LDL Peak Particle Diameter Research Articles

Changes in low-density lipoprotein size phenotypes associate with changes in apolipoprotein C-III glycoforms after dietary interventions

The presence of small dense low-density lipoprotein (LDL) is associated with obesity, type II diabetes, and an increased risk for cardiovascular disease. Apolipoprotein C-III (apoC-III) is involved in the formation of small dense LDL, but the exact mechanisms are still not well defined. ApoC-III is a glycosylated apolipoprotein, with 3 major glycoforms: apoC-III0, apoC-III1, and apoC-III2 that contain 0, 1, or 2 molecules of sialic acid, respectively. In our previous work, we reported an association among apoC-III0 and apoC-III1, but not apoC-III2 with fasting plasma triglyceride levels in obesity and type II diabetes. The goal of this study was to determine the relationship between changes in the major apoC-III glycoforms and small dense LDL levels after dietary interventions. Mass spectrometric immunoassay was performed on fasting plasma samples from 61 subjects who underwent either a high-carbohydrate diet (n=34) or a weight loss intervention (n=27). After both dietary interventions, changes in total apoC-III concentrations were associatedwith changes in LDL peak particle diameter (r=-0.58, P<.0001). Increases in total apoC-III concentrations after the high-carbohydrate diet were associated with decreases in LDL size (r=-0.53, P=.001), and decreases in apoC-III concentrations after weight loss were associated with increases in LDL peak particle diameter (r=-0.54, P=.004). Changes in concentrations of apoC-III1 and apoC-III0, but not apoC-III2, were associated with changes in LDL peak particle diameter in both the weight loss and high-carbohydrate interventions. We conclude that apoC-III0 and apoC-III1, but not apoC-III2 are associated with the formation of small dense LDL.

Comparison of the DASH (Dietary Approaches to Stop Hypertension) diet and a higher-fat DASH diet on blood pressure and lipids and lipoproteins: a randomized controlled trial1–3

Background: The DASH (Dietary Approaches to Stop Hypertension) dietary pattern, which is high in fruit, vegetables, and low-fat dairy foods, significantly lowers blood pressure as well as low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol.Objective: The study was designed to test the effects of substituting full-fat for low-fat dairy foods in the DASH diet, with a corresponding increase in fat and a reduction in sugar intake, on blood pressure and plasma lipids and lipoproteins.Design: This was a 3-period randomized crossover trial in free-living healthy individuals who consumed in random order a control diet, a standard DASH diet, and a higher-fat, lower-carbohydrate modification of the DASH diet (HF-DASH diet) for 3 wk each, separated by 2-wk washout periods. Laboratory measurements, which included lipoprotein particle concentrations determined by ion mobility, were made at the end of each experimental diet.Results: Thirty-six participants completed all 3 dietary periods. Blood pressure was reduced similarly with the DASH and HF-DASH diets compared with the control diet. The HF-DASH diet significantly reduced triglycerides and large and medium very-low-density lipoprotein (VLDL) particle concentrations and increased LDL peak particle diameter compared with the DASH diet. The DASH diet, but not the HF-DASH diet, significantly reduced LDL cholesterol, HDL cholesterol, apolipoprotein A-I, intermediate-density lipoprotein and large LDL particles, and LDL peak diameter compared with the control diet.Conclusions: The HF-DASH diet lowered blood pressure to the same extent as the DASH diet but also reduced plasma triglyceride and VLDL concentrations without significantly increasing LDL cholesterol. This trial was registered at clinicaltrials.gov as NCT01404897.

Interaction between Common Genetic Variants and Total Fat Intake on Low-Density Lipoprotein Peak Particle Diameter: A Genome-Wide Association Study

Background/Aim: Total fat intake has an important impact on the low-density lipoprotein (LDL) peak particle diameter (LDL-PPD) and may interact with nutrient-sensitive single nucleotide polymorphisms (SNPs). The objective was to examine whether there is suggestive evidence of SNP × dietary fat intake interaction effects influencing the LDL-PPD in the Quebec Family Study (QFS) in order to generate hypotheses to be tested in larger studies. Methods: SNPs from a genome-wide association study (GWAS) using Illumina Human610-Quad BeadChip, total fat intake derived from a 3-day weighted food record, and SNP × total fat intake interaction effects were examined on LDL-PPD in 541 QFS subjects. Results: The GWAS analyses 29 identified independent SNP × total fat intake interaction effects on the LDL-PPD at p < 10^-5, including SNPs in the following genes: ABCG2, CPA3, FNBP1, KCNQ3, NBAS, NCALD, OPRL1, NKAIN2, SH3BGRL2, SOX5, and SUSD4. Conclusions: This observational study suggests that multiple SNPs interact with dietary fat intake to influence variation in the LDL-PPD.

Traditional Dietary Pattern Is Associated with Elevated Cholesterol among the Inuit of Nunavik

Our cross-sectional study assessed the associations between dietary patterns and cardiovascular disease (CVD) risk factors among Nunavik Inuit. This study was conducted as part of the 2004 Nunavik Inuit Health Survey, which included the collection of clinical measurements, plasma samples, and diet information from a food frequency questionnaire. A sample of 666 Inuit aged 18 years and older was included in our analyses. Dietary patterns were generated by principal component analysis. Multivariate general linear models adjusting for sex, age, waist circumference, and other potential confounders were used to examine associations between dietary patterns and CVD risk factors. Four distinct patterns were identified, namely the traditional, Western, nutrient-poor food, and healthy patterns. The traditional pattern showed positive associations with plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein B100, LDL peak particle diameter, and oxidized LDL (all P values for trend≤0.04), but showed no association with the total cholesterol:high-density lipoprotein cholesterol ratio or with inflammatory biomarkers (all P values for trend ≥0.19). The nutrient-poor food pattern was positively associated with oxidized LDL (P=0.04), but inversely associated with high-sensitivity C-reactive protein (P<0.0001). The Western and healthy patterns showed no association with any CVD risk factor. Our data show that high adherence to a traditional pattern among Nunavik Inuit is not associated with important changes in CVD risk factors, with the exception of a slight elevation in cholesterol concentrations, most likely attributable to increased n-3 fatty acid intake. Dietary patterns reflecting the recent introduction of market foods in the Inuit diet appear to exert a trivial influence on CVD risk factors.

Abstract 127: The Mediterranean Diet With and Without Weight Loss Improves Several Features of Low-Density Lipoprotein Metabolism in Men With Metabolic Syndrome

Objective To assess the impact of a Mediterranean type diet (MedDiet), without weight loss (-WL) and with weight loss (+WL), on features of LDL and LDL- apolipoprotein (apo) B metabolism in men with metabolic syndrome (MetS). Methods and Results The diet of 19 men with MetS (NCEP-ATP III, age 24-62 years) was first standardized to a typical North American control diet that they consumed for 5 weeks under isoenergetic feeding conditions (all foods and beverages provided). Subjects were then fed a MedDiet for 5 weeks also under isoenergetic conditions (MedDiet-WL), after which they underwent a 20-week weight loss period in free-living conditions (average weight loss -10.2 ± 2.9% body weight, P&lt;0.01). This was followed by consumption of the MedDiet (5 weeks) under isoenergetic conditions (MedDiet+WL). Features of LDL and apo B kinetics were assessed at the end of the three controlled feeding periods. MedDiet-WL reduced VLDL-apoCIII (-41.5%), cholesteryl ester transfer protein (-7.0%) and hepatic lipase concentrations (-7.1%), reduced the proportion of small LDL (LDL&lt;255 å, -11.7%) and increased LDL peak particle diameter (LDL-PPD, +0.7%) as well as the proportion of medium size LDL (LDL255-260 å, +11.1%) vs. control diet (all P&lt;0.05). MedDiet-WL also decreased LDL-apoB pool size (PS, -14.2%) and increased the fractional catabolic rate (FCR) of LDL-apoB (+30.4%) vs. the control diet (both P&lt;0.05), with no change in LDL-apoB production rate (PR). MedDiet+WL was associated with further increase in LDL-PPD (0.2%) and further reduction in VLDL-apoCIII concentrations (-28.7%) compared with MedDiet-WL (both P&lt;0.05) but had no further impact on LDL-apoB PS and on LDL-apoB FCR. Conclusion Data from this controlled feeding study suggest that consumption of MedDiet, even in the absence of weight loss, decreases LDL-C concentrations and LDL-apoB pool size primarily by enhancing the clearance of LDL particles in men with MetS. This is accompanied by a reduction in the proportion of small dense LDL and an increase in LDL particle size. Combining weight loss to MedDiet has no additional impact on LDL-apoB pool size and catabolism but may have further beneficial effects on the LDL particle size phenotype in men with MetS.

Abstract P217: Metabolic Effects of a Nutrient-Dense High Fiber Supplement

Achieving recommended dietary intakes of vitamins and minerals, fiber, and other health-promoting small molecules, such as fruit polyphenolics and essential fatty acids, is difficult, even for healthy adults consuming generally good diets. We assessed the hypothesis that short term consumption of a comprehensive nutrition bar can favorably impact metabolic biomarkers linked to future disease risk. Methods: An approximately 100 kcal nutrition bar containing a vitamin, mineral, and docosahexaenoic acid (DHA)-fortified polyphenolic-rich whole food matrix composed of fruit, walnuts, and dark chocolate blended with insoluble and soluble fiber was developed. Pooled results are presented from 3 pilot trials in which 25 generally healthy adults (15 F, 10 M) were enrolled in 2-wk interventions to study the effect of twice-daily consumption of the bar on plasma lipoprotein subfractions (ion mobility analysis), and redox status (thiol amino acids) in addition to conventional biomarkers associated with dyslipidemia, insulin resistance, and inflammation. All variables were continuous, and paired t-tests were used to test for significant change between baseline and follow-up measures. Results: Mean HDL cholesterol increased by 6.6 + 9.7% ( p = 0.001), predominantly due to a rise in the large buoyant HDL2b subclass which rose from 1665.9 ± 1017.7 to 2089.4 ± 1197.6 nmol/L ( p &lt; 0.0001; 28% increase). Plasma triglyceride and LDL cholesterol levels did not change significantly but there was a trend towards increased LDL peak particle diameter (p = 0.086). Mean plasma homocysteine decreased from 12.6 ± 6.4 to 10.2 ± 3.7 µM (p=0.006, 19.2% decline). Measures of insulin resistance and inflammation did not change. Weight remained stable despite intake of 200 additional daily calories. Participants reported a significant decrease in hunger on an analog scale and compensatory decreased intake of other foods. Summary: Twice daily consumption of a low-calorie complete nutritional supplement increases satiety and large HDL particle concentrations within 2 weeks without weight gain.

Energy Substrate Partitioning and Efficiency in Individuals With Atherogenic Lipoprotein Phenotype

Individuals with an atherogenic lipoprotein phenotype (ALP) characterized by increased levels of small dense low-density lipoprotein (LDL) particles tend to have greater adiposity compared to unaffected subjects. We sought to determine whether this may be related to alterations in energy substrate partitioning or efficiency. These were assessed by indirect calorimetry in men with ALP (ALP(+), n = 7) and unaffected controls (ALP(-), n = 8) during rest (30 min) and exercise (10 min). Gross, net and delta efficiencies were calculated during graded leg-cycle ergometry at workloads of 10 and 50 W. Respiratory exchange ratios (RER) were significantly (P < 0.05) higher in ALP(+) vs. ALP(-) during rest (0.86 ± 0.01 vs. 0.83 ± 0.02) and exercise at 10 W (0.88 ± 0.02 vs. 0.84 ± 0.02) and 50 W (0.92 ± 0.01 vs. 0.87 ± 0.01, respectively) (P < 0.05). Lipid oxidation (kcal/min) was lower in ALP(+) vs. ALP(-) during rest (0.56 ± 0.02 vs. 0.71 ± 0.07) and exercise at 10 W (1.52 ± 0.25 vs. 2.00 ± 0.20) and 50 W (1.28 ± 0.10 vs. 2.32 ± 0.22, respectively) (P < 0.05). Gross and net efficiencies were significantly increased (P = 0.005) in ALP(+) vs. ALP(-) at 10 W. RER was correlated positively with plasma triglyceride during exercise and inversely with high-density lipoprotein (HDL) cholesterol and LDL peak particle diameter during rest and exercise (P < 0.05). These findings suggest that increased muscular efficiency at low exercise intensity and reduced lipid oxidation during rest and exercise may contribute to both dyslipidemia and increased adiposity in individuals with ALP.

Interactions between Dietary Fat Intake and FASN Genetic Variation Influence LDL Peak Particle Diameter

Background: The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on the Quebec Family Study (QFS) revealed a quantitative trait locus for LDL peak particle diameter (LDL-PPD) on the 17q21 region. A positional candidate gene – the fatty acid synthase gene (FASN) – encodes a key enzyme in the biogenesis of membrane lipids. FASN may play a role in the regulation of feeding and may be a potential therapeutic target for obesity and insulin resistance. Methods: Analyses were performed on 592 subjects of the QFS. Dietary fat was estimated by a 3-day food record. LDL-PPD was measured by gradient gel electrophoresis on polyacrylamide gradient gels. Results: Five single nucleotide polymorphisms were genotyped in FASN gene. FASN rs4246444 was associated with LDL-PPD, but only when fat intake was taken into account (p = 0.001). High and low lipid consumers were defined using a cutoff of 35% of dietary fat intake. Carriers of the variant allele showed smaller LDL-PPD only when consuming a high amount of fat. This association remained significant after adjustments for age, sex, body mass index and plasma triglyceride levels. Conclusion: The results suggest that dietary fat intake may modify the effect of the FASN rs4246444 polymorphism on LDL-PPD.

Investigation of LRP8 gene in 1p31 QTL linked to LDL peak particle diameter in the Quebec family study

The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus affecting LDL peak particle diameter (LDL-PPD) and density on the 1p31 region. This region contains the low-density lipoprotein receptor-related protein 8 (LRP8) gene. LRP8, a receptor for apolipoprotein (apo) E, modulates apoE levels, thus contributing to plasma cholesterol and triglyceride (TG) concentrations. We investigate the effects of LRP8 polymorphisms on LDL-PPD, on the relative proportion of small LDL (< 255 Å) and the absolute concentration of cholesterol among the small LDL particles. LRP8 rs5174 was associated with LDL-PPD and estimated cholesterol concentrations in the small LDL particles adjusted for the effects of age and sex ( p = 0.008, p = 0.04, respectively). LRP8 rs3820198 was associated with total and LDL-cholesterol levels as well as with apoB concentrations adjusted for the effects of age and sex ( p = 0.005, p = 0.004 and p = 0.01, respectively) but not with LDL size-related variables. These results suggest that LRP8 gene polymorphisms influence plasma cholesterol levels as well as size and composition of LDL particles.

Associations between Dietary Patterns and LDL Peak Particle Diameter: A Cross-Sectional Study

Objective: Dietary patterns are used to evaluate the effects of overall nutritional habits on health status, and low-density lipoprotein–peak particle diameter (LDL-PPD) has been recognized as an emerging risk factor for cardiovascular disease (CVD). The aim of this study is to verify whether an association exists between dietary patterns and LDL-PPD.Methods: A total of 635 participants aged between 18 and 55 years were included in this cross-sectional study. Nutritional information was collected with a validated food frequency questionnaire. To establish dietary patterns, factor analysis was performed, which led to characterization of the Western and Prudent dietary patterns. Nondenaturing 2%–16% polyacrylamide gradient gel electrophoresis was used to characterize LDL-PPD.Results: The Western pattern was characterized by high consumption of food such as refined grains, French fries, and red meats, and the Prudent pattern by nonhydrogenated fat, vegetables, eggs, and fish. For the Western profile, a negative correlation was found between score value and LDL-PPD before (r = −0.082, p = 0.039) and after adjustment for age (r = −0.080, p = 0.043). A negative correlation between scores for the Prudent profile and the LDL-PPD adjusted for age, sex, plasma triglycerides, and energy was observed (r = −0.12204, p = 0.0021). After division by tertiles and adjustment for the confounding effects of age, sex, plasma triglyceride levels, and energy, a significant difference (p = 0.0015) in LDL-PPD was noted between the highest tertile (255.21 ± 3.61 Å) and the lowest tertile (255.79 ± 3.68 Å) of the Prudent pattern.Conclusions: Dietary patterns, such as the Western and the Prudent, are associated with LDL-PPD. Dietary patterns can be used to assess the effects of nutritional habits on health status.

Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet

Low-fat diets have been shown to increase plasma concentrations of lipoprotein(a) [Lp(a)], a preferential lipoprotein carrier of oxidized phospholipids (OxPLs) in plasma, as well as small dense LDL particles. We sought to determine whether increases in plasma Lp(a) induced by a low-fat high-carbohydrate (LFHC) diet are related to changes in OxPL and LDL subclasses. We studied 63 healthy subjects after 4 weeks of consuming, in random order, a high-fat low-carbohydrate (HFLC) diet and a LFHC diet. Plasma concentrations of Lp(a) (P < 0.01), OxPL/apolipoprotein (apo)B (P < 0.005), and OxPL-apo(a) (P < 0.05) were significantly higher on the LFHC diet compared with the HFLC diet whereas LDL peak particle size was significantly smaller (P < 0.0001). Diet-induced changes in Lp(a) were strongly correlated with changes in OxPL/apoB (P < 0.0001). The increases in plasma Lp(a) levels after the LFHC diet were also correlated with decreases in medium LDL particles (P < 0.01) and increases in very small LDL particles (P < 0.05). These results demonstrate that induction of increased levels of Lp(a) by an LFHC diet is associated with increases in OxPLs and with changes in LDL subclass distribution that may reflect altered metabolism of Lp(a) particles.

Assessment of the validity of the frequently used lipid indices for predicting LDL peak particle diameter in a large cohort of 1955 normal and dyslipidemic subjects

Objectives: To assess the relationship between commonly used lipid indices and LDL peak particle diameter (LDL-PPD) in a large cohort of 1955 subjects. Design and methods: Four statistical methods were used for comparison: correlation, concordance analysis, kappa statistics and receiver operating characteristic curve (ROC) analysis. Results: Plasma triglyceride (TG) levels, TG/HDL-C, LDL-C/apoB, total cholesterol (TC)/TG, LDL-C/TG, and TG/apoB ratios were best correlated with LDL-PPD but none of these ratios accounted for more than 45% of the variation in LDL-PPD. Moreover, across the range of the lipid indices and LDL-PPD quintiles, just under 40% of the values were concordant, with kappas varying between 0.20 and 0.25. Finally, plasma TG levels and the lipid ratios yielded areas under the ROC curve between 0.78 and 0.80. Conclusions: The present study does not support the concept that plasma TG levels and the commonly used lipid indices may be considered as adequate surrogates for the small dense LDL phenotype. Our data also indicate that various lipid indices are not superior to plasma TG levels alone as a clinical tool for prediction of the small dense LDL phenotype.

Effects of Increasing Doses of Atorvastatin on the Atherogenic Lipid Subclasses Commonly Associated With Hypertriglyceridemia

The increased cardiovascular risk associated with hypertriglyceridemia is thought to be due in part to high levels of triglyceride (TG)-rich lipoproteins and small dense low-density lipoprotein (LDL). In this post hoc analysis, effects of increasing doses of atorvastatin (10, 20, 40, and 80 mg) on atherogenic lipid subclasses commonly associated with hypertriglyceridemia were evaluated in 191 men and women who were candidates for lipid-lowering therapy and had baseline TG levels >200 mg/dl (2.3 mmol/L). After 8 weeks of treatment, in addition to significantly decreasing LDL cholesterol and TG levels, atorvastatin significantly increased LDL peak particle diameter (p <0.01) and significantly decreased the concentration of small LDL subclasses IIIa and IIIb (p <0.0001) from baseline at all doses. These effects were more pronounced with higher compared with lower doses of atorvastatin. Each dose of atorvastatin also significantly lowered levels of very LDL, intermediate-density lipoprotein (p <0.0001), and small very LDL subclass 3 (p <0.0001). Greater decreases were achieved by those patients receiving higher doses of atorvastatin (20, 40, and 80 mg). The increase in LDL size correlated with the decrease in TG levels, but not with the decrease in LDL cholesterol levels. However, the decrease in small dense LDL cholesterol concentrations correlated significantly with TG and LDL cholesterol decreases. In conclusion, atorvastatin significantly lowered levels of TG-rich remnant lipoproteins and favorably changed LDL particle size in patients with hypertriglyceridemia. These effects may explain the benefits of statin therapy in high-risk patients with hypertriglyceridemia even when levels of LDL cholesterol are at goal.

LDL Particle Size in Habitual Exercisers, Lean Sedentary Men and Abdominally Obese Sedentary Men

Habitual exercisers enjoy considerable protection from coronary heart disease (CHD). Often, however, only modest differences in traditional CHD risk factors are apparent between habitual exercisers and their sedentary counterparts. For this reason, there is increasing interest in novel predictors of CHD, such as a preponderance of small, dense low-density lipoprotein (LDL) particles. Polyacrylamide gel electrophoresis was used to separate lipoprotein subfractions in 32 lean exercisers, 36 lean sedentary men and 21 obese sedentary men aged 30 - 45 years. Well-validated equations were used to determine LDL concentration and peak particle diameter. Waist girth was used to identify lean (< 100 cm) and obese (>or= 100 cm) individuals. LDL concentration was lower in lean exercisers than in lean sedentary men (2.64 +/- 0.44 vs. 3.76 +/- 0.79 mmol . l (-1), p < 0.001), suggesting that habitual exercise influences this risk factor. In contrast, there were no significant differences in LDL peak particle diameter between lean exercisers, lean sedentary men and obese sedentary men (27.92 +/- 0.67, 28.09 +/- 0.62 and 27.77 +/- 0.77 nm, respectively). In multiple linear regression analysis, triglyceride concentration was the only significant predictor of LDL PPD. These data suggest that habitual exercise influences LDL concentration but does not influence LDL particle size in men aged 30 - 45 years.

Low‐density lipoprotein (LDL) particle size in healthy prepubertal children: The STRIP study

Small, dense low-density lipoprotein (LDL) particles (diameter < 255 Angstrom) are highly atherogenic, and in adults they are associated with an elevated risk of coronary heart disease (CHD). To examine possible contributors to LDL particle size distribution in healthy prepubertal children. We determined LDL particle size in 176 7-y-old children by non-denaturing polyacrylamide gel electrophoresis. Children were divided into two groups in two ways: by using the median of their average LDL particle diameter (261.2 Angstrom) or by using the LDL peak particle diameter (255 Angstrom) as the cut-off point. Children with smaller LDL particles did not significantly differ from children with larger LDL particles with respect to anthropometric variables, serum triglyceride concentration (in all children < 1.7 mmol/L), apoE phenotype, amount and quality of dietary fat, or child's family history of CHD. Furthermore, LDL particle size did not correlate with any of the anthropometric, lipid or nutrient variables. Children with average LDL particle size below the median had higher serum insulin and lower high-density lipoprotein (HDL) cholesterol and apoA-1 concentrations than those with LDL particle size above the median. Our data suggest that many factors related to the development of small, dense LDL particles might have their major impact after the onset of puberty.

Quantitative trait loci influencing low density lipoprotein particle size in African Americans

Genomic regions that influence LDL particle size in African Americans are not known. We performed family-based linkage analyses to identify genomic regions that influence LDL particle size and also exert pleiotropic effects on two closely related lipid traits, high density lipoprotein cholesterol (HDL-C) and triglycerides, in African Americans. Subjects (n = 1,318, 63.0 +/- 9.5 years, 70% women, 79% hypertensive) were ascertained through sibships with two or more individuals diagnosed with essential hypertension before age 60. LDL particle size was measured by polyacrylamide gel electrophoresis, and triglyceride levels were log-transformed to reduce skewness. Genotypes were measured at 366 microsatellite marker loci distributed across the 22 autosomes. Univariate and bivariate linkage analyses were performed using a variance components approach. LDL particle size was highly heritable (h(2) = 0.78) and significantly (P < 0.0001) genetically correlated with HDL-C (rho(G) = 0.32) and log triglycerides (rho(G) = -0.43). Significant evidence of linkage for LDL particle size was present on chromosome 19 [85.3 centimorgan (cM), log of the odds (LOD) = 3.07, P = 0.0001], and suggestive evidence of linkage was present on chromosome 12 (90.8 cM, LOD = 2.02, P = 0.0011). Bivariate linkage analyses revealed tentative evidence for a region with pleiotropic effects on LDL particle size and HDL-C on chromosome 4 (52.9 cM, LOD = 2.06, P = 0.0069). These genomic regions may contain genes that influence interindividual variation in LDL particle size and potentially coronary heart disease susceptibility in African Americans.

Circulating oxidized LDL is associated with parameters of the metabolic syndrome in postmenopausal women

Oxidized low-density lipoproteins (ox-LDL) play a significant role in the development of atherosclerosis. Objective To investigate the relation between circulating ox-LDL and components of the metabolic syndrome (MS) in a sample of 124 postmenopausal women with varying glucose tolerance status. Methods This cross-sectional study included postmenopausal women not using hormone therapy. Ox-LDL concentrations were measured in plasma by a monoclonal antibody (mAb-4E6) based competition ELISA. LDL peak particle diameter (LDL-PPD) was measured by non-denaturating polyacrylamide gradient gel electrophoresis (PAGGE). Presence of the MS was determined according to the definition of the NCEP-ATPIII. Results Circulating ox-LDL concentrations were significantly associated with some factors of the MS such as triglyceride ( r = 0.48; p < 0.0001), high-density lipoprotein cholesterol ( r = −0.34; p = 0.0001) and fasting plasma glucose concentrations ( r = 0.21; p = 0.02). Ox-LDL concentrations were also associated with LDL cholesterol ( r = 0.54; p < 0.0001), total cholesterol ( r = 0.48; p < 0.0001), LDL apolipoprotein B ( r = 0.62; p < 0.0001) and LDL-PPD ( r = −0.18; p < 0.05). Moreover, women with the MS had significantly higher ox-LDL concentrations (79.5 ± 28.3 U/l) compared to women without the MS (64.2 ± 19.9 U/l) ( p < 0.05). Conclusion Ox-LDL concentrations are associated with individual components of the MS and are significantly higher in postmenopausal women with MS compared to healthy postmenopausal women.

Tu-P10:446 Relationship between C-reactive proteine and cerebrovascular stenosis

The fasting atherogenic dyslipidemia of visceral obesity, which includes the presence of small, dense low-density lipoprotein (LDL) particles, is predictive of an increased risk of coronary heart disease (CHD). It has also been suggested that progression of atherosclerosis may be accelerated in the presence of postprandial hyperlipidemia independently from the fasting dyslipidemic state. Studies have shown that the best predictor of postprandial hyperlipidemia and of the small, dense LDL phenotype is fasting triglyceride (TG) concentration. In the present study, we evaluated the impact of postprandial hypertriglyceridemia on the variation in LDL particle size. Fasting (0 hour) and postprandial changes (2, 4, 6, and 8 hours) in LDL particle size were measured by nondenaturing 2% to 16% polyacrylamide gel electrophoresis in a sample of 49 men (mean age ± SD: 46.6 ± 9.2 years) who underwent a standardized breakfast with a high-fat (64% calories as fat) content. The postprandial increase in TG levels was associated with a transient reduction in LDL particle size, the most substantial reduction being observed 4 hours (−1.0 ± 2.4 Å) after the oral fat load. Although there were strong correlations between TG-rich lipoprotein (TRL)-TG levels and LDL particle size in the fasting state (r = −0.71, P < .0001) as well as 4 hours after the oral fat load (r = −0.70, P < .0001), changes in TRL-TG concentrations during the postprandial state (from time 0 to 4 hours) were not associated with changes in LDL particle size during this period (r = −0.04, not significant [NS]). However, among subgroups of men matched for similar fasting TRL-TG levels (n = 12), subjects with the highest total area under the curve (AUC) of TRL-TG after the fat load were characterized by smaller LDL particle size at 6 and 8 hours compared with men with the lowest AUC TRL-TG (P < .02). Men displaying the highest postprandial AUC TRL-TG were also characterized by the greatest accumulation of visceral adipose tissue (AT) (P < .05). These results indicate that the hypertriglyceridemic (hyperTG) state induced by a high-fat meal is associated with a transient reduction in LDL peak particle diameter, which is not proportionate, however, to the level of TG achieved in the postprandial state. Furthermore, despite similar TG levels at baseline, viscerally obese men with an impaired postprandial lipemia had smaller LDL particles at the end of the oral fat load than obese men with a lower accumulation of visceral AT.

LDL particle size, fat distribution and insulin resistance in obese children

The importance of small dense low-density lipoprotein (sdLDL) cholesterol in coronary heart disease has been demonstrated in many studies. Body fat accumulation, especially abdominal adiposity, is one of the important factors modifying the expression of sdLDL in adults. To determine the prevalence of sdLDL in obese children, and to investigate its relationship with anthropometric and metabolic variables. A total of 30 obese children (22 males, 8 females) aged 12.6+/-0.6 years (mean+/-s.e.), who presented to our outpatient clinic with obesity. LDL peak particle diameter was determined using gel electrophoresis. LDL subclasses were classified into sdLDL (pattern B; diameter<25.5 nm) and non-sdLDL (pattern A; diameter>or=25.5 nm). Anthropometric and metabolic variables were also determined to identify factors modifying LDL particle size. sdLDL was detected in 11 children (40.0%). In children with sdLDL, waist/height ratio was significantly higher (P=0.0466), and they had significantly higher triglyceride (TG) (P=0.0035) and lower high-density lipoprotein cholesterol (HDLC) levels (P=0.036). Peak LDL diameter as a continuous variable was significantly correlated with HDLC and TG levels. In multiple regression analysis, body mass index and waist/height ratio were significant determinants of the peak LDL diameter variability. We found a high prevalence of sdLDL in obese children, and a relationship of peak LDL diameter with abdominal fat accumulation, HDLC and TG levels. The presence of sdLDL might be an important risk factor for the metabolic syndrome.

Genotype of the mutant LDL receptor allele is associated with LDL particle size heterogeneity in familial hypercholesterolemia

Small, dense LDL particles have been associated with an increased risk of coronary artery disease. In order to assess the potential contribution of the genotype of the LDL receptor to LDL particle size heterogeneity in familial hypercholesterolemia (FH), we examined the electrophoretic characteristics of LDL particles in a large cohort of FH heterozygotes and controls. A total of 259 FH heterozygotes and 208 controls participated in the study. FH subjects were carriers of one of the nine French Canadian mutations in the LDL receptor gene. LDL particles were characterized by polyacrylamide gradient gel electrophoresis following a 6-week lipid-lowering drug-free baseline period. LDL–peak particle diameter (LDL–PPD), representing the most abundant LDL particle subpopulation, was significantly smaller in FH heterozygotes carrying a negative-receptor mutation than in subjects carrying a defective-receptor mutation (negative-receptor = 257.3 ± 4.1 Å versus defective-receptor = 259.0 ± 4.3 Å, p = 0.0006). No significant difference in plasma CETP concentrations was found between these two genotypic groups. Moreover, compared with controls having low triglyceride levels, negative-receptor subjects with high triglyceride levels had a relative risk of 19.6 ( p < 0.0001) of having small, dense LDL particles while this risk was not significantly increased among defective-receptor subjects. Multivariate analysis showed that the LDL receptor status accounted for 5.7% of the variance in the LDL–PPD after adjustment for covariates. These results suggest that the genotype of the mutant LDL receptor allele was independently associated with variations in LDL–PPD and could partly explain why negative-receptor FH heterozygotes may be at greater risk of cardiovascular disease than defective-receptor FH subjects.