Large HDL Particles Research Articles

Physical Activity, Sedentary Leisure Time, Circulating Metabolic Markers, and Risk of Major Vascular Diseases.

Physical inactivity and sedentary behavior are associated with higher risk of cardiovascular disease (CVD). Little is known about the relevance of circulating metabolites for these associations. A nested case-control study within the prospective China Kadoorie Biobank included 3195 incident CVD cases (2057 occlusive CVD and 1138 intracerebral hemorrhage) and 1465 controls aged 30 to 79 years without prior CVD or statin use at baseline. Nuclear magnetic resonance spectroscopy was used to measure 225 metabolic markers and derived traits in baseline plasma samples. Linear regression was used to relate self-reported physical activity and sedentary leisure time to biomarkers, adjusting for potential confounders. These were contrasted with associations of biomarkers with occlusive CVD risk. Physical activity and sedentary leisure time were associated with >100 metabolic markers, with patterns of associations generally mirroring each other. Physical activity was inversely associated with very low and low-density and positively with large and very large HDL (high-density lipoprotein) particle concentrations. Physical activity was also inversely associated with alanine, glucose, lactate, acetoacetate, and the inflammatory marker glycoprotein acetyls. In general, associations of physical activity and sedentary leisure time with specific metabolic markers were directionally consistent with the associations of these metabolic markers with occlusive CVD risk. Overall, metabolic markers potentially explained ≈70% of the protective associations of physical activity and ≈50% of the positive associations of sedentary leisure time with occlusive CVD. Among Chinese adults, physical activity and sedentary behavior have opposing associations with a diverse range of circulating metabolites, which may partially explain their associations with CVD risk.

Associations of Aerobic Fitness and Maximal Muscular Strength With Metabolites in Young Men

High physical fitness is associated with a reduction in risk of cardiovascular diseases and death, but the underlying mechanisms are insufficiently understood. To determine how aerobic fitness and muscular strength are associated with serum metabolome measures. This cross-sectional study included Finnish men receiving military refresher training from May 5, 2015, to November 28, 2015, representing partly overlapping groups of individuals with the lowest vs highest aerobic fitness and the lowest vs highest muscular strength. Data analyses were conducted from January 1, 2018, to May 31, 2019. The associations of aerobic fitness (determined with maximum oxygen consumption in milliliters per minute per kilogram, measured with maximal cycle ergometer test) and muscular strength (determined with a maximal strength test for lower extremities in kilograms) with 66 metabolome measures from fasting serum samples (nuclear magnetic resonance-based metabolomics) were analyzed. Participants included 580 Finnish men (mean [SD] age, 26.1 [6.5] years). Including overlap between groups, there were 196 men in the lowest aerobic fitness group and 197 men in the highest aerobic fitness group as well as 196 men in the lowest muscular strength group and 197 men in the highest muscular strength group. Of 66 studied metabolome measures, 48 differed between high vs low aerobic fitness groups, including small very low-density lipoprotein (standardized median difference, -0.67; 95% CI, -0.83 to -0.49), large high-density lipoprotein (standardized median difference, 0.89; 95% CI, 0.69-1.15), total triglyceride levels (standardized median difference, -0.52; 95% CI, -0.65 to -0.34), isoleucine (standardized median difference, -0.37; 95% CI, -0.55 to -0.16), leucine (standardized median difference, -0.55; 95% CI, -0.72 to -0.34), phenylalanine (standardized median difference, -0.54; 95% CI, -0.71 to -0.32), glycerol (standardized median difference, -0.64; 95% CI, -0.81 to -0.48), and glycoprotein (standardized median difference, -0.78; 95% CI, -0.95 to -0.62) concentration, a high unsaturation degree of fatty acids (standardized median difference, 0.59; 95% CI, 0.42-0.81), and apolipoprotein B to apolipoprotein A1 ratio (standardized median difference, -0.88; 95% CI, -1.08 to -0.67). Adding aerobic fitness into the regression model after age, education, smoking, use of alcohol, and dietary factors accounted for more than an additional 5% of variation for 25 metabolome measures (R2 range, 5.01%-15.90% by measure). With these 2 criteria, maximal muscular strength was not associated with any metabolome measures. Aerobic fitness was associated with high large high-density lipoprotein particle concentration (R2, 14.97%; 95% CI, 10.65%-20.85%), low apolipoprotein B to apolipoprotein A1 ratio (R2, 14.49%; 95% CI, 10.58%-19.51%), and low glycoprotein concentration (R2, 15.90%; 95% CI, 11.22%-21.51%). Aerobic fitness was also associated with low very low-density lipoprotein, triglyceride, isoleucine, leucine, phenylalanine, glycerol, and glycoprotein concentrations and with a high unsaturation degree of fatty acids. Adjusting for recent physical activity influenced the results minimally. Adjusting for body fat percentage showed that some of the associations were mechanistically associated with body fat percentage. This study provides data on the association of high aerobic fitness with underlying oxidative lipid metabolism associated with a reduction in cardiometabolic risk. High maximal muscular strength is not similarly associated with these benefits.

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.

Mechanisms underlying the cardiometabolic protective effect of walnut consumption in obese people: A cross-over, randomized, double-blind, controlled inpatient physiology study.

To assess the effects of walnuts on cardiometabolic outcomes in obese people and to explore the underlying mechanisms using novel methods including metabolomic, lipidomic, glycomic and microbiome analysis, integrated with lipid particle fractionation, appetite-regulating hormones and haemodynamic measurements. A total of 10 obese individuals were enrolled in this cross-over, randomized, double-blind, placebo-controlled clinical trial. The participants had two 5-day inpatient stays, during which they consumed a smoothie containing 48 g walnuts or a macronutrient-matched placebo smoothie without nuts, with a 1-month washout period between the two visits. Walnut consumption improved aspects of the lipid profile; it reduced fasting small and dense LDL particles (P < 0.02) and increased postprandial large HDL particles (P < 0.01). Lipoprotein insulin resistance score, glucose and the insulin area under the curve (AUC) decreased significantly after walnut consumption (P < 0.01, P < 0.02 and P < 0.04, respectively). Consuming walnuts significantly increased 10 N-glycans, with eight of them carrying a fucose core. Lipidomic analysis showed a robust reduction in harmful ceramides, hexosylceramides and sphingomyelins, which have been shown to mediate effects on cardiometabolic risk. The peptide YY AUC significantly increased after walnut consumption (P < 0.03). No major significant changes in haemodynamic or metabolomic analysis or in microbiome host health-promoting bacteria such as Faecalibacterium were found. These data provide a more comprehensive mechanistic perspective of the effect of dietary walnut consumption on cardiometabolic variables. Lipidomic and lipid nuclear magnetic resonance spectroscopy analysis showed an early but significant reduction in ceramides and other atherogenic lipids with walnut consumption, which may explain the longer-term benefits of walnuts or other nuts on insulin resistance, cardiovascular risk and mortality.

Haptoglobin Phenotype Modulates Lipoprotein-Associated Risk for Preeclampsia in Women With Type 1 Diabetes.

The incidence of preeclampsia (PE) is increased in women with diabetes (∼20% vs ∼5% in the general population), and first trimester lipoprotein profiles are predictive. Haptoglobin (Hp), a protein with functional genetic polymorphisms, has antioxidant, anti-inflammatory, and angiogenic effects. Among people with diabetes, the Hp 2-2 phenotype is associated with cardiorenal disease. To investigate whether Hp phenotype is associated with PE in type 1 diabetes mellitus (T1DM) and/or modulates lipoprotein-associated risks. Multicenter prospective study of T1DM pregnancy. Pregnant women with T1DM (normal albuminuria, normotensive at enrolment, n = 47) studied at three visits, all preceding PE onset: 12.3 ± 1.9, 21.8 ± 1.5, and 31.5 ± 1.6 weeks' gestation (mean ± SD). Hp phenotype and lipoprotein profiles in women with (n = 23) vs without (n = 24) subsequent PE. Hp phenotype did not predict PE, but lipoprotein associations with subsequent PE were confined to women with Hp 2-2, in whom the following associations with PE were observed: increased low-density lipoprotein (LDL) cholesterol, LDL particle concentration, apolipoprotein B (APOB), triacylglycerol/high-density lipoprotein (HDL) cholesterol ratio, and APOB/apolipoprotein AI (APOA1) ratio; decreased HDL cholesterol, APOA1, large HDL particle concentration, and peripheral lipoprotein lipolysis (all P < 0.05). In women with one or two Hp-1 alleles, no such associations were observed. In women with T1DM, although Hp phenotype did not predict PE risk, lipoprotein-related risks for PE were limited to those with the Hp 2-2 phenotype. Hp phenotype may modulate PE risk in diabetes.

High-density lipoprotein (HDL) particle size and concentration changes in septic shock patients

BackgroundSepsis is associated with systemic inflammation that may impact lipoprotein function. In particular, high-density lipoproteins (HDLs) that display pleiotropic protective roles may be dysfunctional in septic conditions. The aim of this study was to evaluate the HDL profile and the inflammatory context in septic shock patients admitted to our intensive care unit (ICU).MethodsIn this study, 20 septic shock patients and 20 controls (ICU patients without septic shock) were included. Plasma samples were collected on days 1, 2 and 7. Total cholesterol and lipoprotein concentrations were determined. HDL profiles were obtained using the Lipoprint® System (non-denaturing electrophoresis). Quantification of pro-inflammatory cytokines (interleukin 1b, 6 and 8), cell-free DNA and lipopolysaccharide-binding protein was also performed.ResultsHDL concentration was statistically lower in septic shock patients than in controls. At days 1 and 2, septic patients had significantly more large-sized HDL than control patients. Patients recovered a normal lipid profile at day 7.ConclusionsOur results emphasize that HDL levels are dramatically decreased in the acute phase of septic shock and that there is a shift toward large HDL particles, which may reflect a major dysfunction of these lipoproteins. Further mechanistic studies are required to explore this shift observed during sepsis.

Differences in Response to Egg Intake Result in Distinct Lipoprotein Profiles While Plasma Concentrations of Carotenoids and Choline Are Not Affected (P08-102-19)

ObjectivesIt has been demonstrated that some individuals (approximately 1/3 of the population) can be classified as hyper-responders to dietary cholesterol. The objective of this study was to evaluate whether the response to dietary cholesterol (provided by eggs) would affect lipoprotein metabolism and the bioavailability of lutein, zeaxanthin and choline, nutritional components present in eggs. MethodsWe recruited 36 healthy subjects who underwent a two-week washout period in which they consumed zero eggs. Participants were then fed 3 eggs (540 additional mg of dietary cholesterol) for 4 weeks. Plasma lipids were measured by use of an automated chemical clinical analyzer; the number of large and small LDL and HDL particles were measured by Nuclear Magnetic Resonance. Plasma lutein and zeaxanthin were determined by use of HPLC and plasma choline by use of LSM spectroscopy. We classified the normal response to dietary cholesterol as 2.2 mg/dL for each additional 100 mg of dietary cholesterol. Therefore, those individuals who had >12 mg/dL increase in plasma cholesterol after the intervention (n = 12) were considered hyper-responders while the other 24 subjects who presented changes in plasma cholesterol ranging from −16 to 9 mg/dL were considered hypo-responders. ResultsCompared to zero eggs, hyper-responders had significant increases in plasma total, LDL and HDL cholesterol (P < 0.001) with no changes in the LDL/HDL ratio. They also had higher concentrations of large LDL (P < 0.01) with no changes in small LDL. In contrast no changes in plasma total LDL or HDL cholesterol or large LDL were observed in hypo-responders after the consumption of 3 eggs/day. Interestingly, both hypo and hyper-responders had significant increases in large HDL particles (12%), plasma lutein (17%), zeaxanthin (30%) and choline (12%) (P < 0.001) compared to zero egg intake. ConclusionsThese results suggest that egg intake increases the bioavailability of carotenoids and choline present in eggs independently of plasma cholesterol response to dietary cholesterol. Further, the observed increases in large HDL in all individuals could be associated with HDL being a major transporter of lutein and zeaxanthin in plasma. Funding SourcesThe Esperance Family and the Egg Nutrition Center.

SAT-081 Advanced Lipoprotein Analysis Demonstrates Atherogenic Lipid Profile in Patients with Lipodystrophy That Improves after Metreleptin Treatment

Lipodystrophies (LD) are defined by deficient adipose tissue, causing low leptin and metabolic disease including severe insulin resistance and hypertriglyceridemia. Recombinant leptin (metreleptin, ML) treatment in LD improves insulin resistance and lowers triglycerides without changing HDL. Detailed measurement of lipoprotein particles using NMR spectroscopy can offer insights into cardiovascular disease (CVD) risk and lipid metabolism beyond a standard lipid panel and has never been performed in LD. We hypothesized that patients with LD would have a more atherogenic lipid profile than controls at baseline, which would be ameliorated with ML treatment secondary to improvements in insulin sensitivity. Patients with LD (N=17) were enrolled in a study evaluating short- and long-term effects of ML on metabolic disease and compared to 51 insulin sensitive (SI<3 on IV glucose tolerance test) sex-matched controls. Lipoprotein profiles were assessed on samples obtained after a 10-12 hour fast using a new deconvolution algorithm, LP4, which reports 27 triglyceride rich lipoprotein particles (TRLP) and 7 HDL particles (HDLP). The major categories are small, medium, and large HDLP and LDL particles (LDLP) and very small, small, medium, large, and very large TRLP. LP4 was compared in controls vs. patients with LD prior to ML. LP4 was compared in patients with LD before vs. after 14 days and 6 months of ML. Particle size, concentration, and concentration of subclasses by size were measured for LDLP, HDLP, and TRLP. Insulin sensitivity before and after ML was measured as glucose disposal (mg/kgFFM/min) during hyperinsulinemic euglycemic clamp. Patients and controls did not differ by age, weight, or BMI. Patients with LD had elevated large TRLP and smaller sized HDLP and LDLP, all associated with increased atherogenicity, vs. controls. Five of 17 patients with LD had chylomicrons present, vs. 0 of 51 controls. ML treatment in LD decreased size and concentration of TRLP, eliminated chylomicrons in all but 1 patient, decreased LDLP concentration, and increased LDLP size. ML treatment did not have major effects on HDLP. Prior to ML in patients with LD, insulin sensitivity negatively correlated with very large TRLP (r= -0.76, p= 0.0007), TRLP size (r= -0.52, p= 0.04), and TRLP TG (r= -0.58, p= 0.02). Short term (Day 0 to Day 14) and long-term changes (Day 0 to 6 months) in insulin sensitivity were not significantly correlated with changes in any lipoprotein parameter. In conclusion, patients with LD had an atherogenic lipoprotein profile at baseline consistent with increased CVD risk, which improved after ML treatment. The presence of fasting chylomicrons in a subset of patients with LD suggests saturation of chylomicron clearance by lipoprotein lipase. Improvements in lipoprotein parameters with ML were independent of improved insulin sensitivity, possibly due to direct effects of ML on lipoprotein metabolism.

Small HDL, diabetes, and proinflammatory effects in macrophages

Atherosclerosis, an inflammatory disease of the arterial wall, is the commonest cause of cardiovascular disease (CVD) events. Elevated levels of high‐density lipoprotein (HDL) cholesterol are generally believed to protect against CVD and to reduce inflammatory activation of macrophages, a key cell type in lesions of atherosclerosis. However, HDL can also exert proinflammatory effects in macrophages by inducing cholesterol depletion. Because small HDL (7–8.5 nm diameter) is most effective in removing cholesterol from cells by the ABCA1 pathway, we hypothesized that small HDL is the most proinflammatory HDL population. Small‐, medium‐ and large HDL populations were isolated from a human apolipoprotein A‐I transgenic LDL receptor‐deficient mouse model (APOA1Tg;Ldlr−/−). Depletion of cholesterol by HDL increased the ability of toll‐like receptor (TLR) ligands to induce proinflammatory mediators in macrophages. This effect was prevented by cholesterol loading of the macrophages. Small HDL had a significantly stronger effect on Tnfa (3‐fold over LPS alone) and Il1b (2.5‐fold over LPS alone) gene expression than medium or large HDL particles. Inhibition or deletion of the sheddase ADAM17 in macrophages prevented the proinflammatory effects of HDL. Patients with type 1 diabetes mellitus (T1DM) exhibit an increased risk of CVD despite having normal or high HDL‐cholesterol. To investigate the effect of diabetes on HDL subpopulations, we crossed a virally‐induced mouse model of T1DM (Ldlr−/−;GpTg) with the human APOA1Tg;Ldlr−/− mouse. The mice (APOA1Tg;Ldlr−/−;GpTg, n=8–10) were injected with a liver‐specific adeno‐associated virus driving expression of human cholesteryl ester transfer protein (hCETP) to mimic human physiology. Diabetic mice had an increased HDL particle concentration (~2‐fold) associated with a significant increase in serum HDL cholesterol efflux capacity through both ABCA1 and ABCG1, compared with non‐diabetic mice. The largest increase was in the small HDL particle concentration (15 μM vs 6 μM in non‐diabetic mice). Moreover, resident peritoneal macrophages from diabetic mice exhibited increased cytokine gene expression, as compared with non‐diabetic littermates. Our findings demonstrate that higher levels of small HDL, as observed in a mouse model of diabetes, can exacerbate inflammatory activation in non‐lipid loaded macrophages in an ADAM17‐dependent manner. We have found similar changes in HDL concentration and function in humans with T1DM, suggesting that our mouse model might provide novel insights into CVD risk in T1DM patients.Support or Funding Informationfunded in part by the National Institutes of Health, grants DP3DK108209, P01HL092969, P30 DK017047, and P01HL128203This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Effect of Cardiorespiratory Fitness on Lipoprotein Particles in Midlife Women

Cardiovascular disease (CVD) risk accelerates in midlife women. Although lipoprotein cholesterol is a risk factor for CVD, increasing evidence suggests that lipoprotein particles may be more related to cardiovascular health. High cardiorespiratory fitness is associated with better lipoprotein particle profiles in men; however, little research has evaluated the effects of cardiorespiratory fitness on lipoprotein particles in midlife women.PURPOSETo evaluate the influence of cardiorespiratory fitness on lipoprotein particle profiles in healthy midlife women.METHODSThe concentration, size, and subtype of high‐density (HDL), low‐density (LDL), very‐low density (VLDL), and intermediate density (IDL) lipoprotein particles was evaluated, along with the number of chylomicrons and triglycerides using nuclear magnetic resonance spectroscopy (LabCorp) in healthy high (n = 25, VO2peak = 46.4 ± 1.6 ml/kg/min, age = 55.8 ± 1.2 yr) and low‐fit (n = 13, VO2peak = 29.1 ± 1.0 ml/kg/min, age = 54.8 ± 1.8 yr) perimenopausal and postmenopausal women. A standard lipoprotein cholesterol profile was also assessed. Differences between high and low‐fit women were evaluated with independent t‐tests or Mann‐Whitney tests. Data are presented as mean ± SEM.RESULTSHigh‐density lipoprotein cholesterol was higher in high compared to low‐fit women (88.6 ± 2.9 vs. 74.7 ± 5.1 mg/dl, p = 0.015), while triglycerides and low‐density lipoprotein cholesterol concentration did not differ based on fitness (p&gt;0.05). Compared to low‐fit women, high fit women had larger HDL particles (10.1 ± 0.1 vs. 9.7 ± 0.1 nm, p = 0.005), and a greater concentration of large (14.8 ± 0.7 vs. 11.0 ± 0.9 mmol/L, p = 0.002), and medium (12.9 ± 0.8 vs. 8.4 ± 0.8 mmol/L, p = 0.002) HDL particles. High‐fit women had larger LDL particles (21.7 ± 0.1 vs. 21.3 ± 0.1 nm, p = 0.005), and a greater concentration of large LDL particles (623.1 ± 32.8 vs. 500.2 ± 52.6 nmol/L, p = 0.045) and medium VLDL particles (10.6 ± 1.2 vs. 6.5 ± 1.6 nmol/L, p = 0.044) compared to low‐fit women. Conversely, low‐fit women had more small VLDL (29.9 ± 2.8 vs. 18.2 ± 2.5 nmol/L, p = 0.007), small HDL (15.4 ± 1.6 vs. 10.2 ± 1.1 mmol/L, p = 0.002), and small LDL particles (311.5 ± 44.7 vs. 145.5 ± 31.4 nmol/L, p = 0.001) compared to high‐fit women.CONCLUSIONThese data indicate that in healthy midlife women, high cardiorespiratory fitness may positively influence lipoprotein particle sizes and concentrations, and that many of these differences are not apparent from a standard lipid profile.Support or Funding InformationAmerican College of Sports Medicine Foundation Doctoral Student Research Grant (Serviente), National Institute on Aging Grant T32‐AG049676 (Pennsylvania State University), University of Massachusetts Amherst Provost's Undergraduate Research Fellowship (Chalvin).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

MENOPAUSAL STAGE INFLUENCES LIPOPROTEIN SUBCLASS PROFILE IN HABITUALLY ACTIVE WOMEN

Menopause is associated with increased cardiovascular disease risk, in part due to worsening cholesterol profile with advancing menopausal stage. The effect of menopausal stage on lipoprotein cholesterol, lipoprotein particle size and number in active midlife women has not been evaluated.PURPOSETo evaluate differences in lipoprotein subclass concentrations between highly‐fit, habitually active women at distinct menopausal stages.METHODSWomen (40–65 yr) were healthy habitually active highly‐fit pre‐, peri‐, and postmenopausal women (PRE, n = 10, VO2peak = 47.0 ± 2.4 ml/kg/min, PERI, n = 12, VO2peak = 49.1 ± 2.4 ml/kg/min, and POST, n = 13, VO2peak = 43.8 ± 1.8 ml/kg/min). Menopausal stage was defined using the STRAW+10 criteria. Particle subclass concentrations and mean particle sizes (were measured using nuclear magnetic resonance spectroscopy (LabCorp). Calculated lipids (total triglyceride, total VLDL and chylomicron triglyceride, and total HDL cholesterol) were also analyzed. Blood samples for lipoprotein particle analysis were collected during days 1–6 of the menstrual cycle for PRE. ANOVAs with Holm‐Sidak post hoc testing were used to determine differences between groups for each lipid outcome. Nonparametric tests were employed if assumptions were not met. Data are presented as mean ± SEM.RESULTSThere was a significant effect of menopause stage on total HDL cholesterol (p = 0.010) with greater HDL cholesterol in POST (88.5 ± 2.2 mg/dl) vs. PRE (72.2 ± 5.7 mg/dl, p = 0.032) and total HDL particle concentration (p = 0.010) with significantly greater total HDL particle concentration in POST (40.2 ± 1.1 μmol/L) compared with PRE (34.9 ± 1.5 μmol/L, p = 0.023) and POST compared with PERI (PERI, 35.5 ± 1.3 μmol/L, p = 0.033). There was a trend for an effect of menopausal status on large HDL particle concentration (p = 0.072) with progressively greater large HDL particle concentration with each advancing stage (PRE 12.1 ± 1.1 μmol/L, PERI, 14.0 ± 1.2 μmol/L, POST, 15.5 ± 0.6 μmol/L). There was no significant effect of menopausal stage on medium or small HDL particle concentration or HDL size (all p&gt;0.05). There was an effect of menopausal stage on large LDL particle concentration (p = 0.039) with greater concentration of large LDL particles in PRE (479 ± 52.6 nmol/L) vs. POST (663 ± 47.5 nmol/L, p = 0.034) but no effect of menopausal stage on small LDL, IDL, or total LDL particle concentration, or LDL size (all p&gt;0.05). There was no effect of menopausal status on any VLDL &amp; chylomicron particle concentration or VLDL size (all p&gt;0.05).CONCLUSIONThese data indicate that in healthy, highly fit women, advancing menopausal stage does not have a negative effect on many lipoprotein particle concentrations. Habitual physical activity may eliminate or potentially reverse some of the negative consequences of menopause on lipids.Support or Funding InformationFunding Sources: American College of Sports Medicine Foundation Doctoral Student Research Grant (Serviente), National Institute on Aging Grant T32‐AG049676 (Pennsylvania State University), University of Massachusetts Amherst Provost's Undergraduate Research Fellowship (Chalvin).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Compositional Features of HDL Particles Interact with Albuminuria to Modulate Cardiovascular Disease Risk.

Lipoproteins containing apolipoprotein B modify associations of elevated urinary albumin excretion (UAE) with cardiovascular disease (CVD). Additionally, it is known that elevated UAE alters high-density lipoprotein functionality. Accordingly, we examined whether HDL features might also modify UAE-associated CVD. Multivariable Cox proportional-hazards modeling was performed on participants of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study at the baseline screening with standard lipid/lipoprotein analyses and, three-to-four years later (second screen), with nuclear magnetic resonance lipoprotein analyses focusing on HDL parameters including HDL particle (HDL-P) and apolipoprotein A-I concentrations. These were used with UAE and derived measures of HDL apoA-I content (apoA-I/HDL-C and apoA-I/HDL-P) in risk models adjusted for gender, age, apoB, diabetes, past CVD history, CRP and GFR. Interaction analysis was also performed. Baseline screening revealed significant associations inverse for HDL-C and apoA-I and direct for apoA-I/HDL-C. The second screening demonstrated associations inverse for HDL-P, large HDL-P, medium HDL-P, HDL size, and apoA-I/HDL-P. Significant interactions with UAE included apoA-I/HDL-C at the baseline screening, and apoA-I/HDL-P and medium HDL-P but not apoA-I/HDL-C at the second screening. We conclude that features of HDL particles including apoA-I/HDL-P, indicative of HDL apoA-I content, and medium HDL-P modify associations of elevated UAE with CVD risk.

U HDL-cholesterolu již zřejmě neplatí "čím výše, tím lépe"

It is very well known from the old epidemiological population studies, that HDL-cholesterol (HDL-C) was in a negative association with coronary events risk. New studies have occurred during the last 10 years that the mentioned association has in fact the U-shaped curve, i.e. lower and higher levels of HDL-C then the optimal one are in an exponential increasing risk. The association of high HDL-C levels with cardiovascular risk is not explained clearly. There might be a hypothesis concerning a change of function of large HDL particles riched of cholesterol esters, which become to be cholesterol donors for the arteries. Key words: cardiovascular risk - HDL-cholesterol - HDL particles.

Cardiovascular Risk Factor Reduction in First Responders Resulting From an Individualized Lifestyle and Blood Test Program: A Randomized Controlled Trial.

We tested the hypothesis that a lifestyle program would improve risk factors linked to cardiovascular disease (CVD) in first responders. A 1-year cluster-randomized controlled clinical trial in 10 cities. Participants were 175 first responders, with increased waist circumference and/or low levels of large (α1) high-density lipoprotein (HDL) particles. The intervention group received personalized online tools and access to telephonic coaching sessions. At 1 year the intervention significantly reduced body weight (P = 0.004) and waist circumference (P = 0.002), increased α1 HDL (P = 0.01), and decreased triglyceride (P = 0.005) and insulin concentrations (P = 0.03). Program adherence was associated with weight loss (P = 0.0005) and increases in α1 HDL (P = 0.03). In first responders, a personalized lifestyle intervention significantly improved CVD risk factors in proportion to program adherence. Changes in large HDL particles were more sensitive indicators of lifestyle changes than HDL-cholesterol measurement. ClinicalTrials.gov: NCT03322046.

Paradox of hypercholesterolaemia in highly trained, keto-adapted athletes

ObjectiveA growing number of ultra-endurance athletes have switched to a very low-carbohydrate/high-fat eating pattern. We compared markers of cholesterol and the lipoprotein profile in a group of elite ultra-runners consuming...

High-Density Lipoprotein Particles, Cell-Cholesterol Efflux, and Coronary Heart Disease Risk.

Objective- The cell-cholesterol efflux capacity of HDL (high-density lipoprotein) is inversely associated with coronary heart disease risk. ABCA1 (ATP-binding cassette transporter A1) plays a crucial role in cholesterol efflux from macrophages to preβ-1-HDL. We tested the hypothesis that coronary heart disease patients have functionally abnormal preβ-1-HDL. Approach and Results- HDL cell-cholesterol efflux capacity via the ABCA1 and the SR-BI (scavenger receptor class B type I) pathways, HDL antioxidative capacity, apo (apolipoprotein) A-I-containing HDL particles, and inflammatory- and oxidative-stress markers were measured in a case-control study of 100 coronary heart disease cases and 100 sex-matched controls. There were significant positive correlations between ABCA1-dependent cholesterol efflux and the levels of small lipid-poor preβ-1 particles ( R2=0.535) and between SR-BI-dependent cholesterol efflux and the levels of large lipid-rich (α-1+α-2) HDL particles ( R2=0.712). Cases had significantly higher (87%) preβ-1 concentrations than controls, but the functionality of their preβ-1 particles (preβ-1 concentration normalized ABCA1-dependent efflux capacity) was significantly lower (-31%). Cases had significantly lower (-12%) mean concentration of large HDL particles, but the functionality of their particles (α-1+α-2 concentration normalized SR-BI-dependent efflux capacity) was significantly higher (22%) compared with that of controls. HDL antioxidative capacity was significantly lower (-16%) in cases than in controls. There were no significant correlations between either preβ-1 functionality or large HDL particle functionality with HDL antioxidative capacity or the concentrations of inflammatory- and oxidative-stress markers. Conclusions- HDL cell-cholesterol efflux capacity is significantly influenced by both the concentration and the functionality of specific HDL particles participating in cell-cholesterol efflux. Coronary heart disease patients have higher than normal preβ-1 concentrations with decreased functionality and lower than normal large HDL particle concentrations with enhanced functionality.

Influence of i.v. lipid emulsion on lipoprotein subclass in preterm infants.

Lipid emulsions given i.v. are normally rapidly metabolized by apoprotein recruited from high-density lipoprotein (HDL) particles in the blood. Very low-birthweight infants (VLBWI), however, have a low rate of lipid clearance from the blood, and therefore lipid emulsions must be given carefully to minimize the risk of hyperlipidemia. The purpose of this study was to evaluate the influence of i.v. lipid emulsion on lipoprotein subclass profile in VLBWI during the early postnatal period. Forty-six VLBWI who had been given different doses of lipid emulsion in the first few days after birth were enrolled in the present study. Triglyceride and cholesterol content of each lipoprotein subclass was measured at 3weeks after birth, and their correlation with the total dose of lipid emulsion was calculated. There was no correlation between the total dose of lipid emulsion and the triglyceride and cholesterol content in any subclasses of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL). There was a significant negative correlation between the total dose of lipid emulsion and the triglyceride content in very large (P < 0.05, r = -0.32), large (P < 0.01, r = -0.47) and medium HDL (P < 0.05, r = -0.34) particles; and the cholesterol content in large (P < 0.01, r = -0.47) and medium HDL (P < 0.01, r = -0.4) particles. Lipid emulsion influenced the triglyceride and cholesterol content of HDL particles in VLBWI, suggesting that lipid emulsion can affect lipid metabolism in this infant population in the early postnatal period.

Metabolomic profiling implicates adiponectin as mediator of a favorable lipoprotein profile associated with NT-proBNP

BackgroundThe N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is an important biomarker for the diagnosis of heart failure. Apart from this and only recently recognized, NT-proBNP levels associate with higher HDL- and lower LDL-cholesterol levels comprising a favorable blood lipid profile. To further examine this observation, the lipoprotein profile in relation to NT-proBNP was examined in-depth by proton nuclear magnetic resonance spectroscopy (1H-NMR). We complemented this investigation with a state-of-the-art untargeted metabolomics approach.MethodsLipoprotein particles were determined by 1H-NMR spectroscopy in 872 subjects without self-reported diabetes from the population-based Study of Health in Pomerania (SHIP)-TREND with available NT-proBNP measurements. Comprehensive metabolomics data for plasma and urine samples were obtained. Linear regression models were performed to assess the associations between serum concentrations of NT-proBNP and the metabolites/lipoprotein particles measured in plasma or urine.ResultsAn increase in serum NT-proBNP was associated with a benefical lipoprotein profile, including a decrease in VLDL, IDL and LDL-particles along with an increase in large HDL particles. These findings were replicated in a second independent cohort. Serum concentrations of NT-proBNP showed significant inverse associations with seven plasma metabolites while associations with 39 urinary metabolites, mostly comprising amino acids and related intermediates, were identified. Mediation analyses revealed adiponection as mediating factor for the associations observed with lipoproteins particles.ConclusionsMost of the metabolic changes associated with NT-proBNP implicate significant influence on the blood lipid profile besides vasodilatory and the diuretic action of BNP signaling. Our data suggest that the more favorable lipoprotein profile as associated with elevated NT-proBNP concentrations in mainly cardiac healthy individuals might relate to adiponectin signaling indicating even indirect cardio-protective effects for NT-proBNP.

Cholesterol efflux capacity of large, small and total HDL particles is unaltered by atorvastatin in patients with type 2 diabetes

Background and aimsResearch on the biologic activities of HDL, such as cholesterol efflux capacity and HDL composition, has allowed the understanding of the effect of interventions directed to improve cardiovascular risk. Previously, statin therapy has shown conflicting results about its effects on cholesterol efflux capacity of HDL; the underlying mechanisms are unclear but studies with positive effects are associated with an increase of HDL-cholesterol levels. We investigated if 10 weeks of atorvastatin therapy changes HDL efflux capacity and the chemical composition of its subpopulations. MethodsIn a before-after design basis, HDL-cholesterol levels, chemical composition and cholesterol efflux capacity from HDL subpopulations isolated by isophynic ultracentrifugation were assessed in plasma samples from 60 patients with type 2 diabetes mellito (T2DM) at baseline and after 10 weeks of treatment with 20 mg atorvastatin. Cholesterol efflux was measured from human THP-1 cells using large, light HDL2b and small, dense 3c subpopulations as well as total HDL as acceptors. Changes of cholesterol efflux and chemical composition of HDL after treatment were analyzed. Correlations among variables potentially involved in cholesterol efflux were evaluated. ResultsA significant decrease of 4% in HDL-cholesterol levels was observed from 47 (42–54) to 45 (39–56) mg/dL, p = 0.02. Cholesterol efflux from total-HDL and HDL2b and 3c subfractions was maintained unchanged after treatment. The total mass of HDL remained unaffected, except for the HDL3a subpopulation accounted for by a significant increase in total protein content. No significant correlations for variables previously known to be associated with cholesterol efflux were found in our study. ConclusionsShort therapy of 10 weeks with 20 mg of atorvastatin does not modify the cholesterol efflux capacity neither the total mass of HDL2b, HDL3c and total HDL. The discrepancy with previous reports may be due to the selective effects among different classes of statins or differences in the approaches to measure cellular cholesterol efflux.

Dietary Inflammatory Index and Biomarkers of Lipoprotein Metabolism, Inflammation and Glucose Homeostasis in Adults.

Accumulating evidence identifies diet and inflammation as potential mechanisms contributing to cardiometabolic risk. However, inconsistent reports regarding dietary inflammatory potential, biomarkers of cardiometabolic health and metabolic syndrome (MetS) risk exist. Our objective was to examine the relationships between a food frequency questionnaire (FFQ)-derived dietary inflammatory index (DII®), biomarkers of lipoprotein metabolism, inflammation and glucose homeostasis and MetS risk in a cross-sectional sample of 1992 adults. Energy-adjusted DII (E-DII) scores derived from an FFQ were calculated. Lipoprotein particle size and subclass concentrations were measured using nuclear magnetic resonance (NMR) spectroscopy. Serum acute-phase reactants, adipocytokines, pro-inflammatory cytokines and white blood cell (WBC) counts were determined. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Our data indicate that a more pro-inflammatory diet, reflected by higher E-DII scores, was associated with potentially pro-atherogenic lipoprotein profiles characterised by increased numbers of large very low density lipoprotein (VLDL), small dense low density lipoprotein (LDL) and high density lipoprotein (HDL) particles and less large LDL and HDL particles (all p < 0.001). Inflammatory profiling identified a range of adverse phenotypes among those with higher E-DII scores, including higher complement component C3 (C3), C-reactive protein (CRP), (both p < 0.05), interleukin 6 (IL-6) and tumour necrosis factor (TNF)-α concentrations, higher WBC counts and neutrophil to lymphocyte ratio (NLR) and lower adiponectin levels (all p < 0.001). MetS risk was increased among those with higher E-DII scores (OR 1.37, 95% CI (1.01, 1.88), p < 0.05), after adjusting for potential confounders. In conclusion, habitual intake of a more pro-inflammatory diet is associated with unfavourable lipoprotein and inflammatory profiles and increased MetS risk.