Plasma High-density Lipoprotein Cholesterol Concentrations Research Articles

Genetic Polymorphisms of Tumor Necrosis Factor-Alpha Modify the Association between Dietary Polyunsaturated Fatty Acids and Plasma High-Density Lipoprotein-Cholesterol Concentrations in a Population of Young Adults

Background/Aims: Genetic polymorphisms in tumor necrosis factor-α (TNF-α) modify the association between polyunsaturated fatty acids (PUFA) and plasma high-density lipoprotein (HDL) cholesterol in a population with type 2 diabetes. The objective of this study was to determine whether this gene × diet interaction is observed in a diabetes-free population and whether it is due to n–3 or n–6 PUFA. Methods: Subjects (n = 595) were aged 20–29 years and genotyped for the TNF-α –238G>A and TNF-α –308G>A polymorphisms. Diet was assessed using a food frequency questionnaire. Subjects were grouped as having no minor A allele at both the –238 and –308 positions (0/0), or one minor A allele at either the –238 (1/0) or the –308 (0/1) position. Results: TNF-α genotypes modified the association between dietary PUFA and HDL-cholesterol concentrations (p = 0.04 for interaction). Among individuals with the 0/0 genotype, total PUFA was positively associated with HDL-cholesterol in both men (p = 0.008) and women (p = 0.03), and for both n–6 (p = 0.004) and n–3 (p = 0.04) PUFA. However, an inverse relationship was observed among men carrying the 1/0 genotype (p = 0.005). Conclusion: These findings demonstrate that TNF-α genotypes modify the association between dietary PUFA and HDL-cholesterol and provide further evidence that inflammation is involved in the reverse cholesterol transport.

Effects of a ferment soy product on the adipocyte area reduction and dyslipidemia control in hypercholesterolemic adult male rats

BackgroundAvailable data on the effects of a fermented soy product enriched with Enterococcus faecium and Lactobacillus Jugurti on circulating lipids and adiposity are not completely settled. This study aimed to observe the effects of a fermented soy product enriched with Enterococcus faecium and Lactobacillus Jugurti on central obesity and dyslipidemia control in Wistar adult male rats.MethodsOver a period of 8 weeks, animals had "ad libitum" food intake and water consumption as well as body weight and food consumption was monitored. The animals were assigned to four different experimental groups: Control Group (C); Control + Fermented Product Group (CPF); Hypercholesterolemic diet group (H); and Hypercholesterolemic + Fermented Product Group (HPF). The HPF and CPF groups received an intragastric administration of 1 ml of fermented product daily. After the experimental period the animals were killed by decapitation, blood was collected to measure cholesterol, triglycerides and HDL-cholesterol plasma concentration. Adipocyte circumference, lipolysis and lipogenis rates were measures using epididymal and retroperitoneal white adipose tissues.ResultsThe results demonstrated that 1 ml/day/rat of the fermented soy product promoted important benefits such as reduced cholesterolemia in hypercholesterolemic diet group and the adipocyte circumference in both control and hypercholesterolemic diet group.ConclusionThe fermented soy product enriched with Enterococcus faecium and Lactobacillus Jugurti decreased circulating lipids levels and reduced adipocyte area in rats.

Therapies to Increase ApoA-I and HDL-Cholesterol Levels

Cholesterol is transported around the body in the form of lipoprotein (lipid/protein) complexes, because it is almost insoluble in water. High-density lipoprotein (HDL) particles transport cholesterol from tissues back to the liver for excretion. Epidemiological studies have shown an inverse relationship between blood levels of HDL-cholesterol (HDL-c) and the incidence of clinically significant atherosclerosis. The beneficial effects of HDL in altering atherosclerotic disease are believed to involve elevated levels of HDL enhancing the efflux of cholesterol from arterial walls, increasing transport of cholesterol from arteries to the liver for excretion. This reverse cholesterol transport (RCT) pathway is used to explain both HDL’s role in lipid metabolism and the inverse association between HDL-c plasma concentration and the risk of cardiovascular disease. Based on the RCT model, ApoA-I is an attractive target for therapeutic intervention. Experimental manipulations to increase production of ApoA-I have been associated with reduced atherogenicity. There is a continuing need for novel therapies that increase the biosynthesis of HDL, to inhibit the progression of and even bring about regression of atherosclerosis. Small molecule compounds that increase the production of endogenous ApoA-I would be attractive therapeutic agents for treating dyslipidemias.

Cholesterol-Lowering and Antioxidant Status-Improving Efficacy of Germinated Giant Embryonic Rice (Oryza sativa L.) in High Cholesterol-Fed Rats

Background/Aims: The purpose of the current study is to investigate the influence of germinated giant embryonic rice consumption on the lipid metabolism and antioxidant system in rats fed a high-cholesterol diet. Methods: Four groups of rats were given a diet containing 1 g cholesterol/kg for 5 weeks. The control group only received a high-cholesterol diet, while the other 3 experimental groups received each of the diets made of germinated giant embryonic rice, giant embryonic rice, or conventional brown rice (hereafter referred to as GGE-D, GE-D, and BR-D, respectively). Plasma and hepatic lipid profiles were measured, and the antioxidant status of liver was examined. Results: The plasma HDL-cholesterol concentration was significantly higher in rats fed GGE-D compared with the source material (GE-D) or BR-D, while there were no differences in the plasma total cholesterol and triglyceride concentrations between the groups. Consequently, the atherogenic indices of the GGE-D and GE-D groups were significantly lower than for the other groups. The plasma and hepatic thiobarbituric acid-reactive substance levels were higher in rats in the order of those fed BR-D > GE-D > GGE-D. While superoxide dismutase and catalase were significantly activated in rats fed both GGE-D and GE-D, glutathione peroxidase was significantly and most effectively activated in those fed GGE-D. Conclusions: The current results indicate that consumption of germinated giant embryonic rice is effective in lowering atherosclerosis cardiovascular disease risk.

Effects of Solid-State Fermented Rice on Lipid Metabolism and Antioxidant Status in High-Cholesterol-Fed Rats

We investigated the effect of solid-state fermented rice cultured with Basidiomycota (sangwhang) and Monascus ruber on lipid metabolism and antioxidant activity. Forty 4-week-old male Sprague-Dawley rats were fed high cholesterol diets in which carbohydrate sources in the treatment groups consisted of non-fermented rice and sangwhang or M. ruber rice at 80% and 20%, respectively, for 5 weeks. Supplementation with sangwhang and M. ruber rice had no effect on growth and food intakes in high-cholesterol-fed rats. The plasma triglyceride concentration was not significantly different among the groups. Supplementation with M. ruber rice resulted in lower plasma and hepatic cholesterol concentrations and atherogenic index compared to the control group, while the plasma high-density lipoprotein-cholesterol concentration was elevated. In addition, fermented rice cultured with M. ruber-supplemented animals had greater bile acid excretion. The M. ruber groups had significantly lower plasma and hepatic levels of thiobarbituric acid-reactive substances than the control group. Moreover, hepatic antioxidant enzyme activities, including catalase and superoxide dismutase, were significantly higher in the M. ruber group. In conclusion, fermented rice, especially M. ruber rice, was very effective for improving the lipid metabolism and reducing oxidative stress by up-regulating the hepatic antioxidant enzymes in high-cholesterol-fed rats.

Isoflavone Glycitein Diminished Plasma Cholesterol in Female Golden Syrian Hamsters

The soybean isoflavones, daidzein, genistein, and glycitein, were hypothesized to act as cholesterol-lowering components, separate from soy protein. Pure synthetic daidzein, genistein, or glycitein (0.9 mmol/kg diet) or a casein-based control diet was fed to groups of 10 female Golden Syrian hamsters for 4 weeks. Hamsters fed glycitein had significantly lower plasma total (by 15%) and non-HDL (by 24%) cholesterol compared with those fed casein (P<0.05). Daidzein and genistein's effects on these lipids did not differ from the effects of either casein or glycitein. Plasma HDL cholesterol and triglyceride concentrations were not significantly affected by dietary treatments. The percentage of urinary recovery of the ingested dose of each isoflavone was glycitein>daidzein>genistein (33.2%, 4.6%, 2.2%, respectively), with the apparent absorption of glycitein significantly greater than that of the other isoflavones. These data suggest that glycitein's greater cholesterol-lowering effect was due to its greater bioavailability, as reflected in its urinary recovery compared with that of the other isoflavones.

Dose-Dependent Regulation of High-Density Lipoprotein Metabolism with Rosuvastatin in the Metabolic Syndrome

Low plasma concentration of high-density lipoprotein (HDL) cholesterol is a risk factor for cardiovascular disease and a feature of the metabolic syndrome. Rosuvastatin has been shown to increase HDL cholesterol concentration, but the mechanisms remain unclear. Twelve men with the metabolic syndrome were studied in a randomized, double-blind, crossover trial of 5-wk therapeutic periods with placebo, 10 mg/d rosuvastatin, or 40 mg/d rosuvastatin, with 2-wk placebo washout between each period. Compared with placebo, there was a significant dose-dependent increase in HDL cholesterol, HDL particle size, and concentration of HDL particles that contain apolipoprotein A-I (LpA-I). The increase in LpA-I concentration was associated with significant dose-dependent reductions in triglyceride concentration and LpA-I fractional catabolic rate, with no changes in LpA-I production rate. There was a significant dose-dependent reduction in the fractional catabolic rate of HDL particles containing both apolipoprotein A-I and A-II (LpA-I:A-II), with concomitant reduction in LpA-I:A-II production rate, and hence no change in LpA-I:A-II concentration. Rosuvastatin dose-dependently increased plasma HDL cholesterol and LpA-I concentrations in the metabolic syndrome. This could relate to reduction in plasma triglycerides with remodeling of HDL particles and reduction in LpA-I fractional catabolism. The findings contribute to understanding mechanisms for the HDL-raising effect of rosuvastatin in the metabolic syndrome with implications for reduction in cardiovascular disease.

Dietary carbohydrates, glycemic load and serum high-density lipoprotein cholesterol concentrations among South Indian adults

To examine the relationship between dietary carbohydrates, glycemic load and high-density lipoprotein cholesterol (HDL-C) concentrations in Asian Indians, a high-risk group for diabetes and premature coronary artery disease. The study population comprised of 2043 individuals aged >/=20 years randomly selected from Chennai Urban Rural Epidemiological Study (CURES), an ongoing population-based study on a representative population of Chennai (formerly Madras) city in southern India. Participants with self-reported history of diabetes or heart disease or on drug therapy for dyslipidemia were excluded from the study. Dietary carbohydrates, glycemic index and glycemic load were assessed using a validated interviewer administered semiquantitative Food Frequency Questionnaire (FFQ). Both dietary glycemic load (P<0.0001) and total dietary carbohydrate intake (P<0.001) were significantly associated with higher serum triglyceride levels and lower serum HDL-C levels. For the lowest to highest quintile of glycemic load, the multivariate-adjusted mean HDL-C values were 44.1 mg per 100 ml and 41.2 mg per 100 ml (6.6% difference, P for trend<0.001), while for total carbohydrate it was less (5% difference, P for trend=0.016). The pattern of decrease in HDL-C for the lowest to highest quintile of glycemic load was more pronounced among men (1st vs 5th quintile: adjusted HDL-C: 4.3 mg per 100 ml decrease (10.3%)) than women (1st vs 5th quintile: adjusted HDL-C: 3.2 mg per 100 ml decrease (6.9%)). Our findings indicate that both total carbohydrates and dietary glycemic load intake are inversely associated with plasma HDL-C concentrations among Asian Indians, with dietary glycemic load having a stronger association.

Interaction between dietary fat intake and the cholesterol ester transfer protein TaqIB polymorphism in relation to HDL-cholesterol concentrations among US diabetic men

Background: A low plasma HDL-cholesterol concentration is a major characteristic of diabetic dyslipidemia. HDL concentrations are determined by both environmental factors and genetic factors. Cholesterol ester transfer protein (CETP) plays an important role in the regulation of HDL metabolism, and the TaqIB polymorphism of the CETP gene has been associated with elevated HDL concentrations.Objective: We examined the association between the CETP TaqIB polymorphism and plasma HDL concentrations and evaluated whether this association was modified by dietary fat intake.Design: We followed 780 diabetic men aged 40–75 y who participated in the Health Professionals Follow-Up Study since its initiation in 1986. The participants had confirmed type 2 diabetes and were free of cardiovascular disease at the time blood was drawn.Results: After adjustment for age, smoking, alcohol consumption, fasting status, hemoglobin A1c, physical activity, total energy intake, and body mass index, HDL concentrations were significantly higher in men with the B2B2 or B1B2 genotype than in those with the B1B1 genotype (adjusted x̄ ± SE: 37.9 ± 0.02, 40.3 ± 0.01, and 42.6 ± 0.02 mg/dL for B1B1, B1B2, and B2B2, respectively; P for trend = 0.0004). This inverse association of the B1 allele with plasma HDL concentrations existed for those with a high consumption of animal fat (P for interaction = 0.02), saturated fat (P for interaction = 0.02), and monounsaturated fat (P for interaction = 0.04).Conclusion: These data confirmed a significant effect of the CETP Taq1 gene on HDL concentrations and suggested a potential interaction between the CETP TaqIB polymorphism and intake of dietary fat on plasma HDL concentration.

Abstract 828: Adiponectin Enhanced ApoA-1- and HDL- mediated Cellular Cholesterol Efflux from Human Monocyte-Derived Macrophages

(Background) Plasma HDL-cholesterol levels are inversely correlated to the risk of CAD. HDL plays a crucial role as a shuttle carrying cholesterol derived from peripheral tissues and transporting it back to the liver. Recently, ATP-binding cassette transporters (ABCA1, ABCG1) have been identified as important membrane receptors to generate HDL by removing cholesterol and phospholipids from macrophage foam cells in the arterial wall. On the other hand, adiponectin (APN) abundantly secreted from adipocytes is one of the important molecules to inhibit the development of atherosclerosis. Epidemiological studies have revealed a positive correlation between plasma HDL-cholesterol and APN concentrations in humans, and APN levels are decreased in patients with CAD. In the current study, we investigated the role of APN on cellular cholesterol efflux from human macrophages. (Methods) Recombinant human APN was prepared. Human monocyte-derived macrophages were isolated from whole blood of healthy volunteers and incubated with RPMI-1640 medium containing 10% type AB serum. After 7 days incubation, the indicated concentrations of recombinant APN were added to the medium containing 0.1% BSA and incubated for 24 hours. The expression of ABCA1 and ABCG1 was measured by real-time quantitative PCR and western blot analyses. Cholesterol efflux from macrophages, previously incubated with [ 3 H]-labeled acetylated LDL, was measured with or without APN and expressed by a percentage of radioactivity of the medium to total radioactivity (cells plus medium). APN was added into the medium containing 0.1% BSA and apoA-1 (10 μg/ml) or HDL (50 μg/ml HDL protein) and incubated for 24 hours. (Results) APN significantly up-regulated the mRNA and protein levels of ABCA1 in human macrophages by 3.6- and 2-fold, respectively. ApoA-1-mediated cholesterol efflux from macrophages was 8.1-fold-increased by APN treatment. Furthermore, the expression of ABCG1 was also significantly increased by APN. HDL-mediated cholesterol efflux was slightly increasd by APN. (Conclusions) In conclusion, APN might act as a protective factor against atherosclerosis by increasing cholesterol efflux from human macrophages in both ABCA1- and ABCG1-dependent pathways.

Sources Of Variability Of Plasma HDL-Cholesterol Levels

Epidemiological data from the Framingham and other prospective studies suggests an inverse correlation between the plasma concentration of HDL-cholesterol (HDL-C) and the incidence of cardiovascular disease. The relationship between HDL-C and its vascular-protective effects is particularly due to the heterogeneity of these particles and their important role in reverse cholesterol transport. It is well-known that many different factors are involved in metabolic regulation of HDL and can affect their plasma concentration. Apolipoprotein A-I, the principal apolipoprotein of HDL, is synthesized and secreted in the intestine and liver, where several enzymatic processes contribute to the biogenesis and the catabolism of HDLs. In this review we report and analyze the main clinical, genetic and environmental determinants of plasma HDL-C concentration; moreover we underline how different laboratory methods of HDL-C dosage can influence the correct assessment of these plasma values. We present a comparison of HDL-C...

Short‐term treatment with ezetimibe, simvastatin or their combination does not alter circulating adiponectin, resistin or leptin levels in healthy men

Statin therapy decreases cardiovascular morbidity and mortality, and ezetimibe, a novel cholesterol absorption inhibitor has both lipid-lowering and anti-atherosclerotic effects in animal models. As several adipokines, that is, adiponectin, high molecular weight (HMW) adiponectin, leptin and/or possibly resistin are involved in the pathogenesis of insulin resistance (IR), dyslipidaemia and atherosclerosis, we investigated whether ezetimibe and/or statin treatment may modulate serum concentrations of these four major adipokines. One-centre, randomized, parallel three-group study in 72 healthy men [mean age 32 +/- 9 years, mean body mass index (BMI) 25.7 +/- 3.2 kg/m(2)]. Seventy-two healthy men. Each group of 24 subjects received a 14-day treatment with either ezetimibe (10 mg/day), simvastatin (40 mg/day) or their combination. Blood was drawn before and after the 14-day treatment period. Lipid levels, IR indices, serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Results Neither ezetimibe nor simvastatin or their combination had any effect on serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Baseline leptin levels correlated positively, while adiponectin and HMW adiponectin negatively, with BMI. Leptin concentrations correlated negatively while adiponectin and HMW adiponectin positively with plasma high-density lipoprotein-cholesterol concentrations. Resistin concentrations were not associated with BMI, lipid levels or indicators of IR. Treatment with ezetimibe, simvastatin or their combination does not alter circulating levels of adiponectin, leptin or resistin in adult healthy men.

Effect of low-fat, fermented milk enriched with plant sterols on serum lipid profile and oxidative stress in moderate hypercholesterolemia

Background: Plant sterol (PS)-enriched foods have been shown to reduce plasma LDL-cholesterol concentrations. In most studies, however, PSs were incorporated into food products of high fat content.Objective: We examined the effect of daily consumption of PS-supplemented low-fat fermented milk (FM) on the plasma lipid profile and on systemic oxidative stress in hypercholesterolemic subjects.Design: Hypercholesterolemic subjects (LDL-cholesterol concentrations ≥130 and ≤ 190 mg/dL; n = 194) consumed 2 low-fat portions of FM in the same meal daily for 6 wk. Subjects were randomly assigned to 2 groups: low-fat FM enriched with 0.8 g PS ester per portion or control FM. Plasma concentrations of lipids, oxidized LDL, β-carotene, β-sitosterol, campesterol, and high-sensitivity C-reactive protein were measured during the trial.Results: Plasma LDL-cholesterol concentrations were reduced by 9.5% and 7.8% after 3 and 6 wk, respectively, in the 1.6-g/d PS group compared with the control group, whereas plasma triacylglycerol and HDL-cholesterol concentrations were not significantly affected. In addition, there were no significant changes in serum β-carotene on normalization to LDL cholesterol during the study period in both groups, whereas plasma concentrations of oxidized LDL were reduced significantly in the PS group compared with the control group (−1.73 compared with 1.40 U/L, respectively; P < 0.05). Plasma sitosterol concentrations were increased by 35% (P < 0.001 compared with control); however, campesterol concentrations did not change during the study period.Conclusion: Daily consumption of 1.6 g PS in low-fat FM efficiently lowers LDL cholesterol in subjects with moderate hypercholesterolemia without deleterious effects on biomarkers of oxidative stress.

Effects of Tea Consumption on Plasma Lipids and Lipoproteins in Apparently Healthy Individuals

Possible alterations in total plasma cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol concentrations were studied in forty healthy human subjects (twenty-two males and eighteen adult females) after twenty eight days of tea consumption. A commercial brand of tea preparation was drunk by each of the subjects and they were made to take two standard cups (4.0g) of tea infusion per day. The result showed a significant decrease in mean HDL-cholesterol and increase in LDL-cholesterol concentrations compared with the mean control values. The mean total cholesterol was statistically unchanged. When the subjects were grouped into males and females, the mean LDL-C concentration was significantly elevated in both male and female groups while the mean HDL-C and triglyceride levels only in female subjects when compared with the corresponding control group. The difference observed in the value of the mean total cholesterol was not statistically significant in individual male and female groups. Findings from this study suggest that tea consumption could affect the metabolism of atherogenic lipid fractions and may thus be important in the aetiology of coronary heart disease. . Keywords : Tea, LDL-cholesterol, HDL-cholesterol, Coronary heart disease. Nigerian Journal of Health and Biomedical Science Vol. 6 (1) 2007: pp. 25-28

Effect of Weight Loss on LDL and HDL Kinetics in the Metabolic Syndrome

The purpose of this study was to examine the effect of weight loss on LDL and HDL kinetics and plasma retinol-binding protein-4 (RBP-4) and adiponectin levels in men with the metabolic syndrome. LDL apolipoprotein (apo)B-100 and HDL apoA-I kinetics were studied in 35 obese men with the metabolic syndrome at the start and end of a 16-week intervention trial of a hypocaloric, low-fat diet (n = 20) versus a weight maintenance diet (n = 15) using a stable isotope technique and multicompartmental modeling. Consumption of the low-fat diet produced significant reductions (P < 0.01) in BMI, abdominal fat compartments, and homeostasis model assessment score compared with weight maintenance. These were associated with a significant increase in adiponectin and a fall in plasma RBP-4, triglycerides, LDL cholesterol, and LDL apoB-100 concentration (P < 0.05). Weight loss significantly increased the catabolism of LDL apoB-100 (+27%, P < 0.05) but did not affect production; it also decreased both the catabolic (-13%) and production (-13%) rates of HDL apoA-I (P < 0.05), thereby not altering plasma HDL apoA-I or HDL cholesterol concentrations. VLDL apoB-100 production fell significantly with weight loss (P < 0.05). The increase in LDL catabolism was inversely correlated with the fall in RBP-4 (r = -0.54, P < 0.05) and the decrease in HDL catabolism with the rise in adiponectin (r = -0.56, P < 0.01). In obese men with metabolic syndrome, weight loss with a low-fat diet decreases the plasma LDL apoB-100 concentration by increasing the catabolism of LDL apoB-100; weight loss also delays the catabolism of HDL apoA-I with a concomitant reduction in the secretion of HDL apoA-I. These effects of weight loss could partly involve changes in RBP-4 and adiponectin levels.

Inability of HDL from abdominally obese subjects to counteract the inhibitory effect of oxidized LDL on vasorelaxation

Abdominal obesity is associated with a decreased plasma concentration of HDL cholesterol and with qualitative modifications of HDL, such as triglyceride enrichment. Our aim was to determine, in isolated aorta rings, whether HDL from obese subjects can counteract the inhibitory effect of oxidized low density lipoprotein (OxLDL) on endothelium-dependent vasodilation as efficiently as HDL from normolipidemic, lean subjects. Plasma triglycerides were 74% higher (P < 0.005) in obese subjects compared with controls, and apolipoprotein A-I (apoA-I) and HDL cholesterol concentrations were 12% and 17% lower (P < 0.05), respectively. HDL from control subjects significantly reduced the inhibitory effect of OxLDL on vasodilation [maximal relaxation (E(max)) = 82.1 +/- 8.6% vs. 54.1 +/- 8.1%; P < 0.0001], but HDL from obese subjects had no effect (E(max) = 47.2 +/- 12.5% vs. 54.1 +/- 8.1%; NS). In HDL from abdominally obese subjects compared with HDL from controls, the apoA-I content was 12% lower (P < 0.05) and the triglyceride-to-cholesteryl ester ratio was 36% higher (P = 0.08)). E(max)(OxLDL + HDL) was correlated with HDL apoA-I content and triglyceride-to-cholesteryl ester ratio (r = 0.36 and r = -0.38, respectively; P < 0.05). We conclude that in abdominally obese subjects, the ability of HDL to counteract the inhibitory effect of OxLDL on vascular relaxation is impaired. This could contribute to the increased cardiovascular risk observed in these subjects.

Defining the metabolic syndrome: Resolving unresolved issues?

Background Several definitions exist for the metabolic syndrome. In concert with the blood pressure and glucose criteria of the NCEP definition, it has now been suggested that the use of fibrates and nicotinic acid be incorporated into the dyslipidemia criteria. While statins are the drugs most widely prescribed for lowering LDL-cholesterol, they also affect triglyceride and HDL-cholesterol levels. The aims of the present study were (1) to investigate how adding lipid-lowering therapy to the NCEP definition might influence the prevalence of the metabolic syndrome and (2) to compare the characteristics of patients identified according to the newly proposed IDF definition with those identified according to the NCEP definition. Methods We conducted a cross-sectional study on 2373 patients with clinically manifest vascular disease. In order to allow for the influence of lipid-lowering therapy on the identification of patients with the metabolic syndrome, the NCEP definition was modified in two ways. In NCEP-rev1, the use of lipid-lowering agents fulfilled the hypertriglyceridemia criterion; in NCEP-rev2, triglycerides and HDL-cholesterol plasma concentrations were recalculated for lipid-lowering agents. Results The prevalence of the metabolic syndrome was 41% according to the NCEP definition, 50% according to the NCEP-rev1, 44% according to the NCEP-rev2, and 52% according to the IDF definition. Patients identified only with the NCEP definition had lower HDL-cholesterol, higher triglycerides, and higher fasting glucoses levels than patients only diagnosed with the IDF definition. Conclusion Adding the use of lipid-lowering drugs to the NCEP definition may lead to the identification of an additional group of patients at an elevated risk for cardiovascular diseases and diabetes. The NCEP definition of the metabolic syndrome identifies patients with a worse cardiovascular risk profile than patients qualifying for the metabolic syndrome with the IDF definition in a cohort of patients with clinical manifestations of vascular disease.

Investigational Drugs Targeting HDL-C Metabolism And Reverse Cholesterol Transport

Low high-density lipoprotein cholesterol (HDL-C) levels are associated with higher risk of cardiovascular disease, even in patients receiving statin therapy. HDL-C has a number of potential atheroprotective mechanisms, including reverse cholesterol transport. HDL-C also has antioxidant, anti-inflammatory, vasodilatory and antithrombotic effects. A number of targets with the potential to raise HDL-C levels and/or increase reverse cholesterol transport have been identified. Plasma concentrations of HDL-C are the net result of the de novo production, catabolism and recycling of HDL-C particles, as well as the contribution to HDL-C from components of other lipoproteins. HDL-C levels can be modified by increasing the production of apolipoprotein A-I or by delaying the clearance of HDL-C from the plasma. Whether manipulation of these drug targets to raise HDL-C will result in cardiovascular event reduction remains to be determined.

Plasma LDL and HDL Cholesterol and Oxidized LDL Concentrations Are Altered in Normo- and Hypercholesterolemic Humans after Intake of Different Levels of Cocoa Powder

Cocoa powder is rich in polyphenols, such as catechins and procyanidins, and has been shown in a variety of subject models to inhibit oxidized LDL and atherogenesis. Our study evaluated plasma LDL cholesterol and oxidized LDL concentrations following the intake of different levels of cocoa powder (13, 19.5, and 26 g/d) in normocholesterolemic and mildly hypercholesterolemic humans. In this comparative, double-blind study, we examined 160 subjects who ingested either cocoa powder containing low-polyphenolic compounds (placebo-cocoa group) or 3 levels of cocoa powder containing high-polyphenolic compounds (13, 19.5, and 26 g/d for low-, middle-, and high-cocoa groups, respectively) for 4 wk. The test powders were consumed as a beverage after the addition of hot water, twice each day. Blood samples were collected at baseline and 4 wk after intake of the test beverages for the measurement of plasma lipids. Plasma oxidized LDL concentrations decreased in the low-, middle-, and high-cocoa groups compared with baseline. A stratified analysis was performed on 131 subjects who had a LDL cholesterol concentrations of ≥3.23 mmol/L at baseline. In these subjects, plasma LDL cholesterol, oxidized LDL, and apo B concentrations decreased, and the plasma HDL cholesterol concentration increased, relative to baseline in the low-, middle-, and high-cocoa groups. The results suggest that polyphenolic substances derived from cocoa powder may contribute to a reduction in LDL cholesterol, an elevation in HDL cholesterol, and the suppression of oxidized LDL.

Effects of a Low–Glycemic Load vs Low-Fat Diet in Obese Young Adults

The results of clinical trials involving diet in the treatment of obesity have been inconsistent, possibly due to inherent physiological differences among study participants. To determine whether insulin secretion affects weight loss with 2 popular diets. Randomized trial of obese young adults (aged 18-35 years; n = 73) conducted from September 2004 to December 2006 in Boston, Mass, and consisting of a 6-month intensive intervention period and a 12-month follow-up period. Serum insulin concentration at 30 minutes after a 75-g dose of oral glucose was determined at baseline as a measure of insulin secretion. Outcomes were assessed at 6, 12, and 18 months. Missing data were imputed conservatively. A low-glycemic load (40% carbohydrate and 35% fat) vs low-fat (55% carbohydrate and 20% fat) diet. Body weight, body fat percentage determined by dual-energy x-ray absorptiometry, and cardiovascular disease risk factors. Change in body weight and body fat percentage did not differ between the diet groups overall. However, insulin concentration at 30 minutes after a dose of oral glucose was an effect modifier (group x time x insulin concentration at 30 minutes: P = .02 for body weight and P = .01 for body fat percentage). For those with insulin concentration at 30 minutes above the median (57.5 microIU/mL; n = 28), the low-glycemic load diet produced a greater decrease in weight (-5.8 vs -1.2 kg; P = .004) and body fat percentage (-2.6% vs -0.9%; P = .03) than the low-fat diet at 18 months. There were no significant differences in these end points between diet groups for those with insulin concentration at 30 minutes below the median level (n = 28). Insulin concentration at 30 minutes after a dose of oral glucose was not a significant effect modifier for cardiovascular disease risk factors. In the full cohort, plasma high-density lipoprotein cholesterol and triglyceride concentrations improved more on the low-glycemic load diet, whereas low-density lipoprotein cholesterol concentration improved more on the low-fat diet. Variability in dietary weight loss trials may be partially attributable to differences in hormonal response. Reducing glycemic load may be especially important to achieve weight loss among individuals with high insulin secretion. Regardless of insulin secretion, a low-glycemic load diet has beneficial effects on high-density lipoprotein cholesterol and triglyceride concentrations but not on low-density lipoprotein cholesterol concentration. clinicaltrials.gov Identifier: NCT00130299.