Lipoprotein Lipid Concentrations Research Articles

Lipoprotein Metabolism, Dyslipidemia, and Lipid-Lowering Therapy in Women: A Comprehensive Review.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a), and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses the diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Plasma metabolic profiles predict future dementia and dementia subtypes: a prospective analysis of 274,160 participants.

Blood-based biomarkers for dementia are gaining attention due to their non-invasive nature and feasibility in regular healthcare settings. Here, we explored the associations between 249 metabolites with all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD) and assessed their predictive potential. This study included 274,160 participants from the UK Biobank. Cox proportional hazard models were employed to investigate longitudinal associations between metabolites and dementia. The importance of these metabolites was quantified using machine learning algorithms, and a metabolic risk score (MetRS) was subsequently developed for each dementia type. We further investigated how MetRS stratified the risk of dementia onset and assessed its predictive performance, both alone and in combination with demographic and cognitive predictors. During a median follow-up of 14.01years, 5274 participants developed dementia. Of the 249 metabolites examined, 143 were significantly associated with incident ACD, 130 with AD, and 140 with VaD. Among metabolites significantly associated with dementia, lipoprotein lipid concentrations, linoleic acid, sphingomyelin, glucose, and branched-chain amino acids ranked top in importance. Individuals within the top tertile of MetRS faced a significantly greater risk of developing dementia than those in the lowest tertile. When MetRS was combined with demographic and cognitive predictors, the model yielded the area under the receiver operating characteristic curve (AUC) values of 0.857 for ACD, 0.861 for AD, and 0.873 for VaD. We conducted the largest metabolome investigation of dementia to date, for the first time revealed the metabolite importance ranking, and highlighted the contribution of plasma metabolites for dementia prediction.

Metabolomic profiling for dyslipidemia in pediatric patients with sickle cell disease, on behalf of the IHCC consortium

BackgroundPrevious study has shown that dyslipidemia is common in patients with Sickle cell disease (SCD) and is associated with more serious SCD complications.MethodsThis study investigated systematically dyslipidemia in SCD using a state-of-art nuclear magnetic resonance (NMR) metabolomics platform, including 147 pediatric cases with SCD and 1234 controls without SCD. We examined 249 metabolomic biomarkers, including 98 biomarkers for lipoprotein subclasses, 70 biomarkers for relative lipoprotein lipid concentrations, plus biomarkers for fatty acids and phospholipids.ResultsSpecific patterns of hypolipoproteinemia and hypocholesterolemia in pediatric SCD were observed in lipoprotein subclasses other than larger VLDL subclasses. Triglycerides are not significantly changed in SCD, except increased relative concentrations in lipoprotein subclasses. Decreased plasma FFAs (including total-FA, SFA, PUFA, Omega-6, and linoleic acid) and decreased plasma phospholipids were observed in SCD.ConclusionThis study scrutinized, for the first time, lipoprotein subclasses in pediatric patients with SCD, and identified SCD-specific dyslipidemia from altered lipoprotein metabolism. The findings of this study depict a broad panorama of lipid metabolism and nutrition in SCD, suggesting the potential of specific dietary supplementation of the deficient nutrients for the management of SCD.

Polygenic risk in Type III hyperlipidaemia and risk of cardiovascular disease: An epidemiological study in UK Biobank and Oxford Biobank

BackgroundType III hyperlipidaemia (T3HL) is characterised by equimolar increases in plasma triglycerides (TG) and cholesterol in <10% of APOE22 carriers conveying high cardiovascular disease (CVD) risk. We investigate the role of a weighted triglyceride-raising polygenic score (TG.PS) precipitating T3HL. MethodsThe TG.PS (restricted to genome-wide significance and weighted by published independent effect estimates) was applied to the Oxford Biobank (OBB, n = 6952) and the UK Biobank (UKB, n = 460,037), to analyse effects on plasma lipid phenotypes. Fasting plasma lipid, lipoprotein biochemistry and NMR lipoprotein profiles were analysed in OBB. CVD prevalence/incidence was examined in UKB. ResultsOne TG.PS standard-deviation (SD) was associated with 13.0% (95% confidence-interval 12.0–14.0%) greater TG in OBB and 15.2% (15.0–15.4%) in UKB. APOE22 carriers had 19.0% (1.0–39.0%) greater TG in UKB. Males were more susceptible to TG.PS effects (4.0% (2.0–6.0%) greater TG with 1 TG.PS SD in OBB, 1.6% (1.3–1.9%) in UKB) than females. There was no interaction between APOE22 and TG.PS, BMI, sex or age on TG. APOE22 carriers had lower apolipoprotein B (apoB) (OBB; −0.35 (−0.29 to −0.40)g/L, UKB; −0.41 (−0.405 to −0.42)g/L). NMR lipoprotein lipid concentrations were discordant to conventional biochemistry in APOE22 carriers.In APOE22 compared with APOE33, CVD was no more prevalent in similarly hypertriglyceridaemic participants (OR 0.97 95%CI 0.76–1.25), but was less prevalent in normolipidaemia (OR 0.81, 95%CI 0.69–0.95); no differences were observed in CVD incidence. ConclusionsTG.PS confers an additive risk for developing T3HL, that is of comparable effect size to conventional risk factors. The protective effect of APOE22 for prevalent CVD is consistent with lower apoB in APOE22 carriers.

P02-02 Human exposure to per-and polyfluoroalkyl substances and effects on plasma lipoprotein subclasses, lipid concentrations and lipoproteins as measured by NMR spectroscopy in men and women and possible gender differences in sensitivity

P02-02 Human exposure to per-and polyfluoroalkyl substances and effects on plasma lipoprotein subclasses, lipid concentrations and lipoproteins as measured by NMR spectroscopy in men and women and possible gender differences in sensitivity

Circulating HDL and Non-HDL Associated Apolipoproteins and Breast Cancer Severity.

Plasma lipids are carried within lipoproteins with various apolipoprotein content. This study evaluates the interest of measuring the apolipoproteins of circulating lipoproteins in breast cancer. Patients with early-stage breast cancer (n = 140) were included. Tumors differed by the expression of estrogen and progesterone receptor (HR− and HR+ for negative and positive expression) and the proliferation marker Ki-67 (≤20% or ≥30%). Apolipoprotein concentrations were determined in plasma, HDL and non-HDL fractions, and results are given in mg/dL, median (25th–75th). Patients did not differ in their plasma and lipoprotein lipid concentrations. HDL apoC-I and non-HDL apoC-II were reduced (1.34 (1.02–1.80) vs. 1.61 (1.32–2.04), p = 0.04; 0.31 (0.18–0.65) vs. 0.63 (0.39–1.02), p = 0.01; respectively), in RH-/high Ki-67 patients in comparison to RH-/low Ki-67 patients, while plasma apoD and HDL apoD were higher (3.24 (2.99–4.16) vs. 3.07 (2.39–3.51), p = 0.04; 2.74 (2.36–3.35) vs. 2.45 (2.01–2.99), p = 0.04; respectively). When RH+/high Ki-67 patients were compared with RH+/low Ki-67 patients, HDL apoC-I and HDL apoC-III were higher (1.56 (1.20–1.95) vs. 1.35 (1.10–1.62), p = 0.02; 2.80 (2.42–3.64) vs. 2.38 (1.69–2.96), p = 0.02; respectively). The distribution of exchangeable apolipoproteins, such as apoC-I, apoC-II, apoC-III, apoD, between lipoproteins is linked to the severity of breast cancer.

Sex-specific associations of adiposity with cardiometabolic traits in the UK: A multi-life stage cohort study with repeat metabolomics.

BackgroundSex differences in cardiometabolic disease risk are commonly observed across the life course but are poorly understood and may be due to different associations of adiposity with cardiometabolic risk in females and males. We examined whether adiposity is differently associated with cardiometabolic trait levels in females and males at 3 different life stages.Methods and findingsData were from 2 generations (offspring, Generation 1 [G1] born in 1991/1992 and their parents, Generation 0 [G0]) of a United Kingdom population-based birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). Follow-up continues on the cohort; data up to 25 y after recruitment to the study are included in this analysis. Body mass index (BMI) and total fat mass from dual-energy X-ray absorptiometry (DXA) were measured at mean age 9 y, 15 y, and 18 y in G1. Waist circumference was measured at 9 y and 15 y in G1. Concentrations of 148 cardiometabolic traits quantified using nuclear magnetic resonance spectroscopy were measured at 15 y, 18 y, and 25 y in G1. In G0, all 3 adiposity measures and the same 148 traits were available at 50 y. Using linear regression models, sex-specific associations of adiposity measures at each time point (9 y, 15 y, and 18 y) with cardiometabolic traits 3 to 6 y later were examined in G1. In G0, sex-specific associations of adiposity measures and cardiometabolic traits were examined cross-sectionally at 50 y. A total of 3,081 G1 and 4,887 G0 participants contributed to analyses. BMI was more strongly associated with key atherogenic traits in males compared with females at younger ages (15 y to 25 y), and associations were more similar between the sexes or stronger in females at 50 y, particularly for apolipoprotein B–containing lipoprotein particles and lipid concentrations. For example, a 1 standard deviation (SD) (3.8 kg/m2) higher BMI at 18 y was associated with 0.36 SD (95% confidence interval [CI] = 0.20, 0.52) higher concentrations of extremely large very-low-density lipoprotein (VLDL) particles at 25 y in males compared with 0.15 SD (95% CI = 0.09, 0.21) in females, P value for sex difference = 0.02. By contrast, at 50 y, a 1 SD (4.8 kg/m2) higher BMI was associated with 0.33 SD (95% CI = 0.25, 0.42) and 0.30 SD (95% CI = 0.26, 0.33) higher concentrations of extremely large VLDL particles in males and females, respectively, P value for sex difference = 0.42. Sex-specific associations of DXA-measured fat mass and waist circumference with cardiometabolic traits were similar to findings for BMI and cardiometabolic traits at each age. The main limitation of this work is its observational nature, and replication in independent cohorts using methods that can infer causality is required.ConclusionsThe results of this study suggest that associations of adiposity with adverse cardiometabolic risk begin earlier in the life course among males compared with females and are stronger until midlife, particularly for key atherogenic lipids. Adolescent and young adult males may therefore be high priority targets for obesity prevention efforts.

Enhancing the Cardiovascular Protective Effects of a Healthy Dietary Pattern with Wolfberry (Lycium barbarum): A Randomized Controlled Trial

Abstract Objectives The study aimed to investigate the impact of wolfberry (Lycium barbarum) consumption as part of a healthy dietary pattern on cardiovascular health in Singaporean middle-aged and older adults. It was hypothesized that the consumption of wolfberry could further enhance the cardiovascular protective effects of a healthy dietary pattern. Methods This was a 16 week, parallel design, randomized controlled trial where 40 Singaporean men and women (aged 50 to 64 years) received dietary counselling to follow a healthy dietary pattern either with or without 15 g/day of dried whole wolfberry, cooked and consumed as part of their meals. Blood pressure, serum lipid-lipoprotein concentrations and dietary compliance using 3-day food records were monitored every 4 weeks. Further evaluation of cardiovascular disease (CVD) biomarkers, broadly classified as serological (total nitrate/nitrite, endothelin-1, intercellular adhesion molecule-1, angiopoietin-1, angiopoietin-2 and von-Willebrand factor), structural (carotid intima-media thickness using B-mode ultrasonography) and functional (flow-mediated dilation using B-mode ultrasonography and circulating endothelial progenitor cells (CD34+/KDR+) by fluorescence-activated cell sorting) were analyzed before and after intervention. Results Adherence to a healthy dietary pattern contributed to a time dependent effect on both the plasma total nitrate/nitrite (P &amp;lt; 0.01) and plasma endothelin-1 (P &amp;lt; 0.005) which were raised and lowered respectively at week 16. However, changes were significant only in the wolfberry group (total nitrate/nitrite: 15.9 ± 1.8 to 19.4 ± 2.2 μmol/L, P &amp;lt; 0.05; endothelin-1: 1.31 ± 0.12 to 1.11 ± 0.10 ng/L, P &amp;lt; 0.01) and not in the control group. Moreover, a significant increase in serum high density lipoprotein (HDL) cholesterol was also detected solely in the wolfberry group (1.56 ± 0.10 to 1.65 ± 0.10 mmol/L, P &amp;lt; 0.05). The other serological, structural and functional biomarkers of cardiovascular health showed no observable change after the intervention. Conclusions Incorporating wolfberry to your daily meals may augment the cardiovascular protective benefits of a healthy dietary pattern by improving the regulation of vascular tone and plasma lipid-lipoprotein profile in Singaporean middle-aged and older adults. Funding Sources Ministry of Education, Singapore.

Skin Carotenoid Status Is a Potential Surrogate Marker for Cardiovascular Disease Risk Determination in Middle-Aged and Older Adults

Abstract Objectives The study aimed to examine the associations between skin carotenoid status and plasma carotenoids with classical cardiovascular disease (CVD) risk factors among a middle-aged and older Singaporean population. It was hypothesized that skin carotenoid status and plasma carotenoids could be used as an indicator for CVD risk. Methods This cross-sectional study recruited 45 men and 59 women, aged 50 to 75 years, from a community in Singapore (n = 104). Dietary information was obtained using 3-day food records, skin carotenoid status was measured using resonance Raman spectroscopy and plasma carotenoids were analyzed with high-performance liquid chromatography. CVD risk was determined using classical risk factors including blood pressure (BP), serum lipid-lipoprotein concentrations, as well as overall CVD risk predictors such as the number of metabolic syndrome components and a 10-year CVD risk prediction using the Framingham Heart Study risk score calculator. Results Multiple linear regression with covariate adjustments indicated that skin carotenoid status and plasma carotenoids were inversely associated with systolic BP (skin: standardized regression coefficient (β) = −0.341, P &amp;lt; 0.001; plasma: β = −0.258, P &amp;lt; 0.05), diastolic BP (skin: β = −0.378, P &amp;lt; 0.001; plasma: β = −0.309, P &amp;lt; 0.005) as well as both the number of metabolic syndrome components (skin: β = −0.383, P &amp;lt; 0.001; plasma: β = −0.434, P &amp;lt; 0.001) and the 10-year CVD risk prediction (skin: β = −0.347, P &amp;lt; 0.001; plasma: β = −0.334, P &amp;lt; 0.001). The associations between skin carotenoid status with metabolic syndrome and the 10-year CVD risk were null with the inclusion of plasma carotenoids as a covariate which suggested its role as a mediator. Despite the positive linear association between skin carotenoid status and dietary carotenoids intake (Pearson's coefficient: 0.204, P &amp;lt; 0.001), dietary carotenoids were not directly correlated with the CVD risk factors analyzed. Conclusions Skin carotenoid status can function not only as a dietary biomarker, but also, as a potential surrogate marker for CVD risk in middle-aged and older Singaporeans. Funding Sources National University of Singapore Ministry of Education, Singapore Agency for Science, Technology and Research (Singapore).

1338-P: Lipoprotein Insulin Resistance Scores Decrease after a Lifestyle Intervention among Obese Adolescents with Prediabetes

Introduction: Insulin resistance (IR) is associated with impaired lipid metabolism. The Lipoprotein Insulin Resistance Index (LP-IR) is a novel composite biomarker that estimates IR from lipoprotein particle size and concentration, and prospectively predicts type 2 diabetes (T2D) in adults. Less is known about LP-IR and T2D risk in youth. This study evaluated the effect of a lifestyle intervention on LP-IR scores in obese Latino youths with prediabetes. Methods: Obese Latino adolescents (n=27, 15.5±1.1 years, 13 male/14 female) with prediabetes (defined as a 2-hour, post-challenge glucose ≥120 mg/dL) completed a 12-week intervention including nutrition education (one hour/week) and moderate-to-vigorous physical activity (three hours/week). Measurements at baseline and 12 weeks included anthropometrics, total, large, medium, and small lipoprotein particle concentrations (VLDL and chylomicron, LDL, and HDL), mean lipoprotein particle sizes (VLDL, LDL, HDL), lipid concentrations (total triglyceride, VLDL and chylomicron triglyceride, and HDL cholesterol), and LP-IR scores using nuclear magnetic resonance spectroscopy. Results: After adjusting for body fat and sex, significant reductions in LP-IR scores (63.2±14.4 vs. 59.0±15.5 units, p=0.013), large VLDL and chylomicron particle concentration (9.1±7.8 vs. 7.3±6.2 nmol/L, p=0.004), total HDL particle concentration (30.2±4.3 vs. 28.3±3.9 μmol/L, p=0.013), total triglyceride concentration (144.5±91.9 vs. 122.9±77.9 mg/dL, p=0.002), as well as VLDL and chylomicron triglyceride concentration (117.5±66.7 vs. 102.0±55.7 mg/dL, p=0.020) were observed following lifestyle intervention. Conclusion: Lifestyle intervention significantly reduces LP-IR scores and lipoprotein particle parameters in obese adolescents with prediabetes and may decrease future risk of cardiometabolic disorders through improvements in insulin resistance and lipoprotein metabolism. Disclosure A.M. Renteria-Mexia: None. M. Olson: None. M.A. Connelly: Employee; Self; LabCorp. S. Vega-López: None. A. Williams: None. G.Q. Shaibi: None. Funding National Institute on Minority Health and Health Disparities (P20MD002316, U54MD002316); Programa para el Desarrollo Profesional Docente, para el Tipo Superior, México (to A.M.R-M.)

Effect of Dietary Counseling on a Comprehensive Metabolic Profile from Childhood to Adulthood

ObjectivesTo study the effects of repeated, infancy-onset dietary counseling on a detailed metabolic profile. Effects of dietary saturated fat replacement on circulating concentrations of metabolic biomarkers still remain unknown.Study designThe Special Turku Coronary Risk Factor Intervention Project (STRIP) study is a longitudinal, randomized atherosclerosis prevention trial in which repeated dietary counseling aimed at reducing the proportion of saturated fat intake. Nuclear magnetic resonance metabolomics quantified circulating metabolites from serum samples assessed at age 9 (n = 554), 11 (n = 553), 13 (n = 508), 15 (n = 517), 17 (n = 457), and 19 (n = 417) years.ResultsThe intervention reduced dietary intake of saturated fat (mean difference in daily percentage of total energy intake: −2.1 [95% CI −1.9 to −2.3]) and increased intake of polyunsaturated fat (0.6 [0.5-0.7]). The dietary counseling intervention led to greater serum proportions of polyunsaturated fatty acids (P < .001), with greater proportions of both circulating omega-3 (P = .02) and omega-6 (P < .001) fatty acids. The proportion of saturated fatty acids in serum was lower for both boys and girls in the intervention group (P < .001), whereas the serum proportion of monounsaturated fat was lower for boys in the intervention group only (P < .001). The intervention also reduced circulating intermediate-density lipoprotein and low-density lipoprotein lipid concentrations (P < .01). Dietary intervention effects on nonlipid biomarkers were minor except from greater concentrations of glutamine in the intervention group.ConclusionsRepeated dietary counseling from infancy to early adulthood yielded favorable effects on multiple circulating fatty acids and lipoprotein subclass lipids, particularly in boys. These molecular effects substantiate the beneficial role of saturated fat replacement on the metabolic risk profile.Trial registrationClinicalTrials.gov: NCT00223600.

Spectrophotometry and Ultracentrifugation for Measurement of Plasma Lipids in Dogs with Diabetes Mellitus.

BackgroundThere are conflicting reports of plasma lipoprotein lipid content in dogs with diabetes mellitus (DM).ObjectivesTo determine lipoprotein lipid content of plasma of dogs with DM by spectrophotometry and ultracentrifugation; to compare lipoprotein lipid content in diabetic and healthy dogs; and to quantify apolipoprotein B‐100 (ApoB) in dogs with DM.Animals22 dogs with DM and 9 healthy dogs.MethodsCross‐sectional study. Triglyceride (TG), total cholesterol (TC), and high‐density lipoprotein cholesterol (HDL‐C) concentrations were measured by spectrophotometry. Very low‐density lipoprotein cholesterol (VLDL‐C) and low‐density lipoprotein cholesterol (LDL‐C) concentrations were calculated after ultracentrifugation. Non‐HDL‐C cholesterol was calculated by subtracting HDL‐C from TC. ApoB was quantified by ELISA. The Mann‐Whitney test was used for comparison of median lipoprotein concentrations, and Spearman's correlation was used to assess associations between ApoB and lipoprotein fractions.ResultsAll values are reported in mg/dL. Median TG (122), TC (343.5), HDL‐C, (200), VLDL‐C, (27) LDL‐C (68), non‐HDL‐C (114), and ApoB (320) were significantly higher in dogs with DM, compared to healthy dogs (57, 197, 168, 12, 16, 31, and 258, respectively, P‐values 0.0079, <0.001, 0.029, 0.011, <0.001, <0.001, 0.025, respectively). A significant association was found between ApoB and LDL‐C (Spearman's rho = 0.41, P = 0.022) and between ApoB and non‐HDL‐C (Spearman's rho = 0.40, P = 0.027).Conclusions and Clinical ImportanceDyslipidemia of dogs with DM is characterized by pronounced increases in LDL‐C and non‐HDL‐C concentrations, although all lipoprotein fractions are significantly increased. Knowledge of specific lipoprotein fraction alterations in dogs with DM can enhance treatment options for diabetic dyslipidemia in dogs.

Lipoprotein cholesterol and triglyceride concentrations associated with dog body condition score; effect of recommended fasting duration on sample concentrations in Japanese private clinics.

The objectives of this study were to survey clinics’ guidance about recommended fasting duration (FD) prior to lipoprotein analysis, and to characterize lipoprotein cholesterol and triglyceride concentrations in obese and overweight dogs categorized on the basis of the 5-point body condition score (BCS) scale. A dataset was created from lipoprotein analysis medical records of 1,538 dogs from 75 breeds in 354 clinics from 2012 to 2013. A phone survey was conducted to obtain the clinics’ FD. Two-level linear mixed-effects models were applied to the data. Over 50% of the clinics said they recommended fasting for 12 hr or more. Dogs in clinics with FD 12 hr or more had lower chylomicron triglyceride concentrations than those in clinics with FD less than 8 hr (P=0.05). Mean (± SEM) BCS at sampling was 3.7 ± 0.02. Obese and overweight dogs had higher very low density lipoprotein (VLDL) and high density lipoprotein (HDL) cholesterol and triglyceride concentrations than ideal dogs (P<0.05), but no such difference was found for low density lipoprotein cholesterol and triglyceride concentrations (P≥0.07). Across all BCS, as dog age rose from 0 to 8 years old, HDL cholesterol concentrations decreased by 13.5 mg/dl, whereas VLDL triglyceride concentrations increased by 81.7 mg/dl (P<0.05). In conclusion, FD of 8 hr or less may affect lipoprotein lipid concentrations. Obese and overweight dogs were characterized as having high VLDL and HDL cholesterol and triglyceride concentrations.

Plant stanol esters lower LDL cholesterol level in statin-treated subjects with type 1 diabetes by interfering the absorption and synthesis of cholesterol

Objective We investigated the effects of plant stanol esters (STAEST) on serum cholesterol and lipoprotein lipid concentrations and serum non-cholesterol sterols in patients with type 1 diabetes who were on statin treatment. Methods In a randomized, double-blind, parallel study the intervention group ( n = 12) consumed vegetable oil-based spread enriched with STAEST (3.0 g/d of plant stanols), and the control group ( n = 12) consumed the same spread containing no added plant stanols for 4 weeks. Results Serum total, LDL and non-HDL cholesterol concentrations were decreased by 9.6, 16.4 and 15.3% compared with the baseline concentrations in the STAEST group ( P < 0.05 for all). The respective reductions were 7.8, 14.8 and 12.2% compared with the controls ( P < 0.05 for all). No effects on HDL cholesterol or serum triglyceride concentrations were found. The STAEST consumption significantly decreased serum plant sterol concentrations and the ratios to cholesterol by 30–32 and 25–27% ( P < 0.05 for all) compared with the baseline levels, respectively. Cholesterol synthesis markers were not increased in the STAEST group, but serum lathosterol to campesterol ratio was significantly increased by 57% compared with the baseline levels indicating increased cholesterol synthesis at least to some extent in compensation for decreased cholesterol absorption. However, cholesterol homeostasis, intact at baseline and in the control group also during the intervention was lost in the STAEST group. Conclusion STAEST significantly decreased serum total, LDL and non-HDL cholesterol concentrations and thus offers an additional benefit to cholesterol lowering in patients with type 1 diabetes who are on statin treatment.

The effect of whole grain wheat sourdough bread consumption on serum lipids in healthy normoglycemic/normoinsulinemic and hyperglycemic/hyperinsulinemic adults depends on presence of the APOE E3/E3 genotype: a randomized controlled trial

BackgroundEpidemiological studies associate consumption of whole grain foods, including breads, with reduced cardiovascular disease (CVD) risk; however, few studies have compared wheat whole grains with wheat refined grains.MethodsThis study investigated effects of 6-week consumption of whole grain wheat sourdough bread in comparison to white bread on fasting serum lipids in normoglycemic/normoinsulinemic (NGI; n = 14) and hyperglycemic/hyperinsulinemic (HGI; n = 14) adults. The influence of single-nucleotide polymorphisms, 3 within the APOE gene (E2, E3, E4) and 2 within the hepatic lipase gene promoter (LIPC -514C>T, LIPC -250G>A) were considered.ResultsAt baseline, HGI participants had significantly higher body weight, waist circumference, body fat, and fasted glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), glucagon, triacylglycerols (TAG) and TAG:HDL-cholesterol, compared to NGI participants; however, none of these in addition to none of the other serum lipids, differed between bread treatments, within either participant group. For participants with the APOE E3/E3 genotype, LDL-cholesterol (P = 0.02) increased in the NGI group (n = 7), and TAG (P = 0.03) and TAG:HDL-cholesterol (P = 0.04) increased in the HGI group (n = 10), following consumption of whole grain wheat sourdough compared to white bread.ConclusionsIn summary, 6-week consumption of whole grain wheat sourdough bread did not significantly modulate serum lipids in NGI or HGI adults; however, it significantly increased LDL-cholesterol, TAG and TAG:HDL-cholesterol in participants with the APOE E3/E3 genotype. These data add to limited literature comparing wheat whole grains to wheat refined grains on CVD risk and highlight the need to consider genetic variation in relation to lipoprotein lipid content and CVD risk.

Characterization of metabolic interrelationships and in silico phenotyping of lipoprotein particles using self-organizing maps

Plasma lipid concentrations cannot properly account for the complex interactions prevailing in lipoprotein (patho)physiology. Sequential ultracentrifugation (UCF) is the gold standard for physical lipoprotein isolations allowing for subsequent analyses of the molecular composition of the particles. Due to labor and cost issues, however, the UCF-based isolations are usually done only for VLDL, LDL, and HDL fractions; sometimes with the addition of intermediate density lipoprotein (IDL) particles and the fractionation of HDL into HDL(2) and HDL(3) (as done here; n = 302). We demonstrate via these data, with the lipoprotein lipid concentration and composition information combined, that the self-organizing map (SOM) analysis reveals a novel data-driven in silico phenotyping of lipoprotein metabolism beyond the experimentally available classifications. The SOM-based findings are biologically consistent with several well-known metabolic characteristics and also explain some apparent contradictions. The novelty is the inherent emergence of complex lipoprotein associations; e.g., the metabolic subgrouping of the associations between plasma LDL cholesterol concentrations and the structural subtypes of LDL particles. Importantly, lipoprotein concentrations cannot pinpoint lipoprotein phenotypes. It would generally be beneficial to computationally enhance the UCF-based lipoprotein data as illustrated here. Particularly, the compositional variations within the lipoprotein particles appear to be a fundamental issue with metabolic and clinical corollaries.

Long-term effect of calcium-vitamin D3 fortified milk on blood pressure and serum lipid concentrations in healthy older men

Some epidemiological and clinical studies have shown that increased dairy consumption or calcium and/or vitamin D supplementation can have a beneficial effect on blood pressure, and lipid and lipoprotein concentrations. The aim of this study was to assess the long-term effects of calcium-vitamin D(3) fortified milk on blood pressure and lipid-lipoprotein concentrations in community-dwelling older men. This is a substudy of a 2-year randomized controlled trial in which 167 men aged >50 years were assigned to receive either 400 ml per day of reduced fat (approximately 1%) milk fortified with approximately 1000 mg of calcium and 800 IU of vitamin D(3) or to a control group receiving no additional fortified milk. Weight, blood pressure, lipid and lipoprotein concentrations were measured every 6 months. Participants on lipid-lowering (n=32) or antihypertensive medication (n=39) were included, but those who commenced, increased or decreased their medication throughout the intervention were excluded (n=27). In the 140 men included in this study (milk, n=73; control, n=67), there were no significant effects of the calcium-vitamin D(3) fortified milk on weight, systolic or diastolic blood pressure, total cholesterol, high-density lipoprotein or low-density lipoprotein cholesterol or triglyceride concentrations at any time throughout the intervention. Similar results were observed after excluding men taking antihypertensive or lipid-lowering medication or limiting the analysis to those with baseline calcium intakes <1000 mg per day and/or with hypovitaminosis D (25(OH)D <75 nmol/l). Supplementation with reduced-fat calcium-vitamin D(3) fortified milk did not have a beneficial (nor detrimental) effect on blood pressure, lipid or lipoprotein concentrations in healthy community-dwelling older men.

A large discoidal lipoprotein present in only one of two closely related crayfish

The hemolymph lipoproteins of two European freshwater crayfish, Astacus astacus and Astacus leptodactylus, were isolated and characterized. The former species possesses two sex-independent lipoproteins, which can be related to the formerly described high-density lipoprotein (HDL)/beta-glucan binding protein and very high-density lipoprotein/clotting protein from other crustaceans. The latter species, however, contains an additional third lipoprotein with a unique structure. It is a large discoidal HDL with a diameter of 42 nm, a thickness of 7 nm and a density of 1.1 g/ml. SDS-PAGE revealed two different apolipoproteins with molecular masses of 240 and 85 kDa, respectively, arranged in a 1:1 stoichiometry as judged from cross linking experiments. The lipid content of this lipoprotein was 67%, far higher than in every other crustacean lipoprotein described so far. The native molecular mass of this HDL-type lipoprotein was estimated to be about 930 kDa. The lipid content of the other lipoproteins ranged between 25 and 30% for the HDL/beta-glucan binding protein and 6-8% for the VHDL/clotting protein.

A novel Bayesian approach to quantify clinical variables and to determine their spectroscopic counterparts in 1H NMR metabonomic data

BackgroundA key challenge in metabonomics is to uncover quantitative associations between multidimensional spectroscopic data and biochemical measures used for disease risk assessment and diagnostics. Here we focus on clinically relevant estimation of lipoprotein lipids by 1H NMR spectroscopy of serum.ResultsA Bayesian methodology, with a biochemical motivation, is presented for a real 1H NMR metabonomics data set of 75 serum samples. Lipoprotein lipid concentrations were independently obtained for these samples via ultracentrifugation and specific biochemical assays. The Bayesian models were constructed by Markov chain Monte Carlo (MCMC) and they showed remarkably good quantitative performance, the predictive R-values being 0.985 for the very low density lipoprotein triglycerides (VLDL-TG), 0.787 for the intermediate, 0.943 for the low, and 0.933 for the high density lipoprotein cholesterol (IDL-C, LDL-C and HDL-C, respectively). The modelling produced a kernel-based reformulation of the data, the parameters of which coincided with the well-known biochemical characteristics of the 1H NMR spectra; particularly for VLDL-TG and HDL-C the Bayesian methodology was able to clearly identify the most characteristic resonances within the heavily overlapping information in the spectra. For IDL-C and LDL-C the resulting model kernels were more complex than those for VLDL-TG and HDL-C, probably reflecting the severe overlap of the IDL and LDL resonances in the 1H NMR spectra.ConclusionThe systematic use of Bayesian MCMC analysis is computationally demanding. Nevertheless, the combination of high-quality quantification and the biochemical rationale of the resulting models is expected to be useful in the field of metabonomics.

Uso de tabaco e perfil lipídico-lipoprotéico plasmático em adolescentes

To analyze the impact of tobacco use on plasma lipid lipoprotein profile in representative sample of adolescents. A sample of 452 subjects (246 girls and 206 boys) 15 to 18 years old were included in the study. Each participant completed a structured and self-administered questionnaire concerning tobacco use. Plasma lipid-lipoprotein concentrations were measured by standard procedures. Differences between mean values were evaluated by analysis of covariance, controlling for saturated fat and cholesterol intake. Odds ratio was used to estimate the relative risk of the smokers being classified with an undesirable level of a plasma lipidlipoprotein parameter. The proportion of smokers was 20.9% for boys and 15.4% for girls. The average consumption of cigarettes per day was 9.2+/-4.7 for boys and 5.6+/-3.1 for girls. When compared with non-smokers, boy and girl smokers showed a significantly higher serum levels of total cholesterol, LDL-cholesterol, triglycerides and apolipoprotein B100, and significantly lower serum levels of HDL-cholesterol. Adolescent smokers tended to show a two-fold higher risk of altered lipid-lipoprotein levels than non-smokers. The present data could imply that intervention promoting a healthy lifestyle, including non smoking, should start at an early age to prevent or delay development of atherosclerotic lesions and ultimately to minimize the appearance of premature coronary heart disease in adults.