C (rs662799) and c.553G>T (rs2075291). The frequencies of the CC genotype of -1131T>C (0.165) and the T allele of c.553G>T (0.119) were significantly higher in hypertriglyceridemic patients than in normotriglyceridemic subjects (0.061 and 0.070, respectively; all p<0.001). In the control and case groups, both the -1131T>C and c.553G>T variants were associated with higher triglyceride and lower HDL cholesterol levels. Controls with the -1131CC variant had lower apoA5 concentrations than controls with the -1131TT variant. Similar effects of the -1131T>C variant on apoA5 were observed in the cases. In the hypertriglyceridemic group, the -1131T>C variant was associated with a smaller LDL particle size, higher levels of oxidized LDL and malondialdehyde, and higher brachial-ankle pulse wave velocity. The -1131T>C and c.553G>T polymorphisms were associated with hypertriglyceridemia in the study population, but only the -1131T>C polymorphism directly affected apoA5 concentrations. Hypertriglyceridemic patients carrying the APOA5 -1131T>C polymorphism exhibited increased atherogenic LDL levels and arterial stiffness, probably due to an effect of the -1131T>C polymorphism on apoA5 concentrations.

[Effects of dressing containing plant sterol on serum cholesterol concentration and the safety evaluation in borderline or mildly hypercholesterolemic Japanese subjects].

PubMed

Kurokawa, Masanori; Masuda, Yasunobu; Noda, Mitsuhiro; Usuda, Mika; Takeda, Sayaka; Hasegawa, Mineo; Homma, Yasuhiko; Sugano, Michihiro

2008-01-01

In a placebo-controlled double-blind study, we examined the effects of dressing containing plant sterol (PS) on blood lipids and the safety in Japanese borderline or mildly hypercholesterolemic subjects. Fifty-nine subjects [total cholesterol (TC) concentration > or = 200 mg/dL] were randomly divided into two groups and were given daily 15 g of dressing containing 800 mg of PS [PS(+)-group] or without PS [PS(-)-group] for 12 weeks. Every 4 weeks, fasting blood was examined and subjective symptoms were analyzed. Serum TC, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB) concentrations did not change in the PS(-)-group, while TC and ApoB significantly decreased in the PS(+)-group at 8 and 12 weeks and LDL-C at 4, 8 and 12 weeks. Moreover, serum TC, LDL-C and ApoB concentrations were significantly lower than those of PS(-)-group at 8 and 12 weeks. Other laboratory tests were all in normal ranges and no adverse events were observed. The results indicated that PS-containing dressing decreased serum TC, LDL-C and ApoB concentrations in borderline or mildly hypercholesterolemic subjects. It is therefore proved that the dressing containing PS is helpful in maintaining blood cholesterol level normal and hence, the health of Japanese.

Plasma HDL-cholesterol and triglycerides, but not LDL-cholesterol, are associated with insulin secretion in non-diabetic subjects.

PubMed

Natali, Andrea; Baldi, Simona; Bonnet, Fabrice; Petrie, John; Trifirò, Silvia; Tricò, Domenico; Mari, Andrea

2017-04-01

Experimental data support the notion that lipoproteins might directly affect beta cell function, however clinical data are sparse and inconsistent. We aimed at verifying whether, independently of major confounders, serum lipids are associated with alterations in insulin secretion or clearance non-diabetic subjects. Cross sectional and observational prospective (3.5yrs), multicentre study in which 1016 non-diabetic volunteers aged 30-60yrs. and with a wide range of BMI (20.0-39.9kg/m 2 ) were recruited in a setting of University hospital ambulatory care (RISC study). baseline fasting lipids, fasting and OGTT-induced insulin secretion and clearance (measured by glucose and C-peptide modeling), peripheral insulin sensitivity (by the euglycemic clamp). Lipids and OGTT were repeated in 980 subjects after 3.5years. LDL-cholesterol did not show independent associations with fasting or stimulated insulin secretion or clearance. After accounting for potential confounders, HDL-cholesterol displayed negative and triglycerides positive independent associations with fasting and OGTT insulin secretion; neither with insulin clearance. Low HDL-cholesterol and high triglycerides were associated with an increase in glucose-dependent and a decrease in non-glucose-dependent insulin secretion. Over 3.5years both an HDL-cholesterol decline and a triglycerides rise were associated with an increase in fasting insulin secretion independent of changes in body weight or plasma glucose. LDL-cholesterol does not seem to influence any major determinant of insulin bioavailability while low HDL-cholesterol and high triglycerides might contribute to sustain the abnormalities in insulin secretion that characterize the pre-diabetic state. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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.

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.

Reasons for the upsetting cholesterol level during the community investigation from residents, physicians, and social aspects: the China Cholesterol Education Program (CCEP).

PubMed

Xie, Jiang; Guan, Fei; Wang, Jia-Hong; Hu, Da-Yi

2011-10-01

The community medical center is the first barrier for lipid control. We aimed to survey the residents' cholesterol condition in the community, and pursue the reasons for the upsetting results from various aspects. Residents and physicians were recruited from four community centers. Residents completed questionnaires and a physical examination as well as biochemical analysis. Physicians were also asked to complete a questionnaire, some of which were about basic knowledge of lipids. About 37.0% male and 48.1% female had elevated cholesterol levels. Residents' blood pressure (BP), fasting glucose (FG), body mass index (BMI), and waist circumference (WC) were positively associated with their low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Framingham risk scoring (FRS) was strongly related to cholesterol (P < 0.001 for LDL-C and TC). Residents' higher education grade was positively related to a normal cholesterol condition (P < 0.001), while personal income was negatively related to it. Rural residents had higher percent of population with normal cholesterol level (normal cholesterol rate) than their city counterpart (P < 0.001). Although physicians with college education had a much higher lipid knowledge level themselves, the physicians' factors had almost no relationship with the residents' cholesterol levels. Management of hypercholesterolemia should be an important component of health strategy in Beijing. Education is imperative for residents as well as for physicians.

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

Apple peel bioactive rich extracts effectively inhibit in vitro human LDL cholesterol oxidation.

PubMed

Thilakarathna, Surangi H; Rupasinghe, H P Vasantha; Needs, Paul W

2013-05-01

Apple peels are rich in antioxidant bioactives and hence can possess the ability to inhibit human low density lipoprotein cholesterol (LDL-C) oxidation. LDL-C oxidation is known to initiate atherosclerotic plaque formation. Unique quercetin-rich (QAE) and triterpene-rich (TAE) apple peel extracts, their constituent compounds and three in vivo quercetin metabolites were investigated for in vitro LDL-C oxidation inhibition. Both extracts effectively inhibited Cu(2+)-induced LDL-C oxidation. IC(50) of QAE and TAE for LDL-C oxidation products were 0.06-8.29 mg/L and 29.58-95.49 mg/L, respectively. Quercetin compounds, chlorogenic acid and phloridzin could contribute more to the effectiveness of QAE at physiological concentrations. The three in vivo quercetin metabolites; quercetin-3'-sulfate, quercetin-3-glucuronic acid and isorhamnetin-3-glucuronic acid were effective at physiological concentrations and therefore, QAE can be effective in LDL-C oxidation inhibition under physiological conditions. Constituent TAE compounds did not perform well under Cu(2+)-induction. Overall, both extracts effectively inhibited LDL-C oxidation in vitro. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

Oxidized LDL but not total LDL is associated with HbA1c in individuals without diabetes.

PubMed

Spessatto, Débora; Brum, Liz Marina Bueno Dos Passos; Camargo, Joíza Lins

2017-08-01

This study investigates the association between HbA1c, LDL and oxi-LDL in individuals without diabetes (DM). One hundred and ninety-six individuals, without DM, were enrolled and divided into three groups according to HbA1c and fasting plasma glucose values. HbA1c, oxi-LDL, LDL, and other biochemical measurements of lipid profile were also carried out. oxi-LDL levels showed significant differences among all groups and group 3 presented higher values [34U/L (27-46); 44U/L (37-70); and 86U/L (49-136); p<0.001; for groups 1, 2 and 3, respectively]. There was also a significant difference in oxi-LDL/HDL and oxi-LDL/LDL ratios among all groups (p<0.001). There was no significant difference in total cholesterol (TC), triglycerides and LDL values among groups. HbA1c showed moderate positive associations with oxi-LDL (r=0.431; p<0.001), oxi-LDL/HDL ratio (r=0.423, p<0.001), and oxi-LDL/LDL ratio (r=0.359, p<0.001). There were lower associations between HbA1c and TC (r=0.142; p=0.048), triglycerides (r=0.155; p=0.030), LDL (r=0.148; p=0.039), non-HDL (r=0.192; p=0.007) and Apo B (r=0.171, p<0.001). The positive associations between HbA1c and oxi-LDL, oxi-LDL/HDL and oxi-LDL/LDL ratios remained significant even after adjustment by multiple linear regression analysis for the variables alcohol consumption, use of medicine, BMI, and age. oxi-LDL levels are significantly associated with HbA1c in non-diabetic individuals. However, the levels of traditional atherogenic lipids only showed a weak association with HbA1c levels. Those at high risk of developing DM or cardiovascular disease have higher levels of oxi-LDL. These data favor to the use of HbA1c as a biomarker to identify individuals at risk of developing complications even in non-diabetic glycemic levels. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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

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.

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

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.

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

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

A randomized trial and novel SPR technique identifies altered lipoprotein-LDL receptor binding as a mechanism underlying elevated LDL-cholesterol in APOE4s

PubMed Central

Calabuig-Navarro, M. V.; Jackson, K. G.; Kemp, C. F.; Leake, D. S.; Walden, C. M.; Lovegrove, J. A.; Minihane, A. M.

2017-01-01

At a population level APOE4 carriers (~25% Caucasians) are at higher risk of cardiovascular diseases. The penetrance of genotype is however variable and influenced by dietary fat composition, with the APOE4 allele associated with greater LDL-cholesterol elevation in response to saturated fatty acids (SFA). The etiology of this greater responsiveness is unknown. Here a novel surface plasmon resonance technique (SPR) is developed and used, along with hepatocyte (with the liver being the main organ modulating lipoprotein metabolism and plasma lipid levels) uptake studies to establish the impact of dietary fatty acid composition on, lipoprotein-LDL receptor (LDLR) binding, and hepatocyte uptake, according to APOE genotype status. In men prospectively recruited according to APOE genotype (APOE3/3 common genotype, or APOE3/E4), triglyceride-rich lipoproteins (TRLs) were isolated at fasting and 4–6 h following test meals rich in SFA, unsaturated fat and SFA with fish oil. In APOE4s a greater LDLR binding affinity of postprandial TRL after SFA, and lower LDL binding and hepatocyte internalization, provide mechanisms for the greater LDL-cholesterol raising effect. The SPR technique developed may be used for the future study of the impact of genotype, and physiological and behavioral variables on lipoprotein metabolism. Trial registration number NCT01522482. PMID:28276521

oxLDL induces endothelial cell proliferation via Rho/ROCK/Akt/p27kip1 signaling: opposite effects of oxLDL and cholesterol loading.

PubMed

Zhang, Chongxu; Adamos, Crystal; Oh, Myung-Jin; Baruah, Jugajyoti; Ayee, Manuela A A; Mehta, Dolly; Wary, Kishore K; Levitan, Irena

2017-09-01

Oxidized modifications of LDL (oxLDL) play a key role in the development of endothelial dysfunction and atherosclerosis. However, the underlying mechanisms of oxLDL-mediated cellular behavior are not completely understood. Here, we compared the effects of two major types of oxLDL, copper-oxidized LDL (Cu 2+ -oxLDL) and lipoxygenase-oxidized LDL (LPO-oxLDL), on proliferation of human aortic endothelial cells (HAECs). Cu 2+ -oxLDL enhanced HAECs' proliferation in a dose- and degree of oxidation-dependent manner. Similarly, LPO-oxLDL also enhanced HAEC proliferation. Mechanistically, both Cu 2+ -oxLDL and LPO-oxLDL enhance HAEC proliferation via activation of Rho, Akt phosphorylation, and a decrease in the expression of cyclin-dependent kinase inhibitor 1B (p27 kip1 ). Both Cu 2+ -oxLDL or LPO-oxLDL significantly increased Akt phosphorylation, whereas an Akt inhibitor, MK2206, blocked oxLDL-induced increase in HAEC proliferation. Blocking Rho with C3 or its downstream target ROCK with Y27632 significantly inhibited oxLDL-induced Akt phosphorylation and proliferation mediated by both Cu 2+ - and LPO-oxLDL. Activation of RhoA was blocked by Rho-GDI-1, which also abrogated oxLDL-induced Akt phosphorylation and HAEC proliferation. In contrast, blocking Rac1 in these cells had no effect on oxLDL-induced Akt phosphorylation or cell proliferation. Moreover, oxLDL-induced Rho/Akt signaling downregulated cell cycle inhibitor p27 kip1 Preloading these cells with cholesterol, however, prevented oxLDL-induced Akt phosphorylation and HAEC proliferation. These findings provide a new understanding of the effects of oxLDL on endothelial proliferation, which is essential for developing new treatments against neovascularization and progression of atherosclerosis. Copyright © 2017 the American Physiological Society.

The effect of defatted cocoa powder on cholesterol-induced changes of serum lipids in rats

PubMed

Ahmad, Mousa Numan; Amr, Amira Mohammad

2017-06-05

Cocoa has been known for many health benefits, but its lipid-lowering activity still remains unresolved. To investigate effects of varying amounts of defatted cocoa on serum lipids in cholesterol-fed rats. Forty-eight male Sprague-Dawley rats were randomly assigned into four cholesterol-free (control) and four cholesterol-supplemented (experimental) diets containing 0, 1, 2 or 3% defatted cocoa (DC) and given ad libitumto the rats for ten weeks. Serum total cholesterol (TC), low- and very low-density lipoprotein cholesterol (LDL-C and VLDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were quantified, atherogenic index (AI) was calculated, and other biological parameters were assessed. Food intake and body weight did not respond to DC. Compared to 0% DC, 3% DC had the most prominent effect on serum lipids inducing significant fall in LDL-C and TG, and rise in TC/TG in cholesterol-deprived rats, and increase in VLDL-C and AI, and decrease in HDL-C in cholesterol-fed rats. Compared to cholesterol-deprived rats, 3% DC caused significant rise in VLDL-C, AI and TC/TG, and fall in TG in cholesterol-fed rats. This lipid-modifying effect was markedly substantiated by corresponding linear trend responses to DC. Differences in lipid variables of rats fed on DC diets were less evident. Results suggest that, in contrast to cholesterol-free situations, defatted cocoa is seemingly incapable of counteracting the atherogenic effect of cholesterol in rats, perhaps in an interaction that is likely to have clinical implications in cardiometabolic conditions.

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.

[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.

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 ...

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.

Animal source food intake and association with blood cholesterol, glycerophospholipids and sphingolipids in a northern Swedish population.

PubMed

Igl, Wilmar; Kamal-Eldin, Afaf; Johansson, Asa; Liebisch, Gerhard; Gnewuch, Carsten; Schmitz, Gerd; Gyllensten, Ulf

2013-01-01

The high intake of game meat in populations with a subsistence-based diet may affect their blood lipids and health status. To examine the association between diet and circulating levels of blood lipid levels in a northern Swedish population. We compared a group with traditional lifestyle (TLS) based on reindeer herding (TLS group) with those from the same area with a non-traditional lifestyle (NTLS) typical of more industrialized regions of Sweden (NTLS group). The analysis was based on self-reported intake of animal source food (i.e. non-game meat, game meat, fish, dairy products and eggs) and the serum blood level of a number of lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglycerides (TG), glycerophospholipids and sphingolipids]. The TLS group had higher cholesterol, LDL and HDL levels than the reference group. Of the TLS group, 65% had cholesterol levels above the threshold for increased risk of coronary heart disease (≥ 240 mg/dl), as compared to 38% of the NTLS group. Self-reported consumption of game meat was positively associated with TC and LDL. The high game meat consumption of the TLS group is associated with increased cholesterol levels. High intake of animal protein and fat and low fibre is known to increase the risk of cardiovascular disease, but other studies of the TLS in northern Sweden have shown comparable incidences of cardiovascular disease to the reference (NTLS) group from the same geographical area. This indicates that factors other than TC influence disease risk. One such possible factor is dietary phospholipids, which are also found in high amounts specifically in game meat and have been shown to inhibit cholesterol absorption.

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

A nutraceutical approach (Armolipid Plus) to reduce total and LDL cholesterol in individuals with mild to moderate dyslipidemia: Review of the clinical evidence.

PubMed

Barrios, Vivencio; Escobar, Carlos; Cicero, Arrigo Francesco Giuseppe; Burke, David; Fasching, Peter; Banach, Maciej; Bruckert, Eric

2017-02-01

Compelling evidence supports the effectiveness of the reduction of total and LDL cholesterol (TC and LDL-C) in primarily preventing cardiovascular events, within the framework of life-long prevention programs mainly consisting in lifestyle changes. Pharmacological treatment should be introduced when lifestyle changes, including use of nutraceuticals, have failed. ESC/EAS guidelines list a number of nutraceutical compounds and functional foods which have been individually studied in randomized, controlled clinical trials (RCTs). To date only a proprietary formulation of three naturally occurring substances with putative complementary lipid-lowering properties - red yeast rice, policosanol and berberine - combined with folic acid, astaxanthin, and coenzyme Q10 (Armolipid Plus ® ) has been extensively investigated in several RCTs, 7 of which were placebo-controlled, 2 were ezetimibe comparators and 4 were "real life" studies comparing diet and Armolipid Plus to diet alone. The trials included mostly patients with mild to moderate dyslipidemia, treated for 6-48 weeks. The trials also included special populations and patients in whom statins were contraindicated or who could not tolerate them. Armolipid Plus has proved to be able to achieve significant reductions in TC (11-21%) and in LDL-C (15-31%) levels, which is equivalent to expectations from low dose statins. In patients intolerant to statins, who do not achieve their therapeutic target with ezetimibe, Armolipid Plus can achieve a further 10% improvement in TC and LDL-C. The safety and tolerability of Armolipid Plus were excellent, thought likely due to the intentional combination of low doses of its active ingredients: low enough not to be associated with untoward effects, but high enough to exert therapeutic effects in combination with other complementary substances. Consequently, in the event of intolerance to statins, Armolipid Plus offers an effective alternative, which is devoid of the safety risks

[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 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.

Dyslipidemia in subclinical hypothyroidism requires assessment of small dense low density lipoprotein cholesterol (sdLDL-C).

PubMed

Saric, Maida Seferovic; Jurasic, Miljenka-Jelena; Sovic, Slavica; Kranjcec, Bojana; Glivetic, Tatjana; Demarin, Vida

2017-09-26

Usually both hypothyroidism and hyperthyroidism are related to the cardiovascular and cerebrovascular disease development. The relationship between subclinical hypothyroidism has been widely investigated but the findings remain controversial. The aim of the present study was to evaluate the lipid profile in patients with subclinical hypothyroidism (SHypo) in comparison to controls and to determine the association of SHypo and dyslipidemia in attempt to find importance of small dense low-density lipoprotein cholesterol (sdLDL-C) in atherosclerosis. In this study we included 100 women, aged 30 to 70 years that were divided into subgroups according to their age. According to the values of levels of thyroid hormones they were divided into euthyroid (control) group (n = 64) and (newly discovered) subclinical hypothyroidism (SHypo) group (n = 36). A high-sensitivity C-reactive protein (hs-CRP) and lipid profile, including small dense low-density lipoprotein cholesterol (sdLDL-C) were determined. Body weight and height were measured and BMI calculated. History of the current illness, medication, alcohol consumption and cigarettes smoking were noted. Changed lipid profile as well as elevated triglycerides and sdLDL-C were observed in the group with subclinical hypothyroidism compared to the control group. It is important to determine serum lipid levels, especially serum sdLDL-C levels at an early stage of subclinical hypothyroidism, since they represent atherogenic LDL particles and are better indicators for dyslipidaemia in subclinical hypothyroidism and the development of atherosclerosis with potential complications such as cardiovascular and cerebrovascular diseases.

Butter increased total and LDL cholesterol compared with olive oil but resulted in higher HDL cholesterol compared with a habitual diet.

PubMed

Engel, Sara; Tholstrup, Tine

2015-08-01

Butter is known to have a cholesterol-raising effect and, therefore, has often been included as a negative control in dietary studies, whereas the effect of moderate butter intake has not been elucidated to our knowledge. We compared the effects of moderate butter intake, moderate olive oil intake, and a habitual diet on blood lipids, high-sensitivity C-reactive protein (hsCRP), glucose, and insulin. The study was a controlled, double-blinded, randomized 2 × 5-wk crossover dietary intervention study with a 14-d run-in period during which subjects consumed their habitual diets. The study included 47 healthy men and women (mean ± SD total cholesterol: 5.22 ± 0.90 mmol/L) who substituted a part of their habitual diets with 4.5% of energy from butter or refined olive oil. Study subjects were 70% women with a mean age and body mass index (in kg/m²) of 40.4 y and 23.5, respectively. Butter intake increased total cholesterol and LDL cholesterol more than did olive oil intake (P < 0.05) and the run-in period (P < 0.005 and P < 0.05, respectively) and increased HDL cholesterol compared with the run-in period (P < 0.05). No difference in effects was observed for triacylglycerol, hsCRP, insulin, and glucose concentrations. The intake of saturated fatty acids was significantly higher in the butter period than in the olive oil and run-in periods (P < 0.0001). Moderate intake of butter resulted in increases in total cholesterol and LDL cholesterol compared with the effects of olive oil intake and a habitual diet (run-in period). Furthermore, moderate butter intake was also followed by an increase in HDL cholesterol compared with the habitual diet. We conclude that hypercholesterolemic people should keep their consumption of butter to a minimum, whereas moderate butter intake may be considered part of the diet in the normocholesterolemic population. © 2015 American Society for Nutrition.

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.

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

Self-Reported Snoring Is Associated with Dyslipidemia, High Total Cholesterol, and High Low-Density Lipoprotein Cholesterol in Obesity: A Cross-Sectional Study from a Rural Area of China.

PubMed

Zhang, Naijin; Chen, Yintao; Chen, Shuang; Jia, Pengyu; Guo, Xiaofan; Sun, Guozhe; Sun, Yingxian

2017-01-17

Studies to explore the relationship between self-reported snoring and dyslipidemia, especially high total cholesterol (TC) and high low-density lipoprotein cholesterol (LDL-C), in the general population are still lacking. Our study was designed to examine whether self-reported snoring is significantly associated with dyslipidemia and ascertain the effects of different snoring intensities on dyslipidemia. There were 10,139 participants in our study. After adjustment for all confounding factors, self-reported snoring (OR = 1.207; p = 0.003), moderate (OR = 1.229; p = 0.015), strong (OR = 1.222; p = 0.033), and very strong (OR = 1.467; p = 0.012) snoring intensity, but not low (OR = 1.110; p = 0.224) snoring intensity, were significantly associated with dyslipidemia among adults with BMI (body mass index) ≥ 25 kg/m². In addition, self-reported snoring was significantly associated with high TC (OR = 1.167; p = 0.048) and high LDL-C (OR = 1.228; p = 0.044), rather than low HDL-C (OR = 1.171; p = 0.057) and high triglyceride (TG) (OR = 1.110; p = 0.141). In conclusion, adults with BMI ≥ 25 kg/m² and who experience snoring, especially moderate, strong, and very strong intensity levels of snoring, should be on the alert regarding the possibility of dyslipidemia, especially high LDL-C and high TC.

PCSK9 Inhibitors: Novel Therapeutic Strategies for Lowering LDL-Cholesterol.

PubMed

Liu, Zhao-Peng; Wang, Yan

2018-04-22

Statins are currently the major therapeutic strategies to lower low-density lipoprotein cholesterol (LDL-C) levels. However, a number of hypercholesterolemia patients still have a residual cardiovascular disease (CVD) risk despite taking the maximum-tolerated dose of statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein receptor (LDLR), inducing its degradation in the lysosome and inhibiting LDLR recirculating to the cell membranes. The gain-of-function mutations in PCSK9 elevate the LDL-C levels in plasma. Therefore, PCSK9 inhibitors become novel therapeutic approaches in the treatment of hypercholesterolemia. Several PCSK9 inhibitors have been under investigation, and much progress has been made in clinical trials, especially for monoclonal antibodies (MoAbs). Two MoAbs, evolocumab and alirocumab, are now in clinical use. In this review, we summarize the development of PCSK9 inhibitors, including antisense oligonucleotides (ASOs), small interfering RNA (siRNA), small molecule inhibitor, MoAbs, mimetic peptides and adnectins, and the related safety issues. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Asian patients with dyslipidemia in an urban population: Effect of ethnicity on their LDL-cholesterol treatment goals.

PubMed

Tan, Ngiap Chuan; Koh, Kim Hwee; Goh, Chin Chin; Koh, Yi Ling Eileen; Goh, Soo Chye Paul

2016-01-01

Dyslipidemia is the primary risk factor for arthrosclerosis. It is the most common chronic disease among the multiethnic Asian population in Singapore. Local national health survey has shown ethnic variability in achieving control of dyslipidemia. This study aimed to determine the proportion of patients in primary care, who achieved their low-density lipoprotein (LDL)-cholesterol treatment goals, stratified by the local major ethnic groups. It also evaluated the factors that affected their dyslipidemia control, including diet, exercise and medication usage. Research assistants administered questionnaires on adult patients with physician-diagnosed dyslipidemia to determine their views on diet, exercise, and medications in this cross-sectional study in 2 local primary care clinics. Their lipid profiles were retrieved from their laboratory reports in their electronic health records. Chi-square and Fisher exact tests were used for the categorical demographics and questionnaire variables, (P < .05: statistically significant). Logistic regression was performed using these significant variables to determine the adjusted odds of the ethnic groups. A total of 1093 eligible patients completed the questionnaires. The proportion of Chinese, Malay, and Indian patients who achieved LDL-cholesterol goals was 78.3%, 67.9%, and 68.5%, respectively. Among those who self-reported taking their favorite cholesterol-rich food occasionally when their cholesterol became controlled, 35.8% Indians failed to achieve treatment goals, compared to 20.1% Chinese and 30.9% Malay patients. Regular medication adherence was associated with 81.8% Chinese, 69.0% Malay, and 69.7% Indian reaching treatment goals. More Chinese met LDL-cholesterol treatment goals compared to Malays and Indians. Lipid-lowering medications enabled but smoking hindered their achievement of these treatment goals. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Association between Low-density lipoprotein cholesterol and occipital periventricular hyperintensities in a group of Chinese patients: an observational study.

PubMed

Duan, Dazhi; Shen, Lin; Cui, Chun; Shu, Tongsheng; Zheng, Jian

2017-02-27

While occipital periventricular hyperintensities (OPVHs) are among the most common mild white matter hyperintensities, the clinical factors associated with OPVHs remain unclear. In this study, we investigated the role of clinical factors in development of pure OPVHs. This study included 97 patients with OPVHs and 73 healthy controls. Univariate analysis of clinical factors in OPVH patients and controls was followed by binomial logistic regression analysis to identify clinical factors significantly associated with OPVHs. Univariate analysis indicated that age, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein-B (Apo-B) levels differed significantly between the OPVH patients and controls (p < 0.05). Age and gender were correlated with OPVH scores (p < 0.05), while LDL-C, triglycerides, Apo-B and TC were anti-correlated with OPVHs scores (p < 0.05). Multivariate analysis indicated that LDL-C is negatively correlated with OPVHs (p < 0.05), and age is positively correlated with OPVHs (p < 0.001). In summary, LDL-C was negatively and age was positively associated with OPVHs among Chinese patients in a hospital.

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.

Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol

PubMed Central

Lange, Leslie A.; Hu, Youna; Zhang, He; Xue, Chenyi; Schmidt, Ellen M.; Tang, Zheng-Zheng; Bizon, Chris; Lange, Ethan M.; Smith, Joshua D.; Turner, Emily H.; Jun, Goo; Kang, Hyun Min; Peloso, Gina; Auer, Paul; Li, Kuo-ping; Flannick, Jason; Zhang, Ji; Fuchsberger, Christian; Gaulton, Kyle; Lindgren, Cecilia; Locke, Adam; Manning, Alisa; Sim, Xueling; Rivas, Manuel A.; Holmen, Oddgeir L.; Gottesman, Omri; Lu, Yingchang; Ruderfer, Douglas; Stahl, Eli A.; Duan, Qing; Li, Yun; Durda, Peter; Jiao, Shuo; Isaacs, Aaron; Hofman, Albert; Bis, Joshua C.; Correa, Adolfo; Griswold, Michael E.; Jakobsdottir, Johanna; Smith, Albert V.; Schreiner, Pamela J.; Feitosa, Mary F.; Zhang, Qunyuan; Huffman, Jennifer E.; Crosby, Jacy; Wassel, Christina L.; Do, Ron; Franceschini, Nora; Martin, Lisa W.; Robinson, Jennifer G.; Assimes, Themistocles L.; Crosslin, David R.; Rosenthal, Elisabeth A.; Tsai, Michael; Rieder, Mark J.; Farlow, Deborah N.; Folsom, Aaron R.; Lumley, Thomas; Fox, Ervin R.; Carlson, Christopher S.; Peters, Ulrike; Jackson, Rebecca D.; van Duijn, Cornelia M.; Uitterlinden, André G.; Levy, Daniel; Rotter, Jerome I.; Taylor, Herman A.; Gudnason, Vilmundur; Siscovick, David S.; Fornage, Myriam; Borecki, Ingrid B.; Hayward, Caroline; Rudan, Igor; Chen, Y. Eugene; Bottinger, Erwin P.; Loos, Ruth J.F.; Sætrom, Pål; Hveem, Kristian; Boehnke, Michael; Groop, Leif; McCarthy, Mark; Meitinger, Thomas; Ballantyne, Christie M.; Gabriel, Stacey B.; O’Donnell, Christopher J.; Post, Wendy S.; North, Kari E.; Reiner, Alexander P.; Boerwinkle, Eric; Psaty, Bruce M.; Altshuler, David; Kathiresan, Sekar; Lin, Dan-Yu; Jarvik, Gail P.; Cupples, L. Adrienne; Kooperberg, Charles; Wilson, James G.; Nickerson, Deborah A.; Abecasis, Goncalo R.; Rich, Stephen S.; Tracy, Russell P.; Willer, Cristen J.; Gabriel, Stacey B.; Altshuler, David M.; Abecasis, Gonçalo R.; Allayee, Hooman; Cresci, Sharon; Daly, Mark J.; de Bakker, Paul I.W.; DePristo, Mark A.; Do, Ron; Donnelly, Peter; Farlow, Deborah N.; Fennell, Tim; Garimella, Kiran; Hazen, Stanley L.; Hu, Youna; Jordan, Daniel M.; Jun, Goo; Kathiresan, Sekar; Kang, Hyun Min; Kiezun, Adam; Lettre, Guillaume; Li, Bingshan; Li, Mingyao; Newton-Cheh, Christopher H.; Padmanabhan, Sandosh; Peloso, Gina; Pulit, Sara; Rader, Daniel J.; Reich, David; Reilly, Muredach P.; Rivas, Manuel A.; Schwartz, Steve; Scott, Laura; Siscovick, David S.; Spertus, John A.; Stitziel, Nathaniel O.; Stoletzki, Nina; Sunyaev, Shamil R.; Voight, Benjamin F.; Willer, Cristen J.; Rich, Stephen S.; Akylbekova, Ermeg; Atwood, Larry D.; Ballantyne, Christie M.; Barbalic, Maja; Barr, R. Graham; Benjamin, Emelia J.; Bis, Joshua; Boerwinkle, Eric; Bowden, Donald W.; Brody, Jennifer; Budoff, Matthew; Burke, Greg; Buxbaum, Sarah; Carr, Jeff; Chen, Donna T.; Chen, Ida Y.; Chen, Wei-Min; Concannon, Pat; Crosby, Jacy; Cupples, L. Adrienne; D’Agostino, Ralph; DeStefano, Anita L.; Dreisbach, Albert; Dupuis, Josée; Durda, J. Peter; Ellis, Jaclyn; Folsom, Aaron R.; Fornage, Myriam; Fox, Caroline S.; Fox, Ervin; Funari, Vincent; Ganesh, Santhi K.; Gardin, Julius; Goff, David; Gordon, Ora; Grody, Wayne; Gross, Myron; Guo, Xiuqing; Hall, Ira M.; Heard-Costa, Nancy L.; Heckbert, Susan R.; Heintz, Nicholas; Herrington, David M.; Hickson, DeMarc; Huang, Jie; Hwang, Shih-Jen; Jacobs, David R.; Jenny, Nancy S.; Johnson, Andrew D.; Johnson, Craig W.; Kawut, Steven; Kronmal, Richard; Kurz, Raluca; Lange, Ethan M.; Lange, Leslie A.; Larson, Martin G.; Lawson, Mark; Lewis, Cora E.; Levy, Daniel; Li, Dalin; Lin, Honghuang; Liu, Chunyu; Liu, Jiankang; Liu, Kiang; Liu, Xiaoming; Liu, Yongmei; Longstreth, William T.; Loria, Cay; Lumley, Thomas; Lunetta, Kathryn; Mackey, Aaron J.; Mackey, Rachel; Manichaikul, Ani; Maxwell, Taylor; McKnight, Barbara; Meigs, James B.; Morrison, Alanna C.; Musani, Solomon K.; Mychaleckyj, Josyf C.; Nettleton, Jennifer A.; North, Kari; O’Donnell, Christopher J.; O’Leary, Daniel; Ong, Frank; Palmas, Walter; Pankow, James S.; Pankratz, Nathan D.; Paul, Shom; Perez, Marco; Person, Sharina D.; Polak, Joseph; Post, Wendy S.; Psaty, Bruce M.; Quinlan, Aaron R.; Raffel, Leslie J.; Ramachandran, Vasan S.; Reiner, Alexander P.; Rice, Kenneth; Rotter, Jerome I.; Sanders, Jill P.; Schreiner, Pamela; Seshadri, Sudha; Shea, Steve; Sidney, Stephen; Silverstein, Kevin; Smith, Nicholas L.; Sotoodehnia, Nona; Srinivasan, Asoke; Taylor, Herman A.; Taylor, Kent; Thomas, Fridtjof; Tracy, Russell P.; Tsai, Michael Y.; Volcik, Kelly A.; Wassel, Chrstina L.; Watson, Karol; Wei, Gina; White, Wendy; Wiggins, Kerri L.; Wilk, Jemma B.; Williams, O. Dale; Wilson, Gregory; Wilson, James G.; Wolf, Phillip; Zakai, Neil A.; Hardy, John; Meschia, James F.; Nalls, Michael; Singleton, Andrew; Worrall, Brad; Bamshad, Michael J.; Barnes, Kathleen C.; Abdulhamid, Ibrahim; Accurso, Frank; Anbar, Ran; Beaty, Terri; Bigham, Abigail; Black, Phillip; Bleecker, Eugene; Buckingham, Kati; Cairns, Anne Marie; Caplan, Daniel; Chatfield, Barbara; Chidekel, Aaron; Cho, Michael; Christiani, David C.; Crapo, James D.; Crouch, Julia; Daley, Denise; Dang, Anthony; Dang, Hong; De Paula, Alicia; DeCelie-Germana, Joan; Drumm, Allen DozorMitch; Dyson, Maynard; Emerson, Julia; Emond, Mary J.; Ferkol, Thomas; Fink, Robert; Foster, Cassandra; Froh, Deborah; Gao, Li; Gershan, William; Gibson, Ronald L.; Godwin, Elizabeth; Gondor, Magdalen; Gutierrez, Hector; Hansel, Nadia N.; Hassoun, Paul M.; Hiatt, Peter; Hokanson, John E.; Howenstine, Michelle; Hummer, Laura K.; Kanga, Jamshed; Kim, Yoonhee; Knowles, Michael R.; Konstan, Michael; Lahiri, Thomas; Laird, Nan; Lange, Christoph; Lin, Lin; Lin, Xihong; Louie, Tin L.; Lynch, David; Make, Barry; Martin, Thomas R.; Mathai, Steve C.; Mathias, Rasika A.; McNamara, John; McNamara, Sharon; Meyers, Deborah; Millard, Susan; Mogayzel, Peter; Moss, Richard; Murray, Tanda; Nielson, Dennis; Noyes, Blakeslee; O’Neal, Wanda; Orenstein, David; O’Sullivan, Brian; Pace, Rhonda; Pare, Peter; Parker, H. Worth; Passero, Mary Ann; Perkett, Elizabeth; Prestridge, Adrienne; Rafaels, Nicholas M.; Ramsey, Bonnie; Regan, Elizabeth; Ren, Clement; Retsch-Bogart, George; Rock, Michael; Rosen, Antony; Rosenfeld, Margaret; Ruczinski, Ingo; Sanford, Andrew; Schaeffer, David; Sell, Cindy; Sheehan, Daniel; Silverman, Edwin K.; Sin, Don; Spencer, Terry; Stonebraker, Jackie; Tabor, Holly K.; Varlotta, Laurie; Vergara, Candelaria I.; Weiss, Robert; Wigley, Fred; Wise, Robert A.; Wright, Fred A.; Wurfel, Mark M.; Zanni, Robert; Zou, Fei; Nickerson, Deborah A.; Rieder, Mark J.; Green, Phil; Shendure, Jay; Akey, Joshua M.; Bustamante, Carlos D.; Crosslin, David R.; Eichler, Evan E.; Fox, P. Keolu; Fu, Wenqing; Gordon, Adam; Gravel, Simon; Jarvik, Gail P.; Johnsen, Jill M.; Kan, Mengyuan; Kenny, Eimear E.; Kidd, Jeffrey M.; Lara-Garduno, Fremiet; Leal, Suzanne M.; Liu, Dajiang J.; McGee, Sean; O’Connor, Timothy D.; Paeper, Bryan; Robertson, Peggy D.; Smith, Joshua D.; Staples, Jeffrey C.; Tennessen, Jacob A.; Turner, Emily H.; Wang, Gao; Yi, Qian; Jackson, Rebecca; Peters, Ulrike; Carlson, Christopher S.; Anderson, Garnet; Anton-Culver, Hoda; Assimes, Themistocles L.; Auer, Paul L.; Beresford, Shirley; Bizon, Chris; Black, Henry; Brunner, Robert; Brzyski, Robert; Burwen, Dale; Caan, Bette; Carty, Cara L.; Chlebowski, Rowan; Cummings, Steven; Curb, J. David; Eaton, Charles B.; Ford, Leslie; Franceschini, Nora; Fullerton, Stephanie M.; Gass, Margery; Geller, Nancy; Heiss, Gerardo; Howard, Barbara V.; Hsu, Li; Hutter, Carolyn M.; Ioannidis, John; Jiao, Shuo; Johnson, Karen C.; Kooperberg, Charles; Kuller, Lewis; LaCroix, Andrea; Lakshminarayan, Kamakshi; Lane, Dorothy; Lasser, Norman; LeBlanc, Erin; Li, Kuo-Ping; Limacher, Marian; Lin, Dan-Yu; Logsdon, Benjamin A.; Ludlam, Shari; Manson, JoAnn E.; Margolis, Karen; Martin, Lisa; McGowan, Joan; Monda, Keri L.; Kotchen, Jane Morley; Nathan, Lauren; Ockene, Judith; O’Sullivan, Mary Jo; Phillips, Lawrence S.; Prentice, Ross L.; Robbins, John; Robinson, Jennifer G.; Rossouw, Jacques E.; Sangi-Haghpeykar, Haleh; Sarto, Gloria E.; Shumaker, Sally; Simon, Michael S.; Stefanick, Marcia L.; Stein, Evan; Tang, Hua; Taylor, Kira C.; Thomson, Cynthia A.; Thornton, Timothy A.; Van Horn, Linda; Vitolins, Mara; Wactawski-Wende, Jean; Wallace, Robert; Wassertheil-Smoller, Sylvia; Zeng, Donglin; Applebaum-Bowden, Deborah; Feolo, Michael; Gan, Weiniu; Paltoo, Dina N.; Sholinsky, Phyliss; Sturcke, Anne

2014-01-01

Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98th or <2nd percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments. PMID:24507775

Type of dyslipidemia and achievement of the LDL-cholesterol goal in chronic kidney disease patients at the University Hospital.

PubMed

Sangsawang, Tamon; Sriwijitkamol, Apiradee

2015-01-01

Chronic kidney disease (CKD) has been defined as a coronary artery disease risk equivalent. Therefore, the current guideline has been recommended for CKD patients to reach and maintain a low-density lipoprotein-cholesterol (LDL-C) goal of less than 100 mg/dL. However, the data regarding the achievement of LDL-C goal in these patients is lacking. This study was conducted to evaluate the types of dyslipidemia affecting patients with CKD stages 3 and 4 and to determine whether these patients achieved LDL-C goal. We performed a retrospective chart review of patients with CKD stage 3 or 4 and dyslipidemia who were followed-up at Siriraj Hospital between October 2011 and September 2012. In total, 150 patients with CKD stage 3 or 4 and dyslipidemia were recruited. The mean age was 72±10 years, and the body mass index was 25.6±4 kg/m(2); 60% had CKD stage 3 with an estimated glomerular filtration rate of 34±12 mL/min/1.73 m(2), and 54% had type 2 diabetes. The percentage of patients with hypercholesterolemia was 78%, hypertriglyceridemia 54%, and low high-density lipoprotein-C 36%. Of these, 52% had mixed hyperlipidemia. Statin treatment was prescribed to 87% of the patients, of which only 31.3% achieved the LDL-C goal according to the National Cholesterol Education Program and the European Society of Cardiology/European Atherosclerosis Society recommendations. Patients who did not achieve the LDL-C goal had a higher cholesterol level at diagnosis and higher prevalence of type 2 diabetes and stroke than those who achieved it. Two-thirds of CKD patients with hyperlipidemia had mixed hyperlipidemia. Despite the high frequency of statin treatment, only one-third of patients with CKD achieved the LDL-C goal. Thus, a developmental plan for the management of dyslipidemia in patients with CKD should be implemented to increase their achievement of the LDL-C goal.

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.

Lipoprotein-Cholesterol Fractions in Marginalized Roma versus Majority Population.

PubMed

Hubková, Beáta; Bódy, Gabriel; Mašlanková, Jana; Birková, Anna; Frišman, Eugen; Kraus, Vladimír; Mareková, Mária

2018-01-06

The trend of modern clinical biochemistry is to emphasize the composition and the quality of lipoproteins over their quantity. The serum lipoprotein fractions and subfractions were analyzed by the Lipoprint Lipoprotein Subfractions Testing System, the parameters of lipid profile, as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triacylglycerides (TAG) were determined by an automated selective biochemical analyzer. Our results showed a significantly lower concentration of cholesterol in the LDL fractions 1 and 2 and in the HDL fractions 8 to 10 in Roma compared to the majority population. The most significant differences between Roma and the majority population when considering body mass index (BMI), waist-to-hip ratio and the index of central obesity were in very low-density lipoproteins (VLDL), intermediate-density lipoproteins, fraction A (IDL-A) and LDL-2. The last two listed were significantly higher in the majority population. VLDL was significantly higher in overweight or obese Roma men and in Roma men with central obesity compared to men from the majority population, as well as in Roma women with normal weight and physiological waist-to-hip ratio compared to the women from majority population. Our study is among the first describing the distribution of lipoprotein subfractions in different ethnic groups.

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

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.

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.

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 ...

Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol.

PubMed

Lange, Leslie A; Hu, Youna; Zhang, He; Xue, Chenyi; Schmidt, Ellen M; Tang, Zheng-Zheng; Bizon, Chris; Lange, Ethan M; Smith, Joshua D; Turner, Emily H; Jun, Goo; Kang, Hyun Min; Peloso, Gina; Auer, Paul; Li, Kuo-Ping; Flannick, Jason; Zhang, Ji; Fuchsberger, Christian; Gaulton, Kyle; Lindgren, Cecilia; Locke, Adam; Manning, Alisa; Sim, Xueling; Rivas, Manuel A; Holmen, Oddgeir L; Gottesman, Omri; Lu, Yingchang; Ruderfer, Douglas; Stahl, Eli A; Duan, Qing; Li, Yun; Durda, Peter; Jiao, Shuo; Isaacs, Aaron; Hofman, Albert; Bis, Joshua C; Correa, Adolfo; Griswold, Michael E; Jakobsdottir, Johanna; Smith, Albert V; Schreiner, Pamela J; Feitosa, Mary F; Zhang, Qunyuan; Huffman, Jennifer E; Crosby, Jacy; Wassel, Christina L; Do, Ron; Franceschini, Nora; Martin, Lisa W; Robinson, Jennifer G; Assimes, Themistocles L; Crosslin, David R; Rosenthal, Elisabeth A; Tsai, Michael; Rieder, Mark J; Farlow, Deborah N; Folsom, Aaron R; Lumley, Thomas; Fox, Ervin R; Carlson, Christopher S; Peters, Ulrike; Jackson, Rebecca D; van Duijn, Cornelia M; Uitterlinden, André G; Levy, Daniel; Rotter, Jerome I; Taylor, Herman A; Gudnason, Vilmundur; Siscovick, David S; Fornage, Myriam; Borecki, Ingrid B; Hayward, Caroline; Rudan, Igor; Chen, Y Eugene; Bottinger, Erwin P; Loos, Ruth J F; Sætrom, Pål; Hveem, Kristian; Boehnke, Michael; Groop, Leif; McCarthy, Mark; Meitinger, Thomas; Ballantyne, Christie M; Gabriel, Stacey B; O'Donnell, Christopher J; Post, Wendy S; North, Kari E; Reiner, Alexander P; Boerwinkle, Eric; Psaty, Bruce M; Altshuler, David; Kathiresan, Sekar; Lin, Dan-Yu; Jarvik, Gail P; Cupples, L Adrienne; Kooperberg, Charles; Wilson, James G; Nickerson, Deborah A; Abecasis, Goncalo R; Rich, Stephen S; Tracy, Russell P; Willer, Cristen J

2014-02-06

Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Association of APOA5 -1131T>C polymorphism and serum lipid levels in patients with type 2 diabetes.

PubMed

Celap, Ivana; Simundic, Ana-Maria; Nikolac, Nora; Kackov, Sanja; Katalinic, Darko

2013-10-01

Significant abnormalities in lipid metabolism are frequently present in patients with type 2 diabetes mellitus (T2DM). Hypertriglyceridemia, a highly proatherogenic state, is associated with increased risk of coronary artery disease. Genetic polymorphism APOA5 -1131T>C has been recognized as a significant contributor to hypertriglyceridemia in both healthy and diabetic populations. The aim of the study was to investigate the association of APOA5 -1131T>C polymorphism with the serum levels of triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol in patients with T2DM. In total, 234 DNA samples from patients with T2DM were genotyped using the PCR-RFLP method. Serum lipid levels were measured using standard laboratory methods. Obtained APOA5 -1131T>C genotype frequencies were 89% (T/T) and 11% (T/C+C/C). There was no significant association between APOA5 -1131T>C genotypes and triglyceride levels (1.90 mM [1.32-2.74] vs. 1.78 mM [1.54-3.05] for T/T vs. T/C+C/C genotype; p=0.553), HDL cholesterol levels (1.30 mM [1.10-1.40] vs. 1.30 mM [1.05-1.40] for T/T vs. T/C+C/C; p=0.534), and LDL cholesterol levels (3.1 mM [2.3-3.8] vs. 3.0 mM [2.2-3.5] for T/T vs. T/C+C/C; p=0.313). Our results suggest that hypertriglyceridemia in patients with T2DM is not likely to be associated with the APOA5 -1131T>C polymorphism.

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

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 ...

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.

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.

Industry sponsorship bias in research findings: a network meta-analysis of LDL cholesterol reduction in randomised trials of statins

PubMed Central

Dias, Sofia; Ades, A E

2014-01-01

Objective To explore the risk of industry sponsorship bias in a systematically identified set of placebo controlled and active comparator trials of statins. Design Systematic review and network meta-analysis. Eligibility Open label and double blind randomised controlled trials comparing one statin with another at any dose or with control (placebo, diet, or usual care) for adults with, or at risk of developing, cardiovascular disease. Only trials that lasted longer than four weeks with more than 50 participants per trial arm were included. Two investigators assessed study eligibility. Data sources Bibliographic databases and reference lists of relevant articles published between 1 January 1985 and 10 March 2013. Data extraction One investigator extracted data and another confirmed accuracy. Main outcome measure Mean absolute change from baseline concentration of low density lipoprotein (LDL) cholesterol. Data synthesis Study level outcomes from randomised trials were combined using random effects network meta-analyses. Results We included 183 randomised controlled trials of statins, 103 of which were two-armed or multi-armed active comparator trials. When all of the existing randomised evidence was synthesised in network meta-analyses, there were clear differences in the LDL cholesterol lowering effects of individual statins at different doses. In general, higher doses resulted in higher reductions in baseline LDL cholesterol levels. Of a total of 146 industry sponsored trials, 64 were placebo controlled (43.8%). The corresponding number for the non-industry sponsored trials was 16 (43.2%). Of the 35 unique comparisons available in 37 non-industry sponsored trials, 31 were also available in industry sponsored trials. There were no systematic differences in magnitude between the LDL cholesterol lowering effects of individual statins observed in industry sponsored versus non-industry sponsored trials. In industry sponsored trials, the mean change from baseline LDL

Imputation of Baseline LDL Cholesterol Concentration in Patients with Familial Hypercholesterolemia on Statins or Ezetimibe.

PubMed

Ruel, Isabelle; Aljenedil, Sumayah; Sadri, Iman; de Varennes, Émilie; Hegele, Robert A; Couture, Patrick; Bergeron, Jean; Wanneh, Eric; Baass, Alexis; Dufour, Robert; Gaudet, Daniel; Brisson, Diane; Brunham, Liam R; Francis, Gordon A; Cermakova, Lubomira; Brophy, James M; Ryomoto, Arnold; Mancini, G B John; Genest, Jacques

2018-02-01

Familial hypercholesterolemia (FH) is the most frequent genetic disorder seen clinically and is characterized by increased LDL cholesterol (LDL-C) (>95th percentile), family history of increased LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) in the patient or in first-degree relatives, presence of tendinous xanthomas or premature corneal arcus, or presence of a pathogenic mutation in the LDLR , PCSK9 , or APOB genes. A diagnosis of FH has important clinical implications with respect to lifelong risk of ASCVD and requirement for intensive pharmacological therapy. The concentration of baseline LDL-C (untreated) is essential for the diagnosis of FH but is often not available because the individual is already on statin therapy. To validate a new algorithm to impute baseline LDL-C, we examined 1297 patients. The baseline LDL-C was compared with the imputed baseline obtained within 18 months of the initiation of therapy. We compared the percent reduction in LDL-C on treatment from baseline with the published percent reductions. After eliminating individuals with missing data, nonstandard doses of statins, or medications other than statins or ezetimibe, we provide data on 951 patients. The mean ± SE baseline LDL-C was 243.0 (2.2) mg/dL [6.28 (0.06) mmol/L], and the mean ± SE imputed baseline LDL-C was 244.2 (2.6) mg/dL [6.31 (0.07) mmol/L] ( P = 0.48). There was no difference in response according to the patient's sex or in percent reduction between observed and expected for individual doses or types of statin or ezetimibe. We provide a validated estimation of baseline LDL-C for patients with FH that may help clinicians in making a diagnosis. © 2017 American Association for Clinical Chemistry.

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.

Agmatine ameliorates atherosclerosis progression and endothelial dysfunction in high cholesterol-fed rabbits.

PubMed

El-Awady, Mohammed S; Suddek, Ghada M

2014-06-01

The aim of this work was to explore possible effects of agmatine, an endogenous inhibitor of inducible nitric oxide synthase (iNOS), against hypercholesterolemia-induced lipid profile changes and endothelial dysfunction. Hypercholesterolemia was induced by feeding rabbits with a high-cholesterol diet (HCD, 0.5%) for 8 weeks. Another HCD-fed group was orally administered agmatine (10 mg/kg/day) during weeks 5 through 8. Serum lipid profile, malondialdehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) were determined. Aorta was isolated to analyse vascular reactivity, atherosclerotic lesions and intima/media (I/M) ratio. HCD induced a significant increase in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). Agmatine administration significantly decreased HCD-induced elevations in serum TC and LDL-C, MDA, LDH and NO while significantly increased HDL-C levels. Additionally, agmatine significantly protected against HCD-induced attenuation of rabbit aortic endothelium-dependent relaxation to acetylcholine. HCD and agmatine did not significantly influence aortic endothelium-independent relaxation to sodium nitroprusside. Moreover, agmatine significantly reduced the elevation in aortic atherosclerotic lesion area and I/M ratio. This study is the first to reveal that agmatine has the ability to ameliorate hypercholesterolemia-induced lipemic-oxidative and endothelial function injuries possibly by its antioxidant potential and/or iNOS inhibition. © 2014 Royal Pharmaceutical Society.

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.

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...

Inclusion of Almonds in a Cholesterol-Lowering Diet Improves Plasma HDL Subspecies and Cholesterol Efflux to Serum in Normal-Weight Individuals with Elevated LDL Cholesterol.

PubMed

Berryman, Claire E; Fleming, Jennifer A; Kris-Etherton, Penny M

2017-08-01

Background : Almonds may increase circulating HDL cholesterol when substituted for a high-carbohydrate snack in an isocaloric diet, yet little is known about the effects on HDL biology and function. Objective: The objective was to determine whether incorporating 43 g almonds/d in a cholesterol-lowering diet would improve HDL subspecies and function, which were secondary study outcomes. Methods: In a randomized, 2-period, crossover, controlled-feeding study, a diet with 43 g almonds/d (percentage of total energy: 51% carbohydrate, 16% protein, and 32% total and 8% saturated fat) was compared with a similar diet with an isocaloric muffin substitution (58% carbohydrate, 15% protein, and 26% total and 8% saturated fat) in men and women with elevated LDL cholesterol. Plasma HDL subspecies and cholesterol efflux from J774 macrophages to human serum were measured at baseline and after each diet period. Diet effects were examined in all participants ( n = 48) and in normal-weight (body mass index: <25; n = 14) and overweight or obese (≥25; n = 34) participants by using linear mixed models. Results: The almond diet, compared with the control diet, increased α-1 HDL [mean ± SEM: 26.7 ± 1.5 compared with 24.3 ± 1.3 mg apolipoprotein A-I (apoA-I)/dL; P = 0.001]. In normal-weight participants, the almond diet, relative to the control diet, increased α-1 HDL (33.7 ± 3.2 compared with 28.4 ± 2.6 mg apoA-I/dL), the α-1 to pre-β-1 ratio [geometric mean (95% CI): 4.3 (3.3, 5.7) compared with 3.1 (2.4, 4.0)], and non-ATP-binding cassette transporter A1 cholesterol efflux (8.3% ± 0.4% compared with 7.8% ± 0.3%) and decreased pre-β-2 (3.8 ± 0.4 compared with 4.6 ± 0.4 mg apoA-I/dL) and α-3 (23.5 ± 0.9 compared with 26.9 ± 1.1 mg apoA-I/dL) HDL ( P < 0.05). No diet effects were observed in the overweight or obese group. Conclusions: Substituting almonds for a carbohydrate-rich snack within a lower-saturated-fat diet may be a simple strategy to maintain a favorable

Lysosomal regulation of cholesterol homeostasis in tuberous sclerosis complex is mediated via NPC1 and LDL-R.

PubMed

Filippakis, Harilaos; Alesi, Nicola; Ogorek, Barbara; Nijmeh, Julie; Khabibullin, Damir; Gutierrez, Catherine; Valvezan, Alexander J; Cunningham, James; Priolo, Carmen; Henske, Elizabeth P

2017-06-13

Tuberous sclerosis complex (TSC) is a multisystem disease associated with hyperactive mTORC1. The impact of TSC1/2 deficiency on lysosome-mediated processes is not fully understood. We report here that inhibition of lysosomal function using chloroquine (CQ) upregulates cholesterol homeostasis genes in TSC2-deficient cells. This TSC2-dependent transcriptional signature is associated with increased accumulation and intracellular levels of both total cholesterol and cholesterol esters. Unexpectedly, engaging this CQ-induced cholesterol uptake pathway together with inhibition of de novo cholesterol synthesis allows survival of TSC2-deficient, but not TSC2-expressing cells. The underlying mechanism of TSC2-deficient cell survival is dependent on exogenous cholesterol uptake via LDL-R, and endosomal trafficking mediated by Vps34. Simultaneous inhibition of lysosomal and endosomal trafficking inhibits uptake of esterified cholesterol and cell growth in TSC2-deficient, but not TSC2-expressing cells, highlighting the TSC-dependent lysosome-mediated regulation of cholesterol homeostasis and pointing toward the translational potential of these pathways for the therapy of TSC.

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

Intermittent fasting during Ramadan causes a transient increase in total, LDL, and HDL cholesterols and hs-CRP in ethnic obese adolescents.

PubMed

Radhakishun, Nalini; Blokhuis, Charlotte; van Vliet, Mariska; von Rosenstiel, Ines; Weijer, Olivier; Heymans, Martijn; Beijnen, Jos; Brandjes, Dees; Diamant, Michaela

2014-08-01

The radical change of lifestyle during Ramadan fast has shown to affect cardiometabolic risk variables in adults. In youth, however, no studies are available. We aimed to evaluate the effect of Ramadan fast on Body Mass Index (BMI) and the cardiometabolic profile of obese adolescents. A prospective cohort study was conducted. We measured weight, height, body composition, blood pressure, heart rate, glucose, insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, triglycerides, and high sensitivity C-reactive protein (hs-CRP) levels before, during the last week of and at 6 weeks after Ramadan. Twenty-five obese adolescents were included. BMI and glucose metabolism did not change after Ramadan or at 6 week after cessation of Ramadan. At the end of Ramadan, a significant decrease in body fat percentage was observed, while significant increases in heart rate, total cholesterol, LDL cholesterol, HDL cholesterol, and hs-CRP were found (all P < 0.05). Six weeks after Ramadan, all parameters returned to baseline levels. In this sample of 25 ethnic obese adolescents transient cardiometabolic changes were observed during Ramadan fasting. Since most of these changes were reversible within 6 weeks, there seems no harm or benefit for obese adolescents to participate in Ramadan.

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.

Association of cholesterol, LDL, HDL, cholesterol/ HDL and triglyceride with all-cause mortality in life insurance applicants.

PubMed

Fulks, Michael; Stout, Robert L; Dolan, Vera F

2009-01-01

Determine the relationship between various lipid tests and all-cause mortality in life insurance applicants stratified by age and sex. By use of the Social Security Death Master File, mortality was determined in 1,488,572 life insurance applicants from whom blood samples were submitted to Clinical Reference Laboratory. There were 41,020 deaths observed in this healthy adult population during a median follow-up of 12 years (range 10 to 14 years). Results were stratified by 4 age-sex subpopulations: females, ages 20 to 59 or 60+; and males, ages 20 to 59 or 60+. Those with serum albumin < 3.6 mg/dL or fructosamine > or = 2.1 mmol/L were excluded. The middle 50% of lipid values specific to each of these 4 age-sex subpopulations was used as the reference band. The mortality rates in bands representing other percentiles of lipid values were compared with the mortality rate in the reference band within each age-sex subpopulation. In contrast to some published findings from general populations, lipid test results are only moderately predictive of all-cause mortality risk in a life insurance applicant population and that risk is dependent on age and sex. At ages below 60, HDL values are associated with a "J" shaped mortality curve and at ages 60+, total cholesterol is associated with a "U" shaped curve. The total cholesterol/HDL ratio may serve as a useful single measure to predict mortality risk, but only if stratified by age and sex, and only if high HDL values at younger ages and lower total cholesterol values at ages 60+ are recognized as being associated with increased risk as well. Using LDL or non-HDL cholesterol instead of total cholesterol does not improve mortality risk discrimination; neither does using total cholesterol or triglyceride values in addition to the total cholesterol/HDL ratio. The total cholesterol/HDL ratio is the best single measure of all-cause mortality risk among the various lipid tests but is useful only if viewed on an age- and sex

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.

Effects of Chinese Dietary Pattern of Fat Content, n-6/n-3 Polyunsaturated Fatty Acid Ratio, and Cholesterol Content on Lipid Profile in Rats

PubMed Central

Zou, Xian-Guo; Huang, Yu-Hua; Xu, Tong-Cheng; Fan, Ya-Wei; Li, Jing

2018-01-01

This study aims to investigate the effect of Chinese diet pattern of fat content (30% or 36.06%), n-6/n-3 polyunsaturated fatty acid (PUFA) ratio (5 : 1 or 9 : 1), and cholesterol content (0.04 or 0.057 g/kg total diet) on lipid profile using a rat model. Results showed that rats' body weights (BWs) were controlled by the simultaneous intakes of cholesterol level of 0.04 g/kg total diet and n-6/n-3 ratio of 5 : 1. In addition, under high-fat diet, increased cholesterol feeding led to increased total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels and decreased triacylglycerols (TG) in rats' plasma. However, high density lipoprotein cholesterol (HDL-C) level and the ratios of HDL-C/LDL-C and HDL-C/TC in rats' plasma increased in response to simultaneous intakes of low n-6/n-3 ratio (5 : 1) and cholesterol (0.04 g/kg total diet) even under high-fat diet. Moreover, as the n-6/n-3 PUFA ratio in the diet decreased, the proportion of n-3 PUFAs increased in plasma, liver, and muscle and resulted in the decrease of n-6/n-3 PUFA ratio. PMID:29744358

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

Inhibition of the NLRP3 inflammasome attenuates foam cell formation of THP-1 macrophages by suppressing ox-LDL uptake and promoting cholesterol efflux.

PubMed

Chen, Liang; Yao, Qiying; Xu, Siwei; Wang, Hongyan; Qu, Peng

2018-01-01

The NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome plays an important role in the development of atherosclerosis. The activated NLRP3 inflammasome has been reported to promote macrophage foam cell formation, but not all studies have obtained the same result, and how NLRP3 inflammasome is involved in the formation of foam cells remains elusive. We used selective NLRP3 inflammasome inhibitors and NLRP3-deficient THP-1 cells to assess the effect of NLRP3 inflammasome inhibition on macrophage foam cell formation, oxidized low-density lipoprotein (ox-LDL) uptake, esterification, and cholesterol efflux, as well as the expression of associated proteins. Inhibition of the NLRP3 inflammasome attenuated foam cell formation, diminished ox-LDL uptake, and promoted cholesterol efflux from THP-1 macrophages. Moreover, it downregulated CD36, acyl coenzyme A: cholesterol acyltransferase-1 and neutral cholesterol ester hydrolase expression; upregulated ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) expression; but had no effect on the expression of scavenger receptor class A and ATP-binding cassette transporter G1. Collectively, our findings show that inhibition of the NLRP3 inflammasome decreases foam cell formation of THP-1 macrophages via suppression of ox-LDL uptake and enhancement of cholesterol efflux, which may be due to downregulation of CD36 expression and upregulation of ABCA1 and SR-BI expression, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimization of bioactive compounds in buckwheat sprouts and their effect on blood cholesterol in hamsters.

PubMed

Lin, Li-Yun; Peng, Chiung-Chi; Yang, Ya-Lu; Peng, Robert Y

2008-02-27

Nutrient levels in buckwheats that were maximized in day 8 sprouts (D8SP) included total phenolics, quercetin, and l-ascorbic acid, whereas those of oxalic, malic, tartaric, and citric acids, rutin, and gamma-aminobutyric acid (GABA) were found to reach maximum levels on day 10. Ethanolic extract of D8SP (2.5 mg/mL) revealed potent free-radical scavenging (FRS) and antioxidative (ANO) capabilities. However, its Fe2+-chelating capability was only moderate. To further study the hypolipidemic activity of D8SP, 36 Syrian hamsters were grouped into six groups and fed for 28 days, respectively, with (i) control meal, (ii) high fat plus high cholesterol meal, (iii) high fat plus high cholesterol plus 2.5% of buckwheat seeds, (iv) high fat plus high cholesterol plus 25% of buckwheat seeds, (v) high fat plus high cholesterol plus 2.5% of D8SP, and (vi) high fat plus high cholesterol plus 25% of D8SP. High seed meal prominently enhanced body weight gain, whereas high sprout meal exhibited the highest feed efficiency. Ratios of liver/body weight (L/B) were significantly lowered by all BS meals. Although low seed meal reduced serum total cholesterol (TC) levels (p<0.05), its effect was still inferior to the high seed and sprout meals (p<0.01). In contrast, serum triglyceride (TG) levels were lowered only by the high seed and sprout meals (p<0.05). Alternatively, levels of serum low-density lipoprotein cholesterol (LDL-C) were significantly suppressed by all buckwheat meals (p<0.01). Serum high-density lipoprotein cholesterol (HDL-C) levels were increased, however, insignificantly. Nutraceutically more meaningful is that both LDL-C/HDL-C and TC/HDL-C ratios were significantly lowered (p<0.01). Apparently, hepatic TC levels were significantly reduced, whereas hepatic TG levels were totally unaffected. Conclusively, sprouting triggers a variety of nutritional changes in buckwheats. Day 8 sprouts, consisting of high polyphenolic and moderate quercetin contents, are nutraceutically

Cholesterol-lowering effects and mechanisms in view of bile acid pathway of resveratrol and resveratrol-glucuronides

USDA-ARS?s Scientific Manuscript database

Resveratrol (Res) was previously reported to be capable of lowering plasma TC and LDL-C. The mechanism behind Res is not clearly understood, although it is presumed to have an effect on bile acid metabolism in the liver: a significant way in eliminating cholesterol from the body. As one of the major...

Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor-deficient mice

PubMed Central

Subramanian, Savitha; Han, Chang Yeop; Chiba, Tsuyoshi; McMillen, Timothy S.; Wang, Shari A.; Haw, Antonio; Kirk, Elizabeth A.; O’Brien, Kevin D.; Chait, Alan

2009-01-01

Objective Chronic systemic inflammation accompanies obesity and predicts development of cardiovascular disease. Dietary cholesterol has been shown to increase inflammation and atherosclerosis in LDL receptor-deficient (LDLR-/-) mice. This study was undertaken to determine whether dietary cholesterol and obesity have additive effects on inflammation and atherosclerosis. Methods and Results LDLR-/- mice were fed chow, high fat, high carbohydrate (diabetogenic) diet without (DD) or with added cholesterol (DDC) for 24 weeks. Effects on adipose tissue, inflammatory markers and atherosclerosis were studied. Despite similar weight gain between DD and DDC groups, addition of dietary cholesterol increased insulin resistance relative to DD. Adipocyte hypertrophy, macrophage accumulation and local inflammation were observed in intra-abdominal adipose tissue in DD and DDC, but were significantly higher in the DDC group. Circulating levels of the inflammatory protein serum amyloid A (SAA) were 4.4-fold higher in DD animals and 15-fold higher in DDC animals than controls, suggesting chronic systemic inflammation. Hepatic SAA mRNA levels were similarly elevated. Atherosclerosis was increased in the DD-fed animals and further increased in the DDC group. Conclusions Obesity-induced macrophage accumulation in adipose tissue is exacerbated by dietary cholesterol. These local inflammatory changes in adipose tissue are associated with insulin resistance, systemic inflammation and increased atherosclerosis in this mouse model. PMID:18239153

Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol.

PubMed

Xiao, Changting; Dash, Satya; Morgantini, Cecilia; Hegele, Robert A; Lewis, Gary F

2016-07-01

Notwithstanding the effectiveness of lowering LDL cholesterol, residual CVD risk remains in high-risk populations, including patients with diabetes, likely contributed to by non-LDL lipid abnormalities. In this Perspectives in Diabetes article, we emphasize that changing demographics and lifestyles over the past few decades have resulted in an epidemic of the "atherogenic dyslipidemia complex," the main features of which include hypertriglyceridemia, low HDL cholesterol levels, qualitative changes in LDL particles, accumulation of remnant lipoproteins, and postprandial hyperlipidemia. We briefly review the underlying pathophysiology of this form of dyslipidemia, in particular its association with insulin resistance, obesity, and type 2 diabetes, and the marked atherogenicity of this condition. We explain the failure of existing classes of therapeutic agents such as fibrates, niacin, and cholesteryl ester transfer protein inhibitors that are known to modify components of the atherogenic dyslipidemia complex. Finally, we discuss targeted repurposing of existing therapies and review promising new therapeutic strategies to modify the atherogenic dyslipidemia complex. We postulate that targeting the central abnormality of the atherogenic dyslipidemia complex, the elevation of triglyceride-rich lipoprotein particles, represents a new frontier in CVD prevention and is likely to prove the most effective strategy in correcting most aspects of the atherogenic dyslipidemia complex, thereby preventing CVD events. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

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.

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.

Visit-to-visit cholesterol variability correlates with coronary atheroma progression and clinical outcomes.

PubMed

Clark, Donald; Nicholls, Stephen J; St John, Julie; Elshazly, Mohamed B; Kapadia, Samir R; Tuzcu, E Murat; Nissen, Steven E; Puri, Rishi

2018-04-21

Utilizing serial intravascular ultrasonography (IVUS), we aimed to exam the association of intra-individual lipid variability, coronary atheroma progression, and clinical outcomes. We performed a post hoc patient-level analysis of nine clinical trials involving 4976 patients with coronary artery disease who underwent serial coronary IVUS in the setting of a range of medical therapies. We assessed the associations between progression in percent atheroma volume (ΔPAV), clinical outcomes, and visit-to-visit lipid variability including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC)/HDL-C, and apolipoprotein B (ApoB). Variability of lipid parameters was measured using intra-individual standard deviation over 3, 6, 12, 18, and 24 months. Atherogenic lipoprotein variability significantly associated with ΔPAV [odds ratio (95% confidence interval; P-value), LDL-C: 1.09 (1.02, 1.17, P = 0.01); non-HDL-C: 1.10 (1.02, 1.18, P = 0.01); TC/HDL-C: 1.14 (1.06, 1.24, P = 0.001); ApoB: 1.13 (1.03, 1.24, P = 0.01)]. Survival curves revealed significant stepwise relationships between cumulative major adverse cardiovascular events and increasing quartiles of atherogenic lipoprotein variability at 24-months follow-up (log-rank P < 0.01 for all lipoproteins except HDL-C). Stronger associations were noted between achieved lipoprotein levels and ΔPAV [LDL-C: 1.27 (1.17, 1.39; P < 0.001); non-HDL-C: 1.32 (1.21, 1.45; P < 0.001); TC/HDL-C: 1.31 (1.19, 1.45; P < 0.001); ApoB: 1.20 (1.07, 1.35; P = 0.003)]. Greater visit-to-visit variability in atherogenic lipoprotein levels significantly associates with coronary atheroma progression and clinical outcomes, although the association between achieved atherogenic lipoproteins and atheroma progression appears stronger. These data highlight the importance of achieving low and consistent atherogenic lipoprotein levels to promote

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.

ATVB Council Statement: Non-statin LDL-lowering Therapy and Cardiovascular Risk Reduction

PubMed Central

Hegele, Robert A.; Gidding, Samuel S.; Ginsberg, Henry N.; McPherson, Ruth; Raal, Frederick J.; Rader, Daniel J.; Robinson, Jennifer G.; Welty, Francine K.

2015-01-01

Pharmacologic reduction of low-density lipoprotein (LDL) cholesterol using statin drugs is foundational therapy to reduce cardiovascular disease (CVD) risk. Here we consider the place of non-statin therapies that also reduce LDL cholesterol in prevention of CVD. Among conventional non-statins, placebo-controlled randomized clinical trials showed that bile acid sequestrants, niacin and fibrates given as monotherapy each reduce CVD end points. From trials in which patients’ LDL cholesterol was already well-controlled on a statin, adding ezetimibe incrementally reduced CVD end points, while adding a fibrate or niacin showed no incremental benefit. Among emerging non-statins, monoclonal antibodies against proprotein convertase subtilisin kexin type 9 (PCSK9) added to a statin and given for up to 78 weeks showed preliminary evidence of reductions in CVD outcomes. While these promising early findings contributed to the recent approval of these agents in Europe and the US, much larger and longer duration outcomes studies are ongoing for definitive proof of CVD benefits. Other non-statin agents recently approved in the US include lomitapide and mipomersen, which both act via distinctive LDL-receptor independent mechanisms to substantially reduce LDL cholesterol in homozygous familial hypercholesterolemia. We also address some unanswered questions, including measuring alternative biochemical variables to LDL cholesterol, evidence for treating children with monitoring of subclinical atherosclerosis, and potential risks of extremely low LDL cholesterol. As evidence for benefit in CVD prevention accumulates, we anticipate that clinical practice will shift towards more assertive LDL-lowering treatment, using both statins and non-statins initiated earlier in appropriately selected patients. PMID:26376908

Cardiovascular protection of deep-seawater drinking water in high-fat/cholesterol fed hamsters.

PubMed

Hsu, Chin-Lin; Chang, Yuan-Yen; Chiu, Chih-Hsien; Yang, Kuo-Tai; Wang, Yu; Fu, Shih-Guei; Chen, Yi-Chen

2011-08-01

Cardiovascular protection of deep-seawater (DSW) drinking water was assessed using high-fat/cholesterol-fed hamsters in this study. All hamsters were fed a high-fat/cholesterol diet (12% fat/0.2% cholesterol), and drinking solutions were normal distiled water (NDW, hardness: 2.48ppm), DSW300 (hardness: 324.5ppm), DSW900 (hardness: 858.5ppm), and DSW1500 (hardness: 1569.0ppm), respectively. After a 6-week feeding period, body weight, heart rates, and blood pressures of hamsters were not influenced by DSW drinking waters. Serum total cholesterol (TC), triacylglycerol (TAG), atherogenic index, and malondialdehyde (MDA) levels were decreased (p<0.05) in the DSW-drinking-water groups, as compared to those in the NDW group. Additionally, increased (p<0.05) serum Trolox equivalent antioxidant capacity (TEAC), and faecal TC, TAG, and bile acid outputs were measured in the DSW-drinking-water groups. Hepatic low-density-lipoprotein receptor (LDL receptor) and cholesterol-7α-hydroxylase (CYP7A1) gene expressions were upregulated (p<0.05) by DSW drinking waters. These results demonstrate that DSW drinking water benefits the attenuation of high-fat/cholesterol-diet-induced cardiovascular disorders in hamsters. Copyright © 2011 Elsevier Ltd. All rights reserved.

Lipid peroxidative damage in the erythrocytes and elevation of serum LDL-cholesterol, apolipoprotein-B, ferritin and uric acid with age and in coronary heart disease patients.

PubMed

El-Gebali, H H; Tahir, S A; Haider, S S; El-Fakhri, M M

2000-02-01

To determine the normal serum levels of LDL-cholesterol, apolipoprotein-B, ferritin, uric acid, and the extent of erythrocytes lipid peroxidation in healthy control group subjects and to compare them with coronary heart disease patients. Secondly, to study the effects of age and sex on these parameters. The blood samples from 150 healthy Libyan control group subjects (110 men and 40 women) were classified into 3 groups according to their age. Group I consisted of 76 subjects with an age range from 20 to 35 years. Group II consisted of 45 subjects with an age range from 36 to 50 years. Group III consisted of 29 subjects with an age range from 51 to 74 years. The blood samples from these groups were analyzed for LDL-cholesterol, apolipoprotein-B, ferritin and uric acid levels. Lipid peroxidation was compared in the erythrocytes of 56 selected healthy control group subjects (31 men and 11 women) of the aforementioned age groups. These parameters have shown age-dependent elevation in their levels. Meanwhile, LDL-cholesterol and Apolipoprotein-B levels in female subjects were higher than those of males. However, lipid peroxidation in the erythrocytes has revealed a statistically significant increase with increasing age. The comparison between 93 selected, sex and age matched, healthy control group subjects with 87 selected coronary heart disease patients (55 men and 45 women) with an age range from 30 to 74 years (49.6+13.25) has demonstrated significantly higher concentration of LDL-cholesterol, Apolipoprotein-B, ferritin and uric acid in coronary heart disease patients than those of healthy control group subjects. Meanwhile, lipid peroxidation was also significantly enhanced in coronary heart disease patients compared with healthy control group subjects. Our study has revealed that an increase in the lipid peroxidation in erythrocytes with age and during coronary heart disease, makes red cell membranes more vulnerable to free radical damage via formation of reactive

Attainment of LDL Cholesterol Treatment Goals in Children and Adolescents With Familial Hypercholesterolemia. The SAFEHEART Follow-up Registry.

PubMed

Saltijeral, Adriana; Pérez de Isla, Leopoldo; Alonso, Rodrigo; Muñiz, Ovidio; Díaz-Díaz, José Luis; Fuentes, Francisco; Mata, Nelva; de Andrés, Raimundo; Díaz-Soto, Gonzalo; Pastor, José; Pinilla, José Miguel; Zambón, Daniel; Pinto, Xavier; Badimón, Lina; Mata, Pedro

2017-06-01

Little is known about the characteristics of persons with familial hypercholesterolemia (FH) younger than 18 years, the lipid-lowering therapy used in these patients, and the lipid goals reached in real life. Our aim was to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients younger than 18 years enrolled in a large national registry. We analyzed patients younger than 18 years enrolled in a large ongoing registry of molecularly-defined patients with FH in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was analyzed in relation to the use of lipid-lowering therapy. We enrolled 392 individuals younger than 18 years. Of these, 217 were molecularly-diagnosed FH patients and had a complete follow-up. The median follow-up time was 4.69 years (interquartile range, 2.48-6.38 years), 68.2% of FH patients were on statins, and 41.5% patients had LDL-C < 130mg/dL. Statin use was the only predictor of LDL-C goal attainment. This study shows that a high proportion of FH patients younger than 18 years have high LDL-C levels and fail to achieve recommended LDL-C targets. Statin use was the only independent predictor of LDL-C goal achievement. No safety concerns were detected during follow-up. These results indicate that many FH patients are not adequately controlled and that there is still room for treatment improvement. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

A dietary cholesterol challenge study to assess Chlorella supplementation in maintaining healthy lipid levels in adults: a double-blinded, randomized, placebo-controlled study.

PubMed

Kim, Sangmi; Kim, Joohee; Lim, Yeni; Kim, You Jin; Kim, Ji Yeon; Kwon, Oran

2016-05-13

Previous animal studies suggested that Chlorella, a unicellular green alga, has a preventive role in maintaining serum cholesterol levels against excess dietary cholesterol intake. This study aimed to conduct a pioneering investigation to clarify this issue in healthy subjects by adopting a dietary cholesterol challenge, which has not been used previously in similar studies of Chlorella in hypercholesterolemia. In this double blind, randomized, placebo-controlled study, 34 participants ingested 510 mg of dietary cholesterol from three eggs concomitantly with a usual dose of Chlorella (5 g/d) or a matched placebo for 4 weeks. The dietary cholesterol challenge induced consistently higher concentrations of serum total cholesterol (TC, P < 0.001), LDL-C (P = 0.004), and HDL-C (P = 0.010) compared with baseline values, suggesting that the challenge was reliable. Thus, we observed a preventive action of Chlorella in maintaining serum TC versus placebo levels (3.5 % versus 9.8 %, respectively; P = 0.037) and LDL-C versus placebo levels (1.7 % versus 14.3 %, respectively; P = 0.012) against excessive dietary cholesterol intake and in augmenting HDL-C versus placebo levels (8.3 % versus 3.8 %, respectively). Furthermore, serum α-carotene showed the best separation between the placebo and Chlorella groups (R(2)X and R(2)Y > 0.5; Q(2) > 0.4). The results suggest that a fully replicated dietary cholesterol challenge may be useful in assessing the effectiveness of dietary supplements in maintaining the serum lipid profiles of adults whose habitual diets are high in cholesterol. WHO International Clinical Trials Registry Platform ( KCT0000258 ).

APOC3 Loss-of-Function Mutations, Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Cardiovascular Risk: Mediation- and Meta-Analyses of 137 895 Individuals.

PubMed

Wulff, Anders B; Nordestgaard, Børge G; Tybjærg-Hansen, Anne

2018-03-01

Loss-of-function mutations in APOC3 associate with low remnant cholesterol levels and low risk of ischemic vascular disease (IVD). Because some studies show an additional association with low levels of low-density lipoprotein cholesterol (LDL-C), low LDL-C may explain the low risk of IVD in APOC3 loss-of-function heterozygotes. We tested to what extent the low risk of IVD in APOC3 loss-of-function heterozygotes is mediated by low plasma remnant cholesterol and LDL-C. In APOC3 loss-of-function heterozygotes versus noncarriers, we first determined remnant cholesterol and LDL-C levels in meta-analyses of 137 895 individuals. Second, we determined whether the association with LDL-C was masked by lipid-lowering therapy. Finally, using mediation analysis, we determined the fraction of the low risk of IVD and ischemic heart disease mediated by remnant cholesterol and LDL-C. In meta-analyses, remnant cholesterol was 43% lower (95% confidence interval, 40%-47%), and LDL-C was 4% lower (1%-6%) in loss-of-function heterozygotes (n=776) versus noncarriers. In the general population, LDL-C was 3% lower in loss-of-function heterozygotes versus noncarriers, 4% lower when correcting for lipid-lowering therapy, and 3% lower in untreated individuals ( P values, 0.06-0.008). Remnant cholesterol mediated 37% of the observed 41% lower risk of IVD and 54% of the observed 36% lower risk of ischemic heart disease; corresponding values mediated by LDL-C were 1% and 2%. The low risk of IVD observed in APOC3 loss-of-function heterozygotes is mainly mediated by the associated low remnant cholesterol and not by low LDL-C. Furthermore, the contribution of LDL-C to IVD risk was not masked by lipid-lowering therapy. This suggests APOC3 and remnant cholesterol as important new targets for reducing cardiovascular risk. © 2018 American Heart Association, Inc.

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.

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...

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.

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

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.

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 ...

Treatment patterns and low-density lipoprotein cholesterol (LDL-C) goal attainment among patients receiving high- or moderate-intensity statins.

PubMed

Fox, Kathleen M; Tai, Ming-Hui; Kostev, Karel; Hatz, Maximilian; Qian, Yi; Laufs, Ulrich

2018-05-01

European clinical guidelines recommend a low-density lipoprotein cholesterol (LDL-C) goal of < 70 mg/dL. Statin use varies and past studies suggest low rates of real-world goal attainment. This study describes LDL-C goal attainment among atherosclerotic CV disease (ASCVD) patients with various utilization patterns of moderate- or high-intensity statins in routine care. This retrospective cohort study used electronic medical records data from the QuintilesIMS® Disease Analyzer (> 2 million individuals annually) to identify ASCVD (coronary atherosclerosis, stable/unstable angina, myocardial infarction, ischemic stroke, transient ischemic attack, aneurysm, peripheral artery disease) patients on moderate-/high-intensity statin in Germany. Proportion of patients with LDL-C < 70 mg/dL was determined using the lowest LDL-C value for each patient (index) in 2012, 2013, and 2014, while on statin. Treatment patterns were assessed for patients with at least 1 year of post-index follow-up. Results were stratified by year and treatment pattern [no change, switch, dose up-/down-titration, discontinuation (≥ 90 day gap)]. In > 14,000 patients assessed in each year (mean age 71 years, 35% female, 8-12% taking high-intensity statins), approximately 80% had LDL-C ≥ 70 mg/dL. Treatment patterns were assessed for most (88-93%) patients. Approximately 79-81% of patients made no change to statin regimens, 1% switched statins, 14-16% discontinued; 1% of moderate-intensity patients up-titrated, and 3% of all patients down-titrated. LDL-C goal attainment in these treatment pattern groups was 20, 16-24, 17, 11-14, and 17-19%, respectively. Majority of ASCVD patients had LDL-C ≥ 70 mg/dL while on moderate-/high-intensity statins. Despite low LDL-C goal attainment, few patients changed their treatment regimens.

Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

PubMed

Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

2017-03-01

Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

Effect of honey on serum cholesterol and lipid values.

PubMed

Münstedt, Karsten; Hoffmann, Sven; Hauenschild, Annette; Bülte, Michael; von Georgi, Richard; Hackethal, Andreas

2009-06-01

Small studies have suggested that honey benefits patients with high cholesterol concentrations. The present study aimed to confirm this finding in a larger group of subjects. Sixty volunteers with high cholesterol, stratified according to gender and hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin) treatment (yes/no), were randomized to receive 75 g of honey solution or a honey-comparable sugar solution once daily over a period of 14 days. Baseline measurements, including body mass index (BMI) and lipid profile, were obtained, and subjects also completed dietary questionnaires and the Inventory for the Assessment of Negative Bodily Affect-Trait form (INKA-h) questionnaire. Measurements were repeated 2 weeks later. BMI and high-density lipoprotein (HDL) cholesterol values were significantly correlated (r = -0.487; P < .001) as were BMI and a lower ratio of low-density lipoprotein (LDL) cholesterol to HDL cholesterol (r = 0.420; P < .001), meaning that subjects with a high BMI had a lower HDL cholesterol value. INKA-h scores and LDL cholesterol values were also significantly correlated (r = 0.273, P = .042). Neither solution influenced significantly cholesterol or triglyceride values in the total group; in women, however, the LDL cholesterol value increased in the sugar solution subgroup but not in the women taking honey. Although ingesting honey did not reduce LDL cholesterol values in general, women may benefit from substituting honey for sugar in their diet. Reducing the BMI lowers the LDL cholesterol value, and psychological interventions also seem important and merit further investigation.

Impact of healthy lifestyle on mortality in people with normal blood pressure, LDL cholesterol, and C-reactive protein.

PubMed

King, Dana E; Mainous, Arch G; Matheson, Eric M; Everett, Charles J

2013-02-01

To investigate the impact of healthy lifestyle on cardiovascular risk and mortality in people without a history of cardiovascular disease and without elevation of lipid, blood pressure, or inflammatory markers. Cohort study. Study of a diverse sample of adults in the NHANES III follow-up Mortality Survey, to determine the benefit of adhering to healthy lifestyle habits (five or more fruits and vegetables/day, regular exercise, or being non-obese (body mass index 18.5-29.9 kg/m(2)), no current smoking, moderate alcohol consumption) in adults without common cardiovascular risk factors such as elevated cholesterol (low-density lipoprotein, LDL, cholesterol >130 mg/dl), inflammation (C-reactive protein, CRP, >3.0 mg/l, or hypertension (blood pressure >140/90 mmHg). Of 11,841 participants, 14.9% were adherent to all five healthy habits. After controlling for age, race, and gender, individuals with lower LDL cholesterol (HR 6.33, 95% CI 2.80-14.30), low CRP (HR 3.48, 95% CI 2.23-5.41), or normal blood pressure (HR 2.87, 95% CI 1.58-5.20) and 0-1 healthy habits had significantly higher all-cause (shown) and cardiovascular mortality than people adhering to all five healthy habits. People without common risk factors and lacking only 1-2 of the healthy habits remained at higher risk of all-cause mortality. People without a history of cardiovascular disease who lack common cardiovascular risk factors remain at significantly greater risk of cardiovascular and all-cause mortality if they do not adhere to a healthy lifestyle. Strategies to encourage adopting healthy lifestyles should be implemented among individuals across all risk levels.

Effect of insulin analog initiation therapy on LDL/HDL subfraction profile and HDL associated enzymes in type 2 diabetic patients.

PubMed

Aslan, Ibrahim; Kucuksayan, Ertan; Aslan, Mutay

2013-04-24

Insulin treatment can lead to good glycemic control and result in improvement of lipid parameters in type 2 diabetic patients. This study was designed to evaluate the effect of insulin analog initiation therapy on low-density lipoprotein (LDL)/ high-density lipoprotein (HDL) sub-fractions and HDL associated enzymes in type 2 diabetic patients during early phase. Twenty four type 2 diabetic patients with glycosylated hemoglobin (HbA1c) levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs (0.4 U/kg/day) plus metformin. Glycemic profiles were determined over 72 hours by continuous glucose monitoring system (CGMS) and blood samples were obtained from all patients at 24 and 72 hours. Plasma levels of cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-I) were determined by enzyme-linked immunosorbent assay (ELISA). Measurement of CETP and LCAT activity was performed via fluorometric analysis. Paraoxonase (PON1) enzyme activity was assessed from the rate of enzymatic hydrolysis of phenyl acetate to phenol formation. LDL and HDL subfraction analysis was done by continuous disc polyacrylamide gel electrophoresis. Mean blood glucose, total cholesterol (TC), triglyceride (TG) and very low-density lipoprotein cholesterol (VLDL-C) levels were significantly decreased while HDL-C levels were significantly increased after insulin treatment. Although LDL-C levels were not significantly different before and after insulin initiation therapy a significant increase in LDL-1 subgroup and a significant reduction in atherogenic LDL-3 and LDL-4 subgroups were observed. Insulin analog initiation therapy caused a significant increase in HDL-large, HDL- intermediate and a significant reduction in HDL-small subfractions

Triglyceride to high-density lipoprotein cholesterol ratio and carotid intima-medial thickness in Chinese adolescents with newly diagnosed type 2 diabetes mellitus.

PubMed

Li, Xin; Deng, You-Ping; Yang, Miao; Wu, Yu-Wen; Sun, Su-Xin; Sun, Jia-Zhong

2016-03-01

To investigate the relationship between triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and carotid intima-medial thickness (CIMT) in Chinese youth and adolescents with newly diagnosed type 2 diabetes mellitus (T2DM). Ninety-eight subjects aged 10-24 yr with newly-diagnosed T2DM had general inflammation, anthropometric, laboratory and CIMT data collected, and were divided into three groups based on TG/HDL-C tertiles. There were no significant differences in gender, age, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and carotid arterial diameter (CAD) among the groups based on TG/HDL-C tertiles. Across TG/HDL-C tertiles, there was a significant progressive increase in body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), homeostasis model assessment-estimated insulin resistance (HOMA-IR), TG, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and CIMT (all P < 0.01 or P < 0.05), while HDL-C was decreased significantly across the groups (P < 0.01). In general linear regression model, TG/HDL-C was an independent determinant of CIMT even after adjusting for BMI, SBP, DBP, TG, TC, LDL-C, HDL-C, HbA1c and HOMA-IR. TG/HDL-C ratio, the marker of small dense LDL particles, is an independent determinant of CIMT in Chinese youth and adolescents with newly diagnosed T2DM, and may be a simple and helpful tool in predicting the increased CIMT in such patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Antihypercholesterolemic effect of Bacopa monniera linn. on high cholesterol diet induced hypercholesterolemia in rats.

PubMed

Kamesh, Venkatakrishnan; Sumathi, Thangarajan

2012-12-01

To explore the effect of alcoholic extract of Bacopa monniera (AEBM) on high cholesterol diet-induced rats. The shade-dried and coarsely powdered whole plant material (Bacopa monniera) was extracted with 90% ethanol, finally filtered and dried in vacuum pump. The experimental rats were divided into 4 groups: control (group-I), Rats fed with hypercholesterolemic diet (HCD) for 45 days [4% cholesterol (w/w) and 1% cholic acid], Rats fed with HCD for 45 days+AEBM (40mg/kg, body weight/day orally) for last 30 days (group-III) and AEBM alone (group-IV). Blood and tissues (Aorta) were removed to ice cold containers for various biochemical and histological analysis. AEBM treatment significantly decreased the levels of TC, TG, PL, LDL, VLDL, atherogenic index, LDL/HDL ratio, and TC/HDL ratio but significantly increased the level of HDL when compared to HCD induced rats. Activities on liver antioxidant status (SOD, CAT, GPx, GR, GST) were significantly raised with concomitant reduction in the level of LPO were obtained in AEBM treated rats when compared to HCD rats. Treatment with AEBM significantly lowered the activity of SGOT, LDH and CPK. Histopathology of aorta of cholesterol fed rat showed intimal thickening and foam cell deposition were noted. These results suggests that AEBM extended protection against various biochemical changes and aortic pathology in hypercholesterolemic rats. Thus the plant may therefore be useful for therapeutic treatment of clinical conditions associated hypercholesterolemia. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

A low-fat spread with added plant sterols and fish omega-3 fatty acids lowers serum triglyceride and LDL-cholesterol concentrations in individuals with modest hypercholesterolaemia and hypertriglyceridaemia.

PubMed

Blom, Wendy A M; Koppenol, Wieneke P; Hiemstra, Harry; Stojakovic, Tatjana; Scharnagl, Hubert; Trautwein, Elke A

2018-05-03

The primary and secondary objectives were to investigate the triglyceride (TG) and LDL-cholesterol (LDL-C) lowering effects of a spread with added plant sterols (PS) and fish oil as compared to a placebo spread. This study had a randomized, double-blind, placebo-controlled, parallel group design with two intervention arms. Following a 2-week placebo run-in period, 260 healthy individuals with modestly elevated blood TG (≥ 1.4 mmol/L) and LDL-C (≥ 3.4 mmol/L) concentrations consumed either the placebo or intervention spread for 4 weeks. The intervention spread contained 2.0 g/day PS and 1.0 g/day eicosapentaenoic acid (EPA) + docosahexanoic acid (DHA) from fish oil. Fasting serum lipids and apolipoproteins (Apo) (exploratory) were measured at the end of the run-in and intervention phases. Four-week consumption of the intervention spread resulted in significantly lower TG (- 10.6%, 95% CI - 16.0 to - 4.9%; P < 0.001) and LDL-C concentrations (- 5.2%; 95% CI - 7.8 to - 2.4%) as compared to placebo. Total cholesterol (- 3.9%; 95% CI - 6.1 to - 1.5%), non-HDL-C (- 5.4%; 95% CI - 8.1 to - 2.7%), remnant-cholesterol (- 8.1%; 95% CI - 3.4 to - 12.5%), ApoAII (- 2.9%; 95% CI - 5.5 to - 0.2%), ApoCIII (- 7.7%; 95% CI - 12.1 to - 3.1%) and ApoB (- 3.2%; 95% CI - 5.9 to - 0.4%) concentrations were also significantly lower, as compared to placebo. No significant treatment effects were found for HDL-cholesterol, ApoAI, ApoCII, Apo E or ApoB/ApoAI. Four-week consumption of the intervention spread led to significant and clinically relevant decreases in serum TG, LDL-C and other blood lipid concentrations. The study was registered at clinicaltrials.gov (NCT 02728583).

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.

The association between achieving low-density lipoprotein cholesterol (LDL-C) goal and statin treatment in an employee population.

PubMed

Burton, Wayne N; Chen, Chin-Yu; Schultz, Alyssa B; Edington, Dee W

2010-02-01

Statin medications are recommended for patients who have not achieved low-density lipoprotein cholesterol (LDL-C) goals through lifestyle modifications. The objective of this retrospective observational study was to examine statin medication usage patterns and the relationship with LDL-C goal levels (according to Adult Treatment Panel III guidelines) among a cohort of employees of a major financial services corporation. From 1995 to 2004, a total of 1607 executives participated in a periodic health examination program. An index date was assigned for each study participant (date of their exam) and statin medication usage was determined from the pharmacy claims database for 365 days before the index date. Patients were identified as adherent to statins if the medication possession ratio was > or =80%. In all, 150 (9.3%) executives filled at least 1 statin prescription in the 365 days prior to their exam. A total of 102 statin users (68%) were adherent to statin medication. Among all executives who received statin treatment, 70% (odds ratio [OR] = 2.30, 95% confidence interval [CI] = 1.82, 2.90) achieved near-optimal (<130 mg/dL) and 30% (OR = 1.78, 95% CI = 1.15, 2.76) achieved optimal (<100 mg/dL) LDL-C goals, which is significantly higher than the rates among statin nonusers (55% and 21%). Adherent statin users were more likely to achieve recommended near-optimal LDL-C goals compared to statin nonusers (overall P = 0.002; adherent: OR = 2.75, 95% CI = 1.662, 4.550), while nonadherent statin users were more likely to achieve the optimal goal compared to statin nonusers (OR = 2.223; CI = 1.145, 4.313). Statin usage was associated with improvements in LDL-C goal attainment among executives who participated in a periodic health examination. Appropriate statin medication adherence should be encouraged in working populations in order to achieve LDL-C goals.

Levels of triglycerides, cholesterol, LDL, HDL and glucose in patients with schizophrenia, unipolar depression and bipolar disorder.

PubMed

Wysokiński, Adam; Strzelecki, Dominik; Kłoszewska, Iwona

2015-01-01

The aim of this study is to investigate differences in triglycerides (TGA), cholesterol (TC), HDL, LDL and glucose (FPG) levels in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Results for 2305 Caucasian patients were included in the study (1377 women, 59.7%; mean age 45.6). Mean TGA level was: schizophrenia: 139.9±90.6 mg/dL, unipolar depression: 125.4±70.8 mg/dL, bipolar disorder: 141.1±81.9 mg/dL, bipolar depression: 147.7±82.8 mg/dL mg/dL, bipolar mania: 120.2±76.1 mg/dL, inter-group differences were significant (p<0.001). Mean TC level was: schizophrenia: 188.5±40.4 mg/dL, unipolar depression: 198.8±50.7 mg/dL, bipolar disorder: 194.4±48.3 mg/dL, bipolar depression: 198.9±48.8 mg/dL, bipolar mania: 180.1±43.8 mg/dL, inter-group differences were significant (p<0.001). Mean HDL level was: schizophrenia: 45.3±13.9 mg/dL, unipolar depression: 48.1±14.8 mg/dL, bipolar disorder: 45.4±15.3 mg/dL, bipolar depression: 45.1±15.4 mg/dL, bipolar mania: 46.4±15.1 mg/dL, inter-group differences were significant (p<0.001). Mean LDL level was: schizophrenia: 115.4±34.7 mg/dL, unipolar depression: 125.7±44.1 mg/dL, bipolar disorder: 120.9±42.1 mg/dL, bipolar depression: 124.5±43.1 mg/dL, bipolar mania: 109.3±36.9 mg/dL, inter-group differences were significant (p<0.001). Mean FPG level was: schizophrenia: 95.9±24.9 mg/dL, unipolar depression: 94.8±22.9 mg/dL, bipolar disorder: 97.2±24.4 mg/dL, bipolar depression: 98.3±25.3 mg/dL, bipolar mania: 93.9±21.1 mg/dL, inter-group differences were not significant (p=0.08). Odds ratios for glucose and lipids abnormalities, correlations with age, sex distribution in diagnostic groups for normal ranges of glucose and lipids, differences in glucose and lipids levels between the age groups were also calculated. Our results confirm that there is a high prevalence of lipid and glucose abnormalities in patients with schizophrenia and mood disorders (both unipolar and

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.

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 ...

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.

Cholesterol and Women's Health

MedlinePlus

... having a high LDL cholesterol level lead to cardiovascular disease? • Besides abnormal cholesterol, what are other risk factors for cardiovascular disease? • What are some risk factors for cardiovascular disease ...

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.

Novel natural food colourant G8000 benefits LDL- and HDL-cholesterol in humans.

PubMed

Peres, Rogerio Correa; Gollücke, Andrea Pitelli Boiago; Soares, Clayton; Machado, Patricia; Viveiros Filho, Vitor; Rocha, Silvana; Morais, Damila Rodrigues; Bataglion, Giovana Anceski; Eberlin, Marcos Nogueira; Ribeiro, Daniel Araki

2015-01-01

The aim of this study was to investigate the phenolic composition of a natural food colourant (G8000™) as well as its effects on plasma markers after 28-day consumption by healthy individuals at a dietary dose (70 g). Parameters of total cholesterol and its fractions, triglycerides and plasma enzymes biomarkers of muscle injury were measured. Major compounds identified in G8000™ by ESI-MS showed the presence of anthocyanins, organic acids, phenolic acids as well as monosaccharides. HDL levels significantly increased from 43 ± 10.2 mg/dL to 95 ± 16.9 mg/dL. LDL levels significantly decreased from 110 ± 40.9 mg/dL to 69 ± 39 mg/dL (p < 0.001). No significant statistical differences (p > 0.05) were observed for total cholesterol, triglycerides and VLDL. After the intake, plasma enzyme CK-MB decreased from 20 ± 12.1 U/L to 10 ± 1.9 U/L while LDH levels increased from 275 ± 124.4 U/L to 317 ± 114.7 U/L (p < 0.005). No significant differences were observed for CK levels. Taken together, dietary intake of natural colourant G8000™ was able to exert beneficial effects on atherosclerosis biomarkers.

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.

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.

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.

The Expected Cardiovascular Benefit of Plasma Cholesterol Lowering with or Without LDL-C Targets in Healthy Individuals at Higher Cardiovascular Risk.

PubMed

Cesena, Fernando Henpin Yue; Laurinavicius, Antonio Gabriele; Valente, Viviane A; Conceição, Raquel D; Santos, Raul D; Bittencourt, Marcio S

2017-06-01

There is controversy whether management of blood cholesterol should be based or not on LDL-cholesterol (LDL-c) target concentrations. To compare the estimated impact of different lipid-lowering strategies, based or not on LDL-c targets, on the risk of major cardiovascular events in a population with higher cardiovascular risk. We included consecutive individuals undergoing a routine health screening in a single center who had a 10-year risk for atherosclerotic cardiovascular disease (ASCVD) ≥ 7.5% (pooled cohort equations, ACC/AHA, 2013). For each individual, we simulated two strategies based on LDL-c target (≤ 100 mg/dL [Starget-100] or ≤ 70 mg/dL [Starget-70]) and two strategies based on percent LDL-c reduction (30% [S30%] or 50% [S50%]). In 1,897 subjects (57 ± 7 years, 96% men, 10-year ASCVD risk 13.7 ± 7.1%), LDL-c would be lowered from 141 ± 33 mg/dL to 99 ± 23 mg/dL in S30%, 71 ± 16 mg/dL in S50%, 98 ± 9 mg/dL in Starget-100, and 70 ± 2 mg/dL in Starget-70. Ten-year ASCVD risk would be reduced to 8.8 ± 4.8% in S50% and 8.9 ± 5.2 in Starget-70. The number of major cardiovascular events prevented in 10 years per 1,000 individuals would be 32 in S30%, 31 in Starget-100, 49 in S50%, and 48 in Starget-70. Compared with Starget-70, S50% would prevent more events in the lower LDL-c tertile and fewer events in the higher LDL-c tertile. The more aggressive lipid-lowering approaches simulated in this study, based on LDL-c target or percent reduction, may potentially prevent approximately 50% more hard cardiovascular events in the population compared with the less intensive treatments. Baseline LDL-c determines which strategy (based or not on LDL-c target) is more appropriate at the individual level. Há controvérsias sobre se o controle do colesterol plasmático deve ou não se basear em metas de concentração de colesterol LDL (LDL-c). Comparar o impacto estimado de diferentes estratégias hipolipemiantes, baseadas ou não em metas de LDL-c, sobre o

Lipoprotein profiles and serum peroxide levels of aged women consuming palmolein or oleic acid-rich sunflower oil diets.

PubMed

Cuesta, C; Ródenas, S; Merinero, M C; Rodríguez-Gil, S; Sánchez-Muniz, F J

1998-09-01

To investigate the hypercholesterolemic effects of a dietary exchange between 16:0 and 18:1 while 18:2 was at relatively lower level (approximately 4%) in aged women with initially high total serum cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) values and with high intakes of dietary cholesterol. Subjects were assigned to two consecutive 28 d periods. In the first period all subjects followed an oleic acid-rich diet in the form of oleic acid-rich sunflower oil. This was followed by a second period rich in palmitic acid in the form of palmolein. Nutrient intakes, serum lipids, lipoproteins, antioxidant vitamins, peroxides and LDL-peroxides were measured at two dietary periods. Instituto de Nutrición y Bromatología (CSIC), Departamento de Nutrición y Bromatología I (Nutrición) and Sección Departamental de Quimica Analítica, Universidad Complutense, Madrid, Spain. The palmolein period led to an increase in TC (P < 0.001; 17.7%) and serum apolipoprotein (Apo) B levels (P < 0.001; 18.0%). LDL-C and LDL-Apo B concentrations were higher (P < 0.001, 4.33+/-0.94 mmol/L and P < 0.01, 1.08+/-0.20 g/L, respectively) following this period than following the oleic acid-rich sunflower oil diet (3.56+/-0.85 mmol/L, 0.93+/-0.16g/L, respectively). No significant differences were observed in the TC/high density lipoprotein cholesterol (TC/HDL-C) ratio between the two dietary periods. Serum and LDL-peroxides were lower (P < 0.01, 49.5%, and P < 0.001, 69.0%, respectively) after the palmolein diet than after the oleic acid-rich sunflower oil diet. The palmolein diet significantly increased TC, LDL-C, Apo B, VLDL-ApoB, LDL-ApoB in women with TC > or = 6.21 mmol/L or with TC < 6.21 mmol/L, but the increase in Apo B, LDL-C and LDL-Apo B was greater among the women with high TC. The palmolein diet increased HDL-C in women with high or with low TC but this rise was on the borderline of statistical significance (P = 0.06) only in normocholesterolemics. Serum and LDL

Continuous transport of a small fraction of plasma membrane cholesterol to endoplasmic reticulum regulates total cellular cholesterol

PubMed Central

Infante, Rodney Elwood; Radhakrishnan, Arun

2017-01-01

Cells employ regulated transport mechanisms to ensure that their plasma membranes (PMs) are optimally supplied with cholesterol derived from uptake of low-density lipoproteins (LDL) and synthesis. To date, all inhibitors of cholesterol transport block steps in lysosomes, limiting our understanding of post-lysosomal transport steps. Here, we establish the cholesterol-binding domain 4 of anthrolysin O (ALOD4) as a reversible inhibitor of cholesterol transport from PM to endoplasmic reticulum (ER). Using ALOD4, we: (1) deplete ER cholesterol without altering PM or overall cellular cholesterol levels; (2) demonstrate that LDL-derived cholesterol travels from lysosomes first to PM to meet cholesterol needs, and subsequently from PM to regulatory domains of ER to suppress activation of SREBPs, halting cholesterol uptake and synthesis; and (3) determine that continuous PM-to-ER cholesterol transport allows ER to constantly monitor PM cholesterol levels, and respond rapidly to small declines in cellular cholesterol by activating SREBPs, increasing cholesterol uptake and synthesis. DOI: http://dx.doi.org/10.7554/eLife.25466.001 PMID:28414269

Lactic-fermented egg white reduced serum cholesterol concentrations in mildly hypercholesterolemic Japanese men: a double-blind, parallel-arm design.

PubMed

Matsuoka, Ryosuke; Usuda, Mika; Masuda, Yasunobu; Kunou, Masaaki; Utsunomiya, Kazunori

2017-05-30

Lactic-fermented egg white (LE), produced by lactic acid fermentation of egg white, is an easy-to-consume form of egg white. Here we assessed the effect of daily consumption of LE for 8 weeks on serum total cholesterol (TC) levels. The study followed a double-blind, parallel-arm design and included 88 adult men with mild hypercholesterolemia (mean ± standard error) serum TC levels, 229 ± 1.6 mg/dL; range, 204-259 mg/dL). The subjects were randomly divided into three groups, which consumed LE containing 4, 6, or 8 g of protein daily for 8 weeks. Blood samples were collected before starting LE consumption (baseline) and at 4 and 8 weeks to measure serum TC and low-density lipoprotein cholesterol (LDL-C) levels. After 8 weeks of consumption, serum TC levels in the 8 g group decreased by 11.0 ± 3.7 mg/dL, a significant decrease compared to baseline (p < 0.05) and a significantly greater decrease than for the 4 g group (3.1 ± 3.4 mg/dL; p < 0.05). Serum LDL-C levels in the 8 g group decreased by 13.7 ± 3.1 mg/dL, again a significant decrease compared with baseline (p < 0.05) and a significantly greater decrease than that for the 4 g group (2.1 ± 2.9 mg/dL; p < 0.05). Consumption of LE for 8 weeks at a daily dose of 8 g of proteins reduced serum TC and LDL-C levels in men with mild hypercholesterolemia, suggesting this may be effective in helping to prevent arteriosclerotic diseases. This clinical trial was retrospectively registered with the Japan Medical Association Center for Clinical Trials, (JMA-IIA00279; registered on 13/03/2017; https://dbcentre3.jmacct.med.or.jp/JMACTR/App/JMACTRE02_04/JMACTRE02_04.aspx?kbn=3&seqno=6530 ).

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

The Success Story of LDL Cholesterol Lowering.

PubMed

Pedersen, Terje R

2016-02-19

We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence. © 2016 American Heart Association, Inc.

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 ...

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.

Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial.

PubMed

Armitage, Jane; Bowman, Louise; Wallendszus, Karl; Bulbulia, Richard; Rahimi, Kazem; Haynes, Richard; Parish, Sarah; Peto, Richard; Collins, Rory

2010-11-13

Lowering of LDL cholesterol reduces major vascular events, but whether more intensive therapy safely produces extra benefits is uncertain. We aimed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk. We undertook a double-blind randomised trial in 12,064 men and women aged 18-80 years with a history of myocardial infarction. Participants were either currently on or had clear indication for statin therapy, and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not. Randomisation to either 80 mg or 20 mg simvastatin daily was done centrally using a minimisation algorithm. Participants were assessed at 2, 4, 8, and 12 months after randomisation and then every 6 months until final follow-up. The primary endpoint was major vascular events, defined as coronary death, myocardial infarction, stroke, or arterial revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN74348595. 6031 participants were allocated 80 mg simvastatin daily, and 6033 allocated 20 mg simvastatin daily. During a mean follow-up of 6·7 (SD 1·5) years, allocation to 80 mg simvastatin produced an average 0·35 (SE 0·01) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg. Major vascular events occurred in 1477 (24·5%) participants allocated 80 mg simvastatin versus 1553 (25·7%) of those allocated 20 mg, corresponding to a 6% proportional reduction (risk ratio 0·94, 95% CI 0·88-1·01; p=0·10). There were no apparent differences in numbers of haemorrhagic strokes (24 [0·4%] vs 25 [0·4%]) or deaths attributed to vascular (565 [9·4%] vs 572 [9·5%]) or non-vascular (399 [6·6%] vs 398 [6·6%]) causes. Compared with two (0·03%) cases of myopathy in patients taking 20 mg simvastatin daily, there were 53 (0·9%) cases in the 80 mg group. The 6% (SE 3·5%) reduction in major vascular events with a further 0·35 mmol/L reduction in

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

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).

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.

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�

HEMOGLOBIN A1C, BLOOD PRESSURE, AND LDL-CHOLESTEROL CONTROL AMONG HISPANIC/LATINO ADULTS WITH DIABETES: RESULTS FROM THE HISPANIC COMMUNITY HEALTH STUDY/STUDY OF LATINOS (HCHS/SOL).

PubMed

Casagrande, Sarah Stark; Aviles-Santa, Larissa; Corsino, Leonor; Daviglus, Martha L; Gallo, Linda C; Espinoza Giacinto, Rebeca A; Llabre, Maria M; Reina, Samantha A; Savage, Peter J; Schneiderman, Neil; Talavera, Gregory A; Cowie, Catherine C

2017-10-01

To determine the prevalence of Hispanic/Latino adults with diabetes who meet target hemoglobin A1c, blood pressure (BP), and low-density-lipoprotein cholesterol (LDL-C) recommendations, and angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blocker (ARB) and statin medication use by heritage and sociodemographic and diabetes-related characteristics. Data were cross-sectional, collected between 2008 and 2011, and included adults age 18 to 74 years who reported a physician diagnosis of diabetes in the Hispanic Community Health Study/Study of Latinos (N = 2,148). Chi-square tests compared the prevalence of hemoglobin A1c, BP, and LDL-C targets and ACE/ARB and statin use across participant characteristics. Predictive margins regression was used to determine the prevalence adjusted for sociodemographic characteristics. The overall prevalence of A1c <7.0% (53 mmol/mol), BP <130/80 mm Hg, and LDL-C <100 mg/dL was 43.0, 48.7, and 36.6%, respectively, with 8.4% meeting all three targets. Younger adults aged 18 to 39 years with diabetes were less likely to have A1c <7.0% (53 mmol/mol) or LDL-C <100 mg/dL compared to those aged 65 to 74 years; younger adults were more likely to have BP <130/80 mm Hg (P<.05 for all). Individuals of Mexican heritage were significantly less likely to have A1c <7.0% (53 mmol/mol) compared to those with Cuban heritage, but they were more likely to have BP <130/80 mm Hg compared to those with Dominican, Cuban, or Puerto Rican heritage (P<.05 for all); there was no difference in LDL-C by heritage. Overall, 38.2% of adults with diabetes were taking a statin, and 50.5% were taking ACE/ARB medications. Hemoglobin A1c, BP, and LDL-C control are suboptimal among Hispanic/Latinos with diabetes living in the U.S. With 8.4% meeting all three recommendations, substantial opportunity exists to improve diabetes control in this population. A1c = hemoglobin A1c; ABC = hemoglobin A1c, blood pressure, low-density-lipoprotein cholesterol; ACE

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.

Lp-PLA2 silencing protects against ox-LDL-induced oxidative stress and cell apoptosis via Akt/mTOR signaling pathway in human THP1 macrophages.

PubMed

Zheng, HuaDong; Cui, DaJiang; Quan, XiaoJuan; Yang, WeiLin; Li, YingNa; Zhang, Lin; Liu, EnQi

2016-09-02

Atherosclerosis is a disease of the large- and medium-size arteries that is characterized by the formation of atherosclerotic plaques, in which foam cells are the characteristic pathological cells. However, the key underlying pathomechanisms are still not fully elucidated. In this study, we investigated the role of lipoprotein-associated phospholipase A2 (Lp-PLA2) in ox-LDL-induced oxidative stress and cell apoptosis, and further, elucidated the potential machanisms in human THP1 macrophages. Flow cytometry and western blot analyses showed that both cell apoptosis and Lp-PLA2 expression were dose-dependently elevated after ox-LDL treatment for 24 h and also time-dependently increased after 50 mg/L ox-LDL incubation in THP1 macrophages. In addition, Lp-PLA2 silencing decreased ox-LDL-induced Lp-PLA2 and CD36 expression in THP1 macrophages. We also found that the levels of oil red O-staining, triglyceride (TG) and total cholesterol (TC) were significantly upregulated in ox-LDL-treated THP1 cells, but inhibited by Lp-PLA2 silencing. Furthermore, ox-LDL treatment resulted in significant increases of ROS and MDA but a marked decrease of SOD, effects that were reversed by Lp-PLA2 silencing in THP1 cells. Lp-PLA2 silencing reduced ox-LDL-induced cell apoptosis and caspase-3 expression in THP1 cells. Moreover, Lp-PLA2 siRNA transfection dramatically lowered the elevated levels of p-Akt and p-mTOR proteins in ox-LDL-treated THP1 cells. Both PI3K inhibitor LY294002 and mTOR inhibitor rapamycin decreased the augmented caspase-3 expression and TC content induced by ox-LDL, respectively. Taken together, these results revealed that Lp-PLA2 silencing protected against ox-LDL-induced oxidative stress and cell apoptosis via Akt/mTOR signaling pathway in human THP1 macrophages. Copyright © 2016 Elsevier Inc. All rights reserved.

Antioxidant and anti-inflammatory effects of flavocoxid in high-cholesterol-fed rabbits.

PubMed

El-Sheakh, Ahmed R; Ghoneim, Hamdy A; Suddek, Ghada M; Ammar, El-Sayed M

2015-12-01

Flavocoxid is a mixed extract containing baicalin and catechin, and it acts as a dual balanced inhibitor of cyclooxygenase-1 (COX-1) and COX-2 peroxidase enzyme activities with a significant inhibition of 5-lipoxygenase (5-LOX) enzyme activity in vitro. Flavocoxid downregulates gene or protein expression of several inflammatory markers and exerts also strong antioxidant activity in several experimental models. Inflammation and oxidative stress contribute in the pathogenesis of atherosclerosis. In the present study, an experimental rabbit model of hypercholesterolemia was developed and the effects of flavocoxid were evaluated. Rabbits were divided into four groups-normal control, high-cholesterol-diet (HCD)-fed group, HCD plus flavocoxid (20 mg/kg/day), or HCD plus atorvastatin (10 mg/kg/day). Blood samples were collected at the end of the experiment for measuring serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD). In addition, the aorta was removed for measurement of antioxidant status, vascular reactivity, and intima/media (I/M) ratio. Elevated levels of serum TC, TGs, LDL-C, and CRP were measured in HCD group. Moreover, HCD caused a significant increase in serum and aortic MDA concomitantly with a reduction in serum and aortic GSH and SOD. Immunohistochemical staining of aortic specimens from HCD-fed rabbits revealed high expression levels of both tumor necrosis factor-alpha (TNF-α) and nuclear factor (NF)-κB. Rabbits in flavocoxid group showed significantly lower levels of serum CRP, serum, and aortic MDA and higher levels of serum HDL-C, serum, and aortic GSH and SOD compared to HCD group. HCD-induced elevations in serum TC and LDL-C did not significantly affected by flavocoxid treatment. Additionally, flavocoxid significantly enhanced rabbit aortic endothelium-dependent relaxation to acetylcholine and

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.

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.

Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction: a double-blind randomised trial

PubMed Central

Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group

2010-01-01

Summary Background Lowering of LDL cholesterol reduces major vascular events, but whether more intensive therapy safely produces extra benefits is uncertain. We aimed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk. Methods We undertook a double-blind randomised trial in 12 064 men and women aged 18–80 years with a history of myocardial infarction. Participants were either currently on or had clear indication for statin therapy, and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not. Randomisation to either 80 mg or 20 mg simvastatin daily was done centrally using a minimisation algorithm. Participants were assessed at 2, 4, 8, and 12 months after randomisation and then every 6 months until final follow-up. The primary endpoint was major vascular events, defined as coronary death, myocardial infarction, stroke, or arterial revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN74348595. Findings 6031 participants were allocated 80 mg simvastatin daily, and 6033 allocated 20 mg simvastatin daily. During a mean follow-up of 6·7 (SD 1·5) years, allocation to 80 mg simvastatin produced an average 0·35 (SE 0·01) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg. Major vascular events occurred in 1477 (24·5%) participants allocated 80 mg simvastatin versus 1553 (25·7%) of those allocated 20 mg, corresponding to a 6% proportional reduction (risk ratio 0·94, 95% CI 0·88–1·01; p=0·10). There were no apparent differences in numbers of haemorrhagic strokes (24 [0·4%] vs 25 [0·4%]) or deaths attributed to vascular (565 [9·4%] vs 572 [9·5%]) or non-vascular (399 [6·6%] vs 398 [6·6%]) causes. Compared with two (0·03%) cases of myopathy in patients taking 20 mg simvastatin daily, there were 53 (0·9%) cases in the 80 mg group. Interpretation The 6% (SE 3·5%) reduction in major

LDL-cholesterol lowering effect of a new dietary supplement: an open label, controlled, randomized, cross-over clinical trial in patients with mild-to-moderate hypercholesterolemia.

PubMed

Magno, S; Ceccarini, G; Pelosini, C; Jaccheri, R; Vitti, J; Fierabracci, P; Salvetti, G; Airoldi, G; Minale, M; Saponati, G; Santini, F

2018-05-24

Hypercholesterolemia is a major risk factor for cardiovascular disorders and requires specific intervention through an adequate lifestyle (diet and physical exercise) and, if necessary, an appropriate drug treatment. Lipid-lowering drugs, although generally efficacious, may sometimes cause adverse events. A growing attention has been devoted to the correction of dyslipidemias through the use of dietary supplements. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K, L-arginine, coenzyme Q10 and ascorbic acid, named Argicolina (A), compared to a commercially available product containing monacolin K and coenzyme Q10, Normolip 5 (N). This was a single center, controlled, randomized, open-label, cross-over clinical study enrolling 20 Caucasian outpatients aged 18-75 years with serum LDL-C between 130 and 180 mg/dL. Patients assumed two different dietary supplements (A and N) both containing monacolin K 10 mg for 8 weeks each, separated by a 4-week wash-out period. Evaluated parameters were: Total cholesterol (Tot-C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose, aspartate aminotransferase, alanine aminotransferase, creatinekinase, gamma-glutamyl-transpeptidase, brachial arterial pressure and heart rate, measured at the start and at the end of each treatment period. Safety was monitored through the study. LDL-C decreased by 23.3% during treatment with N (p < 0.0001) and by 25.6% during treatment with A (p < 0.0001); the LDL-C mean reduction was 36.4 (95% CI: 45,6-27,1) mg/dL during N treatment and 40.1 (95% CI: 49.2-30,9) mg/dL during A treatment. Tot-C decreased significantly (p < 0.0001) within each treatment period. HDL-C increase was negligible during A whereas it was significant during N. TG diminished markedly during A and not significantly during N. The difference between treatments was not

Total cholesterol and neuropsychiatric symptoms in Alzheimer's disease: the impact of total cholesterol level and gender.

PubMed

Hall, James R; Wiechmann, April R; Johnson, Leigh A; Edwards, Melissa; Barber, Robert C; Cunningham, Rebecca; Singh, Meharvan; O'Bryant, Sid E

2014-01-01

Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are a major factor in nursing home placement and a primary cause of stress for caregivers. Elevated cholesterol has been linked to psychiatric disorders and has been shown to be a risk factor for AD and to impact disease progression. The present study investigated the relationship between cholesterol and NPS in AD. Data on cholesterol and NPS from 220 individuals (144 females, 76 males) with mild-to-moderate AD from the Texas Alzheimer's Research and Care Consortium (TARCC) cohort were analyzed. The total number of NPS and symptoms of hyperactivity, psychosis, affect and apathy were evaluated. Groups based on total cholesterol (TC; ≥200 vs. <200 mg/dl) were compared with regard to NPS. The impact of gender was also assessed. Individuals with high TC had lower MMSE scores as well as significantly more NPS and more symptoms of psychosis. When stratified by gender, males with high TC had significantly more NPS than females with high TC or than males or females with low TC. The role of elevated cholesterol in the occurrence of NPS in AD appears to be gender and symptom specific. A cross-validation of these findings will have implications for possible treatment interventions, especially for males with high TC.

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

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.

FH Afrikaner-3 LDL receptor mutation results in defective LDL receptors and causes a mild form of familial hypercholesterolemia.

PubMed

Graadt van Roggen, J F; van der Westhuyzen, D R; Coetzee, G A; Marais, A D; Steyn, K; Langenhoven, E; Kotze, M J

1995-06-01

Three founder-related gene mutations (FH Afrikaner-1, -2, and -3) that affect the LDL receptor are responsible for 90% of the familial hypercholesterolemia (FH) in South African Afrikaners. Patients heterozygous for the FH Afrikaner-1 (FH1) mutation, which results in receptors having approximately 20% of normal receptor activity, have significantly lower plasma cholesterol levels and milder clinical symptoms than heterozygotes with the FH Afrikaner-2 mutation, which completely abolishes LDL receptor activity. In this study we re-created the FH3 mutation (Asp154-->Asn) in exon 4 by site-directed mutagenesis and analyzed the expression of the mutant receptors in Chinese hamster ovary cells. The mutation resulted in the formation of LDL receptors that are markedly defective in their ability to bind LDL, whereas binding of apoE-containing beta-VLDL is less affected. The mutant receptors are poorly expressed on the cell surface as a result of significant degradation of receptor precursors. The plasma cholesterol levels of 31 FH3 heterozygotes were similar to FH1 heterozygotes but significantly lower than FH2 heterozygotes. The FH1 and FH3 heterozygotes also tended to be less severely affected clinically (by coronary heart disease and xanthomata) than FH2 patients. This study demonstrates that mutational heterogeneity in the LDL receptor gene influences the phenotypic expression of heterozygous FH and that severity of expression correlates with the activity of the LDL receptor measured in vitro. The results further indicate that knowledge of the specific mutation underlying FH in heterozygotes is valuable in determining the potential risk of premature atherosclerosis and should influence the clinical management of FH patients.

Relevance of the triglyceride-to-high-density lipoprotein cholesterol ratio as an important lipid fraction in apparently healthy, young, and middle-aged Indian men

PubMed Central

Kohli, Aparna; Siddhu, Anupa; Pandey, Ravindra M.; Reddy, K. Srinath

2017-01-01

Context: Cardiovascular disease (CVD) is the largest cause of mortality in Indians. Insulin resistance and related dyslipidemia of increased triglyceride (TG), small dense low-density lipoprotein (sd-LDL) particles, and decreased high-density lipoprotein-cholesterol (HDL-C) are associated with increased risk of CVD. TG/HDL-C ratio could be a potential surrogate marker for this South Asian phenotype. Data are scarce on the relevance of TG/HDL-C ratio as a useful lipid marker among Indians. Aims: To study the prevalence of TG/HDL-C ratio among healthy, young, and middle-aged Indian men (25–44 years) and its relationship with other lipid and nonlipid factors. Subjects and Methods: In this cross-sectional analysis, fasting blood samples from 236 healthy participants recruited from an urban community setting were tested for TG/HDL-C ratio, HDL-C, TG, total cholesterol (TC), non-HDL-C, TC/HDL-C, high-sensitivity C-reactive protein, body mass index (BMI), and body fat. Results: Mean (standard deviation) age of participants was 34.7 (7.7) years; median (interquartile range) TG/HDL-C ratio was 4 (2.85-5.2). More than half (51.3%) the participants (n = 121) recorded abnormal TG/HDL-C ratio (≥4.0). Across tertiles of TG/HDL-C ratio, there was a significant trend of higher conventional lipid parameters such as non-HDL-C*, TC/HDL-C ratio*, TG*, HDL-C*, TC**; and non-lipid parameters body-fat* and BMI*** (*P < 0.001, **P = 0.015, ***P = 0.002). LDL-C showed moderate and nonsignificant (P = 0.646) increase across tertiles. Conclusion: In a sample of apparently healthy, young, and middle-aged Indian men abnormal TG/HDL-C ratio levels were observed among more than half the participants. The TG/HDL-C ratio was closely associated with other lipid parameters and measures of adiposity, such as BMI and body fat, apart from its previously documented unique association with sd-LDL particles. TG/HDL-C ratio should be evaluated in future for risk prediction of incident CVD among Indians

Relevance of the triglyceride-to-high-density lipoprotein cholesterol ratio as an important lipid fraction in apparently healthy, young, and middle-aged Indian men.

PubMed

Kohli, Aparna; Siddhu, Anupa; Pandey, Ravindra M; Reddy, K Srinath

2017-01-01

Cardiovascular disease (CVD) is the largest cause of mortality in Indians. Insulin resistance and related dyslipidemia of increased triglyceride (TG), small dense low-density lipoprotein (sd-LDL) particles, and decreased high-density lipoprotein-cholesterol (HDL-C) are associated with increased risk of CVD. TG/HDL-C ratio could be a potential surrogate marker for this South Asian phenotype. Data are scarce on the relevance of TG/HDL-C ratio as a useful lipid marker among Indians. To study the prevalence of TG/HDL-C ratio among healthy, young, and middle-aged Indian men (25-44 years) and its relationship with other lipid and nonlipid factors. In this cross-sectional analysis, fasting blood samples from 236 healthy participants recruited from an urban community setting were tested for TG/HDL-C ratio, HDL-C, TG, total cholesterol (TC), non-HDL-C, TC/HDL-C, high-sensitivity C-reactive protein, body mass index (BMI), and body fat. Mean (standard deviation) age of participants was 34.7 (7.7) years; median (interquartile range) TG/HDL-C ratio was 4 (2.85-5.2). More than half (51.3%) the participants ( n = 121) recorded abnormal TG/HDL-C ratio (≥4.0). Across tertiles of TG/HDL-C ratio, there was a significant trend of higher conventional lipid parameters such as non-HDL-C*, TC/HDL-C ratio*, TG*, HDL-C*, TC**; and non-lipid parameters body-fat* and BMI*** (* P < 0.001, ** P = 0.015, *** P = 0.002). LDL-C showed moderate and nonsignificant ( P = 0.646) increase across tertiles. In a sample of apparently healthy, young, and middle-aged Indian men abnormal TG/HDL-C ratio levels were observed among more than half the participants. The TG/HDL-C ratio was closely associated with other lipid parameters and measures of adiposity, such as BMI and body fat, apart from its previously documented unique association with sd-LDL particles. TG/HDL-C ratio should be evaluated in future for risk prediction of incident CVD among Indians.

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.

Effect of LDL cholesterol, statins and presence of mutations on the prevalence of type 2 diabetes in heterozygous familial hypercholesterolemia.

PubMed

Climent, Elisenda; Pérez-Calahorra, Sofía; Marco-Benedí, Victoria; Plana, Nuria; Sánchez, Rosa; Ros, Emilio; Ascaso, Juan F; Puzo, Jose; Almagro, Fátima; Lahoz, Carlos; Civeira, Fernando; Pedro-Botet, Juan

2017-07-17

Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vulnerable to type 2 diabetes mellitus (T2DM), although the mechanism is unknown. The aims of the present study were to assess the effects of low density lipoprotein (LDL) cholesterol concentration and the presence of FH-causing mutations on T2DM prevalence in HeFH. Data were collected from the Dyslipidemia Registry of the Spanish Arteriosclerosis Society. Inclusion criteria were definite or probable HeFH in patients aged ≥18 years. T2DM prevalence in HeFH patients was compared with data of the general population. 1732 patients were included. The prevalence of T2DM was lower in patients with HeFH compared with the general population (5.94% vs 9.44%; OR: 0.606, 95% CI 0.486-0.755, p < 0.001). Risk factors for developing T2DM were male sex, age, body mass index, hypertension, baseline triglyceride levels and years on statin therapy. The prevalence of T2DM in HeFH patients was 40% lower than that observed in the general population. Gene mutations and LDL cholesterol concentrations were not risk factors associated with the prevalence of T2DM in patients with HeFH. The prevalence of T2DM in patients with HeFH was 40% lower than in the general population matched for age and sex.

Impact of interferon-free antivirus therapy on lipid profiles in patients with chronic hepatitis C genotype 1b

PubMed Central

Endo, Daisuke; Satoh, Kenichi; Shimada, Noritomo; Hokari, Atsushi; Aizawa, Yoshio

2017-01-01

AIM To investigate the influence of interferon-free antivirus therapy on lipid profiles in chronic hepatitis C virus genotype 1b (HCV1b) infection. METHODS Interferon-free antiviral agents were used to treat 276 patients with chronic HCV1b infection, and changes in serum lipids of those who achieved sustained virologic response (SVR) were examined. The treatment regimen included 24 wk of daclatasvir plus asunaprevir (DCV + ASV) or 12 wk of sofosbuvir plus ledipasvir (SOF + LDV). SVR was achieved in 121 (85.8%) of 141 patients treated with DCV + ASV and 132 (97.8%) of 135 patients treated with SOF + LDV. In the two patient groups (DCV + ASV-SVR and SOF + LDV-SVR), serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides were measured at baseline during treatment and at 4 and 12 wk after treatment. Then, longitudinal changes in lipid profiles were analyzed. RESULTS Serum levels of TC, LDL-C, and HDL-C were significantly increased throughout the observation period in both the DCV + ASV-SVR and SOF + LDV-SVR groups. During antivirus treatment, the increases in TC and LDL-C were significantly greater in the SOF + LDV-SVR group than in the DCV + ASV-SVR group (P < 0.001). At 4 and 12 wk after the therapy, serum levels of TC and LDL-C were similar between the two groups and were significantly greater than those at baseline. Approximately 75%-80% of the increase in TC was derived from an increased LDL-C. In multiple regression analysis, the difference in therapy protocol (DCA + ASV or SOF + LDV) was an independent predictor that was significantly associated with the increase in TC and LDL-C at 4 wk of therapy. CONCLUSION Serum cholesterol significantly increased during SOF + LDV treatment. After treatment, HCV elimination was associated with a similar increase in cholesterol regardless of the therapy protocol. PMID:28428715

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.

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

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

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.

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

Total red meat intake of ≥0.5 servings/d does not negatively influence cardiovascular disease risk factors: a systemically searched meta-analysis of randomized controlled trials12

PubMed Central

O’Connor, Lauren E; Kim, Jung Eun; Campbell, Wayne W

2017-01-01

Background: Observational associations between red meat intake and cardiovascular disease (CVD) are inconsistent. There are limited comprehensive analyses of randomized controlled trials (RCTs) that investigate the effects of red meat consumption on CVD risk factors. Objective: The purpose of this systematically searched meta-analysis was to assess the effects of consuming ≥0.5 or <0.5 servings of total red meat/d on CVD risk factors [blood total cholesterol (TC), LDL cholesterol, HDL cholesterol, triglycerides, ratio of TC to HDL cholesterol (TC:HDL), and systolic and diastolic blood pressures (SBP and DBP, respectively)]. We hypothesized that the consumption of ≥0.5 servings of total red meat/d would have a negative effect on these CVD risk factors. Design: Two researchers independently screened 945 studies from PubMed, Cochrane Library, and Scopus databases and extracted data from 24 qualified RCTs. Inclusion criteria were 1) RCT, 2) subjects aged ≥19 y, 3) consumption of ≥0.5 or <0.5 total red meat servings/d [35 g (1.25 ounces)], and 4) reporting ≥1 CVD risk factor. We performed an adjusted 2-factor nested ANOVA mixed-effects model procedure on the postintervention values of TC, LDL cholesterol, HDL cholesterol, TC:HDL cholesterol, triglycerides, SBP, and DBP; calculated overall effect sizes of change values; and used a repeated-measures ANOVA to assess pre- to postintervention changes. Results: Red meat intake did not affect lipid-lipoprotein profiles or blood pressure values postintervention (P > 0.05) or changes over time [weighted mean difference (95% CI): −0.01 mmol/L (−0.08, 0.06 mmol/L), 0.02 mmol/L (−0.05, 0.08 mmol/L), 0.03 mmol/L (−0.01, 0.07 mmol/L), and 0.04 mmol/L (−0.02, 0.10 mmol/L); −0.08 mm Hg (−0.26, 0.11 mm Hg); and −1.0 mm Hg (−2.4, 0.78 mm Hg) and 0.1 mm Hg (−1.2, 1.5 mm Hg) for TC, LDL cholesterol, HDL cholesterol, triglycerides, TC:HDL cholesterol, SBP, and DBP, respectively]. Among all subjects, TC, LDL

Nordic Walking Training Causes a Decrease in Blood Cholesterol in Elderly Women Supplemented with Vitamin D.

PubMed

Prusik, Krzysztof; Kortas, Jakub; Prusik, Katarzyna; Mieszkowski, Jan; Jaworska, Joanna; Skrobot, Wojciech; Lipinski, Marcin; Ziemann, Ewa; Antosiewicz, Jedrzej

2018-01-01

Different studies have demonstrated that regular exercise can induce changes in the lipid profile, but results remain inconclusive. Available data suggest that correction of vitamin D deficiency can improve the lipid profile. In this study, we have hypothesized that Nordic Walking training will improve lipid profile in elderly women supplemented with vitamin D. A total of 109 elderly women (68 ± 5.12 years old) took part in the study. First group [experimental group (EG): 35 women] underwent 12 weeks of Nordic Walking (NW) training combined with vitamin D supplementation (4,000 IU/day), second group [supplementation group (SG): 48 women] was only supplemented with vitamin D (4,000 IU/day), and third group [control group (CG): 31 women] was not subject to any interventions. Blood analysis of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and 25-OH-D 3 was performed at baseline and after the 12 weeks of NW training. Additionally, a battery of field tests specifically developed for older adults was used to assess the components of functional fitness. The same blood analysis was repeated for the EG 6 months after the main experiment. After 12 weeks of NW training and vitamin D supplementation, in the EG a decrease in TC, LDL-C, and TG was observed. In the SG, no changes in the lipid profile were observed, whereas in the CG an increase in the HDL-C level was noticed. Positive physical fitness changes were only observed in the EG. Our obtained data confirmed baseline assumption that regular exercise induces positive alternations in lipid profile in elderly women supported by supplementation of vitamin D.

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

The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of insulin resistance but not of β cell function in a Chinese population with different glucose tolerance status.

PubMed

Zhou, Meicen; Zhu, Lixin; Cui, Xiangli; Feng, Linbo; Zhao, Xuefeng; He, Shuli; Ping, Fan; Li, Wei; Li, Yuxiu

2016-06-07

Triglyceride/high-density lipoprotein-cholesterol (TG/HDL-C) ratio was a surrogate marker of IR; however, the relationship of TG/HDL-C with IR might vary by ethnicity. This study aims to investigate whether lipid ratios-TG/HDL-C, cholesterol/high-density lipoprotein-cholesterol (TC/HDL-C) ratio, low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol (LDL-C/HDL-C)) could be potential clinical markers of insulin resistance (IR) and β cell function and further to explore the optimal cut-offs in a Chinese population with different levels of glucose tolerance. Four hundred seventy-nine subjects without a history of diabetes underwent a 75 g 2 h Oral Glucose Tolerance Test (OGTT). New-onset diabetes (n = 101), pre-diabetes (n = 186), and normal glucose tolerance (n = 192) were screened. IR was defined by HOMA-IR > 2.69. Based on indices (HOMA-β, early-phase disposition index [DI30], (ΔIns30/ΔGlu30)/HOMA-IR and total-phase index [DI120]) that indicated different phases of insulin secretion, the subjects were divided into two groups, and the lower group was defined as having inadequate β cell compensation. Logistic regression models and accurate estimates of the areas under receiver operating characteristic curves (AUROC) were obtained. In all of the subjects, TG/HDL, TC/HDL-C, LDL-C/HDL-C, and TG were significantly associated with IR. The AUROCs of TG/HDL-C and TG were 0.71 (95 % CI: 0.66-0.75) and 0.71 (95 % CI: 0.65-0.75), respectively. The optimal cut-offs of TG/HDL-C and TG for IR diagnosis were 1.11 and 1.33 mmol/L, respectively. The AUROCs of TC/HDL-C and LDL-C/HDL-C were 0.66 and 0.65, respectively, but they were not acceptable for IR diagnosis. TG/HDL-C,LDL-C/HDL-C and TG were significantly associated with HOMA-β, but AUROCs were less than 0.50; therefore, the lipid ratios could not be predictors of basal β cell dysfunction. None of the lipid ratios was associated with early-phase insulin secretion. Only TG/HDL-C and

Human LDL Structural Diversity Studied by IR Spectroscopy

PubMed Central

Fernández-Higuero, José A.; Salvador, Ana M.; Martín, Cesar; Milicua, José Carlos G.; Arrondo, José L. R.

2014-01-01

Lipoproteins are responsible for cholesterol traffic in humans. Low density lipoprotein (LDL) delivers cholesterol from liver to peripheral tissues. A misleading delivery can lead to the formation of atherosclerotic plaques. LDL has a single protein, apoB-100, that binds to a specific receptor. It is known that the failure associated with a deficient protein-receptor binding leads to plaque formation. ApoB-100 is a large single lipid-associated polypeptide difficulting the study of its structure. IR spectroscopy is a technique suitable to follow the different conformational changes produced in apoB-100 because it is not affected by the size of the protein or the turbidity of the sample. We have analyzed LDL spectra of different individuals and shown that, even if there are not big structural changes, a different pattern in the intensity of the band located around 1617 cm−1 related with strands embedded in the lipid monolayer, can be associated with a different conformational rearrangement that could affect to a protein interacting region with the receptor. PMID:24642788

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

Effects of metformin on metabolite profiles and LDL cholesterol in patients with type 2 diabetes.

PubMed

Xu, Tao; Brandmaier, Stefan; Messias, Ana C; Herder, Christian; Draisma, Harmen H M; Demirkan, Ayse; Yu, Zhonghao; Ried, Janina S; Haller, Toomas; Heier, Margit; Campillos, Monica; Fobo, Gisela; Stark, Renee; Holzapfel, Christina; Adam, Jonathan; Chi, Shen; Rotter, Markus; Panni, Tommaso; Quante, Anne S; He, Ying; Prehn, Cornelia; Roemisch-Margl, Werner; Kastenmüller, Gabi; Willemsen, Gonneke; Pool, René; Kasa, Katarina; van Dijk, Ko Willems; Hankemeier, Thomas; Meisinger, Christa; Thorand, Barbara; Ruepp, Andreas; Hrabé de Angelis, Martin; Li, Yixue; Wichmann, H-Erich; Stratmann, Bernd; Strauch, Konstantin; Metspalu, Andres; Gieger, Christian; Suhre, Karsten; Adamski, Jerzy; Illig, Thomas; Rathmann, Wolfgang; Roden, Michael; Peters, Annette; van Duijn, Cornelia M; Boomsma, Dorret I; Meitinger, Thomas; Wang-Sattler, Rui

2015-10-01

Metformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin. We analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on metabolite concentrations, we quantified 131 metabolites in fasting serum samples and used multivariable linear regression models in three independent cross-sectional studies (n = 151 patients with T2D treated with metformin [mt-T2D]). Additionally, we used linear mixed-effect models to study the longitudinal KORA samples (n = 912) and performed mediation analyses to investigate the effects of metformin intake on blood lipid profiles. We combined genotyping data with the identified metformin-associated metabolites in KORA individuals (n = 1,809) and explored the underlying pathways. We found significantly lower (P < 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. These findings were controlled for conventional risk factors of T2D and replicated in two independent studies. Furthermore, we observed that the levels of these metabolites decreased significantly in patients after they started metformin treatment during 7 years' follow-up. The reduction of these metabolites was also associated with a lowered blood level of LDL cholesterol (LDL-C). Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target. Our results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C. Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease. © 2015 by the American

LDL electronegativity index: a potential novel index for predicting cardiovascular disease.

PubMed

Ivanova, Ekaterina A; Bobryshev, Yuri V; Orekhov, Alexander N

2015-01-01

High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL) and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(-)] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(-), methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk.

LDL electronegativity index: a potential novel index for predicting cardiovascular disease

PubMed Central

Ivanova, Ekaterina A; Bobryshev, Yuri V; Orekhov, Alexander N

2015-01-01

High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL) and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(–)] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(–), methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk. PMID:26357481

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.

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

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.

Sex, Prescribing Practices and Guideline Recommended, Blood Pressure, and LDL Cholesterol Targets at Baseline in the BARI 2D Trial

PubMed Central

Magee, Michelle F.; Tamis-Holland, Jacqueline E.; Lu, Jiang; Bittner, Vera A.; Brooks, Maria Mori; Lopes, Neuza; Jacobs, Alice K.; Study Group, BARI 2D

2015-01-01

Background. Research has shown less aggressive treatment and poorer control of cardiovascular disease (CVD) risk factors in women than men. Methods. We analyzed sex differences in pharmacotherapy strategies and attainment of goals for hemoglobin A1c (HbA1c), blood pressure (BP), and low density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and established coronary artery disease enrolled into the BARI 2D trial. Results. Similar numbers of drugs were prescribed in both women and men. Women were less frequent on metformin or sulfonylurea and more likely to take insulin and to be on higher doses of hydroxymethylglutaryl-CoA reductase inhibitors (statins) than men. After adjusting for baseline differences and treatment prescribed, women were less likely to achieve goals for HbA1c (OR = 0.71, 95% CI 0.57, 0.88) and LDL-C (OR = 0.64, 95% CI 0.53, 0.78). More antihypertensives were prescribed to women, and yet BP ≤ 130/80 mmHg did not differ by sex. Conclusions. Women entering the BARI 2D trial were as aggressively treated with drugs as men. Despite equivalent treatment, women less frequently met targets for HbA1c and LDL-C. Our findings suggest that there may be sex differences in response to drug therapies used to treat diabetes, hypertension, and hyperlipidemia. PMID:25873955

Long Noncoding RNA HOXC-AS1 Suppresses Ox-LDL-Induced Cholesterol Accumulation Through Promoting HOXC6 Expression in THP-1 Macrophages.

PubMed

Huang, Chuan; Hu, Yan-Wei; Zhao, Jing-Jing; Ma, Xin; Zhang, Yuan; Guo, Feng-Xia; Kang, Chun-Min; Lu, Jing-Bo; Xiu, Jian-Cheng; Sha, Yan-Hua; Gao, Ji-Juan; Wang, Yan-Chao; Li, Pan; Xu, Bang-Ming; Zheng, Lei; Wang, Qian

2016-11-01

Atherosclerosis is a common pathological basis of cardiovascular disease, which remains the leading cause of mortality. Long noncoding RNAs (lncRNAs) are newly studied non-protein-coding RNAs involved in gene regulation, but how lncRNAs exert regulatory effect on atherosclerosis remains unclear. In this study, we found that lncRNA HOXC cluster antisense RNA 1 (HOXC-AS1) and homeobox C6 (HOXC6) were downregulated in carotid atherosclerosis by performing microarray analysis. The results were verified in atherosclerotic plaques and normal arterial intima tissues by quantitative reverse transcription PCR and western blot analysis. Lentivirus-mediated overexpression of HOXC-AS1 induced HOXC6 expression at mRNA and protein levels in THP-1 macrophages. Besides, oxidized low-density lipoprotein (Ox-LDL) decreased expression of HOXC-AS1 and HOXC6 in a time-dependent manner. Induction of cholesterol accumulation by Ox-LDL could be partly suppressed by overexpression of HOXC-AS1.

Myeloperoxidase-generated reactive nitrogen species convert LDL into an atherogenic form in vitro

PubMed Central

Podrez, Eugene A.; Schmitt, David; Hoff, Henry F.; Hazen, Stanley L.

1999-01-01

Oxidized LDL is implicated in atherosclerosis; however, the pathways that convert LDL into an atherogenic form in vivo are not established. Production of reactive nitrogen species may be one important pathway, since LDL recovered from human atherosclerotic aorta is enriched in nitrotyrosine. We now report that reactive nitrogen species generated by the MPO-H2O2-NO2– system of monocytes convert LDL into a form (NO2-LDL) that is avidly taken up and degraded by macrophages, leading to massive cholesterol deposition and foam cell formation, essential steps in lesion development. Incubation of LDL with isolated MPO, an H2O2-generating system, and nitrite (NO2–)— a major end-product of NO metabolism—resulted in nitration of apolipoprotein B 100 tyrosyl residues and initiation of LDL lipid peroxidation. The time course of LDL protein nitration and lipid peroxidation paralleled the acquisition of high-affinity, concentration-dependent, and saturable binding of NO2-LDL to human monocyte–derived macrophages and mouse peritoneal macrophages. LDL modification and conversion into a high-uptake form occurred in the absence of free metal ions, required NO2–, occurred at physiological levels of Cl–, and was inhibited by heme poisons, catalase, and BHT. Macrophage binding of NO2-LDL was specific and mediated by neither the LDL receptor nor the scavenger receptor class A type I. Exposure of macrophages to NO2-LDL promoted cholesteryl ester synthesis, intracellular cholesterol and cholesteryl ester accumulation, and foam cell formation. Collectively, these results identify MPO-generated reactive nitrogen species as a physiologically plausible pathway for converting LDL into an atherogenic form. PMID:10359564

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.

All about Cholesterol

MedlinePlus

... more information. J If you smoke or use e-cigarettes, quit. J Lose weight if needed. Eating healthy, ... lower LDL cholesterol. They also help lower your risk for a heart attack or stroke. Adults with ...

An in vivo assessment of the cholesterol-lowering efficacy of Lactobacillus plantarum ECGC 13110402 in normal to mildly hypercholesterolaemic adults

PubMed Central

Buttarazzi, Ivan; Kolida, Sofia; Quercia, Sara; Baldini, Jessica; Swann, Jonathan R.; Brigidi, Patrizia; Gibson, Glenn R.

2017-01-01

Coronary heart disease (CHD) is one of the major causes of death and disability in industrialised countries, with elevated blood cholesterol an established risk factor. Total plasma cholesterol reduction in populations suffering from primary hypercholesterolemia may lower CHD incidence. This study investigated the cholesterol reducing capacity of Lactobacillus plantarum ECGC 13110402, a strain selected for its high bile salt hydrolase activity, in 49 normal to mildly hypercholesterolaemic adults. Primary efficacy outcomes included effect on blood lipids (total cholesterol (TC), low density lipoproteins (LDL-C), high density lipoproteins (HDL-C) and triacylgycerides (TAG), inflammatory biomarkers and occurrence/severity of gastrointestinal side effects to establish safety and tolerance of the intervention. Secondary outcomes included blood pressure, immune biomarkers, gut microbiota characterisation and metabonome changes. The study was run in a parallel, double blind, placebo controlled, randomised design in which the active group ingested 2x109 CFU encapsulated Lactobacillus plantarum ECGC 13110402 twice daily. Daily ingestion of the active treatment resulted in a statistically significant reduction in LDL-C in volunteers with baseline TC<5mM during the 0–12 week period (13.9%, P = 0.030), a significant reduction in TC in volunteers with baseline TC≥6mM in the 0–6 week period (37.6%, P = 0.045), a significant decrease in TAG (53.9% P = 0.030) and an increase in HDL-C (14.7%, P = 0.007) in the over 60 years population in the 6–12 week period. A statistically significant reduction in systolic blood pressure was also observed across the active study group in the 6-12-week period (6.6%, P = 0.003). No impact on gastrointestinal function and side effects was observed during the study. Similar to blood and urine metabonomic analyses, faecal metagenomics did not reveal significant changes upon active or placebo intake. The results of this study suggest that

Bakery products enriched with phytosterol esters, alpha-tocopherol and beta-carotene decrease plasma LDL-cholesterol and maintain plasma beta-carotene concentrations in normocholesterolemic men and women.

PubMed

Quílez, Joan; Rafecas, Magda; Brufau, Gemma; García-Lorda, Pilar; Megías, Isabel; Bulló, Mònica; Ruiz, Joan A; Salas-Salvadó, Jordi

2003-10-01

The hypocholesterolemic effects of phytosterols have not been evaluated in bakery products, and the addition of liposoluble antioxidants to the carrier has never been tested. We investigated the effects of consuming croissants and magdalenas (Spanish muffins) enriched with sterol esters, alpha-tocopherol and beta-carotene on plasma lipid and fat-soluble antioxidant concentrations in normocholesterolemic, habitual consumers of bakery products following their usual diet and lifestyle. Using a randomized, double-blind, placebo-controlled design, the control (C) group (n = 29) received two pieces daily (standard croissant and muffin) and the sterol ester (SE) group (n = 28), the same products with sterol esters added (3.2 g/d) for 8 wk. Total and LDL cholesterol (LDL-C) decreased in the SE group by 0.24 mmol/L (P < 0.01) and 0.26 mmol/L (P < 0.005), respectively, whereas these variables did not change in the control group. The total difference in total and LDL-C changes between groups was 0.38 mmol/L (8.9%) and 0.36 mmol/L (14.7%), respectively (P < 0.001). Within-group changes in HDL cholesterol, triacylglycerol or lipoprotein(a) concentrations did not differ. Similarly, within-group changes over time in plasma tocopherol and carotenoid concentrations did not differ between groups. Our findings suggest that bakery products are excellent carriers for phytosterols, and their consumption is associated with a decrease in total and LDL-C concentrations, with no changes in alpha-tocopherol and beta-carotene. The ability of bakery products to include sufficient quantities of beta-carotene to compensate for a potential deficiency, and the fact that their efficacy was not associated with the time of day at which they were consumed, are interesting findings.

Cholesterol and Statins

MedlinePlus

... es th se en d In the intestines, fat, carbohydrates and proteins are broken down. These nutrients are ... as the primary treatment. Eating a low-saturated-fat, low-cholesterol diet should help lower your LDL (bad ...

Cholesterol, APOE genotype, and Alzheimer disease

PubMed Central

Hall, K.; Murrell, J.; Ogunniyi, A.; Deeg, M.; Baiyewu, O.; Gao, S.; Gureje, O.; Dickens, J.; Evans, R.; Smith-Gamble, V.; Unverzagt, F.W.; Shen, J.; Hendrie, H.

2010-01-01

Objective To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria. Methods Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's Disease and Related Disorders Association criteria. Results Logistic regression models showed interaction after adjusting for age and gender between APOE-ε4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p = 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-ε4 allele, but not in those with APOE-ε4. There was no significant association between levels of triglycerides and AD risk in those without APOE-ε4. Conclusions There was a significant interaction between cholesterol, APOE-ε4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies. PMID:16434658

Low IDL-B and high LDL-1 subfraction levels in serum of ALS patients.

PubMed

Delaye, J B; Patin, F; Piver, E; Bruno, C; Vasse, M; Vourc'h, P; Andres, C R; Corcia, P; Blasco, H

2017-09-15

Converging evidence highlights that lipid metabolism plays a key role in ALS pathophysiology. Dyslipidemia has been described in ALS patients and may be protective but peripheral lipoprotein subclasses have never been studied. We collected sera from 30 ALS patients and 30 gender and age-matched controls. We analyzed 11 distinct lipoprotein subclasses by linear polyacrylamide gel electrophoresis (Lipoprint, Quantimetrix Corporation, USA). We also measured lipoprotein (a), apolipoprotein B, and apolipoprotein E levels. ALS patients had significant higher total cholesterol, HDL-cholesterol, and LDL-cholesterol levels than controls (p<0.0001, p=0.0007, and p=0.0065, respectively). The LDL-1 subfraction concentration was higher (1.03±0.41 vs. 0.71±0.28mmol/L; p=0.0006) and the IDL-B subfraction lower (6.5±2% vs. 8.0±2%; p=0.001) in ALS patients than controls. Our preliminary work confirmed the association between ALS and dyslipidemia. The low IDL-B levels may explain the hepatic steatosis frequently reported in ALS. The high levels of the cholesterol-rich LDL-1 subfraction is consistent with previously reported hypercholesterolemia. This study describes, for the first time, the distribution of serum lipoproteins in ALS patients, with low IDL-B and high LDL-1 subfraction level. Copyright © 2017 Elsevier B.V. All rights reserved.

Lipid profiles in the untreated patients with Hashimoto thyroiditis and the effects of thyroxine treatment on subclinical hypothyroidism with Hashimoto thyroiditis.

PubMed

Tagami, Tetsuya; Tamanaha, Tamiko; Shimazu, Satoko; Honda, Kyoko; Nanba, Kazutaka; Nomura, Hidenari; Yoriko, Sakane Ueda; Usui, Takeshi; Shimatsu, Akira; Naruse, Mitsuhide

2010-01-01

To evaluate the prevalence of dyslipidemia in the population of Hashimoto thyroiditis, we reviewed medical records on the consecutive 1181 cases with adult Hashimoto thyroiditis and 830 cases were adopted for the study. First, the serum TSH level increased and serum free T4 level decreased, slightly but significantly, with increasing age. There were significant positive correlations between serum TSH levels and lipid parameters such as total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), non-HDL-C and LDL-C/HDL-C ratio (L/H). In contrast, there were significant negative correlations between serum free T4 levels and all of these lipid parameters. According to the thyroid function, the cases were classified into 4 groups such as thyrotoxicosis (TT), euthyroidism (EU), subclinical hypothyroidism (SH) and overt hypothyroidism (OH). TC, HDL-C, non-HDL-C and LDL-C of TT were significantly lower than those in EU. In contrast, TC, TG, non-HDL-C, LDL-C, L/H and age of OH were significantly higher than those in EU. Interestingly, LDL-C and L/H of SH were significantly higher compared with EU. Thirty-two of SH patients were treated with small doses of levothyroxine and the effects on the lipid profile were examined. The TC, non-HDL-C, LDL-C and L/H were significantly decreased after treatment. In conclusion, the prevalence of dyslipidemia increases along with hypofunction of the thyroid and T4 replacement therapy may improve lipid profile in the cases of SH with Hashimoto thyroiditis.

Self-reported adherence by MARS-CZ reflects LDL cholesterol goal achievement among statin users: validation study in the Czech Republic.

PubMed

Ladova, Katerina; Matoulkova, Petra; Zadak, Zdenek; Macek, Karel; Vyroubal, Pavel; Vlcek, Jiri; Morisky, Donald E

2014-10-01

Measuring self-reported adherence may contribute to minimizing the risk of therapy failure. Hence, the main aim of the study was to assess the psychometric properties of the Czech version of Medication Adherence Report Scale (MARS-CZ) and its appropriateness for use in long-term statin therapy where goal levels of low-density lipoprotein cholesterol (LDL-c) should be achieved. Anonymous structured interview was performed to determine self-reported adherence by MARS-CZ in outpatients chronically treated with statins. At the same time, medication records were reviewed for inclusion of patients into groups of those who achieved and do not achieved LDL-c goal according to cardiovascular risk level. Reliability and validity of MARS-CZ were tested as well as the relationship between adherence and LDL-c goal achievement was examined. A total of 136 (86.6%) patients completed the interview; mean age was 66.1 years; 49.3% were male. The mean score of MARS-CZ was 24.4 and showed positive skewing. Satisfactory internal consistency (Cronbach's α=0.54), strong test-retest reliability (r=0.83, P<0.001; intra-class correlation=0.63, 95% confidence interval: 0.35-0.81) and positive correlation with eight-item Morisky Medication Adherence Scale (r=0.62, P<0.001) were indicated. Low validity values were found between MARS-CZ and 12-item Short Form Health Survey mental and physical subscales. MARS-CZ score significantly correlated with LDL-c goal achievement (P<0.05) when all patients who achieved LDL-c goal (35%) reported high adherence to statin. MARS-CZ score also correlated with cardiovascular risk level and doctor's judgments on adjusting treatment targets for each patient. This study proved MARS-CZ as an acceptable self-reported adherence measure. In routine clinical practice, MARS-CZ could be helpful to reveal medication non-adherence before the alteration of drug regimen and thereby contributing to enhancement of statin therapy management. © 2014 John Wiley & Sons, Ltd.

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.

The Mediterranean Diet decreases LDL atherogenicity in high cardiovascular risk individuals: a randomized controlled trial.

PubMed

Hernáez, Álvaro; Castañer, Olga; Goday, Alberto; Ros, Emilio; Pintó, Xavier; Estruch, Ramón; Salas-Salvadó, Jordi; Corella, Dolores; Arós, Fernando; Serra-Majem, Lluis; Martínez-González, Miguel Ángel; Fiol, Miquel; Lapetra, José; de la Torre, Rafael; López-Sabater, M Carmen; Fitó, Montserrat

2017-09-01

Traditional Mediterranean diet (TMD) protects against cardiovascular disease through several mechanisms such as decreasing LDL cholesterol levels. However, evidence regarding TMD effects on LDL atherogenic traits (resistance against oxidation, size, composition, cytotoxicity) is scarce. We assessed the effects of a 1-year intervention with a TMD on LDL atherogenic traits in a random sub-sample of individuals from the PREDIMED study (N = 210). We compared two TMDs: one enriched with virgin olive oil (TMD-VOO, N = 71) and another with nuts (TMD-Nuts, N = 68), versus a low-fat control diet (N = 71). After the TMD-VOO intervention, LDL resistance against oxidation increased (+6.46%, p = 0.007), the degree of LDL oxidative modifications decreased (-36.3%, p<0.05), estimated LDL particle size augmented (+3.06%, p = 0.021), and LDL particles became cholesterol-rich (+2.41% p = 0.013) relative to the low-fat control diet. LDL lipoproteins became less cytotoxic for macrophages only relative to baseline (-13.4%, p = 0.019). No significant effects of the TMD-Nuts intervention on LDL traits were observed versus the control diet. Adherence to a TMD, particularly when enriched with virgin olive oil, decreased LDL atherogenicity in high cardiovascular risk individuals. The development of less atherogenic LDLs could contribute to explaining some of the cardioprotective benefits of this dietary pattern. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ocimum basilicum ethanolic extract decreases cholesterol synthesis and lipid accumulation in human macrophages.

PubMed

Bravo, Elena; Amrani, Souliman; Aziz, Mohammed; Harnafi, Hicham; Napolitano, Mariarosaria

2008-12-01

Macrophage lipid accumulation induced by low density lipoproteins (LDL) plays a pivotal role in atherosclerotic plaque development. Previous work showed that Ocimum basilicum extract, used as hypocholesterolemic agent by traditional medicine in Morocco, has hypolipidemic activity in rat acute hyperlipimidemia. This study investigated the effects of ethanolic extract of O. basilicum on lipid accumulation in human macrophages. As modification of LDL increase atherogenicity of the particles we evaluated the effects of the extract on LDL oxidation. The extract caused a dose-related increase of LDL-resistance to Cu(2+)-induced oxidation. Furthermore, at the dose of 60 microg/ml, significantly decreases the accumulation of macrophage lipid droplets induced by modified LDL evaluated as by red-oil staining. Cholesterol esterification and triacylglycerol synthesis in the cells were not affected. Macrophage treatment with 60 microg/ml, but not 20 microg/ml, of the extract reduced newly synthesized unesterified cholesterol by about 60% and decreased scavenger receptors activity by about 20-30%, evaluated by the internalization of cholesterol carried by [(3)H]CE-aggregated-LDL. The results suggest that O. basilicum ethanolic extract has the capability to reduce foam cell formation through the reduction of cholesterol synthesis and the modulation of the activity of surface scavenger receptors.

Diet × genotype interactions in hepatic cholesterol and lipoprotein metabolism in Atlantic salmon (Salmo salar) in response to replacement of dietary fish oil with vegetable oil.

PubMed

Morais, Sofia; Pratoomyot, Jarunan; Torstensen, Bente E; Taggart, John B; Guy, Derrick R; Bell, J Gordon; Tocher, Douglas R

2011-11-01

The present study investigates the effects of genotype on responses to alternative feeds in Atlantic salmon. Microarray analysis of the liver transcriptome of two family groups, lean or fat, fed a diet containing either a fish oil (FO) or a vegetable oil (VO) blend indicated that pathways of cholesterol and lipoprotein metabolism might be differentially affected by the diet depending on the genetic background of the fish, and this was further investigated by real-time quantitative PCR, plasma and lipoprotein biochemical analysis. Results indicate a reduction in VLDL and LDL levels, with no changes in HDL, when FO is replaced by VO in the lean family group, whereas in fat fish fed FO, levels of apoB-containing lipoproteins were low and comparable with those fed VO in both family groups. Significantly lower levels of plasma TAG and LDL-TAG were measured in the fat group that was independent of diet, whereas plasma cholesterol was significantly higher in fish fed the FO diet in both groups. Hepatic expression of genes involved in cholesterol homeostasis, β-oxidation and lipoprotein metabolism showed relatively subtle changes. A significantly lower expression of genes considered anti-atherogenic in mammals (ATP-binding cassette transporter A1, apoAI, scavenger receptor class B type 1, lipoprotein lipase (LPL)b (TC67836) and LPLc (TC84899)) was found in lean fish, compared with fat fish, when fed VO. Furthermore, the lean family group appeared to show a greater response to diet composition in the cholesterol biosynthesis pathway, mediated by sterol-responsive element-binding protein 2. Finally, the presence of three different transcripts for LPL, with differential patterns of nutritional regulation, was demonstrated.

New therapeutic principles in dyslipidaemia: focus on LDL and Lp(a) lowering drugs

PubMed Central

Norata, Giuseppe Danilo; Ballantyne, Christie M.; Catapano, Alberico Luigi

2013-01-01

Dyslipidaemias play a key role in determining cardiovascular risk; the discovery of statins has contributed a very effective approach. However, many patients do not achieve, at the maximal tolerated dose, the recommended goals for low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol, and apolipoprotein B (apoB). Available agents combined with statins can provide additional LDL-C reduction, and agents in development will increase therapeutic options impacting also other atherogenic lipoprotein classes. In fact, genetic insights into mechanisms underlying regulation of LDL-C levels has expanded potential targets of drug therapy and led to the development of novel agents. Among them are modulators of apoB containing lipoproteins production and proprotein convertase subtilisin/kexin type-9 inhibitors. Alternative targets such as lipoprotein(a) also require attention; however, until we have a better understanding of these issues, further LDL-C lowering in high and very high-risk patients will represent the most sound clinical approach. PMID:23509227

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.

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.

Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice

PubMed Central

Merkel, Martin; Velez-Carrasco, Wanda; Hudgins, Lisa C.; Breslow, Jan L.

2001-01-01

Heart-healthy dietary recommendations include decreasing the intake of saturated fatty acids (SFA). However, the relative benefit of replacing SFA with monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), or carbohydrates (CARB) is still being debated. We have used two mouse models of atherosclerosis, low density lipoprotein receptor-deficient (LDLRKO) and apolipoprotein E-deficient (apoEKO) mice to measure the effects of four isocaloric diets enriched with either SFA, MUFA, PUFA, or CARB on atherosclerotic lesion area and lipoprotein levels. In LDLRKO mice, compared with the SFA diet, the MUFA and CARB diets significantly increased atherosclerosis in both sexes, but the PUFA diet had no effect. The MUFA and CARB diets also increased very low density lipoprotein-cholesterol (VLDL-C) and LDL-cholesterol (LDL-C) in males and VLDL-C levels in females. Analysis of data from LDLRKO mice on all diets showed that atherosclerotic lesion area correlated positively with VLDL-C levels (males: r = 0.47, P < 0.005; females: r = 0.52, P < 0.001). In contrast, in apoEKO mice there were no significant dietary effects on atherosclerosis in either sex. Compared with the SFA diet, the CARB diet significantly decreased VLDL-C in males and the MUFA, PUFA, and CARB diets decreased VLDL-C and the CARB diet decreased LDL-C in females. In summary, in LDLRKO mice the replacement of dietary SFA by either MUFA or CARB causes a proportionate increase in both atherosclerotic lesion area and VLDL-C. There were no significant dietary effects on atherosclerotic lesion area in apoEKO mice. These results are surprising and suggest that, depending on the underlying genotype, dietary MUFA and CARB can actually increase atherosclerosis susceptibility, probably by raising VLDL-C levels through a non-LDL receptor, apoE-dependent pathway. PMID:11606787

Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice.

PubMed

Merkel, M; Velez-Carrasco, W; Hudgins, L C; Breslow, J L

2001-11-06

Heart-healthy dietary recommendations include decreasing the intake of saturated fatty acids (SFA). However, the relative benefit of replacing SFA with monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), or carbohydrates (CARB) is still being debated. We have used two mouse models of atherosclerosis, low density lipoprotein receptor-deficient (LDLRKO) and apolipoprotein E-deficient (apoEKO) mice to measure the effects of four isocaloric diets enriched with either SFA, MUFA, PUFA, or CARB on atherosclerotic lesion area and lipoprotein levels. In LDLRKO mice, compared with the SFA diet, the MUFA and CARB diets significantly increased atherosclerosis in both sexes, but the PUFA diet had no effect. The MUFA and CARB diets also increased very low density lipoprotein-cholesterol (VLDL-C) and LDL-cholesterol (LDL-C) in males and VLDL-C levels in females. Analysis of data from LDLRKO mice on all diets showed that atherosclerotic lesion area correlated positively with VLDL-C levels (males: r = 0.47, P < 0.005; females: r = 0.52, P < 0.001). In contrast, in apoEKO mice there were no significant dietary effects on atherosclerosis in either sex. Compared with the SFA diet, the CARB diet significantly decreased VLDL-C in males and the MUFA, PUFA, and CARB diets decreased VLDL-C and the CARB diet decreased LDL-C in females. In summary, in LDLRKO mice the replacement of dietary SFA by either MUFA or CARB causes a proportionate increase in both atherosclerotic lesion area and VLDL-C. There were no significant dietary effects on atherosclerotic lesion area in apoEKO mice. These results are surprising and suggest that, depending on the underlying genotype, dietary MUFA and CARB can actually increase atherosclerosis susceptibility, probably by raising VLDL-C levels through a non-LDL receptor, apoE-dependent pathway.

Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity.

PubMed

Ma, Xingzhe; Bi, Enguang; Huang, Chunjian; Lu, Yong; Xue, Gang; Guo, Xing; Wang, Aibo; Yang, Maojie; Qian, Jianfei; Dong, Chen; Yi, Qing

2018-05-09

CD8 + T cells can be polarized into IL-9-secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8 + or CD4 + T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo. Mechanistic studies showed that IL-9 was indispensable for Tc9 cell persistence and antitumor effects, and cholesterol or its derivatives inhibited IL-9 expression by activating liver X receptors (LXRs), leading to LXR Sumoylation and reduced p65 binding to Il9 promoter. Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function. © 2018 Ma et al.

Long-term consumption of a raw food diet is associated with favorable serum LDL cholesterol and triglycerides but also with elevated plasma homocysteine and low serum HDL cholesterol in humans.

PubMed

Koebnick, Corinna; Garcia, Ada L; Dagnelie, Pieter C; Strassner, Carola; Lindemans, Jan; Katz, Norbert; Leitzmann, Claus; Hoffmann, Ingrid

2005-10-01

High consumption of vegetables and fruits is associated with reduced risk for cardiovascular disease. However, little information is available about diets based predominantly on consumption of fruits and their health consequences. We investigated the effects of an extremely high dietary intake of raw vegetables and fruits (70-100% raw food) on serum lipids and plasma vitamin B-12, folate, and total homocysteine (tHcy). In a cross-sectional study, the lipid, folate, vitamin B-12, and tHcy status of 201 adherents to a raw food diet (94 men and 107 women) were examined. The participants consumed approximately 1500-1800 g raw food of plant origin/d mainly as vegetables or fruits. Of the participants, 14% had high serum LDL cholesterol concentrations, 46% had low serum HDL cholesterol, and none had high triglycerides. Of raw food consumers, 38% were vitamin B-12 deficient, whereas 12% had an increased mean corpuscular volume (MCV). Plasma tHcy concentrations were correlated with plasma vitamin B-12 concentrations (r = -0.450, P < 0.001), but not with plasma folate. Plasma tHcy and MCV concentrations were higher in those in the lowest quintile of consumption of food of animal origin (P(trend) < 0.001). This study indicates that consumption of a strict raw food diet lowers plasma total cholesterol and triglyceride concentrations, but also lowers serum HDL cholesterol and increases tHcy concentrations due to vitamin B-12 deficiency.

FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver.

PubMed

Papazyan, Romeo; Liu, Xueqing; Liu, Jingwen; Dong, Bin; Plummer, Emily M; Lewis, Ronald D; Roth, Jonathan D; Young, Mark A

2018-06-01

Obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist that regulates bile acid and lipid metabolism. FXR activation induces distinct changes in circulating cholesterol among animal models and humans. The mechanistic basis of these effects has been elusive because of difficulties in studying lipoprotein homeostasis in mice, which predominantly package circulating cholesterol in HDLs. Here, we tested the effects of OCA in chimeric mice whose livers are mostly composed (≥80%) of human hepatocytes. Chimeric mice exhibited a human-like ratio of serum LDL cholesterol (LDL-C) to HDL cholesterol (HDL-C) at baseline. OCA treatment in chimeric mice increased circulating LDL-C and decreased circulating HDL-C levels, demonstrating that these mice closely model the cholesterol effects of FXR activation in humans. Mechanistically, OCA treatment increased hepatic cholesterol in chimeric mice but not in control mice. This increase correlated with decreased SREBP-2 activity and target gene expression, including a significant reduction in LDL receptor protein. Cotreatment with atorvastatin reduced total cholesterol, rescued LDL receptor protein levels, and normalized serum LDL-C. Treatment with two clinically relevant nonsteroidal FXR agonists elicited similar lipoprotein and hepatic changes in chimeric mice, suggesting that the increase in circulating LDL-C is a class effect of FXR activation.

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.

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.

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

Assessment of the relationship between lipid parameters and obesity indices in non-diabetic obese patients: a preliminary report.

PubMed

Stępień, Anna; Stępień, Mariusz; Wlazeł, Rafał N; Paradowski, Marek; Banach, Maciej; Rysz, Jacek

2014-12-16

The aim of this cross-sectional study was to examine the relationship between obesity and lipid markers. We divided 66 non-diabetic adult obese patients (mean age: 55.8±11.6 years) into 3 groups according to body mass index (BMI). All patients were measured for waist circumference (WC), hip circumference (HC), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body adiposity index (BAI), and visceral adiposity index (VAI). Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were determined, and lipid indices TC/HDL, LDL/HDL, and TG/HDL were also estimated. TC and LDL-C in Group III were lower than in Group I (5.0±1.0 vs. 6.0±1.0 mmol/L, and 2.9±0.9 vs. 3.8±1.2 mmol/L; p<0.05 for both). Negative correlations were found between: BMI and TC, LDL, and HDL (r=-0.291; r=-0.310, r=-0.240, respectively); and WC, WHR, VAI, and HDL (r=-0.371, r=-0.296, r=-0.376, respectively). Positive correlations were found between WC, WHR, and TG/HDL (r=0.279, r=0.244, respectively) and between VAI and: TC (r=0.327), TG (r=0.885), TC/HDL (r=0.618), LDL/HDL (r=0.480), and TG/HDL (r=0.927). Obesity is associated with lipid disturbances, especially with HDL-C reduction, in obese non-diabetic patients. VAI is strongly related to lipid profile and thus may be the most valuable obesity index in obese patients with dyslipidemias.

[Correlation of retinol binding protein 4 with 
metabolic indexes of glucose and 
lipid, bile cholesterol saturation index].

PubMed

Wang, Wen; Li, Nianfeng

2015-06-01

To measure retinol binding protein 4 (RBP4) levels in serum and bile and to analyze their relationship with insulin resistance, dyslipidemia or cholesterol saturation index (CSI).
 A total of 60 patients with gallstone were divided into a diabetes group (n=30) and a control group (n=30). The concentrations of RBP4 in serum and bile were detected by enzyme-linked immunosorbent assay (ELISA). Enzyme colorimetric method was used to measure the concentration of biliary cholesterol, bile acid and phospholipid. Biliary CSI was calculated by Carey table. Partial correlation and multiple linear regression analysis were used to evaluate the correlation between the RBP4 levels in serum or bile and the above indexes.
 The RBP4 concentrations in serum and bile in the diabetes group were significantly elevated compared with those in the control group (both P<0.01). There was no significant difference in the serum total bile acid (TBA), serum triglyceride (TG), serum high-density lipoprotein (HDL), bile TBA, bile total cholesterol (TC) , bile phospholipids and bile CSI between the 2 groups (all P>0.05); but the serum TC, low density lipoprotein (LDL), fasting blood glucose (FBG), fasting insulin (FINS), and homeostasis model assessment for insulin resistance (HOMA-IR) in the diabetes group were significantly increased compared to those in the control group (all P<0.05). The partial correlation analysis, which was adjusted by age, showed that the bile RBP4 was positively correlated with body mass index (BMI), waist circumference (WC), FINS, FBG, TC, LDL and HOMA-IR (r=0.283, 0.405, 0.685, 0.667, 0.553, 0.424 and 0.735, respectively), and the serum RBP4 was also positively correlated with the WC, FINS, FBG, TC, LDL and HOMA-IR (r=0.317, 0.734, 0.609, 0.528, 0.386 and 0.751, respectively). Stepwise multivariate linear regression analysis suggested that the HOMA-IR, BMI and WC were independently correlated with the level of bile RBP4 (multiple regression equation: Ybile RBP4

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.

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.

Correlation analysis between the LDL-C in serum and the onset of transient ischemic attack caused by CSVD.

PubMed

Chen, Yaqi; Hu, Mei; Gong, Hongying

2017-08-01

The aim of this study was to investigate the correlation between the low-density lipoprotein cholesterol (LDL-C) in serum and the onset of transient ischemic attack caused by cerebral small vascular disease (CSVD). Between September 2012 and September 2015, 249 patients who were diagnosed as CSVD were randomly enrolled in this study. According to MRI results, patients were divided into the patient and control groups. In the patient group, the patients were further subdivided into the white matter lesion (WML) group (n=86) and lacunar infarction (LI) group (n=53). Head MRI and/or CT were conducted on all the patients. This included T1 and T2 phases, diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR). Additionally, mini-mental status examination (MMSE) test and Montreal cognitive assessment (MoCA) test were carried out on all the patients. As a result, the age, total cholesterol (TC) level and low-density lipoprotein (LDL) levels in the patient group were higher than those in the control group (p<0.05). The MMSE and MoCA scores in the patient group were significantly lower than those in the control group (p<0.05). With all the risk factors being set as independent variables and small vessel disease (SVD) as the dependent variable, we performed the logistic regression analysis and correlation analysis for paired data, and found that the increase in LDL was correlated to the onset of SVD, OR=1,321. After adjustment of other risk factors, we enrolled the level of triglyceride (TG) into the multivariable analysis and obtained a statistically significant difference (p<0.05). In conclusion, LDL is a major risk factor affecting the onset of transient ischemic attack (TIA) induced by CSVD. Patients with hyperlipidemia should receive head MRI or CT examination to eliminate the probability of the existence of CSVD. To reduce the occurrence of adverse events in clinical practice, we can perform early intervention in SVD by decreasing the level of

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.

A systematic review of high-oleic vegetable oil substitutions for other fats and oils on cardiovascular disease risk factors: implications for novel high-oleic soybean oils.

PubMed

Huth, Peter J; Fulgoni, Victor L; Larson, Brian T

2015-11-01

High-oleic acid soybean oil (H-OSBO) is a trait-enhanced vegetable oil containing >70% oleic acid. Developed as an alternative for trans-FA (TFA)-containing vegetable oils, H-OSBO is predicted to replace large amounts of soybean oil in the US diet. However, there is little evidence concerning the effects of H-OSBO on coronary heart disease (CHD)(6) risk factors and CHD risk. We examined and quantified the effects of substituting high-oleic acid (HO) oils for fats and oils rich in saturated FAs (SFAs), TFAs, or n-6 (ω-6) polyunsaturated FAs (PUFAs) on blood lipids in controlled clinical trials. Searches of online databases through June 2014 were used to select studies that defined subject characteristics; described control and intervention diets; substituted HO oils compositionally similar to H-OSBO (i.e., ≥70% oleic acid) for equivalent amounts of oils high in SFAs, TFAs, or n-6 PUFAs for ≥3 wk; and reported changes in blood lipids. Studies that replaced saturated fats or oils with HO oils showed significant reductions in total cholesterol (TC), LDL cholesterol, and apolipoprotein B (apoB) (P < 0.05; mean percentage of change: -8.0%, -10.9%, -7.9%, respectively), whereas most showed no changes in HDL cholesterol, triglycerides (TGs), the ratio of TC to HDL cholesterol (TC:HDL cholesterol), and apolipoprotein A-1 (apoA-1). Replacing TFA-containing oil sources with HO oils showed significant reductions in TC, LDL cholesterol, apoB, TGs, TC:HDL cholesterol and increased HDL cholesterol and apoA-1 (mean percentage of change: -5.7%, -9.2%, -7.3%, -11.7%, -12.1%, 5.6%, 3.7%, respectively; P < 0.05). In most studies that replaced oils high in n-6 PUFAs with equivalent amounts of HO oils, TC, LDL cholesterol, TGs, HDL cholesterol, apoA-1, and TC:HDL cholesterol did not change. These findings suggest that replacing fats and oils high in SFAs or TFAs with either H-OSBO or oils high in n-6 PUFAs would have favorable and comparable effects on plasma lipid risk factors and

A Systematic Review of High-Oleic Vegetable Oil Substitutions for Other Fats and Oils on Cardiovascular Disease Risk Factors: Implications for Novel High-Oleic Soybean Oils12

PubMed Central

Huth, Peter J; Fulgoni, Victor L; Larson, Brian T

2015-01-01

High–oleic acid soybean oil (H-OSBO) is a trait-enhanced vegetable oil containing >70% oleic acid. Developed as an alternative for trans-FA (TFA)-containing vegetable oils, H-OSBO is predicted to replace large amounts of soybean oil in the US diet. However, there is little evidence concerning the effects of H-OSBO on coronary heart disease (CHD)6 risk factors and CHD risk. We examined and quantified the effects of substituting high-oleic acid (HO) oils for fats and oils rich in saturated FAs (SFAs), TFAs, or n–6 (ω-6) polyunsaturated FAs (PUFAs) on blood lipids in controlled clinical trials. Searches of online databases through June 2014 were used to select studies that defined subject characteristics; described control and intervention diets; substituted HO oils compositionally similar to H-OSBO (i.e., ≥70% oleic acid) for equivalent amounts of oils high in SFAs, TFAs, or n–6 PUFAs for ≥3 wk; and reported changes in blood lipids. Studies that replaced saturated fats or oils with HO oils showed significant reductions in total cholesterol (TC), LDL cholesterol, and apolipoprotein B (apoB) (P < 0.05; mean percentage of change: −8.0%, −10.9%, −7.9%, respectively), whereas most showed no changes in HDL cholesterol, triglycerides (TGs), the ratio of TC to HDL cholesterol (TC:HDL cholesterol), and apolipoprotein A-1 (apoA-1). Replacing TFA-containing oil sources with HO oils showed significant reductions in TC, LDL cholesterol, apoB, TGs, TC:HDL cholesterol and increased HDL cholesterol and apoA-1 (mean percentage of change: −5.7%, −9.2%, −7.3%, −11.7%, −12.1%, 5.6%, 3.7%, respectively; P < 0.05). In most studies that replaced oils high in n–6 PUFAs with equivalent amounts of HO oils, TC, LDL cholesterol, TGs, HDL cholesterol, apoA-1, and TC:HDL cholesterol did not change. These findings suggest that replacing fats and oils high in SFAs or TFAs with either H-OSBO or oils high in n–6 PUFAs would have favorable and comparable effects on

Outdoor temperature is associated with serum HDL and LDL.

PubMed

Halonen, Jaana I; Zanobetti, Antonella; Sparrow, David; Vokonas, Pantel S; Schwartz, Joel

2011-02-01

While exposures to high and low air temperatures are associated with cardiovascular mortality, the underlying mechanisms are poorly understood. The risk factors for cardiovascular disease include high levels of total cholesterol and low-density lipoprotein (LDL), and low levels of high-density lipoprotein (HDL). We investigated whether temperature was associated with changes in circulating lipid levels, and whether this might explain part of the association with increased cardiovascular events. The study cohort consisted of 478 men in the greater Boston area with a mean age of 74.2 years. They visited the clinic every 3-5 years between 1995 and 2008 for physical examination and to complete questionnaires. We excluded from analyses all men taking statin medication and all days with missing data, resulting in a total of 862 visits. Associations between three temperature variables (ambient, apparent, and dew point temperature) and serum lipid levels (total cholesterol, HDL, LDL, and triglycerides) were studied with linear mixed models that included possible confounders such as air pollution and a random intercept for each subject. We found that HDL decreased -1.76% (95% CI: from -3.17 to -0.32, lag 2 days), and -5.58% (95% CI: from -8.87 to -2.16, moving average of 4 weeks) for each 5°C increase in mean ambient temperature. For the same increase in mean ambient temperature, LDL increased by 1.74% (95% CI: 0.07-3.44, lag 1 day) and 1.87% (95% CI: 0.14-3.63, lag 2 days). These results were also similar for apparent and dew point temperatures. No changes were found in total cholesterol or triglycerides in relation to temperature increase. Changes in HDL and LDL levels associated with an increase in ambient temperature may be among the underlying mechanisms of temperature-related cardiovascular mortality. Copyright © 2010 Elsevier Inc. All rights reserved.

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

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.

Clinical usefulness of metabolic risk factors to identify young asymptomatic women adults with subclinical atherosclerosis: A cross-sectional study.

PubMed

Qin, Guangming; Chen, Zhihao; Su, Weiwei; Geng, Xiaoge; Chen, Xiaojun; Xu, Xiang; Pan, Wensheng

2017-03-01

Interventions of cardiovascular disease should be implemented in early ages. But most studies were performed in middle aged or elderly adults because of the low prevalence in young, especially for women. We investigate the association between metabolic risk factors and subclinical atherosclerosis in young asymptomatic women adults, using carotid intima-media thickness (CIMT) as a marker of the atherosclerotic process.We performed a cross-sectional study of 950 Chinese young asymptomatic women adults (37.28 ± 5.16 years) who underwent a routine health screening examination. Triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), fasting blood glucose (FBG), homocysteine (HCY), gamma glutamyltransferase (GGT), uric acid, and CIMT were measured.Out of 950 subjects, 16 (1.7%) were detected with increased CIMT. Significant differences existed in the indicators including age, body mass index (BMI), TC, TG, LDL-C, LDL-C/HDL-C, non-HDL-C, and TC/HDL-C. Although TG, LDL-C, non-HDL-C, TC/HDL-C, and TG/HDL-C were the significant indicators when adjusted for age only, age, LDL-C/HDL-C, FBG, and GGT were the only independent relative indicators of increased CMIT that entered the multivariate model. The area under receiver operating characteristic curve for a linear combination of age, LDL-C/HDL-C, FBG, and GGT was 0.809 (95% confidence interval = 0.712-0.906), superior to any of the variables taken alone (age, AUC = 0.707; FBG, AUC = 0.710; LDL-C/HDL-C, AUC = 0.695; GGT, AUC = 0.648).The combined assessment of age, LDL-C/HDL-C, FBG, and GGT contributes to an early detection for subclinical atherosclerosis, providing guidance to clinicians for women's early interventions of latent cardiovascular disease. Neither of the above four individual indicators is qualified alone.

Status of non-HDL-cholesterol and LDL-cholesterol among subjects with and without metabolic syndrome.

PubMed

Khan, Sikandar Hayat; Asif, Naveed; Ijaz, Aamir; Manzoor, Syed Mohsin; Niazi, Najumusaquib Khan; Fazal, Nadeem

2018-04-01

To to compare non-high-density lipoprotein and low-density lipoprotein cholesterol among subjects with or without metabolic syndrome, glycation status and nephropathic changes. The comparative cross-sectional study was carried out from Dec 21, 2015, to Nov 15, 2016, at the department of pathology and medicine PNS HAFEEZ and department of chemical pathology and clinical endocrinology (AFIP), and comprised patients of either gender visiting the out-patient department for routine screening. They were evaluated for anthropometric indices, blood pressure and sampled for lipid profile, fasting plasma glucose, glycated haemoglobin, insulin, and urine albumin-to-creatinine ratio. Subjects were segregated based upon presence (Group1) or absence (Group2) of metabolic syndrome based upon criteria of National Cholesterol Education Programme and the International Diabetes Federation. Differences in high and low density lipoprotein cholesterols were calculated between the groups. Of the 229 subjects, 120(52.4%) were women and 109(47.6%) were men. Overall, there were 107(46.7%) subjects in Group 1, and 122(53.3%) in Group 2. Non-high-density lipoprotein cholesterol was significantly different between subjects with and without metabolic syndrome as per both the study criteria (p<0.05 each). . Non-high-density lipoprotein cholesterol levels were higher in subjects with metabolic syndrome.

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...

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.

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.

Increased IL18 mRNA levels in peripheral artery disease and its association with triglyceride and LDL cholesterol levels: a pilot study.

PubMed

Deser, Serkan Burc; Bayoglu, Burcu; Besirli, Kazım; Cengiz, Mujgan; Arapi, Berk; Junusbekov, Yerik; Dirican, Ahmet; Arslan, Caner

2016-06-01

Peripheral artery disease (PAD) typically refers to lower limb vessel ischemia caused by atherosclerotic stenosis of lower extremity arteries. IL18 is a pleiotropic pro-inflammatory cytokine reported to function as an inflammatory biomarker in cardiovascular diseases. IL18 activity is balanced by high-affinity naturally occurring IL18-binding protein (IL18BP). This study aimed to determine whether IL18, IL18 BP mRNA levels and -137 G/C (rs187238) polymorphism, which was previously associated with IL18 gene transcriptional activity, were associated with PAD etiology. IL18, IL18BP mRNA levels from peripheral blood mononuclear cells and -137 G/C (rs187238) polymorphism were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and RT-PCR, respectively, in 55 PAD patients (26 aorta-iliac, 29 femoro-popliteal) and 61 disease-free controls. IL18 mRNA levels were increased in PAD patients compared with healthy controls (p = 0.09); however, did not reach a statistical significant level, also did not significantly differ between aorta-iliac and femoro-popliteal occlusive PAD subgroups (p = 0.285). However, IL18BP mRNA levels were significantly lower in PAD group compared with controls (p < 0.001). Genotype frequencies of rs187238 polymorphism did not significantly differ between PAD patients and controls (p = 0.385). IL18 mRNA levels were significantly correlated with triglycerides and LDL cholesterol levels in PAD patients (p = 0.003, p = 0.014, respectively). HDL cholesterol levels were negatively correlated with IL18 mRNA levels in controls (p = 0.05). This report is a preliminary study to show an association between IL18, IL18BP mRNA levels and PAD and suggests that the IL18 gene may have a significant relationship with triglyceride and LDL cholesterol levels in PAD patients.

Dietary cholesterol, heart disease risk and cognitive dissonance.

PubMed

McNamara, Donald J

2014-05-01

In the 1960s, the thesis that dietary cholesterol contributes to blood cholesterol and heart disease risk was a rational conclusion based on the available science at that time. Fifty years later the research evidence no longer supports this hypothesis yet changing the dietary recommendation to limit dietary cholesterol has been a slow and at times contentious process. The preponderance of the clinical and epidemiological data accumulated since the original dietary cholesterol restrictions were formulated indicate that: (1) dietary cholesterol has a small effect on the plasma cholesterol levels with an increase in the cholesterol content of the LDL particle and an increase in HDL cholesterol, with little effect on the LDL:HDL ratio, a significant indicator of heart disease risk, and (2) the lack of a significant relationship between cholesterol intake and heart disease incidence reported from numerous epidemiological surveys. Over the last decade, many countries and health promotion groups have modified their dietary recommendations to reflect the current evidence and to address a now recognised negative consequence of ineffective dietary cholesterol restrictions (such as inadequate choline intake). In contrast, health promotion groups in some countries appear to suffer from cognitive dissonance and continue to promote an outdated and potentially hazardous dietary recommendation based on an invalidated hypothesis. This review evaluates the evidence for and against dietary cholesterol restrictions and the potential consequences of such restrictions.

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.

Synergistic effects of psyllium in the dietary treatment of hypercholesterolemia.

PubMed

Neal, G W; Balm, T K

1990-10-01

We investigated psyllium fiber supplementation as a means of enhancing the cholesterol-lowering effect of the phase I American Heart Association diet. Fifty-nine subjects with total serum cholesterol (TC) levels ranging from 5.56 to 10.24 mmol/L (215 to 396 mg/dL) were given a 2-month dietary lead-in followed by 3 months of diet only (29 subjects) or diet supplemented with 20.4 g of psyllium daily (30 subjects). Unlike women, men had a significant decrease in levels of both TC (-8.0%) and low-density lipoprotein cholesterol (LDL-C) (-10.1%) during the dietary lead-in. Psyllium supplementation resulted in an additional 5.5% reduction in the TC levels as compared to diet alone. Psyllium supplementation combined with dietary lead-in resulted in an overall 17.3% decrease in the TC and a 20.0% decrease in LDL-C for men, with decreases of 7.7% and 11.6%, respectively, for women. Psyllium effectively enhances the cholesterol-lowering effect of the phase I diet.

High-dose ascorbic acid decreases cholesterolemic factors of an atherogenic diet in guinea pigs.

PubMed

Filis, Konstantinos; Anastassopoulou, Aikaterini; Sigala, Fragiska; Theodorou, Dimitrios; Manouras, Andreas; Leandros, Emanouel; Sigalas, Panagiotis; Hepp, Wolfgang; Bramis, John

2007-03-01

The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks. Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01). High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

Cholesterol biosynthesis in normocholesterolemic patients after cholesterol removal by plasmapheresis.

PubMed

Feillet, C; Cristol, J P; Michel, F; Kanouni, T; Navarro, R; Navarro, M; Monnier, L; Descomps, B

1997-01-01

Plasmapheresis and low-density lipoprotein (LDL)-apheresis are recognized procedures for the treatment of hyperlipidemia resistant to diet and lipid-lowering drugs and provide information on cholesterol synthesis in hypercholesterolemic patients. However, cholesterol synthesis after acute cholesterol removal from plasma has never been investigated in normocholesterolemic patients. In this study, cholesterol synthesis was evaluated in three normocholesterolemic patients by determination of plasma lathosterol, lathosterol-to-cholesterol ratio, and plasma mevalonic acid. In a short-term kinetic study, samples were collected before and after plasmapheresis and every 6 hours during 24 hours. In the second part of the study, cholesterol synthesis was evaluated daily for 3 days. In normocholesterolemic patients, cholesterol returns to basal levels in 3 days. However, cholesterol removal did not result in a significant increase in lathosterol-to-cholesterol ratio or in plasma mevalonic acid, despite a slight increase in lathosterol. In contrast, when repeated plasma exchanges induced a dramatic hypocholesterolemia (< 1 mmol/liter), an acute but transient stimulation of cholesterol synthesis was observed (lathosterol/cholesterol ratio and MVA, respectively, increase from 8.2 to 22.3 and from 28 nmol/liter to 98 nmol/liter). This study shows that cholesterol synthesis is not stimulated by plasmapheresis in normocholesterolemic patients but is enhanced in dramatic hypocholesterolemic patients (< 1 mmol/liter).

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

Serum cholesterol concentrations among Navajo Indians.

PubMed Central

Sugarman, J R; Gilbert, T J; Percy, C A; Peter, D G

1992-01-01

Navajo Indians have been reported by earlier investigators to have low concentrations of serum lipids and a low prevalence of hyperlipidemia, as well as low rates of ischemic heart disease. However, no data on serum lipid concentrations among Navajos have been reported for more than two decades. The authors conducted a study to determine the distribution of concentrations of serum total cholesterol (TC), high density lipoprotein cholesterol, low density lipoprotein cholesterol, and triglyceride among persons 25-74 years old living in a representative community on the Navajo Indian reservation. Data are reported for 255 subjects, 105 men and 150 women, ages 25-74 years. The authors compared these data to those for the general population as determined by the second National Health and Nutrition Examination Survey (NHANES II). TC concentrations among Navajo men were similar to those from NHANES II. TC concentrations among younger Navajo women were similar to those for women younger than 55 years from NHANES II, but were significantly lower among older Navajo women. While 27.6 percent of men ages 25-74 years studied in NHANES II had TC concentrations greater than 240 milligrams per deciliter, 33.8 percent of Navajo men had similarly elevated TC. However, the prevalence of serum TC concentrations greater than 240 milligrams per deciliter among Navajo women (17.5 percent) was about half that among women studied in NHANES II (32.9 percent). A similar pattern was found for low density lipoprotein cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1738814

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

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

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.

Apolipoprotein C3 (-455T>C) polymorphism confers susceptibility to nonalcoholic fatty liver disease in the Southern Han Chinese population

PubMed Central

Li, Min-Rui; Zhang, Sheng-Hong; Chao, Kang; Liao, Xian-Hua; Yao, Jia-Yan; Chen, Min-Hu; Zhong, Bi-Hui

2014-01-01

AIM: To investigate the relationship between Apolipoprotein C3 (APOC3) (-455T>C) polymorphism and nonalcoholic fatty liver disease (NAFLD) in the Southern Chinese Han population. METHODS: In this prospective case-control study, we recruited 300 NAFLD patients and 300 healthy controls to a cohort representing Southern Chinese Han population at The First Affiliated Hospital, Sun Yat-sen University, from January to December 2012. Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing were used to genotype the APOC3 (-455T>C) variants. RESULTS: After adjusting for age, gender, and body-mass index, TC and CC genotypes were found to increase the susceptibility to NAFLD compared to the TT genotype, with adjusted odds ratios (ORs) of 1.77 (95%CI: 1.16-2.72) and 2.80 (95%CI: 1.64-4.79), respectively. Further stratification analysis indicated that carriers of the CC genotype was more susceptible to insulin resistance (IR) than those of the TT genotype, with an OR of 3.24 (95%CI: 1.52-6.92). The CC genotype also was associated with a significantly higher risk of hypertension, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL) (P < 0.05). No association was found between the APOC3 (-455T>C) polymorphism and obesity, impaired glucose tolerance, hyperuricemia, hypercholesterolemia, or high levels of low-density lipoprotein cholesterol (LDL) (P > 0.05). CONCLUSION: APOC3 (-455T>C) genetic variation is involved in the susceptibility to developing NAFLD, IR, hypertension, hypertriglyceridemia, and low HDL in the Southern Chinese Han population. PMID:25320541

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.

ATP-binding cassette transporter 1 participates in LDL oxidation by artery wall cells.

PubMed

Reddy, Srinivasa T; Hama, Susan; Ng, Carey; Grijalva, Victor; Navab, Mohamad; Fogelman, Alan M

2002-11-01

We have previously reported that products of the lipoxygenase pathway, hydroperoxyoctadecadienoic acid and hydroperoxyeicosatetraenoic acid, as well as cholesterol linoleate hydroperoxides, collectively termed seeding molecules, are removed by apolipoprotein A-I (apoA-I) from the artery wall cells and render low density lipoprotein (LDL) resistant to oxidation by human artery wall cells. The mechanisms by which oxidized lipids are transported and/or transferred to lipoproteins and the pathways by which apoA-I facilitates their removal remain unclear. ATP-binding cassette transporter 1 (ABCA1) is known to facilitate the release of cellular phospholipids and cholesterol from the plasma membrane to apoA-I and high density lipoprotein. Therefore, we evaluated whether ABCA1 participates in LDL oxidation. In this report, we show that (1) chemical inhibitors of ABCA1 function, glyburide and DIDS, block artery wall cell-mediated oxidative modification of LDL, (2) inhibition of ABCA1 with the use of antisense (but not sense) oligonucleotides prevents LDL-induced lipid hydroperoxide formation and LDL-induced monocyte chemotactic activity by the artery wall cells, and (3) oxysterols that induce ABCA1 expression, such as 22(R)hydroxycholesterol, enhance cell-mediated LDL oxidation. Furthermore, we also show that 22(R)hydroxycholesterol induces the production of reactive oxygen species in the artery wall cells, which can be removed by incubating the artery wall cells with apoA-I. Our data suggest that ABCA1 plays an important role in artery wall cell-mediated modification/oxidation of LDL by modulating the release of reactive oxygen species from artery wall cells that are necessary for LDL oxidation.

How can we further improve the LDL-cholesterol target level achievement rate based on the Hungarian MULTI GAP 2011 study results and considering the new European dyslipidemia guidelines?

PubMed

Mark, Laszlo; Paragh, György; Karadi, Istvan; Reiber, Istvan; Pados, Gyula; Kiss, Zoltan

2012-09-08

Despite the continuous improvement of the quality of lipid lowering therapy the achievement of target values is still not satisfactory, mainly in the very high cardiovascular risk category patients, where the goal of low density lipoprotein cholesterol (LDL-C) is 1.80 mmol/l. The trends in lipid lowering treatment of 17420 patients from different studies conducted between 2004 and 2010 were compared to that of 1626 patients of MULTI GAP (MULTI Goal Attainment Problem) 2011 treated by general practitioners (GPs) and specialists. In MULTI GAP 2011 the mean LDL-C level ± SD) of patients treated by GPs was found to be 2.87 ±1.01 mmol/l, the target value of 2.50 was achieved by 40% of them, in the specialists' patients the mean LDL-C level proved to be 2.77 ±1.10 mmol/l and the achievement rate was 45%. In the 2.50 mmol/l achievement rate of GPs' patients a satisfactory improvement was observed in the studied years, but the 1.80 mmol/l LDL-C goal in 2011 was attained only in 11% of very high risk cases. There was a linear correlation between the patient compliance estimated by the physicians and the LDL-C achievement rate. As the number of very high risk category patients has been increased according to the new European dyslipidemia guidelines, growing attention needs to be placed on attainment of the 1.80 mmol/l LDL-C level. Based on the results of the MULTI GAP studies, improving patients' adherence and the continuous training of physicians are necessary.

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.

Association between early pregnancy vitamin D status and changes in serum lipid profiles throughout pregnancy.

PubMed

Lepsch, Jaqueline; Eshriqui, Ilana; Farias, Dayana Rodrigues; Vaz, Juliana S; Cunha Figueiredo, Amanda C; Adegboye, Amanda Rodrigues Amorim; Brito, Alex; Mokhtar, Rana; Allen, Lindsay H; Holick, Michael F; Kac, Gilberto

2017-05-01

To evaluate the associations between first trimester 25-hydroxyvitamin D [25(OH)D] status and changes in high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), triglyceride (TG) concentrations, TG/HDL-c, and TC/HDL-c ratios throughout pregnancy. We hypothesized that first trimester 25(OH)D inadequacy is associated with lower concentrations of HDL-c and higher LDL-c, TC, TG, TG/HDL-c, and TC/HDL-c ratios throughout pregnancy. A prospective cohort study with 3 visits at 5-13 (baseline), 20-26, and 30-36 gestational weeks, recruited 194 pregnant women attending a public health care center in Rio de Janeiro, Brazil. Plasma 25(OH)D concentrations were measured in the first trimester using liquid chromatography-tandem mass spectrometry. 25(OH)D concentrations were classified as adequate (≥75nmol/L) or inadequate (<75nmol/L). Serum TC, HDL-c, and TG concentrations were measured enzymatically. Crude and adjusted longitudinal linear mixed-effects models were employed to evaluate the association between the first trimester 25(OH)D status and changes in serum lipid concentrations throughout pregnancy. Confounders adjusted for in the multiple analysis were age, homeostatic model assessment (HOMA), early pregnancy BMI, leisure time physical activity before pregnancy, energy intake, and gestational age. At baseline, 69% of the women had inadequate concentrations of 25(OH)D. Women with 25(OH)D inadequacy had higher mean LDL-c than those with adequate concentrations (91.3 vs. 97.5mg/dL; P=0.064) at baseline. TC, HDL-c, LDL-c TG, TG/HDL-c ratios, and TC/HDL-c ratios, increased throughout pregnancy independently of 25(OH)D concentrations (ANOVA for repeated measures P<0.001). The adjusted models showed direct associations between the first trimester 25(OH)D status and changes in TC (β=9.53; 95%CI=1.12-17.94), LDL-c (β=9.99; 95% CI=3.62-16.36) concentrations, and TC/HDL-c ratios (β=0.16; 95% CI=0.01-0.31) throughout

Effect of calcium lactate supplementation on cholesterol concentration in patients with hyperlipidaemia and previous viral hepatitis: a preliminary report.

PubMed

Andryskowski, G; Chojnowska-Jezierska, J; Broncel, M; Barylski, M; Banach, M

2008-01-01

The aim of the study was to estimate the effect of calcium supplementation on cholesterol concentrations in patients with hyperlipidaemia and previous viral hepatitis. The study comprised 43 patients, aged 28 to 82 years (21 with type 2 hyperlipidaemia). The control group included 22 healthy subjects. After four weeks of a hypolipaemic diet (wash-out period), the patients with type 2 hyperlipidaemia were recruited to a group administered a complex preparation containing 170 mg of calcium lactate and 60 mg of vitamin C (Calcium C, Polfa-Lodz SA, Poland) at a dose of one tablet three times a day. After four weeks of active therapy, the concentration of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) decreased by 4, 6 and 8%, respectively. Statistical significance was obtained for only TC (p = 0.03) when comparing the group of patients with hypercholesterolaemia before and after the therapy with the calcium preparation. A statistically insignificant increase of high-density lipoprotein cholesterol (HDL-C) of 1% was observed. Within the four-week period of calcium supplementation at a dose of 510 mg/24 h, the total concentration of calcium decreased by 3%, whereas the concentration of ionised calcium increased by 7%. None of the obtained values was of statistical significance. In patients with type 2 hyperlipidaemia and previous viral hepatitis, a four-week supplementation of calcium in a calcium lactate preparation beneficially modified the lipid profile. I t statistically significantly decreased the total cholesterol concentration by 4% (p = 0.03), did not cause any significant changes in serum calcium concentration, was well tolerated and did not induce any side effects.

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice.

PubMed

van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-05-01

Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (-31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (-70%) and secretion (-28%) by peritoneal macrophages. Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. © 2015 The British Pharmacological Society.

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.

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...

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

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.

Effects of a very high saturated fat diet on LDL particles in adults with atherogenic dyslipidemia: A randomized controlled trial.

PubMed

Chiu, Sally; Williams, Paul T; Krauss, Ronald M

2017-01-01

Previous studies have shown that increases in LDL-cholesterol resulting from substitution of dietary saturated fat for carbohydrate or unsaturated fat are due primarily to increases in large cholesterol-enriched LDL, with minimal changes in small, dense LDL particles and apolipoprotein B. However, individuals can differ by their LDL particle distribution, and it is possible that this may influence LDL subclass response. The objective of this study was to test whether the reported effects of saturated fat apply to individuals with atherogenic dyslipidemia as characterized by a preponderance of small LDL particles (LDL phenotype B). Fifty-three phenotype B men and postmenopausal women consumed a baseline diet (55%E carbohydrate, 15%E protein, 30%E fat, 8%E saturated fat) for 3 weeks, after which they were randomized to either a moderate carbohydrate, very high saturated fat diet (HSF; 39%E carbohydrate, 25%E protein, 36%E fat, 18%E saturated fat) or low saturated fat diet (LSF; 37%E carbohydrate, 25%E protein, 37%E fat, 9%E saturated fat) for 3 weeks. Compared to the LSF diet, consumption of the HSF diet resulted in significantly greater increases from baseline (% change; 95% CI) in plasma concentrations of apolipoprotein B (HSF vs. LSF: 9.5; 3.6 to 15.7 vs. -6.8; -11.7 to -1.76; p = 0.0003) and medium (8.8; -1.3 to 20.0 vs. -7.3; -15.7 to 2.0; p = 0.03), small (6.1; -10.3 to 25.6 vs. -20.8; -32.8 to -6.7; p = 0.02), and total LDL (3.6; -3.2 to 11.0 vs. -7.9; -13.9 to -1.5; p = 0.03) particles, with no differences in change of large and very small LDL concentrations. As expected, total-cholesterol (11.0; 6.5 to 15.7 vs. -5.7; -9.4 to -1.8; p<0.0001) and LDL-cholesterol (16.7; 7.9 to 26.2 vs. -8.7; -15.4 to -1.4; p = 0.0001) also increased with increased saturated fat intake. Because medium and small LDL particles are more highly associated with cardiovascular disease than are larger LDL, the present results suggest that very high saturated fat intake may increase

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

Serum level of triglycerides is a potent risk factor comparable to LDL cholesterol for coronary heart disease in Japanese patients with type 2 diabetes: subanalysis of the Japan Diabetes Complications Study (JDCS).

PubMed

Sone, Hirohito; Tanaka, Sachiko; Tanaka, Shiro; Iimuro, Satoshi; Oida, Koji; Yamasaki, Yoshimitsu; Oikawa, Shinichi; Ishibashi, Shun; Katayama, Shigehiro; Ohashi, Yasuo; Akanuma, Yasuo; Yamada, Nobuhiro

2011-11-01

Risk factors for cardiovascular complications in Japanese patients with diabetes have not been fully elucidated. Our objective was to determine incidence of and risk factors for coronary heart disease (CHD) and stroke in Japanese diabetic patients. We conducted a prospective study at 59 hospitals throughout Japan. Patients included 940 men and 831 women with type 2 diabetes (mean age, 58.2 yr) without a history of cardiovascular complications who were followed for a median of 7.86 yr. This was an observational study. Incidence of CHD and stroke was evaluated. Incidences of CHD and stroke per 1000 person-years were 9.59 and 7.45, respectively, whereas those of myocardial and brain infarctions were 3.84 and 6.29, respectively. Multivariate Cox analysis revealed that the serum log-transformed triglyceride level was a potent and independent predictor of CHD [hazard ratio (HR) = 1.54; 95% confidence interval (CI) = 1.22-1.94 per 1 sd increase), comparable to low-density lipoprotein (LDL) cholesterol (HR = 1.49; 95% CI = 1.25-1.78 per 1 sd increase). Triglycerides and LDL cholesterol linearly and continuously increased CHD risk, and subjects in the top third for both had markedly high risks of CHD, and their effects were possibly additive. However, serum triglycerides worked independently of blood pressure levels. Systolic blood pressure was the only significant predictor for stroke except for age (HR = 1.31; 95% CI = 1.04-1.65, per 1 sd increase). In Japanese patients with type 2 diabetes, the serum triglyceride level was a leading predictor of CHD, comparable to LDL cholesterol. Because the serum triglyceride level is not a leading predictor of CHD in diabetic subjects in Western countries, ethnic group-specific strategies for prevention of diabetic macroangiopathy may be indicated.

Comparative effects of hawthorn (Crataegus pinnatifida Bunge) pectin and pectin hydrolyzates on the cholesterol homeostasis of hamsters fed high-cholesterol diets.

PubMed

Zhu, Ru-Gang; Sun, Yan-Di; Li, Tuo-Ping; Chen, Gang; Peng, Xue; Duan, Wen-Bin; Zheng, Zheng-Zheng; Shi, Shu-Lei; Xu, Jing-Guo; Liu, Yan-Hua; Jin, Xiao-Yi

2015-08-05

This study aims to compare the effects of feeding haw pectin (HP), haw pectin hydrolyzates (HPH), and haw pectin pentasaccharide (HPPS) on the cholesterol metabolism of hypercholesterolemic hamsters induced by high-cholesterol diets. The animals were fed a standard diet (SD), high-cholesterol diet (HCD), or HCD plus HP, HPH, or HPPS at a dose of 300mg/kg body weight for 4weeks. Results showed that HPPS was more effective than HP and HPH in decreasing the body weight gain (by 38.2%), liver weight (by 16.4%), and plasma and hepatic total cholesterol (TC; by 23.6% and 27.3%, respectively) of hamsters. In addition, the bile acid levels in the feces were significantly higher by 39.8% and 132.8% in the HPH and HPPS groups than in the HCD group. Such changes were not noted in the HP group. However, the HP group had higher cholesterol excretion capacities than the HPH and HPPS groups by inhibiting cholesterol absorption in the diet, with a 21.7% increase in TC excretion and a 31.1% decrease in TC absorption. Thus, HPPS could be a promising anti-atherogenic dietary ingredient for the development of functional food to improve cholesterol metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Goal attainments and their discrepancies for low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) in over 2,000 Chinese patients with known coronary artery disease or type 2 diabetes.

PubMed

He, Yong-Ming; Yang, Xiang-Jun; Zhao, Xin; Xu, Hai-Feng

2015-04-01

Low density lipoprotein cholesterol (LDL-C) is primary treatment target for patients with dislipidemia. The apolipoprotein B (apo B), an emerging biomarker for cardiovascular risk prediction, appears to be superior to the LDL-C. However, little is known about goal attainments and their discrepancies for LDL-C and apo B in Chinese patients with known CAD or DM. A total of 2,172 hospitalized patients with known coronary artery disease (CAD) or DM, aged >27 years of old, were enrolled. The success rates for apo B and LDL-C goal attainments were evaluated and compared by categorization and by sex. When the success rates for apo B were compared with the ones for LDL-C, the former was higher than the latter across all categorizations, with the statistically significant differences seen in all patients, CAD alone and DM alone (P<0.0001), but not in coexistence of CAD and DM (P=0.190). The trend toward to higher success rates for LDL-C and apo B goal attainments in men than in women were noteworthy across all categorizations although only in all patients and in DM alone patients were the statistically significant differences found (P<0.01). The LDL-C lags behind the apo B in goal attainments in Chinese patients. Whether these discrepancies are associated with the occurrence differences for CAD and for stroke between the East Asia and the Western countries warrants further study.

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

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.

PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE.

PubMed

Ason, Brandon; van der Hoorn, José W A; Chan, Joyce; Lee, Edward; Pieterman, Elsbet J; Nguyen, Kathy Khanh; Di, Mei; Shetterly, Susan; Tang, Jie; Yeh, Wen-Chen; Schwarz, Margrit; Jukema, J Wouter; Scott, Rob; Wasserman, Scott M; Princen, Hans M G; Jackson, Simon

2014-11-01

LDL cholesterol (LDL-C) contributes to coronary heart disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases LDL-C by inhibiting LDL-C clearance. The therapeutic potential for PCSK9 inhibitors is highlighted by the fact that PCSK9 loss-of-function carriers exhibit 15-30% lower circulating LDL-C and a disproportionately lower risk (47-88%) of experiencing a cardiovascular event. Here, we utilized pcsk9(-/-) mice and an anti-PCSK9 antibody to study the role of the LDL receptor (LDLR) and ApoE in PCSK9-mediated regulation of plasma cholesterol and atherosclerotic lesion development. We found that circulating cholesterol and atherosclerotic lesions were minimally modified in pcsk9(-/-) mice on either an LDLR- or ApoE-deficient background. Acute administration of an anti-PCSK9 antibody did not reduce circulating cholesterol in an ApoE-deficient background, but did reduce circulating cholesterol (-45%) and TGs (-36%) in APOE*3Leiden.cholesteryl ester transfer protein (CETP) mice, which contain mouse ApoE, human mutant APOE3*Leiden, and a functional LDLR. Chronic anti-PCSK9 antibody treatment in APOE*3Leiden.CETP mice resulted in a significant reduction in atherosclerotic lesion area (-91%) and reduced lesion complexity. Taken together, these results indicate that both LDLR and ApoE are required for PCSK9 inhibitor-mediated reductions in atherosclerosis, as both are needed to increase hepatic LDLR expression. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Red Cabbage Microgreens Lower Circulating Low-Density Lipoprotein (LDL), Liver Cholesterol, and Inflammatory Cytokines in Mice Fed a High-Fat Diet.

PubMed

Huang, Haiqiu; Jiang, Xiaojing; Xiao, Zhenlei; Yu, Lu; Pham, Quynhchi; Sun, Jianghao; Chen, Pei; Yokoyama, Wallace; Yu, Liangli Lucy; Luo, Yaguang Sunny; Wang, Thomas T Y

2016-12-07

Cardiovascular disease (CVD) is the leading cause of death in the United States, and hypercholesterolemia is a major risk factor. Population studies, as well as animal and intervention studies, support the consumption of a variety of vegetables as a means to reduce CVD risk through modulation of hypercholesterolemia. Microgreens of a variety of vegetables and herbs have been reported to be more nutrient dense compared to their mature counterparts. However, little is known about the effectiveness of microgreens in affecting lipid and cholesterol levels. The present study used a rodent diet-induced obesity (DIO) model to address this question. C57BL/6NCr mice (n = 60, male, 5 weeks old) were randomly assigned to six feeding groups: (1) low-fat diet; (2) high-fat diet; (3) low-fat diet + 1.09% red cabbage microgreens; (4) low-fat diet + 1.66% mature red cabbage; (5) high-fat diet + 1.09% red cabbage microgreens; (6) high-fat diet + 1.66% mature red cabbage. The animals were on their respective diets for 8 weeks. We found microgreen supplementation attenuated high-fat diet induced weight gain. Moreover, supplementation with microgreens significantly lowered circulating LDL levels in animals fed the high-fat diet and reduced hepatic cholesterol ester, triacylglycerol levels, and expression of inflammatory cytokines in the liver. These data suggest that microgreens can modulate weight gain and cholesterol metabolism and may protect against CVD by preventing hypercholesterolemia.

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.

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.

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice

PubMed Central

van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-01-01

Background and Purpose Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Experimental Approach Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Key Results Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (−31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (−70%) and secretion (−28%) by peritoneal macrophages. Conclusions and Implications Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. PMID:25572138

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.

Increased binding of LDL and VLDL to apo B,E receptors of hepatic plasma membrane of rats treated with Fibernat.

PubMed

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

2003-10-01

Research has focussed on the hypocholesterolemic effects of certain types of dietary fiber such as enhancing conversion of hepatic cholesterol to bile acids or increase in catabolism of low density lipoprotein (LDL) via the apo B,E receptor. The effect of oral administration of a unique fibre cocktail of fenugreek seed powder, guar gum and wheat bran (Fibernat) and its varied effects on some aspects of lipid metabolism and cholesterol homeostasis in rats were examined. Rats were administered Fibernat along with the atherogenic diet containing 1.5 % cholesterol and 0.1 % cholic acid. Amounts of hepatic lipids, hepatic and fecal bile acids and activity of hepatic triglyceride lipase (HTGL) were determined. Transmission electron microscopic examination of the liver tissue and extent of uptake of (125)I-LDL and (125)I-VLDL by the hepatic apo B,E receptor was carried out. Food intake and body weight gain were similar between the 3 different dietary groups. Fibernat intake significantly increased apo B,E receptor expression in rat liver as reflected by an increase in the maximum binding capacity (B(max)) of the apo B,E receptor to (125)I-LDL and (125)I-VLDL. The activity of HTGL was increased by approximately 1.5-fold in Fibernat-fed rats as compared to those fed the atherogenic diet alone. A marked hypocholesterolemic effect was observed. Cholesterol homeostasis was achieved in Fibernat-fed rats. Two possible mechanisms are postulated to be responsible for the observed hypocholesterolemic effect a) an increase in conversion of cholesterol to bile acids and b) possibly by intra-luminal binding which resulted in increased fecal excretion of bile acids and neutral sterols. The resulting reduction in cholesterol content of liver cells coupled with upregulation of hepatic apo B,E receptors and increased clearance of circulating atherogenic lipoproteins-LDL and very low density lipoprotein (LDL and VLDL)-is the main mechanism involved in the hypocholesterolemic effect of

Work, sleep, and cholesterol levels of U.S. long-haul truck drivers

PubMed Central

LEMKE, Michael K.; APOSTOLOPOULOS, Yorghos; HEGE, Adam; WIDEMAN, Laurie; SÖNMEZ, Sevil

2016-01-01

Long-haul truck drivers in the United States experience elevated cardiovascular health risks, possibly due to hypercholesterolemia. The current study has two objectives: 1) to generate a cholesterol profile for U.S. long-haul truck drivers; and 2) to determine the influence of work organization characteristics and sleep quality and duration on cholesterol levels of long-haul truck drivers. Survey and biometric data were collected from 262 long-haul truck drivers. Descriptive analyses were performed for demographic, work organization, sleep, and cholesterol measures. Linear regression and ordinal logistic regression analyses were conducted to examine for possible predictive relationships between demographic, work organization, and sleep variables, and cholesterol outcomes. The majority (66.4%) of drivers had a low HDL (<40 mg/dL), and nearly 42% of drivers had a high-risk total cholesterol to HDL cholesterol ratio. Sleep quality was associated with HDL, LDL, and total cholesterol, and daily work hours were associated with LDL cholesterol. Workday sleep duration was associated with non-HDL cholesterol, and driving experience and sleep quality were associated with cholesterol ratio. Long-haul truck drivers have a high risk cholesterol profile, and sleep quality and work organization factors may induce these cholesterol outcomes. Targeted worksite health promotion programs are needed to curb these atherosclerotic risks. PMID:28049935

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 Effect of Deployment on Cholesterol Levels of Active Duty Personnel

DTIC Science & Technology

2006-05-01

fairly good results regarding cholesterol levels. It was noted that several members returned from deployment with elevated levels, sometimes to the...LDL cholesterol and low HDL cholesterol (Downs, John R., Beere, Polly A., Whitney, Edwin, Clearfield, Michael, Weis, Stephen, Rochen, Jeffrey, Stein...specific ages, including cholesterol screenings beginning at age 25. Given the age of the majority of this population, one might expect relatively good

[Association between food behavior and hypercholesterolemia-LDL in university students].

PubMed

Salazar Ruiz, Erika Nohemi; Márquez Sandoval, Yolanda Fabiola; Vizmanos Lamotte, Bárbara; Altamirano Martínez, Martha Betzaida; Salgado Bernabé, Aralia Berenice; Salgado Goytia, Lorenzo; Muñoz Valle, José Francisco; Parra Rojas, Isela

2015-06-01

Hypercholesterolemia-LDL (H-LDL) is associated with increased risk of cardiovascular disease. The association between H-LDL and feeding has focused on nutritional aspects. The study of the association between eating behavior (EB) and H-LDL in university students, could provide nutritional elements for correction and/or prevention in this population. To assess the association between EB and H-LDL in university students. A cross-sectional study was carried out in a sample of 167 students from the Autonomous University of Guerrero, Mexico. LDL cholesterol in serum was measured and a concentration ≥100 mg/dL was considered hypercholesterolemia. The EB was assessed using a previously validated questionnaire. The association between EB and H-LDL was determined with a bivariate logistic regression, adjusting for sex, age, socioeconomic status, smoking, energy intake, physical activity, presence or absence of obesity and family history. Eating lunch (morning snack) was related with 63% lower risk of H-LDL (OR 0.37; 95% CI 0.15, 0.90). Take food away from home once or twice a week was associated with a fourfold increased risk of H-LDL (R 5.14; 95% CI 1.12, 23.62). Subjects who reported consuming excess food (1 or 2, and 3 or more times/week) had higher risk of H-LDL (OR 3.26; 95% CI 1.10, 9.64 and OR 10.52; 95% CI 2.66, 41.60 respectively). Some usual EB of the university students (Guerrero, Mexico) involve greater risk of H-LDL. To encourage actions corrective and/or preventive focused on these EB, could improve the health of this population. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

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.

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.

Effectiveness of treat-to-target strategy for LDL-cholesterol control in type 2 diabetes: post-hoc analysis of data from the MIND.IT study.

PubMed

Ardigò, Diego; Vaccaro, Olga; Cavalot, Franco; Rivellese, Albarosa Angela; Franzini, Laura; Miccoli, Roberto; Patti, Lidia; Boemi, Massimo; Trovati, Mariella; Zavaroni, Ivana

2014-04-01

The paper presents a post-hoc analysis of the intensity of dyslipidaemia care operated in the first 2 years of Multiple-Intervention-in-type-2-Diabetes.ITaly (MIND.IT) study. MIND.IT is a multicentric, randomized, two-parallel arm trial involving 1461 type 2 diabetic patients at high cardiovascular (CV) risk. The study compares the usual care (UC) of CV prevention with a multifactorial intensive care (IC) approach aiming at achieving target values for the main CV risk factors according to a step-wise treat-to-target approach. Proportion of patients on target for low-density lipoprotein cholesterol (LDL-C) was about 10% at baseline and increased significantly more with IC than UC (43 vs. 27%; p < 0.001). However, the majority (57%) of patients, in this intended intensively treated cohort, failed to achieve the proposed target. Average LDL-C decreased from 144 ± 35 to 108 ± 31 mg/dl with IC and from 142 ± 28 to 118 ± 32 with UC (p-for-interaction <0.0001). IC was associated with a significantly greater increase in statin prescription and lower withdrawal from treatment than UC (43 vs. 11% and 28 vs. 61%, respectively; both p < 0.001). However, the new treatments were characterized in both groups by the use of low starting doses (≤ 10 mg of atorvastatin, equivalent dose in more than 90% of patients) without increase in case of missed target. The application of a multifactorial treat-to-target intervention is associated with a significant improvement in LDL-C beyond usual practice. However, the change in LDL-C appears to be more related to an increased number of treated patients and a decreased treatment withdrawal than to a true treat-to-target approach.

Effect of long-term optional ingestion of canola oil, grape seed oil, corn oil and yogurt butter on serum, muscle and liver cholesterol status in rats.

PubMed

Asadi, Farzad; Shahriari, Ali; Chahardah-Cheric, Marjan

2010-01-01

The aim of the present study was to determine the effect of long-term optional intake of vegetable oils (canola, grape seed, corn) and yogurt butter on the serum, liver and muscle cholesterol status. Twenty-five male Wistar rats were randomly categorized into five groups (n=5) as follows: control, canola oil, grape seed oil, corn oil and manually prepared yogurt butter. In each group, 24h two bottle choice (oil and water) tests were performed for 10 weeks. Serum cholesterol values showed a trend to decrease in grape seed oil, corn oil and yogurt butter groups compared to the control. Optional intake of yogurt butter made a significant increase in HDL-C values (42.34+/-9.98 mg/dL) yet decrease in LDL-C values (11.68+/-2.06 mg/dL) compared to the corresponding control (19.07+/-3.51; 30.96+/-6.38 mg/dL, respectively). Furthermore, such findings were concomitant with a significant decrease in the liver TC levels (1.75+/-0.31 mg/g liver) and an increase in the muscle TC levels (1.85+/-0.32 mg/g liver) compared to the corresponding control (2.43+/-0.31; 0.94+/-0.14 mg/g liver, respectively). Optional intake of manually prepared yogurt butter has more beneficial effects on serum lipoprotein cholesterol values with some alterations in the liver and muscle cholesterol states than the vegetable oils. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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

Estimation of the prevalence of familial hypercholesterolaemia in a rural Afrikaner community by direct screening for three Afrikaner founder low density lipoprotein receptor gene mutations.

PubMed

Steyn, K; Goldberg, Y P; Kotze, M J; Steyn, M; Swanepoel, A S; Fourie, J M; Coetzee, G A; Van der Westhuyzen, D R

1996-10-01

We have determined the prevalence of familial hypercholesterolaemia (FH) in a rural Afrikaner community by means of direct DNA screening for three founder-related Afrikaner low density lipoprotein (LDL) receptor gene mutations. A random sample of 1612 persons, aged 15-64 years, was selected as a subsample of 4583 subjects from an Afrikaner community living in the south-western Cape, South Africa. Participants who had a total serum cholesterol (TC) in the high TC category as defined in the consensus recommendations by the Southern African Heart Foundation, were screened for three founder-related LDL receptor gene mutations, causing FH in 90% of Afrikaners. Of the subsample, 201 participants (12.5%) had TC levels above the 80th percentile. In this group the combined prevalence of the three common Afrikaner LDL receptor gene defects (D206E, FH Afrikaner-1; V408M, FH Afrikaner-2; D154N, FH Afrikaner-3) was calculated as 1: 83. When taking into account the reported background prevalence of other FH gene defects of 1:500 in this community, their overall prevalence of FH was estimated to be 1:72. The significant differences found between the FH patients and other high risk patients with raised cholesterol levels were higher TC and LDL cholesterol levels and lower high density lipoprotein cholesterol levels in FH patients. The treatment status of the molecularly identified FH patients and other hypercholesterolaemic persons suggests that this condition is inadequately diagnosed and poorly managed in this study population. An extrapolation to the entire South African population suggests that there are about 112000 FH patients in the country who are under-diagnosed as a group and therefore not receiving the care that would help to reduce the burden of FH-associated ischaemic heart disease in South Africa.

Fasting Might Not Be Necessary Before Lipid Screening: A Nationally Representative Cross-sectional Study

PubMed Central

Skinner, Asheley Cockrell; Perrin, Eliana M.

2011-01-01

BACKGROUND: There are barriers to fasting lipid screening for at-risk children. Results of studies in adults have suggested that lipid testing might be reliably performed without fasting. OBJECTIVE: To examine population-level differences in pediatric lipid values based on length of fast before testing. METHODS: We used the National Health and Nutrition Examination Survey (1999–2008) to examine total cholesterol (TC), HDL (high-density lipoprotein), LDL (low-density lipoprotein), and triglyceride cholesterol components on the basis of the period of fasting. Young children fasted for varying times before being tested, and children older than 12 years were asked to fast; however, adherence was variable. We used ordinary least-squares regression to test for differences in lipid values that were based on fasting times, controlling for weight status, age, race, ethnicity, and gender. RESULTS: TC, HDL, LDL, or triglyceride values were available for 12 744 children. Forty-eight percent of the TC and HDL samples and 80% of the LDL and triglyceride samples were collected from children who had fasted ≥8 hours. Fasting had a small positive effect for TC, HDL, and LDL, resulting in a mean value for the sample that was 2 to 5 mg/dL higher with a 12-hour fast compared with a no-fast sample. Fasting time had a negative effect on triglycerides (β = −0.859; P = .02), which resulted in values in the fasting group that were 7 mg/dL lower. DISCUSSION: Comparison of cholesterol screening results for a nonfasting group of children compared with results for a similar fasting group resulted in small differences that are likely not clinically important. Physicians might be able to decrease the burden of childhood cholesterol screening by not requiring prescreening fasting for these components. PMID:21807697

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

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.

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.

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...

Evaluation of the hypocholesterolemic effect and phytochemical screening of the hydroethanolic extract of Crataegus aronia from Jordan.

PubMed

Al-Hallaq, Entisar K; Afifi, Fatma U; Abdalla, Shtaywy S

2012-01-01

Chemical screening of the leaves and flowers of Crataegus aronia resulted in the isolation of hyperoside, quercetin, rutin and beta-sitosterol for the first time from this plant. The effects of the hydroethanolic extract of C. aronia (CAHE) on hypercholesterolemic rats were investigated. The rats, treated orally for four weeks with 400 mg/kg/day CAHE, exhibited significant decreases in serum total cholesterol (TC) and low-density lipoprotein (LDL). The results were compared with those obtained after oral administration of atorvastatin (10 mg/kg/day). Furthermore, 10-week daily co-administration of a high cholesterol diet and CAHE (200 mg/kg/day) prevented the increase in TC and LDL. These observations indicate that CAHE has a hypocholesterolemic effect.

Phthalocyanine-labeled LDL for tumor imaging and photodynamic therapy

NASA Astrophysics Data System (ADS)

Li, Hui; Marotta, Diane; Kim, Soungkyoo; Chance, Britton; Glickson, Jerry D.; Busch, Theresa M.; Zheng, Gang

2005-01-01

Current limitation of both near-infrared (NIR) tumor imaging and photodynamic therapy (PDT) is their lack of sufficient tumor-to-tissue contrast due to the relatively non-specific nature of delivering dye to the tumor, which has led to false negatives for NIR imaging and inadequate therapeutic ratio for PDT. Hence, agents targeting "cancer signatures", i.e. molecules that accumulate selectively in cancer cells, are particular attractive. One of these signatures is low-density-lipoprotein receptor (LDLR), which is overexpressed in many tumors. We have developed pyropheophorbide cholesterol oleate reconstituted LDL as a LDLR-targeting photosensitizer (PS) and demonstrated its LDLR-mediated uptake in vitro and in vivo. To improve the labeling efficiency for achieving high probe/protein ratio, tetra-t-butyl silicon phthalocyanine bearing two oleate moieties at its axial positions, (tBu)4SiPcBOA, was designed and synthesized. This compound was designed to 1) prevent the PS aggregation; 2) improve the PS solubility in non-polar solvent; and 3) maximize the PS binding to LDL phospholipid monolayer. Using this novel strategy, (tBu)4SiPcBOA was reconstituted into LDL (r-SiPcBOA-LDL) with a very high payload (500:1 molar ratio). In addition, (tBu)4SiPcBOA reconstituted acetylated LDL (r-SiPcBOA)-AcLDL with similar payload was also prepared. Since Ac-LDL cannot bind to LDLR, (r-SiPcBOA)-AcLDL can serve as the negative control to evaluate LDLR targeting specificity. For biological evaluation of these new agents, confocal microscopy and in vitro PDT protocols were performed using LDLR-overexpressing human hepatoblastoma G2 (HepG2) tumor model. These studies suggest that LDL serves as a delivery vehicle to bring large amount of the NIR/PDT agents selectively to tumor cells overexpressing LDLR.

The association between lipid parameters and obesity in university students.

PubMed

Hertelyova, Z; Salaj, R; Chmelarova, A; Dombrovsky, P; Dvorakova, M C; Kruzliak, P

2016-07-01

Abdominal obesity is associated with high plasma triglyceride and with low plasma high-density lipoprotein cholesterol levels. Objective of the study was to find an association between plasma lipid and lipoprotein levels and anthropometric parameters in abdominal obesity in Slovakian university students. Lipid profile and anthropometric parameters of obesity were studied in a sample of 419 probands, including 137 men and 282 women. Males had higher values of non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and very low-density lipoprotein cholesterol (VLDL-C) than females, but these differences were not significant. Females had significantly (P < 0.05) higher TC and HDL-C (P < 0.001) than males. In comparison, all anthropometric parameters in the males were significantly (P < 0.001) higher than in the females. A positive correlation between non-HDL-C, TG, VLDL-C and anthropometric parameters (BMI, WC, WHR, WHtR) was found at P < 0.001. LDL was positively correlated with BMI, WCF, WHtR and TC with BMI, WHtR at P < 0.001. We also observed a correlation between TC-WCF and LDL-WHR at P < 0.01. A negative correlation was found between HDL and all monitored anthropometric parameters at P < 0.001. On the other hand, no correlation between TC and WHR was detected. This study shows an association between plasma lipid and lipoprotein levels and anthropometric parameters in abdominal obesity in young people, predominantly university students.

Lipid content in hepatic and gonadal adipose tissue parallel aortic cholesterol accumulation in mice fed diets with different omega-6 PUFA to EPA plus DHA ratios.

PubMed

Wang, Shu; Matthan, Nirupa R; Wu, Dayong; Reed, Debra B; Bapat, Priyanka; Yin, Xiangling; Grammas, Paula; Shen, Chwan-Li; Lichtenstein, Alice H

2014-04-01

Diets with low omega (ω)-6 polyunsaturated fatty acids (PUFA) to eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) ratios have been shown to decrease aortic cholesterol accumulation and have been suggested to promote weight loss. The involvement of the liver and gonadal adipose tissue (GAT) in mediating these effects is not well understood. LDL receptor null mice were used to assess the effect of an atherogenic diet with different ω-6:EPA+DHA ratios on weight gain, hepatic and GAT lipid accumulation, and their relationship to atherosclerosis. Four groups of mice were fed a high saturated fat and cholesterol diet (HSF ω-6) alone, or with ω-6 PUFA to EPA+DHA ratios up to 1:1 for 32 weeks. Liver and GAT were collected for lipid and gene expression analysis. The fatty acid profile of liver and GAT reflected the diets. All diets resulted in similar weight gains. Compared to HSF ω-6 diet, the 1:1 ratio diet resulted in lower hepatic total cholesterol (TC) content. Aortic TC was positively correlated with hepatic and GAT TC and triglyceride. These differences were accompanied by significantly lower expression of CD36, ATP-transporter cassette A1, scavenger receptor B class 1, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), acetyl-CoA carboxylase alpha, acyl-CoA synthetase long-chain family member 5, and stearoyl-coenzyme A desaturase 1 (SCD1) in GAT, and HMGCR, SCD1 and cytochrome P450 7A1 in liver. Dietary ω-6:EPA+DHA ratios did not affect body weight, but lower ω-6:EPA+DHA ratio diets decreased liver lipid accumulation, which possibly contributed to the lower aortic cholesterol accumulation. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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.

Atheroprotective effects of Cuphea carthagenensis (Jacq.) J. F. Macbr. in New Zealand rabbits fed with cholesterol-rich diet.

PubMed

Barboza, Lorena Neris; Lívero, Francislaine Aparecida Dos Reis; Prando, Thiago Bruno Lima; Ribeiro, Rita de Cassia Lima; Lourenço, Emerson Luiz Botelho; Budel, Jane Manfron; de Souza, Lauro Mera; Acco, Alexandra; Dalsenter, Paulo Roberto; Gasparotto, Arquimedes

2016-07-01

Although Cuphea carthagenensis (Jacq.) J. F. Macbr. is used in Brazilian folk medicine in the treatment of atherosclerosis and circulatory disorders, no study evaluating these effects has been conducted. The aim of this study was to evaluate the possible hypolipemiant and antiatherogenic activity of the ethanol soluble fraction obtained from C. carthagenensis (ES-CC) in an experimental atherosclerosis model using New Zealand (NZ) rabbits undergoing cholesterol-rich diet (CRD). Dyslipidemia and atherogenesis were induced by administration of standard commercial diet increased of 1% cholesterol (CRD) for 8 weeks. ES-CC was orally administered at doses of 10, 30 and 100mg/kg, once daily for four weeks, starting from the 4th week of CRD diet. Body weight measurements were weekly carried out from the beginning of experiments for 8 weeks. Serum levels of triglyceride (TG), total cholesterol (TC) and their fractions (LDL-C, VLDL-C and HDL-C) were measured at the beginning of experiments and at weeks four and eight. After euthanasia of rabbits, aorta segments (aortic arc, thoracic, abdominal and iliac segments) were macroscopically and microscopically evaluated and the intima and media layers of the arteries were measured. Additionally, the antioxidant activity of ES-CC and its influence on the functioning of hepatic antioxidant enzymes were also determined. CRD induced dyslipidemia and major structural changes in the aortic wall. In addition, an increase in lipid peroxidation and a reduction of hepatic glutathione and serum nitrite levels were observed. Treatment with ES-CC was able to prevent the increase in TC, LDL-C, VLDL-C levels and triglycerides and promoted an increase in HDL-C levels in NZ rabbits. These effects were accompanied by a significant reduction in oxidative stress and modulation of the catalase and superoxide dismutase function. Moreover, the intima and media layers of the arterial segments were significantly reduced by ES-CC treatment. This study

CER-001, a HDL-mimetic, stimulates the reverse lipid transport and atherosclerosis regression in high cholesterol diet-fed LDL-receptor deficient mice.

PubMed

Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Ackermann, Rose; Sy, Gavin; Bluteau, Alice; Cholez, Guy; Keyserling, Constance; Lalwani, Narendra; Paolini, John F; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

2014-01-01

CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and phospholipids that was designed to mimic the beneficial properties of nascent pre-β HDL. In this study, we have evaluated the capacity of CER-001 to perform reverse lipid transport in single dose studies as well as to regress atherosclerosis in LDLr(-/-) mice after short-term multiple-dose infusions. CER-001 induced cholesterol efflux from macrophages and exhibited anti-inflammatory response similar to natural HDL. Studies with HUVEC demonstrated CER-001 at a concentration of 500 μg/mL completely suppressed the secretion of cytokines IL-6, IL-8, GM-CSF and MCP-1. Following infusion of CER-001 (10mg/kg) in C57Bl/6J mice, we observed a transient increase in the mobilization of unesterified cholesterol in HDL particles containing recombinant human apoA-I. Finally we show that cholesterol elimination was stimulated in CER-001 treated animals as demonstrated by the increased cholesterol concentration in liver and feces. In a familial hypercholesterolemia mouse model (LDL-receptor deficient mice), the infusion of CER-001 caused 17% and 32% reductions in plaque size, 17% and 23% reductions in lipid content after 5 and 10 doses given every 2 days, respectively. Also, there was an 80% reduction in macrophage content in the plaque following 5 doses, and decreased VCAM-1 expression by 16% and 22% in the plaque following 5 and 10 intravenous doses of CER-001, respectively. These data demonstrate that CER-001 rapidly enhances reverse lipid transport in the mouse, reducing vascular inflammation and promoting regression of diet-induced atherosclerosis in LDLr(-/-) mice upon a short-term multiple dose treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

The effect of exemestane, anastrozole, and tamoxifen on lipid profiles in Japanese postmenopausal early breast cancer patients: final results of National Surgical Adjuvant Study BC 04, the TEAM Japan sub-study.

PubMed

Hozumi, Y; Suemasu, K; Takei, H; Aihara, T; Takehara, M; Saito, T; Ohsumi, S; Masuda, N; Ohashi, Y

2011-08-01

In this Tamoxifen Exemestane Adjuvant Multinational Japan sub-study, we evaluated the time course of changes in serum lipids in postmenopausal women with hormone-sensitive early breast cancer treated with exemestane, anastrozole, or tamoxifen for postoperative adjuvant therapy. A total of 154 breast cancer patients were assigned to receive exemestane, anastrozole, or tamoxifen in this randomized open-label study. Serum lipid parameters including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured during 1 year of treatment. TC and LDL-C rapidly decreased in patients treated with tamoxifen at 3 months. Compared with anastrozole and exemestane patients, TC and LDL-C were significantly lower at all assessment time points in tamoxifen patients (P < 0.05). TG increased in tamoxifen patients; it was significantly higher compared with exemestane patients at all assessment time points (P < 0.05). HDL-C slightly decreased in exemestane patients; it was significantly lower compared with anastrozole patients at 3 months and 1 year (P = 0.0179 and 0.0013, respectively). Changes of lipid profiles in Japanese postmenopausal women treated with tamoxifen were relatively favorable, while exemestane and anastrozole had no clinically significant effect on the serum lipids.

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.

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.

LDL-cholesterol lowering activity of a blend of rice bran oil and safflower oil (8:2) in patients with hyperlipidaemia: a proof of concept, double blind, controlled, randomised parallel group study.

PubMed

Malve, Harshad; Kerkar, Prafulla; Mishra, Nidheesh; Loke, Sanjita; Rege, N N; Marwaha-Jaspal, Ankita; Jainani, Kiran J

2010-11-01

Cardiovascular diseases have emerged as major health burden worldwide in recent times. Low density lipoprotein cholesterol (LDL-C) serves as the primary marker for cardiovascular diseases. Reports suggest that rice bran oil has antihyperlipidaemic properties. However, current evidence suggests that no single oil can provide the recommended dietary fat ratio. Hence the present study was undertaken in patients with hyperlipidaemia to study effects of substitution of the cooking oil with a blend of 80% rice bran oil and 20% safflower oil on LDL-C levels. The selected patients (n = 73) were randomly assigned either to the study oil group (blend under study) or control oil group (the oil which the patient was using before). The lipid profile was monitored monthly in these patients for 3 months during which they consumed the oil as per the randomisation. At each follow up, LDL-C levels showed a significant reduction from baseline in the study oil group and reduction was more than that observed in the control group. It was also observed that the percentage of the respondents was higher in the study oil group. At the end of the study period, 82% patients from this group had LDL levels less than 150 mg% as against 57% in the control group. Thus, the substitution of usual cooking oil with a blend of rice bran oil and safflower oil (8:2) was found to exert beneficial effects on the LDL-C levels shifting them to low-risk lipid category.

The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial.

PubMed

Baigent, Colin; Landray, Martin J; Reith, Christina; Emberson, Jonathan; Wheeler, David C; Tomson, Charles; Wanner, Christoph; Krane, Vera; Cass, Alan; Craig, Jonathan; Neal, Bruce; Jiang, Lixin; Hooi, Lai Seong; Levin, Adeera; Agodoa, Lawrence; Gaziano, Mike; Kasiske, Bertram; Walker, Robert; Massy, Ziad A; Feldt-Rasmussen, Bo; Krairittichai, Udom; Ophascharoensuk, Vuddidhej; Fellström, Bengt; Holdaas, Hallvard; Tesar, Vladimir; Wiecek, Andrzej; Grobbee, Diederick; de Zeeuw, Dick; Grönhagen-Riska, Carola; Dasgupta, Tanaji; Lewis, David; Herrington, William; Mafham, Marion; Majoni, William; Wallendszus, Karl; Grimm, Richard; Pedersen, Terje; Tobert, Jonathan; Armitage, Jane; Baxter, Alex; Bray, Christopher; Chen, Yiping; Chen, Zhengming; Hill, Michael; Knott, Carol; Parish, Sarah; Simpson, David; Sleight, Peter; Young, Alan; Collins, Rory

2011-06-25

Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and ISRCTN54137607. 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74-0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76-1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60-0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68-0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL

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.

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.

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.

Potential use of cholesterol lipoprotein profile to confirm obesity status in dogs.

PubMed

Mori, Nobuko; Lee, Peter; Kondo, Kazuo; Kido, Toshimi; Saito, Terumasa; Arai, Toshiro

2011-04-01

A common sign of obesity, in dogs, is hyperlipidemia, which is characterized by hypercholesterolemia and/or hypertriglycemia. Hyperlipidemia can be caused by a quantitative increase in circulating lipoproteins (LP) or by a higher lipid concentration in the various LP classes. In this study, we sought to determine whether aberrations occur with cholesterol lipoprotein profile, especially with sub HDL-cholesterol fraction % in obese dogs. Using clinically healthy and disease free (no overt signs) body condition score classified obese dogs, of all ages, we attempted to determine the influence of age, gender and obesity status on cholesterol lipoprotein profiling. Overall, no aberration in pattern was observed in obese dogs <8 years of age. However, in older obese animals (≥8 years of age), the general aberration pattern to cholesterol lipoprotein observed was that a significant decrease in HDL2 and 3 fraction % occurs with a concomitant increase in either HDL1-Cho or VLDL and LDL -Cho fraction % depending on gender. Linear regression analysis indicated that obesity status appears to significantly affect total cholesterol, HDL2 and 3-Cho, VLDL and LDL-Cho levels (P=0.02, 0.046, and 0.045, respectively), whereas it is borderline with HDL1-Cho (P=0.062). On the other hand, age significantly influenced TG, Total cholesterol, and HDL1-Cho levels (P=0.009, 0.006, and 0.002, respectively), while gender influenced VLDL and LDL-Cho (P=0.024) level. Therefore, aberrations in cholesterol lipoprotein profile pattern might be of potential use to assess and diagnose obesity status, in conjunction with BCS, especially of older overweight animals which might be considered borderline obese. © Springer Science+Business Media B.V. 2011

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.

Acid sphingomyelinase-deficient macrophages have defective cholesterol trafficking and efflux.

PubMed

Leventhal, A R; Chen, W; Tall, A R; Tabas, I

2001-11-30

Cholesterol efflux from macrophage foam cells, a key step in reverse cholesterol transport, requires trafficking of cholesterol from intracellular sites to the plasma membrane. Sphingomyelin is a cholesterol-binding molecule that transiently exists with cholesterol in endosomes and lysosomes but is rapidly hydrolyzed by lysosomal sphingomyelinase (L-SMase), a product of the acid sphingomyelinase (ASM) gene. We therefore hypothesized that sphingomyelin hydrolysis by L-SMase enables cholesterol efflux by preventing cholesterol sequestration by sphingomyelin. Macrophages from wild-type and ASM knockout mice were incubated with [(3)H]cholesteryl ester-labeled acetyl-LDL and then exposed to apolipoprotein A-I or high density lipoprotein. In both cases, [(3)H]cholesterol efflux was decreased substantially in the ASM knockout macrophages. Similar results were shown for ASM knockout macrophages labeled long-term with [(3)H]cholesterol added directly to medium, but not for those labeled for a short period, suggesting defective efflux from intracellular stores but not from the plasma membrane. Cholesterol trafficking to acyl-coenzyme A:cholesterol acyltransferase (ACAT) was also defective in ASM knockout macrophages. Using filipin to probe cholesterol in macrophages incubated with acetyl-LDL, we found there was modest staining in the plasma membrane of wild-type macrophages but bright, perinuclear fluorescence in ASM knockout macrophages. Last, when wild-type macrophages were incubated with excess sphingomyelin to "saturate" L-SMase, [(3)H]cholesterol efflux was decreased. Thus, sphingomyelin accumulation due to L-SMase deficiency leads to defective cholesterol trafficking and efflux, which we propose is due to sequestration of cholesterol by sphingomyelin and possibly other mechanisms. This model may explain the low plasma high density lipoprotein found in ASM-deficient humans and may implicate L-SMase deficiency and/or sphingomyelin enrichment of lipoproteins as novel

Relationship of baseline HDL subclasses, small dense LDL and LDL triglyceride to cardiovascular events in the AIM-HIGH clinical trial

PubMed Central

Albers, John J; Slee, April; Fleg, Jerome L; O’Brien, Kevin D; Marcovina, Santica M

2016-01-01

Background and aims Previous results of the AIM-HIGH trial showed that baseline levels of the conventional lipid parameters were not predictive of future cardiovascular (CV) outcomes. The aims of this secondary analysis were to examine the levels of cholesterol in high density lipoprotein (HDL) subclasses (HDL2-C and HDL3-C), small dense low density lipoprotein (sdLDL-C), and LDL triglyceride (LDL-TG) at baseline, as well as the relationship between these levels and CV outcomes. Methods Individuals with CV disease and low baseline HDL-C levels were randomized to simvastatin plus placebo or simvastatin plus extended release niacin (ERN), 1,500 to 2,000 mg/day, with ezetimibe added as needed in both groups to maintain an on-treatment LDL-C in the range of 40 to 80 mg/dL. The primary composite endpoint was death from coronary disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebrovascular revascularization. HDL-C, HDL3-C, sdLDL-C and LDL-TG were measured at baseline by detergent-based homogeneous assays. HDL2-C was computed by the difference between HDL-C and HDL3-C. Analyses were performed on 3,094 study participants who were already on statin therapy prior to enrollment in the trial. Independent contributions of lipoprotein fractions to CV events were determined by Cox proportional hazards modeling. Results Baseline HDL3-C was protective against CV events (HR: 0.84, p=0.043) while HDL-C, HDL2-C, sdLDL-C and LDL-TG were not event-related (HR: 0.96, p=0.369; HR: 1.07, p=0.373; HR: 1.05, p=0.492; HR: 1.03, p=0.554, respectively). Conclusions The results of this secondary analysis of the AIM-HIGH Study indicate that levels of HDL3-C, but not other lipoprotein fractions, are predictive of CV events, suggesting that the HDL3 subclass may be primarily responsible for the inverse association of HDL-C and CV disease. PMID:27320173

Cholesterol, APOE genotype, and Alzheimer disease: an epidemiologic study of Nigerian Yoruba.

PubMed

Hall, K; Murrell, J; Ogunniyi, A; Deeg, M; Baiyewu, O; Gao, S; Gureje, O; Dickens, J; Evans, R; Smith-Gamble, V; Unverzagt, F W; Shen, J; Hendrie, H

2006-01-24

To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria. Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's Disease and Related Disorders Association criteria. Logistic regression models showed interaction after adjusting for age and gender between APOE-epsilon4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p= 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-epsilon4 allele, but not in those with APOE-epsilon4. There was no significant association between levels of triglycerides and AD risk in those without APOE-epsilon4. There was a significant interaction between cholesterol, APOE-epsilon4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies.

Association of CILP2 and ACE Gene Polymorphisms with Cardiovascular Risk Factors in Slovak Midlife Women

PubMed Central

Luptáková, Lenka; Benčová, Dominika; Siváková, Daniela; Cvíčelová, Marta

2013-01-01

The aim of this study is to assess the association of two polymorphisms, the cartilage intermediate layer protein 2 (CILP2) G/T and angiotensin converting enzyme (ACE) I/D, with blood pressure and anthropometrical and biochemical parameters related to the development of cardiovascular disease. The entire study sample comprised 341 women ranging in age from 39 to 65 years. The CILP2 genotypes were determined by PCR-RFLP and the ACE genotypes by PCR. The Bonferroni pairwise comparisons showed the effect of the CILP2 genotype on high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), apoB-to-apoA1 ratio, the total cholesterol (TC)-to-HDL-C ratio, non-HDL-C, and the LDL-C-to-HDL-C ratio (P < 0.05). Here, higher mean levels of HDL-C and lower mean levels of the remaining above mentioned lipid parameters were registered in the GT/TT genotype carriers than in GG carriers. Statistically significant association was identified between the ACE genotype and the following parameters: TC, LDL-C, and non-HDL-C (P < 0.05). The II genotype can lower serum level of TC (B = 0.40), LDL-C (B = 0.37), and non-HDL-C levels. The results of this study suggest that the minor T allele of CILP2 gene and I allele of ACE gene have a protective effect against elevated serum lipid and lipoprotein levels. PMID:24350279

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.

Effect of different fat-enriched meats on non-cholesterol sterols and oxysterols as markers of cholesterol metabolism: Results of a randomized and cross-over clinical trial.

PubMed

Baila-Rueda, L; Mateo-Gallego, R; Pérez-Calahorra, S; Lamiquiz-Moneo, I; de Castro-Orós, I; Cenarro, A; Civeira, F

2015-09-01

Different kinds of fatty acids can affect the synthesis, absorption, and elimination of cholesterol. This study was carried out to assess the associations of cholesterol metabolism with the intake of two meats with different fatty acid composition in healthy volunteers. The study group was composed of 20 subjects (12 males and eight females; age, 34.4 ± 11.6 years; body mass index (BMI), 23.5 ± 2.3 kg/m(2); low-density lipoprotein (LDL) cholesterol, 2.97 ± 0.55 mmol/l; high-density lipoprotein (HDL) cholesterol, 1.61 ± 0.31 mmol/l; triglycerides (TG), 1.06 ± 0.41 mmol/l) who completed a 30-day randomized and cross-over study to compare the cholesterol metabolism effect of 250 g of low-fat lamb versus 250 g of high-fat lamb per day in their usual diet. Cholesterol absorption, synthesis, and elimination were estimated from the serum non-cholesterol sterol and oxysterol concentrations analyzed by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). No changes in weight, plasma lipids, or physical activity were observed across the study. Cholesterol intestinal absorption was decreased with both diets. Cholesterol synthesis and elimination decreased during the low-fat lamb dietary intervention (ρ = 0.048 and ρ = 0.005, respectively). Acute changes in the diet fat content modify the synthesis, absorption, and biliary elimination of cholesterol. These changes were observed even in the absence of total and LDL cholesterol changes in plasma. ClinicalTrials.gov PRS, NCT02259153. Copyright © 2015 Elsevier B.V. All rights reserved.

HEMOGLOBIN A1C, BLOOD PRESSURE, AND LDL-CHOLESTEROL CONTROL AMONG HISPANIC/LATINO ADULTS WITH DIABETES: RESULTS FROM THE HISPANIC COMMUNITY HEALTH STUDY/STUDY OF LATINOS (HCHS/SOL)

PubMed Central

Casagrande, Sarah Stark; Aviles-Santa, Larissa; Corsino, Leonor; Daviglus, Martha L.; Gallo, Linda C.; Espinoza Giacinto, Rebeca A.; Llabre, Maria M.; Reina, Samantha A.; Savage, Peter J.; Schneiderman, Neil; Talavera, Gregory A.; Cowie, Catherine C.

2018-01-01

Objective To determine the prevalence of Hispanic/Latino adults with diabetes who meet target hemoglobin A1c, blood pressure (BP), and low-density-lipoprotein cholesterol (LDL-C) recommendations, and angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blocker (ARB) and statin medication use by heritage and sociodemographic and diabetes-related characteristics. Methods Data were cross-sectional, collected between 2008 and 2011, and included adults age 18 to 74 years who reported a physician diagnosis of diabetes in the Hispanic Community Health Study/Study of Latinos (N = 2,148). Chi-square tests compared the prevalence of hemoglobin A1c, BP, and LDL-C targets and ACE/ARB and statin use across participant characteristics. Predictive margins regression was used to determine the prevalence adjusted for sociodemographic characteristics. Results The overall prevalence of A1c <7.0% (53 mmol/mol), BP <130/80 mm Hg, and LDL-C <100 mg/dL was 43.0, 48.7, and 36.6%, respectively, with 8.4% meeting all three targets. Younger adults aged 18 to 39 years with diabetes were less likely to have A1c <7.0% (53 mmol/mol) or LDL-C <100 mg/dL compared to those aged 65 to 74 years; younger adults were more likely to have BP <130/80 mm Hg (P<.05 for all). Individuals of Mexican heritage were significantly less likely to have A1c <7.0% (53 mmol/mol) compared to those with Cuban heritage, but they were more likely to have BP <130/80 mm Hg compared to those with Dominican, Cuban, or Puerto Rican heritage (P<.05 for all); there was no difference in LDL-C by heritage. Overall, 38.2% of adults with diabetes were taking a statin, and 50.5% were taking ACE/ARB medications. Conclusion Hemoglobin A1c, BP, and LDL-C control are suboptimal among Hispanic/Latinos with diabetes living in the U.S. With 8.4% meeting all three recommendations, substantial opportunity exists to improve diabetes control in this population. PMID:28816530

Translating Cholesterol Guidelines Into Primary Care Practice: A Multimodal Cluster Randomized Trial

PubMed Central

Eaton, Charles B.; Parker, Donna R.; Borkan, Jeffrey; McMurray, Jerome; Roberts, Mary B.; Lu, Bing; Goldman, Roberta; Ahern, David K.

2011-01-01

PURPOSE We wanted to determine whether an intervention based on patient activation and a physician decision support tool was more effective than usual care for improving adherence to National Cholesterol Education Program guidelines. METHODS A 1-year cluster randomized controlled trial was performed using 30 primary care practices (4,105 patients) in southeastern New England. The main outcome was the percentage of patients screened for hyperlipidemia and treated to their low-density lipoprotein (LDL) and non–high-density lipoprotein (HDL) cholesterol goals. RESULTS After 1 year of intervention, both randomized practice groups improved screening (89% screened), and 74% of patients in both groups were at their LDL and non-HDL cholesterol goals (P <.001). Using intent-to-treat analysis, we found no statistically significant differences between practice groups in screening or percentage of patients who achieved LDL and non-HDL cholesterol goals. Post hoc analysis showed practices who made high use of the patient activation kiosk were more likely to have patients screened (odds ratio [OR] = 2.54; 95% confidence interval [CI], 1.97–3.27) compared with those who made infrequent or no use. Additionally, physicians who made high use of decision support tools were more likely to have their patients at their LDL cholesterol goals (OR = 1.27; 95% CI, 1.07–1.50) and non-HDL goals (OR = 1.23; 95% CI, 1.04–1.46) than low-use or no-use physicians. CONCLUSION This study showed null results with the intent-to-treat analysis regarding the benefits of a patient activation and a decision support tool in improving cholesterol management in primary care practices. Post hoc analysis showed a potential benefit in practices that used the e-health tools more frequently in screening and management of dyslipidemia. Further research on how to incorporate and increase adoption of user-friendly, patient-centered e-health tools to improve screening and management of chronic diseases and

Optimal Serum Cholesterol Concentrations are Associated with Accelerated Bone Loss in African Ancestry Men

PubMed Central

Kuipers, Allison L.; Miljkovic, Iva; Evans, Rhobert; Bunker, Clareann H.; Patrick, Alan L.; Zmuda, Joseph M.

2016-01-01

Purpose Studies of lipid and lipoprotein cholesterol associations with bone mineral density (BMD) and bone loss have been inconclusive, and longitudinal data are sparse. Therefore, the aim of this study was to test if fasting serum lipid and lipoprotein cholesterol levels are associated with areal and volumetric BMD and BMD change, Methods We determined the association of serum triglycerides, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol concentrations with cross-sectional and longitudinal (mean follow-up: 6.1 years) measures of BMD in a cohort of 1289 in African ancestry men (mean age: 56.4 years). Fasting serum triglycerides, HDL and LDL were measured at baseline concurrent with BMD assessments. Dual-energy X-ray absorptiometry was used to quantify integral hip BMD and peripheral quantitative computed tomography at the radius and tibia was used to quantify volumetric BMD. Men were categorized as optimal, borderline or high-risk for triglyceride, HDL and LDL concentrations based on adult treatment panel III guidelines. Results Lower serum triglyceride or LDL and higher HDL concentrations were associated with lower trabecular BMD at baseline (all p<0.05). Similarly, men classified as having optimal levels of LDL, HDL or triglycerides at baseline experienced the greatest integral BMD loss at the hip and trabecular BMD loss at the tibia (all p<0.05), independent of potential confounding factors. Conclusions We found that clinically optimal serum lipid and lipoprotein cholesterol concentrations were associated with accelerated bone loss among Afro-Caribbean men. Further studies are needed to better understand the mechanisms involved and potential clinical significance of these findings. PMID:26602914

Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism: A Randomized, Controlled Feeding Study in Humans

PubMed Central

Lin, Xiaobo; Racette, Susan B.; Lefevre, Michael; Ma, Lina; Spearie, Catherine Anderson; Steger-May, Karen; Ostlund, Richard E.

2011-01-01

Background Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that ezetimibe combined with phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism. Methods and Results Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo + phytosterol placebo, (2) 10 mg ezetimibe/day + phytosterol placebo, and (3) 10 mg ezetimibe/day + 2.5 g phytosterols/day, for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and LDL cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/day, 95% CI 368 to 828) relative to control (2161 mg/day, 1112 to 3209) and ezetimibe alone (1054 mg/day, 546 to 1561, both P < 0.0001). Fecal cholesterol excretion was significantly greater (P < 0.0001) with combined treatment (962 mg/day, 757 to 1168) relative to control (505 mg/day, 386 to 625) and ezetimibe alone (794 mg/day, 615 to 973). Plasma LDL cholesterol values during control, ezetimibe alone, and ezetimibe + phytosterols averaged 129 (95% CI: 116 to 142), 108 (97 to 119), and 101 (90 to 112) mg/dL (P < 0.0001 relative to control). Conclusion The addition of phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma LDL cholesterol. The large cumulative action of combined dietary and pharmacologic treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia. PMID:21768544

[Characterization of lipid profile in primary health care users in Portugal].

PubMed

Cortez-Dias, Nuno; Robalo Martins, Susana; Belo, Adriana; Fiúza, Manuela

2013-12-01

To characterize the distribution of total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C) and triglycerides in primary health care users. We performed a cross-sectional study in a primary care setting, involving 719 general practitioners based on stratified distribution proportional to the population density of each region of Portugal. The first two adult patients scheduled for an appointment on a given day were invited to participate. A questionnaire was applied to assess sociodemographic, clinical and laboratory data including lipid profile. The study included 16 856 individuals (mean age 58.1±15.1 years; 61.6% women). Data on TC, LDL-C, HDL-C and triglycerides were available for 95.9% (n=16 159), 59.1% (n=9956), 95.4% (n=16 074) and 97.9% (n=16 494) of the population, respectively. Hypercholesterolemia (TC ≥200 mg/dl) was detected in 47%, and 38.4% had high levels of LDL-C (≥130 mg/dl). Hypertriglyceridemia (≥200 mg/dl) and low HDL-C (<40 mg/dl) were less prevalent, affecting roughly 13% of the population. Dyslipidemia was more common in middle-aged men and in post-menopausal women. Of the population aged over 40, 54.1% met eligibility criteria for lipid-lowering therapy and 44.7% were medicated with statins, but only 16.0% of these had TC ≤175 mg/dl. Dyslipidemia is highly prevalent in primary health care users in Portugal. It is particularly common in middle-aged men and post-menopausal women, who should be considered target groups for preventive public health measures. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts

PubMed Central

Aulchenko, Yurii S; Ripatti, Samuli; Lindqvist, Ida; Boomsma, Dorret; Heid, Iris M; Pramstaller, Peter P; Penninx, Brenda W J H; Janssens, A Cecile J W; Wilson, James F; Spector, Tim; Martin, Nicholas G; Pedersen, Nancy L; Kyvik, Kirsten Ohm; Kaprio, Jaakko; Hofman, Albert; Freimer, Nelson B; Jarvelin, Marjo-Riitta; Gyllensten, Ulf; Campbell, Harry; Rudan, Igor; Johansson, Åsa; Marroni, Fabio; Hayward, Caroline; Vitart, Veronique; Jonasson, Inger; Pattaro, Cristian; Wright, Alan; Hastie, Nick; Pichler, Irene; Hicks, Andrew A; Falchi, Mario; Willemsen, Gonneke; Hottenga, Jouke-Jan; de Geus, Eco J C; Montgomery, Grant W; Whitfield, John; Magnusson, Patrik; Saharinen, Juha; Perola, Markus; Silander, Kaisa; Isaacs, Aaron; Sijbrands, Eric J G; Uitterlinden, Andre G; Witteman, Jacqueline C M; Oostra, Ben A; Elliott, Paul; Ruokonen, Aimo; Sabatti, Chiara; Gieger, Christian; Meitinger, Thomas; Kronenberg, Florian; Döring, Angela; Wichmann, H-Erich; Smit, Johannes H; McCarthy, Mark I; van Duijn, Cornelia M; Peltonen, Leena

2009-01-01

Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 × 10-8), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 × 10-11; LDL, P = 2.6 × 10-10), TMEM57 (TC, P = 5.4 × 10-10), CTCF-PRMT8 region (HDL, P = 8.3 × 10-16), DNAH11 (LDL, P = 6.1 × 10-9), FADS3-FADS2 (TC, P = 1.5 × 10-10; LDL, P = 4.4 × 10-13) and MADD-FOLH1 region (HDL, P = 6 × 10-11). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors. PMID:19060911

Effects of soy bean on serum paraoxonase 1 activity and lipoproteins in hyperlipidemic postmenopausal women.

PubMed

Shidfar, Farzad; Ehramphosh, Elham; Heydari, Iraj; Haghighi, Ladan; Hosseini, Sharieh; Shidfar, Shahrzad

2009-05-01

Because of an unfavorable serum lipoprotein profile, postmenopausal women are at risk of cardiovascular disease. Soy protein may help protect against these risk factors, although its effect on paraoxonase 1 (PON1) is not clear. The aim of the present study was to determine the effects of soy protein on serum concentration of lipoproteins and PON1 activity in hypercholesterolemic postmenopausal women. In a double-blind randomized clinical trial with a parallel design, 52 hypercholesterolemic postmenopausal women were randomly assigned to 50 g/day soy protein containing 164 mg isoflavones or placebo, for 10 weeks. Serum lipoproteins and PON1 activity were measured at baseline and at the 10th week. There was significant increase in PON1 activity (P=0.029) and a significant decrease in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), LDL-C/high-density lipoprotein cholesterol (HDL-C), triacylglycerol/HDL-C and TC/HDL-C in the soy group compared with the placebo group (P=0.001, P=0.008, P=0.012, P=0.04 and P=0.029, respectively) at the end of the study. Similarly, PON1 activity was significantly increased (P=0.015) and LDL-C, TC, LDL-C/HDL-C, triacylglycerol/HDL-C and TC/HDL-C were significantly decreased (P=0.001, P=0.002, P=0.001, P=0.016 and P=0.001) at the end of the study compared with the beginning value in soy group. Soy protein reduces the cardiovascular disease risk in postmenopausal women because of both modest reductions in serum lipoproteins and an increase in PON1 activity.

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

Longitudinal Study of Low Serum LDL and Depressive Symptom Onset in Postmenopause

PubMed Central

Persons, Jane E.; Robinson, Jennifer G.; Coryell, William H.; Payne, Martha E.; Fiedorowicz, Jess G.

2016-01-01

Objective The aim of this study was to characterize the relationship between serum low-density lipoprotein cholesterol (LDL-c) and subsequent depressive symptoms onset in postmenopausal women. We secondarily assessed serum high-density lipoprotein (HDL-c), total cholesterol, and triglycerides. Methods This population-based prospective cohort study utilizes data from 24,216 50-79 year old participants of the Women’s Health Initiative, which originally ran from 1993-2005 and has since incorporated two extension studies, with the most recent culminating in 2015. Fasting lipids were measured for all participants at baseline, and for a subset through six years of follow-up. Depressive symptoms were characterized using the Burnam eight-item scale for depressive disorders (Center for Epidemiologic Studies-Depression/Diagnostic Interview Schedule short form) at baseline and over follow-up, using a cutpoint of 0.06 to indicate presence of depressive symptoms. Results The lowest quintile of LDL-c was associated with an increased risk of subsequent depressive symptoms (HR=1.25, CI 1.05-1.49, p=0.01) and follow-up analyses demonstrated that the elevated risk appeared to be confined to the lowest decile (LDL-c <100 mg/dL). Further, this elevated risk was moderated by lipid-lowering drug treatment. Elevated risk was demonstrated among those who reported no lipid-lowering medication use (HR=1.23, CI 1.03-1.47, p=0.02), but not among those reporting use (HR=0.65, CI 0.18-2.29, p=0.50). Conclusion Among postmenopausal women, untreated serum LDL-c below 100 mg/dL was associated with an increased risk of developing depressive symptoms. No excess risk was observed in those attaining LDL-c <100 mg/dl with lipid-lowering therapy. These findings have important implications for risk assessment, treatment considerations, and mechanistic insight. PMID:26930520

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...

Obesity induced during sexual maturation is linked to LDL-triacylglycerols in Yucatan miniature swine.

PubMed

Sébert, Sylvain P; Lecannu, Gérard; Sené, Sandrine; Hucteau, Séverine; Chetiveaux, Maud; Ouguerram, Khadija; Champ, Martine M-J

2005-08-01

The incidence of childhood obesity is rising dramatically throughout industrialised countries. To evaluate and study the impact of childhood obesity on lipoprotein metabolism, we developed a new animal model of premature obesity. Yucatan mini-pigs aged 4 months were studied over a 12-month period from childhood to adulthood. Animals were divided into two groups: the first group were overfed a Western misbalanced diet; the second group were normally fed a recommended human-type diet. Cholesterol and triacylglycerol concentrations in VLDL-, LDL- and HDL-lipoproteins were followed from baseline to adulthood by fast protein liquid chromatography. At 10 (the end of sexual maturation) and 16 months old (adulthood), liver, visceral and subcutaneous adipose tissues were sampled. Real-time RT-PCR was performed in order to compare apo AI, apo B, apo C-III, PPAR-alpha, insulin receptor and lipoprotein lipase gene expression between groups and ages. Differences between groups were observed only after sexual maturity. Adult overfed mini-pigs had a higher LDL-cholesterol:HDL-cholesterol ratio (P < 0.05; 0.55 (SE 0.06) for overfed v. 0.42 (SE 0.04) for normally fed pigs at the tenth month of the study). In both groups, VLDL-triacylglycerol decreased (P < 0.05). VLDL-triacylglycerol evolution in the overfed group was associated with an increase in LDL-triacylglycerol plasma concentrations (P < 0.05) after sexual maturation. LDL-triacylglycerol concentration in overfed mini-pigs went from an average of 0.28 mmol/l before sexual maturation to reach an average concentration of 0.56 mmol/l afterwards. This phenomenon has never been observed in similar studies when obesity is induced in adult mini-pigs and may represent a specific hallmark of an obesity induced during sexual maturity.

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.

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.

Development of a new LDL-based transport system for hydrophobic/amphiphilic drug delivery to cancer cells.

PubMed

Huntosova, Veronika; Buzova, Diana; Petrovajova, Dana; Kasak, Peter; Nadova, Zuzana; Jancura, Daniel; Sureau, Franck; Miskovsky, Pavol

2012-10-15

Low-density lipoproteins (LDL), a natural in vivo carrier of cholesterol in the vascular system, play a key role in the delivery of hydrophobic/amphiphilic photosensitizers to tumor cells in photodynamic therapy of cancer. To make this delivery system even more efficient, we have constructed a nano-delivery system by coating of LDL surface by dextran. Fluorescence spectroscopy, confocal fluorescence imaging, stopped-flow experiments and flow-cytometry were used to characterize redistribution of hypericin (Hyp), a natural occurring potent photosensitizer, loaded in LDL/dextran complex to free LDL molecules as well as to monitor cellular uptake of Hyp by U87-MG cells. It is shown that the redistribution process of Hyp between LDL molecules is significantly suppressed by dextran coating of LDL surface. The modification of LDL molecules by dextran does not inhibit their recognition by cellular LDL receptors and U-87 MG cellular uptake of Hyp loaded in LDL/dextran complex appears to be similar to that one observed for Hyp transported by unmodified LDL particles. Thus, it is proposed that dextran modified LDL molecules could be used as a basis for construction of a drug transport system for targeted delivery of hydrophobic/amphiphilic drugs to cancer cells expressing high level of LDL receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

Variants for HDL-C, LDL-C and Triglycerides Identified from Admixture Mapping and Fine-Mapping Analysis in African-American Families

PubMed Central

Shetty, Priya B.; Tang, Hua; Feng, Tao; Tayo, Bamidele; Morrison, Alanna C.; Kardia, Sharon L.R.; Hanis, Craig L.; Arnett, Donna K.; Hunt, Steven C.; Boerwinkle, Eric; Rao, D.C.; Cooper, R.S.; Risch, Neil; Zhu, Xiaofeng

2015-01-01

Background Admixture mapping of lipids was followed-up by family-based association analysis to identify variants for cardiovascular disease in African-Americans. Methods and Results The present study conducted admixture mapping analysis for total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides. The analysis was performed in 1,905 unrelated African-American subjects from the National Heart, Lung and Blood Institute’s Family Blood Pressure Program. Regions showing admixture evidence were followed-up with family-based association analysis in 3,556 African-American subjects from the FBPP. The admixture mapping and family-based association analyses were adjusted for age, age2, sex, body-mass-index, and genome-wide mean ancestry to minimize the confounding due to population stratification. Regions that were suggestive of local ancestry association evidence were found on chromosomes 7 (LDL-C), 8 (HDL-C), 14 (triglycerides) and 19 (total cholesterol and triglycerides). In the fine-mapping analysis, 52,939 SNPs were tested and 11 SNPs (8 independent SNPs) showed nominal significant association with HDL-C (2 SNPs), LDL-C (4 SNPs) and triglycerides (5 SNPs). The family data was used in the fine-mapping to identify SNPs that showed novel associations with lipids and regions including genes with known associations for cardiovascular disease. Conclusions This study identified regions on chromosomes 7, 8, 14 and 19 and 11 SNPs from the fine-mapping analysis that were associated with HDL-C, LDL-C and triglycerides for further studies of cardiovascular disease in African-Americans. PMID:25552592

The cholesterol-lowering effect of coconut flakes in humans with moderately raised serum cholesterol.

PubMed

Trinidad, Trinidad P; Loyola, Anacleta S; Mallillin, Aida C; Valdez, Divinagracia H; Askali, Faridah C; Castillo, Joan C; Resaba, Rosario L; Masa, Dina B

2004-01-01

This study investigated the effect of coconut flakes on serum cholesterol levels of humans with moderately raised serum cholesterol in 21 subjects. The serum total cholesterol of subjects differed and ranged from 259 to 283 mg/dL. The study was conducted in a double-blind randomized crossover design on a 14-week period, consisting of four 2-week experimental periods, with each experimental period separated by a 2-week washout period. The test foods were as follows: corn flakes as the control food, oat bran flakes as the reference food, and corn flakes with 15% and 25% dietary fiber from coconut flakes (made from coconut flour production). Results showed a significant percent reduction in serum total and low-density lipoprotein (LDL) cholesterol (in mg/dL) for all test foods, except for corn flakes, as follows: oat bran flakes, 8.4 +/- 1.4 and 8.8 +/- 6.0, respectively; 15% coconut flakes, 6.9 +/- 1.1 and 11.0 +/- 4.0, respectively; and 25% coconut flakes, 10.8 +/- 1.3 and 9.2 +/- 5.4, respectively. Serum triglycerides were significantly reduced for all test foods: corn flakes, 14.5 +/- 6.3%; oat bran flakes, 22.7 +/- 2.9%; 15% coconut flakes, 19.3 +/- 5.7%; and 25% coconut flakes, 21.8 +/- 6.0%. Only 60% of the subjects were considered for serum triglycerides reduction (serum triglycerides >170 mg/dL). In conclusion, both 15% and 25% coconut flakes reduced serum total and LDL cholesterol and serum triglycerides of humans with moderately raised serum cholesterol levels. Coconut flour is a good source of both soluble and insoluble dietary fiber, and both types of fiber may have significant role in the reduction of the above lipid biomarker. To our knowledge, this is the first study conducted to show a relationship between dietary fiber from a coconut by-product and a lipid biomarker. Results from this study serves as a good basis in the development of coconut flakes/flour as a functional food, justifying the increased production of coconut and coconut by-products.

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

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

Protective effect of exercise and alpha tocopherol on atherosclerosis promotion in hypercholesterolemic domestic rabbits

NASA Astrophysics Data System (ADS)

Shekh, Mudhir S.; Mahmud, Almas M. R.

2017-09-01

This study was designed to determine effects of exercise training (Moderate and severe) and alpha tocopherol on lipid profiles and organ weights in hypercholesterolemic domestic rabbits. Hypercholesterolemia (HC) and atherosclerotic lesions were induced by feeding the male rabbits the standard chow supplemented with 1% cholesterol (atherogenic diet) for 36 days. Experimental rabbits were divided into seven groups: normal (T1), HC control (T2), HC plus alpha tocopherol (0.5mg /animal/day) (T3), HC plus moderate exercise 40 minutes/day (0.5km/day) 5 days/week (T4), HC plus severe exercise 40 minutes/day (1km/day) 5 days/week (T5), HC plus alpha tocopherol plus moderate exercise (T6) and HC plus alpha tocopherol plus severe exercise (T7). After the treatment period of 36th day, blood samples were collected and total cholesterol (TC), Triglyceride (TG), Very low-density lipoprotein (VLDL)-cholesterol, High-density lipoproteins (HDL)-cholesterol, Low-density lipoprotein (LDL)-cholesterol, serum glucose, body and organ weights were assayed and compared with hypercholesterolemic control. Combination of moderate exercise with alpha tocopherol produced significant reduction (P<0.01) in TG and high significant decrement (P<0.001), in VLDL-cholesterol, TC and LDL-cholesterol compared with hypercholesterolemic rabbits. Serum TC, LDL and VLDL (P<0.001) and TG (P<0.01) significantly increased when compared with normal rabbits diet, while, HDL decreased (P<0.05) significantly. Severe exercise group showed no significant change in all lipid profiles. However, the decrement in the above parameters was comparable with hypercholesterolemic rabbits in combination of severe exercise with alpha tocopherol. The results suggest that the combination of moderate exercise with alpha tocopherol can be exploited for prevention of atherosclerosis in hypercholesterolemic rabbits.

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

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

Traditional dietary pattern is associated with elevated cholesterol among the Inuit of Nunavik.

PubMed

Labonté, Marie-Ève; Dewailly, Eric; Lucas, Michel; Chateau-Degat, Marie-Ludivine; Couture, Patrick; Lamarche, Benoît

2014-08-01

Our cross-sectional study assessed the associations between dietary patterns and cardiovascular disease (CVD) risk factors among Nunavik Inuit. This study was conducted as part of the 2004 Nunavik Inuit Health Survey, which included the collection of clinical measurements, plasma samples, and diet information from a food frequency questionnaire. A sample of 666 Inuit aged 18 years and older was included in our analyses. Dietary patterns were generated by principal component analysis. Multivariate general linear models adjusting for sex, age, waist circumference, and other potential confounders were used to examine associations between dietary patterns and CVD risk factors. Four distinct patterns were identified, namely the traditional, Western, nutrient-poor food, and healthy patterns. The traditional pattern showed positive associations with plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein B100, LDL peak particle diameter, and oxidized LDL (all P values for trend≤0.04), but showed no association with the total cholesterol:high-density lipoprotein cholesterol ratio or with inflammatory biomarkers (all P values for trend ≥0.19). The nutrient-poor food pattern was positively associated with oxidized LDL (P=0.04), but inversely associated with high-sensitivity C-reactive protein (P<0.0001). The Western and healthy patterns showed no association with any CVD risk factor. Our data show that high adherence to a traditional pattern among Nunavik Inuit is not associated with important changes in CVD risk factors, with the exception of a slight elevation in cholesterol concentrations, most likely attributable to increased n-3 fatty acid intake. Dietary patterns reflecting the recent introduction of market foods in the Inuit diet appear to exert a trivial influence on CVD risk factors. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Three-dimensional cryoEM reconstruction of native LDL particles to 16Å resolution at physiological body temperature.

PubMed

Kumar, Vibhor; Butcher, Sarah J; Öörni, Katariina; Engelhardt, Peter; Heikkonen, Jukka; Kaski, Kimmo; Ala-Korpela, Mika; Kovanen, Petri T

2011-05-09

Low-density lipoprotein (LDL) particles, the major carriers of cholesterol in the human circulation, have a key role in cholesterol physiology and in the development of atherosclerosis. The most prominent structural components in LDL are the core-forming cholesteryl esters (CE) and the particle-encircling single copy of a huge, non-exchangeable protein, the apolipoprotein B-100 (apoB-100). The shape of native LDL particles and the conformation of native apoB-100 on the particles remain incompletely characterized at the physiological human body temperature (37 °C). To study native LDL particles, we applied cryo-electron microscopy to calculate 3D reconstructions of LDL particles in their hydrated state. Images of the particles vitrified at 6 °C and 37 °C resulted in reconstructions at ~16 Å resolution at both temperatures. 3D variance map analysis revealed rigid and flexible domains of lipids and apoB-100 at both temperatures. The reconstructions showed less variability at 6 °C than at 37 °C, which reflected increased order of the core CE molecules, rather than decreased mobility of the apoB-100. Compact molecular packing of the core and order in a lipid-binding domain of apoB-100 were observed at 6 °C, but not at 37 °C. At 37 °C we were able to highlight features in the LDL particles that are not clearly separable in 3D maps at 6 °C. Segmentation of apoB-100 density, fitting of lipovitellin X-ray structure, and antibody mapping, jointly revealed the approximate locations of the individual domains of apoB-100 on the surface of native LDL particles. Our study provides molecular background for further understanding of the link between structure and function of native LDL particles at physiological body temperature.

Beneficial effects of coconut water feeding on lipid metabolism in cholesterol-fed rats.

PubMed

Sandhya, V G; Rajamohan, T

2006-01-01

The purpose of this study was to determine the effect of coconut water feeding in cholesterol-fed rats. Male albino rats were fed tender coconut water and mature coconut water at a dose level of 4 mL/100 g of body weight. Cholesterol feeding caused a marked increase in total cholesterol, very low-density lipoprotein (VLDL) + low-density lipoprotein (LDL) cholesterol, and triglycerides in serum. Administration of coconut water counteracts the increase in total cholesterol, VLDL + LDL cholesterol, and triglycerides, while high-density lipoprotein cholesterol was higher. Lipid levels in the tissues viz. liver, heart, kidney, and aorta were markedly decreased in cholesterol-fed rats supplemented with coconut water. Feeding coconut water resulted in increased activities of 3-hydroxy-3-methylglutaryl-CoA reductase in liver, lipoprotein lipase in heart and adipose tissue, and plasma lecithin:cholesterol acyl transferase, while lipogenic enzymes showed decreased activities. An increased rate of cholesterol conversion to bile acid and an increased excretion of bile acids and neutral sterols were observed in rats fed coconut water. Histopathological studies of liver and aorta revealed much less fatty accumulation in these tissues in cholesterol-fed rats supplemented with coconut water. Feeding coconut water resulted in increased plasma L-arginine content, urinary nitrite level, and nitric oxide synthase activity. These results indicate that both tender and mature coconut water has beneficial effects on serum and tissue lipid parameters in rats fed cholesterol-containing diet.

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.

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.

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.

Effects of physical examination and diet consultation on serum cholesterol and health-behavior in the Korean pilots employed in commercial airline.

PubMed

Choi, Yun Young; Kim, Ki Youn

2013-01-01

An objective of this study is to search how physical examination and diet consultation can influence those risk factors of cardiovascular disease. The subjects were 326 pilots of the "B" airline company in Korea whose total cholesterol values were over 220 mg/dl on their regular physical examinations from April 2006 to December 2008. They were divided into two groups, one who had diet consultation (an intervention group) and a control group. The physical examination components used to each group were body mass index (BMI), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride (TG). The behavioral, anthropometric and biomedical measurements were collected at each visit. This study compares and investigates the changes of serum cholesterol and also the health-behavior at each physical examination. Within the intervention group significant improvements were observed for total cholesterol, BMI (body mass index) and HDL (high density lipoprotein). The normalizing rates for cholesterol level to decrease down to lower than 200 mg/dl were 17.7% in intervention group and 8.7% in control group, which is statistically significantly higher among the intervention group. The odds ratio of diet consultation was 2.80 (95% CI=1.35-5.79), which indicates that it is a significantly contributing factor to normalize the serum cholesterol value down to lower than 200 mg/dl. Based on result, it is recommended to have regular physical examination and intensive management with diet and exercise consultation.

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.

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.

Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice.

PubMed

Liu, Ting Ting; Zeng, Yi; Tang, Kun; Chen, XueMeng; Zhang, Wei; Xu, Xiao Le

2017-07-01

Dihydromyricetin, the most abundant flavonoid in Ampelopsis grossedentata, exerts numerous pharmacological activities, including anti-inflammatory, antioxidant, hepatoprotective, and lipid regulatory activities; however, its protective effect against atherosclerosis remains poorly understood. The aim of the present study was to evaluate the effects of dihydromyricetin on high fat diet (HFD)-induced atherosclerosis using LDL receptor deficient (LDLr -/- ) mice. Blood samples were collected for determination of serum lipid profiles, oxidized LDL (ox-LDL) and pro-inflammatory cytokines. Histology, hepatic lipid content, quantification of atherosclerosis, assessment of oxidative stress and inflammation were performed on liver and aorta samples by molecular biology methods. The effects of dihydromyricetin on ox-LDL-induced human umbilical vein endothelial cells (HUVECs) dysfunction and foam cell formation were further studied. (1) Dihydromyricetin ameliorated hyperlipidemia, reduced serum ox-LDL, IL-6 and TNF-α levels in HFD-fed LDLr -/- mice. Moreover, (2) dihydromyricetin suppressed hepatic lipid accumulation and increased protein expressions of PPARα, LXRα and ABCA1. (3) It inhibited atherosclerotic lesion formation and favoured features of plaque stability. (4) Dihydromyricetin prevented hepatic and aortic inflammation as evidenced by the reduced IL-6 and TNF-α mRNA expression; (5) it prevented hepatic and aortic oxidative stress by normalizing activities of antioxidant enzymes in the liver and suppressing reactive oxygen species generation and NOX2 protein expression in both liver and aorta; (6) it inhibited oxLDL-induced injury, monocytes adhesion and oxidative stress in HUVECs and (7) inhibited macrophage foam cell formation and enhanced cholesterol efflux. These findings suggest that dihydromyricetin could reduce atherosclerosis via its pleiotropic effects, including improvement of endothelial dysfunction, inhibition of macrophage foam cell formation

Association Between Baseline LDL-C Level and Total and Cardiovascular Mortality After LDL-C Lowering: A Systematic Review and Meta-analysis.

PubMed

Navarese, Eliano P; Robinson, Jennifer G; Kowalewski, Mariusz; Kolodziejczak, Michalina; Andreotti, Felicita; Bliden, Kevin; Tantry, Udaya; Kubica, Jacek; Raggi, Paolo; Gurbel, Paul A

2018-04-17

Effects on specific fatal and nonfatal end points appear to vary for low-density lipoprotein cholesterol (LDL-C)-lowering drug trials. To evaluate whether baseline LDL-C level is associated with total and cardiovascular mortality risk reductions. Electronic databases (Cochrane, MEDLINE, EMBASE, TCTMD, ClinicalTrials.gov, major congress proceedings) were searched through February 2, 2018, to identify randomized clinical trials of statins, ezetimibe, and PCSK9-inhibiting monoclonal antibodies. Two investigators abstracted data and appraised risks of bias. Intervention groups were categorized as "more intensive" (more potent pharmacologic intervention) or "less intensive" (less potent, placebo, or control group). The coprimary end points were total mortality and cardiovascular mortality. Random-effects meta-regression and meta-analyses evaluated associations between baseline LDL-C level and reductions in mortality end points and secondary end points including major adverse cardiac events (MACE). In 34 trials, 136 299 patients received more intensive and 133 989 received less intensive LDL-C lowering. All-cause mortality was lower for more vs less intensive therapy (7.08% vs 7.70%; rate ratio [RR], 0.92 [95% CI, 0.88 to 0.96]), but varied by baseline LDL-C level. Meta-regression showed more intensive LDL-C lowering was associated with greater reductions in all-cause mortality with higher baseline LDL-C levels (change in RRs per 40-mg/dL increase in baseline LDL-C, 0.91 [95% CI, 0.86 to 0.96]; P = .001; absolute risk difference [ARD], -1.05 incident cases per 1000 person-years [95% CI, -1.59 to -0.51]), but only when baseline LDL-C levels were 100 mg/dL or greater (P < .001 for interaction) in a meta-analysis. Cardiovascular mortality was lower for more vs less intensive therapy (3.48% vs 4.07%; RR, 0.84 [95% CI, 0.79 to 0.89]) but varied by baseline LDL-C level. Meta-regression showed more intensive LDL-C lowering was associated with a greater reduction in