Lipoprotein Particle Size Research Articles

N-3 polyunsaturated fatty acids improve lipoprotein particle size and concentration in Japanese patients with type 2 diabetes and hypertriglyceridemia: a pilot study

BackgroundPatients with type 2 diabetes are at high risk for cardiovascular disease. Although hydroxymethylglutaryl-CoA reductase inhibitors (statins) can reduce cardiovascular events, residual risk remains even after target low-density lipoprotein cholesterol (LDL-C) levels have been achieved. Lipoprotein particle size and fraction changes are thought to contribute to such risks. The purpose of this study was to evaluate the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), predominantly eicosapentaenoic acid and docosahexaenoic acid, on lipoprotein particle size, concentration, and glycemic control in Japanese patients with type 2 diabetes and hypertriglyceridemia.MethodsThis was a multicenter, prospective, open-label, single arm study. We enrolled 14 patients with type 2 diabetes and hypertriglyceridemia treated with statins and dipeptidyl peptidase-4 inhibitors with glycated hemoglobin (HbA1c) < 8.0%, LDL-C < 120 mg/dL, and fasting triglyceride ≥150 mg/dL. After a 12-week observation period, they were treated with 4 g/day n-3 PUFAs for 12 weeks. Lipoprotein particle sizes, concentrations, lipoprotein insulin resistance (LPIR) scores, lipid profiles, HbA1c, and fasting plasma glucose (FPG) were measured before and after treatment. Lipoprotein profiles were measured by nuclear magnetic resonance spectroscopy. Data were analyzed using Wilcoxon signed-rank tests.ResultsConcentrations of total cholesterol (P < 0.001), LDL-C (P = 0.003), and triglyceride (P < 0.001) decreased following n-3 PUFA administration. N-3 PUFAs decreased the size of very low-density lipoprotein (VLDL; P < 0.001) particles, but did not affect LDL or high-density lipoprotein (HDL) particles. The concentration of large LDL increased, whereas small LDL decreased, causing the large to small LDL ratio to increase significantly (P = 0.042). Large VLDL and chylomicron concentrations significantly decreased, as did the large to small VLDL ratio (all P < 0.001). FPG levels unchanged, whereas HbA1c levels slightly increased. LPIR scores improved significantly (P = 0.001).ConclusionsN-3 PUFAs partly improved atherogenic lipoprotein particle size and concentration, and produced less atherogenic lipoprotein subclass ratios in patients that achieved target LDL-C levels and glycemic control. These results suggest that n-3 PUFAs may reduce residual cardiovascular risk factors in statin-treated patients with type 2 diabetes and hypertriglyceridemia.Trial registrationThe study was registered at UMIN-ID: UMIN000013776.

Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies.

ObjectivesLipid profiles are altered by active disease in patients with rheumatoid arthritis (RA) and may be further modified by treatment with Janus kinase inhibitors and other disease-modifying antirheumatic drugs.MethodsLipid data were analysed from phase II and III studies of 4 mg (n=997) and 2 mg (n=479) oral baricitinib administered once daily in patients with moderate-to-severe active RA. Lipoprotein particle size and number and GlycA were evaluated with nuclear magnetic resonance in one phase III study. The effect of statin therapy on lipid levels was evaluated in patients on statins at baseline and in patients who initiated statins during the study.ResultsTreatment with baricitinib was associated with increased levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides, but no significant change in LDL-C:HDL-C ratio. Lipid levels plateaued after 12 weeks of treatment. Baricitinib treatment increased large LDL and decreased small, dense LDL particle numbers and GlycA. Lipid changes from baseline were not significantly different between baseline statin users and non-users. In patients who initiated statin therapy during the study, LDL-C, triglycerides (baricitinib 4 mg only) and apolipoprotein B decreased to pre-baricitinib levels; HDL-C and apolipoprotein A-I levels remained elevated.ConclusionsBaricitinib was associated with increased LDL-C, HDL-C and triglyceride levels, but did not alter the LDL-C:HDL-C ratio. Evaluation of cardiovascular event rates during long-term treatment is warranted to further characterise these findings and their possible clinical implications.Trial registration numberNCT00902486, NCT01469013, NCT01185353, NCT01721044, NCT01721057, NCT01711359, NCT01710358, NCT01885078.

In women with PCOS, waist circumference is a better surrogate of glucose and lipid metabolism than disease status per se.

Cardiometabolic abnormalities are recognized in polycystic ovary syndrome (PCOS). However, over-emphasis on PCOS as a risk factor potentially results in over-investigation and treatment of some women with and under-recognition of cardiometabolic risk in obese women without PCOS. Our objective was to explore the association between waist circumference (WC) and indices of glucose and lipid metabolism in women with and without PCOS. (i) An exploratory cross-sectional study investigating association of potential cardiometabolic risk markers (PCOS status, anthropometric measures, hsCRP, HOMA-IR, SHBG, testosterone) with indices of glucose (frequently sampled intravenous glucose tolerance test) and lipid metabolism (postprandial studies and lipoprotein particle size) in 61 women with (n=29) and without (n=32) PCOS; (ii) a cross-sectional study in 103 PCOS women and 102 BMI-matched controls to explore if between-group differences in indices of lipid and glucose metabolism persist after adjusting for WC. NIH criteria were used for PCOS diagnosis. Study 1: Univariate correlations and stepwise regression modelling identified waist circumference (WC), as a better surrogate than PCOS status, independently predicting multiple variables of glucose and lipid metabolism. Study 2: Fasting insulin and triglyceride, hsCRP and insulin resistance (according to HOMA-IR and SiM [Avignon index]) were greater, while fasting HDL was lower in women with PCOS compared to BMI-matched women without PCOS. None of these differences persisted when a subset of 80 women with PCOS was compared with 80 women without PCOS, pair-matched for WC. Some cardiometabolic abnormalities in PCOS are related to central obesity, and following adjustment for WC does not differ from normal subjects. Waist circumference measurement has potential to take precedence over PCOS status as part of the assessment of cardiometabolic risk in reproductive-age women.

Lipoprotein profile assessed by 2D-1H-NMR and subclinical atherosclerosis in children with familial hypercholesterolaemia

Background and aimsFamilial hypercholesterolaemia (FH) is underdiagnosed in children. In addition to lipid concentrations, lipoprotein particle quantity and quality could influence cardiovascular risk. We aimed to perform a comprehensive plasma lipid study, including lipoprotein particle number and size assessment by two-dimensional nuclear magnetic resonance (2D-1H-NMR), in children with FH compared to non-affected children and to evaluate the clinical value of these factors as subclinical atherosclerosis biomarkers. MethodsOne hundred eighty-three children participating in the broad “Hypercholesterolemia Early Detection Programme” (Decopin Project) were recruited. They were categorized as FH, if they had either a positive genetic test or clinical certainty, or as control children (CCh). Medical history, anthropometry and clinical variables were recorded. Standard biochemical measurements were performed. The lipoprotein profile was studied by 2D-1H-NMR. Carotid intima-media thickness (cIMT) was assessed by sonography in 177 children. ResultsFH children had a significant 36% increase in LDL particles. The small LDL fraction was increased by 33% compared to CCh. The relative relationship between large, medium and small LDL and the mean LDL particle size was similar between FH children and CCh. The total and small LDL particle numbers were directly associated with and contributed to the determination of the mean cIMT according to bivariate and multivariate analyses in FH children. ConclusionsThe higher cholesterol levels of FH children are due to an overall increased number of all LDL particle subclasses, including a notable 33% increase in small LDL. Total and small LDL particle number shows a good correlation with cIMT in FH children.

Hemoglobin level and lipoprotein particle size

BackgroundAlterations in lipoprotein size are associated with increased cardiovascular disease risk. Higher hemoglobin levels may indicate a higher risk of atherosclerosis and was previously associated with obesity, metabolic syndrome, and insulin resistance. No previous studies have investigated an association between hemoglobin concentration and lipoprotein particle size.MethodsWe conducted a population-based, cross-sectional study of 766 Caucasian, middle-aged subjects (341 men and 425 women) born in Pieksämäki, Finland, who were categorized into five age groups. The concentrations and sizes of lipoprotein subclass particles were analyzed by high-throughput nuclear magnetic resonance (NMR) spectroscopy.ResultsLarger very low density lipoprotein (VLDL) particle diameter was associated with higher hemoglobin concentrations in men (p = 0.003). There was a strong relationship between smaller high density lipoprotein (HDL) particle size and higher hemoglobin concentration in both men and women as well as with smaller low density lipoprotein (LDL) particle size and higher hemoglobin concentration in men and women (p < 0.001; p = 0.009, p = 0.008). VLDL particle concentration had a moderate positive correlation with hemoglobin concentration (r = 0.15; p < 0.001). LDL particle concentration showed a statistical trend suggesting increasing particle concentration with increasing hemoglobin levels (r = 0.08; p = 0.05).ConclusionHigher hemoglobin levels are associated with larger VLDL, smaller LDL, and smaller HDL particle sizes and increasing amounts of larger VLDL and smaller LDL particles. This suggests that a higher hemoglobin concentration is associated with an unfavorable lipoprotein particle profile that is part of states that increase cardiovascular disease risk like diabetes and metabolic syndrome.

Lipoprotein particle sizes in patients undergoing kidney transplantation.

Asymptomatic atherosclerotic disease is prevalent in the middle-aged group of kidney transplant recipients. In order to improve the estimation of their cardiovascular risk, dyslipidaemia pattern is very important to be evaluated. Knowledge of the lipid particle spectrum in patients undergoing kidney transplantation could help the clinicians to timely start intervention and prevention of atherosclerosis with an early hypolipidemic statin treatment (Tab. 2, Ref. 20).

EPHA6 rs4857055 C\u2009>\u2009T polymorphism associates with hypertension through triglyceride and LDL particle size in the Korean population

BackgroundErythropoietin-producing human hepatocellular (Eph) receptors might contribute to the development of atherosclerosis. A genome-wide association study indicated that the Eph receptor A6 gene (EPHA6) associated with at least 1 blood pressure (BP) phenotype. The objective of the present study was to determine whether EPHA6 is a novel candidate gene for hypertension in a Korean population.MethodsA total 2146 study participants with normotension and hypertension were included. Genotype data were obtained using a Korean Chip. To assess the association between single-nucleotide polymorphisms (SNPs) and BP, we performed a linear regression analysis, which showed that rs4850755 in the EPHA6 gene was the SNP most highly associated with both systolic and diastolic BP.ResultsThe presence of the TT genotype of the EPHA6 rs4857055 C > T SNP was associated with a higher risk of hypertension after adjusting for age, sex, body mass index (BMI), smoking, and drinking [odds ratio 1.533, P = 0.001]. In the control group, significant associations were observed between systolic BP and the rs4857055 polymorphism and between diastolic BP and the rs4857055 polymorphism. In the hypertension group, a significant association was observed between systolic BP and the rs4857055 polymorphism. In the hypertension group, subjects with the TT genotype showed significantly higher systolic BP than CC subjects. Additionally, in the hypertension group, TT carriers showed a higher tendency of serum triglyceride (P = 0.069) and significantly higher apolipoprotein B (P = 0.015) and smaller low-density lipoprotein (LDL) particle size (P < 0.001) than either TC or CC subjects.ConclusionsThese results could suggest that the EPHA6 rs4857055 C > T SNP is a novel candidate gene for hypertension in the Korean population. Additionally, the TT genotype could be associated with hypertriglyceridemia and small LDL particle size in hypertension.

A cross-sectional and longitudinal study between association of n-3 polyunsaturated fatty acids derived from fish consumption and high-density lipoprotein heterogeneity

Decreased high-density lipoprotein (HDL) particle size, cholesterol poor, apolipoprotein A-I-rich HDL particles leading to smaller HDL particle size, may be associated with an anti-atherosclerotic effect. The data are sparse regarding the relationship between n-3 polyunsaturated fatty acids [n-3 PUFAs: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)] and HDL particle size. This study was designed as a hospital-based cross-sectional study to investigate the relationship between the serum levels of n-3 PUFAs and the HDL-cholesterol/apolipoprotein A-1 ratio, as estimated by the HDL particle size, in patients with the presence of one or more risk factors for atherosclerotic cardiovascular disease (ASCVD). Six hundred and forty sequential patients were enrolled in this study. The serum levels of EPA and DHA showed a strong correlation (r = 0.736, p < 0.0001). However, in a multivariate regression analysis after adjustment for ASCVD risk factors, increased serum DHA (β = − 0.745, p = 0.021), but not serum EPA (β = − 0.414, p = 0.139) or EPA + DHA (β = 0.330, p = 0.557) level, was identified as an independent indicator of decreased HDL particle size. In 476 patients followed up for at least 6 months, the absolute change (Δ) in the HDL-cholesterol/apolipoprotein A-1 ratio decreased significantly as the quartile of the Δ DHA level increased (p = 0.014), whereas no significant difference in the Δ HDL-cholesterol/apolipoprotein A-1 ratio was noted with the increase in the quartile of the Δ EPA level. Moreover, a multivariate regression analysis identified increased DHA level and decreased estimated low-density lipoprotein (LDL) particle size measured relative to the mobility value of LDL with polyacrylamide gel electrophoresis (i.e., relative LDL migration: LDL-Rm value), as independent predictors of decreased HDL-cholesterol/apolipoprotein A-1 ratio (β = − 0.171, p = 0.0003 and β = − 0.142, p = 0.002). The results suggest that increased serum DHA level, but not EPA level, might be associated with decreased HDL-cholesterol/apolipoprotein A-1 ratio, an indicator of estimated HDL particle size. Further studies are needed to investigate the useful clinical indices and outcomes of these patients.Clinical Trial Registration Information UMIN (http://www.umin.ac.jp/), Study ID: UMIN000010603.

Effect of Evolocumab on Lipoprotein Particles

The level of low-density lipoprotein cholesterol (LDL-C) reflects the cholesterol carried mainly by low-density lipoprotein particles (LDL-P). LDL-C, however, does not always correlate with LDL-P because of the variable amounts of cholesterol per particle. Consideration of LDL-P concentrations in addition to LDL-C may help guide therapeutic decisions in a select number of patients. Evolocumab is a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9 that lowers both LDL-C and cardiovascular events. To evaluate the effect of evolocumab on serum levels and size of lipoprotein particles, we conducted a post hoc subanalysis of 619 patients from the Durable Effect of PCSK9 Antibody Compared with Placebo Study or DESCARTES trial, a 52-week, randomized, double-blind, placebo-controlled, global study of patients with hyperlipidemia. At baseline, mean LDL-P concentration was 1077 nmol/L for the placebo group and 1100 nmol/L for the evolocumab group. In patients receiving evolocumab, week 52 total LDL-P concentration decreased to 610 nmol/L, a treatment difference of 50% versus placebo. Evolocumab also reduced concentrations of medium very low-density lipoprotein particles (VLDL-P), small VLDL-P, and intermediate-density lipoprotein particle: median (Q1, Q3) changes were -15.2% (-48, 48), -29% (-54, 18), and -36% (-70, 22), respectively. Mean (95% confidence interval) % changes in total LDL particle size in the evolocumab group was -1.7 (-2.0, -1.4); % changes in HDL and VLDL particle sizes were 1.1 (0.7, 1.5) and 8.7 (7.0, 10.5), respectively. Changes in total LDL, HDL, and VLDL particle sizes (vs placebo) were all significant (p <0.001). In conclusion, evolocumab significantly lowers atherogenic lipoprotein particles including low-density and remnant lipoproteins.

Association of plasminogen activator inhibitor-1 and low-density lipoprotein heterogeneity as a risk factor of atherosclerotic cardiovascular disease with triglyceride metabolic disorder: a pilot cross-sectional study.

We hypothesized that an increase in plasminogen activator inhibitor 1 (PAI-1) might reduce low-density lipoprotein (LDL) particle size in conjunction with triglyceride (TG) metabolism disorder, resulting in an increased risk of atherosclerotic cardiovascular disease (ASCVD). This study was carried out as a hospital-based cross-sectional study in 537 consecutive outpatients (mean age: 64 years; men: 71%) with one or more risk factors for ASCVD from April 2014 to October 2014 at the Cardiovascular Center of Nihon University Surugadai Hospital. The estimated LDL-particle size was measured as relative LDL migration using polyacrylamide gel electrophoresis with the LipoPhor system.The plasma PAI-1 level, including the tissue PA/PAI-1 complex and the active and latent forms of PAI-1, was determined using a latex photometric immunoassay method. A multivariate regression analysis after adjustments for ASCVD risk factors showed that an elevated PAI-1 level was an independent predictor of smaller-sized LDL-particle in both the overall patients population (β=0.209, P<0.0001) and a subset of patients with a serum low-density lipoprotein cholesterol (LDL-C) level lower than 100 mg/dl (β=0.276, P<0.0001). Furthermore, an increased BMI and TG-rich lipoprotein related markers [TG, remnant-like particle cholesterol, apolipoprotein (apo) B, apo C-II, and apo C-III] were found to be independent variables associated with an increased PAI-1 level in multivariate regression models. A statistical analysis of data from nondiabetic patients with well-controlled serum LDL-C levels yielded similar findings. Furthermore, in the 310 patients followed up for at least 6 months, a multiple-logistic regression analysis after adjustments for ASCVD risk factors identified the percent changes of the plasma PAI-1 level in the third tertile compared with those in the first tertile as being independently predictive of decreased LDL-particle size [odds ratio (95% confidence interval): 2.11 (1.12/3.40), P=0.02]. The plasma PAI-1 levels may be determined by the degree of obesity and TG metabolic disorders. These factors were also shown to be correlated with a decreased LDL-particle size, increasing the risk of ASCVD, even in nondiabetic patients with well-controlled serum LDL-C levels.

Effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibition with Bococizumab on Lipoprotein Particles in Hypercholesterolemic Subjects

PurposeMonoclonal antibody inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) elicit significant reductions in serum LDL-C levels. However, little is known about their effects on lipoprotein particles. The purpose of this analysis was to evaluate the effect of PCSK9 inhibition with bococizumab (RN316/PF-04950615), a humanized monoclonal antibody to PCSK9, on LDL, VLDL, and HDL particle concentration and size in hypercholesterolemic subjects. MethodsData from 3 double-blind, placebo-controlled, randomized studies were analyzed. In study 1, a total of 67 hypercholesterolemic subjects received IV placebo or bococizumab 0.25, 0.5, 1, or 1.5 mg/kg weekly for 4 weeks. In studies 2 and 3, a total of 135 hypercholesterolemic subjects taking statins received IV placebo or bococizumab 0.25, 1, 3, or 6 mg/kg monthly for 12 weeks. Lipoprotein particle concentration and size were measured by using nuclear magnetic resonance spectroscopy. FindingsOverall, the majority of subjects were men (51.9%) aged >50 years of age and of white ethnic origin. In total, 189 subjects with both baseline and 2-week posttreatment data were included in the analysis. After PCSK9 inhibition with bococizumab 0.5, 1, 1.5, 3, and 6 mg/kg, concentrations of total LDL, total small LDL, and small VLDL particles decreased significantly versus baseline and placebo (P < 0.05), whereas concentrations of HDL particles increased (P < 0.05). The size of the LDL, VLDL, and HDL particles increased after PCSK9 inhibition. Reductions in LDL-C and total LDL particle concentrations were highly correlated. ImplicationsThe effect of inhibiting PCSK9 with bococizumab on lipoprotein particle concentration and size are consistent with the general mechanism of PCSK9 inhibitors in blocking PCSK9-mediated downregulation of LDL receptors. PCSK9 inhibition has the potential to provide a clinical benefit through the modulation of atherogenic lipoprotein particles in addition to LDL-C lowering, and this effect will likely be assessed in future analyses of data from cardiovascular outcomes trials of PCSK9 monoclonal antibodies that are currently being conducted. ClinicalTrials.gov identifiers: NCT01243151, NCT01342211, and NCT01350141.

Lipoprotein particle number and size distribution in apparently healthy spanish population according to sex and age, assessed by nuclear magnetic resonance

Aim: Advanced lipoprotein testing has been proposed for improving assessment of cardiovascular disease risk. The aim of this study was to characterize normal lipoprotein profile in apparently healthy Spanish population, determined by 2D diffusion-ordered 1H-Nuclear Magnetic Resonance (NMR) spectroscopy.

P5310Association of n-3 polyunsaturated fatty acids with high-density lipoprotein particle size: a pilot cross-sectional study

P5310Association of n-3 polyunsaturated fatty acids with high-density lipoprotein particle size: a pilot cross-sectional study

Lipoprotein insulin resistance score and risk of incident diabetes during extended follow-up of 20 years: The Women's Health Study

Type II diabetes (T2D) is preceded by prolonged insulin resistance and relative insulin deficiency incompletely captured by glucose metabolism parameters, high-density lipoprotein (HDL) cholesterol and triglycerides. Whether lipoprotein insulin resistance (LPIR) score, a metabolomic marker, is associated with incident diabetes and improves risk reclassification over traditional markers on extended follow-up. Among 25,925 nondiabetic women aged 45years or older, LPIR was measured by nuclear magnetic resonance spectroscopy as a weighted score of very low density lipoprotein, low-density lipoprotein, and HDL particle sizes, and their subsets concentrations. We run adjusted cox regression models for LPIR with incident T2D (20.4years median follow-up). Adjusting for demographics, body mass index, life style factors, blood pressure, and T2D family history, the LPIR hazard ratio for T2D (hazard ratio [HR] per standard deviation, 95% confidence interval) was 1.95 (1.85, 2.06). Further adjusting for HbA1c, C-reactive protein, triglycerides, HDL and low-density lipoprotein cholesterol, LPIR HR was attenuated to 1.41 (1.31, 1.53) and had the strongest association with T2D after HbA1C in mutually adjusted models. The association persisted even in those with optimal clinical profiles, adjusted HR per standard deviation 1.91 (1.17, 3.13). In participants deemed at intermediate T2D risk by the Framingham Offspring T2D score, LPIR led to a net reclassification of 0.145 (0.117, 0.175). In middle-aged or older healthy women followed prospectively for over 20years, LPIR was robustly associated with incident T2D, including among those with an optimal clinical metabolic profile. LPIR improved T2D risk classification and may guide early and targeted prevention strategies.

Serum oxidized LDL and the factors associated with LDL oxidation in black South African type 2 diabetes mellitus patients

Diabetes is a metabolic disorder that is increasing in prevalence at a very fast pace in developing countries such as South Africa. There is a strong link between diabetes and cardiovascular disease with studies showing that diabetic patients are two to four times more likely to suffer from cardiovascular disease than healthy people. The dysregulation of lipid and lipoprotein metabolism and the subsequent oxidation of low-density lipoprotein (LDL) is one of the major reasons for the increased cardiovascular risk associated with diabetes. The main objective of this study was to analyze the concentrations of oxidized LDL in diabetic patients and to uncover factors associated with oxidized LDL. In total, 67 type 2 diabetic mellitus patients and 48 healthy control participants participated in the cross-sectional study. Oxidized LDL concentration in serum and the total antioxidant status were determined by ELISA, while the size of LDL and high-density lipoprotein (HDL) particles were determined by gradient gel electrophoresis. The concentration of oxidized LDL was significantly elevated in the diabetic patients. The diabetic patients also had a significantly higher percentage of small dense LDL and a higher concentration of triglycerides than the control group, while their peak LDL size and the total antioxidant capacity were significantly lower than those in the control group. The percentage of small dense LDL, triglycerides, peak LDL size, and total antioxidant capacity also varied significantly across the quartiles of oxidized LDL in the entire study population. Multiple regression analysis revealed that triglyceride and glycated hemoglobin were the most important parameters to be independently associated with oxidized LDL concentrations. The diabetic patients had high concentrations of small dense LDL and oxidized LDL. The concentrations of the highly atherogenic oxidized LDL particles were found to be independently associated with the concentrations of triglycerides and glycated hemoglobin. This indicated that proper diabetic control could reduce the risk of cardiovascular disease in these individuals.

Lipoprotein particle number and size predict vascular structure and function better than traditional lipids in adolescents and young adults

In adults, dyslipidemia is associated with higher carotid thickness and arterial stiffness, predictors of cardiovascular events. In young subjects, lipid concentrations have not been consistently associated with vascular measures. The objective of the study was to compare nuclear magnetic resonance (NMR) measures of lipoprotein particle number (low-density lipoprotein [LDL] particle, low-density lipoprotein [HDL] particle, very low-density lipoprotein [VLDL] particle) and size (LDL size, HDL size, and VLDL size) to determine if they were associated with vascular measures more strongly than lipid concentrations (LDL cholesterol, HDL cholesterol, and triglyceride [TG]). We evaluated 214 lean (L), 228 obese (O), and 214 diabetic (T2DM) subjects aged 10 to 24years (33% male and 39% Caucasian). Cardiovascular risk factors, vascular structure, and arterial stiffness were measured. General linear models were constructed including demographics, risk factors, and traditional or NMR lipid parameters. A composite vascular function score was developed as the outcome in receiver operator characteristic scores for determining which lipid parameter was superior in predicting vascular damage. Risk factors worsened from L to O to T. However, LDL cholesterol was similar in O and T, whereas LDL size differentiated the 3 groups (T>O>L, P≤.0001). Models demonstrated the superiority of NMR values, which entered for all but 1 vascular outcome and explained more of the variance than traditional lipid concentrations. Receiver operator characteristic curves demonstrated that NMR values were superior in predicting vascular outcomes. Models stratified by race were similar but cutpoints predicting vascular outcomes differed by race for TG, TG/HDL, and VLDL. Lipoprotein particle number and size are more strongly related to vascular structure and function than traditional lipid values. NMR lipid measures may be a better indicator of risk for target organ damage than traditional lipid measures in adolescents and young adults.

Apolipoprotein C-III Levels and Incident Coronary Artery Disease Risk: The EPIC-Norfolk Prospective Population Study.

Apolipoprotein C-III (apoC-III) is a key regulator of triglyceride metabolism. Elevated triglyceride-rich lipoproteins and apoC-III levels are causally linked to coronary artery disease (CAD) risk. The mechanism(s) through which apoC-III increases CAD risk remains largely unknown. The aim was to confirm the association between apoC-III plasma levels and CAD risk and to explore which lipoprotein subfractions contribute to this relationship between apoC-III and CAD risk. Plasma apoC-III levels were measured in baseline samples from a nested case-control study in the European Prospective Investigation of Cancer (EPIC)-Norfolk study. The study comprised 2711 apparently healthy study participants, of whom 832 subsequently developed CAD. We studied the association of baseline apoC-III levels with incident CAD risk, lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy and inflammatory biomarkers. ApoC-III levels were significantly associated with CAD risk (odds ratio, 1.91; 95% confidence interval, 1.48-2.48 for highest compared with lowest quintile), retaining significance after adjustment for traditional CAD risk factors (odds ratio, 1.47; 95% confidence interval, 1.11-1.94). ApoC-III levels were positively correlated with triglyceride levels, (r=0.39), particle numbers of very-low-density lipoprotein (r=0.25), intermediate-density lipoprotein (r=0.23), small dense low-density lipoprotein (r=0.26), and high-sensitivity C-reactive protein (r=0.15), whereas an inverse correlation was observed with large low-density lipoprotein particle number (r=-0.11), P<0.001 for each. Mediation analysis indicated that the association between apoC-III and CAD risk could be explained by triglyceride elevation (triglyceride, very-low-density lipoprotein, and intermediate-density lipoprotein particles), small low-density lipoprotein particle size, and high-sensitivity C-reactive protein. ApoC-III levels are significantly associated with incident CAD risk. Elevated levels of remnant lipoproteins, small dense low-density lipoprotein, and low-grade inflammation may explain this association.

Lipoprotein Heterogeneity Early in Pregnancy and Preterm Birth.

Background The concentration and size of lipoprotein particles are associated with race, inflammation, and disease. When triglycerides are high, as in pregnancy, lipoprotein particle size may have physiologic importance beyond conventional lipid measurements. We considered that lipoprotein particles may be related to preterm birth (PTB) and explored race differences. Materials and Methods Samples were collected at 9 weeks' gestation (22 PTB [&lt; 37 weeks]; 42 term births [≥ 37 weeks]). Lipids were assayed using standard techniques. Concentrations of high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein particles (HDL-P, LDL-P, and VLDL-P, respectively) and markers of systemic inflammation were quantified using nuclear magnetic resonance spectroscopy and related to PTB. Results Women with PTB had lower VLDL-P (− 10.66 nmol/L, p = 0.03) and higher systemic inflammation (+ 19.2 µmol/L, p = 0.02) compared with women with term births, independent of race, pre-pregnancy body mass index, and smoking. Black versus white women had lower VLDL-P and higher HDL cholesterol (both p &lt; 0.05). Race-specific results indicated that large HDL-P and inflammation (glycoprotein B) were higher with PTB versus term birth among black women only. Conclusion Women with PTB had lower VLDL-P early in pregnancy, which may represent impaired lipid response. Black–white differences in the lipoprotein profile are similar to nonpregnant adults, but race-specific lipoprotein and inflammation associations with PTB warrant further study.

Lipoprotein particle size in women with type 1 diabetes mellitus and its relationship to carotid intima-media thickness

Lipoprotein particle size in women with type 1 diabetes mellitus and its relationship to carotid intima-media thickness

High‐Density Lipoprotein Cholesterol Concentrations and Particle Size Are Modified by Dietary Zinc in Men

ObjectiveTo measure biomarkers of lipid metabolism in response to a marginal zinc depletion, repletion, and supplementation in healthy male subjects.MethodsEighteen male subjects between ages of 18–45 consumed a controlled diet (80% carbohydrate, 10% fat, 10% protein) with two levels of dietary zinc. Phase I: Low zinc: 6 mg/day with 1.5 mg of phytate (2 weeks); Phase II: Zinc repletion: 10 mg/day with no phytate (4 weeks). Thereafter, a 25 mg/day zinc supplement was administered with an ad libitum diet for 3 weeks (Phase III). Targeted analysis of lipids and lipoprotein particle size were performed using standard methodology.ResultsPlasma zinc levels remained unchanged during Phases I and II in all subjects; they increased by 17.4 ± 3.8% (mean ± SE) at the end of supplementation (phase III). Apo‐A1 decreased significantly from 119.2 ± 13.2 mg/dL (mean ± SD) to 110.2 ± 13.2 mg/dL (p=0.003) at the end of the low zinc period. Apo‐A1 remained low at the end of phase II, but returned back to baseline after supplementation. A similar pattern was observed in HDL‐c and HDL‐L (large buoyant HDL particles) levels across the three phases. Plasma triglyceride levels increased during the 6‐week high‐carbohydrate diet, but were not modified by shifts in dietary zinc. Based on our previous observation of higher DNA strand breaks in the low zinc metabolic period and literature reports linking cancer to low HDL‐c levels, we performed a correlation analysis of DNA strand breaks and HDL subspecies. Our results show that the percent changes in HDL‐L and DNA strand breaks from phase I to II are negatively correlated (r=−0.45; p=0.05).ConclusionResults from our studies show that low zinc combined with a high carbohydrate diet increased biomarkers of dyslipidemia, but provision of adequate dietary zinc or a zinc supplement for a short period of time mitigated the increase in these biomarkers.Support or Funding InformationHarvest Plus