Lipoprotein Particle Size Research Articles

Predictive associations between serum fatty acids and lipoproteins in healthy non-obese Norwegians: implications for cardiovascular health.

A battery of methods for multivariate data analysis has been used to assess the associations between concentrations of fatty acids (FAs) and lipoprotein subclasses and particle size in serum for a normolipidemic population of ethnic Norwegians living in the rural Fjord region. Significant gender differences were found in the lipoprotein and FA patterns. Predictive FA patterns were revealed for lipoprotein features of importance for cardiovascular (CV) health. Thus, the subclasses of atherogenic small and very small low density lipoprotein (LDL) particles and the same subclasses of high density lipoprotein (HDL) particles were associated with a pattern of saturated FAs and mono-unsaturated C16-C18 FAs. Eicosapentaenoic acid (EPA) and the ratio of EPA to arachidonic acid (AA) had strongest associations to features that promotes CV health: (i) large average size of HDL and LDL particles, and, (ii) small average size of very low density lipoprotein (VLDL) particles. Total concentration of HDL in both genders correlated to EPA, but docosahexaenoic acid (DHA) correlated just as strongly for women. For men, docosapentaenoic acid (DPA) showed stronger association to HDL concentration than EPA. For both genders, concentration of large LDL particles showed associations to levels of EPA, but stronger to DHA and DPA. High values of EPA/AA seem to be the strongest single biomarker for good CV health in both men and women.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-015-0886-4) contains supplementary material, which is available to authorized users.

Effect of consuming novel foods consisting high oleic canola oil, barley β-glucan, and DHA on cardiovascular disease risk in humans: the CONFIDENCE (Canola Oil and Fibre with DHA Enhanced) study – protocol for a randomized controlled trial

BackgroundMetabolic syndrome (MetS) has been identified as a major contributor to the development of cardiovascular disease (CVD). Current recommendations for dietary management of people with MetS involve quantitative and qualitative modifications of food intake, such as high consumption of vegetables, fruits, and whole grain foods. The results from our previous human trials revealed the potential of the dietary components high-oleic acid canola oil (HOCO)-docosahexaenoic acid (DHA) and high molecular weight barley β-glucan individually in managing CVD risk factors. Foods with a combination of HOCO-DHA and barley β-glucan have never been tested for their effects on CVD risk. The objective is to determine the effects of consuming novel foods HOCO-DHA, and barley β-glucan on managing CVD risk factors in people with MetS.Methods/DesignWe are conducting a randomized, single-blind crossover trial with four treatment phases of 28 days each separated by a 4-week washout interval. Participants (n=35) will be provided with weight-maintaining, healthy balanced diet recommendations according to their energy requirements during the intervention periods. Participants will receive muffins and cookies as treatment foods in a random order and will consume at least one meal per day at the research center under supervision. The four treatments include muffins and cookies consisting of (1) all-purpose flour and HOCO-DHA (50 g/day); (2) barley flour (4.36 g/day of β-glucan) and a blend of sunflower oil, safflower oil, and butter as control oil (50 g/day); (3) barley flour (4.36 g/day of β-glucan) and HOCO-DHA (50 g/day; dosage of DHA would be 3 g/day); and (4) all-purpose flour and control oil (50 g/day). At the beginning and end of each phase, we will evaluate anthropometrics; systolic and diastolic blood pressure; blood lipid profile; low-density lipoprotein subfractions and particle size; 10-year Framingham CVD risk score; inflammatory status; and plasma and red blood cell fatty acid profiles, fecal microbiome, and body composition by dual-energy X-ray absorptiometry.ConclusionCholesterol synthesis will also be studied, using a stable isotope approach. The proposed study will lead to innovation of novel food products, which may result in improvement in the overall cardiovascular health of humans.Trial registrationClinical trials.gov identifier: NCT02091583. Date of registration: 12 March 2014.

Lipid metabolism in patients infected with Nef-deficient HIV-1 strain

BackgroundHIV protein Nef plays a key role in impairing cholesterol metabolism in both HIV infected and bystander cells. The existence of a small cohort of patients infected with Nef-deficient strain of HIV presented a unique opportunity to test the effect of Nef on lipid metabolism in a clinical setting. MethodsHere we report the results of a study comparing six patients infected with Nef-deficient strain of HIV (ΔNefHIV) with six treatment-naïve patients infected with wild-type HIV (WT HIV). Lipoprotein profile, size and functionality of high density lipoprotein (HDL) particles as well as lipidomic and microRNA profiles of patient plasma were analyzed. ResultsWe found that patients infected with ΔNefHIV had lower proportion of subjects with plasma HDL-C levels <1 mmol/l compared to patients infected with WT HIV. Furthermore, compared to a reference group of HIV-negative subjects, there was higher abundance of smaller under-lipidated HDL particles in plasma of patients infected with WT HIV, but not in those infected with ΔNefHIV. Lipidomic analysis of plasma revealed differences in abundance of phosphatidylserine and sphingolipids between patients infected with ΔNefHIV and WT HIV. MicroRNA profiling revealed that plasma abundance of 24 miRNAs, many of those involved in regulation of lipid metabolism, was differentially regulated by WT HIV and ΔNefHIV. ConclusionOur findings are consistent with HIV protein Nef playing a significant role in pathogenesis of lipid-related metabolic complications of HIV disease.

Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduced body adiposity and Lp-PLA2 activity in overweight subjects

The effect of consumption of two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, on weight loss, body adiposity and lipoprotein-associated phospholipase A2 (Lp-PLA2) activities in overweight subjects was examined. After 12-week probiotic treatment, the probiotic group presented reductions in body weight (−0.65 ± 0.23 kg), body fat percentage (−0.57 ± 0.19%) and body fat mass (−616 ± 161 g) measured using DEXA, and L1 subcutaneous fat area (−2.68 ± 1.31 cm2) measured using CT, compared to baseline. The probiotic group exhibited greater reductions in oxidized low density lipoprotein (ox-LDL) (P < 0.001) and Lp-PLA2 (P < 0.001) and a greater increase in low density lipoprotein (LDL) particle size (P = 0.001) than the placebo. The change (△, difference from baseline) in total fat mass correlated with △ Lp-PLA2 (r = 0.480, P < 0.001), which correlated with △ ox-LDL (r = 0.537, P < 0.001). Probiotic-induced weight loss was associated with reductions in fat mass, which correlated with the changes in Lp-PLA2 activities (ClinicalTrials.gov: NCT02492698).

De novo hepatic steatosis drives atherogenic risk in liver transplantation recipients.

Nonalcoholic fatty liver disease is associated with cardiovascular disease (CVD) in the general population. Despite a high prevalence of de novo hepatic steatosis after liver transplantation (LT), there are no data exploring the association between hepatic steatosis after LT and atherogenic risk. The aim of the study was to explore the impact of hepatic steatosis on serum atherogenic markers in liver transplantation recipients (LTRs). Biomarkers of CVD risk were compared in 89 LTRs with no known history of dyslipidemia, ischemic heart disease, or graft cirrhosis. To avoid potential confounders, LTRs on oral hypoglycemic agents, exogenous insulin, corticosteroids, or lipid-lowering therapy were excluded. Only patients for whom histological assessment was available after LT were included in the study. Thirty-five LTRs had de novo hepatic steatosis after LT, whereas 54 did not. Both cohorts were similar with regards to age, sex, ethnicity, and follow-up from LT. Additionally, the traditional lipid profile was similar between the 2 cohorts. LTRs with hepatic steatosis had higher serum concentrations of small-dense low-density lipoprotein cholesterol (sdLDL-C; 34.8 ± 16.9 versus 22.7 ± 11.2 mg/dL; P < 0.001), sdLDL-C to low-density lipoprotein cholesterol ratio (32.6 ± 11.6 versus 24.6 ± 10.2; P < 0.01), small-dense low-density lipoprotein particle concentration (sdLDL-P; 770 ± 440 versus 486 ± 402 nmol/L; P < 0.01), very low density lipoprotein particle concentration (VLDL-P; 7.90 ± 7.91 versus 3.86 ± 3.18 nmol/L; P < 0.01), and very low density lipoprotein size (VLDL-size; 51.9 ± 6.4 versus 48.7 ± 6.3 nm; P = 0.06). LTRs with hepatic steatosis had higher serum insulin concentrations (27.8 ± 41.8 versus 11.7 ± 7.8 uU/mL; P < 0.01) but similar fasting glucose and hemoglobin A1c. Steatosis grade was directly related to sdLDL-C, sdLDL-P, insulin, VLDL-P, and VLDL-size. In multivariate analysis, the association between steatosis grade and sdLDL-C (β = 0.03; P = 0.029), VLDL-size (β = 0.316; P = 0.04), and low-density lipoprotein particle size (β = -0.27; P = 0.05) was independent of sex, body mass index, age, diabetes mellitus, time from transplant, and indication for LT. In conclusion, de novo hepatic steatosis after LT is associated with atherogenic lipoproteins and independent of traditional CVD risk factors.

Lipoprotein Particles in Adolescents and Young Women With PCOS Provide Insights Into Their Cardiovascular Risk.

Adult women with polycystic ovarian syndrome (PCOS) have an increased risk for cardiovascular disease, but the evidence for this is controversial in adolescents and young women with PCOS. Measurement of low-density lipoprotein (LDL) particle number, measured by nuclear magnetic resonance spectroscopy is a novel technology to assess cardiovascular risk. The objective of the study was to evaluate lipoprotein particle number and size in young women with PCOS and its relationship with insulin resistance and hyperandrogenism. This was a cross-sectional case control study. The study was conducted at a clinical research center. Women with PCOS (n = 35) and normal controls (n = 20) participated in the study. Blood samples and anthropometric measures were obtained. LDL particle size and number were measured using nuclear magnetic resonance spectroscopy. A secondary outcome was to investigate the correlation of LDL particle number with high-sensitivity C-reactive protein, waist to hip ratio, hyperandrogenism, insulin resistance, and adiponectin. Women with PCOS had higher LDL particle number when compared with healthy controls (935 ± 412 vs 735 ± 264, P = .032); LDL particle number correlated strongly with high-sensitivity C-reactive protein (r = 0.37, P = .006) and waist-to-hip (r = 0.57, P = .0003). The higher LDL particle number was driven mainly due to differences in the small LDL particle number (sLDLp), with PCOS patients having more sLDLp (348 ± 305 vs 178 ± 195, P = .015). The sLDLp correlated with the Matsuda index (r = -0.51, P = .0001), homeostasis model assessment index of insulin resistance (r = 0.41, P = .002), and adiponectin (r = -0.46, P = .0004) but not with T. Adolescent and young women with PCOS have an atherogenic lipoprotein profile suggestive of increased cardiovascular risk that appears to be driven by the degree of visceral adiposity and insulin resistance.

The effect of metformin on the lipoprotein profile and lipoprotein particle size in the carotid atherosclerosis: Metformin for insulin resistance (camera) trial

Aim: Metformin, the most widely used treatment for type 2 diabetes (T2DM), has been shown to reduce total-cholesterol, LDL-cholesterol and triglyceride levels though this relationship has typically been studied in patients with T2DM not on statin therapy. Metformin is currently being investigated for potential cardiovascular benefit in patients without T2DM. We investigated whether metformin changes the profile of lipoprotein subclasses in patients already on statin therapy.

Modification of lipoprotein and glucose metabolism, vascular inflammatory biomarkers and neuropathy after weight loss following bariatric surgery

Modification of lipoprotein and glucose metabolism, vascular inflammatory biomarkers and neuropathy after weight loss following bariatric surgery

Liposcale: A novel advanced lipoprotein test based on 2D diffusion-ordered 1H NMR spectroscopy

Aim: Determination of lipoprotein particle size and particle number using advanced lipoprotein tests (ALTs) is of particular interest since the LDL particle number has been shown to improve cardiovascular disease risk prediction. Here we present the Liposcale test, a novel ALT based on 2D diffusion-ordered 1H NMR spectroscopy.

Metabolic dysfunction in obese Hispanic women with polycystic ovary syndrome.

Are certain ethnic groups with polycystic ovary syndrome (PCOS) at increased risk of metabolic disorders? Obese Hispanic women with PCOS are at increased risk of metabolic disorders compared with age- and BMI-matched obese non-Hispanic white women with PCOS in the USA. Ethnic differences in body composition and metabolic risk are well established. PCOS is a common disorder in women of reproductive age and is associated with high rates of insulin resistance, glucose intolerance and dyslipidemia. A cross-sectional observational study was performed at an Academic Medical Center on 60 women of reproductive age with PCOS. Blood was obtained after fasting from 17 Hispanic, 22 non-Hispanic black and 21 non-Hispanic white women with PCOS who were similar in age and BMI. Anthropometric parameters, insulin, lipid and lipoprotein levels (measured by nuclear magnetic resonance) were compared between the three groups. Age and BMI did not differ between the groups. Hispanic women with PCOS had higher waist-to-hip ratio (WHR) (P = 0.02), homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.03) and a more atherogenic lipid and lipoprotein profile consisting of lower high-density lipoprotein (HDL) (P = 0.02), higher low-density lipoprotein (LDL) particle number (P = 0.02), higher very low-density lipoprotein particle (VLDL) size (P = 0.03) and lower LDL (P = 0.03) and HDL particle size (P = 0.005) compared with non-Hispanic white women. The differences in HDL, HOMA-IR, VLDL and LDL size did not persist after adjustment for WHR while differences in LDL particle number (P = 0.04) and HDL size (P = 0.01) persisted. The sample size for the three groups was small but the findings were still significant. The women were mostly obese so the ethnic differences in metabolic disorders may not apply to non-obese women with PCOS. Independent of BMI, obese, reproductive age, Hispanic women with PCOS in the USA had a greater degree of abdominal obesity, insulin resistance and dyslipidemia. Hispanic women with PCOS may benefit from more focused management of metabolic parameters. This project was supported by the following National Institutes of Health grants: K23 DK080988-01A1 to S.S. and UL1RR029879 to CTSA at University of Illinois. None of the authors report any conflict of interests.

Abstract P210: Lipoprotein Profiles in Patients With and Without Psoriasis

Introduction: Psoriasis is associated with chronically heightened systemic inflammatory tone and increased risk for cardiovascular disease. It remains to be established if the psoriatic state itself associates with dyslipidemia. Hypothesis: The lipid profile of patients with psoriasis is more atherogenic compared to disease-free control patients. Methods: The concentration and size of lipoprotein particles were measured using nuclear magnetic resonance spectroscopy in 221 patients with a diagnosis of psoriasis (53.6% men; mean age=56.6 years; mild cases=31%; moderate/severe only skin=27%; arthritis=27%)) and 689 disease-free persons matched by sex and age. We compared means of lipoprotein particle concentration and size using a univariate general linear model and adjusting for body-mass index, waist circumference, diabetes, use of lipid lowering-drugs, as well as duration/severity of psoriasis. Results: Patients with psoriasis were more overweight, had larger waist circumference, and a higher frequency of diabetes and use of lipid-lowering drugs. Total LDL particle means (nmol/L) for the psoriasis and control groups were 1436 (1378-1494) vs. 1420 (1388-1452) (P=0.4), respectively. The mean concentration of IDL was higher in patients with psoriasis compared to controls: 143.6 (130.7-156.5) vs. 106.1 (99.1-113.2), P&lt;0.01. Large and small LDL particle concentrations were similar between groups. Large VLDL/chylomicron particle concentrations (nmol/L) were higher in psoriasis patients compared to controls 6.1 (5.2-7.0) vs. 4.0 (3.6-4.5) (P&lt;0.01). Total HDL particle and subfractions were not statistically different between groups. The mean size (nm) of VLDL was higher in psoriasis patients: 50.2 (49.2-51.2) vs. 46.2 (45.6-46.7) (P&lt;0.001) for psoriasis and controls, respectively. In contrast, mean sizes of LDL and HDL particles were similar (P=0.3). Adjustment for covariates above mentioned did not change these findings. The absence/presence of arthritis did not change the results. Conclusion: Patients with psoriasis have a more atherogenic lipid profile compared to controls with higher levels of IDL and VLDL of large and small size. In addition, the greater mean size of VLDL particles in psoriasis compared to controls suggests enhanced secretion of triglyceride loaded VLDL, impaired lipolysis and impaired clearance of remnant IDL.

Liposcale: a novel advanced lipoprotein test based on 2D diffusion-ordered 1H NMR spectroscopy

Determination of lipoprotein particle size and number using advanced lipoprotein tests (ALTs) is of particular importance to improve cardiovascular risk prediction. Here we present the Liposcale test, a novel ALT based on 2D diffusion-ordered (1)H NMR spectroscopy. Our method uses diffusion coefficients to provide a direct measure of the mean particle sizes and numbers. Using 177 plasma samples from healthy individuals and the concentration of ApoB and ApoA from isolated lipoprotein fractions, our test showed a stronger correlation between the NMR-derived lipoprotein particle numbers and apolipoprotein concentrations than the LipoProfile(®) test commercialized by Liposcience. We also converted LDL particle numbers to ApoB equivalents (milligrams per deciliter) and our test yielded similar values of LDL-ApoB to the LipoProfile(®) test (absolute mean bias of 8.5 and 7.4 mg/dl, respectively). In addition, our HDL particle number values were more concordant with the calibrated values determined recently using ion mobility. Finally, principal component analysis distinguished type 2 diabetic patients with and without atherogenic dyslipidemia (AD) on a second cohort of 307 subjects characterized using the Liposcale test (area under the curve = 0.88) and showed concordant relationships between variables explaining AD. Altogether, our method provides reproducible and reliable characterization of lipoprotein particles and it is applicable to pathological states such as AD.

Effect of pistachio consumption on plasma lipoprotein subclasses in pre-diabetic subjects

Background and aimsNuts have been demonstrated to improve several cardiovascular risk factors and the lipid profile in diabetic and pre-diabetic subjects. However, analysis of conventional serum lipid profiles does not completely explain the atherogenic risk associated with pre-diabetes. We therefore investigated whether chronic consumption of pistachio modifies the lipoprotein subclasses to a healthier profile in pre-diabetic subjects. Methods and resultsRandomized cross-over clinical trial in 54 subjects with pre-diabetes. Subjects consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out. Diets were isocaloric and matched for protein, fiber and saturated fatty acids. Nuclear magnetic resonance (NMR) was performed to determine changes in plasma lipoprotein subclasses. Small low-density lipoprotein particles (sLDL-P) significantly decreased after pistachio consumption compared to the nut-free diet (P = 0.023). The non-high-density lipoprotein particles (non-HDL-P i.e. VLDL-P plus LDL-P) significantly decreased under the PD compared to CD (P = 0.041). The percentage of sHDL-P increased by 2.23% after the PD compared with a reduction of 0.08% after the CD (P = 0.014). Consequently, the overall size of HDL-P significantly decreased in the PD (P = 0.007). ConclusionChronic pistachio consumption could modify the lipoprotein particle size and subclass concentrations independently of changes in total plasma lipid profile, which may help to explain the decreased risk of cardiovascular disease and mortality associated with those individuals who frequently consumed nuts. Registration numberThis study is registered at www.clinicaltrials.gov as NCT01441921.

Lipoprotein particles and incident type 2 diabetes in the multi-ethnic study of atherosclerosis.

OBJECTIVEIn the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated associations of baseline levels of a lipoprotein-based insulin resistance (IR) index (LP-IR), IR-related lipoprotein particles, mean particle sizes, and lipids, with incident type 2 diabetes, independent of confounders, glucose, insulin, and HOMA-IR.RESEARCH DESIGN AND METHODSAmong 5,314 adults aged 45–84 years without baseline diabetes or cardiovascular disease, 656 cases of diabetes were identified during a mean follow-up of 7.7 years. Lipoprotein particle concentrations, size, and LP-IR were determined by nuclear magnetic resonance spectroscopy of stored baseline plasma. Potential effect modification, by race/ethnicity, sex, baseline use of lipid-lowering medications or hormone therapy, or glucose strata (<90, 90–99, and ≥100 mg/dL), was also evaluated.RESULTSHigher levels of LP-IR, large VLDL particles (VLDL-P), small LDL particles, triglycerides (TG), and TG–to–HDL cholesterol (HDL-C) ratio and lower levels of large HDL particles, smaller HDL and LDL size, and larger VLDL size were significantly associated with incident diabetes adjusted for confounders and glucose or insulin. These also were similar by race/ethnicity, sex, and treatment group. Associations were similar for LP-IR, large VLDL-P, mean VLDL size, TG, and TG–to–HDL-C ratio; they persisted for LP-IR, large VLDL-P, or mean VLDL size adjusted for HOMA-IR or TG–to–HDL-C ratio and glucose but not for the TG–to–HDL-C ratio adjusted for LP-IR or for HOMA-IR or insulin if adjusted for LP-IR and glucose.CONCLUSIONSAmong ethnically diverse men and women, LP-IR, large VLDL-P, large VLDL size, TG, and TG–to–HDL-C ratio were associated with incident diabetes independent of established risk factors, glucose, insulin, or HOMA-IR, as well as the use of lipid-lowering medications or hormone therapy.

Reference values for high-density lipoprotein particle size and volume by dynamic light scattering in a Brazilian population sample and their relationships with metabolic parameters

BackgroundCurrent data indicate that the size of high-density lipoprotein (HDL) may be considered an important marker for cardiovascular disease risk. We established reference values of mean HDL size and volume in an asymptomatic representative Brazilian population sample (n=590) and their associations with metabolic parameters by gender. MethodsSize and volume were determined in HDL isolated from plasma by polyethyleneglycol precipitation of apoB-containing lipoproteins and measured using the dynamic light scattering (DLS) technique. ResultsAlthough the gender and age distributions agreed with other studies, the mean HDL size reference value was slightly lower than in some other populations. Both HDL size and volume were influenced by gender and varied according to age. HDL size was associated with age and HDL-C (total population); non- white ethnicity and CETP inversely (females); HDL-C and PLTP mass (males). On the other hand, HDL volume was determined only by HDL-C (total population and in both genders) and by PLTP mass (males). ConclusionsThe reference values for mean HDL size and volume using the DLS technique were established in an asymptomatic and representative Brazilian population sample, as well as their related metabolic factors. HDL-C was a major determinant of HDL size and volume, which were differently modulated in females and in males.

Modulation of host lipid metabolism by hepatitis C virus: Role of new therapies.

It is well established that hepatitis C virus (HCV) infection and replication relies on host lipid metabolism. HCV proteins interact and associate with lipid droplets to facilitate virion assembly and production. Besides, circulating infective particles are associated with very low-density lipoprotein. On the other hand, higher serum lipid levels have been associated with sustained viral response to pegylated interferon and ribavirin therapy in chronic HCV infection, suggesting a relevant role in viral clearance for host proteins. Host and viral genetic factors play an essential role in chronic infection. Lipid metabolism is hijacked by viral infection and could determine the success of viral replication. Recently development of direct acting antiviral agents has shown a very high efficacy (> 90%) in sustained viral response rates even for cirrhotic patients and most of the viral genotypes. HCV RNA clearance induced by Sofosbuvir has been associated with an increased concentration and size of the low-density lipoprotein particles. In this review, host genetic factors, viral factors and the interaction between them will be depicted to clarify the major issues involved in viral infection and lipid metabolism.

0339: Estimation of small LDL level using the simple precipitation method in Tunisian coronary artery disease patients with and without type 2 diabetes

Small dense LDL particles (sdLDL), with greater suceptibility to oxydation, are well-recognized risk marker for coronary artery disease (CAD) and type 2 diabetes mellitus. The aim of the present study sought to separate sdLDL subfraction by heparin-magnesiun precipitation method and to evaluate the possible association of low-density lipoprotein (LDL) particle size CAD and type 2 diabetes mellitus. Forty eight CAD (with or without type 2 diabetes mellitus) patients and 51 apparently healthy subjects were included in this study. sdLDL-cholesterol (sdLDL-C) measured after heparin-magnesiun precipitation. LDL-Cholesterol (LDL-C) was calculated by the Friedwald formula and large, buoyant LDL-Cholesterol (lrgLDL-C) was estimated by subtraction. The prevalence of sdLDL was strongly related with the CAD risk level. However, large, buoyant LDL-C showed no significant decrease in CAD patients. LDL-C decreased significantly in CAD without diabetes (CADd-) when compared to controls. Its level significantly lower in CAD with diabetes (CADd+) patients with respect to healthy and to CADd-patients. Small density LDL-C increased significantly in coronary patients (with or without diabetes). However, lrgLDL-C was significantly decreased only in (CADd+) group compared to controls (0.73±0.02 vs 2.02±0.04; p= 0.03 respectively). A negative correlation (r=–0.22, p=0.03) between TG and sdLDL-C levels was observed when all groups are geathred, and was not found in controls and CAD patients (with or without diabetes). No correlation could be evidenced between HDL-C and sdLDL-C concentrations in all groups nor in CAD group. elevated sdLDL-C level may contribute to atherosclerosis that renforce the developement of coronaropathy. The decrease of lrgLDL seems to be attribuated to diabetes mellitus rather than to CAD.

Low-density-lipoprotein particle size predicts a poor outcome in patients with atherothrombotic stroke.

Background and PurposeLow-density lipoprotein (LDL) particle size is considered to be one of the more important cardiovascular risk factors, and small LDL particles are known to have atherogenic potential. The aim of this study was to determine whether LDL particle size is associated with stroke severity and functional outcome in patients with atherothrombotic stroke.MethodsBetween January 2009 and May 2011, 248 patients with first-episode cerebral infarction who were admitted to our hospital within 7 days after symptom onset were prospectively enrolled. LDL particle size was measured using the nondenaturing polyacrylamide gradient gel electrophoresis assay. Stroke severity was assessed by applying the National Institutes of Health Stroke Scale (NIHSS) at admission. Functional outcome was investigated at 3 months after the index stroke using the modified Rankin Scale (mRS), and poor functional outcome was defined as an mRS score of ≥3.ResultsThe LDL particle size in the 248 patients was 25.9±0.9 nm (mean±SD). LDL particle size was inversely correlated with the degree of cerebral artery stenosis (p=0.010). Multinomial multivariate logistic analysis revealed that after adjustment for age, sex, and variables with p<0.1 in univariate analysis, LDL particle size was independently and inversely associated with stroke severity (NIHSS score ≥5; reference, NIHSS score 0-2; odds ratio=0.38, p=0.028) and poor functional outcome (odds ratio=0.44, p=0.038).ConclusionsThe results of this study demonstrate that small LDL particles are independently correlated with stroke outcomes. LDL particle size is thus a potential biomarker for the prognosis of atherothrombotic stroke.

Characterization of lipid composition and high-density lipoprotein function in HIV-infected individuals on stable antiretroviral regimens.

There is an increase in the cardiovascular disease (CVD) morbidity in individuals infected with HIV that may be due to inflammatory lipid modulation not captured by traditional lipid measures. The objective of this study was to perform advanced lipoprotein phenotyping inclusive of the high-density lipoprotein (HDL) cholesterol efflux capacity and lipoprotein particle concentration and size in a well-phenotyped group of 118 patients infected with HIV. We used simple and multivariable analyses to determine the associations between advanced lipoprotein parameters and known cardiometabolic risk factors. Participants were on stable antiretroviral therapy (ART) and had benign traditional lipid panels [median total cholesterol, low-density lipoprotein (LDL)-C, HDL-C, and triglycerides of 178 mg/dl, 108 mg/dl, 44 mg/dl, and 122.5 mg/dl, respectively]. However, advanced lipoprotein phenotyping demonstrated an elevation of LDL particle number (median of 1,233 nmol/liter) and a decrease in LDL size (median of 20.4 nm), along with a decrease in protective, large HDL particles (median of 3.15 μmol/liter) and reduced HDL cholesterol efflux capacity in comparison to controls of other studies. HDL cholesterol efflux capacity was associated with HDL levels (β=0.395, p<0.001), small LDL particle concentration (β=-0.198, p=0.031), insulin sensitivity by the Matsuda index (β=0.218, p=0.029), and the Framingham Risk Score (β=-0.184, p=0.046). We demonstrate an atherogenic lipoprotein profile by NMR spectroscopy and HDL efflux measurement in a group of HIV-infected patients on stable ART with normal lipid panels.

Inflammation, adiposity, and atherogenic dyslipidemia in rheumatoid arthritis: is there a paradoxical relationship?

Dyslipidemia is highly prevalent in rheumatoid arthritis (RA) and appears to be present very early in the RA disease process, in some studies even before a diagnosis of clinical RA has been made. The association between lipid measures and the risk of cardiovascular disease (CVD) in RA appears to be paradoxical, whereby lower levels of total cholesterol (TC), low-density lipoprotein (LDL-C), and atherogenic ratios are associated with higher CVD risk. This may be due to the lipid-lowering effects of RA-related systemic inflammation. Therefore, standard CVD risk calculators have been shown to underperform in RA. Data also suggest that lipoprotein particle sizes and the apolipoprotein cargo of lipoproteins skew toward atherogenic dyslipidemia in RA and may contribute to the initiation and progression of atherosclerosis. Inflammatory burden in RA may also alter the anti-inflammatory and atheroprotective roles associated with high-density lipoprotein cholesterol (HDL-C). Adipose tissue is quantitatively increased in RA patients compared with matched non-RA controls and may be more inflamed and metabolically dysfunctional compared with an otherwise similar non-RA patient. In vitro, animal, and a handful of non-RA human, studies suggest that inflamed, metabolically dysfunctional adipose tissue contributes directly to lower HDL-C levels. In turn, lower HDL-C that has been altered functionally by inflammation may lead to expanded adipose mass and further adipose dysfunction and inflammation. In the last part of this review, we speculate how the RA disease state may recapitulate these processes.