LDL Particle Size Research Articles

Dyslipidemia in women with polycystic ovary syndrome

Dyslipidemia is a very common metabolic abnormality in women with polycystic ovary syndrome (PCOS). Insulin resistance is a key pathophysiology of PCOS, thus dyslipidemia in women with PCOS may be consistent with those found in an insulin resistant state. In recent meta-analysis, triglycerides and low-density lipoprotein (LDL) cholesterol levels were 26 mg/dL and 12 mg/dL higher, and high-density lipoprotein cholesterol concentration was 6 mg/dL lower in women with PCOS than those of controls. Alterations in LDL quality also have been reported in women with PCOS: women with PCOS have an increased proportion of atherogenic small dense LDL or decreased mean LDL particle size. However, in a recent Korean study, non-obese Korean women with PCOS had no significant quantitative or qualitative changes in LDL cholesterol profile. Lipoprotein (a) has been identified as an independent risk factor for coronary heart disease, and its elevation in PCOS patients has been consistently reported in diverse studies including non-obese Korean population. Some studies have investigated apolipoprotein (Apo) A-I and ApoC-I levels in women with PCOS and levels of ApoA-I, which has cardio-protective effects, were significantly lower in women with PCOS than those of controls. ApoC-I is known to increase the postprandial serum lipid level that is common in coronary artery disease patients, and one study reported that such an elevation may be the earliest variation of lipid abnormality in women with PCOS. In conclusion, women with PCOS should receive a complete lipid test, and lifestyle modification, including diet and exercise, is the first line therapy for all women with PCOS and is particularly important for those with dyslipidemia.

Abstract 9918: Novel and Profound Lipid Effects of GSK1292263, a Potent and Selective GPR119 Agonist, in Dyslipidemic Subjects

GSK1292263 (GSK263), a GPR119 agonist, improves glucose regulation in animal models of diabetes, but has no effect on plasma glucose in type 2 diabetics. Unexpectedly, GSK263 lowered fasting LDLc and triglycerides (TG), while increasing HDLc in these diabetic subjects. The study aim was to determine whether GSK263 improves lipid profiles in dyslipidemic, non-diabetic subjects when dosed alone or with atorvastatin (NCT# 01218204). Eligible subjects on statin/Vytorin therapy were washed off these drugs for 4 weeks. After washout, they were randomized to receive (i) 100mg (n=11), 300mg (n=12) or 800mg (n=13) QD of GSK263 or placebo (n=11) for 2 weeks; or (ii) 10mg atorvastatin (A10) or 80mg atorvastatin (A80) for a 4-week Run-in period. After the atorvastatin Run-in, (i) A10 was co-dosed with: 100mg (n=11), 300mg (n=11), 800mg (n=11) QD GSK263, placebo (n=12) or 10mg ezetimibe (n=13), and (ii) A80 was co-dosed with: 800mg (n=12) QD GSK263 or placebo (n=13). Fasting plasma lipids and NMR lipoprotein particles (LipoProfile) were measured at baseline and after 2 weeks of dosing. By ANCOVA (change from baseline), 800mg GSK263 significantly increased fasting HDLc by 20.7% (95% CI 9.8 to 31.6%), reduced fasting LDLc by 21.8% (95% CI -32.1 to -11.2%), and reduced fasting TGs by 54.8% (95% CI -70.8 to -38.9%) when compared to placebo. TG AUCs (wm 0-24h) fell by 41.3% (95% CI -61.9 to -20.8%). Similar effects were seen when co-dosed with A10 and A80. The lipid effects were dose-dependent, with GSK263 100mg having minimal effect. GSK263 may reduce apoB100, apoE and CRP, but had no clear effect on apoA1. NMR analysis suggests that GSK263 (i) reduced VLDL and chylomicron particle number and VLDL particle size, (ii) reduced LDL and IDL particle number and increased LDL particle size, and (iii) increased HDL particle number and size, especially when co-administered with atorvastatin. GSK263 was generally well tolerated over the dose range of 100mg to 800mg QD administered for 14 days. The majority of AEs associated with GSK1292263 were mild in intensity. GSK263 has significant effects on plasma lipids and lipoprotein particles in dyslipidemic patients when dosed alone and with atorvastatin. Studies are on-going to investigate the novel mechanisms underlying these lipid effects.

Discovery of candidate phospholipid biomarkers in human lipoproteins with coronary artery disease by flow field-flow fractionation and nanoflow liquid chromatography–tandem mass spectrometry

In this study, an analytical method is demonstrated to identify and develop potential phospholipid (PL) biomarkers of high density lipoprotein (HDL) and low density lipoprotein (LDL) in plasma from individuals with coronary artery disease (CAD) by employing a combination of off-line multiplexed hollow fiber flow field-flow fractionation (MxHF5) and nanoflow liquid chromatography–electrospray ionization-tandem mass spectrometry (nLC–ESI-MS–MS). HDL and LDL particles of human plasma were sorted by size at a semi-preparative scale using MxHF5, after which PL extracts of each lipoprotein fraction were qualitatively and quantitatively analyzed by nLC–ESI-MS–MS. Experiments were performed using plasma samples from 10 CAD patients and 10 controls. Quantitative analysis of the 93 PL species identified yielded a selection of 19 species from HDL fractions and 10 from LDL fractions exhibiting at least a five fold change in average concentration in CAD patients. Among the selected species, only a few were found exclusively in patient HDL fractions (18:3-LPA and 20:2/16:0-PG), control HDL fractions (16:0/16:1-PC, 20:1/20:4-PE, and 16:1-LPA), and control LDL fractions (16:0/22:3-PG). Moreover, 16:1/18:2-PC was detected from both HDL and LDL fractions of controls but disappeared in CAD patients. Although the typical change in lipoproteins for CAD is well known, with decreased levels of HDLs and reduced LDL particle size, the current study provides fundamental information on the molecular level of lipoprotein variation which can be utilized for diagnostic and therapeutic tracking.

High levels of very long-chain saturated fatty acid in erythrocytes correlates with atherogenic lipoprotein profiles in subjects with metabolic syndrome

AimVery long chain saturated fatty acid (VLCFA) levels in erythrocytes are associated with metabolic syndrome (MS). However, the relationship between levels of the VLCFA ligonoceric acid (C24:0) in erythrocytes and the atherogenic lipoprotein profiles and inflammatory state in MS remain unclear. MethodsBased on the International Diabetes Federation (IDF) definition of MS, 195 apparently healthy males were assigned to either an MS group (n=38) or a non-MS group (n=157). Fatty acid composition of erythrocytes was determined by gas liquid chromatography. ResultsErythrocytes from the MS group had a significantly higher level of C24:0 than cells from the non-MS group (4.06±0.48% versus 3.88±0.34%; p=0.03). C24:0 levels were significantly correlated with several components of MS. The C24:0 levels showed a significant negative correlation with LDL and HDL particle size. Multivariate linear regression analysis showed that C24:0 levels were independently correlated with LDL particle size after adjusting for age and each MS criterion. C24:0 levels were also positively correlated with log-transformed high-sensitivity CRP levels (p=0.04). ConclusionC24:0 levels in erythrocytes are associated with specific atherogenic lipoprotein profiles and inflammation status in subjects with MS.

Increased oxidative stress in normal-weight postmenopausal women with metabolic syndrome compared with metabolically healthy overweight/obese individuals

ObjectiveThe purpose of this study was to assess whether the metabolically healthy overweight/obese phenotype is associated with decreased oxidative stress compared with normal-weight individuals with metabolic syndrome (MetS). Materials/MethodsPlasma oxidized LDL (ox-LDL) and urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) were analyzed in a cross-sectional study of 1846 healthy postmenopausal women. Participants were classified by presence (n=569) or absence (n=1277) of MetS and by BMI (18.5–24.9kg/m2=normal weight, n=1254; ≥25kg/m2=overweight/obese, n=592). MetS was diagnosed with the modified National Cholesterol Education Program Adult Treatment Panel III criteria. ResultsCompared to normal weight women with MetS (n=296), metabolically healthy overweight/obese women (n=319) showed lower blood pressure, triglyceride, and glucose and higher HDL cholesterol, adiponectin, and LDL particle size. Ox-LDL was higher in overweight/obese women without MetS than in normal weight women without MetS (n=958) but was lower than in women with MetS. Urinary 8-epi-PGF2α level was about 11% lower in women without MetS than in women with MetS. Normal weight women with MetS had greater odds of having ox-LDL (multivariate odds ratio [OR] 2.42, 95% CI: 1.65–3.55) and 8-epi-PGF2α (OR 1.49; CI: 1.03–2.14) levels in the top quartile compared to normal weight women without MetS after adjusting for age, drinking, smoking, total- and LDL-cholesterol, and high sensitivity C-reactive protein. Additionally, there was no significant correlation between ox-LDL and 8-epi-PGF2α. ConclusionsThe metabolically healthy overweight/obese phenotype was associated with a better overall metabolic profile and less oxidative stress than that observed in normal weight individuals with MetS. Furthermore, there was a lack of association between ox-LDL and 8-epi-PGF2α.

Association of Lipoprotein Subfractions and Coronary Artery Calcium In Patient at Intermediate Cardiovascular Risk

More precise estimation of the atherogenic lipid parameters could improve identification of residual risk beyond what is possible using traditional lipid risk factors. The aim of the present study was to explore the association between advanced analysis of lipoprotein subfractions and the prevalence of coronary artery calcium. Consecutive participants at intermediate cardiovascular risk who were undergoing computed tomographic assessment of coronary calcium (calcium score) were included. Using a validated ultracentrifugation method (the vertical autoprofile II test), cholesterol in eluting lipoprotein subfractions [i.e., low- (LDL), very-low-, intermediate-, and high-density lipoprotein subclasses, lipoprotein (a), and predominant LDL distribution] was directly quantified. A total of 410 patients were included (29% women, mean age 57 years), of whom 297 (72.4%) had coronary artery calcium. LDL pattern B (predominance of small dense particles) emerged as an independent predictor of coronary calcium after adjustment for traditional risk factors (odds ratio 4.46, 95% confidence interval 1.19 to 16.7). However, after additional stratification for dyslipidemia, as defined by conventional lipid profiling, a statistically significant prediction was only retained for high-density lipoprotein subfraction 2 (odds ratio 3.45, 95% confidence interval 2.03 to 50.1) and "real" LDL (odds ratio 6.10, 95% confidence interval 1.26 to 23.41) in the normolipidemia group and for lipoprotein (a) (odds ratio 7.81, 95% confidence interval 1.41 to 43.5) in the dyslipidemic group. In conclusion, advanced assessment of the lipoprotein subfractions [i.e., LDL pattern B, high-density lipoprotein subfraction 2, "real" LDL, and lipoprotein (a)] using the vertical autoprofile II test provided additional information to that of conventional risk factors on the prevalence of coronary artery calcium in patients at intermediate cardiovascular risk.

Nevirapine vs efavirenz in virologically supressed patients: differences in lipoprotein subclasses and inflammatory biomarkers

BackgroundThe interaction between lipid disturbances and inflammatory markers is not well known in patients on antiretroviral therapy (ART). As nevirapine (NVP) is associated with a better lipid profile than efavirenz (EFV), we investigated the relationships between lipid profiles, lipoprotein subclasses and inflammatory biomarkers in patients with prolonged viral suppression with either NVP or EFV and no obvious clinical inflammation.Methods122 clinically stable HIV‐infected patients with HIV‐1 RNA <20 copies longer than 6 months on NNRTI therapy were studied. 72 (59%) were on EFV and 50 (41%) on NVP. Any potentially inflammatory co‐morbid diseases (concurrent viral hepatitis, diabetes, hypertension, chronic liver or renal diseases), or statin treatment, were exclusion criteria. Inflammatory biomarkers included hsCRP, LpPLA2, sCD40L, IL‐6, IL‐8, t‐PA, MCP‐1, p‐selectin and VCAM‐1. Lipoprotein subclass measures (VLDL, LDL, IDL and HDL particle number and size) were obtained by the use of proton nuclear magnetic resonance spectroscopy.Results82% were male; median age 45 years. Median CD4 count 550/μL (IQR 324). Median time since HIV diagnosis 96 months (IQR 102) and accumulated time on ART 50 months (IQR 101). Patients on NVP had higher time since HIV diagnosis (126.9 [66.7] vs. 91.3 [6.6] months, p=0.008) a prolonged time on ART (89.6 [54.6] vs. 62.3 [52.2] months, p=0.01) and were older (47.7 vs. 40.7 years, p=0.001) than those on EFV. NVP‐treated patients presented increased HDL‐c (55.8 [16] vs. 48.8 [10.7] mg/dL, p=0.007) and apoA1 levels (153.4 [31.9] vs. 141.5 [20.5] mg/dL, p=0.02), and reduced apoB/apoA1 ratio (0.68 [0.1] vs 0.61 [0.1], p=0.003) than EFV‐treated patients. No differences in inflammatory markers or lipoprotein subclasses were found between NVP and EFV. In patients with extreme lipid values (less favorable: 75th percentiles of LDL, small/dense LDLp and small HDLp, or more favorable: HDL p75 and apoB/apoA1 ratio p25), no consistent differences in inflammatory biomarkers were found.ConclusionsPatients with prolonged viral suppression on NVP present significantly higher HDL and apoA1 levels and reduced apoB/apoA1 ratios than those on EFV, but no differences were found in lipoprotein particles nor inflammatory biomarkers. Relationships between lipid parameters and inflammatory biomarkers in NNRTI‐treated patients are complex and do not show a linear relationship in this study.

Adding Ezetimibe to Statin Treatment: is LDL-C Lowering the Only benefit?

Arimura T, Miura S, Ike A et al. Comparison of the efficacy and safety of statin and statin/ezetimibe therapy after coronary stent implantation in patients with stable angina. J. Cardiol. 60(2), 111–118 (2012). Adding ezetimibe to low-dose statins can result in more high-risk patients (e.g., those with coronary heart disease) who achieve LDL cholesterol (LDL-C) goals compared with statin monotherapy (even after doubling the dose). However, it is uncertain whether this strategy results in slower atherosclerosis progression. In a recently published study, statin + ezetimibe combination lowered LDL-C levels more than statin monotherapy in patients with stable coronary heart disease. This incremental decrease was not associated with significant differences in in-stent restenosis or major clinical outcome rates. This article will discuss whether ezetimibe can add to the benefits of statins on atherosclerosis and cardiovascular risk reduction in relation to further LDL-C lowering and lipid-modifying properties, including triglyceride lowering and increased LDL particle size. In addition, the role of ezetimibe in preventing statin-related dose-dependent increases in the risk of muscle-related toxicity and new-onset diabetes is discussed.

Lipids and lipoproteins in adolescents with prediabetes

There is concern in both adults and adolescents about diabetes as a cardiovascular disease risk equivalent. This means that the risk for cardiovascular disease in a patient with diabetes is similar to that in patients with already extant cardiovascular disease. There also is concern that clustering of traditional cardiovascular disease risk factors leads to accelerated atherosclerosis. In this issue of The Journal, Magge et al report on the lipoprotein profile of obese adolescents with prediabetes. The authors found that those with prediabetes (impaired fasting glucose) had higher concentrations of small low-density lipoprotein (LDL) particles and smaller LDL particle size, as well as higher concentration of small high-density lipoprotein (HDL) particles and smaller HDL particle size compared with youth with a normal concentration of glucose normoglycerinic youth. These results demonstrate that obese adolescents with prediabetes already have a more atherogenic lipoprotein profile. This emphasizes the need for early intervention to prevent obesity and for those who are obese to prevent the development of prediabetes. Article page 881▶ Prediabetic Obese Adolescents have a More Atherogenic Lipoprotein Profile Compared with Normoglycemic Obese PeersThe Journal of PediatricsVol. 161Issue 5PreviewTo compare lipoprotein profiles of prediabetic to normoglycemic obese adolescents. Full-Text PDF

Effect of age on atherogenicity of LDL and inflammatory markers in healthy women

Background and aimSince using LDL level alone is insufficient as a method to identify individuals with incident coronary artery disease (CAD), other factors may be implicated in the pathogenesis of CAD. Additionally, controversy still remains regarding whether there is an age-related increase in circulating cytokines in healthy individuals. We investigated the influence of age on atherogenicity of LDL and inflammatory markers in healthy women. Methods and resultsTwo thousand nine hundred forty four healthy women form 30–79 years old (23.3 ± 0.05 kg/m2) were categorized into 5 age groups: 30–39, 40–49, 50–59, 60–69 and 70–79 years. BMI, smoking, drinking, and metabolic syndrome prevalence adjusted mean values of total-cholesterol progressively increased from the group age 30–39 years to the group age 40–49 and 50–59 years and thereafter decreased in the group age 60–69 and 70–79 years. Serum concentrations of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were higher in women aged 60–79 years than women aged 30–59 years. Plasma ox-LDL levels increased in the group age 50–59 years compared with the group age 30–39 and 40–49 years and further increased in the group age 60–69 and 70–79 years. Mean values of LDL particle size were smaller in women aged 60–79 years than those in women aged 30–59 years. After adjustment for BMI, smoking, drinking, and metabolic syndrome status, age was positively correlated with LDL-cholesterol (r = 0.095, P < 0.001), oxidized LDL (r = 0.305, P < 0.001), hs-CRP (r = 0.150, P < 0.001), TNF-α (r = 0.171, P < 0.001) and IL-6 (r = 0.294, P < 0.001) and negatively with LDL particle size (r = −0.239, P < 0.001). ConclusionOur results indicate that LDL atherogenicity and inflammatory mediators can be better markers of CAD risk than known risk factors such as elevated concentrations of total- and LDL-cholesterol, decreased HDL-cholesterol levels and smoking in old healthy women.

Oxidized high-density lipoprotein is associated with increased plasma glucose in non-diabetic dyslipidemic subjects

BackgroundOxidized high-density lipoprotein (oxHDL) has reduced capacity for cholesterol efflux and some of other anti-atherogenic properties of HDL, but the role of oxHDL in the pathogenesis of cardiometabolic disease has not been fully demonstrated. This study investigated the association of oxHDL with plasma glucose (PG) and the other atherosclerotic risk variables in non-diabetic dyslipidemic subjects. MethodsConventional atherosclerotic markers and LDL particle size (LDL-PS), as determined by gel electrophoresis, were measured in 155 non-diabetic subjects (mean age of 57years) with dyslipidemia. Serum oxHDL levels were quantified using an antibody against oxidized human apoA-I in a sandwich ELISA format. ResultsMultiple regression analysis adjusted for possible confounders revealed that HDL-cholesterol was independently, significantly and positively correlated with LDL-PS and oxHDL. By multiple regression analysis, oxHDL was independently, significantly and positively correlated with fasting PG (β=0.19, P=0.01). Subjects in the highest PG tertile group had approximately 30% higher oxHDL levels than the lowest PG tertile group. ConclusionsThese results suggest that high PG levels may contribute to the HDL oxidation, irrespective of HDL-cholesterol levels, even in non-diabetic subjects with dyslipidemia, and that the measurement of oxHDL may be a useful marker of dysfunctional HDL.

Dietary cholesterol affects plasma lipid levels, the intravascular processing of lipoproteins and reverse cholesterol transport without increasing the risk for heart disease.

The associations between dietary cholesterol and heart disease are highly controversial. While epidemiological studies and clinical interventions have shown the lack of correlation between cholesterol intake and cardiovascular disease (CVD) risk, there is still concern among health practitioners and the general population regarding dietary cholesterol. In this review, several clinical studies utilizing cholesterol challenges are analyzed in terms of changes that occur in lipoprotein metabolism resulting from excess consumption of cholesterol. Dietary cholesterol has been shown to increase both LDL and HDL in those individuals who respond to a cholesterol challenge without altering the LDL cholesterol/HDL cholesterol ratio, a key marker of CVD risk. Further, dietary cholesterol has been shown to increase only HDL with no changes in LDL with average cholesterol consumption and during weight loss interventions. Ingestion of cholesterol has also been shown to increase the size of both LDL and HDL particles with the associated implications of a less atherogenic LDL particle as well as more functional HDL in reverse cholesterol transport. Other changes observed in lipoprotein metabolism are a greater number of large LDL and decreases in small LDL subfractions. All this information put together points to specific roles of dietary cholesterol in substantially altering intravascular processing of lipoproteins as well as reverse cholesterol transport.

Surrogate Lipid Markers for Small Dense Low-Density Lipoprotein Particles in Overweight Youth

To determine if the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL) and non-HDL cholesterol concentration could identify youth with small dense low-density lipoprotein (LDL). One hundred forty-one (75 black and 66 white) overweight adolescents (9 to <18 years) had a fasting measurement of plasma lipids and LDL particle concentrations and size. Receiver operating characteristic curves were used to indicate the ability of different TG/HDL ratios and non-HDL cholesterol concentrations to identify overweight youth with atherogenic LDL concentration and size. Youth with a TG/HDL ratio of ≥3 vs <3 had higher concentrations of small dense LDL (1279.5 ± 60.1 vs 841.8 ± 24.2 nmol/L, P < .001) and smaller LDL particle size (20.3 ± 0.1 vs 21.2 ± 0.1 nm, P < .001). In receiver operating characteristic analyses a TG/HDL cut-point of 3 best predicted LDL concentration in white youth, and 2.5 in black youth. Non-HDL cholesterol cut-point of 120 mg/dL and 145 mg/dL predicted LDL particle concentration in white and in black youth, respectively. TG/HDL ratio with body mass index or waist circumference explained 71% and 79% of the variance, respectively, in total small LDL. TG/HDL ratio and non-HDL cholesterol can identify overweight youth with atherogenic LDL particles. These easily obtained clinical lipid markers, in combination with body mass index and waist circumference, could be cost effective, in observational or interventional studies, for screening and follow-up of youth at heightened risk for atherogenic LDL.

Regulation of low-density lipoprotein subfractions by carbohydrates

This article aims at reviewing the recent findings that have been made concerning the crosstalk of carbohydrate metabolism with the generation of small, dense low-density lipoprotein (LDL) particles, which are known to be associated with an adverse cardiovascular risk profile. Studies conducted during the past few years have quite unanimously shown that the quantity of carbohydrates ingested is associated with a decrease of LDL particle size and an increase in its density. Conversely, diets that aim at a reduction of carbohydrate intake are able to improve LDL quality. Furthermore, a reduction of the glycaemic index without changing the amount of carbohydrates ingested has similar effects. Diseases with altered carbohydrate metabolism, for example, type 2 diabetes, are associated with small, dense LDL particles. Finally, even the kind of monosaccharide the carbohydrate intake consists of is important concerning LDL particle size: fructose has been shown to alter the LDL particle subclass profile more adversely than glucose in many recent studies. LDL particle quality, rather than its quantity, is affected by carbohydrate metabolism, which is of clinical importance, in particular, in the light of increased carbohydrate consumption in today's world.

Oxidative stress and small, dense low-density lipoproteins: current and future perspectives

Small, dense low-density lipoproteins (LDLs) are more susceptible to oxidation than their larger, more buoyant counterparts and therefore the biological modification of these LDL particles may, in part, be responsible for their atherogenic properties. Kotani et al. found that at multiple regression analysis there was an independent and significant inverse correlation between the mean LDL particle size and the oxidative stress status; notably, the authors adjusted not only for the traditional cardiovascular risk factors, but also for drug treatments. Higher levels of small, dense LDL concentrations significantly contribute to atherosclerosis, and lipoprotein size and subfractions may refine cardiovascular disease risk assessment.

Association of apolipoprotein A-V concentration with apolipoprotein A5 gene -1131T&gt;C polymorphism and fasting triglyceride levels

The relationship between the apolipoprotein A5 gene (APOA5) -1131T>C polymorphism and triglyceride levels is well established, but the association between circulating apolipoprotein A-V (apoA-V) concentrations and APOA5 -1131T>C genotypes and triglyceride levels remains controversial. Normotriglyceridemic controls (n = 1526) and hypertriglyceridemic cases (n = 744) were genotyped for APOA5-1131T>C. ApoA-V, triglycerides, insulin, free fatty acids, and lipoprotein profiles were analyzed. APOA5-1131C minor allele frequency was significantly greater in hypertriglyceridemic patients than normotriglyceridemic controls. ApoA-V concentrations were not significantly different between controls and cases. Normotriglyceridemic controls with T/C and C/C showed lower apoA-V concentrations (14% and 27%, respectively), than did T/T controls. Similar genotypic effects on apoA-V were found in hypertriglyceridemic cases. In both groups, APOA5-1131T>C was associated with higher triglycerides, smaller LDL particle size, and lower HDL-cholesterol. We observed a negative correlation between apoA-V and triglyceride in controls and a positive correlation in hypertriglyceridemic patients, regardless of genotype. We observed a positive correlation between apoA-V and free fatty acids in both groups, regardless of genotype, and a positive correlation between apoA-V and HDL-cholesterol in controls (T/T, T/C, or C/C) and hypertriglyceridemic patients (T/T or T/C). APOA5-1131C may lead to reduced apoA-V with concomitantly reduced lipoprotein lipase activation, resulting in greater serum triglycerides, although the correlation between apoA-V and triglyceride was reversed when triglyceride was greater than 150 mg/dL.

Serum adiponectin level is correlated with the size of HDL and LDL particles determined by high performance liquid chromatography

ObjectiveAdiponectin (APN) improves insulin resistance and prevents atherosclerosis, and HDL removes cholesterol from atherosclerotic lesions. We have demonstrated that serum HDL-cholesterol (HDL-C) and APN concentrations are positively correlated and that APN accelerates reverse cholesterol transport (RCT) by increasing HDL synthesis in the liver and cholesterol efflux from macrophages. We previously reported that APN reduced apolipoprotein (apo) B secretion from the liver. It is well-known that insulin resistance influences the lipoprotein profile. In this study, we investigated the clinical significance of APN levels and insulin resistance in lipoprotein metabolism. Material/methodWe investigated the correlation between serum APN concentration, HOMA-R, the lipid concentrations and lipoprotein particle size by high-performance liquid chromatography (HPLC) in 245 Japanese men during an annual health checkup. ResultsSerum APN level was positively correlated with the cholesterol content in large LDL and HDL particles, but inversely correlated with the cholesterol content in large VLDL and small LDL particles. HOMA-R was negatively correlated with the cholesterol content in large LDL and HDL particles and positively correlated with the cholesterol content in large VLDL and small LDL particles. By multivariate analysis, APN was correlated with the particle size of LDL-C and HDL-C independently of age, BMI and HOMA-R. ConclusionsAPN may be associated with the formation of both HDL and LDL particles, reflecting the enhancement of RCT and the improvement in TG-rich lipoprotein metabolism and insulin resistance.

Prediabetic Obese Adolescents have a More Atherogenic Lipoprotein Profile Compared with Normoglycemic Obese Peers

To compare lipoprotein profiles of prediabetic to normoglycemic obese adolescents. Cross-sectional study of 95 obese, pubertal adolescents (12-17 years), who underwent oral glucose tolerance test, lipid panel, and lipoprotein subclass particle analysis (nuclear magnetic resonance spectroscopy). Univariate and linear regression analyses compared prediabetic and normoglycemic groups. Of 95 obese adolescents enrolled in the study, 22.1% (n = 21) had prediabetes. They were similar to normoglycemic adolescents (n = 74) in age, race, body mass index, standard lipids, total low-density lipoprotein particles (LDL-P), and total high-density lipoprotein particles (HDL-P). However, prediabetics had higher concentrations of small LDL-P (714.0 ± 288.0 vs 537.7 ± 266.5 nmol/L, P = .01) and smaller LDL-P size (20.73 ± 0.41 vs 21.18 ± 0.65 nm, P = .003), than normoglycemic youth. Prediabetics had higher small HDL-P (18.5 ± 3.8 vs 16.6 ± 3.9 umol/L, P = .046), lower large HDL-P (4.49 ± 2.0 vs 6.32 ± 2.6 umol/L, P = .004), and smaller HDL-P size (8.73 ± 0.31 vs 9.01 ± 0.39 nm, P = .003). After adjusting for demographics, Tanner stage, and body mass index using multiple linear regression, all differences remained significant except for small HDL-P. After additional adjustment for Homeostasis Model Assessment-Insulin Resistance Index, only LDL-P size difference remained significant. Obese prediabetic adolescents have a significantly more atherogenic lipoprotein profile compared with obese normoglycemic peers. Prediabetic adolescents may benefit from more aggressive interventions to decrease future cardiovascular risk.

Weight change and lipoprotein particle concentration and particle size: A cohort study with 6.5-year follow-up

ObjectiveObesity and overweight are related to unfavourable lipoprotein subclass profiles. Here we studied the relation between weight change and lipoprotein particle concentrations and sizes in a general population cohort in a longitudinal setting. MethodsThe cohort included 683 adults with a 6.5-year follow-up. Lipoprotein particle subclasses and mean particle sizes of VLDL, LDL, and HDL were measured by nuclear magnetic resonance spectroscopy. ResultsDuring the follow-up period, a weight loss of at least 5% was associated with decreased particle concentrations of all apoB-containing subclasses and increased concentrations of large HDL particles. Coherently, weight gain (≥5%) was associated with increases in all apoB-containing subclasses and decreases in total and medium HDL particle concentrations. The relatively largest increase occurred for large HDL particle concentration (24.1%, 95% CI 15.8–32.5) in weight loss and for large VLDL particle concentration (33.0%, 19.6–46.4) in weight gain. Weight change correlated positively with changes in apoB-containing lipoprotein particle concentrations and also with the change in average VLDL particle size. Negative correlations were found between weight change and the change in average LDL (r = −0.10) and HDL (r = −0.32) particle size, but not between weight change and total HDL particle concentration. ConclusionModerate weight loss is related to favourable and weight gain to unfavourable changes in lipoprotein subclass profiles. These population level findings underline the importance of weight control as a modifier of cardiovascular risk factors.

Effects of Extended-release Niacin/Laropiprant on Apolipoprotein B, LDL-Cholesterol, and Non-HDL-cholesterol Targets in Patients with Type 2 Diabetes

s 285 small low-density lipoprotein particle (LDL-P) and CHD risk. Purpose: To compare the effects of niacin extendedrelease/simvastatin (NER/S) therapy on lipoprotein particles to atorvastatin (Atv) from the SUPREME study. Methods: This is a post-hoc analysis of 137 patients with dyslipidemia from a 12-week, randomized, study of patients treated with daily NER/S (n 5 74, 1000/40 mg x 4 weeks; 2000/40 mg x 8 weeks) or Atv (n 5 63, 40 mg x 12 weeks). A total of 137 patients had particle concentration and size measurements at baseline (BL) and 12 wk by NMR spectroscopy. Results: Patients in both treatment groups had comparable particle values at BL. Treatment with NER/S resulted in a greater increase in large HDL-P concentration (P 5 .078), significantly greater decrease in small HDL-P concentration (P , .05), and significantly greater increase in HDL-P size (P , .001), HDL-C and apoA-I vs Atv. Treatment with NER/S also significantly decreased the concentration of total LDL-P (P , .05) and small LDL-P (P , .05) and significantly increased LDL-P size (P , .01) vs Atv (Table 1). Conclusions: Compared with Atv 40 mg monotherapy, combination therapy NER/S at 2000/40 mg results in multiple favorable changes in both HDL and LDLmetrics. These data show that NER/S treatment promotes a greater shift toward less atherogenic lipoprotein subclasses than Atv.