LDL Particle Size Research Articles

Association of lecithin-cholesterol acyltransferase activity measured as a serum cholesterol esterification rate and low-density lipoprotein heterogeneity with cardiovascular risk: a cross-sectional study.

The cholesterol-esterifying enzyme, lecithin-cholesterol acyltransferase (LCAT), is believed to play a key role in reverse cholesterol transport. However, recent investigations have demonstrated that higher LCAT activity levels increase the formation of triglyceride (TG)-rich lipoproteins (TRLs) and atherogenesis. We hypothesized that higher LCAT activity measured as a serum cholesterol esterification rate by the endogenous substrate method might increase the formation of TRLs and thereby alter low-density lipoprotein (LDL) heterogeneity. The estimated LDL particle size [relative LDL migration (LDL-Rm)] was measured by polyacrylamide gel electrophoresis with the LipoPhor system (Joko, Tokyo, Japan) in 538 consecutive patients with at least risk factor for atherosclerosis. Multivariate regression analysis after adjustments for traditional risk factors identified elevated TRL-related marker (TG, remnant-like particle cholesterol, apolipoprotein C-II, and apolipoprotein C-III) levels as independent predictors of smaller-sized LDL particle size, both in the overall subject population and in the subset of patients with serum LDL cholesterol levels of <100mg/dL. Area under the receiver operating characteristic curve of the LCAT activity (0.79; sensitivity 60%; specificity 84.8%) was observed for the evaluation of the indicators of an LDL-Rm value of ≥0.40, which suggests the presence of large amounts of small-dense LDL. The results lend support to the hypothesis that increased LCAT activity may be associated with increased formation of TRLs, leading to a reduction in LDL particle size. Therefore, to reduce the risk of atherosclerotic cardiovascular disease, it may be of importance to pay attention not only to a quantitative change in the serum LDL-C, but also to the LCAT activity which is possibly associated with LDL heterogeneity.

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.

Inter‐relationship Between the In vivo Metabolism of Apolipoprotein B100‐Containing Lipoproteins and LDL Particle Size and LDL Particle Number

Studies have shown that small dense LDL particles confer an increased risk of coronary heart disease (CHD) compared with large LDL. LDL particle number is also an important risk factor for CHD.The objective was to investigate the inter‐relationship between the in vivo kinetics of apolipoprotein (apo) B100‐containing lipoproteins and LDL particle size (LDLsi) and LDL particle number (LDL‐apoB).This analysis is based on data from 154 male and female subjects among whom in vivo lipoprotein kinetics were investigated using a bolus/infusion of D3‐leucine. LDLsi was assessed by non‐denaturing polyacrylamide gradient gel electrophoresis. Participants' mean age (±SD) was 44.7±12.6 yrs. Mean body mass index (BMI) and triglyceride levels were 28.6±4.7 kg/m2 and 1.97±1.4 mmol/l respectively.LDLsi correlated positively with plasma adiponectin levels (age and BMI‐adjusted Spearman r=0.41, P&lt;0.001) and the fractional catabolic rate (FCR) of VLDL‐apoB (r=0.43, P&lt;0.001) and negatively with plasma TG (r=‐0.42 P&lt;0.001) and the pool size of VLDL‐apoB (r=‐0.38, P&lt;0.001). Plasma LDL‐apoB levels correlated positively with the production rate of VLDL‐apoB (r=0.27, P=0.006) and negatively LDL‐apoB FCR (r=‐0.59, P&lt;0.001). LDL‐apoB showed no correlation with plasma TG (r=0.07, P=0.47), LDLsi (r=0.18, P=0.08) and adiponectin (r=‐0.02, P=0.82).These data suggest that LDL size and LDL particle number are determined by distinct metabolic pathways.Funding provided by the Canadian Institutes of Health Research and the Chair of Nutrition, Université Laval

EFFECT OF LOW GLYCEMIC INDEX DIET ON APOLIPOPROTEIN B AND LDL PARTICLE SIZE

BackgroundApolipoprotein B (Apo B) and small LDL particles have been strongly associated with increased coronary artery disease while low glycemic index diets (GI) may reduce risk. We have therefore assessed the effect of consumption of a low GI diet on Apo B and LDL particle size.Methods155 type 2 diabetic subjects treated with antihyperglycemic agents were randomized and completed either 6 months of high fiber or low glycemic index dietary advice in a parallel design. Serum samples were obtained pre‐treatment and at the end of the 6 month study period.ResultsThere was no significant treatment difference in Apo B but a significant reduction in estimated small dense LDL cholesterol (sdLDL‐C) on the low GI diet by ‐0.15 ± 0.08 mmol/L compared to the high fiber diet (p=0.048). No significant treatment differences were seen in LDL particle size distribution. Dietary glycemic load, not glycemic index, correlated positively to serum levels of sdLDL‐c (Rho=0.17, p=0.036), while correlated negatively with serum levels of medium LDL particles (Rho=‐0.17, p=0.042) and large LDL particles (Rho=‐0.18, p=0.026).ConclusionThese findings suggest a benefit of low glycemic index diets in reduction of sdLDL‐c levels in type 2 diabetes.Funding Canadian Institutes of Health Research, Canada Research Chair Endowment of the Federal Government of Canada, and Barilla (Italy).

The Impact of Virgin Coconut and Safflower Oils on Lipids and Cytokines in Postmenopausal Women

12 women (58.8+3.7 yr, 26.4+4.6 kg/m2) were recruited for a randomized cross‐over study. They consumed 30g virgin coconut oil (CO) or high‐oleic safflower oil (SO) for 28 days (28‐d washout period between oils, 28 d of food records). Diet was not altered. A lipid panel and cytokines (proinflammatory: IL‐1β, IL‐6, and TNF‐α &amp; anti‐inflammatory: IL10) were obtained pre/post each oil intervention after 12‐hr fast. Data were analyzed using SPSS. MIXED ANOVA showed no intervention effect. Comparisons were analyzed using paired t‐test. Results showed CO significantly raised total cholesterol, TC (+17.0+22.0 mg/dL), low‐density lipoprotein, LDL (+12.1+16.0 mg/dL) &amp; high‐density lipoprotein, HDL (+6.3+7.1 mg/dL) (all p&lt;0.05) but lowered triglycerides, TG (‐8.6+32.1 mg/dL, p=NS). SO lowered TC (‐5.2+15.7 mg/dL), LDL (‐4.9 + 12.5 mg/dL), HDL (‐1.9+5.3 mg/dL), and increased TG (+8.0+48.4) but changes were not significant. TC and HDL were significantly different between test oils, p&lt;0.05. The TC/HDL ratio change showed a neutral effect of both CO and SO, Δ pre/post each= 0 mg/dL. Cytokines results varied. One person had adverse reactions to CO &amp; increased inflammation. CO decreased IL‐1β (cytokine indicative for neurological degeneration) for each person who had a detected sample. CO and SO varied in their impact on other cytokines on an individual basis, some showing increased inflammation, others decreasing inflammation in no consistent manner. Both CO &amp; SO had a neutral impact on lipids. The varied nature of inflammatory markers suggest that there may be epigenetic interactions. More research needs to be conducted to evaluate LDL particle size. Larger sample sizes are needed to determine impact on cytokines before recommendations can be made.

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.

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.

Systemic Inflammatory Markers Are Closely Associated with Atherogenic Lipoprotein Subfractions in Patients Undergoing Coronary Angiography.

Objective. To investigate the relationship between inflammatory markers and atherogenic lipoprotein subfractions. Methods. We studied 520 eligible subjects who were not receiving any lipid-lowering therapy. The inflammatory markers including white blood cell (WBC) count, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR), and D-dimer were measured. A multimarker inflammatory index was developed. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) separation processes were performed using Lipoprint System. Results. In age- and sex-adjusted analysis, several inflammatory markers (WBC count, hs-CRP, fibrinogen, and ESR) were positively related to circulating non-HDL cholesterol and remnant cholesterol (p < 0.05, all). Among lipoprotein subfractions, we observed a positive association of inflammatory markers with very low-density lipoprotein cholesterol, small LDL cholesterol, and LDL score (p < 0.05, all). Meanwhile, a negative association was detected between inflammatory markers and mean LDL particle size (p < 0.05) or large HDL cholesterol (p < 0.05). Moreover, we found that the relationships between multimarker index quartiles and small LDL cholesterol, LDL score, and mean LDL particle size were slightly stronger in patients with CAD. Conclusions. Systemic inflammatory markers are positively correlated with small LDL cholesterol and LDL score while being negatively linked with mean LDL particle size and large HDL cholesterol, highlighting the potential contribution to increased cardiovascular risk.

Relation of plasma PCSK9 levels to lipoprotein subfractions in patients with stable coronary artery disease.

BackgroundPlasma PCSK9 levels was positively associated with low-density lipoprotein (LDL) cholesterol (LDL-C) and atherosclerosis, while PCSK9 may also be implicated in the metabolism of lipoprotein subfractions. The study was to examine the association of plasma PCSK9 with lipoprotein subfractions in patients with stable coronary artery disease (CAD).MethodsA total of 281 consecutive, stable CAD patients who were not treated with lipid-lowering drugs were enrolled. The baseline clinical characteristics were collected, the plasma PCSK9 levels were determined using ELISA, and the LDL and high-density lipoprotein (HDL) subfractions were analyzed by Lipoprint System. The association of plasma PCSK9 levels with the lipoprotein subfractions was investigated.ResultsIn the overall population, plasma PCSK9 levels were positively associated with the concentration of LDL-C, intermediate LDL-C, small LDL-C, and LDL score, while negatively correlated with mean LDL particle size. PCSK9 levels were positively associated with the concentration of HDL-C, intermediate HDL-C and small HDL-C. Multivariable regression analysis revealed that the plasma PCSK9 levels were significantly and independently associated with the concentration of intermediate LDL-C (β = 0.152, p = 0.013), small LDL-C (β = 0.179, p = 0.004), LDL score (β = 0.121, p = 0.043), and mean LDL particle size (β = -0.130, p = 0.035), while not HDL subfractions. Interestingly, when investigated in male and female patients separately, these relationships were only found in male but not in female, and the small HDL-C exhibited an association with PCSK9 levels in male patients (β = 0.149, p = 0.045).ConclusionsPCSK9 levels were independently associated with the changes of lipoprotein subfractions, suggesting a potential interaction between PCSK9 and lipoprotein subfractions in CAD.

Effects of icosapent ethyl on lipoprotein particle concentration and size in statin-treated patients with persistent high triglycerides (the ANCHOR Study)

Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid ethyl ester approved at a dose of 4 g/day as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe hypertriglyceridemia (TG ≥ 500 mg/dL). In this prespecified exploratory analysis from the ANCHOR study of patients at high cardiovascular risk with TG ≥ 200 and <500 mg/dL despite statin control of low-density lipoprotein cholesterol, we assessed the effects of IPE on lipoprotein particle concentration and size and examined correlations of atherogenic particles with apolipoprotein B (ApoB). Nuclear magnetic resonance spectroscopy was used to measure lipoprotein particle concentration and size. Compared with placebo (n = 211), IPE 4 g/day (n = 216) significantly reduced concentrations of: total (12.2%, P = .0002), large (46.4%, P < .0001), and medium (12.1%, P = .0068) very-low-density lipoprotein (VLDL) particles; total (7.7%, P = .0017) and small (13.5%, P < .0001) LDL particles; and total (7.4%, P < .0001) and large (31.0%, P < .0001) high-density lipoprotein particles. Atherogenic lipoprotein particles (total VLDL and total LDL) correlated with ApoB at baseline (R(2) = 0.57) and week 12 (R(2) = 0.65) as did total LDL particle concentration at baseline (R(2) = 0.53) and week 12 (R(2) = 0.59). Compared with placebo, IPE 4 g/day significantly reduced VLDL (7.7%, P < .0001) and high-density lipoprotein (1.2%, P = .0014) particle sizes with a modest but significant increase in LDL particle size (0.5%, P = .0031). Compared with placebo, treatment with IPE 4 g/day for 12 weeks reduced key atherogenic lipoprotein particle concentrations. At both baseline and end of study, atherogenic lipoprotein concentrations correlated with ApoB.

Discordance between apolipoprotein B and low-density lipoprotein particle number is associated with insulin resistance in clinical practice

Discordance between measures of atherogenic lipoprotein particle number (apolipoprotein B [ApoB] and low-density lipoprotein [LDL] particle number by nuclear magnetic resonance spectroscopy [LDL-PNMR]) is not well understood. Appropriate treatment considerations in such cases are unclear. To assess discordance between apoB determined by immunoassay and LDL-PNMR in routine clinical practice, and to characterize biomarker profiles and other clinical characteristics of patients identified as discordant. Two retrospective cohorts were evaluated. First, 412,013 patients with laboratory testing performed by Health Diagnostic Laboratory, Inc., as part of routine care; and second, 1411 consecutive patients presenting for risk assessment/reduction at 6 US outpatient clinics. Discordance was quantified as a percentile difference (LDL-PNMR percentile - apoB percentile) and attainment of percentile cutpoints (LDL-PNMR≥1073nmol/L or apoB≥69mg/dL). A wide range of cardiovascular risk factors were compared. ApoB and LDL-PNMR values were highly correlated (R(2)=0.79), although substantial discordance was observed. Similar numbers of patients were identified as at-risk by LDL-PNMR when apoB levels were < 69mg/dL (5%-6%) and by apoB values when LDL-PNMR was <1073nmol/L (6%-7%). Discordance (LDL-PNMR>apoB) was associated with insulin resistance, smaller LDL particle size, increased systemic inflammation, and low circulating levels of "traditional" lipids, whereas discordance (apoB>LDL-PNMR) was associated with larger LDL particle size, and elevated levels of lipoprotein(a) and lipoprotein-associated phospholipase A2 (Lp-PLA2). Discordance between apoB and LDL-PNMR in routine clinical practice is more widespread than currently recognized and may be associated with insulin resistance.

Abstract 17805: Association of LpPLA2 with Lipoprotein Subclasses, Inflammation, Atherosclerosis &amp; Endothelial Dysfunction in a Web-Based Lifestyle Intervention Study: Baptist Employee Healthy Heart Study (BEHHS)

INTRODUCTION: A recent meta-analysis demonstrated that Lipoprotein-associated phospholipase A 2 (LpPLA 2 ) activity is associated with CVD events. However, the mechanisms which mediate this risk are poorly established. This study aims to assess the cross-sectional association between LpPLA 2 and components of an advanced lipid panel, subclinical CVD and markers of inflammation. METHODS: The Baptist Employee Healthy Heart Study (BEHHS) is an ongoing study examining the effect of web-based interventions on reducing CVD risk in individuals with metabolic syndrome &amp; type II diabetes mellitus. Cardio IQ™ Ion Mobility lipoprotein fractionation was utilized for advanced lipid subclass measurement resulting in direct quantification of particles in each lipoprotein sub-class fraction. Endothelial function was assessed using endoPAT2000 (Itamar, Israel) and individuals older than 35 years had CT scan for coronary artery calcium (CAC). LpPLA 2 was measured by Enzyme-linked Immunosorbent Assay (ELISA). RESULTS: The population consisted of 182 individuals, 74% female with a mean age of 51±10 years (range 25 - 72). Overall the median plasma LpPLA 2 level was 199 ng/mL. In univariate analyses, there was a significant association with several lipid subclasses and with hs-CRP. After adjusting for risk factors, LpPLA 2 was independently associated with LDL-c and LDL particle size, Large LDL subclass A, small IDL, small, medium and large VLDL, and with hs-CRP. On the other hand there was no association between LpPLA 2 mass and HOMA-IR, reactive hyperemia index or presence of CAC. CONCLUSIONS: LpPLA 2 is significantly associated with several lipoprotein sub-classes and with systemic inflammation without affecting vascular endothelial function or atherosclerosis. Further studies are required to determine if lifestyle interventions affect LpPLA2 and how this may translate to reduced systemic inflammation and an improvement in cardiometabolic profile.

Abstract 19088: Independent Association of Lipoprotein Sub-fractions by Ion Mobility Analysis with Anthropometric and Ectopic Visceral fat on Cardiac CT Examinations in a High risk Population: The Baptist Employee Healthy Heart Study (BEHHS)

Introduction: Visceral adiposity is associated with increased CVD risk. Ectopic fat deposition is linked with lipotoxicity, metabolic derangement, insulin resistance, and atherosclerosis. The lipoprotein(LP) subclasses are established risk markers for CVD mortality. We evaluated for the association of ectopic visceral fat measures [pericardial (PCF), Epicardial (EPC)], traditional adiposity measures [waist: hip ratio (WHR), Body Mass index (BMI), waist circumference (WC)] and the LP subclasses. Methods: The Baptist Employee Healthy Heart Study (BEHHS) an ongoing study examines the effect of web based interventions on reducing CVD risk in subjects with metabolic syndrome and type II diabetes mellitus. We measured PCF and EPC adipose tissue volumes from the 16-slice multi-detector computed tomography (MDCT) (GE AWW 3D Workstation). Cardio IQ™ Ion Mobility LP fractionation was utilized for advanced lipid subclass measurement resulting in direct quantification of particles in each LP sub-class fraction. Results: The population had 182 participants, 74% women, 49% Hispanic, mean age of 52 ± 9 years. The median PCF volume was 130 (97-166) cc, EPC volume 112(78-265) cc, mean WC 105±15 cm, BMI 34±6 kg/m2 ,WHR was 0.94 (SD 0.09). There was no correlation between BMI, and WC with any of the LP. WHR was significantly correlated with LDL particle size LDL large (A), , IDL small, and HDL large, see table 1. These associations were not significant in multivariate regression analysis. On the other hand PCF and ECP were significantly correlated with a wide spectrum of the LPs. After an adjusted robust regression, they remained significantly associated with IDL(large), LDL(total), VLDL(small), VLDL(medium) and VLDL(large). Conclusion: This demonstrates association between the ectopic adiposity and LP subclasses compared to traditional obesity measures. Further follow-up is needed to assess the interplay of lifestyle intervention in improving cardiometabolic profile

Participation in a Social-Support Physical Activity Intervention Modestly Improves Lipoprotein Cholesterol Distribution Among Postpartum Sedentary Hispanic Women.

The effects of moderate intensity walking on lipoprotein remodeling in postpartum Hispanic women are unknown. Sedentary postpartum Hispanic women (28.2 ± 5.6 y; BMI = 29.3 ± 3.3 kg/m2) participating in a social support physical activity (PA) intervention, were randomly assigned to a 12-month walking program (walkers; n = 22; target 150 min/wk, moderate intensity) or a control group (nonwalkers; n = 22). Fasting lipids and cholesterol distribution within low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles were measured at baseline (BL), 6 months, and 12 months. Walkers had an 11% increase and nonwalkers a 7% decrease in HDL cholesterol from 6 to 12 months (P = .0367) without an effect on LDL cholesterol. Whereas nonwalkers had virtually no change in mean LDL particle size, walkers had a borderline reduction in LDL size from BL (268.7 ± 4.1 Å) to 6 months (266.9 ± 4.9 Å), followed by a significant increase in size by 12 months (269.7 ± 4.1 Å; P = .011). The proportion of cholesterol in large LDL particles decreased by 15% from BL to 6 months, but subsequently increased 25% by 12 months among walkers; changes among nonwalkers were smaller and in opposite direction (4% and -3%, respectively; P = .0004). Participation in the social-support PA intervention resulted in slightly increased HDL cholesterol concentrations and a modest and beneficial shift toward larger, less atherogenic LDL particles.

Meal timing during alternate day fasting: Impact on body weight and cardiovascular disease risk in obese adults.

Alternate day fasting (ADF; 24-h feeding/24-h 25% energy intake at lunchtime), is effective for weight loss, but diet tolerability is questionable. Moving the fast day meal to dinnertime, or dividing it into smaller meals, may improve tolerability. Accordingly, this study compared the effects of ADF with three meal times on body weight and heart disease risk. Obese subjects (n = 74) were randomized to 1 of 3 groups for 8 weeks: 1) ADF-L: lunch, 2) ADF-D: dinner, or 3) ADF-SM: small meals. Body weight decreased similarly (P < 0.001) in all groups (ADF-L: 3.5 ± 0.4 kg, ADF-D 4.1 ± 0.5 kg, ADF-SM 4.0 ± 0.5 kg). Reductions (P < 0.001) in fat mass and visceral fat were also comparable. Plasma lipids remained unchanged, and low density lipoprotein (LDL) particle size increased (P < 0.05) in all groups (1.3 ± 0.5 Å). Systolic blood pressure decreased (P < 0.05) by ADF-SM only. Fasting glucose, insulin, and HOMA-IR remained unchanged. Thus, allowing individuals to consume the fast day meal at dinner or small meals produces similar weight loss and cardio-protection as consuming the meal at lunch. This flexibility in meal timing may increase tolerability and long-term adherence to ADF protocols.

The effect of rosuvastatin on low-density lipoprotein subfractions in patients with impaired fasting glucose.

Prediabetes substantially increases cardiovascular risk. We examined the effect of rosuvastatin on the quantity and quality of low-density lipoprotein cholesterol (LDL-C) in patients with dyslipidemia having impaired fasting glucose (IFG) compared to normoglycemic patients with dyslipidemia. This was a prospective observational study including patients with dyslipidemia and IFG (IFG group, n = 49) matched with normoglycemic patients with dyslipidemia (control group, n = 64). Study participants, following dietary intervention, were prescribed rosuvastatin 10 or 20 mg/d to achieve LDL-C goals. Baseline as well as 24 weeks posttreatment changes in the serum lipid profile were evaluated. Moreover, analysis of the LDL subfraction profile was conducted using a polyacrylamide tube gel electrophoresis method. Similar effects were observed in lipid profile in both treatment groups. Patients with IFG experienced a greater decrease in the cholesterol concentration of small dense LDL particles (-65.7%, P < .001 vs baseline) compared to controls (-38.5%, P < .001 vs baseline; P = .018 vs patients with IFG). There was no significant difference in the changes of cholesterol concentration of large and buoyant LDL particles in the IFG group when compared to the control group. A greater increase in the mean LDL particle size (+1.5%, P < .001 vs baseline) was noted in the IFG group compared to the control group at 24 weeks (+0.4%, P = .028 vs baseline; P = .008 vs IFG group). Targeting dyslipidemia with rosuvastatin was associated with more favorable changes in the LDL subfraction profile in patients with IFG compared to normoglycemic ones.

Replacing with whole grains and legumes reduces Lp-PLA2 activities in plasma and PBMCs in patients with prediabetes or T2D

To determine dietary effects on circulating lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and enzyme activity in peripheral blood mononuclear cells (PBMCs), 99 patients with impaired fasting glucose, impaired glucose tolerance, or newly-diagnosed T2D were randomly assigned to either a control group (usual diet with refined rice) or the whole grain and legume group. Substitution of whole grains and legumes for refined rice was associated with the replacement of 7% of energy from carbohydrates with energy from protein (about 4%) and fat. After 12 weeks, the whole grain and legume group showed a significant decrease in fasting glucose, insulin, homeostasis model assessment-insulin resistance, hemoglobin A1c, malondialdehyde, plasma Lp-PLA2 activity, and oxidized LDL (ox-LDL), and an increase in LDL particle size. The changes (Δs) in these variables in the whole grain and legume group were significantly different from those in controls after adjustment for the baseline levels. When all subjects were considered, Δ plasma Lp-PLA2 positively correlated with Δ glucose, Δ PBMC Lp-PLA2, Δ ox-LDL, and Δ urinary 8-epi-prostaglandin F2α after being adjusted for confounding factors. The Δ PBMC Lp-PLA2 correlated positively with Δ glucose and Δ ox-LDL, and negatively with Δ LDL particle size and baseline PBMC Lp-PLA2 The substitution of whole grains and legumes for refined rice resulted in a reduction in Lp-PLA2 activities in plasma and PBMCs partly through improved glycemic control, increased consumption of protein relative to carbohydrate, and reduced lipid peroxides.

PCSK9 levels in abdominally obese men: Association with cardiometabolic risk profile and effects of a one-year lifestyle modification program

ObjectivesStudies performed in rodents have suggested a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in insulin resistance and impaired body fat distribution. Our objective was to examine the relationships between markers of adiposity and insulin resistance and plasma PCSK9 levels in humans. In addition, we explored the effect of a one-year lifestyle modification program on plasma PCSK9 levels in abdominally obese, dyslipidemic men. MethodsPlasma PCSK9 levels were measured by ELISA in 175 abdominally obese, dyslipidemic sedentary men. Of these abdominally obese men, 117 non-diabetic individuals completed a one-year lifestyle modification program aiming at increasing cardiorespiratory fitness levels and improving nutritional quality. ResultsWe found no association between plasma PCSK9 levels and body mass index, waist circumference, fat and fat-free mass, or visceral and subcutaneous adipose tissue measured by computed tomography. Compared to men with the lowest PCSK9 levels (bottom tertile), those with the highest PCSK9 levels (top tertile) had the most detrimental lipoprotein-lipid profile including lower LDL particle size (253.6 ± 4.0 vs. 251.6 ± 4.0 Å, p < 0.05) and higher apolipoprotein C-III levels (36.8 ± 10.6 vs. 32.3 ± 32.3, p < 0.05). These men were also characterized by higher HOMA-IR indices (6.78 ± 3.01 vs. 5.54 ± 2.91, p < 0.05). After one year, study participants lost on average 6.7 ± 4.6 kg (p < 0.0001). Plasma PCSK9 decreased by 9.2 ± 53.7 ng/ml (3.8%, p = 0.07). ConclusionsPlasma PCSK9 levels are not associated with body fat distribution indices, modestly associated with markers of insulin resistance and LDL particle size and are slightly affected by a lifestyle modification program in abdominally obese men.

Visceral leishmaniasis is associated with marked changes in serum lipid profile.

Infection is often accompanied by lipid profile alterations. The aim of this study was to evaluate the lipid profile changes in patients with visceral leishmaniasis (VL). We included 15 patients [10 men, aged 50 (24-82) years old] with VL and 15 age- and sex-matched controls. The parameters estimated at diagnosis and 4 months after VL resolution were total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), apolipoproteins (apo) A-Ι, B, E, C-II, C-III, lipoprotein (a) [Lp(a)], activities of lipoprotein-associated phospholipase A2 (Lp-PLA2), HDL-Lp-PLA2, PON1 (paraoxonase 1) and cholesterol ester transfer protein (CETP), cytokines (interleukins 1β and 6 and tumour necrosis factor α), as well as LDL subfraction profile. Patients with VL at diagnosis had lower levels of TC, LDL-C, apoΒ and Lp(a), and higher TG and apoE concentrations compared with 4 months after VL resolution. The activities of Lp-PLA2, HDL-Lp-PLA2 and ΡΟΝ1 were reduced at diagnosis compared with post-treatment values. VL patients had decreased levels of both large and sdLDL-C at diagnosis; no effect on mean LDL particle size was observed. Patients with VL at diagnosis had decreased HDL-C and apoA-I concentrations; these increased 4 months after VL resolution, but remained lower compared with controls. The activities of HDL-Lp-PLA2 and PON1 remained lower in patients after VL resolution compared with controls. Patients with VL exhibit increased TG levels and decreased cholesterol subclasses at diagnosis. HDL-C, apoA-I and associated enzymes remain lower 4 months after VL resolution compared with controls.

LDL particle size and distribution in children with type 1 diabetes

LDL particle size and distribution in children with type 1 diabetes