HDL Subfractions Research Articles

A rapid and precise method for measuring plasma apoE-rich HDL using polyethylene glycol and cation-exchange chromatography: a pilot study on the clinical significance of apoE-rich HDL measurements

BackgroundHigh-density lipoprotein (HDL) containing apolipoprotein E (apoE-rich HDL) represents only a small portion of plasma HDL. Reliable methods for determining and isolating apoE-rich HDL have not been well studied. MethodsWe established a novel analytical method for apoE-rich HDL using polyethylene glycol and a cation-exchange column (PEG-column method). Furthermore, we examined biochemical correlates of apoE-rich HDL-cholesterol (HDL-C) in 36 patients who underwent coronary computed tomographic angiography. ResultsOur PEG-column method demonstrated high reproducibility (coefficient of variation <3.52%) and linearity up to 15mg/dl for apoE-rich HDL-C concentrations. Isolated apoE-rich HDL exhibited a larger diameter (14.8nm) than apoE-poor HDL (10.8nm) and contained both apoE and apoA-I. ApoE-rich HDL-C concentrations correlated significantly with triglycerides (rs=−0.646), LDL size (rs=0.472), adiponectin (rs=0.476), and other lipoprotein components. No significant correlation was obtained with the coronary calcium score. Multiple regression analysis revealed that plasma triglycerides and adiponectin concentrations remained significant independent predictors of apoE-rich (adjusted R2=0.486) but not apoE-poor HDL-C. ConclusionsThe PEG-column method demonstrated, to various degrees, significant correlations between HDL subfractions and several lipid-related biomarkers involved in an atherogenic lipoprotein profile. Our separation technique for apoE-rich HDL is useful to clarify the role of apoE-rich HDL in atherosclerosis.

Do HDL and LDL subfractions play a role in atherosclerosis in end-stage renal disease (ESRD) patients?

Significantly increased cardiovascular mortality in patients with chronic kidney (CKD) disease cannot be explained by traditional risk factors. Recent studies revealed that the quality of HDL and LDL cholesterol may be more important than their serum levels. The aim of this study was to assess which LDL and HDL subfractions were more abundant in end-stage renal disease (ESRD) patients and to analyse whether subfraction distribution could be associated with accelerated atherosclerotic processes. This study included 50 ESRD patients undergoing dialysis and 20 healthy volunteers. LDL and HDL subfractions were analysed in serum with the use of Lipoprint system. All patients had intima-media thickness (IMT) measured. Statistically significant differences in subfractions between control and study group were observed in case of: HDL1 (p<0.0001), HDL2 (p=0.009), HDL3 (p<0.0001), HDL4 (p=0.003), HDL5 (p=0.01), HDL7 (p<0.0001), HDL8 (p<0.0001), HDL9 (p<0.0001), HDL10 (p<0.0001), large HDL (p<0.0001), HDL Small (p<0.0001) as well as IDL-B (p=0.014), IDLA (p=0.011), LDL2 (p=0.007). Significant differences were also observed in HDL and LDL subfraction distribution between haemodialysis patients with normal and increased IMT: HDL6 (p=0.020), HDL Large (HDL1-3) (p=0.017), HDL Intermediate (HDL4-7) (p=0.017). This study revealed that ESRD influenced HDL subfractions. In HD patients, large HDL subfractions are more abundant while small HDL fraction is more frequent in healthy persons. It failed to show the influence of end-stage disease on LDL subfraction levels. Shift in HDL subfractions might be responsible for the increased risk of atherosclerosis in CKD patients.

GENDER SPECIFICS OF SUBFRACTIONAL PLASMA LIPOPROTEIDS DISTRIBUTION

Aim. To find out, whether there is specifics of subfractional distribution of plasma lipoproteides in men and women depending on coronary atherosclerosis. Material and methods. Totally 310 patients included (203 males, 107 females), underwent coronary arteriography; lesion of artery was assessed with Gensini Score (GS). Subfractional spectrum of plasma lipoproteides was studied via electrophoresis in 3% polyacrylamid gel with Lipoprint system (Quantimetrix Lipoprint System, USA). Results. In the group without lesion (GS =0) gender differences of lipids, apolipoproteides and glucose utilization parameters were absent. Among coronary atherosclerosis patients (GS >0) males had lower concentrations of low and high density cholesterol (LDL, HDL), as Apo A1 and Apo B. Males with GS =0, as with GS >0 differed from females by lower lipoproteides of intermediate density (LID) — LID B and LID A, and higher part of LDL 2 and small dense particles LDL 3, but mean size of LDL particles was smaller. There were no differences in HDL subfractions distribution among men and women, but in men only if coronary atherosclerosis, there were lower cholesterol concentrations found in all HDL subfractions. Conclusion. Gender differences are revealed in subfractional spectrum of LID and LDL: in men regardless coronary atherosclerosis with the same and even lower level of LDL cholesterol there was accumulation of more atherogenic small dense LDL particles. Gender differences in the part of HDL subfractions were not found, but in men concentration of cholesterol in each of subfractions, with coronary lesion, was lower than in women.

Effects of exchanging carbohydrate or monounsaturated fat with saturated fat on inflammatory and thrombogenic responses in subjects with abdominal obesity: A randomized controlled trial

Modification of the amount and type of dietary fat has diverse effects on cardiovascular risk. We recruited 54 abdominally obese subjects to participate in a prospective cross-over design, single-blind trial comparing isocaloric 2000kcal MUFA or carbohydrate-enriched diet with SFA-enriched diet (control). The control diet consisted of 15E% protein, 53E% carbohydrate and 32E% fat (12E% SFA, 13E% MUFA). A total of ∼7E% of MUFA or refined carbohydrate was exchanged with SFA in the MUFA-rich and carbohydrate-rich diets respectively for 6-weeks. Blood samples were collected at fasting upon trial commencement and at week-5 and 6 of each dietary-intervention phase to measure levels of cytokines (IL-6, IL-1β), C-reactive protein (CRP), thrombogenic markers (E-selectin, PAI-1, D-dimer) and lipid subfractions. Radial pulse wave analysis and a 6-h postprandial mixed meal challenge were carried out at week-6 of each dietary intervention. Blood samples were collected at fasting, 15 and 30min and hourly intervals thereafter till 6h after a mixed meal challenge (muffin and milkshake) with SFA or MUFA (872.5kcal, 50g fat, 88g carbohydrates) or CARB (881.3kcal, 20g fat, 158g carbohydrates)- enrichment corresponding to the background diets. No significant differences in fasting inflammatory and thrombogenic factors were noted between diets (P>0.05). CARB meal was found to increase plasma IL-6 whereas MUFA meal elevated plasma D-dimer postprandially compared with SAFA meal (P<0.05). Comparing the 3 meals, there were similar postprandial elevations in IL-6 and D-dimer and postprandial reductions in PAI-1, augmentation index and pressure (time effect: P<0.05). CARB diet was found to reduce HDL3 by 7.8% and increase small dense HDL (sdHDL) by 8.6% compared with SFA diet (P<0.05). SFA diet increased large HDL subfractions compared with both CARB and MUFA diets by 4.9% and 6.6% (P<0.05), respectively. Overall, the evidence presented in this study suggests that the replacement of SFA with MUFA or refined carbohydrates may not improve inflammatory and thrombogenic markers in abdominally overweight individuals. Indeed increased refined carbohydrates consumption adversely impacts fasting HDL subfractions. This trial was registered under ClinicalTrials.gov. Identifier no. NCT01665482.

Short-term isocaloric fructose restriction lowers apoC-III levels and yields less atherogenic lipoprotein profiles in children with obesity and metabolic syndrome

Background and aimsDietary fructose may play a role in the pathogenesis of metabolic syndrome (MetS). In a recently published study of obese children with MetS, we showed that isocaloric fructose restriction reduced fasting triglyceride (TG) and LDL-cholesterol (LDL-C). In these ancillary analyses, we tested the hypothesis that these effects were also accompanied by improved quantitative and qualitative changes in LDL and HDL subclasses and their apolipoproteins; as well as change in VLDL, particularly apoC-III. MethodsObese children with MetS (n = 37) consumed a diet that matched self-reported macronutrient composition for nine days, with the exception that dietary fructose was reduced from 11.7 ± 4.0% to 3.8 ± 0.5% of daily calories and substituted with glucose (in starch). Participants underwent fasting biochemical analyses on Days 0 and 10. HDL and LDL subclasses were analyzed using the Lipoprint HDL and LDL subfraction analysis systems from Quantimetrix. ResultsSignificant reductions in apoB (78 ± 24 vs. 66 ± 24 mg/dl) apoC-III (8.7 ± 3.5 vs. 6.5 ± 2.6 mg/dl) and apoE (4.6 ± 2.3 vs. 3.6 ± 1.1 mg/dl), all p < 0.001) were observed. LDL size increased by 0.87 Å (p = 0.008). Small dense LDL was present in 25% of our cohort and decreased by 68% (p = 0.04). Small HDL decreased by 2.7% (p < 0.001) and large HDL increased by 2.4% (p = 0.04). The TG/HDL-C ratio decreased from 3.1 ± 2.5 to 2.4 ± 1.4 (p = 0.02). These changes in fasting lipid profiles correlated with changes in insulin sensitivity. ConclusionsIsocaloric fructose restriction for 9 days improved lipoprotein markers of CVD risk in children with obesity and MetS. The most dramatic reduction was seen for apoC-III, which has been associated with atherogenic hypertriglyceridemia.

Circulation Research “In This Issue” Anthology

Circulation Research “In This Issue” Anthology

Abstract 547: Proteomic Correlation of Gel Filtration Lipoprotein Subfractions with Atheroprotective Functions of HDL

HDL has been shown to possess a variety of cardio-protective functions, including removal of excess cholesterol from the periphery, inhibition of oxidation, and stimulation of endothelial function. It has been proposed that various HDL sub-particles exist, each with distinct protein and lipid compositions. We hypothesized that fractionation of plasma would separate HDL particles with different protein compositions into distinct populations responsible for different HDL functions. Plasma from 10 healthy adults was fractionated by gel filtration and the protein composition of phospholipid containing fractions was analyzed by mass spectrometry. Each fraction was assessed for its ability to efflux cholesterol from macrophages, as well as its ability to inhibit LDL oxidation. Correlations were made between individual proteins in the HDL fractions and their ability to participate in both functional assays. One peak of activity was found in the cholesterol efflux assay when analyzing fractions in the HDL range. Cholesterol efflux activity did not correlate strongly with any protein in the HDL range of fractions, though there was a weak correlation with Protein S (r=0.337, p&lt;0.01). However, the phospholipid (PL) and cholesterol (CH) concentration of the fractions correlated strongly with efflux (r=0.75. and r=0.61 respectively, both p&lt;0.00001) across all fractions (both LDL and HDL). In contrast, the PL or CH content were not correlated with anti-oxidation activity. However, there were 2 strong peaks of anti-oxidation activity in the HDL range that did correlate with specific proteins (all values of r&gt;0.3 and p&lt;0.05). Activity in the first peak, fraction 25, in the small HDL range, correlated most strongly with ceruloplasmin and inter-α-trypsin inhibitor 4, while activity in the second peak, fraction 28, in the minimally lipidated/free protein range, correlated with gelsolin and albumin. In conclusion, we have shown that PL and CH correlate more strongly with cholesterol efflux than any protein in the HDL sub-fractions, while the protein composition of particular HDL sub-fractions is a better indicator of its anti-oxidative capacity than the PL or CH concentration.

Effects of gender, age and menopausal status on serum apolipoprotein concentrations.

To undertake a comprehensive evaluation of apolipoprotein risk markers for cardiovascular disease (CVD) according to gender, age and menopausal status. Cross-sectional analysis of independent associations of gender, age and menopause with serum apolipoproteins. Apparently healthy Caucasian premenopausal (n = 109) and postmenopausal (n = 252) women not taking oral contraceptives or hormone replacement, and Caucasian men (n = 307). Serum apolipoprotein (apo) B, A-I and A-II concentrations were measured, plus serum total cholesterol, low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), triglycerides, cholesterol in HDL subfractions and the apoB/apoA-I, LDL-C/apoB, HDL-C/apoA-I and HDL-C/apoA-II ratios. Analyses were undertaken with and without standardization for confounding characteristics and in 5-year age ranges. Overall, apoB concentrations were highest in men but in women rose with age and menopause to converge, in the age range of 50-55 years, with concentrations in men. The LDL-C/apoB ratio was generally higher in women than in men. ApoA-I concentrations were highest in postmenopausal women and lowest in men (standardized median (IQR) 144 (130, 158) vs 119 (108, 132) g/l, respectively, P < 0·001). ApoA-II concentrations were also highest in postmenopausal women but were lowest in premenopausal women (40·3 (37·5, 44·5) vs 32·9 (30·5, 35·7) g/l, respectively, P < 0·001). Nevertheless, postmenopausal women had HDL-C/apoA-I and HDL-C/apoA-II ratios approaching the lowest ratios, which were seen in men. Consistent with adverse effects on CVD risk, male gender, ageing in women and menopause were associated with increased apoB concentrations, and menopause and male gender were associated with a decreased cholesterol content of HDL particles.

Tanshinone IIA affects the HDL subfractions distribution not serum lipid levels: Involving in intake and efflux of cholesterol

Aim of studyTanshinone IIA is an active component of the traditional Chinese medicine. This study aimed at investigating the mechanism of tanshinone IIA on anti-atherosclerosis, which may be because of that Tanshinone IIA can affect the HDL subfractions distribution and then regulate reverse cholesterol transport. Materials and methodsA model of hyperlipidaemia in rats was used. Tanshinone IIA was given daily after hyperlipidaemia. In vivo, lipid deposition and morphological changes in liver were analyzed; HDL subfractions and lipid level in serum as well as in liver were measured; the expression of genes related to cholesterol intake in liver and peritoneal macrophage cholesterol efflux were evaluated. In vitro, HepG2 cells and THP-1 cells were pretreated with tanshinone IIA and subsequently with ox-LDL to evaluate the total cholesterol and the expression of related genes. ResultsTanshinone IIA reduced the lipid deposition in liver. Moreover, it did not affect the serum lipid levels but reduced the levels of HDL middle subfractions and increased the levels of HDL large subfractions. Furthermore, tanshinone IIA could regulate the expressions of CYP7A1, LDL-R, SREBP2 and LCAT in the liver as well as the ABCA1 and CD36 in macrophage cells which is involving in the cholesterol intake and efflux respectively. It could reduce lipid accumulation caused by ox-LDL induction, and that also regulate the expressions of LDL-R, HMGCR and SREBP2 in HepG2 and ABCA1, CD36 in THP-1 cells. ConclusionA novel finding that tanshinone IIA was not reduce the serum lipid level but affects the HDL subfractions distribution and thereby regulating the intake and efflux of cholesterol.

Paraoxonase-1 activity is positively related to phospholipid transfer protein activity in type 2 diabetes mellitus: Role of large HDL particles

ObjectivesHigh density lipoprotein (HDL)-associated paraoxonase-1 (PON-1) exerts anti-oxidative properties, whereas phospholipid transfer protein (PLTP) is able to convert mature HDL into larger and smaller HDL particles. Here we tested associations of PON-1 with PLTP in type 2 diabetes mellitus (T2DM), a condition characterized by lower PON-1 activity and higher PLTP activity. Design and methodsSerum PON-1 (arylesterase activity), plasma PLTP activity (liposome-vesicle HDL system), and (apo)lipoproteins were measured in 81 T2DM subjects (mean age 59±9years; 31 women; no insulin treatment). In 48 participants, HDL subfractions were measured by nuclear magnetic resonance spectroscopy. ResultsIn univariate correlation analysis, PON-1 activity was positively related to PLTP activity (r=0.348, p=0.001). PLTP activity was positively related to blood pressure, body mass index and triglycerides, whereas PON-1 activity was positively to HDL cholesterol and apoA-I (p<0.05 to <0.01 for each). Both PLTP activity and PON-I activity were positively related to large HDL particles (r=0.379, p=0.008 and r=0.411, p=0.004, respectively). In multivariable linear regression analysis, PON-1 activity was associated with PLTP activity independent of clinical covariates and HDL cholesterol or apoA-I (β=0.340, p=0.001 and β=0.320, p=0.003, respectively). The association of PON-1 activity with PLTP activity was lost in analysis which included large HDL particles (large HDL: β=0.411, p=0.004). ConclusionsPON-1 activity is positively related to PLTP activity in T2DM, raising the possibility that PLTP could act to maintain PON-1. This association may in part be attributable to a common relationship of PON-1 and PLTP with large HDL particles.

HDL cholesterol and stroke risk: The Multi-Ethnic Study of Atherosclerosis

Background and purposeAccurate identification of risk factors for stroke is important for public health promotion and disease prevention. HDL cholesterol is a potential risk factor, yet its role in stroke risk is unclear, as is whether HDL cholesterol content or particle number might be a better indicator of stroke risk. Furthermore, the degree to which ethnicity moderates the risk is unknown. As such, the current study examines the associations between incident stroke and both HDL cholesterol concentration and particle number, and assesses the moderating role of race and ethnicity. MethodsThe sample is a racially diverse cohort of US adults between the ages of 45–84 years enrolled in the Multi-Ethnic Study of Atherosclerosis between 2000 and 2002 and followed until December 2011. The associations among cholesterol content and stroke risk, particle number and stroke risk, and the interaction with race were explored. ResultsThe incidence of stroke was 2.6%. HDL cholesterol concentration (mmol/L) (Hazard Ratio (HR) = .56; 95% Confidence Interval (CI): .312–.988) and number of large HDL particles (μmol/L) (HR = .52, CI: .278–.956) were associated with lower stroke risk. When interactions with race were evaluated, the relationship between both HDL variables and stroke were significant in Blacks, but not other races. ConclusionsHigher HDL cholesterol and a higher concentration of large particles are associated with lower risk of stroke in Blacks. Further research is needed to elucidate the mechanisms by which HDL subfractions may differentially affect stroke outcome in different races/ethnicities.

Circulating non–HDL-C levels were more relevant to atherogenic lipoprotein subfractions compared with LDL-C in patients with stable coronary artery disease

Conflicting results have been yielded as to whether low-density lipoprotein (LDL) cholesterol (LDL-C) or non-high-density lipoprotein (HDL) cholesterol (non-HDL-C) is a better marker of coronary artery disease (CAD) risk. Recently, plasma LDL and HDL subfractions have been suggested to be more accurately reflecting the lipoproteins' atherogenicity. We sought to compare the relationship between LDL-C or non-HDL-C and lipoprotein subfractions. We conducted a cross-sectional study in 351 consecutive stable CAD patients without lipid-lowering therapy. The LDL and HDL separations were performed using the Lipoprint System. The LDL-C levels were measured directly, and the non-HDL-C levels were calculated. The cholesterol concentrations of LDL (large, medium, and small) and HDL (small) particles were increased (all P<.001) by non-HDL-C or LDL-C quartiles, whereas the mean LDL particle size and cholesterol concentrations of HDL (large) were decreased (both P<.001) by non-HDL-C quartiles. In age- and gender-adjusted analysis, the cholesterol in small LDL was much strongly related to non-HDL-C than to LDL-C (r=0.539 vs 0.397, both P<.001). Meanwhile, the mean LDL particle size was more closely associated with non-HDL-C than LDL-C (r=-0.336 vs r=-0.136, both P<.05). Significantly, the cholesterol in large HDL was negatively correlated with non-HDL-C (r=-0223, P<.001) but not with LDL-C. These correlations were further confirmed by the fully adjusted multivariable linear regression analysis. Non-HDL-C, in comparison to LDL-C, was more relevant to atherogenic lipoprotein subfractions in patients with stable CAD, supporting that it may be better in assessing cardiovascular risk.

Increased cholesterol efflux capacity in metabolic syndrome: Relation with qualitative alterations in HDL and LCAT.

Metabolic syndrome (MetS) is associated with changes in HDL levels, composition and sub-fraction profile. Whether these alterations affect HDL anti-atherogenic function, specifically measured as its capacity to perform cholesterol efflux, is not yet clearly known. To evaluate the relation between serum cholesterol efflux capacity and the changes in HDL composition and sub-fraction profile in MetS. In 35 non-treated MetS patients and 15 healthy controls, HDL mediated cholesterol efflux was measured as the ability of apoB-depleted serum to accept cholesterol from cholesterol-loaded BHK cells expressing either ABCA1 or ABCG1. Additionally we determined: lipid profile, HDL sub-fractions (NMR) and LCAT mass (ELISA). Isolated HDL (δ:1.063-1.210 g/mL) was chemically characterized. Pre-β1-HDL was determined by 2D-electrophoresis in a sub-group of MetS and controls (n = 6 each). Surprisingly, MetS patients presented higher ABCA1 mediated cholesterol efflux (10.4 ± 1.8 vs. 8.7 ± 0.3%; p = 0.0001), without differences in ABCG1 efflux. In MetS, HDL showed reduction in particle size and number (p < 0.02) and lower large/small HDL ratio (p = 0.05), as well as triglyceride enrichment (p = 0.0001). Pre-β1-HDL was increased in MetS (p = 0.048) and correlated with ABCA1-cholesterol efflux (r = 0.64; p = 0.042). LCAT mass showed a tendency to reduction in MetS (p = 0.08), and inversely correlated with ABCA1-cholesterol efflux (r = -0.51; p = 0.001), independently of obesity and insulin-resistance (β = -0.40, p = 0.034). This is the first description of ABCA1 mediated cholesterol efflux in MetS. Regardless the reduced HDL-cholesterol, in vitro cholesterol efflux capacity by ABCA1 was enhanced, linked to increased pre-β1-HDL and slightly reduced in LCAT mass that would probably reflect a delay in reverse cholesterol transport occurring in MetS.

Efecto del ejercicio sobre las subpoblaciones HDL, la enzima lecitina-colesterol acil-transferasa y la proteína transportadora de ésteres de colesterol en estudiantes de Medicina

ObjectiveTo evaluate exercise effect on HDL subpopulations, lecithin-cholesterol acyltransferase enzyme and ester transfer protein cholesterol levels in medical students. MethodPopulation was divided voluntarily into 2 groups, exercise and no exercise. Waist circumference and body mass index were measured; subfractions HDL2 and HDL3 by ion precipitation and LCAT and CETP enzymes Enzyme-Linked Immuno-Sorbent Assay (ELISA). ResultsLipidrisk profile increased in both groups; HDL, HDL2 and HDL3 decreased in both groups, but only the HDL2 decreased significantly in students who exercised. LCAT and CETP remained without significant changes, however, in the exercise group, there was statistically significant decrease in HDL2 and LCAT in women. ConclusionsThis study shows that exercise does alter some variables such as waist circumference, body mass index and HDL3. These changes are dependent on gender, but despite the intervention of 3 months with an exercise program, it fails reducing lipid risk factors in this medical student populations, given their environment, which complicates their metabolic response to exercise.

Elevated Lipoprotein Lipase Activity Does Not Account for the Association Between Adiponectin and HDL in Type 1 Diabetes.

Increased high-density lipoprotein cholesterol (HDL-C) is common in type 1 diabetes (T1D) and is associated both with hyperadiponectinemia and with elevated lipoprotein lipase activity (LPL). Because adiponectin has been shown to increase LPL expression, elevated LPL may link the hyperadiponectinemia in T1D with increased HDL. The purpose of this study was to determine whether LPL activity accounts for the association between adiponectin and HDL in T1D. A cohort of 127 patients with T1D attending the Diabetes Clinic at the University of Miami and 103 healthy control subjects were recruited. HDL-C and adiponectin were measured in the full cohort and in a subgroup, HDL subfractions were obtained by ultracentrifugation, and LPL and hepatic lipase were measured in postheparin plasma. Total HDL-C and the lowest density HDL subfraction, apolipoprotein A-I, LPL activity, and adiponectin levels were higher in subjects with T1D than in control subjects (P < .05). Both adiponectin and LPL activity were directly associated with total HDL-C and its lowest density subfraction, but adiponectin and LPL were not correlated (P = 0.13). Adiponectin alone explained 11.6% and adiponectin plus LPL explained 23.8% of the HDL-C variance. In a multivariate model, adiponectin remained an independent predictor of HDL-C along with LPL and serum creatinine, explaining together 27% of HDL-C variance. Adiponectin was strongly associated with HDL-C in T1D, suggesting that hyperadiponectinemia is linked to the elevated HDL-C in this population. However, this relationship is independent of the association between LPL and HDL-C. Thus, elevated adiponectin and LPL activity are independently related to increased HDL-C in T1D.

Impaired antioxidant HDL function is associated with premature myocardial infarction.

There is growing evidence that the predictive value of HDL cholesterol levels for cardiovascular risk stratification is limited in patients with coronary artery disease (CAD). HDL function seems to be a more sensitive surrogate of cardiovascular risk estimation than simple serum levels. Therefore, we aimed to assess whether impaired antioxidant HDL function is involved in the development of premature acute myocardial infarction (AMI). In this multicentre case-control study, we compared the antioxidant function of HDL, measured by the HDL inflammatory index (HII), and HDL particle size in 184 patients comprising 92 patients with AMI at a very young age (≤40years of age) and 92 age- and gender-matched controls. Antioxidant capacities of HDL were significantly impaired in the acute phase of AMI (HII of 1·50 [IQR 1·10-1·74] vs. 0·56 [IQR 0·41-0·86] in controls, P<0·001 as well as in the chronic stable phase 1year after the event (HII of 0·85 [IQR 0·72-1·03] vs. 0·56 [IQR 0·41-0·86], P<0·001) compared to controls. Moreover, HDL function in the stable phase remained significantly associated with premature MI in adjusted logistic regression analysis with an OR of 2·24 per SD increase of HII (95% CI 1·28-3·91; P=0·005). Analyses of HDL size revealed a significant correlation between all HDL subfractions and HDL function in controls, whereas this correlation was lost for large and intermediate HDL in AMI patients. Impaired antioxidant function of HDL is independently associated with the development of premature AMI. The maintenance of HDL function might evolve into a significant therapeutic target, especially in patients with premature CAD.

HDL and LDL subfractions and coronary atherosclerosis in adult males

HDL and LDL subfractions and coronary atherosclerosis in adult males

Pleiotropic eff ects of HDL subfractions and HDL-associated enzymes on protection against coronary artery disease

Objective High-density lipoprotein cholesterol (HDL-C) levels are inversely related to the risk of coronary artery disease (CAD). Alterations in HDL-C subclass distribution and HDL-associated enzyme activities may be more important than total HDL levels for the progression of CAD. We intended to investigate the relationship of HDL-C subclass distribution and HDL-associated enzyme activities with CAD.Method and results Our study included 101 patients with stable coronary artery disease, and 64 healthy subjects. Serum levels of HDL lipoprotein-associated-phospholipase A2 (HDL-LpPLA2), paraoxonase 1 (PON1), and HDL subfraction distribution were measured. We found increased small HDL (sHDL) subfractions in patients with one-vessel disease (P < 0.001). We also found a reverse correlation between total HDL-C levels and aff ected vessel number (P <0.05). Plasma HDL-Lp PLA2 enzyme level was higher in each vessel disease category compared to the control group (P < 0.001). However, PON1 enzyme activity in patients with CAD was not statically signifi cant. Plasma SHDL, HDL-Lp PLA2 enzyme and Lp(a) were signifi cantly diff erent between subjects with CAD and control participants.Conclusions We demonstrated decreased SHDL particles and a lower cardioprotective HDL-LpPLA2 enzyme activity in all patient subgroups compared to controls. Measurement of total HDL-C level only may not be suffi cient to predict CAD risk.

Dyslipidemia and cardiovascular disease in women.

Cardiovascular disease is the major cause of death in women in developed countries. Dyslipidemia is highly prevalent in women, particularly after the menopause. Elevated low-density lipoprotein cholesterol (LDL-C) has been identified as the key lipid parameter in both genders whereas HDL-cholesterol and triglycerides have been more closely associated, in some studies, with cardiovascular risk in women. Menopause has been shown to be associated with an increase in total and LDL-cholesterol and a decrease in HDL-cholesterol (predominantly in the HDL2 subfraction). Despite its beneficial effects on the lipid profile, hormone replacement therapy is not recommended for primary or secondary prevention of cardiovascular disease in women. The latest meta-analysis of statin trials with gender-specific outcomes showed a similar benefit in women and men. The addition of ezetimibe to simvastatin in patients with acute coronary syndromes showed a further reduction of the primary endpoint in both genders. While there are no gender-related differences in drug treatment of dyslipidemia, current guidelines, to avoid overtreatment, strongly suggest risk estimation before initiating lipid-lowering treatment in women without manifest cardiovascular disease.

Cholesterol efflux capacity as a novel biomarker for incident cardiovascular events: has high-density lipoprotein been resuscitated?

HDL cholesterol efflux capacity and incident cardiovascular events Rohatgi et al N Engl J Med 2014;371:2383–2393. Although low levels of high-density lipoprotein cholesterol (HDL-C) represent a strong independent risk marker inversely associated with cardiovascular disease (CVD), large interventional trials have failed to translate the increases in HDL-C into reductions in cardiovascular events. As HDL plasma levels represent a pool of the different HDL subfractions, which may vary in their structure and function, its levels may not capture adequately the dynamic process of reverse cholesterol transport. This has led attention to be focused on markers of HDL function, for example, cholesterol efflux capacity, further supported by a recent population-based cohort study that has related it with incident atherosclerotic cardiovascular events, suggesting HDL hypothesis may need to be revisited. HDL particles are responsible for the reverse cholesterol transport, the physiological mechanism by which the cholesterol in peripheral tissues and cells is transferred to the liver for biliary excretion.1,2 Reverse cholesterol transport is considered an important atheroprotective mechanism because it facilitates the removal of excess cholesterol from lipid-laden macrophages in the arterial wall and the subsequent reduction in the proinflammatory responses; in its first steps, the reverse cholesterol transport requires HDL particles to act as extracellular acceptors of cholesterol from these cells.1,2 The cholesterol efflux capacity (CEC), that is, the ability of HDL particles to accept cholesterol esters from cholesterol-loaded macrophages, represents, therefore, a key process within the mechanism of reverse cholesterol transport.1,2 In animal models, cholesterol efflux can modulate the severity of atherosclerosis, and in humans, CEC has been related to prevalent coronary artery disease independently of HDL-C levels in cross-sectional studies.3 In a recent article published by Rohatgi et al in the New England Journal of Medicine , CEC was for …