LDL Subfractions Research Articles

Sport as Medicine for Dyslipidemia (and Other Risk Factors).

Dyslipidemia is a common condition characterized by abnormal lipid levels in the blood, which can increase the risk of cardiovascular disease. Physical activity and participation in sports have been shown to have a positive impact on lipid profiles and reduce the risk of dyslipidemia. Additionally, regular physical activity can lead to weight loss and improved insulin sensitivity, both of which are associated with improved lipid profiles. This review aims to provide an overview on the utility of physical activity in the management of dyslipidemia. Improvements in lipid profiles were observed across both short- and long-term durations of high-intensity interval training (HIIT) and moderate intensity interval training (MIIT). However, it seems that more significant improvements in lipid profiles can be achieved with longer periods of physical activity and more intense exercise regimens. Several studies have investigated the relationship between aerobic exercise and HDL cholesterol (HDL-C), and the results suggest that HDL-C levels are more responsive to aerobic exercise compared to LDL cholesterol (LDL-C) and triglycerides (TG). Although findings on the effect of aerobic exercise on LDL-C levels have been inconsistent, there may still be beneficial changes in LDL-C subfractions that could provide cardiovascular protection. One such subfraction is plasma Lp(a), which contains Apo(a). However, unlike other LDL subfractions, Lp(a) is determined by genetics and is not influenced by physical activity. Therefore, it cannot be improved through exercise. Exercise is commonly believed to lead to a decrease in plasma TG concentrations. However, it is important to note that the baseline TG level may play a crucial role in determining the effect of exercise on the TG response. Factors such as individual variability and metabolic differences can influence the response of TG levels to exercise. Overall, exercise plays a crucial role in improving lipid profiles and promoting cardiovascular health. In conclusion, sport can be considered a form of medicine for dyslipidemia. Regular physical activity and participation in sports can improve lipid profiles, reduce the risk of cardiovascular disease, and improve overall health. It is essential to incorporate exercise and a healthy lifestyle into one's daily routine to prevent and manage dyslipidemia effectively.

Continuous and Marked Increase of Japanese HDL Associates Paradoxically with their Nutritional Shift.

Plasma HDL has evidently increased for decades among Japanese, exclusively in HDL particles containing apoA-I but not A-II. Its metabolic background is yet to be elucidated. Trends in plasma lipoproteins were analyzed by examining data on total cholesterol, triglyceride and HDL-cholesterol, which are available in the public database of the National Health and Nutrition Examination Survey of Japan (NHNESJ) and in the clinical data of SRL Co., from 1989 to 2019, estimating cholesterol (C) in non-HDL, VLDL, LDL, and sub-fractions of LDL using the equations by Sampson et al. Food intake and supply data in NHNSJ and in the UN Food and Agriculture Organization were also analyzed in relation to the lipoprotein analysis. HDL-C levels showed a steady increase in men and women throughout the period as per the data retrieved in NHNSJ and SRL data. It is noted to be higher in women than men (from 46.8 to 52.7, and from 58.4 to 68.3 in mg/dl, respectively). Triglyceride and VLDL-C were higher in men but sex difference was not apparent in non-HDL-C and LDL-C levels, while these parameters slightly decreased in both sexes. The increase in HDL was most prominent in women in the age of 50 - 59 (from 57.0 to 73.4). The age-dependent HDL trend was reversed among women during the study period, as increasing instead of decreasing. This increase in HDL was found to coincide with lowered fish/meat ratio in food intake among Japanese. Marked increase in plasma HDL among Japanese is age- and sex-dependent and exhibited an apparent paradoxical association with lowered fish/meat ratio in their diet. Further investigation is required to elucidate the background for these findings.

Effect of PCSK9 inhibition with evolocumab on the concentration and composition of LDL subfractions in high-risk patients with cardiovascular disease

Effect of PCSK9 inhibition with evolocumab on the concentration and composition of LDL subfractions in high-risk patients with cardiovascular disease

The Role of Small Dense LDL Cholesterol and Ischemia Modified Albumin in Patients with Hyperlipidemia

Background: The analysis of lipid profiles is a crucial step for cardiovascular risk evaluation, prevention, and therapeutic management. Small dense LDL (sdLDL) is one of the distinct subfractions of LDL and is established to have pro-atherogenic properties. Ischemia-modified albumin (IMA) is an early biomarker arising as a result of oxidative stress and ischemia. Objective: This study aimed to determine serum levels of sdLDL and IMA in patients with hyperlipidemia. Methods: Seventy-four patients with hyperlipidemia and 35 healthy controls were included. sdLDL was determined by the heparin-magnesium precipitation method. IMA was measured quantified manually with the colorimetric method. The patient group was divided into three groups: HyperTG (n=11), HyperLDL (n=38), and combined hyperlipidemia (n=25). Results: Median serum sdLDL and IMA levels were higher in patients with hyperlipidemia than healthy participants (both, p<0.001). Elevated sdLDL levels were observed in the HyperLDL group compared to the HyperTG group and the combined hyperlipidemia group (p<0.001). Cut-off values for the detection of patients with hyperlipidemia were >70 mg/dL for sdLDL and >0.7 AU for IMA, and both parameters showed considerably high levels of sensitivity and specificity. Multiple logistic regression analysis revealed that high sdLDL (p=0.042) and high IMA (p<0.001) were independently associated with hyperlipidemia after adjusting for age and sex. Conclusion: Serum sdLDL and IMA levels could be used as biomarkers for dyslipidemia-associated diseases. Further studies with larger sample size are needed to validate the impact of sdLDL on the pathogenesis of atherogenesis, and its value in the diagnosis and prognosis hyperlipidemia. Keywords: Small dense LDL, Lipoprotein, Ischemia modified albumin, IMA, Atherosclerosis

Relationship between serum Betatrophin, GPIHBP1, and LDL subfractions in patients with gestational diabetes mellitus

ObjectivesGestational diabetes mellitus (GDM) leads to changes in the lipid metabolism. In this study, we aimed to compare serum levels of LDL subfractions, betatrophin, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) between patients with GDM and healthy pregnant women. Design and MethodsWe designed a prospective case-control study with 41 pregnant women. Subjects were divided into two groups: GDM and control. Betatrophin and GPIHBP1 levels were measured by ELISA method. Lipoprint LDL subfraction kit was used to perform LDL subfraction analysis electrophoretically. ResultsSerum levels of LDL6 subfraction, betatrophin, and GPIHBP1 were found to be higher in GDM group compared to the controls (p < 0.001). The mean LDL size were also found larger in GDM group. A positive correlation was found between betatrophin and GPIHBP1 levels (rho = 0.96, p < 0.001). ConclusionsOur findings suggest that betatrophin, and GPIHBP1 levels were found to be increased in GDM. This maybe the result of adaptive mechanisms in response to insulin resistance, but also this relationship should be evaluated for their effects on impaired lipid metabolism and lipoprotein lipase metabolism. There is a need for further prospective studies with larger samples to fully elucidate the mechanisms of this relationship both in pregnant patients and the other patient groups.

Cholesterol efflux capacity is increased in subjects with familial hypercholesterolemia in a retrospective case–control study

Familial Hypercholesterolemia (FH) is characterized by an increase in Low-Density Lipoprotein Cholesterol (LDL-C) and by premature Cardiovascular Disease (CVD). However, it remains to be fully elucidated if FH impairs cholesterol efflux capacity (CEC), and whether CEC is related to lipoprotein subfraction distribution. This study aimed at comparing FH patients and age, sex and BMI matched controls in terms of LDL and HDL subfraction distribution as well as CEC. Forty FH patients and 80 controls, matched for age, sex and BMI, were enrolled in this case–control study. LDL and HDL subfractions were analyzed using the Quantimetrix Lipoprint System. CEC was evaluated as aq-CEC and ABCA1-CEC. FH subjects showed a significantly higher concentration of all LDL subfractions, and a shift from large to small HDL subfraction pattern relative to controls. FH subjects with previous CVD event had smaller LDL lipoproteins than controls and FH subjects without previous CVD event. Both aq-CEC and ABCA1-CEC were increased in FH patients with respect to controls. To conclude, FH subjects had a metabolic profile characterized not only by higher LDL-C but also by shift from large to small HDL subfraction phenotype. However, FH subjects showed an increase CEC than controls.

Estimated sdLDL-C for predicting high-risk coronary plaque features in psoriasis: a prospective observational study

BackgroundPsoriasis (PSO) is a skin disorder with systemic inflammation and high coronary artery disease risk. A distinct lipid phenotype occurs in psoriasis, which is characterized by high plasma triglycerides (TGs) with typically normal or even low LDL-C. The extent to which cholesterol on LDL subfractions, such as small dense LDL-C (sdLDL-C), are associated with vulnerable coronary plaque characteristics in PSO remains elusive.MethodsA recently developed equation for estimating sdLDL-C from the standard lipid panel was utilized in a PSO cohort (n = 200) with 4-year follow-up of 75 subjects. Coronary plaque burden was assessed by quantitative coronary computed tomography angiography (CCTA). Multivariate regression analyses were used for establishing associations and prognostic value of estimated sdLDL-C.ResultsEstimated sdLDL-C was positively associated with non-calcified burden (NCB) and fibro-fatty burden (FFB), which remained significant after multivariate adjustment for NCB (β = 0.37; P = 0.050) and LDL-C adjustment for FFB (β = 0.29; P < 0.0001). Of note, total LDL-C calculated by the Friedewald equation was not able to capture these associations in the study cohort. Moreover, in the regression modelling estimated sdLDL-C was significantly predicting necrotic burden progression over 4 years follow-up (P = 0.015), whereas LDL-C did not. Finally, small LDL particles (S-LDLP) and small HDL particles (S-HDLP), along with large and medium TG-rich lipoproteins (TRLPs) had the most significant positive correlation with estimated sdLDL-C.ConclusionsEstimated sdLDL-C has a stronger association than LDL-C with high-risk features of coronary atherosclerotic plaques in psoriasis patients.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifiers: NCT01778569

Associations of perfluoroalkyl substances (PFAS) with lipid and lipoprotein profiles

BackgroundPerfluoroalkyl substances (PFAS) are man-made chemicals with unique properties that are widely distributed in humans and the environment. Recent studies suggest that PFAS are involved in cholesterol metabolism, however, the mechanisms underlying the associations are poorly understood.ObjectiveWe aimed to evaluate associations of plasma PFAS with detailed lipid and lipoprotein subfractions in an adult population of men and women.MethodsWe measured concentrations of cholesterol and triglycerides in lipoprotein subfractions, apolipoprotein subclasses, as well as fatty acid and different phospholipid measures, using serum proton nuclear magnetic resonance (1H-NMR), and four plasma PFAS using liquid chromatography-mass spectrometry (UHPLC-MS/MS). Measurements were available for 493 participants (all aged 50 years, 50% female). Multivariable linear regression was used to estimate the association of four PFAS with 43 different 1H-NMR measures, with adjustment for body mass index (BMI), smoking, education, and physical activity.ResultsWe found that perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), but not perfluorohexanesulfonate (PFHxS), concentrations were consistently positively associated with concentrations of cholesterol in lipoprotein subfractions, apolipoproteins, as well as composite fatty acid- and phospholipid profiles. The most consistent associations were found for the relationship of PFAS with total cholesterol in intermediate-density lipoprotein (IDL), across all low-density lipoprotein (LDL) subfractions and small high-density lipoprotein (HDL). Moreover, we found weak to null evidence for an association of any of the measured 13 triglyceride lipoprotein subfractions with PFAS.ConclusionsOur results suggest that plasma PFAS concentrations are associated with cholesterol in small HDL, IDL and all LDL subfractions, as well as apolipoproteins and composite fatty acid and phospholipid profiles but to a lesser extent with triglycerides in lipoproteins. Our findings draw attention to the need for more detailed measurements of lipids across various lipoprotein subfractions and subclasses in assessing the role of PFAS in lipid metabolism.ImpactBy performing an in-depth characterization of circulating cholesterol and triglycerides in lipoprotein subfractions, apolipoprotein, fatty acid, and phospholipid concentrations, this study has expanded upon the limited literature available on the associations of plasma PFAS concentrations beyond clinical routine laboratory testing for lipids.

Exploring the Association between Low-Density Lipoprotein Subfractions and Major Adverse Cardiovascular Outcomes-A Comprehensive Review.

Cardiovascular disease (CVD) impacts hundreds of millions of people each year and is the main cause of death worldwide, with atherosclerosis being its most frequent form of manifestation. Low-density lipoproteins (LDL) have already been established as a significant cardiovascular risk factor, but more recent studies have shown that small, dense LDLs are the ones more frequently associated with a higher overall risk for developing atherosclerotic cardiovascular disease. Ever since atherogenic phenotypes were defined for the first time, LDL subfractions have been continuously analyzed in order to identify those with a higher atherogenic profile that could further become not only high-accuracy, effective prognostic biomarkers, but also treatment targets for novel lipid-lowering molecules. This review sets out to comprehensively evaluate the association between various LDL-subfractions and the risk of further developing major adverse cardiovascular events, by assessing both genetical and clinical features and focusing on their physiopathological characteristics, chemical composition, and global ability to predict long-term cardiovascular risk within the general population. Further research is required in order to establish the most beneficial range of LDL-C levels for both primary and secondary prevention, as well as to implement LDL subfraction testing as a routine protocol, separately from the general assessment of the other traditional cardiovascular risk factors.

The Oxidized Lipoproteins In Vivo: Its Diversity and Behavior in the Human Circulation

A high concentration of low-density lipoproteins (LDLs) in circulation has been well-known as a major risk factor for cardiovascular diseases. The presence of oxidized LDLs (oxLDLs) in atherosclerotic lesions and circulation was demonstrated using anti-oxLDL monoclonal antibodies. The so-called "oxLDL hypothesis", as a mechanism for atherosclerosis development, has been attracting attention for decades. However, the oxLDL has been considered a hypothetical particle since the oxLDL present in vivo has not been fully characterized. Several chemically modified LDLs have been proposed to mimic oxLDLs. Some of the subfractions of LDL, especially Lp(a) and electronegative LDL, have been characterized as oxLDL candidates as oxidized phospholipids that stimulate vascular cells. Oxidized high-density lipoprotein (oxHDL) and oxLDL were discovered immunologically in vivo. Recently, an oxLDL-oxHDL complex was found in human plasma, suggesting the involvement of HDLs in the oxidative modification of lipoproteins in vivo. In this review, we summarize our understanding of oxidized lipoproteins and propose a novel standpoint to understand the oxidized lipoproteins present in vivo.

Effect of high-fat diet and morning or evening exercise on lipoprotein subfraction profiles: secondary analysis of a randomised trial

We investigated the effect of a high-fat diet (HFD) on serum lipid subfractions in men with overweight/obesity and determined whether morning or evening exercise affected these lipid profiles. In a three-armed randomised trial, 24 men consumed an HFD for 11 days. One group of participants did not exercise (n = 8, CONTROL), one group trained at 06:30 h (n = 8, EXam), and one group at 18:30 h (n = 8, EXpm) on days 6–10. We assessed the effects of HFD and exercise training on circulating lipoprotein subclass profiles using NMR spectroscopy. Five days of HFD induced substantial perturbations in fasting lipid subfraction profiles, with changes in 31/100 subfraction variables (adjusted p values [q] < 0.05). Exercise training induced a systematic change in lipid subfraction profiles, with little overall difference between EXam and EXpm. Compared with CONTROL, exercise training reduced serum concentrations of > 20% of fasting lipid subfractions. EXpm reduced fasting cholesterol concentrations in three LDL subfractions by ⁓30%, while EXam only reduced concentration in the largest LDL particles by 19% (all q < 0.05). Lipid subfraction profiles changed markedly after 5 days HFD in men with overweight/obesity. Both morning and evening exercise training impacted subfraction profiles compared with no exercise.

Alterations of NMR-Based Lipoprotein Profile Distinguish Unstable Angina Patients with Different Severity of Coronary Lesions.

Non-invasive detection of unstable angina (UA) patients with different severity of coronary lesions remains challenging. This study aimed to identify plasma lipoproteins (LPs) that can be used as potential biomarkers for assessing the severity of coronary lesions, determined by the Gensini score (GS), in UA patients. We collected blood plasma from 67 inpatients with angiographically normal coronary arteries (NCA) and 230 UA patients, 155 of them with lowGS (GS ≤ 25.4) and 75 with highGS (GS > 25.4), and analyzed it using proton nuclear magnetic resonance spectroscopy to quantify 112 lipoprotein variables. In a logistic regression model adjusted for four well-known risk factors (age, sex, body mass index and use of lipid-lowering drugs), we tested the association between each lipoprotein and the risk of UA. Combined with the result of LASSO and PLS-DA models, ten of them were identified as important LPs. The discrimination with the addition of selected LPs was evaluated. Compared with the basic logistic model that includes four risk factors, the addition of these ten LPs concentrations did not significantly improve UA versus NCA discrimination. However, thirty-two selected LPs showed notable discrimination power in logistic regression modeling distinguishing highGS UA patients from NCA with a 14.9% increase of the area under the receiver operating characteristics curve. Among these LPs, plasma from highGS patients was enriched with LDL and VLDL subfractions, but lacked HDL subfractions. In summary, we conclude that blood plasma lipoproteins can be used as biomarkers to distinguish UA patients with severe coronary lesions from NCA patients.

Lipoprotein Subfractions Associated with Endothelial Function in Previously Healthy Subjects with Newly Diagnosed Sleep Apnea-A Pilot Study.

Obstructive sleep apnea (OSA) activates several pathophysiological mechanisms which can lead to the development of vascular diseases. Endothelial dysfunction (ED) is an initial step in the development of atherosclerosis. The association between ED and OSA has been described in several studies, even in previously healthy subjects. High-density lipoproteins (HDL) were generally considered to be atheroprotective, and low-density lipoprotein (LDL) to be an atherogenic component of lipoproteins. However, recent findings suggest a pro-atherogenic role of small HDL subfractions (8-10) and LDL subfractions (3-7). This study aimed to evaluate the relationship between endothelial function and lipid subfractions in previously healthy OSA subjects. We prospectively enrolled 205 subjects with sleep monitoring. Plasma levels of triacylglycerols, total cholesterol, LDL, HDL, and their subfractions were assessed. Endothelial function was determined using peripheral arterial tonometry, and reperfusion hyperemia index (RHI) was assessed. Plasma levels of small and intermediate HDL subfractions have statistically significant pro-atherogenic correlations with endothelial function (p = 0.015 and p = 0.019). In other lipoprotein levels, no other significant correlation was found with RHI. In stepwise multiple linear regression analysis, small HDL (beta = -0.507, p = 0.032) was the only significant contributor in the model predicting RHI. In our studied sample, a pro-atherogenic role of small HDL subfractions in previously healthy subjects with moderate-to-severe OSA was proven.

Association between measured or calculated small dense low-density lipoprotein cholesterol and oxidized low-density lipoprotein in subjects with or without type 2 diabetes mellitus.

Small dense low-density lipoprotein (sdLDL) possesses atherogenic potential and is predicted to be susceptible to atherogenic modifications, which further increases its atherogenicity. However, studies on the association between measured or estimated sdLDL cholesterol (sdLDL-C) levels and atherogenic modification in diverse population groups are lacking. Surplus serum samples were collected from male subjects with type 2 diabetes mellitus (DM) under treatment (n= 300) and without DM (non-DM; n= 150). sdLDL and oxidized LDL (oxLDL) levels were measured using the Lipoprint LDL subfractions kit (Quantimetrix Corporation) and the Mercodia oxidized LDL competitive enzyme-linked immunosorbent assay kit (Mercodia), respectively. The estimated sdLDL-Cs were calculated from two relevant equations. The effects of sdLDL-C on oxLDL were assessed using multiple linear regression (MLR) models. The mean (±SD) of measured sdLDL-C and oxLDL concentrations were 11.8± 10.0mg/dl and 53.4± 14.2U/L in the non-DM group and 0.20 ± 0.81 mg/dl and 46.0± 15.3U/L in the DM group, respectively. The effects of measured sdLDL-Cs were significant (p= 0.031), whereas those of estimated sdLDL-Cs were not (p= 0.060, p= 0.116) in the non-DM group in the MLR models. The effects of sdLDL-Cs in the DM group were not significant. In the general population, high level of sdLDL-C appeared to be associated with high level of oxLDL. The equation for estimating sdLDL-C developed from a general population should be applied with caution to a special population, such as patients with DM on treatment.

Nuclear Magnetic Resonance-Based Metabolomics to Predict Early and Late Adverse Outcomes in Ischemic Stroke Treated with Intravenous Thrombolysis.

Metabolic perturbations and inflammatory mediators play a fundamental role in both early and late adverse post-acute ischemic stroke outcomes. Using data from the observational MAGIC (MArker bioloGici nell'Ictus Cerebrale) study, we evaluated the effect of 130 serum metabolic features, using a nuclear magnetic spectroscopy approach, on the following outcomes: hemorrhagic transformation at 24 h after stroke, non-response to intravenous thrombolytic treatment with the recombinant tissue plasminogen activator (rt-PA), and the 3 month functional outcome. Blood circulating metabolites, lipoproteins, and inflammatory markers were assessed at the baseline and 24 h after rt-PA treatment. Adjusting for the major determinants for unfavorable outcomes (i.e., age, sex, time onset-to-treatment, etc.), we found that acetone and 3-hydroxybutyrate were associated with symptomatic hemorrhagic transformation and with non-response to rt-PA; while 24 h after rt-PA, levels of triglycerides high-density lipoprotein (HDL) and triglycerides low-density lipoprotein (LDL) were associated with 3 month mortality. Cholesterol and phospholipids levels, mainly related to smaller and denser very low-density lipoprotein (VLDL) and LDL subfractions were associated with 3 month poor functional outcomes. We also reported associations between baseline 24 h relative variation (Δ) in VLDL subfractions and ΔC-reactive protein, Δinterleukin-10 levels with hemorrhagic transformation. All observed metabolic changes reflect a general condition of energy failure, oxidative stress, and systemic inflammation that characterize the development of adverse outcomes.

Modulation of Lipid Profile and Lipoprotein Subfractions in Overweight/Obese Women at Risk of Cardiovascular Diseases through the Consumption of Apple/Berry Juice

Polyphenol-rich foods protect the cellular systems of the human body from oxidative damage, thereby reducing the risk of chronic diseases such as cardiovascular disease (CVD). We investigated the effect of phenolic-rich apple/berry juice (chokeberry, blueberry, and cranberry) on lipidemic profiles in overweight/obese women. The 6 week single-arm pre-post intervention study involved 20 women (mean age 52.95 ± 5.8 years, body mass index ≥25 kg/m2, and ≥1 CVD risk factors) consuming 300 mL/day of the apple/berry juice. Lipid profile, low-density lipoprotein (LDL) subfractions assessed using Lipoprint® electrophoresis, and other parameters related to cardiovascular risk (C-reactive protein, glucose, blood pressure) were analyzed before and again after the intervention in the monitored group of women. High-density lipoprotein cholesterol (HDL-C) increased from 1.30 ± 0.29 to 1.55 ± 0.32, magnesium from 0.85 ± 0.03 to 0.90 ± 0.05, and total antioxidant status from 1.68 ± 0.08 to 1.81 ± 0.10. The LDL/HDL ratio significantly decreased from 3.40 ± 0.99 to 2.66 ± 0.63 mmol/L, and the glucose from 5.50 ± 0.72 to 5.24 ± 0.74 mmol/L. However, the hs-CRP did not change significantly. Women with atherogenic subfractions LDL3-7 at baseline (n = 6) showed a significant reduction from 0.45 ± 0.19 to 0.09 ± 0.07 mmol/L. Overweight/obese women may benefit from apple/berry juice as part of a healthy lifestyle to improve their lipid profile, and thus, contribute to cardiovascular health.

Small LDL subfractions are associated with coronary atherosclerosis despite no differences in conventional lipids.

Lipoprotein subfractions currently represent a new source of cardiovascular disease (CVD) risk markers that may provide more information than conventional lipid measures. We aimed to investigate whether lipoprotein subfractions are associated with coronary atherosclerosis in patients without prior known CVD. Fasting serum samples from 60 patients with suspected coronary artery disease (CAD) were collected before coronary angiography and analyzed by nuclear magnetic resonance (NMR) spectroscopy. The severity of coronary atherosclerosis was quantified by the Gensini score (≤20.5 = nonsignificant coronary atherosclerosis, 20.6-30.0 = intermediate coronary atherosclerosis, ≥30.1 = significant CAD). Differences in lipoprotein subfractions between the three Gensini groups were assessed by two-way ANOVA, adjusted for statin use. Despite no differences in conventional lipid measures between the three Gensini groups, patients with significant CAD had higher apolipoprotein-B/apolipoprotein-A1 ratio, 30% more small and dense low-density lipoprotein 5 (LDL-5) particles, and increased levels of cholesterol, triglycerides, and phospholipids within LDL-5 compared with patients with nonsignificant coronary atherosclerosis and intermediate coronary atherosclerosis (P ≤ 0.001). In addition, the low-density lipoprotein (LDL) cholesterol/high-density lipoprotein cholesterol ratio, and triglyceride levels of LDL 4 were significantly increased in patients with significant CAD compared with patients with nonsignificant coronary atherosclerosis. In conclusion, small and dense lipoprotein subfractions were associated with coronary atherosclerosis in patients without prior CVD. Additional studies are needed to explore whether lipoprotein subfractions may represent biomarkers offering a clinically meaningful improvement in the risk prediction of CAD.

High-Density Lipoprotein Suppresses Neutrophil Extracellular Traps Enhanced by Oxidized Low-Density Lipoprotein or Oxidized Phospholipids.

Neutrophil extracellular traps (NETs) are found in patients with various diseases, including cardiovascular diseases. We previously reported that copper-oxidized low-density lipoprotein (oxLDL) promotes NET formation of neutrophils, and that the resulting NETs increase the inflammatory responses of endothelial cells. In this study, we investigated the effects of high-density lipoproteins (HDL) on NET formation. HL-60-derived neutrophils were treated with phorbol 12-myristate 13-acetate (PMA) and further incubated with oxLDL and various concentrations of HDL for 2 h. NET formation was evaluated by quantifying extracellular DNA and myeloperoxidase. We found that the addition of native HDL partially decreased NET formation of neutrophils induced by oxLDL. This effect of HDL was lost when HDL was oxidized. We showed that oxidized phosphatidylcholines and lysophosphatidylcholine, which are generated in oxLDL, promoted NET formation of PMA-primed neutrophils, and NET formation by these products was completely blocked by native HDL. Furthermore, we found that an electronegative subfraction of LDL, LDL(-), which is separated from human plasma and is thought to be an in vivo oxLDL, was capable of promoting NET formation. These results suggest that plasma lipoproteins and their oxidative modifications play multiple roles in promoting NET formation, and that HDL acts as a suppressor of this response.

Effect of high-fat diet and exercise in the morning or evening on lipid subfractions among men with overweight/obesity: a randomised trial

Abstract Background Although main lipid fractions in the blood, such as HDL and LDL, are associated with risk of cardiovascular disease (CVD), the risk associated with different subfractions of these particles varies. For example, small dense LDL particles are associated with significantly increased CVD risk while larger LDL particles are not. Purpose To investigate the effect of a high-fat diet on serum lipid subfractions in men with overweight/obesity and to determine whether morning or evening exercise affected the lipid subfraction profile. Methods In a three-armed randomised trial, 24 men (aged 36±4 years, body mass index 31.2±2.3 kg/m2) consumed a high-fat diet (HFD; 65% energy from fat) for 11 days. One group of participants (n=8, control) did not exercise, while one group (n=8) exercised in the morning (06:30 hours) and one group (n=8) in the evening (18:30 hours) on days 6–10. We measured the effect of HFD, and that of morning or evening exercise, on fasting circulating lipoprotein subclass profiles determined using nuclear magnetic resonance spectroscopy. We performed a principal component analysis and partial least squares discriminant analyses to investigate patterns of changes in lipid subfractions after 5 days of HFD and a repeated measures ANOVA simultaneous component analysis (RM-ASCA) to determine multivariate changes in lipoprotein profiles between the three groups. To determine univariate effects of HFD on lipoprotein subclasses, we used Benjamini-Hochberg-adjusted paired samples t-tests. We used linear mixed models to determine between-group differences in lipoprotein subfractions after exercise in the morning or evening, compared to no exercise. Results Lipid subfraction profiles changed substantially after 5 days of HFD, with significant changes in 31 of 100 subfraction variables (adjusted p-values &amp;lt;0.05). Total serum cholesterol in LDL increased from 113±26 mg/dL to 122±26 mg/dL after 5 days of HFD (adjusted p=0.039) due to increased cholesterol in larger LDL particles (LDL-2 and LDL-3, Figure 1). Exercise induced a systematic change in lipid subfraction profiles, with small overall differences between morning versus evening exercise. Morning and evening exercise reduced serum concentrations of 20% and 24% of fasting lipid subfraction variables, respectively, compared to the control group (Figure 2). Evening exercise reduced fasting cholesterol concentrations in three LDL subfractions by 20%, 26% and 86%, respectively, while morning exercise only reduced concentration in the largest LDL particles by 12% (adjusted p-values &amp;lt;0.05 compared to the control group for all). Discussion and conclusion We found a marked change in lipid subfraction profiles after only five days of HFD among men with overweight/obesity. Exercise, either in the morning or in the evening, induced a substantial change in lipid subfraction profile compared with no exercise during an HFD. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation

Changes in lipoproteins associated with lipid-lowering and antiplatelet strategies in patients with acute myocardial infarction.

Despite lipid-lowering and antiplatelet therapy, the pattern of residual lipoproteins seems relevant to long-term cardiovascular outcomes. This study aims to evaluate the effects of combined therapies, commonly used in subjects with acute myocardial infarction, in the quality of low-density lipoprotein (LDL) particles. Prospective, open-label trial, included patients with acute myocardial infarction. Patients were randomized to antiplatelet treatment (ticagrelor or clopidogrel) and subsequently to lipid-lowering therapy (rosuvastatin or simvastatin/ezetimibe) and were followed up for six months. Nonlinear optical properties of LDL samples were examined by Gaussian laser beam (Z-scan) to verify the oxidative state of these lipoproteins, small angle X-ray scattering (SAXS) to analyze structural changes on these particles, dynamic light scattering (DLS) to estimate the particle size distribution, ultra violet (UV)-visible spectroscopy to evaluate the absorbance at wavelength 484 nm (typical from carotenoids), and polyacrylamide gel electrophoresis (Lipoprint) to analyze the LDL subfractions. Simvastatin/ezetimibe with either clopidogrel or ticagrelor was associated with less oxidized LDL, and simvastatin/ezetimibe with ticagrelor to lower cholesterol content in the atherogenic subfractions of LDL, while rosuvastatin with ticagrelor was the only combination associated with increase in LDL size. The quality of LDL particles was influenced by the antiplatelet/lipid-lowering strategy, with ticagrelor being associated with the best performance with both lipid-lowering therapies. Trial registration: NCT02428374.