High-density Lipoprotein Subfractions Research Articles

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease.

Chronic kidney disease (CKD) is a worldwide health problem with steadily increasing occurrence. Significantly elevated cardiovascular morbidity and mortality have been observed in CKD. Cardiovascular diseases are the most important and frequent cause of death of CKD patients globally. The presence of CKD is related to disturbances in lipoprotein metabolism whose consequences are dyslipidemia and the accumulation of atherogenic particles. CKD not only fuels the reduction of high-density lipoprotein (HDL) cholesterol concentration, but also it modifies the composition of this lipoprotein. The key role of HDL is the participation in reverse cholesterol transport from peripheral tissues to the liver. Moreover, HDL prevents the oxidation of low-density lipoprotein (LDL) cholesterol by reactive oxygen species (ROS) and protects against the adverse effects of oxidized LDL (ox-LDL) on the endothelium. Numerous studies have demonstrated the ability of HDL to promote the production of nitric oxide (NO) by endothelial cells (ECs) and to exert antiapoptotic and anti-inflammatory effects. Increasing evidence suggests that in patients with chronic inflammatory disorders, HDLs may lose important antiatherosclerotic properties and become dysfunctional. So far, no therapeutic strategy to raise HDL, or alter the ratio of HDL subfractions, has been successful in slowing the progression of CKD or reducing cardiovascular disease in patients either with or without CKD.

Rationale and design of the expanded combination of evolocumab plus empagliflozin in diabetes: EXCEED-BHS3 trial.

Background:Patients with type 2 diabetes mellitus (T2DM) remain at increased cardiovascular residual risk and endothelial dysfunction, even after optimizing metabolic control and treatment by sodium-glucose-2 transporter inhibitors (SGLT2-is). The present study was based on the hypothesis that proprotein convertase subtilisin/kexin 9 inhibitor (PCSK9i) therapy may mitigate endothelial dysfunction in T2DM patients who are on regular treatment by SGLT2-i.Methods:The EXCEED-BHS3 is a prospective, single-center, investigator-blinded, open-label, randomized clinical trial. Participants (n = 110) will be randomized (1:1) to either empagliflozin 25 mg/day alone or empagliflozin 25 mg/day plus evolocumab 140 mg every 2 weeks in addition to optimal medical care. The primary endpoint was defined as the change in the 1-min flow-mediated dilation (FMD) after 16 weeks of treatment. The secondary endpoint is the FMD change after ischemia/reperfusion injury protocol (reserve FMD) after 16 weeks of treatment. Exploratory outcomes comprise the change in FMD and reserve FMD after 8 weeks of treatment and the change after 16 weeks of treatment in the following parameters: plasma levels of nitric oxide, vascular cell adhesion molecule-1 and isoprostane, high-density lipoprotein (HDL) and low-density lipoprotein subfractions profile, HDL function, blood pressure, body mass index, waist circumference and adipokines.Conclusion:This will be the first study to evaluate the add-on effect of PCSK9i on endothelial function of T2DM patients under regular use of empagliflozin.Trial registration:ClinicalTrials.gov identifier: NCT03932721

Effects of Different Intensities of Circuit Resistance Training on Plasma level of High-Density Lipoprotein Subfractions and Apolipoprotein M in Untrained Young Men

Effects of Different Intensities of Circuit Resistance Training on Plasma level of High-Density Lipoprotein Subfractions and Apolipoprotein M in Untrained Young Men

Relation of oxidized-low-density lipoprotein and high-density lipoprotein subfractions in non-treated patients with coronary artery disease

BackgroundOxidized-low-density lipoprotein (ox-LDL), as well as high-density lipoprotein (HDL) and its subfractions play important role in the development of coronary artery disease (CAD). MethodsA total of 1417 individuals who received selective coronary angiography (CAG) without lipids-lowering treatments were consecutively enrolled. Patients were divided into CAD (n = 942) and non-CAD group (n = 475). The severity of CAD was assessed by Gensini Scores (GS) system. The correlations of ox-LDL with HDL subfractions were analyzed. ResultsCompared with non-CAD subjects, CAD patients had higher ox-LDL but lower concentrations of HDL cholesterol (p = 0.002) and large HDL subfractions (p = 0.004). And ox-LDL was negatively correlated with large HDL subfractions in patients with severe CAD (p < 0.05). Moreover, ox-LDL was elevated and large HDL subfractions decreased with the increase of the number of stenotic coronary arteries and GS (p < 0.05, respectivelly). ConclusionsThe correlations between ox-LDL and cholesterol level of large HDL particles varied among CAD and non-CAD, and CAD with different severities of atherosclerosis.

Associations between the lipid profile and the development of hypertension in young individuals - the preliminary study.

IntroductionHypertension is the leading direct cause of death in the world and one of the most important risk factors for cardiovascular disease (CVD). Elevated blood pressure (BP) often coexists with lipid disorders and is an additional factor that increases CV risk. Nowadays, we are able to distinguish low density lipoproteins (LDL) and high density lipoproteins (HDL) subfractions. Except LDL also HDL small subfractions can increase the risk of CV events. Therefore, we aimed to investigate the associations between changes of lipoprotein subfractions and the risk of hypertension development.Material and methodsIn 2-year long study 200 volunteers with normal blood pressure at the age of 19–32 years were included. Each volunteer underwent detailed medical examination, 12-lead electrocardiogram was taken at rest, echocardiogram, lipid subfraction assessment (using Lipoprint®) and two 24-hour BP measurements.ResultsMean total cholesterol concentration was 189 mg/dl (4.89 mmol/l), with mean LDL concentration of 107 mg/dl (2.77 mmol/l), HDL of 63 mg/dl (1.63 mmo/l), very low-density lipoprotein (VLDL) of 40 mg/dl (1.04 mmol/l) and triglycerides (TG) of 89 mg/dl (1.00 mmol/l). Subfractions LDL 1–3 were most abundant, LDL 4–5 making up a marginal portion and LDL 6–7 were not observed. Whereas, subfractions HDL 4–6 were most abundant, in lower concentration was present HDL 1–3 and HDL 8–10. We showed that increased systolic blood pressure coreclated significantly with HDL cholesterol concentrations (p = 0.0078), HDL intermediate subgractions (p = 0.0451), with HDL-3 subfraction (p = 0.0229), and intermediate density lipoprotein-A (IDL-A) (p = 0.038). A significant correlation between increased diastolic blood pressure and HDL lipoprotein levels (p = 0.0454) was only observed.ConclusionsObtained results indicating correlation between total HDL levels and HDL-3 subfraction concentration (for systolic BP) and the tendency to develop hypertension.

Distinct phospholipid and sphingolipid species are linked to altered HDL function in apolipoprotein A-I deficiency

Familial apolipoprotein A-I (apoA-I) deficiency (FAID) involving low levels of both apoA-I and high-density lipoprotein (HDL) cholesterol is associated with accelerated atherosclerosis. The objective of this study was to define distinctive patterns in the lipidome of HDL subpopulations in FAID in relationship to antiatherogenic activities. Five HDL subfractions were isolated by ultracentrifugation from plasma of FAID Caucasian patients (n=5) and age-matched healthy normolipidemic Caucasian controls (n=8), and the HDL lipidome (160 molecular species of 9 classes of phospholipids and sphingolipids) was quantitatively evaluated. Increased concentrations of numerous molecular species of lysophosphatidylcholine (up to 12-fold), ceramides (up to 3-fold), phosphatidylserine (up to 34-fold), phosphatidic acid (up to 71-fold), and phosphatidylglycerol (up to 20-fold) were detected throughout all five HDL subpopulations as compared with their counterparts from controls, whereas concentrations of phosphatidylethanolamine species were decreased (up to 5-fold). Moderately to highly abundant, within their lipid class, species of phosphatidylcholine, sphingomyelin, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, and ceramide featuring multiple unsaturations were primarily affected by apoA-I deficiency; their HDL content, particularly that of phosphatidylcholine (34:2), was strongly correlated with HDL function, impaired in FAID. Metabolic pathway analysis revealed that sphingolipid, glycerophospholipid, and linoleic acid metabolism was significantly affected by FAID. These data reveal that altered content of specific phospholipid and sphingolipid species is linked to deficient antiatherogenic properties of HDL in FAID.

UPTAKE OF CHOLESTEROL ESTERS BEING A PART OF THE DIFFERENT FRACTIONS OF BLOOD PLASMA LIPOPROTEINS BY RATS ORGANS AND TISSUES

The paper deals with the functions of the main classes of blood plasma lipoproteins (LP) that are associated with the transport of cholesterol esters included in their composition. The aim of the study was to investigate the features of the uptake of cholesterol esters associated with plasma LP fractions (very low (VLDL), low (LDL), and high density LPs (HDL)) by rat organs and tissues, and to show the participation of various subfractions of HDL (HDL 2 and HDL 3 ) as specific cholesterol carriers in the main steroid-producing organs of rats. Material and methods. The in vivo studies with intravenous LP injection of 14 C labeled cholesterol oleate ( 14 C-OCh) associated with plasma LP fractions have been carried out. Results. Intravenous injection of a 14 C-OCh) in the composition with VLDL led to the maximal mark uptake by the liver. Three times less uptake of labeled cholesterol was observed in the adrenal glands, testes and heart muscle. In other tissues radioactivity gradually decreased in the raw: spleen > lungs > kidneys > thyroid gland and adipose tissue. After the injection of 14 C-OCh in the composition of LDL marked predominant uptake of the label by the adrenal glands, testes, and liver. A feature of the use of HDL as a carrier platform for 14 C-OCh is the high accumulation of label in steroid-producing organs: the adrenal glands and testis. The dynamics of uptake of 14 C-OCh in the composition of HDL by the adrenal glands and testes of rats in different time intervals after injection (30 min, 3, 6 and 12 h) was studied. Adrenal cells actively uptake 14 C-OCh from HDL, as a result of which the radioactivity of the tissue increased rapidly and after 30 minutes almost reached its maximum. In contrast to the adrenal glands uptake of the testis was characterized by a gradual increase in radioactivity with a maximum of 6 hours and a rather sharp decrease to 12 hours from the beginning of the experiment. In vitro experiments showed the differences in the effect of HDL 2 and HDL 3 on the corticosterone production by the adrenal glands of rats. Conclusions. The paper presents the features of uptake of cholesterol esters by organs and tissues of rats depending on the used LP-transporter (VLDL, LDL, HDL). In addition, the results suggest that HDL 3 subfraction may be the more preferred source of cholesterol for steroid synthesis in the adrenal cortex of rats compared to HDL 2 subfraction.

Weight loss achieved by bariatric surgery modifies high-density lipoprotein subfractions and low-density lipoprotein oxidation towards atheroprotection

ObjectivesWeight loss achieved by laparoscopic adjustable gastric banding (LAGB) induces an increase in high-density lipoprotein cholesterol (HDLc) but a small effect on low-density lipoprotein (LDL), although changes in their quality (size and composition) are uncertain. Our aim was to study the impact of weight loss, achieved 13-months after LAGB, on inflammation and dyslipidemia, focusing on HDL and LDL subfractions, and oxidized LDL (oxLDL). Design & methodsWe evaluated standard lipid profile, HDL and LDL subfractions, oxLDL, interleukin (IL)-6 and C-reactive protein (CRP), in twenty obese patients, before (T0) and 13-months after LAGB (T1), and in seventeen healthy controls. ResultsAt T1, patients showed lower body weight (12% median weight loss) and anthropometric indices; reduction in TG, atherogenic indices, oxLDL, oxLDL/LDL ratio, CRP and IL-6, and enhancement in HDLc; an increase in large HDL and intermediate HDL subfractions, and a decrease in small HDL subfraction; LDL subfractions were not modified. Percentual change (%Δ) of oxLDL, from T0 to T1, correlated significantly and positively with %Δ of small HDL subfraction and with %Δ of body mass index. ConclusionsWeight loss induced atheroprotective changes on inflammation, and lipid profile, enhancing larger HDL, the more atheroprotective subfraction, reducing the less protective subclass, small HDL, and reducing oxLDL and oxLDL/LDL ratio. Quality of lipoproteins appears useful cardiovascular risk biomarkers, deserving further studies.

Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration: Evidence from the EYE-RISK and European Eye Epidemiology Consortia

Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. Pooled analysis of cross-sectional data. Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. AMD features and stage; lipid measurements. HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14-1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91-0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P= 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10-1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P= 7.7× 10-7), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P= 1.0× 10-6 and P= 1.6× 10-4). Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered.

Increased electronegativity of high-density lipoprotein in uremia patients impairs its functional properties and is associated with the risk of coronary artery disease

Background and aimsUremia patients have impaired high-density lipoprotein (HDL) function and a high risk of coronary artery disease (CAD). Increased lipoprotein electronegativity can compromise lipoprotein function, but the effect of increased HDL electronegativity on HDL function and its association with CAD in uremia patient are not clear.We aimed to assess HDL electronegativity and various properties of HDL in uremia patients and investigate whether electronegative HDL is a risk factor for CAD in these individuals. MethodsHDL from 60 uremia patients and 43 healthy controls was separated into 5 subfractions (H1H5) with increasing electronegativity by using anion-exchange chromatography. Lipoprotein content was analyzed by gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry. HDL anti-oxidant, anti-apoptosis and cholesterol efflux activities were examined by fluorescence-based assays. ResultsThe percentage of H5 HDL (H5%) was significantly higher in uremia patients than in controls (p < 0.001). The concentration of apolipoprotein (Apo) AI was lower and apolipoprotein modifications were more prevalent in uremia HDL subfractions than in control HDL subfractions. Carbamylation of ApoAI and ApoCIII was increased in more electronegative HDL subfractions from uremia patients. Anti-oxidant activity, anti-apoptotic activity, and cholesterol efflux capability were reduced in HDL subfractions from uremia patients when compared with control HDL subfractions. Multiple logistic regression analysis showed that H5% was associated with CAD risk in uremia patients. ConclusionsIn HDL of uremia patients, increased electronegativity is accompanied by compositional changes and impaired function. Our findings indicate that increased H5% is associated with increased CAD risk in uremia patients.

Changes in serum afamin and vitamin E levels after selective LDL apheresis.

Afamin is a plasma vitamin E-binding glycoprotein partially associated with ApoA1-containing high-density lipoprotein (HDL) subfractions. In a previous study, the serum vitamin E decreased after low-density lipoprotein (LDL) apheresis, while vitamin E/cholesterol ratio increased. We aimed to study the effect of LDL apheresis on serum afamin level. The serum level of afamin and oxidized LDL were measured by enzyme-linked immunosorbent assay in six severe heterozygous FH patients before and after their first LDL apheresis treatments and in seven healthy controls. We also investigated the changes in total cholesterol, LDL-C, HDL-C, ApoB, ApoA1, HDL subfractions, and α- and γ-tocopherol levels during the treatment. HDL subfractions were detected by an electrophoretic method on polyacrylamide gel (Lipoprint). Serum α- and γ-tocopherol levels were detected by gas chromatography-mass spectrometry. The first treatment sessions decreased serum afamin levels by an average of 9.4%. Total cholesterol, LDL-C, HDL-C and ApoA1 levels decreased by 52.6; 61.8; 10.5; and 14.1%, respectively. We found that α- and γ-tocopherol levels markedly decreased (by 34.1 and 32.9%, respectively), while α- tocopherol/cholesterol and γ-tocopherol/cholesterol ratios significantly increased (by 41.4 and 40.3%, respectively). Oxidized LDL levels significantly decreased. There was a shift toward the larger HDL subfractions. LDL apheresis moderately decreases the circulating levels of afamin parallel to lowering HDL-C and ApoA1 levels. Tocopherol levels decreases markedly compared to afamin levels, however, beneficial changes in vitamin E/cholesterol ratios, oxidized LDL levels and HDL subfraction distribution were detected. These additional effects of LDL apheresis may result in further cardiovascular risk reduction in FH patients.

Diabetes alters the association between high-density lipoprotein subfractions and carotid intima-media thickness: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

High-density lipoprotein cholesterol comprises a group of heterogeneous subfractions that might have differential effects on atherosclerosis. Moreover, prior investigations suggest that the presence of diabetes (T2D) modifies the impact of some subfractions on atherosclerosis. In this study, we aimed to evaluate the association between high-density lipoprotein cholesterol subfractions and carotid intima-media thickness in the baseline assessment of the Brazilian Longitudinal Study of Adult Health participants from the São Paulo investigation centre. We evaluated 3930 individuals between 35 and 74 years without previous cardiovascular disease not using lipid-lowering drugs. High-density lipoprotein cholesterol subfractions (HDL2-C and HDL3-C) were measured by vertical ultracentrifugation (vertical auto profile). The relationship between each high-density lipoprotein cholesterol subfraction and carotid intima-media thickness was analysed by multiple linear regression models. Total high-density lipoprotein cholesterol, as well as HDL2-C and HDL3-C, was negatively associated with carotid intima-media thickness after adjustment for demographic data (all p < 0.001) and traditional risk factors (all p < 0.05). When stratified by T2D status, the HDL2-C/HDL3-C ratio showed a negative association with carotid intima-media thickness in participants with T2D ( p = 0.032), even after fully controlling for confounding variables, including total high-density lipoprotein cholesterol. HDL2-C, HDL3-C and HDL2/HDL3-C ratio are inversely associated with carotid intima-media thickness after adjustment for traditional risk factors. Association of the HDL2-C/HDL3-C ratio is modified by the presence of diabetes, being more pronounced in diabetic individuals.

Association between apolipoprotein E genotypes and panic disorder in Turkish population

Aim: In this study, we aimed to investigate possible interactions among the apolipoprotein E (ApoE) and panic disorder (PD), taking into account serum cholesterol levels and subfractions.Methods: ApoE genotyping was performed by real-time polymerase chain reaction in DNA samples of PD patient group (n = 45) and healthy control group (n = 50). The serum lipid levels, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) subfraction analysis were examined.Results: There was a significant difference of ApoE genotypes in patient and control groups. The E3/E3 genotypes lower whereas E4 allele carriers were significantly higher in PD group ApoE4allele carriers had 3.2-fold higher risk of PD. PD group had significantly lower LDL and HDL levels. In spite of the decreased levels of total LDL, antiatherogenic large LDL subgroup was significantly lower in a patient with PD. Antiatherogenic large HDL and Intermediate HDL levels were lower, while atherogenic small HDL subfraction was significantly higher in PD group. Furthermore, Apo E3/E3 genotype carriers had significantly higher large LDL, HDL, large HDL, intermediate HDL level, and also had highest HDL between all the groups. ApoE4 allele carriers while they had highest atherogenic small HDL level.Conclusion: E4 allele can be associated with PD as an eligible risk factor, the E3/E3 could be a risk-reducing factor for PD. Patients with PD not only had lower LDL and HDL levels but also they have higher atherogenic LDL and HDL subfractions. Also, E3/E3 genotype carriers had convenient but ApoE4 carriers had atherogenic plasma cholesterol levels and subfractions.

Plasminogen Activator Inhibitor-1 Level Correlates with Lipoprotein Subfractions in Obese Nondiabetic Subjects.

Background The elevated level of plasminogen activator inhibitor-1 (PAI-1) in obese subjects with metabolic syndrome and in patients with type 2 diabetes is well established. The association of plasma PAI-1 and lipid metabolism is still unclear. The aim of the present study was to determine the relationship between plasma PAI-1 levels and the distribution of lipoprotein subfractions in obese and lean nondiabetic individuals. Subjects and Methods We enrolled fifty nondiabetic obese patients and thirty-two healthy volunteers. Lipoprotein subfractions were detected with Lipoprint System. Plasma PAI-1, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) concentrations were determined with enzyme-linked immunosorbent assay (ELISA), while serum paraoxonase-1 (PON1) activities were measured by spectrophotometry. Results The TNF-α, IL-6, oxidized low-density lipoprotein (oxLDL), and MPO levels were found to be significantly higher, while PON1 paraoxonase and arylesterase activities were nonsignificantly lower in the obese patients. Strong significant negative correlations were found between plasma PAI-1 concentration and mean LDL size, as well as between PAI-1 concentrations and the levels of the large and intermediate high-density lipoprotein (HDL) subfractions. In multiple regression analysis, PAI-1 was predicted by waist circumference and intermediate HDL subfraction. Conclusion The significant correlations between PAI-1 levels and lipoprotein subfractions indicate the link between PAI-1 and lipid metabolism in obesity.

Association between high-density lipoprotein subfractions and low-grade inflammation, insulin resistance, and metabolic syndrome components: The ELSA-Brasil study

High-density lipoprotein cholesterol (HDL-C) can be divided into subfractions, which may have variable effects in atherogenesis. The results about the association between HDL-C subfractions and risk factors for cardiovascular disease are mixed. The objective of this study was to analyze the association between HDL-C subfractions and each metabolic syndrome component, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and C-reactive protein (CRP). Four thousand five hundred thirty-two individuals between 35 and 74years old without previous manifest cardiovascular disease not using fibrates were enrolled. HDL-C subfractions were separated by vertical ultracentrifugation (vertical auto profile-in mg/dL) into HDL2-C and HDL3-C. HDL2-C/HDL3-C ratio, HOMA-IR, and high-sensitivity CRP were also included in the analysis. Mean age of participants was 51±9years, and 54.8% were women. In univariate analysis, HDL-C, HDL2-C, and HDL3-C were all inversely associated with each of the metabolic syndrome defining factors, HOMA-IR values, and serum CRP. We also observed a negative association between HDL2-C/HDL3-C ratio with the variables aforementioned even after adjusting for smoking, alcohol use, physical activity, and HDL-C levels (P<.01). HDL-C and its subfractions (HDL2-C and HDL3-C) are inversely associated with the defining features of metabolic syndrome, insulin resistance, and systemic inflammation. In addition, the HDL2-C/HDL3-C ratio measured by vertical auto profile is significantly associated with the former factors even after comprehensive adjustment for HDL-C and other confounding variables.

Lipid Metabolism in Patients with End-Stage Renal Disease: A Five Year Follow-up Study

Patients with end-stage renal disease (ESRD) exhibit high morbidity as well as mortality for atherosclerotic cardiovascular diseases (CVD). Therefore, we investigated differences in individual lipoprotein classes and subclasses in ESRD patients under chronic high volume hemodiafiltration (HV-HDF) in comparison with a control group. We also assessed the prognosis of these patients and analyzed these parameters after 5 years follow-up. 57 patients and 50 controls were enrolled. We analysed high density (HDL) and low density (LDL) lipoprotein subfractions using the Quantimetrix Lipoprint(R) system. Subfractions were correlated with selected clinical-biochemical parameters including risk factors for atherosclerotic CVD at the beginning of and after 5 years follow-up. Fourteen patients survived the 5-year follow-up. Follow-up results revealed a shift toward smaller HDL subfractions. In lipoproteins carrying apolipoprotein B, there was a shift of cholesterol from very low density (VLDL) to intermediate density (IDL) lipoproteins and LDLs. Hypolipidaemic therapy did not influence lipoprotein profiles in HV-HDF patients. 1. HV-HDF patients exhibit specific lipid profiles with elevated triacylglycerol, low HDL and LDL and higher content of cholesterol in remnant particles (VLDL and IDL) at the expense of large LDL. HDL subfractions were linked to the number of risk factors for CVD in the control group only. 2. Baseline lipoprotein profiles did not differ between survivors and non-survivors. Non-survivors had higher CRP and lower HDL-C. 3. During the 5 year follow-up period, cholesterol in HDL particles and lipoproteins carrying apolipoprotein B redistributed in survivors towards smaller particles, thus resembling the profile of control patients.

Abstract P195: High-density Lipoprotein Subfractions Are Associated With Low-grade Inflammation, Insulin Resistance and Metabolic Syndrome Components: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Background: HDL cholesterol (HDL-C) can be divided into subfractions, which may have variable association with atherogenic process. There are mixed results about the association between HDL-C subfractions and risk factors for cardiovascular disease. Hypothesis: HDL-C subfractions have different associations with metabolic syndrome, low-grade inflammation and insulin resistance. Methods: 4,532 individuals between 35 and 74 years without previous cardiovascular disease not in use of fibrates were enrolled. HDL-C subfractions were separated by vertical ultracentrifugation (Vertical Auto Profile - in mg/dl) in HDL 2 -C and HDL 3 -C. HDL 2 -C/HDL 3 -C ratio, insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (CRP) were also included in the analysis. Results: The mean age was 51 ± 9 years, and 54.8% were women. In univariate analysis, HDL-C, HDL 2 -C, and HDL 3 -C were all inversely associated with each of the MetS defining factors, HOMA-IR values, and serum CRP. It was also observed a negative association between HDL 2 -C/HDL 3 -C ratio with the variables mentioned above even after adjusting for smoking, alcohol use, physical activity, and HDL-C levels (p &lt;0.01). Conclusion: HDL-C and both subfractions are inversely associated with all the factors that define MetS, insulin resistance and low-grade inflammation. Additionally, the HDL 2 -C/HDL 3 -C subfractions ratio assessed by VAP is also significantly associated with the former factors even after further adjustment for total HDL-C and other confounding variables.

Serum obestatin level strongly correlates with lipoprotein subfractions in non-diabetic obese patients

BackgroundObestatin is a ghrelin-associated peptide, derived from preproghrelin. Although many of its effects are unclear, accumulating evidence supports positive actions on both metabolism and cardiovascular function. To date, level of obestatin and its correlations to the lipid subfractions in non-diabetic obese (NDO) patients have not been investigated.MethodsFifty NDO patients (BMI: 41.96 ± 8.6 kg/m2) and thirty-two normal-weight, age- and gender-matched healthy controls (BMI: 24.16 ± 3.3 kg/m2) were enrolled into our study. Obestatin level was measured by ELISA. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions, intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) levels and mean LDL size were detected by nongradient polyacrylamide gel electrophoresis (Lipoprint).ResultsSerum level of obestatin was significantly lower in NDO patients compared to controls (3.01 ± 0.5 vs. 3.29 ± 0.6 μg/ml, p < 0.05). We found significant negative correlations between the level of obestatin and BMI (r = − 0.33; p < 0.001), level of serum glucose (r = − 0.27, p < 0.05), HbA1c (r = − 0.38; p < 0.001) and insulin (r = − 0.34; p < 0.05). Significant positive correlation was found between obestatin level and the levels of ApoA1 (r = 0.25; p < 0.05), large HDL subfraction ratio and level (r = 0.23; p < 0.05 and r = 0.24; p < 0.05), IDL (r = 0.25 p < 0.05) and mean LDL size (r = 0.25; p < 0.05). Serum VLDL ratio and level negatively correlated with obestatin (r = − 0.32; p < 0.01 and r = − 0.21; p = 0.05). In multiple regression analysis obestatin was predicted only by VLDL level.ConclusionsBased on our data, measurement of obestatin level in obesity may contribute to understand the interplay between gastrointestinal hormone secretion and metabolic alterations in obesity.

Biomarkers of Cardiovascular Risk in Haemodialysis Patients.

All stages of chronic kidney disease (CKD) are associated with increased risks of atherosclerosis and cardiovascular morbidity and mortality. According to studies, levels of copeptin, growth differentiation factor-15 (GDF-15) and heart fatty-acid binding protein (h-FABP) are increased in dialysis patients. This study included 50 patients (19 women, 31 men) chronically undergoing haemodialysis. The concentration of markers such as: copeptin, GDF-15, h-FABP, troponin and serum creatine kinase MB (CKMB) was measured with the use of ELISA tests. Serum concentration of 10 high-density lipoprotein (HDL) subfractions and 7 low-density lipoprotein (LDL) subfractions was analysed with the use of Lipoprint™ system (Quantimetrix Corp.). In this study, we observed higher copeptin level, lower percentage share of cholesterol HDL4 subfraction and higher percentage share of small HDL particles subfraction in HD patients with diabetes mellitus than in those without diabetes. We also found significantly lower percentage share of cholesterol HDL5 subfraction in patients with GDF-15 > 3rd quartile (Q3) compared with those with GFD-15 ≤ Q3. Finally, it was observed that the percentage share of cholesterol HDL5 subfraction was significantly lower in patients with h-FABP > Q3, and the share of intermediate HDL subfractions was significantly lower in haemodialysis (HD) patients with h-FABP > 75 percentile. The fact that increased level of one biomarker correlated with higher values of other markers may suggest that their concentration depends on the severity of disease. The obtained results also suggest that the measurement of copeptin may support the diagnosis of cardiovascular problems in dialysis patients.

Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies

IntroductionIdentifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. MethodsWe studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined. ResultsWe discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors. DiscussionCirculating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia.