Showing papers on "High-density lipoprotein published in 2006"
TL;DR: The evidence supports a dose-dependent beneficial effect of fish oil on serum triglycerides, particularly among people with more elevated levels, and fish oil consumption also modestly improves HDL cholesterol, increases LDL cholesterol levels, but does not appear to adversely affect glucose homeostasis.
723 citations
TL;DR: A preferential increase in circulating concentrations of HDL particles possessing normalized antiatherogenic activity is therefore a promising therapeutic strategy for the treatment of common metabolic diseases featuring dyslipidemia, inflammation, and premature atherosclerosis.
Abstract: High-density lipoproteins (HDL) possess key atheroprotective biological properties, including cellular cholesterol efflux capacity, and anti-oxidative and anti-inflammatory activities. Plasma HDL particles are highly heterogeneous in physicochemical properties, metabolism, and biological activity. Within the circulating HDL particle population, small, dense HDL particles display elevated cellular cholesterol efflux capacity, afford potent protection of atherogenic low-density lipoprotein against oxidative stress and attenuate inflammation. The antiatherogenic properties of HDL can, however be compromised in metabolic diseases associated with accelerated atherosclerosis. Indeed, metabolic syndrome and type 2 diabetes are characterized not only by elevated cardiovascular risk and by low HDL-cholesterol (HDL-C) levels but also by defective HDL function. Functional HDL deficiency is intimately associated with alterations in intravascular HDL metabolism and structure. Indeed, formation of HDL particles with attenuated antiatherogenic activity is mechanistically related to core lipid enrichment in triglycerides and cholesteryl ester depletion, altered apolipoprotein A-I (apoA-I) conformation, replacement of apoA-I by serum amyloid A, and covalent modification of HDL protein components by oxidation and glycation. Deficient HDL function and subnormal HDL-C levels may act synergistically to accelerate atherosclerosis in metabolic disease. Therapeutic normalization of attenuated antiatherogenic HDL function in terms of both particle number and quality of HDL particles is the target of innovative pharmacological approaches to HDL raising, including inhibition of cholesteryl ester transfer protein, enhanced lipidation of apoA-I with nicotinic acid and infusion of reconstituted HDL or apoA-I mimetics. A preferential increase in circulating concentrations of HDL particles possessing normalized antiatherogenic activity is therefore a promising therapeutic strategy for the treatment of common metabolic diseases featuring dyslipidemia, inflammation, and premature atherosclerosis.
691 citations
TL;DR: The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses, which are not reflected by conventional lipoprotein cholesterol measures, help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol.
Abstract: Background— Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease (CHD) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). We examined whether measurement of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle subclasses provides additional information relative to CHD risk reduction. Methods and Results— This is a prospective nested case-control study of 364 men with a new CHD event (nonfatal myocardial infarction or cardiac death) during a 5.1-year (median) follow-up and 697 age-matched controls. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo. Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models. Gemfibrozil treat...
547 citations
TL;DR: A critical role is established for intestinal ABCA1 in plasma HDL biogenesis in vivo and the data suggest that HDL derived from intestinalABCA1 is secreted directly into the circulation and that HDL in lymph is predominantly derived from the plasma compartment.
Abstract: Plasma HDL cholesterol levels are inversely related to risk for atherosclerosis. The ATP-binding cassette, subfamily A, member 1 (ABCA1) mediates the rate-controlling step in HDL particle formation, the assembly of free cholesterol and phospholipids with apoA-I. ABCA1 is expressed in many tissues; however, the physiological functions of ABCA1 in specific tissues and organs are still elusive. The liver is known to be the major source of plasma HDL, but it is likely that there are other important sites of HDL biogenesis. To assess the contribution of intestinal ABCA1 to plasma HDL levels in vivo, we generated mice that specifically lack ABCA1 in the intestine. Our results indicate that approximately 30% of the steady-state plasma HDL pool is contributed by intestinal ABCA1 in mice. In addition, our data suggest that HDL derived from intestinal ABCA1 is secreted directly into the circulation and that HDL in lymph is predominantly derived from the plasma compartment. These data establish a critical role for intestinal ABCA1 in plasma HDL biogenesis in vivo.
490 citations
TL;DR: The composite data suggest that via physical association with plasma lipoproteins, FIAF acts as a powerful signal from fat and other tissues to prevent fat storage and stimulate fat mobilization.
404 citations
TL;DR: In this article, the authors found that women with systemic lupus erythematosus (SLE) have a 7-50-fold increased risk of coronary artery disease (CAD).
Abstract: Objective
Women with systemic lupus erythematosus (SLE) have a 7–50-fold increased risk of coronary artery disease (CAD). In the general population, oxidized low-density lipoprotein (ox-LDL) increases the risk for CAD. Normal high-density lipoproteins (HDLs) protect LDL from oxidation; proinflammatory HDLs do not. This study was undertaken to determine whether patients with SLE, who have chronic inflammation that causes oxidative damage, have more proinflammatory HDL and higher levels of ox-LDL, thus predisposing them to atherosclerosis.
Methods
One hundred fifty-four women with SLE, 48 women with rheumatoid arthritis (RA), and 72 healthy controls were studied. The ability of the patients' HDL to prevent oxidation of normal LDL was measured. Values >1.0 (the value assigned for LDL oxidation in the absence of HDL) after the addition of HDL indicated proinflammatory HDL. Plasma ox-LDL levels were measured as the amount of oxidation produced by the patient's LDL after the removal of HDL.
Results
SLE patients had more proinflammatory HDL (mean ± SD score 1.02 ± 0.57, versus 0.68 ± 0.28 in controls [P 1.0 (P < 0.006 between all groups). Levels of ox-LDL correlated with levels of proinflammatory HDL (r = 0.37, P < 0.001). SLE patients with CAD had significantly higher proinflammatory HDL scores than patients without CAD (P < 0.001).
Conclusion
HDLs are proinflammatory in a significant proportion of SLE patients and are associated with elevated levels of ox-LDL. Abnormal HDLs impair the ability to prevent LDL oxidation and may predispose to atherosclerosis.
384 citations
Journal Article•
TL;DR: This study indicated that Ramadan fasting led to a decrease in glucose and weight, and it seems that the effect of Ramadan fasting on serum lipid levels may be closely related to the nutritional diet or biochemical response to starvation.
Abstract: Introduction Ramadan is the holiest month in the Islamic calendar and Muslims fast during this month. We designed this study to evaluate the effect of Ramadan fasting on plasma lipids and lipoproteins. Methods This cohort study was performed during Ramadan in December 2002 (Islamic year 1423). The subjects were 81 students of Tehran University of Medical Sciences. We evaluated weight, body mass index (BMI), glucose, triglyceride (TG), cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), and very low density lipoprotein (VLDL), before and after Ramadan. Results Body weight and BMI both decreased during Ramadan fasting in both genders. Glucose and HDL decreased and LDL increased significantly during fasting in Ramadan, but there was no significant change in total cholesterol, TG and VLDL. We did not find any association between TG, cholesterol, LDL, VLDL, HDL and the following variables: sex, body weight changes, and two or three instances of meals before Ramadan. Triglyceride level also increased in students with normal BMI while it decreased in overweight subjects. Conclusion This study indicated that Ramadan fasting led to a decrease in glucose and weight. Although there was a significant reduction in meal frequency, a significant increase in LDL and decrease in HDL was noted during Ramadan. It seems that the effect of Ramadan fasting on serum lipid levels may be closely related to the nutritional diet or biochemical response to starvation.
310 citations
TL;DR: It is suggested that non-HDL cholesterol level is a stronger predictor ofCHD risk than LDL cholesterol; that is, VLDL cholesterol may play a critical role in the development of CHD.
Abstract: To determine if non–high-density lipoprotein (HDL) cholesterol is a more useful predictor of coronary heart disease (CHD) risk than low-density lipoprotein (LDL) cholesterol and if very-low-density lipoprotein (VLDL) cholesterol is an independent predictor of CHD risk, data from the Framingham Heart Study (2,693 men, 3,101 women) were used for this analysis. All subjects were aged ≥30 years and free of CHD at baseline, and incident CHD was the end point (618 men, 372 women). Cox proportional-hazards models were used to assess the risk for CHD (relative risks and 95% confidence intervals) on the basis of the joint distribution of LDL cholesterol and non-HDL cholesterol (in milligrams per deciliter), as well as LDL cholesterol, non-HDL cholesterol, and VLDL cholesterol as continuous variables. After multivariate adjustment, within non-HDL cholesterol level, no association was found between LDL cholesterol and the risk for CHD, whereas within LDL cholesterol levels, a strong positive and graded association between non-HDL cholesterol and risk for CHD was observed. When the analysis was repeated within triglyceride levels (
271 citations
TL;DR: It is suggested that ABCG1 and ABCG4 act in concert with ABCA1 to maximize the removal of excess cholesterol from cells and to generate cholesterol-rich lipoprotein particles.
268 citations
TL;DR: It is found that plasma ANGPTL3 levels significantly correlated with plasma HDL cholesterol and HDL-PL levels in human subjects and post-heparin plasma in Angptl3-knockout mice had higher phospholipase activity than did that in wild-type mice, suggesting that the activity of endogenous EL is elevated in Angpton-deficient mice.
Abstract: Objectives— A low level of high-density lipoprotein (HDL) in plasma has been recognized as an aspect of metabolic syndrome and as a crucial risk factor of cardiovascular events However, the physiological regulation of plasma HDL levels has not been completely defined Current studies aim to reveal the contribution of angiopoietin-like protein3 (angptl3), previously known as a plasma suppressor of lipoprotein lipase, to HDL metabolism Methods and Results— Angptl3-deficient mice showed low plasma HDL cholesterol and HDL phospholipid (PL), and which were increased by ANGPTL3 supplementation via adenovirus In vitro, ANGPTL3 inhibited the phospholipase activity of endothelial lipase (EL), which hydrolyzes HDL-PL and hence decreases plasma HDL levels, through a putative heparin-binding site in the N-terminal domain of ANGPTL3 Post-heparin plasma in Angptl3-knockout mice had higher phospholipase activity than did that in wild-type mice, suggesting that the activity of endogenous EL is elevated in Angptl3-deficient mice Furthermore, we established an ELISA system for human ANGPTL3 and found that plasma ANGPTL3 levels significantly correlated with plasma HDL cholesterol and HDL-PL levels in human subjects Conclusions— Angptl3 acts as an inhibitor of EL and may be involved in the regulation of plasma HDL cholesterol and HDL-PL levels in humans and rodents
248 citations
TL;DR: It is suggested that SCD1 plays a pivotal role in the regulation of hepatic and plasma triglyceride accumulation, possibly by modulating the MUFA-to-SFA ratio.
Abstract: Stearoyl-coenzyme A desaturase (SCD) is the rate-limiting enzyme necessary for the biosynthesis of monounsaturated fatty acids. In this study, we investigated the regulation of mouse SCD1 by liver X receptor (LXR) and its role in plasma lipoprotein metabolism upon LXR activation. In vivo, the SCD1 gene remained induced upon LXR activation in the absence of sterol regulatory element-binding protein 1c (SREBP-1c), a known transcriptional regulator of SCD1. Serial deletion and point mutation analyses in reporter gene assays, as well as a gel mobility shift assay, identified an LXR response element in the mouse SCD1 promoter. In addition, SCD1 deficiency prevented the hypertriglyceridemic effect and reduced hepatic triglyceride accumulation associated with LXR activation despite induced hepatic expression of SREBP-1c protein and several SREBP1c and LXR target genes involved in lipoprotein metabolism. Unlike wild-type mice, SCD1-deficient mice failed to elevate the hepatic triglyceride monounsaturated acid (MUFA)/saturated fatty acid (SFA) ratio despite induction of the SCD2 gene. Together, these findings suggest that SCD1 plays a pivotal role in the regulation of hepatic and plasma triglyceride accumulation, possibly by modulating the MUFA-to-SFA ratio. In addition, SCD1 deficiency also increased plasma high-density lipoprotein cholesterol levels induced by LXR activation.
TL;DR: CETP expression in E3L mice shifts the distribution of cholesterol from HDL to VLDL/LDL, reduces plasma-mediated SR-BI–dependent cholesterol efflux, and represents a clear pro-atherogenic factor in E2L mice, which is a valuable model for the preclinical evaluation of HDL-raising interventions on atherosclerosis development.
Abstract: OBJECTIVE - The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still undergoing debate. Therefore, we evaluated the effect of human CETP expression on atherosclerosis in APOE*3-Leiden (E3L) mice with a humanized lipoprotein profile. METHODS AND RESULTS - E3L mice were crossbred with human CETP transgenic mice. On a chow diet, CETP expression increased plasma total cholesterol (TC) (+43%; P<0.05). To evaluate the effects of CETP on the development of atherosclerosis, mice were fed a Western-type diet containing 0.25% cholesterol, leading to 4.3-fold elevated TC levels in both E3L and CETP.E3L mice (P<0.01). On both diets, CETP expression shifted the distribution of cholesterol from high-density lipoprotein (HDL) toward very-low-density lipoprotein (VLDL)/low-density lipoprotein (LDL). Moreover, plasma of CETP.E3L mice had reduced capacity (-39%; P<0.05) to induce SR-BI-mediated cholesterol efflux from Fu5AH cells than plasma of E3L mice. After 19 weeks on the Western-type diet, CETP.E3L mice showed a 7.0-fold increased atherosclerotic lesion area in the aortic root compared with E3L mice (P<0.0001). CONCLUSIONS - CETP expression in E3L mice shifts the distribution of cholesterol from HDL to VLDL/LDL, reduces plasma-mediated SR-BI-dependent cholesterol efflux, and represents a clear pro-atherogenic factor in E3L mice. We anticipate that the CETP.E3L mouse will be a valuable model for the preclinical evaluation of HDL-raising interventions on atherosclerosis development. © 2006 American Heart Association, Inc. Chemicals / CAS: cholesterol, 57-88-5; Antigens, CD36; apolipoprotein E3 (Leidein); Apolipoprotein E3; Apolipoproteins E; Carrier Proteins; CETP protein, human; Cholesterol Ester Transfer Proteins; Cholesterol, 57-88-5; Glycoproteins; Lipids; Lipoproteins; Lipoproteins, HDL
TL;DR: A model in which PON1 acts as a lipolactonase to break down oxidized lipids and to generate LPC is proposed, which involves LPC release in an LPC dose-dependent manner.
TL;DR: Enhanced in vivo serum fat clearance, and the first demonstrated in vitro upregulation in human skeletal musclefat utilization and ABCA1 expression, suggests peripheral fat utilization and lipidation as potential mechanisms toward these HDL:TG effects.
Abstract: Objectives— Exercise increases fatty acid oxidation (FAO), improves serum high density lipoprotein cholesterol (HDLc) and triglycerides (TG), and upregulates skeletal muscle peroxisome proliferator activated receptor (PPAR)δ expression. In parallel, PPARδ agonist-upregulated FAO would induce fatty-acid uptake (via peripheral lipolysis), and influence HDLc and TG-rich lipoprotein particle metabolism, as suggested in preclinical models. Methods and Results— Healthy volunteers were allocated placebo (n=6) or PPARδ agonist (GW501516) at 2.5 mg (n=9) or 10 mg (n=9), orally, once-daily for 2 weeks while hospitalized and sedentary. Standard lipid/lipoproteins were measured and in vivo fat feeding studies were conducted. Human skeletal muscle cells were treated with GW501516 in vitro and evaluated for lipid-related gene expression and FAO. Serum TG trended downwards (P=0.08, 10 mg), whereas TG clearance post fat-feeding improved with drug (P=0.02). HDLc was enhanced in both treatment groups (2.5 mg P=0.004, 10 mg...
TL;DR: Findings indicate that HHcy inhibits reverse cholesterol transport by reducing circulating HDL via inhibiting apoA-I protein synthesis and enhancing HDL-C clearance.
Abstract: We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine β-synthase–/apolipoprotein E–deficient (CBS−/−/apoE−/−) mice. We observed that plasma homocysteine (Hcy) concentrations are negatively correlated with HDL-C and apolipoprotein A1 (apoA-I) in patients with CAD. We found the loss of large HDL particles, increased HDL-free cholesterol, and decreased HDL protein in CBS−/−/apoE−/− mice, and attenuated cholesterol efflux from cholesterol-loaded macrophages to plasma in CBS−/−/apoE−/− mice. ApoA-I protein was reduced in the plasma and liver, but hepatic apoA-I mRNA was unchanged in CBS−/−/apoE−/− mice. Moreover, Hcy (0.5 to 2 mmol/L) reduced the levels of apoA-I protein but not mRNA and inhibited apoA-1 protein synthesis in mouse primary hepatocytes. Further, plasma lecithin:cholesterol acyltransferase (LCAT) substrate reactivity was decreased, LCAT specific activity increased, and plasma LCAT protein levels unchanged in apoE−/−/CBS−/− mice. Finally, the clearance of plasma HDL cholesteryl ester, but not HDL protein, was faster in CBS−/−/apoE−/− mice, correlated with increased scavenger receptor B1, and unchanged ATP-binding cassette transporter A1 protein expression in the liver. These findings indicate that HHcy inhibits reverse cholesterol transport by reducing circulating HDL via inhibiting apoA-I protein synthesis and enhancing HDL-C clearance.
TL;DR: Overall, increased consumption of full-fat dairy products and naturally derived trans fatty acids did not cause significant changes in cardiovascular disease risk variables, as may be expected on the basis of current health recommendations.
TL;DR: The results suggest that hyperhomocysteinemia may increase risk of atherosclerosis by decreasing expression of ApoA-I and increasing expression of CYP7A1.
Abstract: Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by nutritional or genetic disturbances in homocysteine metabolism. A polymorphism in methylenetetrahydrofolate reductase (MTHFR) is the most common genetic cause of mild hyperhomocysteinemia. To examine mechanisms by which an elevation in plasma homocysteine leads to vascular disease, we first performed microarray analyses in livers of Mthfr-deficient mice and identified differentially expressed genes that are involved in lipid and cholesterol metabolism. Microarrays and RT-PCR showed decreased mRNA for apolipoprotein A (ApoA)-IV and for ApoA-I and increased mRNA for cholesterol 7alpha hydroxylase (Cyp7A1) in Mthfr(+/-) mice compared with Mthfr(+/+) mice. Western blotting revealed that ApoA-I protein levels in liver and plasma of Mthfr(+/-) mice were 52% and 62% of levels in the respective tissues of Mthfr(+/+) mice. We also performed Western analysis for plasma ApoA-I protein levels in 60 males with coronary artery disease and identified a significant (P<0.01) negative correlation (-0.33) between ApoA-I and plasma homocysteine levels. This cohort also displayed a negative correlation (-0.24, P=0.06) between high-density lipoprotein cholesterol and plasma homocysteine. Treatment of HepG2 cells with supraphysiological levels of 5 mmol/L homocysteine reduced peroxisome proliferator-activated receptor (PPAR) alpha and ApoA-I protein levels and decreased ApoA-I promoter activity. Transfection with a PPARalpha construct upregulated ApoA-I and MTHFR. Our results suggest that hyperhomocysteinemia may increase risk of atherosclerosis by decreasing expression of ApoA-I and increasing expression of CYP7A1.
TL;DR: It is demonstrated that PON2 plays a protective role in atherosclerosis, and Enhanced inflammatory properties of LDL, attenuated anti-atherogenic capacity of high density lipoprotein, and a heightened state of oxidative stress coupled with an exacerbated inflammatory response from Pon2-deficient macrophages appear to be the main mechanisms behind the larger atherosclerotic lesions in PON1- deficient mice.
Journal Article•
TL;DR: The retina is capable of rapid uptake of circulating LDL via an LDLR-mediated process primarily occurring in the RPE and also possibly Müller cells and the results suggest that blood-borne LDL represents a significant contributor to the steady-state levels of cholesterol and possibly other lipids in the retina.
Abstract: Purpose In this study we examined the uptake of circulating lipoproteins into the retina, using a naturally fluorescent cholesterol analog for imaging and deuterated cholesterol for quantification by mass spectroscopy. The purpose of this study was to better understand cholesterol uptake, transport and homeostasis in the retina. Methods Human low density lipoprotein (LDL) and high density lipoprotein (HDL) were labeled with the fluorescent cholesterol analog cholesta-5,7,9(11)-trien-3beta-ol (CTL) and deuterated cholesterol (25,26,26,26,27,27,27-[2H]cholesterol, D7Ch). Rats were injected intravenously with CTL-LDL, CTL-HDL and D7Ch-LDL. Fluorescent confocal microscopy was used to image the uptake of CTL and mass spectroscopy was used to quantify D7Ch. Immunohistochemistry and fluorescent confocal microscopy were used to localize apoB (an LDL marker protein) and LDL receptor (LDLR) protein in rat and monkey retinas. Results CTL-specific fluorescence was imaged by confocal microscopy in the retinal pigment epithelium (RPE), choriocapillaris and parts of the neural retina within 2 h post-injection and was visualized in the photoreceptor outer segments by 4 h. Replacing LDL with HDL as the CTL carrier gave a less robust and more delayed labeling of retinal layers. Human apolipoprotein B (apoB) was also localized in the rat choriocapillaris and RPE by 4 h post-injection. Human apoB was detected by immunoblot analysis in the rat retina primarily as a about 70 kDa protein, suggesting proteolytic degradation. LDL-mediated uptake of cholesterol was quantified by mass spectroscopy using deuterated cholesterol in place of CTL. In addition, apoB and LDLR were localized in monkey retina by immunohistochemistry. Conclusions The retina is capable of rapid uptake of circulating LDL via an LDLR-mediated process primarily occurring in the RPE and also possibly Muller cells. Despite the dominance of HDL over LDL in rat serum, LDL appears to be the preferred carrier for cholesterol transport to and uptake by the retina. The results also suggest that blood-borne LDL represents a significant contributor to the steady-state levels of cholesterol and possibly other lipids in the retina.
TL;DR: This meta-analysis of 23 trials strongly supports the notion that the sum of percent reduction in low- density lipoprotein-C plus percent increase in high-density lipop Protein-C predicts benefits much more effectively than either lipop protein component.
Abstract: Purpose of reviewOur analysis presents an alternative hypothesis to the prevailing view that low-density lipoprotein-C is the only important target of lipid therapyRecent findingsTwo recently published studies showed surprising results In the Armed Forces Regression Study, low-density lipoprotein-
TL;DR: Lactobacillus fermentum did not appear to produce a major change in serum lipid fractions, but a small effect cannot be excluded, and there were no significant changes over time or between treatments in total cholesterol, high density lipoprotein cholesterol or triglycerides.
Abstract: Background and Aims There is increasing interest in the use of natural therapies to reduce elevated low density lipoprotein (LDL) cholesterol. This study assessed the effects of PCC ® Lactobacillus fermentum on LDL cholesterol and other lipid fractions. Methods and results This was a single centre, double blind, placebo-controlled, parallel design trial in volunteers having total cholesterol ≥4mmol/L. Subjects ( n =46) were randomised to receive either Lactobacillus fermentum 2 capsules twice daily (each capsule containing 2×10 9 colony forming units) or matching placebo for a period of 10weeks. Main outcome measures were percentage changes in LDL cholesterol and other lipids, changes in liver enzymes and other safety tests. Two subjects withdrew early in the study, 1 for personal reasons and 1 because of bowel discomfort. Three other subjects experienced some bowel discomfort but still completed the study. LDL cholesterol showed a modest downward trend on both Lactobacillus fermentum and placebo of 7.0% and 5.2% respectively. This trend did not reach statistical significance over time, nor was there a significant difference between the treatment arms. There were no significant changes over time or between treatments noted in total cholesterol, high density lipoprotein cholesterol or triglycerides. There were no significant changes in liver enzymes or other safety parameters with time or between treatments. Conclusion Lactobacillus fermentum did not appear to produce a major change in serum lipid fractions, but a small effect cannot be excluded.
TL;DR: An influence of obstructive sleep apnoea and its therapy on high-density lipoprotein cholesterol levels is demonstrated, independent of age, sex, body mass index, diabetes and lipid lowering medication.
Abstract: Recent studies suggest an association of obstructive sleep apnoea (OSA) with cardiovascular risk factors, such as dyslipidaemia. The present study analyses the effects of OSA and its therapy on serum lipid concentrations in 470 OSA patients in a single centre study. Multivariate regression showed a significant association between the apnoea-hypopnoea index and high-density lipoprotein cholesterol (HDL-C) serum levels (n = 366), independent of age, sex, body mass index, diabetes and lipid lowering medication. There were no independent associations with total cholesterol, triglyceride and low-density lipoprotein cholesterol serum levels. During follow-up (6 months) with effective bilevel or continuous positive airway pressure therapy in 127 patients (lipoproteins: n = 86) without change in their lipid lowering therapy, the mean HDL-C serum level increased significantly by 5.8% from 46.9+/-15.8 to 49.6+/-15.3 mg x dL(-1) (mean+/-SD). An independent relationship was found between the change of apnoea-hypopnoea index and the change of high-density lipoprotein cholesterol or triglycerides, respectively. All patients with abnormal serum lipid/lipoprotein levels improved significantly under bilevel or continuous positive airway pressure therapy. This study demonstrates an influence of obstructive sleep apnoea and its therapy on high-density lipoprotein cholesterol levels.
TL;DR: Although ALA supplementation may cause small decreases in fibrinogen concentrations and fasting plasma glucose, most cardiovascular risk markers do not appear to be affected.
Abstract: OBJECTIVE: To determine whether dietary supplementation with alpha linolenic acid (ALA) can modify established and emerging cardiovascular risk markers. DESIGN: Systematic review and meta-analysis of randomised controlled trials identified by a search of Medline, Embase, Cochrane Controlled Trials Register (CENTRAL), and the metaRegister of Controlled Trials (mRCT). PATIENTS: All human studies were reviewed. MAIN OUTCOME MEASURES: Changes in concentrations of total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, triglyceride, fibrinogen, and fasting plasma glucose, and changes in body mass index, weight, and systolic and diastolic blood pressure. RESULTS: 14 studies with minimum treatment duration of four weeks were reviewed. ALA had a significant effect on three of the 32 outcomes examined in these studies. Concentrations of fibrinogen (0.17 micromol/l, 95% confidence interval (CI) -0.30 to -0.04, p = 0.01) and fasting plasma glucose (0.20 mmol/l, 95% CI -0.30 to -0.10, p < 0.01) were reduced. There was a small but clinically unimportant decrease in HDL (0.01 mmol/l, 95% CI -0.02 to 0.00, p < 0.01). Treatment with ALA did not significantly modify total cholesterol, triglycerides, weight, body mass index, LDL, diastolic blood pressure, systolic blood pressure, VLDL, and apolipoprotein B. CONCLUSIONS: Although ALA supplementation may cause small decreases in fibrinogen concentrations and fasting plasma glucose, most cardiovascular risk markers do not appear to be affected. Further trials are needed, but dietary supplementation with ALA to reduce cardiovascular disease cannot be recommended.
TL;DR: Torcetrapib resulted in substantial dose-dependent elevations in HDL-C, accompanied by moderate decreases in LDL-C at the higher doses, and was generally well tolerated.
TL;DR: Evidence that HDL retroendocytosis represents one of the pathways for cholesterol efflux is presented, as well as three physiologically relevant cell systems, including the liver cell line HepG2, the adrenal cell line Y1BS1, and phorbol myristate acetate-differentiated THP-1 cells as a model for macrophages.
TL;DR: A common CETP promoter polymorphism, which beneficially contributes to higher HDL cholesterol, is paradoxically associated with increased incidence of coronary disease in the general population and may affect coronary risk apart from the level of HDL cholesterol.
Abstract: Background: Several cholesteryl ester transfer protein (CETP) polymorphisms affect high-density lipoprotein (HDL) cholesterol, but the impact of CETP gene variants on incident coronary disease in the general population is uncertain after correction for their effect on HDL cholesterol. Design: We determined relationships between the CETP −629C→A promoter (n = 8141), the TaqIB (n = 8289), and the I405V (n = 8265) polymorphisms, serum lipids, C-reactive protein, and clinical factors with incident coronary heart disease (defined as death from or hospitalization for myocardial infarction, ischemic heart disease, or coronary intervention) during a median of 4.94 yr follow-up. Subjects: A predominantly Caucasian general population was studied. Results: HDL cholesterol was 0.08 mmol/liter higher in −629A carriers than in −629CC homozygotes (P < 0.001). The unadjusted coronary hazard was 1.26 [95% confidence interval (CI), 0.95–1.68; P = 0.11] in A carriers compared with CC homozygotes and increased to 1.46 (95% C...
Journal Article•
TL;DR: Nondiabetic patients with SLE have evidence of significant decrease in sensitivity to insulin, and overall this population has a high prevalence of the metabolic syndrome (18%).
Abstract: OBJECTIVE: Women with systemic lupus erythematosus (SLE) have increased risk of coronary heart disease (CHD) that is not fully explained by the classic CHD risk factors. Insulin resistance is an established risk factor for CHD in the general population. We compared insulin secretion and sensitivity in patients with SLE and healthy controls, and assessed the prevalence of the metabolic syndrome in women with SLE and its relation to circulating oxidized low density lipoprotein (ox-LDL). METHODS: Fasting insulin, glucose, and lipid profiles were measured in nondiabetic women with SLE (>or= 4 revised 1997 criteria) not undergoing antimalarial therapy (n = 44), and in age matched controls recruited from the hospital staff and the local community (n = 45). Using the Homeostatic Model Assessment equations, insulin sensitivity (HOMA-S) and pancreatic beta cell function (HOMA-B) were calculated from fasting insulin and glucose. The metabolic syndrome, defined according to the Adult Treatment Panel (ATP III) criteria, was determined in a consecutive series of 61 women with SLE. RESULTS: Patients with SLE had significantly higher fasting insulin [median (range) 10 (2.8-38) vs 6.6 (3.1-26) mU/l; p < 0.01], higher pancreatic beta cell function (HOMA-B) [165 (54-1567) vs 111 (28-653); p < 0.01], and lower insulin sensitivity (HOMA-S) [0.46 (0.09-1.9) vs 0.73 (0.16-1.3); p < 0.01]. SLE patients also had significantly higher triglycerides (p < 0.01) and lower high density lipoprotein cholesterol (p < 0.01) than controls. HOMA-S did not correlate with disease activity or steroid therapy, but was associated with components of the insulin resistance syndrome. HOMA-S showed a significant negative correlation with levels of ox-LDL in patients, but not in controls. Eleven (18%) patients had the metabolic syndrome. Again, this was not related to current steroid therapy. SLE patients with the metabolic syndrome had no difference in LDL, but had significantly higher levels of ox-LDL. CONCLUSION: Nondiabetic patients with SLE have evidence of significant decrease in sensitivity to insulin, and overall this population has a high prevalence of the metabolic syndrome (18%). Insulin resistance in the context of SLE was not strongly related to current or recent steroid therapy; it was, however, associated with higher levels of ox-LDL. Insulin resistance may therefore represent an additional CHD risk factor in patients with SLE.
Journal Article•
TL;DR: Anti-TNF-a treatment in patients with chronic inflammatory arthritides induces a modest, but sustained, increase in serum HDL-C levels, which may have a favorable effect in reducing the cardiovascular risk in these patients.
Abstract: OBJECTIVE: Tumor necrosis factor-a (TNF-a) is a key cytokine in the pathogenesis of chronic inflammatory arthritides, has proatherogenic effects, and may be positively correlated with impairment of the action of insulin. Patients with chronic inflammatory arthritides have an increased risk for cardiovascular diseases. We assessed whether anti-TNF-a treatment modifies the unfavorable lipid profile induced by chronic inflammatory arthritides. METHODS: Sixty patients (24 with rheumatoid arthritis, 26 ankylosing spondylitis, and 10 psoriatic arthritis) receiving infliximab because of ongoing disease activity despite disease modifying drugs (DMARD) were prospectively studied for 6 months. Lipid profile, total cholesterol/high density lipoprotein cholesterol (TC/HDL-C), and low density lipoprotein cholesterol (LDL-C)/HDL-C ratios, as well as disease activity indices (DAS28 and BASDAI), were assessed. RESULTS: A sustained increase of serum HDL-C was observed [mean increase (95% CI)] 5 (3-7) mg/dl, 3.5 (1-6) mg/dl, and 3 (1-5) mg/dl at 1, 3, and 6 months, respectively (p 130 mg/dl, LDL-C/HDL-C decreased (p < 0.05) during the whole study period and TC/HDL-C decreased (p < 0.05) at 1 and 3 months. CONCLUSION: Anti-TNF-a treatment in patients with chronic inflammatory arthritides induces a modest, but sustained, increase in serum HDL-C levels, which may have a favorable effect in reducing the cardiovascular risk in these patients.
TL;DR: This work states that high‐quality methods for lipoprotein characterization are warranted in studies on various metabolic diseases and should be considered for use in clinical trials.
Abstract: Background High-quality methods for lipoprotein characterization are warranted in studies on various metabolic diseases. Materials and methods An automated system for size-exclusion chromatography (SEC) of lipoproteins using commercially available components is described. Cholesterol or triglyceride content in separated lipoproteins from plasma and interstitial fluid (IF) was continuously determined on-line using microlitre sample volumes. Results The lipoprotein assay showed a good concordance with the classic ultra-centrifugation/ precipitation technique using fresh or frozen samples. Determination of lipoproteins in IF obtained from vacuum-induced skin blisters from 18 healthy subjects revealed that very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels were 18%, 19% and 25%, respectively, of concomitant plasma concentrations. The size-exclusion chromatography (SEC) system also allows for triglyceride determination on-line and it could be shown that the system is advantageous for an accurate determination of triglycerides in conditions when there are high levels of glycerol, e.g. in mice and in patients with hyperglycerolaemia (pseudo-hypertriglyceridaemia). Conclusions The described system should be of value in studies where detailed lipoprotein analysis is warranted and particularly when significant sample series with small volumes are available. Our data also suggest that there is a 4‐5·5-fold concentration gradient between plasma and IF for the three major plasma lipoproteins.
TL;DR: Oxidation of HDL by myeloperoxidase may represent a specific molecular mechanism for converting the cardioprotective lipoprotein into a dysfunctional form, raising the possibility that the enzyme represents a potential therapeutic target for preventing vascular disease in humans.
Abstract: Purpose of reviewEvidence indicates that high density lipoprotein (HDL) is cardioprotective and that several mechanisms are involved. One important pathway is a membrane-associated ATP-binding cassette transporter, ABCA1, that clears cholesterol from macrophage foam cells. Anti-inflammatory and anti