HDL Subfractions Research Articles

A Fluorescence-Based In Vitro Method to Assess Cholesterol Efflux.

Cholesterol efflux (ChE) capacity is associated with the incidence of cardiovascular events and has been proposed as an emerging cardiovascular risk factor. ChE has been traditionally assessed by in vitro radioactive methods but these are not appropriate when assessing a large number of samples. Therefore, alternative, reproducible nonradioactive methods have been developed. This chapter describes a robust nonradioactive method using a fluorescent tracer to assess ChE in vitro.The measurement of ChE in vitro requires three main components: a cholesterol-loaded donor cell, a cholesterol tracer, and a cholesterol acceptor. This method involves labeling of murine macrophage J774A.1 cells using the fluorescent sterol dipyrromethene boron difluoride (BODIPY)-cholesterol. The cholesterol acceptors from humans or animals include lipid-free apolipoprotein (ApoA)-1, high-density lipoprotein (HDL), HDL2 and HDL3 subfractions, serum, plasma or ApoB-depleted serum or plasma. While lipid-free ApoA-1 mediates ChE via only ATP-binding cassette (ABC)A1 transporter, the remaining acceptors mediate ChE via ABCA1 , ABCG1 and scavenger receptor class B type 1 (SRB1) transporters. The reproducibility of this BODIPY-ChE assay is excellent as the intra-assay coefficients of variation (CVs) were <10% (30 replicates on the same day) and the interassay CVs were <14% (10 experiments performed on different days, with 3 replicates each). The fluorescent method therefore represents a reproducible, safe and useful tool to evaluate ChE as an emerging cardiovascular risk factor.

Moderate alcohol consumption and lipoprotein subfractions: a systematic review of intervention and observational studies.

Moderate alcohol consumption is associated with decreased risk of cardiovascular disease (CVD) and improvement in cardiovascular risk markers, including lipoproteins and lipoprotein subfractions. To systematically review the relationship between moderate alcohol intake, lipoprotein subfractions, and related mechanisms. Following PRISMA, all human and ex vivo studies with an alcohol intake up to 60 g/d were included from 8 databases. A total of 17 478 studies were screened, and data were extracted from 37 intervention and 77 observational studies. Alcohol intake was positively associated with all HDL subfractions. A few studies found lower levels of small LDLs, increased average LDL particle size, and nonlinear relationships to apolipoprotein B-containing lipoproteins. Cholesterol efflux capacity and paraoxonase activity were consistently increased. Several studies had unclear or high risk of bias, and heterogeneous laboratory methods restricted comparability between studies. Up to 60 g/d alcohol can cause changes in lipoprotein subfractions and related mechanisms that could influence cardiovascular health. PROSPERO registration no. 98955.

1H-NMR Plasma Lipoproteins Profile Analysis Reveals Lipid Metabolism Alterations in HER2-Positive Breast Cancer Patients.

Simple SummaryLipids’ metabolism deregulation is an established mark of breast cancer, however, no conclusive results have been reported on its effective role in disease development and progression. In this study, we applied straightforward 1H-NMR analysis to deeply explore alterations in circulating lipoproteins in HER2-positive breast cancer patients. The results support the key role played by lipids in the development of this breast cancer histotype and point out a specific lipid trait, characterized by a high plasma level of VLDL subfractions, potentially useful for diagnostic purposes. Moreover, the monitoring of plasma lipoproteins profile changes along the therapeutic interventions was found valuable to predict the clinical outcome.The lipid tumour demand may shape the host metabolism adapting the circulating lipids composition to its growth and progression needs. This study aims to exploit the straightforward 1H-NMR lipoproteins analysis to investigate the alterations of the circulating lipoproteins’ fractions in HER2-positive breast cancer and their modulations induced by treatments. The baseline 1H-NMR plasma lipoproteins profiles were measured in 43 HER2-positive breast cancer patients and compared with those of 28 healthy women. In a subset of 32 patients, longitudinal measurements were also performed along neoadjuvant chemotherapy, after surgery, adjuvant treatment, and during the two-year follow-up. Differences between groups were assessed by multivariate PLS-DA and by univariate analyses. The diagnostic power of lipoproteins subfractions was assessed by ROC curve, while lipoproteins time changes along interventions were investigated by ANOVA analysis. The PLS-DA model distinguished HER2-positive breast cancer patients from the control group with a sensitivity of 96.4% and specificity of 90.7%, mainly due to the differential levels of VLDLs subfractions that were significantly higher in the patients’ group. Neoadjuvant chemotherapy-induced a significant drop in the HDLs after the first three months of treatment and a specific decrease in the HDL-3 and HDL-4 subfractions were found significantly associated with the pathological complete response achievement. These results indicate that HER2-positive breast cancer is characterized by a significant host lipid mobilization that could be useful for diagnostic purposes. Moreover, the lipoproteins profiles alterations induced by the therapeutic interventions could predict the clinical outcome supporting the application of 1H-NMR lipoproteins profiles analysis for longitudinal monitoring of HER2-positive breast cancer in large clinical studies.

1H-magnetic resonance spectroscopy lipoprotein profile in patients with chronic heart failure versus matched controls

Introduction and objectivesAdvanced lipoprotein phenotyping is a better predictor of atherosclerotic cardiovascular risk than cholesterol concentration alone. Lipoprotein profiling in heart failure (HF) is incompletely characterized. We aimed to describe the lipoprotein profile in patients with chronic HF compared with a matched control population. MethodsThis cross-sectional study was performed from May 2006 to April 2014 and included ambulatory patients with chronic HF. Lipid concentrations and the size of main lipoprotein fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein) and the particle concentration of their 3 subfractions (large, medium and small) were assessed using 1H magnetic resonance spectroscopy. ResultsThe 429 included patients with chronic HF were compared with 428 matched controls. Patients with chronic HF had lower total cholesterol and lower mean LDL (1115 vs 1352 nmol/L; P<.001) and HDL (25.7 vs 27.9μmol/L; P <.001) particle concentrations, with this last difference being mediated by a significantly lower concentration of the small subfraction of HDL (15.2 vs 18.6μmol/L; P <.001). Mean very low-density lipoprotein, LDL, and HDL particle size was significantly higher in patients with HF vs controls. All HDL-related differences from controls persisted after adjustment for New York Heart Association functional class or body mass index. We found strong negative correlations of known cardiac biomarkers (N-terminal pro-brain natriuretic peptide and interleukin-1 receptor-like 1) with total and small LDL and HDL fractions and HDL particle size. ConclusionsPatients with chronic HF significantly differ in their lipoprotein profile compared with unaffected controls. Further research is needed to better understand the pathogenic relevance of this difference.

HDL亜分画に影響を及ぼす要因の検討

HDL亜分画に影響を及ぼす要因の検討

Compositional and functional properties of high-density lipoproteins in relation to coronary in-stent restenosis.

In-stent restenosis (ISR) is an unfavorable outcome that occurs in patients after coronary stenting. Use of drugs such as statins as well as drug-eluting stents has only been partially effective in reducing the rate of ISR. Since low high-density lipoprotein cholesterol (HDL-C) concentration is a pivotal cardiovascular disease risk factor, this study aimed to evaluate the compositional and functional alterations of HDL in individuals with ISR. This case-control study included 21 ISR, 26 non-ISR (NISR), 16 angiography-negative, and 18 healthy subjects. Serum HDL2 (d: 1.063-1.125 g/ml) and HDL3 (d: 1.125-1.210 g/ml) subfractions were extracted from each subject using sequential ultracentrifugation. The capacity of HDL to efflux cellular cholesterol from lipid-loaded macrophages as well as to take up free cholesterol (FC) from triglyceride-rich lipoproteins (TGRLs) during lipolysis was assessed. No difference was found in the HDL2 and HDL3 content of free cholesterol and total protein among the groups. The NISR group showed lower triglyceride content in HDL2 and higher phospholipid content in HDL3 relative to healthy subjects. Strong positive correlations were found between the cholesterol efflux capacity (CEC) of HDL2 and its phospholipid content in the healthy (r = 0.50), angiography-negative (r = 0.55) and ISR (r = 0.52) groups. The capacity of apolipoprotein B (apoB)-depleted serum to take up free cholesterol was not different among the groups. Despite some compositional alterations, the capacity of HDL to efflux cholesterol from lipid-loaded macrophages as well as to take up free cholesterol from TGRLs during lipolysis was not associated with ISR in this study.

HDL subfraction distribution in hypertensive patients with high plasma HDL-cholesterol levels

Background and Aims: Low HDL-Cholesterol (HDL-C) levels are associated with increased risk for atherosclerotic cardiovascular disease (ASCVD). However, many studies have indicated that a residual ASCVD risk exists even at high plasma HDL-C levels suggesting that other factors may affect the reverse association between HDL-C levels, including the HDL subfraction profile and HDL functionality and the existence of other ASCVD risk factors.We evaluated the plasma HDL subfraction profile in hypertensivepatients comparedtonormotensive subjects with high HDL-C levels.

Metabolomic signatures associated with depression and predictors of antidepressant response in humans: A CAN-BIND-1 report

One of the biggest challenges in treating depression is the heterogeneous and qualitative nature of its clinical presentations. This highlights the need to find quantitative molecular markers to tailor existing treatment strategies to the individual’s biological system. In this study, high-resolution metabolic phenotyping of urine and plasma samples from the CAN-BIND study collected before treatment with two common pharmacological strategies, escitalopram and aripiprazole, was performed. Here we show that a panel of LDL and HDL subfractions were negatively correlated with depression in males. For treatment response, lower baseline concentrations of apolipoprotein A1 and HDL were predictive of escitalopram response in males, while higher baseline concentrations of apolipoprotein A2, HDL and VLDL subfractions were predictive of aripiprazole response in females. These findings support the potential of metabolomics in precision medicine and the possibility of identifying personalized interventions for depression.

207-OR: Cardiac Autonomic Neuropathy (CAN) and HDL Proteomics in Type 1 Diabetes (T1D)

CAN is a common complication of diabetes mellitus (DM) strongly related to cardiovascular (CV) disease, contributing to high morbidity and mortality. HDL is inversely related to CV disease due to its ability in removing excess cholesterol from cells and antioxidant, anti-inflammatory and vasodilation actions. Apart from plasma HDL cholesterol (HDLc) and apoA-I levels that are not invariably changed in T1D, HDL proteomics may contribute to understand HDL functionality and its association with CAN. A total of 50 individuals with T1D with or without CAN were selected to assess the proteome of HDL subfractions (HDL2 and HDL3). CAN evaluation was performed by Ewing test using the Poly-Spectrum software. HDL subfractions were isolated by ultracentrifugation and proteomics analyzed by parallel reaction monitoring (PRM). Subjects with T1D with (n = 15) and without CAN (n = 35) did not differ in age, sex, body mass index, age at DM diagnosis, duration of DM, and fructosamine, HbA1c, total cholesterol, HDLc and triglycerides values. A total of 45 proteins were found in association with HDL2 and HDL3; three proteins were highlighted because they were more abundant in HDL2 from T1D with CAN: α1-microglobulin/bikunin precursor (AMBP), α1-acid glycoprotein (Orm1) and transthyretin (TTR) (Mann-Whitney test; P values &amp;lt;0.01, 0.03, 0.04, respectively). Orm1 is an acute inflammatory phase protein that regulates sphingolipid homeostasis related to the pathogenesis of diabetic neuropathy. TTR carries thyroid hormones and retinol binding protein and mutations in the TTR gene causes amyloidosis that includes motor and sensory polyneuropathy, neuropathic pain and autonomic dysfunction. The AMBP gene encodes α1microglobulin and bicunin that relates to T1D complications. In conclusion, three proteins with potential for involvement in the pathophysiology of CAN were more abundant in HDL2 in T1D presenting this chronic complication. Disclosure M. T. Toyoshima: None. A. Silva: None. M. M. Santana: None. G. E. Ronsein: None. M. Correa-giannella: None. M. Passarelli: None. Funding FAPESPCNPq

Distinct Fatty Acid Compositions of HDL Phospholipids Are Characteristic of Metabolic Syndrome and Premature Coronary Heart Disease-Family Study.

HDL particles can be structurally modified in atherosclerotic disorders associated with low HDL cholesterol level (HDL-C). We studied whether the lipidome of the main phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelin (SM) species of HDL2 and HDL3 subfractions is associated with premature coronary heart disease (CHD) or metabolic syndrome (MetS) in families where common low HDL-C predisposes to premature CHD. The lipidome was analyzed by LC-MS. Lysophosphatidylcholines were depleted of linoleic acid relative to more saturated and shorter-chained acids containing species in MetS compared with non-affected subjects: the ratio of palmitic to linoleic acid was elevated by more than 30%. A minor PC (16:0/16:1) was elevated (28–40%) in MetS. The contents of oleic acid containing PCs were elevated relative to linoleic acid containing PCs in MetS; the ratio of PC (16:0/18:1) to PC (16:0/18:2) was elevated by 11–16%. Certain PC and SM ratios, e.g., PC (18:0/20:3) to PC (16:0/18:2) and a minor SM 36:2 to an abundant SM 34:1, were higher (11–36%) in MetS and CHD. The fatty acid composition of certain LPCs and PCs displayed a characteristic pattern in MetS, enriched with palmitic, palmitoleic or oleic acids relative to linoleic acid. Certain PC and SM ratios related consistently to CHD and MetS.

Growth hormone replacement may influence the biological action of thyroid hormone on liver and bone tissue

ObjectiveGrowth hormone (GH) replacement alters the peripheral interconversion of thyroxine (T4) and triiodothyronine (T3). However, little is known about the clinical impact of these alterations. We aimed to compare changes observed in the serum T3:T4 ratio with known biological markers of thyroid hormone action derived from different peripheral tissues. DesignWe prospectively studied twenty GH deficient men before and after GH replacement in a tertiary referral endocrine center. Serum biochemical measurements included insulin like growth factor-1 (IGF-1), thyroid hormones (free & total T3, free & total T4 and reverse T3) and TSH. Changes in thyroid hormone concentration were compared to alterations in hepatic and bone biomarkers of thyroid hormone action. ResultsGH replacement provoked a decline in serum free T4 concentration (−1.09 ± 1.99 pmol/L; p = 0.02) and an increase in free T3 (+0.34 ± 0.15 pmol/L; p = 0.03); therefore, the free T3:free T4 ratio increased from 0.40 ± 0.02 to 0.47 ± 0.02 (p = 0.002). Sex hormone binding globulin (SHBG) level was unchanged. However, a decline in serum ferritin (−26.6 ± 8.5 ng/mL; p = 0.005) correlated with a fall in freeT4. Alterations in lipid profile, including a rise in large HDL sub-fractions and Lp (a) (+2.1 ± 21.1 nmol/L; p = 0.002) did not correlate with thyroid hormone levels. Significant increases were recorded in serum bone turnover markers - procollagen type 1 amino-terminal propeptide +57.4%; p = 0.0009, osteocalcin +48.6%; p = 0.0007; c-terminal telopeptides of type 1 collagen +73.7%; p = 0.002. Changes in bone formation markers occurred in parallel with fluctuations in thyroid hormone. ConclusionGH-induced alterations in the thyroid axis are associated with complex, tissue specific effects on thyroid hormone action. Modulation of bone turnover markers suggests that GH may improve the biological action of thyroid hormone on bone.

Arylesterase activity of paraoxonase 1 (PON1) on HDL3 and HDL2: Relationship with Q192R, C-108T, and L55M polymorphisms

BackgroundControversy exists regarding the role of the subfractions of high-density lipoproteins (HDL2 and HDL3) in cardiovascular disease. The functionality of these particles, and their protective role, is due in part to the paraoxonase 1 (PON1) presence in them. The polymorphisms rs662 (Q192R, A/G), rs854560 (L55 M, T/A), and rs705379 (C-108T) of the PON1 gene have been related to enzyme activity and, with the anti-oxidative capacity of the HDL. The objective was to determine the arylesterase PON1 activity in HDL3 and HDL2 and its relationship with the polymorphisms mentioned, in a young population. MethodsThe polymorphisms were determined through mini-sequencing (SnaPshot). The HDL subpopulations were separated via ionic precipitation, cholesterol was measured with enzymatic methods, and PON1 activity was measured through spectrophotometry. ResultsThe results show that the PON1 polymorphisms do not influence the cholesterol in the HDL. A variation between 40.02 and 43.9 mg/dL was in all the polymorphisms without significant differences. Additionally, PON1 activity in the HDL3 subfractions was greater (62.83 ± 20 kU/L) than with HDL2 (35.8 ± 20.8 kU/L) in the whole population and in all the polymorphisms (p < 0.001), and it was independent of the polymorphism and differential arylesterase activity in the Q192R polymorphism (QQ > QR > RR). Thus, 115.90 ± 30.7, 88.78 ± 21.3, 65.29 ± 10.2, respectively, for total HDL, with identical behavior for HDL3 and HDL2. ConclusionsPON1 polymorphisms do not influence the HDL-c, and the PON activity is greater in the HDL3 than in the HDL2, independent of the polymorphism, but it is necessary to delve into the functionality of these findings in different populations.

Changes in the profile of circulating HDL subfractions in severe obese adolescents following a weight reduction program

Background and aimsEpidemiological studies show that obese adolescents are candidates to suffer cardiovascular pathologies in adulthood. In order to detect subfractions with a diagnostic value for future cardiovascular disorders, we analyzed the complete lipoprotein profile of severely obese adolescents. Methods and resultsTwenty-eight obese adolescents free from comorbidities were admitted into a weight reduction program. Anthropometric parameters were monitored. The circulating lipoproteins and glycemia were measured at the beginning and at the end of the study by conventional blood analysis as well as by using lipoprotein electrophoresis. Twenty-one puberty-matched normal-weight adolescents were recruited as controls. After 4 months, participants improved anthropometric parameters. Blood analysis indicated that circulating lipoproteins were in the healthy range during intervention. Nevertheless, results obtained from lipoprotein electrophoresis showed a significant increase in the large high-density lipoprotein subfraction in the obese population at the end of intervention, but significantly lower than normal-weight counterparts. In addition, intermediate- and low-density lipoprotein subfractions were in the healthy range in controls and in obese adolescents during intervention. ConclusionsAltogether, it seems that the obese adolescents with no comorbidities do not develop a clear dyslipidemia. However, low values of large high-density lipoprotein subfractions could be considered as candidate predictors to develop cardiovascular disease in the future. For this reason, diet and exercise are key tools to fight against this pathology. Registration number for clinical trialsISRCTN99414527

NMR Spectroscopic Windows on the Systemic Effects of SARS-CoV-2 Infection on Plasma Lipoproteins and Metabolites in Relation to Circulating Cytokines.

To investigate the systemic metabolic effects of SARS-CoV-2 infection, we analyzed 1H NMR spectroscopic data on human blood plasma and co-modeled with multiple plasma cytokines and chemokines (measured in parallel). Thus, 600 MHz 1H solvent-suppressed single-pulse, spin-echo, and 2D J-resolved spectra were collected on plasma recorded from SARS-CoV-2 rRT-PCR-positive patients (n = 15, with multiple sampling timepoints) and age-matched healthy controls (n = 34, confirmed rRT-PCR negative), together with patients with COVID-19/influenza-like clinical symptoms who tested SARS-CoV-2 negative (n = 35). We compared the single-pulse NMR spectral data with in vitro diagnostic research (IVDr) information on quantitative lipoprotein profiles (112 parameters) extracted from the raw 1D NMR data. All NMR methods gave highly significant discrimination of SARS-CoV-2 positive patients from controls and SARS-CoV-2 negative patients with individual NMR methods, giving different diagnostic information windows on disease-induced phenoconversion. Longitudinal trajectory analysis in selected patients indicated that metabolic recovery was incomplete in individuals without detectable virus in the recovery phase. We observed four plasma cytokine clusters that expressed complex differential statistical relationships with multiple lipoproteins and metabolites. These included the following: cluster 1, comprising MIP-1β, SDF-1α, IL-22, and IL-1α, which correlated with multiple increased LDL and VLDL subfractions; cluster 2, including IL-10 and IL-17A, which was only weakly linked to the lipoprotein profile; cluster 3, which included IL-8 and MCP-1 and were inversely correlated with multiple lipoproteins. IL-18, IL-6, and IFN-γ together with IP-10 and RANTES exhibited strong positive correlations with LDL1–4 subfractions and negative correlations with multiple HDL subfractions. Collectively, these data show a distinct pattern indicative of a multilevel cellular immune response to SARS CoV-2 infection interacting with the plasma lipoproteome giving a strong and characteristic immunometabolic phenotype of the disease. We observed that some patients in the respiratory recovery phase and testing virus-free were still metabolically highly abnormal, which indicates a new role for these technologies in assessing full systemic recovery.

Cardiovascular events, LDL and HDL subfraction size in a cohort of FH patients

Cardiovascular events, LDL and HDL subfraction size in a cohort of FH patients

Lipid Profile, Lipoprotein Subfractions, and Fluidity of Membranes in Children and Adolescents with Depressive Disorder: Effect of Omega-3 Fatty Acids in a Double-Blind Randomized Controlled Study.

Depressive disorder (DD) is a psychiatric disorder whose molecular basis is not fully understood. It is assumed that reduced consumption of fish and omega-3 fatty acids (FA) is associated with DD. Other lipids such as total cholesterol (TCH), LDL-, and HDL-cholesterols (LDL-CH, HDL-CH) also play a role in depression. The primary endpoint of the study was the effect of omega-3 FA on the severity of depression in children and adolescents. This study aimed to investigate the secondary endpoint, relationship between depressive disorder symptoms and lipid profile, LDL- and HDL-cholesterol subfractions, Paraoxonase 1 (PON1) activities, and erythrocyte membrane fluidity in 58 depressed children and adolescents (calculated by the statistical program on the effect size), as well as the effect of omega-3 FA on the monitored parameters. Depressive symptoms were assessed by the Children’s Depression Inventory (CDI), lipid profile by standard biochemical procedures, and LDL- and HDL-subfractions by the Lipoprint system. Basic biochemical parameters including lipid profile were compared with levels in 20 healthy children and were in the physiological range. Improvement of symptoms in the group supplemented with a fish oil emulsion rich in omega-3 FA in contrast to omega-6 FA (emulsion of sunflower oil) has been observed. We are the first to report that omega-3 FAs, but not omega-6 FA, increase large HDL subfractions (anti-atherogenic) after 12 weeks of supplementation and decrease small HDL subfractions (proatherogenic) in depressed children. We found a negative correlation between CDI score and HDL-CH and the large HDL subfraction, but not LDL-CH subfractions. CDI score was not associated with erythrocyte membrane fluidity. Our results suggest that HDL-CH and its subfractions, but not LDL-CH may play a role in the pathophysiology of depressive disorder. The study was registered under ISRCTN81655012.

Effect of weight loss on cardiometabolic risk factors in obese patients

Abstract Background Central obesity and dyslipidemia are a cardinal features of the metabolic syndrome and represents increased cardiometabolic risk. It has been shown that weight loss is capable to improve insulin sensitivity and lipid parameters. The aim of our study was to analyze the effect of a weight-lowering program (diet and physical activity) on LDL- and HDL-cholesterol subfractions and cardiometabolic risk factors (waist circumference, blood pressure, insulin sensitivity, physical fitness). Methods We studied 2 groups of obese subjects, group A composed of 43 patients with obesity grade 1 and 2 (30F/13M; age: 43.2 ±12.4 years; BMI 31.3 ± 6.1 kg/m2); group B composed of patients with obesity grade 3 (6F/7M; age: 34.7 ±9.8 years; BMI 51.7 ± 7.9 kg/m2). The weight loss interventional program (NCT02325804) in duration of 8-week (group A) or 24 weeks (group B) consisted of hypocaloric diet and physical activity. Body composition, physical fitness, blood lipids profile (using the Lipoprint system (Quantimetrix Corp., CA, USA), and insulin sensitivity were measured. Results The average weight loss was 7.3±1.9 kg in group A and 35.3±16.0 kg in group B. Systolic, diastolic blood pressure (BP) as well as heart rate decreased in group A, in group B only systolic BP. Fasting plasma glucose and insulin decreased as well as insulin sensitivity and physical fitness has been improved after intervention. Total, LDL2, HDL2 cholesterol, as well as triglycerides (TG) decreased with weight in group A and total, LDL, TG, VLDL, LDL2 large, and small HDL subfractions decreased and intermediate HDL increased in group B. Conclusions Short term life style intervention (diet and physical activity) in patients with obesity lead to notable improvement of cardiometabolic parameters (decreased body fat mass, improved insulin sensitivity, lipid profile) as well as atheroprotective changes in LDL subfractions. Funding Supported by grants APVV 17-0099; VEGA 2/0129/20; VEGA 2/0072/18 Key messages Short term life style intervention in patients with obesity lead to notable improvement of cardiometabolic parameters. Weight-lowering program (diet and physical activity) lead to positive changes in LDL- and HDL-cholesterol subfractions.

Low plasma apolipoprotein E-rich high-density lipoprotein levels in patients with metabolic syndrome

BackgroundHigh-density lipoprotein (HDL) containing apolipoprotein E (apoE-rich HDL) represents a small portion of plasma HDL. We recently established a method for measuring plasma apoE-rich HDL. This study aimed to investigate the relationship between metabolic syndrome (MetS) and apoE-rich HDL levels. MethodsThe apoE-rich HDL-cholesterol (HDL-C) levels and metabolic characteristics of 113 patients were analyzed. ResultsThe MetS group (n = 58) had significantly lower apoE-rich HDL-C and a lower apoE-rich HDL-C/HDL-C ratio (apoE-HDL (%)) compared to the non-MetS group. The prevalence of MetS was increased when apoE-HDL (%) decreased. In simple regression analyses, apoE-HDL (%) was significantly inversely correlated with visceral fat area (rs = −0.370, P < 0.001) and plasma triglycerides (rs = −0.447, P < 0.001) and positively correlated with low-density lipoprotein (LDL) mean particle size (rs = 0.599, P < 0.001) and HDL mean particle size (rs = 0.512, P < 0.001). Stepwise multiple regression analysis revealed that LDL mean particle size, a component of the atherogenic lipoprotein profile, was an independent predictor of apoE-HDL (%) (adjusted R2 = 0.409). ConclusionsPlasma apoE-rich HDL levels might be a valuable indicator of MetS. These findings may help further understand HDL subfraction analysis in cardiometabolic diseases.

Plasma extracellular vesicle proteins are associated with stress-induced myocardial ischemia in women presenting with chest pain

Diagnosing stable ischemic heart disease (IHD) is challenging, especially in females. Currently, no blood test is available. Plasma extracellular vesicles (EV) are emerging as potential biomarker source. We therefore aimed to identify stress induced ischemia due to stable IHD with plasma extracellular vesicle protein levels in chest pain patients. We analyzed 450 patients suspected for stable IHD who were referred for 82Rb PET/CT in the outpatient clinic. Blood samples were collected before PET/CT and plasma EVs were isolated in 3 plasma subfractions named: TEX, HDL, LDL. In total 6 proteins were quantified in each of these subfractions using immuno-bead assays. CD14 and CystatinC protein levels were independent significant predictors of stress-induced ischemia in the LDL and the HDL subfraction and SerpinC1 and SerpinG1 protein levels in the HDL fraction. Subgroup-analysis on sex revealed that these associations were completely attributed to the associations in women. None of the significant EV proteins remained significant in men. Plasma EV proteins levels are associated with the presence of stable IHD in females presenting with chest pain. This finding, if confirmed in larger cohort studies could be a crucial step in improving diagnostic assessment of women with suspected IHD.

2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD)

It has been demonstrated that diabetic dyslipidaemia is the chief bridge between diabetes and incremental risk of cardiovascular disease in patients with diabetes. However, the characteristics of lipoprotein subfractions distribution in patients with type 2 diabetes (T2D) have not been fully investigated. The aim of present study was to evaluate the distributions of lipoprotein subfractions in T2D patients.A total of 920 patients, who have not received lipid-lowering drug treatment previously, were consecutively enrolled in this study. Based on the evidence of diabetes, patients were divided into T2D group (n=204) and non-T2D group (n=716). Both low- and high-density lipoprotein cholesterol (LDL- and HDL-C) subfractions were analysed using the Quantimetrix Lipoprint System. The distributions of lipoprotein subfractions were evaluated in patients with and without T2D.Compared with non-T2D individuals, the T2D group manifested significantly lower large HDL-C concentration/HDL subfraction percentage, smaller mean LDL particle size but higher small HDL-C and LDL-C concentrations as well as small HDL and LDL subfraction percentages. Moreover, the data indicated that the small HDL-C/ LDL-C concentrations, the small and large HDL subfraction percentages along with the mean LDL particle size were independently related to the existence of T2D (95% CI=1.009–1.067, p=0.009; 95% CI=0.938-0.983, p=0.001; 95% CI=1.023–1.135, p=0.005; 95% CI= 1.005–1.048, p=0.014; 95% CI=0.940-0.999, p=0.040; respectively) assessed by logistic regression analysis.The present study indicated that the changes of lipid profile in patients with T2D are characterised by abnormal distributions of lipoprotein subfractions apart from clinically atherogenic dyslipidaemia.