Subfraction Concentrations Research Articles

Abstract 397: Changes in Lipoprotein Subfraction Concentrations After Treatment with the Cholesteryl Ester Transfer Protein Inhibitor Anacetrapib Alone or in Combination with Atorvastatin

Background Anacetrapib (ANA), a cholesteryl ester transfer protein inhibitor, has been shown to increase plasma HDL cholesterol and reduce LDL cholesterol, both as monotherapy and in combination with atorvastatin (ATORVA). The effects of these regimens on lipoprotein subfractions have not been reported. Methods ApoB-containing lipoprotein particle subfractions were measured by ion mobility in a post-hoc analysis of baseline and 8 week on-treatment samples from 464 dyslipidemic participants who had been randomized to placebo, ATORVA 20 mg/d, or to ANA at several doses administered with and without ATORVA ( clinicaltrials.gov NCT00325455 ). Results ANA (combined 150 mg/d and 300 mg/d groups) significantly reduced total LDL particle concentration by 51%, and levels of large, medium, and small LDL particles (LDL 1, 2, and 3a) by 43-72% but significantly increased levels of the less abundant cholesterol-depleted very small LDL 4a and 4b species by ~64%. In contrast, ATORVA, despite producing a similar reduction of total LDL particle concentration (50%), reduced the levels of all LDL particle subfractions, although the magnitude was smaller for LDL 4a, with a much smaller non-significant reduction for LDL 4b. Compared with ANA monotherapy, results for combination treatment were generally consistent with additive effects. Notably, for individuals with baseline triglyceride (TG) above the median (>154 mg/dL), increases of very small LDL after ANA were markedly attenuated, whereas after ATORVA there was greater reduction of LDL 4a in the higher TG group. Conclusions Similar reductions of LDL levels after ANA or ATORVA were not associated with comparable effects on all LDL particle subfractions, and neither drug was effective in lowering levels of the smallest LDL particles. Assessment of the clinical impact of the effects of ANA on LDL subfractions, and the differential changes in very small LDL in individuals with normal versus elevated TG, await cardiovascular outcome data from REVEAL.

Evaluation of Anti-Herpetic Activity of Methanol Seed Extract and Fractions of Securigera securidaca In vitro

Objectives: Securigera securidaca Degen & Dorfl (Fabaceae) is an annual herb occurring wild in West Asia, Europe and Africa. The seeds of this plant are used for the treatment of disorders such as hyperlipidemia, diabetes, and epilepsy in Iranian folk medicine. Materials: This study was carried out to check antiherpetic substances of crude methanol seed extract of Securigera securidaca and its column chromatographic fractions. The antiherpetic activities of different concentrations (20, 2, 0.2 and 0.02 μg/ml) of crude methanol extract and sub-fractions were tested by use of plaque-forming unit (PFU) assay and the real-time polymerase chain reaction (PCR) assay. Results: The most active fractions analyzed by column chromatography, containing kaempferol and kaempferol- 7-O-glucoside. The apparent effective concentration for 50% plaque reduction (EC50) of crude methanol extract, kaempferol, kaempferol-7-O-glucoside and acyclovir (ACV) were 2, 0.2, 0.1 and 0.1 μg/mL, respectively. Conclusion: These findings demonstrate that kaempferol and kaempferol-7-O-glucoside isolated from S. securidaca may inhibit virus attachment to the cell membrane, virus entry into the cell and viral polymerase

Genome-wide association study indicates variants associated with insulin signaling and inflammation mediate lipoprotein responses to fenofibrate

A shift towards overall larger very low-density lipoprotein (VLDL), and smaller low-density lipoprotein and high-density lipoprotein (HDL) diameters occurs in insulin resistance (IR), which reflects shifts in the distribution of the subfraction concentrations. Fenofibrate, indicated for hypertriglyceridemia, simultaneously reduces IR and shifts in lipoprotein diameter. Individual responses to fenofibrate vary, and we conducted a genome-wide association study to identify genetic differences that could contribute to such differences. Association analysis was conducted between single nucleotide polymorphisms (SNPs) on the Affymetrix 6.0 array and fasting particle diameter responses to a 12-week fenofibrate trial, in 817 related Caucasian participants of the Genetics of Lipid Lowering Drugs and Diet Network. Linear models were conducted, which adjusted for age, sex and study center as fixed effects, and pedigree as a random effect. The top three SNPs associated with each fraction were examined subsequently for associations with changes in subfraction concentrations. SNPs in AHCYL2 and CD36 genes reached, or closely approached, genome-wide levels of significance with VLDL and HDL diameter responses to fenofibrate, respectively (P=4×10(-9) and 8×10(-8)). SNPs in AHCYL2 were associated with a decrease in the concentration of the large VLDL subfraction only (P=0.002). SNPs associated with HDL diameter change were not associated with a single subfraction concentration change (P>0.05) indicating small shifts across all subfractions. We report novel associations between lipoprotein diameter responses to fenofibrate and the AHCYL2 and CD36 genes. Previous associations of these genes with IR emphasize the role of IR in mediating lipoprotein response to fenofibrate.

Changes in lipoprotein subfraction concentration and composition in healthy individuals treated with the CETP inhibitor anacetrapib

We investigated the effects of the cholesteryl ester (CE) transfer protein inhibitor anacetrapib (ANA) on plasma lipids, lipoprotein subfraction concentrations, and lipoprotein composition in 30 healthy individuals. Participants (n = 30) were randomized to ANA 20 mg/day, 150 mg/day, or placebo for 2 weeks. Changes in concentration of lipoprotein subfractions were assessed using ion mobility, and compositional analyses were performed on fractions separated by density gradient ultracentrifugation. ANA 150 mg/day versus placebo resulted in significant decreases in LDL-cholesterol (26%) and apo B (29%) and increases in HDL-cholesterol (82%). Concentrations of medium and small VLDL, large intermediate density lipoprotein (IDL), and medium and small LDL (LDL2a, 2b, and 3a) decreased whereas levels of very small and dense LDL4b were increased. There was enrichment of triglycerides and reduction of CE in VLDL, IDL, and the densest LDL fraction. Levels of large buoyant HDL particles were substantially increased, and there was enrichment of CE, apo AI, and apoCIII, but not apoAII or apoE, in the mid-HDL density range. Changes in lipoprotein subfraction concentrations and composition with ANA 20 mg/day were similar to those for ANA 150 mg/day but were generally smaller in magnitude. The impact of these changes on cardiovascular risk remains to be determined.

High-density lipoprotein cholesterol subfractions HDL2 and HDL3 are reduced in women with rheumatoid arthritis and may augment the cardiovascular risk of women with RA: a cross-sectional study

IntroductionHigher levels of high density lipoprotein (HDL) subfractions HDL3-chol and particularly HDL2-chol protect against cardiovascular disease (CVD), but inflammation reduces the HDL level and may impair its anti-atherogenic effect. Changed HDL composition through the impact of inflammation on HDL subfractions may contribute to the excess risk of CVD in rheumatoid arthritis (RA). In this study, we investigated whether HDL2-chol and HDL3-chol concentrations differ between RA patients and healthy controls, and whether these levels are related to the level of RA disease activity.MethodsNon-fasting blood samples were collected from 45 RA patients and 45 healthy controls. None of the participants had a history of CVD, diabetes, or used lipid-lowering drugs. HDL2-chol and HDL3-chol concentrations were obtained by ultracentrifugation. Regression modeling was used to compare HDL subfraction levels between RA patients and healthy controls, and to analyze the effect of disease activity on HDL2-chol and HDL3-chol.ResultsHDL2-chol and HDL3-chol were significantly lower in RA patients compared to healthy controls (P = 0.01, P = 0.005, respectively). The HDL2:HDL3 ratio was significantly lower in patients compared to controls (P = 0.04). Reduced HDL2-chol and HDL3-chol levels were primarily present in female RA patients and not in male RA patients. A modest effect of the disease activity score in 28 joins ( DAS28) on HDL2-chol concentrations was found, after correction for disease duration, glucocorticosteroid use and body mass index (BMI), with a 0.06 mmol/L decrease with every point increase in DAS28 (P = 0.05). DAS28 did not significantly affect HDL3-chol concentrations (P = 0.186).ConclusionsBoth HDL subfractions but particularly HDL2-chol concentrations were decreased in RA, primarily in women. This seems to be associated with disease activity and is of clinical relevance. The reduction of the HDL subfraction concentrations, particularly the supposedly beneficial HDL2-chol, may negatively impact the cardiovascular risk profile of women with RA.

Abstract 8672: Neutrophil-to-Lymphocyte Ratio Predicts Prognosis in Patients with Chronic Coronary Heart Disease

Purpose: A relationship between blood cell count and survival has been observed both in healthy individuals and in patients with stable angina, unstable angina, myocardial infarction or heart failure. We tested the hypothesis that a complete blood count with subfraction concentrations would provide prognostic information in patients with chronic coronary heart disease (CHD), and that this information is additive to a standard diagnostic work-up. Methods: We prospectively examined 2370 consecutive patients with chronic CHD, defined by a > 50% stenosis at coronary angiography and/or history of myocardial infarction (MI). We examined the association between complete blood count, clinical variables and future cardiac events (cardiac death and non-fatal MI). Results: During follow-up (median 46 months), 147 patients (6.2%) died of cardiac causes and 81 (3.4%) experienced a non-fatal MI. Using univariate analysis, reduced hematocrit (< 36% if male and < 40% if female) and a neutrophil-to-lymphocyte (N/L) ratio > 2.42, but not white blood cell count and platelet count, were significantly associated with a reduced cardiac event-free survival (P < 0.001 and P < 0.0001, respectively). The impact of anemia and high N/L ratio on survival persisted after adjustment for age, diabetes mellitus, left ventricular ejection fraction and angiographic extent of coronary atherosclerosis. The negative prognostic impact of a high N/L ratio persisted even after adjustment for both clinical variables and other routine laboratory variables (risk ratio: 1.57, 95% confidence interval: 1.19 to 2.08, p = 0.0014). Conclusion: An elevated N/L ratio is a significant predictor of adverse prognosis in patients with chronic CHD.

Effects of the PPAR-δ agonist MBX-8025 on atherogenic dyslipidemia

Objective Determine the effects of treatment with a selective PPAR-δ agonist ± statin on plasma lipoprotein subfractions in dyslipidemic individuals. Methods Ion mobility analysis was used to measure plasma concentrations of subfractions of the full spectrum of lipoprotein particles in 166 overweight or obese dyslipidemic individuals treated with the PPAR-δ agonist MBX-8025 (50 and 100 mg/d) ± atorvastatin (20 mg/d) in an 8-week randomized parallel arm double blind placebo controlled trial. Results MBX-8025 at both doses resulted in reductions of small plus very small LDL particles and increased levels of large LDL, with a concomitant reduction in large VLDL, and an increase in LDL peak diameter. This translated to reversal of the small dense LDL phenotype (LDL pattern B) in ∼90% of the participants. Modest increases in HDL particles were confined to the smaller HDL fractions. Atorvastatin monotherapy resulted in reductions in particles across the VLDL–IDL–LDL spectrum, with a significantly smaller reduction in small and very small LDL vs. MBX-8025 100 mg/d (−24.5 ± 5.3% vs. −47.8 ± 4.9%), and, in combination with MBX-8025, a reversal of the increase in large LDL. Conclusion PPAR-δ and statin therapies have complementary effects in improving lipoprotein subfractions associated with atherogenic dyslipidemia.

Novel Lipoprotein Subfraction and Size Measurements in Prediction of Mortality in Maintenance Hemodialysis Patients

Conventional lipid profiles usually cannot predict cardiovascular outcomes in chronic disease states. We hypothesized that novel lipoprotein subfraction concentrations and LDL particle size measurements better predict mortality in maintenance hemodialysis (MHD) patients. Mortality-predictability of LDL particle diameter and lipoprotein subfraction concentrations, measured by novel ion mobility, was examined in a cohort of 235 hemodialysis patients who were followed for up to 6 years using Cox models with adjustment for important covariables. Patients were 54 ± 14 years old (mean ± SD) and included 45% women with total, LDL and HDL cholesterol levels of 143 ± 42, 76 ± 29, and 37 ± 12 mg/dl, respectively. Over 6 years, 71 patients (31%) died. Conventional lipid profile was not associated with mortality. The death hazard ratio (HR, 95% confidence interval) of the highest versus lowest quartiles of very small and large LDL particle concentrations were 2.43 (1.03 to 5.72) and 0.38 (0.15 to 0.96), respectively. Across increasing quartiles of LDL particle diameter, death HRs were 1.00, 0.93 (0.46 to 1.87), 0.43 (0.21 to 0.89), and 0.45 (0.31 to 1.00), respectively. Whereas conventional lipid profile cannot predict mortality in MHD patients, larger novel LDL particle diameter or higher large LDL particle concentrations appear predictive of greater survival, whereas higher very small LDL particle concentration is associated with higher death risk. Examining lipoprotein subfraction modulation in chronic diseases is indicated.

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.

Apolipoprotein L1 nephropathy risk variants associate with HDL subfraction concentration in African Americans

Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with non-diabetic nephropathy in African Americans. ApoL1 proteins associate with high-density lipoprotein (HDL) particles in the circulation. Plasma HDL particle subclass concentrations were compared in 73 African Americans based on APOL1 genotypes to detect differences potentially contributing to renal disease. HDL subclass concentrations were measured using nuclear magnetic resonance spectroscopy in African American first-degree relatives of patients with non-diabetic end-stage renal disease. Participants had estimated glomerular filtration rates (GFRs) > 80 mL/min and lacked albuminuria. Additive effects of the number of APOL1 risk variants on natural logarithm-transformed HDL subclass concentrations were computed. Participants were 58.9% female with mean ± SD age 47.2 ± 13.3 years and GFR 92.4 ± 18.8 mL/min. The numbers with 2, 1 and 0 APOL1 nephropathy risk variants, respectively, were 36, 17 and 20. Mean ± SD medium-sized HDL concentrations were significantly lower for each additional APOL1 risk variant (2 versus 1 versus 0 risk variants: 9.0 ± 5.6 versus 10.1 ± 5.5 versus 13.1 ± 8.2 μmol/L, respectively; P = 0.0222 unadjusted; P = 0.0162 triglyceride- and ancestry adjusted). Lower medium-sized HDL subclass concentrations are present in African Americans based on increasing numbers of APOL1 nephropathy risk variants. Potential mechanistic roles of altered medium HDL concentrations on APOL1-associated renal microvascular diseases should be evaluated.

Serum adipokines and low density lipoprotein subfraction profile in hypopituitary patients with growth hormone deficiency

The aim was to evaluate the concentrations of lipid subfractions in relation to adipokines and metabolic parameters in adult growth hormone (GH)-deficient hypopituitary patients on conventional replacement therapy. The study included 21 GH deficient-hypopituitary patients (age: 36.0 ± 15.1 years, male/female: 7/14) on conventional replacement therapy other than GH and 20 comparable controls (age: 37.3 ± 14.0 years, male/female: 6/14). Lipid subfractions (Lipoprint system), serum adipokine (leptin, adiponectin, resistin) concentrations, body composition, a surrogate marker for insulin resistance (HOMA) and conventional lipid profile were evaluated. No statistically significant difference was found with respect to HOMA, adipokine concentrations and anthropometric parameters between patients and controls except for significantly increased waist-to-hip ratio in hypopituitary group. Total and LDL cholesterol concentrations were significantly higher in the patients. LDL particle size (268.88 ± 3.16 vs. 271.31 ± 3.11 Å, P = 0.151) and small-dense LDL subfraction did not differ significantly. According to logistic regression analysis, triglyceride concentrations ≥1.69 mmol/L was the sole parameter significantly and independently predicted small (<268 Å) LDL particle size (P = 0.019) in the whole group. Increased triglyceride concentrations affect LDL particle size in GH-deficient hypopituitary patients. Small dense LDL seems not directly contribute to atherogenic potential in hypopituitarism.

Elemental allelopathy and antifungal activities of Inula falconeri from Himalaya Pakistan

The leaf leachate of Inula falconeri Hook. f. has been reported to carry allelopathic potential. To analyse its further effects, it was fractionated into five subfractions, i.e. hexane, chloroform, ethyl acetate, n-butanol, and water. The hexane subfraction had the highest specific activity compared with the other four fractions and presented 100% inhibitory effect to germination of lettuce seeds. Chloroform subfraction presented a dose-response effect, and the ethyl acetate subfraction exhibited insignificant inhibitory effect, while n-butanol and water subfractions presented stimulatory effects. Elemental analysis through energy-dispersive X-ray spectroscopy (EDX) showed the composition of 15 different elements with carbon, oxygen, and potassium showing highest weight percentages. In the case of hexane subfraction, highest percentages of silver (1.22%), cadmium (1.44%), manganese (0.71%), and chromium (0.70%) were observed, compared with other subfractions. Chloroform subfraction has high proportions of copper (0.63%), nickel (0.45%), iron (0.37%), calcium (0.22%), and cobalt (0.08%). In the case of ethyl acetate subfraction oxygen (49.66%) and sodium (0.33%) percentage was the highest of all the subfractions, while the other elements were observed in lesser amounts than in other subfractions. The n-butanol subfraction has recorded highest weight of zinc (0.79%) compared with other subfractions while in water subfraction significant amounts of other elements were not observed. To investigate the behaviour of these subfractions against plant pathogens, hexane subfraction (concentration gradients of 1.25, 2.5, and 5 mg/disc) demonstrated significant zones of inhibition against Alternaria alternata and Rhizoctonia solani while only an insignificant effect against Fusarium oxysporum. Thus, using active natural inhibitors of plant pathogens reveals broader perspectives and interests in avoiding losses to cash crops in the local area.

Apolipoprotein CIII bound to apoB-containing lipoproteins is associated with small, dense LDL independent of plasma triglyceride levels in healthy men

ObjectivePlasma levels of both apolipoprotein CIII (apoCIII) and small, dense LDL particles are associated with plasma triglyceride (TG) concentrations, and are markers for cardiovascular disease (CVD) risk. We tested whether there is an association of apoCIII with small, dense LDL levels that is independent of plasma TG level. MethodsFor study I, concentrations of blood lipids, apolipoproteins, and LDL subfractions (analytical ultracentrifugation, AnUC) were measured in 141 healthy middle-aged males. In study II (n=14), density gradient ultracentrifugation of plasma was performed, and 3 fractions in the LDL density range (1.019–1.063g/ml) were collected. ResultsIn study I, plasma levels of apoCIII in apoB-containing lipoproteins (LpB:CIII) were associated positively with concentrations of LDL3 (p<0.001) and LDL4 (p<0.001) and negatively with LDL peak particle size (p<0.05) with adjustment for plasma TG. Stepwise multiple regression analysis showed that LpB:CIII was significantly associated with small, dense LDL (LDL3+LDL4) levels after adjusting for age, BMI, plasma levels of TG, apoB, and HDL-cholesterol. In study II, the molar ratio of apoCIII to apoB in the LDL fraction of highest density (1.049–1.064g/ml) was found to be significantly greater (p<0.001) than that in each of two LDL fractions of lower density (1.033–1.038g/ml; p<0.001 and 1.038–1.049g/ml; p<0.001). ConclusionsIncreased apoCIII content may contribute to metabolic and pathologic properties of small, dense LDL particles.

Forty-Three Loci Associated with Plasma Lipoprotein Size, Concentration, and Cholesterol Content in Genome-Wide Analysis

While conventional LDL-C, HDL-C, and triglyceride measurements reflect aggregate properties of plasma lipoprotein fractions, NMR-based measurements more accurately reflect lipoprotein particle concentrations according to class (LDL, HDL, and VLDL) and particle size (small, medium, and large). The concentrations of these lipoprotein sub-fractions may be related to risk of cardiovascular disease and related metabolic disorders. We performed a genome-wide association study of 17 lipoprotein measures determined by NMR together with LDL-C, HDL-C, triglycerides, ApoA1, and ApoB in 17,296 women from the Women's Genome Health Study (WGHS). Among 36 loci with genome-wide significance (P<5×10−8) in primary and secondary analysis, ten (PCCB/STAG1 (3q22.3), GMPR/MYLIP (6p22.3), BTNL2 (6p21.32), KLF14 (7q32.2), 8p23.1, JMJD1C (10q21.3), SBF2 (11p15.4), 12q23.2, CCDC92/DNAH10/ZNF664 (12q24.31.B), and WIPI1 (17q24.2)) have not been reported in prior genome-wide association studies for plasma lipid concentration. Associations with mean lipoprotein particle size but not cholesterol content were found for LDL at four loci (7q11.23, LPL (8p21.3), 12q24.31.B, and LIPG (18q21.1)) and for HDL at one locus (GCKR (2p23.3)). In addition, genetic determinants of total IDL and total VLDL concentration were found at many loci, most strongly at LIPC (15q22.1) and APOC-APOE complex (19q13.32), respectively. Associations at seven more loci previously known for effects on conventional plasma lipid measures reveal additional genetic influences on lipoprotein profiles and bring the total number of loci to 43. Thus, genome-wide associations identified novel loci involved with lipoprotein metabolism—including loci that affect the NMR-based measures of concentration or size of LDL, HDL, and VLDL particles—all characteristics of lipoprotein profiles that may impact disease risk but are not available by conventional assay.

A Temperature Calibration Procedure for the Sunset Laboratory Carbon Aerosol Analysis Lab Instrument

The Sunset Laboratory Carbon Aerosol Analysis Lab Instrument is widely used for thermal-optical analysis (TOA) of ambient particulate matter samples to measure total carbon (TC), organic carbon (OC), and elemental carbon (EC), and often thermal sub-fractions of OC and EC. TOA operating protocols include a series of plateau temperatures at which the thermal sub-fractions evolve. The temperatures have conventionally been measured by a sensor located in the sample oven but away from the filter sample. However, the TOA protocol used by the Interagency Monitoring of Protected Visual Environments (IMPROVE) network and recently adopted by the U.S. Environmental Protection Agency (EPA) Speciation Trends Network (STN) and Chemical Speciation Network (CSN) specify temperatures to be achieved at the filter. Our goal was to develop a simple calibration method to obtain the target filter temperatures in a Sunset Instrument. This method showed good agreement with the IMPROVE/STN/CSN method and has the advantages of not damaging oven components and of providing a direct comparison of sample oven sensor and filter temperatures at the TOA protocol-specified temperatures. Calibrations performed on four Sunset Instruments yielded different sensor/filter temperature relationships. Ambient PM 2.5 samples analyzed using IMPROVE_A temperatures at the oven sensor compared to IMPROVE_A temperatures at the filter yielded statistically insignificant differences for TC, OC, and EC but statistically significant differences for the carbon sub-fraction concentrations. Temperature calibrations should be performed on each Sunset Instrument to ensure comparability in the carbon sub-fractions being reported, and a simple method has been provided for performing these calibrations.

Ion Mobility Analysis of Lipoprotein Subfractions Identifies Three Independent Axes of Cardiovascular Risk

Whereas epidemiological studies show that levels of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) predict incident cardiovascular disease (CVD), there is limited evidence relating lipoprotein subfractions and composite measures of subfractions to risk for CVD in prospective cohort studies. We tested whether combinations of lipoprotein subfractions independently predict CVD in a prospective cohort of 4594 initially healthy men and women (the Malmö Diet and Cancer Study, mean follow-up 12.2 years, 377 incident cardiovascular events). Plasma lipoproteins and lipoprotein subfractions were measured at baseline with a novel high-resolution ion mobility technique. Principal component analysis (PCA) of subfraction concentrations identified 3 major independent (ie, zero correlation) components of CVD risk, one representing LDL-associated risk, a second representing HDL-associated protection, and the third representing a pattern of decreased large HDL, increased small/medium LDL, and increased triglycerides. The last corresponds to the previously described "atherogenic lipoprotein phenotype." Several genes that may underlie this phenotype-CETP, LIPC, GALNT2, MLXIPL, APOA1/A5, LPL-are suggested by SNPs associated with the combination of small/medium LDL and large HDL. PCA on lipoprotein subfractions yielded three independent components of CVD risk. Genetic analyses suggest these components represent independent mechanistic pathways for development of CVD.

Lipoprotein(a) and Other Serum Lipid Subfractions Influencing Primary Patency After Infrainguinal Percutaneous Transluminal Angioplasty

To evaluate the influence of serum lipid subfraction concentrations on arterial patency after percutaneous transluminal angioplasty (PTA) in patients with infrainguinal peripheral artery occlusive disease (PAOD). From January 2007 to June 2008, a prospective study was conducted involving 39 patients (29 men; mean age 68.6+/-10.0 years) with infrainguinal PAOD in 41 limbs who had preprocedural lipid assessment and underwent successful PTA (<30% residual stenosis). Patient demographics, Fontaine clinical stage classification, Texas University Classification of ulcers, coexisting medical conditions, endovascular procedures, and lipid profiles were collected in a database. Follow-up included clinical and duplex ultrasound evaluation at discharge and at 1, 3, 6, and 12 months. To analyze any correlation between various lipid subfractions and the loss of primary patency (Cox proportional hazards modeling), the patients were dichotomized into high and low groups according to these thresholds: LDL-C >100 mg/dL, HDL-C <40 mg/dL, Lp(a) >30 mg/dL, and an Apo(B)/Apo(A) ratio >0.8 mg/dL. Mean follow-up was 7.5 months (range 3-12). After 1, 3, and 6 months, the primary patency rates by Kaplan-Meier analysis were 94.9%, 73.7%, and 64.1%, respectively. Restenosis at 6 months was significantly related to female gender (HR 95.9, 95% CI 6.8 to 1352.5, p = 0.001), HDL-C <40 mg/dL (HR 86.9, 95% CI 6.4 to 1183.1, p = 0.001), LDL-C >100 mg/dL (HR 9.6, 95% CI 1.6 to 57.4, p = 0.013), and Lp(a) >30 mg/dL (HR 6.1, 95% CI 1.4 to 26.3, p = 0.016). Our results suggest that Lp(a), LDL-C, and HDL-C are independent risk factors for restenosis after infrainguinal PTA.

Advanced Lipoprotein Testing and Subfractionation Are Not (Yet) Ready for Routine Clinical Use

Standard lipid tests measure the cholesterol or triglyceride content of lipoproteins, expressed as mg/dL (or mmol/L) of cholesterol or triglyceride. A standard lipid panel includes total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. These lipids are carried within lipoprotein particles that are heterogeneous in size, density, charge, core lipid composition, specific apolipoproteins, and function.1 A variety of lipoprotein assays have been developed that subfractionate lipoprotein particles according to some of these properties such as size, density, or charge.2 These lipoprotein assays have been proposed for improving assessment of risk of cardiovascular disease (CVD) and for guiding lipid-lowering therapies. They are mostly used today in specialized lipid clinics or research studies, and their general utility for clinical practice is not well delineated.3 In this review, I first provide a summary of current guideline statements that address this topic. Then I give a brief overview of the different laboratory methods available for clinical use and discuss the literature evaluating these methods. Finally, I discuss current limitations to the widespread clinical application of these methods. Response by Superko on p 2404 The Third Adult Treatment Panel of the National Cholesterol Education Program4 and the American Heart Association5 recommend measuring a standard lipid panel in adults and targeting lipid-lowering therapy on the basis of levels of LDL cholesterol, and non-HDL cholesterol in subjects with hypertriglyceridemia. European and Canadian guidelines recommend measuring standard lipids while also emphasizing the total/HDL cholesterol ratio in risk assessment.6,7 Current guidelines do not recommend routine use of advanced lipoprotein tests, mainly because it is unclear how much incremental prognostic information is provided by these tests beyond that available from a standard lipid panel.4,6,7 Recently, an international panel proposed that cardiovascular risk may be more closely related to atherogenic lipoprotein …

Association of white blood cell subfraction concentration with fitness and fatness

ObjectiveTo examine the association between fitness, BMI, and neutrophil, lymphocyte, monocyte, basophil, and eosinophil concentrations in apparently healthy, non-smoking men.DesignCross-sectional study of 452 men from the Aerobics Center Longitudinal Study...

EFFECT OF EZETIMIBE ON LIPOPROTEIN SUBFRACTION CONCENTRATIONS: THE ROLE OF ATORVASTATIN PRETREATMENT

Introduction: Recently published data indicate that the effect of ezetimibe on lipoprotein subfraction distribution in patients receiving statin therapy may differ substantially from that observed in patients treated with ezetimibe monotherapy. The aim of our study was to directly compare the effects of ezetimibe added to established atorvastatin treatment on lipoprotein subfractions with those obtained by ezetimibe monotherapy. Material and methods: Forty dyslipidaemic patients who failed to reach their assigned LDL-C target while on atorvastatin therapy (20 mg/day) for at least 6 months were included in the study. Ezetimibe (10 mg/day) was added to atorvastatin in all patients. The concentrations of the individual lipoprotein subfractions were determined using the Lipoprint method at baseline (prior to the addition of ezetimibe) as well as after 16 weeks of combination treatment. The changes in lipoprotein subfraction concentrations were compared with those observed in 40 age- and sex-matched statin-naive patients receiving ezetimibe monotherapy for 16 weeks. Results: Ezetimibe administration reduced VLDL concentrations either when used as monotherapy or when added to established atorvastatin treatment. However, in contrast to ezetimibe monotherapy, which reduced the concentrations of all LDL subfractions, the addition of ezetimibe in patients receiving atorvastatin decreased LDL cholesterol values exclusively by reducing the concentrations of large, buoyant LDL subfractions. In addition, while ezetimibe monotherapy reduced mainly the concentrations of small, dense LDL subspecies, the addition of ezetimibe in patients receiving atorvastatin equally reduced the concentration of all HDL particles. Conclusions: The effect of ezetimibe on lipoprotein subfractions is significantly affected by previous atorvastatin treatment.