Glucose Control and Lipid Metabolism in African American Patients with Type 2 Diabetes Mellitus and Chronic Hepatitis C Viral Infection

ObjectiveTo compare lipid profiles and glucose control in African American patients with type 2 diabetes mellitus with and without chronic hepatitis C viral (HCV) infection.MethodsThis retrospective study conducted in an academic outpatient setting included African American patients with both type 2 diabetes and HCV, patients with HVC only, and patients with type 2 diabetes only. Serum total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride values were compared among all 3 patient groups.ResultsThe study population included 283 patients, of whom 111 had type 2 diabetes and HCV, 68 had HCV only, and 104 had type 2 diabetes only. Chronic HCV was associated with lower total cholesterol and LDL-cholesterol levels in patients with or without type 2 diabetes. In contrast, elevated serum triglyceride levels associated with diabetes were not reduced in patients with chronic HCV, although diabetes control was better in the diabetes group with HCV than in the diabetes group without HCV (mean hemoglobin A_1c [standard error of the mean]: 7.1% [1.8%] vs 8.8% [2.1%], P < .001). HDL cholesterol was higher in the patients with earlier stages of HCV when compared with HDL cholesterol in the other 2 groups.ConclusionsChronic HCV infection in type 2 diabetic patients decreases serum levels of total and LDL cholesterol, but has no such protective effect on triglyceride levels. HCV infection may alter the cellular pathways of cholesterol and triglyceride metabolism in patients with type 2 diabetes. (Endocr Pract. 2011;17:363-368)     

Concentraciones séricas de colesterol y triglicéridos en pacientes diabéticos con hipotiroidismo subclínico

ObjectiveTo assess whether subclinical hypothyroidism is associated to elevations in serum cholesterol and triglyceride levels in patients with type 2 diabetes.Patients and methodsFrom a total population of 1,112 patients with type 2 diabetes screened for thyroid dysfunction (thyrotropin measurement), a group of 325 patients with normal thyroid function and another group of 29 patients with subclinical hypothyroidism were selected. No patient had known dyslipidemia or was taking lipid lowering medication.ResultsPatients with subclinical hypothyroidism had serum levels of total cholesterol (4.88 ± 0.74 mmol/L), HDL cholesterol (1.37 ± 0.34 mmol/L), LDL cholesterol (2.94 ± 0.58 mmol/L), and triglycerides (1.05 [0.88-1.41] mmol/L) that did not significantly differ from those found in euthyroid patients (4.79 ± 0.83, 1.33 ± 0.36, 2.87 ± 0.76, and 1.11 [0.81-1.43] mmol/L, respectively). Multiple regression analysis showed no association between TSH and serum lipid levels.ConclusionThese results suggest that, in our population, there are no significant differences in serum cholesterol and triglyceride levels between diabetic patients with normal and reduced thyroid function.     

Lipid concentrations and the use of lipid lowering drugs: evidence from a national cross sectional survey

ObjectiveTo evaluate the prevalence of the use of lipid lowering agents and its relation to blood lipid concentrations in English adults.DesignCross sectional survey.SettingEngland, 1998.ParticipantsNationally representative sample of 13 586 adults (aged ⩾16 years) living in non-institutional households.Results Mean total cholesterol concentrations were 5.47 (SE 0.02) mmol/l in men and 5.59 (0.02) mmol/l in women. Mean HDL cholesterol concentrations were 1.28 (0.01) mmol/l in men and 1.55 (0.01) mmol/l in women. Overall, of 10 569 adults who had a valid cholesterol measurement taken 7133 (67.5%; 95% confidence interval 66.5% to 68.4%) had a total cholesterol concentration ⩾5 mmol/l, 2804 (26.5%; 25.7% to 27.4%) had a ratio of total cholesterol to HDL cholesterol ⩾5 mmol/l, and 237 (2.2%; 1.9% to 2.5%) reported taking lipid lowering drugs. Of 117 participants with no history of cardiovascular disease but whose estimated 10 year risk of coronary heart disease was ⩾30% and whose total cholesterol concentration was ⩾5 mmol/l, four (3%) were taking lipid lowering drugs. Of 385 adults aged 16-75 with a history of coronary heart disease and eligible for lipid lowering treatment, 114 (30%; 25% to 34%) were taking lipid lowering drugs, of whom only 50 (44%; 35% to 53%) had a total cholesterol concentration <5 mmol/l.ConclusionsDespite the high prevalence of dyslipidaemia in English adults, the proportion of adults taking lipid lowering drugs in 1998 was only 2.2%. Rates of treatment were low among high risk patients eligible for primary prevention with lipid lowering drugs, and less than one third of patients with established cardiovascular disease received such treatment.     

Changes in plasma high-density lipoprotein cholesterol concentration after weight reduction in grossly obese subjects.

Changes in serum lipoproteins associated with weight loss were assessed in 13 grossly obese (relative weight 183%) patients who had participated in an outpatient semi-starvation diet consisting of liquid protein and carbohydrate. At the follow-up examination an average of six and a half months after the start of refeeding the mean weight loss was 16.1 +/- 4.5 kg or 15% of initial body weight. Significant increases in high-density lipoprotein (HDL) cholesterol of 0.16 +/- 0.05 mmol/l (6 +/- 2 mg/100 ml) and decreases in triglycerides (0.8 +/- 0.23 mmol/l; 73 +/- 20 mg/100 ml) and fasting blood sugar (0.6 +/- 0.22 mmol/l; 11 +/- 4 mg/100 ml) were observed. Changes in HDL cholesterol correlated significantly with changes in weight (r = 0.667) and percentage change in weight. The intercept of the regression equation relating HDL cholesterol to percentage change in weight was -7.3, indicating that a change in HDL cholesterol greater than zero required a weight loss of at least 7.3% of body weight. Thus, weight loss can significantly increase HDL cholesterol concentrations but a considerable amount of weight must be lost to produce a significant increase in HDL cholesterol concentration.     

Impact on lipoprotein profile after long-term testosterone replacement in hypogonadal men.

Testosterone serum levels may influence the lipoprotein metabolism and possibly atherogenic risk. Our aim was to investigate the effects of long-term testosterone supplementation in hypogonadal men on multiple lipoprotein markers. 18 Hypogonadal men were studied before and after 3, 6, and 18 (n = 7) months of treatment with testosterone enanthate. During treatment, serum testosterone and estradiol increased, reaching normal levels (p < 0.0001 and 0.003, respectively). This was associated with a decrease in HDL cholesterol (from 1.40 +/- 0.10 mmol/l to 1.22 +/- 0.08 mmol/l, p < 0.001) after six months at the expense of HDL2 cholesterol (p < 0.01), as well as apoprotein A1 (from 139 +/- 3.4 mg/dl to 126 +/- 3.0 mg/dl, p < 0.005). Hepatic lipase activity increased (p < 0.05) and correlated positively with testosterone (r = 0.56, p < 0.02) and negatively with HDL cholesterol (r = - 0.58, p < 0.02). Total and LDL cholesterol, triglycerides, and apoprotein B did not increase. Among the seven patients who completed 18 months of treatment, triglycerides, total cholesterol, LDL and HDL cholesterol, as well as total cholesterol/HDL cholesterol ratio values did not differ from baseline while apoprotein A1 (p < 0.03) and HDL cholesterol (p < 0.015) remained decreased and hepatic lipase unchanged. Restoration of testosterone levels in hypogonadal men in this study did not reveal unfavorable changes based on total cholesterol/HDL cholesterol and LDL cholesterol/apoprotein B ratios, which are both atherogenic risk markers. Whether the changes in light of lipoprotein metabolism will adversely influence cardiovascular risk over time remains to be determined.     

Prevalence of traditional cardiovascular risk factors for coronary artery disease and elevated fibrinogen among active military personnel in Republic of Serbia: A cross-sectional study

BackgroundIt is well known that less than 1% of the population achieves ideal cardiovascular health, and 65% of patients do not have their conventional risk biomarkers under control. Military service has its own particularities that may contribute to cardiovascular risk.MethodsTo define the preventive strategy goals, we analysed the prevalence of traditional cardiovascular risk factors for coronary artery disease and elevated fibrinogen among active military personnel in the Republic of Serbia.ResultsThe cross-sectional study included 738 individuals older than 20 years, mostly between 31 and 40 years old. The mean value of SBP for the whole group was 122.39± 9.42 mmHg, and for the DBP, it was 79.94±6.56 mmHg. Among active military personnel, 72.7% (533) had prehypertension, and 13.8% (101) was hypertensive. Both body mass and BMI index among the observed age subgroups were found to increase with the age of the patients and cholesterol values. HDL cholesterol values also differed statistically significantly between age subgroups, with the proportion of individuals with HDL less than 1.5 mmol/L in all subgroups being about 85%, the only in the 41-50 age group was lower, 76.4%. LDL cholesterol and the proportion of individuals who had LDL 3.5 increases with the age of patients, and an identical trend was recorded with triglycerides. With ageing, fibrinogen levels increased.ConclusionsThose findings considering cardio and cerebrovascular risk factors would help create a new approach for primary prevention for these categories of individuals.     

非布司他对急性痛风性关节炎患者血清SUA水平及氧化应激的影响

目的:研究非布司他治疗急性痛风性关节炎(AGA)患者的临床疗效及对血清尿酸(SUA)水平及氧化应激的影响。方法:研究对象选取我院2014年6月到2016年10月收治的200例AGA患者,采用随机数字法将其分为对照组和观察组,每组各100例。对照组患者口服别嘌呤醇治疗,观察组患者口服非布司他治疗,均连续治疗24周。比较两组患者治疗前后各时间点的血清SUA、8-羟基脱氧鸟苷(8-OHdG)、3-硝基络氨酸修饰蛋白(3-NT)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)水平的变化。结果:治疗后,观察组各时间点的血清SUA、8-OHdG和3-NT水平均明显低于对照组(P0.01)。治疗后,对照组患者的血清TG、TC、HDL、LDL水平较治疗前无明显变化(P0.05),观察组患者的血清TG水平明显低于治疗前(P0.01),血清HDL水平明显高于治疗前(P0.01),而血清TC和LDL水平比较无明显差异(P0.05)。结论:非布司他治疗AGA的疗效明显,能有效降低血清SUA水平,抑制氧化应激状态,并能改善血脂代谢。     

High prevalence of low HDL cholesterol concentrations and mixed hyperlipidemia in a Mexican nationwide survey

The prevalence of lipid abnormalities revealed in a survey done in 417 Mexican cities is described. Information was obtained on 15,607 subjects, aged 20 to 69 years. In this report, only samples obtained after a 9- to 12-h fast were included (2,256 cases: 953 men and 1,303 women). The population is representative of Mexican urban adults. Mean lipid concentrations were: cholesterol, 4.80 mmol/l; triglycerides, 2.39 mmol/l; HDL cholesterol, 1.00 mmol/l; and LDL cholesterol, 3.06 mmol/l. The most prevalent abnormality was HDL cholesterol below 0.9 mmol/l (46.2% for men and 28.7% for women). Hypertriglyceridemia (>2.26 mmol/l) was the second most prevalent abnormality (24.3%). Severe hypertriglyceridemia (>11.2 mmol/l) was observed in 0.42% of the population. Increased LDL cholesterol (> or =4.21 mmol/l) was observed in 11.2% of the sample. Half of the hypertriglyceridemic subjects had a mixed dyslipidemia or low HDL cholesterol. More than 50% of the low HDL cholesterol cases were not related to hypertriglyceridemia. Insulin resistance was found in 59% of them. In conclusion, the prevalence of hypoalphalipoproteinemia and other forms of dyslipidemia in Mexican adults is very high and it is among the highest previously reported worldwide.     

Identification of sterol acceptors that stimulate cholesterol efflux from human spermatozoa during in vitro capacitation

The nature of cholesterol-binding proteins acting upon human spermatozoa during in vitro capacitation was determined by measuring the efflux of [³H]cholesterol and of [³H]cholesteryl sulfate from labeled spermatozoa. Efflux of [³H]sterols was stimulated when the labeled gametes were incubated in Ham's F-10 medium supplemented with female serum or follicular fluid. Upon centrifugation of capacitated spermatozoa and application of the supernatant to density-gradient ultracentrifugation for lipoprotein analysis, both [³H]cholesterol and [³H]cholesteryl sulfate were found to be carried by very-low-density lipoproteins (VLDL), low-density lipoproteins (VLDL), high-density lipoproteins (HDL), as well as the albumin fraction (d > 1.21) in serum. When the capacitation medium was supplemented with follicular fluid, the [³H]sterols were bound to HDL's and to the albumin fraction; when the latter fraction was analysed by molecular sieve chromatography, 60–70% of the radioactivity eluted in fractions with a mean molecular weight corresponding to that of human serum albumin. Sperm cholesterol efflux was also stimulated when serum or follicular fluid was added to a simplified medium (50 mM Tris-HCl, 0.56% NaCl, pH 7.8); efflux of [³H]cholesterol from labeled gametes progressed in a time-dependent manner, but was low in the absence of serum components. The [³H]cholesterol/cholesterol ratios were higher in the albumin and HDL fractions, indicating some degree of specificity of these sterol acceptors. It was observed that follicular fluid albumin has a [³H]sterol binding capacity that is 2—3-fold higher than that of serum albumin. Commercial human serum albumin also promoted sperm cholesterol efflux. These results provide new information concerning those components of follicular fluid which may play a role in human sperm capacitation and provide further support for the concept that loss of cholesterol from the sperm plasma membrane is an important component of the capacitation process.     

Relations between particle size of HDL and LDL lipoproteins and cholesterol esterification rate

Particle size of low density (LDL) and high density (HDL) lipoproteins and cholesterol esterification rate in HDL plasma (FER(HDL)) are important independent predictors of coronary artery diseases (CAD). In this study we assessed the interrelations between these indicators and routinely examined plasma lipid parameters and plasma glucose concentrations. In 141 men, healthy volunteers, we examined plasma total cholesterol (TC), triglycerides (TG), HDL and LDL cholesterol (HDL-C, LDL-C) and HDL unesterified cholesterol (HDL-UC). Particle size distribution in HDL and LDL was assessed by gradient gel electrophoresis and FER(HDL) was estimated by radioassay. An effect of particle size and FER(HDL) on atherogenic indexes as the Log(TG/HDL-C) and TC/HDL-C was evaluated. Subjects in the study had plasma concentrations (mean +/- S.D.) of TC 5.2+/-0.9 mmol/l, HDL-C 1.2+/-0.3 mmol/l, TG 2.1+/-1.7 mmol/l, glucose 5+/-0.8 mmol/l. Relative concentration of HDL(2b) was 17.6+/-11.5 % and 14.6+/-11.8 % of HDL(3b,c). The mean diameter of LDL particles was 25.8+/-1.5 nm. The increase in FER(HDL) significantly correlated with the decrease in HDL(2b) and LDL particle size (r = -0.537 and -0.583, respectively, P<0.01) and the increase in HDL(3b,c) (0.473, P<0.01). Strong interrelations among TG and HDL-C or HDL-UC and FER(HDL) and particle size were found, but TC or LDL-C did not have such an effect. Atherogenic indexes Log(TG/HDL-C) and TC/HDL-C correlated with FER(HDL) (0.827 and 0.750, respectively, P<0.0001) and with HDL and LDL particle size.     

Sex difference in the regulation of plasma high density lipoprotein cholesterol by genetic and environmental factors

Association between high density lipoprotein (HDL) cholesterol concentration and restriction fragment length polymorphisms at the cholesteryl ester transfer protein (CETP) gene locus was studied in a random population-based cohort of 526 Caucasian subjects (259 men, mean age 50.9 years, and 267 women, mean age 51.8 years). HDL cholesterol concentration was adjusted for age, body mass index, alcohol consumption, smoking and plasma triglyceride and low density lipoprotein cholesterol levels. In females, the HDL cholesterol levels were associated withTagIB polymorphism (1.46 mmol/1 in the B1B1 genotype, 1.56 mmol/l in B 1B2 and 1.72 mmol/1 in B2B2,P = 0.0001 for the trend). In contrast, this was not observed in men (1.24, 1.20, 1.27 mmol/l, NS). The association was seen even in women who were current smokers (1.41, 1.56, 1.75 mmol/l,n = 72,P = 0.007), but not in male smokers (1.26, 1.19, 1.14 mmol/l,n = 102, NS). In male non-smokers the association was weak (1.22, 1.20, 1.32 mmol/l,n = 157,P = 0.05). In postmenopausal women not receiving hormone replacement therapy (n = 108), the association continued to be present, although weaker (1.50, 1.58, 1.70 mmol/l,P = 0.06). CETP activity (n = 101) tended to be lower in subjects with the 132132 genotype. In conclusion, a clear-cut sex difference was observed in the genotype effect on plasma HDL cholesterol levels. The slight attenuation of the gene dosage effect after menopause suggests that the gender difference may be, at least in part, due to sex hormones. A genetic subgroup (men with the 132132 genotype) particularly susceptible to the HDL cholesterol decreasing effect of smoking could be demonstrated.Part of this work was presented at the 67th Scientific Sessions of the American Heart Association, Dallas, Texas, USA, 14–17 November, 1994     

Cross sectional survey of effectiveness of lipid lowering drugs in reducing serum cholesterol concentration in patients in 17 general practices

ObjectiveTo compare the effectiveness of lipid lowering drugs in lowering serum cholesterol concentrations.DesignCross sectional study.Setting17 practices within 17 primary care groups in Trent region, United Kingdom.ParticipantsPatients aged 35 years or over taking lipid lowering drugs and with at least two serum cholesterol concentrations recorded on computer.Results1353 of 2469 (54.8%) patients receiving lipid lowering treatment had a last recorded serum cholesterol concentration of ⩽5 mmol/l. Significantly more patients taking statins achieved the target value for serum cholesterol (5 mmol/l) than those taking fibrates (1307 (57%) v 46 (26%); P<0.0001). Atorvastatin and simvastatin were the most effective drugs in achieving the target. Significant differences were found between lipid lowering drugs for the pretreatment serum cholesterol concentration, the most recent cholesterol concentration, and the associated percentage reduction. Atorvastatin and simvastatin achieved the greatest percentage reduction in serum cholesterol concentrations (30.1%, 95% confidence interval 28.8% to 31.4%, and 28.0%, 26.7% to 29.3%, respectively). Although the mean serum cholesterol concentrations in this unselected population tended to be higher than those in clinical trials, the percentage reduction was consistent with the trials.ConclusionThe ability of individual statins to lower serum cholesterol concentration varied, with atorvastatin and simvastatin being the most effective. The percentage reductions agreed with those of randomised controlled trials indicating likely benefits in unselected patients in primary care. As the initial serum cholesterol concentrations were higher than those in randomised controlled trials, target serum cholesterol values of ⩽5 mmol/l may be unrealistic even for patients taking the most efficacious drugs. Also, the higher initial levels could mean that the absolute reduction in cardiovascular risk in primary care patients is greater than thought.

What is already known on this topic

Statins in patients with coronary heart disease help reduce further cardiovascular events and improve survivalThis seems to be a class effect of statins, although there may be important differences in effectiveness between themLess than half of patients in the community who take lipid lowering drugs achieve target serum cholesterol values

What this study adds

Statins vary in their ability to lower serum cholesterol concentration, with atorvastatin and simvastatin achieving the best resultsThe percentage reductions agreed with those found in randomised controlled trialsSince the initial serum cholesterol concentrations were higher than in trials, absolute risk reductions in primary care patients may be greater than thoughtTarget values of ⩽5 mmol/l may be unrealistic even for patients on the most efficacious drugs, because the initial mean cholesterol values of primary care patients are higher than those of patients in trials     

Development and validation of an LC-MS/MS method for determination of 8-iso-prostaglandin f2 Alpha in human saliva

BackgroundIncreased formation of reactive oxygen species may be caused by the ion release of the metal alloys used in prosthetic dental restorations due to the corrosion process. As products of lipid peroxidation, isoprostanes can be used as a marker for oxidative stress in the body. There are two significant advantages of using isoprostanes as an oxidative stress marker - presence in all fluids in the body and low reactivity. Saliva provides noninvasive, painless, and cost-effective sample collection and can be used as an alternative testing medium of blood and urine.MethodsThis study presents the development and validation of a sample LC-MS/MS method to quantify 8-isoprostaglandin F2-a in human saliva using salt-out assisted liquid-liquid extraction (SALLE).ResultsThe selected sample preparation procedure optimized chromatographic separation and mass detection provided high recovery and sensitivity of the analysis. The calibration curve was obtained in the predefined range 25-329 ng/L with R2 larger than 0.995. Normalized matrix varied between 89.7 % and 113.5%. The method showed sufficient accuracy and precision - accuracy in the range 89.7 %-113.9 %, and precision between 2.3% and 5.4%.ConclusionsThe proposed method is validated according to current EMA/FDA industrial guidance for bioanalysis and offers an appropriate level of sensitivity and sufficient accuracy and precision.     

High-Density Lipoprotein Function in Exudative Age-Related Macular Degeneration

PurposeHigh-density lipoproteins (HDL) have long been implicated in the pathogenesis of age-related macular degeneration (AMD). However, conflicting results have been reported with regard to the associations of AMD with HDL-cholesterol levels. The present study is the first to assess HDL composition and metrics of HDL function in patients with exudative AMD and control patients.MethodsBlood samples were collected from 29 patients with exudative AMD and 26 age-matched control patients. Major HDL associated apolipoproteins were determined in apoB-depleted serum by immunoturbidimetry or ELISA, HDL-associated lipids were quantified enzymatically. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function, including cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities using apoB-depleted serum from study participants.ResultsIn our study, we observed that the HDL associated acute phase protein serum amyloid A (SAA) was significantly increased in AMD patients (p<0.01), whereas all other assessed apolipoproteins including ApoA-I, apoA-II, apoC-II, apoC-III and apoE as well as major HDL associated lipids were not altered. HDL efflux capacity, anti-oxidative capacity and arylesterase activity were not different in AMD patients when compared with the control group. The ability of apoB-depleted serum to inhibit monocyte NF-κB expression was significantly improved in AMD patients (mean difference (MD) -5.6, p<0.01). Moreover, lipoprotein-associated phospholipase A2 activity, a marker of vascular inflammation, was decreased in AMD subjects (MD -24.1, p<0.01).ConclusionsThe investigated metrics of HDL composition and HDL function were not associated with exudative AMD in this study, despite an increased content of HDL associated SAA in AMD patients. Unexpectedly, anti-inflammatory activity of apoB-depleted serum was even increased in our study. Our data suggest that the investigated parameters of serum HDL function showed no significant association with exudative AMD. However, we cannot exclude that alterations in locally produced HDL may be part of the AMD pathogenesis.     

High-performance aqueous gel permeation chromatography of serum lipoproteins: Selective detection of cholesterol by enzymatic reaction

A rapid method for the quantitation of cholesterol in each lipoprotein fraction has been developed which utilizes high-performance aqueous gel permeation chromatography followed by enzymatic reaction using reaction-type high-performance chromatography.Cholesterol in serum lipoproteins eluted from the column could be sensitively and selectively detected by the absorbance at 550 nm following the enzymatic reaction. The sensitivity of the detection for cholesterol measured by A₅₅₀ was compared with that for protein measured by A₂₅₀ using the standard lipoprotein fractions: low-density lipoprotein (LDL) and high-density lipoproteins (HDL₂ and HDL₃). The effects of changing the flow-rate and lengthening the column on the resolution of LDL and HDL were examined. Analyses of serum protein and cholesterol were performed with this method for human and animal subjects.     

Effect of Feeding Xenobiotics on Serum High Density Lipoprotein and Apolipoprotein A-I in Rats

The effects on serum cholesterol level were examined in rats fed on various xenobiotics. The hypercholesterolemia induced by polychlorinated biphenyls (PCB) was characterized in rats, from which lipoproteins were isolated by ultracentrifugation. A dietary addition of 0.03% PCB, 0.3% chloretone, 0.1% aminopyrine, or 0.2% 2,6-di-tert-butyl-p-cresol (BHT) resulted in a significant increase in serum cholesterol, although the chemical structure of each of these xenobiotics was different. The serum cholesterol level was markedly increased by one month of PCB feeding, the effect of PCB on the serum phospholipid level being similar. The serum triglyceride level transiently increased within 7 days of feeding with PCB diet. PCB feeding resulted in the elevation of all lipoproteins, including VLDL, LDL, HDL₁, and HDL₂, a marked increase being observed in HDI₁. Both HDL₁ and HDL₂ isolated from PCB-treated rats contained more apolipoprotein A-I (apo A-I) and less apo E than normal. VLDL isolated from PCB-treated rats had more cholesterol and apo E, but less apo C than that of the control animals. These data demonstrate that PCB feeding resulted in increased VLDL rich in cholesterol and apo E, and increased HDL rich in apo A-I. This experimentally induced hypercholesterolemia resulting in apo A-I-rich HDL would be a useful model for investigating the metabolism of apo-A-I and HDL.     

A Randomized Comparative Trial of Continued Abacavir/Lamivudine plus Efavirenz or Replacement with Efavirenz/Emtricitabine/Tenofovir DF in Hypercholesterolemic HIV-1 Infected Individuals

BackgroundDrug choice and metabolic changes with antiretroviral therapy contribute to cardiovascular risk in persons with HIV-1 infection.MethodsA randomized, 12 week, open-label, comparative study of the impact on lipids of continuation of abacavir/lamivudine (ABC/3TC) plus efavirenz (EFV) or replacement with the single tablet regimen of EFV/emtricitabine/tenofovir DF (EFV/FTC/TDF) in hypercholesterolaemic subjects on successful antiretroviral therapy, with a 12-week extension with all subjects on EFV/FTC/TDF.Results157 subjects received study drug, 79 switched to EFV/FTC/TDF and 78 subjects continued ABC/3TC+EFV. At Week 12, 73 subjects on ABC/3TC+EFV switched to EFV/FTC/TDF. The switch was well tolerated and no subject experienced viral rebound. Median baseline fasting total cholesterol was 6.32mmol/L. 12 weeks following switch, the difference in the means (LSM) between treatment groups (EFV/FTC/TDF minus ABC/3TC+EFV) in total cholesterol change from baseline was -0.74mmol/l (95% CI −1.00, −0.47, p < 0.001). The median change from baseline in total cholesterol following switch in the EFV/FTC/TDF arm was -0.86mmol/l (p < 0.001) compared with +0.01mmol/l (p = 0.45) in the continuation arm at Week 12. Significant (p < 0.001) differences between treatment groups following switch were seen for all lipid fractions from baseline to Week 12: LDL cholesterol (−0.47 mmol/L [−0.70, −0.25]), HDL cholesterol (−0.15 mmol/L [−0.21, −0.08]), triglycerides (−0.43 mmol/L [-0.75, -0.11]), and non HDL cholesterol (−0.56 mmol/L [−0.80, −0.31]). In the extension phase, similar declines in total cholesterol were observed with a median change from Week 12 to Week 24 of −0.73mmol/L (p < 0.001).ConclusionsSwitching from ABC/3TC+EFV to EFV/FTC/TDF in persons with hypercholesterolemia maintains virological control and significantly improves key lipid parameters.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00615810","term_id":"NCT00615810"}}NCT00615810     

The lipid composition of serum lipoproteins in the harbour seal, Phoca vitulina

The density profile of serum lipoproteins and their lipid composition was studied in 12 adult, female harbour seals. The animals were sampled after an approximate 20 hr fast. The density profile of lipoproteins showed that the harbour seals displayed a distinct VLDL (density less than 1.006 g/ml) and HDL band (density about 1.125 g/ml), but no clear LDL band. There was a rather diffuse population of lipoproteins in the density range of 1.019-1.100 g/ml. Mean serum total cholesterol concentration was 5.7 mmol/l; about 60% of this cholesterol was located in the HDL fraction (density greater than 1.063 g/ml). The fasted seals were found to carry 4% of serum total lipids in chylomicrons. These lipoproteins consisted of 51% of triaclyglycerols (on the basis of total chylomicron lipids). The LDL (defined as heparin-manganese precipitable lipoproteins in VLDL and chylomicron-deficient serum) contained 49% of cholesterol and 43% of phospholipids (on the basis of total LDL lipids). The HDL (defined as heparin-manganese soluble lipoproteins in VLDL and chylomicron-deficient serum) contained 36% of cholesterol and 58% of phospholipids (on the basis of total HDL lipids).     

The metabolism of esterified cholesterol in rabbit plasma low density lipoproteins

The metabolism of esterified cholesterol in plasma low density lipoproteins (LDL) has been studied in rabbits. LDL labelled with ³H in the esterified and free cholesterol moieties was isolated from the serum of donar rabbits which has been injected with [³H]mevalonic acid, and subsequently either incubated at 37°C in vitro with unlabelled rabbit serum or unlabelled rabbit lipoprotein fractions, or reinjected into other rabbits.In vitro there was found to be a transfer of 40–60% of the esterified [³H]-cholesterol out of LDL into both the very low density lipoprotein (VLDL) and high density lipoprotein (HDL) fractions which could not be explained in terms of net transfer of esterified cholesterol mass. In the incubations of labelled LDL with either of the other unlabelled lipoprotein fractions, transfers were apparent only if the dialysed 1.21 g/ml infranatant of rabbit serum was also present. The transfer of esterified [³H]cholesterol out of LDL was enhanced when lecithin:cholesterol acyltransferase was active.After reinjecting labelled LDL into other rabbits, it was found that more than half of the esterified [³H]cholesterol removed from the recipient LDL fraction during the first 30 min was not lost from the plasma compartment, but rather was recovered in HDL. There was only minimal in vivo transfer of LDL esterified [³H]cholesterol into VLDL.It has been concluded that in vitro the esterified cholesterol in LDL exchanges with that in both the VLDL and HDL, and that in vivo the esterified cholesterol pools in LDL and HDL may represent parts of a progressively equilibrating plasma pool.     

Comparison of temporal changes in established cardiovascular biomarkers after acute coronary syndrome between Caucasian and Chinese patients with diabetes mellitus

Abstract

Background: Population means of conventional cardiovascular biomarkers are known to differ between ethnic groups. In this study we performed detailed comparisons in the temporal pattern of these biomarkers between Caucasian and Chinese diabetic patients with acute coronary syndrome (ACS).

Methods: We studied differences in temporal changes of established cardiovascular biomarkers, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, cardiac Troponin T (TnT), NT-proBNP and C-reactive protein (CRP), in 48 Chinese and 48 clinically matched Caucasian patients with type 2 diabetes mellitus who were admitted for ACS. Blood samples were collected at regular time intervals during 30?days to 1?year after the index ACS.

Results: In the >30?day post ACS period, mean serum levels of LDL (2.16 vs. 1.47?mmol/L; p-value <0.001), total cholesterol (4.08 vs. 3.11?mmol/L; p-value <0.001), TnT (11.0 vs. 7.76?ng/L; p-value 0.010) and CRP (2.0 vs. 0.78?mg/L; p-value <0.001) were systematically higher in Caucasian than in Chinese patients. HDL and NT-proBNP levels were similar.

Conclusions: Our study showed clinically relevant differences in levels of established cardiovascular biomarkers between Caucasian and Chinese post ACS patients. Further cross-ethnic studies are warranted to determine secondary prevention treatment biomarker targets in specific populations.