Atherogenic Lipoprotein Profile Research Articles

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

Commentary: Shaper and Jones, 'Serum-cholesterol, diet and coronary heart-disease in Africans and Asians in Uganda': 50-year-old findings only need interpretational fine tuning to come up to speed!

Commentary: Shaper and Jones, 'Serum-cholesterol, diet and coronary heart-disease in Africans and Asians in Uganda': 50-year-old findings only need interpretational fine tuning to come up to speed!

Whole egg consumption improves lipoprotein profiles and insulin sensitivity to a greater extent than yolk-free egg substitute in individuals with metabolic syndrome

ObjectiveWe investigated if daily egg feeding, along with carbohydrate restriction, would alter lipoprotein metabolism and influence atherogenic lipoprotein profiles and insulin resistance in men and women with metabolic syndrome (MetS). MethodsIn a randomized, single-blind, parallel design, participants consumed either 3 whole eggs/day (EGG, n=20) or the equivalent amount of yolk-free egg substitute (SUB, n=17), as part of a moderately carbohydrate-restricted diet (25%–30% energy) for 12 weeks. Plasma lipids, apolipoproteins (apos), oxidized LDL (oxLDL), cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT) activities were assessed at baseline and week 12. Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy. ResultsAtherogenic dyslipidemia improved for all individuals as evidenced by reductions in plasma triglycerides, apoC-III, apoE, oxLDL, VLDL particle diameter, large VDL, total IDL, small LDL, and medium LDL particles (P<0.05). Furthermore, there were increases in HDL-cholesterol, large LDL and large HDL particles (P<0.05) for all individuals. However, there were greater increases in HDL-cholesterol and large HDL particles, and reductions in total VLDL and medium VLDL particles for those consuming EGG compared to SUB (P<0.05). Plasma insulin and insulin resistance (HOMA-IR) were reduced, while LCAT activity, and both HDL and LDL diameters increased over time in the EGG group only (P<0.05). ConclusionsIncorporating daily whole egg intake into a moderately carbohydrate-restricted diet provides further improvements in the atherogenic lipoprotein profile and in insulin resistance in individuals with MetS.

GH levels and insulin sensitivity are differently associated with biomarkers of cardiovascular disease in active acromegaly

Acromegaly is characterized by GH excess and insulin resistance. It is not known which of these disorders is responsible for the increased atherogenic risk in these patients. To analyse the associations of GH and homoeostasis model assessment (HOMA) with biomarkers of cardiovascular disease and to compare the above-mentioned variables between patients with active acromegaly and controls. This open cross-sectional study was conducted at a University Hospital. Twenty-two outpatients were compared with sex- and age-matched control subjects. Included clinical features, hormonal status, markers of insulin resistance, lipoprotein profile and biomarkers of cardiovascular disease. Patients presented higher triglyceride (median [IQR]) (1·2[1·1-1·6] vs 0·9[0·6-1·1] mm, P < 0·05), low-density lipoprotein-cholesterol (LDL-C) (mean ± SD) (3·5 ± 0·9 vs 3·0 ± 0·7mm, P < 0·05), apoB (0·98 ± 0·23 vs 0·77 ± 0·22 g/l, P < 0·05), free fatty acid (0·69 ± 0·2 vs 0·54 ± 0·2 mM, P < 0·05), oxidized-LDL (120 ± 22 vs 85 ± 19 U/l, P < 0·05) and endothelin-1 (0·90 ± 0·23 vs 0·72 ± 0·17 ng/l, P < 0·05) levels, increased cholesteryl ester transfer protein (CETP) activity (179 ± 27 vs 138 ± 30%/ml/h, P < 0·01) and lower C reactive protein (CRP) (0·25[0·1-0·9] vs 0·85[0·4-1·4] mg/l; P < 0·05) levels than control subjects. Vascular cell adhesion molecule (VCAM-1) concentration was not different. By multiple linear regression analyses, HOMA explained the variability of triglycerides (25%), high-density lipoprotein-cholesterol (HDL-C) (30%) and CETP activity (28%), while GH independently predicted LDL-C (18%), oxidized-LDL (40%) and endothelin-1 levels (19%). In patients with active acromegaly, GH excess contributes to the development of insulin resistance, and the interaction between both disturbances would be responsible for the appearance of atherogenic pro-oxidative and pro-inflammatory factors. Insulin resistance would be preferably associated with an atherogenic lipoprotein profile and to high CETP activity, while high GH levels would independently predict the increase in LDL-C, ox-LDL and endothelin-1.

Effects of rosuvastatin versus pravastatin on low-density lipoprotein diameter in HIV-1-infected patients receiving ritonavir-boosted protease inhibitor

HIV infection is associated with an atherogenic lipoprotein profile, and ritonavir-boosted protease inhibitors exacerbate this phenotype. We evaluated the effect of 45 days of rosuvastatin versus pravastatin on the low-density lipoprotein (LDL) size and the distribution of LDL subfractions in HIV-1 patients receiving boosted protease inhibitors with elevated LDL levels. Substudy of the randomized double-blind multicentre ANRS 126 VIHstatine trial. Twenty clinical centres in France. HIV-infected patients receiving boosted protease inhibitors with dyslipidaemia (LDL cholesterol > 4.1 mmol/l and triglycerides < 8.8 mmol/l). Rosuvastatin 10 mg/day (n = 39) or pravastatin 40 mg/day (n = 37) for 45 days. LDL size and distribution of LDL subfractions blindly assessed by gradient gel electrophoresis at baseline and at day 45. Rosuvastatin was more effective than pravastatin in increasing the diameter of the LDL peak. The LDL diameter change was 0.33 ± 0.59 nm in the rosuvastatin group versus -0.01 ± 0.52 nm in the pravastatin group (P = 0.021). Rosuvastatin was also more effective in increasing significantly the percentage of large LDL (LDL1, P = 0.038; LDL2, P = 0.031) and in decreasing the percentage of small LDL (LDL3, P = 0.009). Rosuvastatin was more effective than pravastatin in normalizing LDL size and LDL subfraction distributions, leading to a less atherogenic phenotype.

Consumption of Nonfat Milk Results in a Less Atherogenic Lipoprotein Profile: A Pilot Study

Background: An increase in plasma low-density lipoprotein (LDL) is a well-known risk factor in the development of atherosclerosis. Dairy consumption may lower the risk of atherosclerosis; however, studies on the effects of milk on cardiovascular risk factors are still scarce. We were interested in investigating whether the intake of milk improves the atherogenic lipoprotein profile. Aims: We investigated the effects of consuming whole or nonfat milk on plasma lipoprotein composition in healthy Japanese subjects as a pilot study. Methods: Normolipidemic subjects consumed 500 ml of whole milk (whole milk group; n = 7) or nonfat milk (nonfat milk group; n = 7) every day for 2 weeks. Results: The consumption of nonfat milk resulted in a lowering of plasma triglyceride (TG) and phospholipid levels and TG level in high-density lipoprotein (HDL) and increased the plasma apolipoprotein (apo) C-III level. In addition, the TG/cholesterol ratios in HDL and LDL were significantly decreased, and LDL particles became larger. In contrast, the only changes observed following whole milk consumption were increases in the plasma levels of apoC-III and apoE. Conclusions: These findings suggest that consumption of nonfat milk, but not whole milk, may result in a less atherogenic lipoprotein profile, and that the constituents of nonfat milk may improve lipid metabolism.

Abnormal lipoprotein particles and cholesterol efflux capacity in patients with psoriasis

ObjectivesPsoriasis is a Th-1/17 mediated inflammatory disease associated with increased risk of cardiovascular disease (CVD). Inflammation may modulate lipoprotein particle number and directly impair HDL functions, in particular reverse cholesterol transport (RCT). We sought to study how chronic in vivo inflammation modulates lipoprotein particle composition using nuclear magnetic resonance spectroscopy (NMR) and HDL efflux in psoriasis. Methods and resultsWe prospectively enrolled a consecutive sample of patients with psoriasis (n = 122) and compared lipoprotein and metabolic risk factors to patients without psoriasis (n = 134). Fasting lipids, insulin, glucose were measured by standard assays, and lipoprotein concentration and size were measured by NMR. In a random subset (n = 100 each group), HDL efflux capacity was quantified using a validated ex vivo system involving the incubation of macrophages with apolipoprotein B-depleted serum from patients. Traditional lipid concentrations were similar in both groups except for HDL concentration which was lower in psoriasis (43 mg/dl (36–58) vs 50 (42–62), p < 0.01). However, NMR showed an atherogenic profile in psoriasis similar to that observed in diabetes, with significant increase in LDL particle concentration [1210.5 (1002–1498) vs 1115 (935–1291), p = 0.02] with decrease in LDL size [20.6 (20.3–21.1) vs 21.3 (20.6–21.1), p < 0.001] beyond CV risk factors and HOMA-IR (p = 0.001). Finally, HDL efflux capacity was lower in psoriasis compared to controls in fully adjusted models (beta −0.14, p = 0.001). ConclusionsThese data support a more atherogenic lipoprotein profile by NMR and decreased HDL efflux capacity in psoriasis patients compared to controls beyond CVD risk factors. The abnormal lipoprotein particle composition and HDL efflux capacity in psoriasis may provide a link between psoriasis and CVD.

Lipid Effects of Peroxisome Proliferator-Activated Receptor-Δ Agonist GW501516 in Subjects With Low High-Density Lipoprotein Cholesterol

Peroxisome proliferator-activated receptor-δ-induced upregulation in skeletal muscle fatty acid oxidation would predict the modulation of lipid/lipoproteins. GW501516 (2.5, 5.0, or 10.0 mg) or placebo was given for 12 weeks to patients (n=268) with high-density lipoprotein (HDL) cholesterol <1.16 mmol/L. Fasting lipids/apolipoproteins (apos), insulin, glucose, and free fatty acid were measured; changes from baseline were calculated and assessed. A second smaller exploratory study (n=37) in a similar population was conducted using a sequence of 5 and 10 mg dosing for the assessment of lipoprotein particle concentration. GW501516 demonstrated HDL cholesterol increases up to 16.9% (10 mg) and apoA-I increases up to 6.6%. Reductions were observed in low-density lipoprotein (LDL) cholesterol (-7.3%), triglycerides (-16.9%), apoB (-14.9%), and free fatty acids (-19.4%). The exploratory study showed significant reductions in the concentration of very LDL (-19%), intermediate-density lipoprotein (-52%), and LDL (-14%, predominantly a reduction in small particles), whereas the number of HDL particles increased (+10%; predominantly medium and large HDL). GW501516 produced significant changes in HDL cholesterol, LDL cholesterol, apoA1, and apoB. Fewer very LDL and larger LDL support a transition toward less atherogenic lipoprotein profiles. These data are consistent with peroxisome proliferator-activated receptor-δ being a potentially important target for providing cardiovascular protection in metabolic syndrome-like patients.

Nonalcoholic steatohepatitis versus steatosis: Adipose tissue insulin resistance and dysfunctional response to fat ingestion predict liver injury and altered glucose and lipoprotein metabolism

Nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH). Though liver-related risk seems confined to NASH, it is currently unclear whether NASH has a higher risk of cardiovascular disease (CVD) and diabetes than SS as a result of the coexistence of obesity and other cardiometabolic confounders. Adipose tissue is an emerging modulator of liver disease in NAFLD and of cardiometabolic disease in the general population. We evaluated in SS and NASH (1) glucose homeostasis and cardiovascular risk profile and (2) the effect of adipose tissue dysfunction, assessed in fasting conditions and postprandially, on liver injury, glucose and lipoprotein metabolism, and markers of early atherosclerosis. Forty nonobese, nondiabetic, normolipidemic biopsy-proven NAFLD patients (20 with SS and 20 with NASH) and 40 healthy subjects, matched for overall/abdominal adiposity and metabolic syndrome, underwent an oral fat load test, with measurement of plasma triglyceride-rich lipoproteins, oxidized low-density lipoproteins, adipokines, and cytokeratin-18 fragments, and an oral glucose tolerance test with minimal model analysis to yield glucose homeostasis parameters. Circulating endothelial adhesion molecules were measured, and adipose tissue insulin resistance (adipose IR) index and visceral adiposity index were calculated. Despite similar fasting values, compared to SS, NASH showed a more atherogenic postprandial lipoprotein profile, an altered adipokine response (i.e., higher resistin increase and an adiponectin fall), and hepatocyte apoptosis activation after fat ingestion. Adipose IR index, endothelial adhesion molecules, and hepatic insulin resistance progressively increased across NAFLD stages. NASH, but not SS, showed an impaired pancreatic β-cell function. On multiple regression analysis, adipose IR index and postprandial adiponectin independently predicted liver histology and altered cardiometabolic parameters. Adipose tissue dysfunction, including a maladaptive adipokine response to fat ingestion, modulates liver injury and cardiometabolic risk in NAFLD.

Initial combination therapy with metformin plus colesevelam improves lipoprotein particles in patients with early type 2 diabetes mellitus

The bile acid sequestrant colesevelam has been shown to significantly reduce low-density lipoprotein particle concentration (LDL-P) in adults with primary hyperlipidemia or type 2 diabetes mellitus (T2DM). To assess the effect of initial combination therapy with metformin plus colesevelam on lipoprotein particles in patients with T2DM (secondary efficacy variables). This 16-week, randomized, double-blind, placebo-controlled study enrolled drug-naïve adults with T2DM, glycated hemoglobin 6.5%-10.0%, low-density lipoprotein cholesterol (LDL-C)≥100 mg/dL, and triglycerides <500 mg/dL. Patients were randomized 1:1 to either open-label metformin (titrated to 1700 mg/day) plus double-blind colesevelam 3.75 g/day or open-label metformin plus double-blind placebo. In total, 286 patients were randomized (metformin plus colesevelam [n= 145]; metformin plus placebo [n= 141]). Compared with metformin plus placebo, the combination of metformin plus colesevelam significantly reduced LDL-C (mean treatment difference: -16.3%), total cholesterol (-6.1%), non-high-density lipoprotein cholesterol (-8.3%), and apolipoprotein (apo) B (-8.0%) and significantly increased triglycerides (median treatment difference: 18.6%) and apoA-I (mean treatment difference: 4.4%; all P < .001). Metformin plus colesevelam significantly reduced total LDL-P (mean treatment difference: absolute change -186 nmol/L [percent change -11.7%]; both P < .0001), largely attributable to a reduction in small LDL-P, and increased total very-low-density lipoprotein particle concentration (mean treatment difference: absolute change 6 nmol/L; P= .03 [percent change 8.3%; P = .06]) and total high-density lipoprotein particle concentration (1.0 μmol/L; P = .03 [4.5%; P = .01]) versus metformin plus placebo. Initial combination therapy with metformin plus colesevelam improved the atherogenic lipoprotein profile of patients with early T2DM by significantly reducing LDL-P. ClinicalTrials.gov identifier: NCT00570739.

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.

Lipoprotein cholesterol distribution and LDL particle size is proatherogenic in Mexican Americans with metabolic syndrome

To evaluate the association between components of metabolic syndrome (MS) and lipoprotein cholesterol (C) distribution in Mexican‐American adults, the distribution of C in LDL and HDL subfractions and the presence of MS were assessed in 72 healthy participants (25 male, 47 female; age=37±9 y; BMI=28.9±5.3 kg/m2; fasting glucose[FG]=94±14 mg/dL; total‐C=181±36 mg/dL; LDL‐C=115±31 mg/dL; HDL‐C=43±11 mg/dL; triglycerides [TG]=114±61 mg/dL). Participants with MS had smaller LDL particles (267±3Å vs. 271±3Å; p&lt;0.0001) and 2.8 times more C in smaller LDL particles (p=0.001) than those without MS. The number of MS components was inversely correlated with LDL particle size (r=−0.322, p=0.006) and the percentage of HDL‐C in large HDL particles (r=−0.518, p&lt;0.001), and positively correlated with the percentage of total‐C in small LDL particles (r=−0.298, p=0.011). Participants with TG&gt;150mg/dL had smaller LDL particles (266±3Å vs. 271±2Å; p&lt;0.001), less HDL‐C in large HDL particles (15±4% vs. 24±7%; p&lt;0.001), and more HDL‐C in small HDL particles (29±6% vs. 20±7%; p&lt;0.001) than those with normal TG. Participants with elevated waist circumference had 20% less HDL‐C in large HDL particles (20±5% vs. 24±8%; p=0.012). These data suggest that of the components of the MS, elevated TG may be a greater contributor to having a more atherogenic lipoprotein profile among Mexican Americans. Funded by Arizona State University.

LXRβ activation increases intestinal cholesterol absorption, leading to an atherogenic lipoprotein profile

Liver X receptors (LXRs) are essential for the regulation of intestinal cholesterol absorption. Because two isoforms exist, LXRα and LXRβ, with overlapping but not identical functions, we investigated whether LXRα and LXRβ exert different effects on intestinal cholesterol absorption. Wild-type (WT), LXRα(-/-) and LXRβ(-/-) mice were fed control diet, 0.2% cholesterol-enriched diet or 0.2% cholesterol-enriched diet plus the LXR agonist GW3965. When fed a control diet, all three genotypes showed similar levels of cholesterol absorption. Of interest, a significant increase in cholesterol absorption was found in the LXRα(-/-) mice, but not in the WT or LXRβ(-/-) animals, when fed a diet enriched with 0.2% cholesterol or 0.2% cholesterol + GW3965. Reduced faecal neutral sterol excretion and a hydrophobic bile acid profile were also observed in LXRα(-/-) mice. Greater increases in the apolipoprotein (apo)B-containing lipoproteins in serum were seen in the LXRα(-/-) mice. A 0.2% cholesterol +GW3965 diet suppressed intestinal Npc1l1 protein expression to the same extent for all genotypes, while Abca1 and Abcg5 were elevated to the same degree. In the intestine, LXRα and LXRβ seem to exert similar effects on expression of cholesterol-transporting proteins such as Npc1l1. Selective activation of LXRβ may generate effects such as increased cholesterol absorption and elevated serum levels of apoB-containing lipoproteins, which seem to be counteracted by LXRα. Therefore, an intestinal LXRβ-specific pathway might exist in terms of cholesterol transportation in addition to the main pathway.

Abdominal Obesity and Metabolic Alterations in the Menopausal Transition

The prevalence of overweight and obesity is strikingly increasing worldwide. Obesity is a major risk factor for non–insulin-dependent diabetes mellitus, cardiovascular diseases, and cancer, and is also associated with various psychosocial consequences. Menopausal transition is associated with unfavorable changes in body composition and abdominal fat deposition, which is accompanied by an increment of insulin resistance/hyperinsulinemia, a decrease in sex hormone-binding globulin levels and, consequently, an increase in free testosterone and greater androgenicity. Central body fat also correlates with deleterious changes in adipokines and inflammation markers like leptin, C-reactive protein, and adiponectin. In addition, the greater deposition of visceral fat in the menopausal transition contributes to the development of an atherogenic lipoprotein profile, which includes high triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations, as well as an increment of small dense low-density lipoprotein (LDL) subfraction, intermediate density lipoproteins (IDL), apolipoprotein (apo) B/apo A-I ratio and lipoprotein(a).

Abstract 012: Psoriasis is Associated With Atherogenic Lipoprotein Particle Concentration and Size Independent of Cardiometabolic Risk Factors

Introduction: Psoriasis is a chronic inflammatory skin disease associated with increased risk of cardiovascular disease (CVD). We have previously shown that psoriasis is associated with atherogenic lipoprotein particle concentration and size. However, it is unknown whether this association is independent of traditional CVD risk factors or insulin resistance (IR). Methods: We prospectively enrolled a consecutive sample of patients with psoriasis (n=122) and compared cardiometabolic risk factors with an asymptomatic sample without psoriasis from our practice (n=129). Fasting lipids, insulin, glucose were measured by standard assays, and lipoprotein concentration and size were measured by nuclear magnetic resonance (NMR) (LipoScience, North Carolina). HOMA-IR, an estimation of IR, was calculated by standard methods. Multivariable linear regression for adjusted models was performed using STATA12 software. Results: LDL-C and HDL-C were lower in psoriasis compared to controls [106.9 mg/dL (90-132.5) vs 128 (110.2-145.6), p&lt;0.01 and 43 mg/dL (36-58) vs 50 (42-62), p&lt;0.01] with no difference in triglycerides. However, NMR showed an atherogenic profile in psoriasis similar to that observed in diabetes, with significant increase in LDL [1210.5 (1002-1498) vs 1115 (935-1291), p=0.03] particle concentration with a concomitant decrease in LDL size [20.6 (20.3-21.1) vs 21.3 (20.6-21.1), p&lt;0.001] even after adjusting for obesity, tobacco use, hypertension, lipids, and HOMA-IR (p=0.001). An increase in VLDL particle concentration was also seen before [61.9 (38.3-95.3) vs 53.4 (30.4-84.5), p=0.05] and after adjusting for cardiometabolic risk factors (p=0.018). Conclusions: Despite normal lipids, we demonstrate a more atherogenic lipoprotein profile by NMR in psoriasis compared to healthy controls after adjustment for CVD risk factors and IR. These findings suggest that traditional risk factor analysis and lipid testing may not ideally capture the increased CVD risk observed in psoriasis.

Reduced growth hormone secretion in obesity is associated with smaller LDL and HDL particle size

Reduced growth hormone (GH) secretion is observed in obesity and may contribute to increases in cardiovascular disease (CVD) risk. Lipoprotein characteristics including increased small dense low-density lipoprotein (LDL) particles are known independent risk factors for CVD. We hypothesized that reduced GH secretion in obesity would be associated with a more atherogenic lipid profile including increased small dense LDL particles. To evaluate this hypothesis, we studied 102 normal weight and obese men and women using standard GH stimulation testing to assess GH secretory capacity and performed comprehensive lipoprotein analyses including determination of lipoprotein particle size and subclass concentrations using proton NMR spectroscopy. Obese subjects were stratified into reduced or sufficient GH secretion based on the median peak-stimulated GH (≤6·25 μg/l). Obese subjects with reduced GH secretion (n = 35) demonstrated a smaller mean LDL and HDL particle size in comparison to normal weight subjects (n = 33) or obese subjects with sufficient GH (n = 34) by ANOVA (P < 0·0001). Univariate analyses demonstrated peak-stimulated GH was positively associated with LDL (r = 0·50; P < 0·0001) and HDL (r = 0·57; P < 0·0001), but not VLDL (P = 0·06) particle size. Multivariate regression analysis controlling for age, gender, race, ethnicity, tobacco, use of lipid-lowering medication, BMI and HOMA demonstrated peak-stimulated GH remained significantly associated with LDL particle size (β = 0·01; P = 0·01; R(2) = 0·42; P < 0·0001 for overall model) and HDL particle size (β = 0·008; P = 0·001; R(2) = 0·44; P < 0·0001 for overall model). These results suggest reduced peak-stimulated GH in obesity is independently associated with a more atherogenic lipoprotein profile defined in terms of particle size.

Maternal and fetal cord blood lipids in intrauterine growth restriction

Small for gestational age neonates (SGA) could be subdivided into two groups according to the underlying causes leading to low birth weight. Intrauterine growth restriction (IUGR) is a pathologic condition with diminished growth velocity and fetal compromised well-being, while non-growth restricted SGA neonates are constitutionally (genetically determined) small. Antenatal sonographic measurements are used to differentiate these two subgroups. Maternal metabolic changes contribute to the pathogenesis of IUGR. A disturbed lipid metabolism and cholesterol supply might affect the fetus, with consequences for fetal programming of cardiovascular diseases. We evaluated fetal serum lipids and hypothesized a more atherogenic lipoprotein profile in IUGR fetuses. Umbilical cord serum lipids and oxidative modified, low-density lipoprotein (oxLDL) concentrations were measured by colorimetric enzymatic measurements, or by ELISA. Values of IUGR (n=36) and constitutionally small for gestational age neonates (SGA, n=22) were compared with those of healthy, adequate for gestational age, born neonates (CN, n=97). SAS-statistic software was used and two-way ANOVA was adjusted for gestational age at delivery. Fetal high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) concentrations were found to be lower in the IUGR compared to the CN and SGA groups (HDL-C: P<0.001, TC: P<0.01). Atherogenic indices, including the oxLDL/LDL-C ratio, were increased in the IUGR compared to the CN group (oxLDL/LDL-C ratio: P<0.001). Our results support the hypothesis of a disturbed cholesterol supply in IUGR fetuses. Born SGA has been shown to be a risk factor for developing cardiovascular disease later in life. Since HDL-C has anti-inflammatory properties, a reduced HDL-C during fetal development, and an increase in atherogenic indices, might provide a link to this observation in IUGR fetuses.

Postprandial lipemia in pre- and postmenopausal women

Background and Objective:The increased risk for coronary artery disease observed in postmenopausal (PoW) women is partly explained by a more atherogenic lipoprotein profile. Moreover, natural menopause has been associated with an altered postprandial lipid profile. This study was designed to test the hypothesis that young premenopausal (PrW) and PoW may be independently associated with postprandial lipemia and indirectly associated with atherosclerosis.Patients and Methods:A total of 46 healthy PrW and 44 healthy PoW participated in a 5-h intervention study. Blood samples were taken at the baseline and at 1, 2, 3, and 4 h after eating. Total cholesterol, LDL-cholesterol, HDL-cholesterol, fasting, and postprandial triglycerides (PPTG) were determined sequentially in blood samples.Results:PPTG presented significant higher values in PoW compared to PrW (P < 0.05), but other lipids did not significantly differ between groups. PPTG concentrations in PoW were significantly higher than in PrW (P < 0.05). There was a significant time influence (P < 0.05) in TG in PrW and PoW, while time to peak and peak concentration were significantly higher in PoW than PrW. Other lipids were also decreased more in PrW than PoW, but not significantly so. Cholesterol concentrations showed a significant reduction after 2 h, to reach values similar to the baseline after 4 h in PrW but not in PoW. HDL-cholesterol concentration was decreased more in PoW compared to PrW but it was not significant.Conclusions:Lipid postprandial response indicates a higher cardiovascular risk pattern in PoW compared to PrW.

Serum paraoxonase-3 concentration in HIV-infected patients. Evidence for a protective role against oxidation

We investigated the influence of the HIV infection on serum paraoxonase-3 (PON3) concentration and assessed the relationships with lipoprotein-associated abnormalities, immunological response, and accelerated atherosclerosis. We studied 207 HIV-infected patients and 385 healthy volunteers. Serum PON3 was determined by in-house ELISA, and PON3 distribution in lipoproteins was investigated by fast-performance liquid chromatography (FPLC). Polymorphisms of the PON3 promoter were analyzed by the Iplex Gold MassArray(TM) method. PON3 concentrations were increased (about three times) in HIV-infected patients with respect to controls (P < 0.001) and were inversely correlated with oxidized LDL levels (P = 0.038). Long-term use of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy was associated with a decrease of PON3 concentrations. In a multivariate linear regression analysis, these relationships were still strong when the main confounding covariates were considered. PON3 was mainly found in HDL in HIV-infected patients, but a substantial amount of the protein was detected in LDL particles. This study reports for the first time an important increase in serum PON3 concentrations in HIV-infected patients that is associated with their oxidative status and their treatment with NNRTI. Long-term, prospective studies are needed to confirm the possible influence of this enzyme on the course of this disease and its possible utility as an analytical biomarker.

High disaccharide intake associates with atherogenic lipoprotein profile

Increased plasma concentrations of small LDL particles denote an atherogenic lipoprotein phenotype (ALP) that is correlated with increased circulating TAG and reduced HDL-cholesterol. Principal component analyses of subfraction concentrations have previously been used in the Swedish population-based Malmö Diet and Cancer (MDC) cohort to identify three independent components, one pattern representing the ALP. The aim of the present study was to examine the associations between macronutrient intakes and the principal component representing the ALP. We examined 4301 healthy subjects (46-68 years old, 60 % women) at baseline in the MDC cohort. Dietary data were collected using a modified diet history method. Plasma lipoprotein subfractions were measured using a high-resolution ion mobility method. The principal component corresponding to the ALP was significantly associated with a higher intake of disaccharides, and inversely related to protein and alcohol consumption (P < 0·001 for all). The present findings indicate that the ALP may be improved by a low intake of disaccharides, and moderate intakes of protein and alcohol.