Association of maternal HDL2-c concentration in the first trimester and the risk of large for gestational age birth.

BACKGROUND: Maternal lipid levels during pregnancy are critical for fetal development. Recent studies revealed that high-density lipoprotein cholesterol (HDL-c) levels during pregnancy were negatively correlated with birthweight. High-density lipoprotein 2 cholesterol (HDL2-c) is one of the major subclasses of HDL-c, and its relationship with birthweight is unclear. Association of HDL2-c concentration in the first trimester and risk of large for gestational age (LGA) was explored. METHODS: This study recruited pregnant women who registered in Fuxing Hospital from October 2018 to January 2020, had regular obstetric examinations during pregnancy, and delivered between June 2019 and September 2020. Finally, 549 participants were recruited for the study. Maternal demographic characteristics and venous blood were collected at the 6th-14th gestational week, and serum total cholesterol (TC), triglyceride (TG), HDL-c, HDL2-c, high-density lipoprotein 3 cholesterol (HDL3-c), and low-density lipoprotein cholesterol (LDL-c) concentrations were detected. Neonatal characteristics were collected at delivery. A logistic regression model was used to explore the relationship between the first trimester HDL2-c concentration and LGA incidence. A nomogram was developed, and the performance was evaluated with a concordance index. RESULTS: Seventy-five mothers delivered LGA infants, and the LGA incidence was 13.66%. LGA mothers had significantly lower serum HDL-c and HDL2-c concentrations than appropriate for gestational age (AGA) mothers. A logistic regression model showed that HDL2-c concentration was negatively correlated with LGA risk (odds ratio (OR) = 0.237, 95% confidence intervals (CI): 0.099-0.567, P = 0.001) when adjusted for age, prepregnancy body mass index (BMI), and parity. A nomogram was generated using all these risk factors. The area under the curve (AUC) was 0.663 (95% CI: 0.593-0.732). CONCLUSIONS: Maternal HDL2-c concentration in the first trimester was negatively correlated with the risk of LGA.

HDL and Surgery.

In addition to the well-known functions, plasma HDL also plays an important role in postsurgery periods. In this chapter, we summarized the changes of HDL after surgery like bariatric surgery and cardiac surgery. Not only the amount of HDL changed, the HDL components or functions have also been altered after various surgeries. Furthermore, a few HDL-related indexes have been recognized as important clinical predictors after surgery, such as HDL cholesterol efflux capacity, HDL pro-inflammatory index, HDL cholesterol (HDL-C) concentration, and monocyte count to HDL ratio (MHR).

Apolipoprotein A-I modulates HDL particle size in the absence of apolipoprotein A-II.

Human high-density lipoproteins (HDLs) are a complex mixture of structurally related nanoparticles that perform distinct physiological functions. We previously showed that human HDL containing apolipoprotein A-I (APOA1) but not apolipoprotein A-II (APOA2), designated LpA-I, is composed primarily of two discretely sized populations. Here, we isolated these particles directly from human plasma by antibody affinity chromatography, separated them by high-resolution size-exclusion chromatography and performed a deep molecular characterization of each species. The large and small LpA-I populations were spherical with mean diameters of 109 Å and 91 Å, respectively. Unexpectedly, isotope dilution MS/MS with [15N]-APOA1 in concert with quantitation of particle concentration by calibrated ion mobility analysis demonstrated that the large particles contained fewer APOA1 molecules than the small particles; the stoichiometries were 3.0 and 3.7 molecules of APOA1 per particle, respectively. MS/MS experiments showed that the protein cargo of large LpA-I particles was more diverse. Human HDL and isolated particles containing both APOA1 and APOA2 exhibit a much wider range and variation of particle sizes than LpA-I, indicating that APOA2 is likely the major contributor to HDL size heterogeneity. We propose a ratchet model based on the trefoil structure of APOA1 whereby the helical cage maintaining particle structure has two "settings"-large and small-that accounts for these findings. This understanding of the determinants of HDL particle size and protein cargo distribution serves as a basis for determining the roles of HDL subpopulations in metabolism and disease states.

The influence of high-density lipoprotein (HDL) and HDL subfractions on insulin secretion and cholesterol efflux in pancreatic derived ß-cells.

BACKGROUND: High-density lipoprotein (HDL) is considered a complex plasma-circulating particle with subfractions that vary in function, size, and chemical composition. We sought to test the effects of HDL, and HDL subfractions on insulin secretion and cholesterol efflux in the ß-cell line MIN-6. METHODS: We used total HDL and HDL subfractions 2a, 2b, 3a, 3b, and 3c, isolated from human plasma, to test insulin secretion under different glucose concentrations as well as insulin content and cholesterol efflux in the insulinoma MIN-6 cell line. RESULTS: Incubation of MIN-6 cells with low glucose and total HDL increased insulin release two-fold. Meanwhile, when high glucose and HDL were used, insulin release increased more than five times. HDL subfractions 2a, 2b, 3a, 3b, and 3c elicited higher insulin secretion and cholesterol efflux than their respective controls, at both low and high glucose concentrations. The insulin content of the MIN-6 cells incubated with low glucose and any of the five HDL subclasses had a modest reduction compared with their controls. However, there were no statistically significant differences between each HDL subfraction on their capacity of eliciting insulin secretion, insulin content, or cholesterol efflux. CONCLUSIONS: HDL can trigger insulin secretion under low, normal, and high glucose conditions. We found that all HDL subfractions exhibit very similar capacity to increase insulin secretion and cholesterol efflux. This is the first report demonstrating that HDL subfractions act both as insulin secretagogues (under low glucose) and insulin secretion enhancers (under high glucose) in the MIN-6 cell line.

Effects of tibolone or continuous combined oestradiol and norethisterone acetate on lipids, high-density lipoprotein subfractions and apolipoproteins in postmenopausal women in a two-year, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To compare the effects of (a) tibolone, (b) continuous combined oestrogen plus progestogen and (c) placebo on plasma lipid and lipoprotein markers of cardiovascular risk in healthy postmenopausal women. STUDY DESIGN: Randomized, single-centre, placebo-controlled, double-blind study. PATIENTS: One hundred and one postmenopausal women were randomized (1:1:1) into one of three groups taking daily 2.5 mg tibolone, continuous oral oestradiol-17ß 2 mg plus norethisterone acetate 1 mg daily (E2 /NETA) or placebo. MAIN OUTCOME MEASURES: Fasting serum lipid, lipoprotein and apolipoprotein concentrations measured at baseline and after 6, 12 and 24 months of treatment. RESULTS: Both tibolone and E2 /NETA lowered plasma total cholesterol concentrations relative to placebo. With tibolone, high-density lipoprotein cholesterol (HDL-C) was reduced (-27% at 24 months, P < .001), the greatest effect being in the cholesterol-enriched HDL2 subfraction (-40%, P < .001). Tibolone's effect on HDL concentrations was also apparent in the principal HDL protein component, apolipoprotein AI (-29% at 24 months, P < .001). However, there was no significant effect of tibolone on low-density or very low-density lipoprotein cholesterol (LDL-C and VLDL-C, respectively). By contrast, the greatest reduction in cholesterol with E2 /NETA was in LDL-C (-22% at 24 months, P = .008). E2 /NETA reduced HDL-C to a lesser extent than tibolone (-12% at 24 months, P < .001). Effects on HDL apolipoproteins were similarly diminished relative to tibolone. E2 /NETA had no effect on VLDL-C or on the protein component of LDL, apolipoprotein B. CONCLUSION: Tibolone reduces serum HDL. E2 /NETA reduces LDL cholesterol but not apolipoprotein B, suggesting decreased cholesterol loading of LDL. Any impact these changes may have on CVD risk needs further investigation.

Compositional Features of HDL Particles Interact with Albuminuria to Modulate Cardiovascular Disease Risk.

Lipoproteins containing apolipoprotein B modify associations of elevated urinary albumin excretion (UAE) with cardiovascular disease (CVD). Additionally, it is known that elevated UAE alters high-density lipoprotein functionality. Accordingly, we examined whether HDL features might also modify UAE-associated CVD. Multivariable Cox proportional-hazards modeling was performed on participants of the PREVEND (Prevention of Renal and Vascular Endstage Disease) study at the baseline screening with standard lipid/lipoprotein analyses and, three-to-four years later (second screen), with nuclear magnetic resonance lipoprotein analyses focusing on HDL parameters including HDL particle (HDL-P) and apolipoprotein A-I concentrations. These were used with UAE and derived measures of HDL apoA-I content (apoA-I/HDL-C and apoA-I/HDL-P) in risk models adjusted for gender, age, apoB, diabetes, past CVD history, CRP and GFR. Interaction analysis was also performed. Baseline screening revealed significant associations inverse for HDL-C and apoA-I and direct for apoA-I/HDL-C. The second screening demonstrated associations inverse for HDL-P, large HDL-P, medium HDL-P, HDL size, and apoA-I/HDL-P. Significant interactions with UAE included apoA-I/HDL-C at the baseline screening, and apoA-I/HDL-P and medium HDL-P but not apoA-I/HDL-C at the second screening. We conclude that features of HDL particles including apoA-I/HDL-P, indicative of HDL apoA-I content, and medium HDL-P modify associations of elevated UAE with CVD risk.

Gender differences in LDL- and HDL-cholesterol subfractions in patients after the acute ischemic stroke and their association with oxidative stress markers.

The aim of our study was to examine gender differences of LDL- and HDL-cholesterol subfractions in patients after the acute ischemic stroke with focus on small LDL and HDL subfractions, and their association with oxidative stress markers. In addition, we have monitored the 7-day effect of cholesterol-lowering drugs administered to patients after the acute ischemic stroke, on these subfractions. Eighty two stroke patients and 81 age matched controls were included in this study. Blood was collected from patients within 24 h after the stroke (group A) and re-examined at the 7-day follow-up (group B). We have found gender differences in LDL- and HDL-subfractions in stroke patients, lipid-lowering drugs administered to acute ischemic stroke patients significantly reduced all measured parameters of lipoprotein profile. In the group A LDL1 subfraction positively correlated with activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) indicating a protective role of this subfraction. On the contrary, small HDL subfractions positively correlated with lipoperoxide levels and negatively with trolox equivalent antioxidant capacity in plasma suggesting a negative role of these subfractions. In this work we have confirmed the hypothesis of atherogenic properties of small HDL subfractions and anti-atherogenic properties of large LDL1-subfractions.

The effect of weight loss on HDL subfractions and LCAT activity in two genotypes of APOA-II -265T>C polymorphism.

BACKGROUND: People may have different responses to the same environmental changes. It has been reported that genome variations may be responsible for these differences. Also, HDL subfractions may be influenced by different genetic variations. The aim of the present study was to determine gene-diet interactions and to evaluate the influence of weight loss on HDL subfractions between two genotypes of -265 T>C APOA-II polymorphism. METHODS: In the present study, 56 overweight and obese patients with type 2 diabetes mellitus were selected from 697 genotype-specified subjects. After matching for gender, age and BMI at the beginning of the study, an equal number of patients remained on each genotype of APOA-II (TT/TC and CC group). After a 6-week calorie restriction program, 44 patients completed the study. Serum HDL subfractions, including HDL2 and HDL3 and LCAT activity, were compared between the two genotypes and, before and after the intervention, were separated in each genotype. RESULTS: Serum concentration of HDL and its subfractions decreased significantly due to the weight loss. A comparison of the mean changes between the genotypes showed that HDL3 significantly decreased in the CC genotype while, in the TT/TC group, the serum concentration of HDL2 was significantly reduced. However, the increase of LCAT activity was not significant among the two genotypes. CONCLUSION: A comparison of mean changes of variables within two genotype groups showed that C homozygote carriers lead to a general shift toward larger size HDL subfractions and T allele carriers shift toward smaller size HDL subfractions after weight loss.

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

AIM OF STUDY: Tanshinone 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 METHODS: A 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. RESULTS: Tanshinone 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. CONCLUSION: A 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.

Impact of selective LDL apheresis on serum chemerin levels in patients with hypercholesterolemia.

BACKGROUND: Selective low-density lipoprotein (LDL) apheresis is commonly used to treat patients with familial hypercholesterolemia (FH). Chemerin is an adipokine with putative roles in the regulation of lipid metabolism. METHODS: In our pilot study, we measured serum chemerin levels by enzyme-linked immunosorbent assay in six severe heterozygous FH patients before and after their first LDL apheresis treatments using the technique of direct adsorption of lipoproteins (DALI). RESULTS: The first treatment sessions decreased serum chemerin levels by an average of 27.26 %. While following one patient, 12 months of regular LDL apheresis resulted in a permanent reduction in his serum chemerin level. Changes in the lipoprotein subfractions measured by gel electrophoresis (Lipoprint) correlated with the reduction of chemerin levels. Furthermore, we eluted and then measured chemerin bound to the DALI column. CONCLUSION: We conclude that LDL apheresis decreases the circulating level of chemerin by binding the protein to the column and thus improves lipoprotein subfraction pattern.

High-density lipopoprotein antioxidant capacity, subpopulation distribution and paraoxonase-1 activity in patients with systemic lupus erythematosus.

BACKGROUND: The causes of increased cardiovascular risk in systemic lupus erythematosus (SLE) are not understood thoroughly, although presence of traditional cardiovascular risk factors and disease-specific agents were also proposed. In this study, we investigated the quantitative changes in the lipid profile, as well as qualitative characteristics of high-density lipoprotein (HDL) and markers of inflammation and disease activity in SLE patients. METHODS: Lipoprotein levels were determined in 51 SLE patients and 49 healthy controls, matched in age and gender. HDL antioxidant capacity was determined spectrophotometrically with a cell-free method of hemin-induced low-density lipoprotein (LDL) oxidation. Polyacrylamide gel-electrophoresis was used for HDL subfraction analysis. Human paraoxonase-1 (PON1) activity, apolipoprotein A1 (ApoA1) and oxidized LDL concentrations, as well as interleukin-6, high-sensitivity C-reactive protein, serum amyloid A and monocyte chemotactic protein-1 levels were determined. RESULTS: HDL-cholesterol and ApoA1 concentrations decreased significantly in SLE subjects. Also, PON1 arylesterase activity (125.65 ± 26.87 vs. 148.35 ± 39.34 U/L, p = 0.001) and total HDL antioxidant capacity (165.82 ± 58.28% vs. 217.71 ± 54.36%, p < 0.001) were significantly reduced in patients compared to controls. Additionally, all HDL subfraction concentrations were significantly decreased in patients, while the levels of the examined inflammatory markers were significantly elevated in SLE subjects. The latter correlated positively with disease activity, and negatively with HDL concentration and total HDL antioxidant capacity, respectively. PON1 arylesterase activity and erythrocyte sedimentation rate were independent predictors of total HDL antioxidant capacity. CONCLUSIONS: Induced by the systemic inflammation, altered composition and antioxidant activity may diminish the anti-atherogenic effect of HDL and therefore may contribute to the increased cardiovascular risk of SLE patients.

High-density lipoprotein subfractions and influence of endothelial lipase in a healthy Turkish population: a study in a land of low high-density lipoprotein cholesterol.

PURPOSE: Low concentration of high-density lipoprotein (HDL) is prevalent in Turkey. Endothelial lipase (EL) regulates lipoprotein metabolism. Small, lipid-poor HDL particles represent more-efficient cholesterol acceptors than their large, lipid-rich counterparts. The aim of this study was to investigate HDL subfractions and the effect of EL on HDL concentrations in healthy Turkish population. METHODS: 102 healthy subjects were included in the study (mean age 33.6 ± 10.3 years, 42 female). HDL subfractions were assayed by single precipitation method and EL concentrations were measured by competitive enzyme immunoassay. RESULTS: Mean HDL concentrations were 1.45 ± 0.37 mmol/L in women, 1.10 ± 0.30 mmol/L in men. Small HDL subfraction levels did not differ statistically between < 1 mmol/L and ≥ 1.6 mmol/L total HDL groups. Small HDL was not correlated with EL, low density lipoprotein cholesterol (LDL), triglyceride (TG) and age but positively correlated with total cholesterol and HDL (r = 0.2, p = 0.017; r = 0.2, p = 0.028, respectively). Large HDL was not correlated with age, EL and total cholesterol, and negatively correlated with HDL, LDL, TG (r = - 0.7, p < 0.001; r = - 0.2, p = 0.045; r = - 0.3, p < 0.001, respectively). If subjects were divided into two groups as HDL< 1 mmol/L and HDL > 1.6 mmol/L, mean EL concentrations were 475.83 ± 521.77 nmol/L and 529.71 ± 276.92 nmol/L, respectively (p = 0.086). CONCLUSION: There were no differences between small HDL concentrations in the HDL low and high groups. Our data did not support EL to be the reason for low HDL in a healthy Turkish population. Our results in a healthy population may serve as a reference for clinical studies on HDL subfractions.

Effects of phytosterol supplementation on lipoprotein subfractions and LDL particle quality.

Phytosterols are natural components of plant-based foods used as supplements because of their known cholesterol-lowering effect. However, their effects on lipoprotein subfractions and the quality of the LDL particle have not been studied in greater detail. We aimed to evaluate the effects of phytosterols supplements on lipids, lipoproteins subfractions, and on the quality of LDL. A prospective, pilot-type, open label, cross-over study, randomized 23 males in primary prevention of hypercholesterolemia to receive diet or diet plus phytosterol (2.6 g in 2 doses, with meals) for 12 weeks, when treatments were switched for another 12 weeks. Lipoprotein subfractions were analyzed by electrophoresis in polyacrylamide gel (Lipoprint System®). The Sampson equation estimated the small and dense (sd) and large and buoyant (lb) LDL subfractions from the lipid profile. Quality of LDL particle was analyzed by Z-scan and UV-vis spectroscopy. Primary outcome was the comparison of diet vs. diet plus phytosterols. Secondary outcomes assessed differences between baseline, diet and diet plus phytosterol. Non-parametric statistics were performed with p < 0.05. There was a trend to reduction on HDL-7 (p = 0.05) in diet plus phytosterol arm, with no effects on the quality of LDL particles. Heatmap showed strong correlations (ρ > 0.7) between particle size by different methods with both interventions. Diet plus phytosterol reduced TC, increased HDL-c, and reduced IDL-B, whereas diet increased HDL7, and reduced IDL-B vs. baseline (p < 0.05, for all). Phytosterol supplementation demonstrated small beneficial effects on HDL-7 subfraction, compared with diet alone, without effects on the quality of LDL particles.This trial is registered in Clinical Trials (NCT06127732) and can be accessed at https://clinicaltrials.gov .

HDL-Cholesterol Subfraction Dimensional Distribution Is Associated with Cardiovascular Disease Risk and Is Predicted by Visceral Adiposity and Dietary Lipid Intake in Women.

HDL-cholesterol quality, including cholesterol distribution in HDL subfractions, is emerging as a key discriminant in dictating the effects of these lipoproteins on cardiovascular health. This study aims at elucidating the relationship between cholesterol distribution in HDL subfractions and CVD risk factors as well as diet quality and energy density in a population of pre- and postmenopausal women. Seventy-two women aged 52 ± 6 years were characterized metabolically and anthropometrically. Serum HDL-C subfractions were quantified using the Lipoprint HDL System. Cholesterol distribution in large HDL subfractions was lower in overweight individuals and study participants with moderate to high estimated CVD risk, hypertension, or insulin resistance. Cholesterol distribution in large, as opposed to small, HDL subfractions correlated negatively with insulin resistance, circulating triglycerides, and visceral adipose tissue (VAT). VAT was an independent positive and negative predictor of cholesterol distribution in large and small HDL subfractions, respectively. Furthermore, an increase in energy intake could predict a decrease in cholesterol levels in large HDL subfractions while lipid intake positively predicted cholesterol levels in small HDL subfractions. Cholesterol distribution in HDL subfractions may represent an additional player in shaping CVD risk and a novel potential mediator of the effect of diet on cardiovascular health.

HDL subfractions determined by microfluidic chip electrophoresis predict the vulnerability of intracranial plaque: A HRMRI study.

AIM: High-density lipoprotein (HDL) can be divided into several subfractions based on density, size and composition. Accumulative evidence strongly suggests that the subfractions of HDL have very different roles in the pathogenesis of atherosclerosis. The purpose of this study was to further delineate the relationship between HDL subfractions extracted by microfluidic chip electrophoresis and the vulnerability of plaques in patients with intracranial atherosclerosis with a high-resolution magnetic resonance imaging (HRMRI) study. METHODS: We prospectively enrolled patients with single atherosclerotic plaque in the middle cerebral artery (MCA) or basilar artery (BA) between July 2020 and Dec 2022 and performed 3-tesla HRMRI on the relevant artery. The HDL cholesterol concentration and HDL subfractions (HDL-2a, HDL-2b and HDL-3) percentage were analyzed in serum samples from the same patients by electrophoresis on a microfluidics system. RESULTS: A total of 81 MCA or BA plaques [38 (46.9%) symptomatic and 43 (53.1%) asymptomatic] in 81 patients were identified on HRMRI. Patients with symptomatic plaques had a significantly lower HDL-2b level than asymptomatic plaques [symptomatic vs. asymptomatic: 0.16 (0.10-0.18) vs. 0.27(0.21-0.34), p = 0.001]. After adjusting for demographics and vascular risk factors, logistic regression showed that HDL-2b was inversely associated with asymptomatic plaques (B = -0.04, P = 0.017). According to receiver operating characteristic (ROC) curve model analysis, the cutoff point of HDL-2b in predicting asymptomatic plaques was 0.21 mmol/L (Area under curve: 0.719, specificity: 73.7%, sensitivity: 72.1%). Furthermore, plaque enhancement on HRMRI (P < 0.001), positive remodeling (P < 0.001), plaque load (P < 0.001) and luminal stenosis (P < 0.001) were superior among patients with HDL-2b < 0.21 mmol/L. CONCLUSIONS: Our data showed that serum HDL-2b levels may serve as a biomarker for predicting vulnerability in intracranial atherosclerotic plaques.

Separation of the principal HDL subclasses by iodixanol ultracentrifugation.

HDL subclasses detection, in cardiovascular risk, has been limited due to the time-consuming nature of current techniques. We have developed a time-saving and reliable separation of the principal HDL subclasses employing iodixanol density gradient ultracentrifugation (IxDGUC) combined with digital photography. HDL subclasses were separated in 2.5 h from prestained plasma on a three-step iodixanol gradient. HDL subclass profiles were generated by digital photography and gel scan software. Plasma samples (n = 46) were used to optimize the gradient for the resolution of HDL heterogeneity and to compare profiles generated by IxDGUC with gradient gel electrophoresis (GGE); further characterization from participants (n = 548) with a range of lipid profiles was also performed. HDL subclass profiles generated by IxDGUC were comparable to those separated by GGE as indicated by a significant association between areas under the curve for both HDL2 and HDL3 (HDL2, r = 0.896, P < 0.01; HDL3, r = 0.894, P < 0.01). The method was highly reproducible, with intra- and interassay coefficient of variation percentage < 5 for percentage area under the curve HDL2 and HDL3, and < 1% for peak Rf and peak density. The method provides time-saving and cost-effective detection and preparation of the principal HDL subclasses.

Association of CETP and LIPC Gene Polymorphisms with HDL and LDL Sub-fraction Levels in a Group of Indian Subjects: A Cross-Sectional Study.

There is an increasing interest to understand the molecular basis of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) subfractions and their association with coronary artery disease (CAD). The formation of these subfractions is greatly influenced by hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) enzymes. To identify genetic markers influencing LDL and HDL subfractions and their role in CAD we performed a case-control genetic association study on 117 healthy controls and 119 angiographically verified CAD patients. Biochemical analysis was performed using standard assays. HDL-C and LDL-C subfractions were estimated using precipitation methods. Genotyping of C-514T (rs1800588) in the LIPC gene for HL and I405V (rs5882) in the CETP gene was done using PCR-based restriction enzyme analysis and sequencing. Both the polymorphisms were not associated with CAD. The C-514T was associated with increased HDL3-C levels in controls (P = 0.049). The I405V polymorphism was found to be associated with low levels of small dense, LDL (P = 0.038). A multiple regression analysis showed that the effects were dependent on gender and triglyceride levels. We conclude that these polymorphisms are not associated with CAD but are important determinants of HDL-C and small dense LDL particles in our population.

The association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques assessed by near-infrared spectroscopy.

Background: Lipid content in coronary atheromatous plaques, measured by near-infrared spectroscopy (NIRS), can predict the risk of future coronary events. Biomarkers that reflect lipid content in coronary plaques may therefore improve coronary artery disease (CAD) risk assessment. Purpose: We aimed to investigate the association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques in statin-treated patients with stable CAD undergoing percutaneous coronary intervention. Methods: 56 patients with stable CAD underwent three-vessel imaging with NIRS when feasible. The coronary artery segment with the highest lipid content, defined as the maximum lipid core burden index within any 4 mm length across the entire lesion (maxLCBI4mm), was defined as target segment. Lipoprotein subfractions and Lipoprotein a (Lp(a)) were analyzed in fasting serum samples by nuclear magnetic resonance spectroscopy and by standard in-hospital procedures, respectively. Penalized linear regression analyses were used to identify the best predictors of maxLCBI4mm. The uncertainty of the lasso estimates was assessed as the percentage presence of a variable in resampled datasets by bootstrapping. Results: Only modest evidence was found for an association between lipoprotein subfractions and maxLCBI4mm. The lipoprotein subfractions with strongest potential as predictors according to the percentage presence in resampled datasets were Lp(a) (78.1 % presence) and free cholesterol in the smallest high-density lipoprotein (HDL) subfractions (74.3 % presence). When including established cardiovascular disease (CVD) risk factors in the regression model, none of the lipoprotein subfractions were considered potential predictors of maxLCBI4mm. Conclusion: In this study, serum levels of Lp(a) and free cholesterol in the smallest HDL subfractions showed the strongest potential as predictors for lipid content in coronary atheromatous plaques. Although the evidence is modest, our study suggests that measurement of lipoprotein subfractions may provide additional information with respect to coronary plaque composition compared to traditional lipid measurements, but not in addition to established risk factors. Further and larger studies are needed to assess the potential of circulating lipoprotein subfractions as meaningful biomarkers both for lipid content in coronary atheromatous plaques and as CVD risk markers.

Afamin Levels and Their Correlation with Oxidative and Lipid Parameters in Non-diabetic, Obese Patients.

Background: Afamin is a liver-produced bioactive protein and features α- and γ-tocopherol binding sites. Afamin levels are elevated in metabolic syndrome and obesity and correlate well with components of metabolic syndrome. Afamin concentrations, correlations between afamin and vitamin E, afamin and lipoprotein subfractions in non-diabetic, obese patients have not been fully examined. Methods: Fifty non-diabetic, morbidly obese patients and thirty-two healthy, normal-weight individuals were involved in our study. The afamin concentrations were measured by ELISA. Lipoprotein subfractions were determined with gel electrophoresis. Gas chromatography-mass spectrometry was used to measure α- and γ tocopherol levels. Results: Afamin concentrations were significantly higher in the obese patients compared to the healthy control (70.4 ± 12.8 vs. 47.6 ± 8.5 µg/mL, p < 0.001). Positive correlations were found between afamin and fasting glucose, HbA1c, hsCRP, triglyceride, and oxidized LDL level, as well as the amount and ratio of small HDL subfractions. Negative correlations were observed between afamin and mean LDL size, as well as the amount and ratio of large HDL subfractions. After multiple regression analysis, HbA1c levels and small HDL turned out to be independent predictors of afamin. Conclusions: Afamin may be involved in the development of obesity-related oxidative stress via the development of insulin resistance and not by affecting α- and γ-tocopherol levels.

Effect of thyroid function on pre-ß1 high-density lipoprotein levels in patients with Graves' disease undergoing radioiodine treatment.

CONTEXT: The metabolism of HDL is altered in thyroid dysfunctions. Preß-1 HDL is a very small discoidal precursor HDL and promotes cholesterol efflux via ABCA1. The effects of thyroid dysfunctions on pre-ß1 HDL are unknown. Thyroid hormone regulates ANGPTL3 expression, which may participate in HDL metabolism in thyroid dysfunctions. OBJECTIVE: To determine the variation of HDL subfractions, especially preß-1 HDL in thyroid dysfunctions, and whether ANGPTL3 mediates the effect of thyroid function on HDL metabolism. METHODS: We recruited 26 patients with Graves' disease undergoing radioiodine treatment. They were evaluated at three time points: at baseline, when they were hypothyroid after radioiodine treatment, and when they were on stable levothyroxine replacement and euthyroid. RESULTS: The concentrations of smaller HDL particles Preß-1 HDL and HDL3 were highest at the hyperthyroid state, and lowest at the hypothyroid state. While the larger HDL particles HDL2 and HDL1 changed just the opposite. Preß1-HDL and HDL3 were positively correlated to fT3 and fT4, while were negatively correlated to TSH. In contrast, HDL1 was negatively associated with fT3 and fT4, while was positively associated with TSH. The correlations between thyroid hormones and HDL subfractions remained significant after adjusting for ANGPTL3. CONCLUSIONS: There is a shift form smaller HDL particles pre-ß1 HDL and HDL3 to larger HDL particles HDL2 and HDL1 in hypothyroidism, while the change is just the opposite in hyperthyroidism. In future, cholesterol efflux capacity should be measured to determine if the function of HDL particles also changes with the shifting of HDL subfractions.