High-density Lipoprotein Cholesterol Subclasses Research Articles

Association between the proportion of HDL-cholesterol subclasses and the severity of coronary artery stenosis in patients with acute myocardial infarction

Past research has shown an inverse correlation between high-density lipoprotein (HDL) and coronary heart disease (CHD), while recent studies have shown that extremely high or low HDL levels increase the risk of cardiovascular death. To explore the relationships between HDL subtypes and the degree of coronary artery stenosis in patients with acute myocardial infarction (AMI). This was a single-center cross-sectional study. Ultimately, we included 1,200 adult participants with AMI hospitalized from 2017 to 2023. Patients were classified into mild and moderate-severe groups according to their Gensini score. Restricted cubic spline and multivariate logistic regression models were used to explore the associations between HDL subclasses and the severity of coronary stenosis. The adjusted odds ratios (ORs), 95% confidence intervals (CIs), and p values for HDL subclasses in the multivariate logistic model (adjusted for age, gender, hypertension status, diabetes status, stroke status, and kidney disease status) were as follows: HDL-2b: 0.97 (0.95-1.00, p= 0.018) and HDL-3: 0.98 (0.97-0.99, p= 0.008). Subgroup analysis revealed that HDL-3 exhibited a statistically significant impact on the severity of coronary stenosis among individuals <75 years of age and among men, and the influence of HDL-2b on the severity of coronary stenosis was statistically significant only in individuals aged ≥75 years. The relationship between reduced levels of HDL-2b and HDL-3 and the risk of coronary stenosis exhibited a linear pattern and was significantly modified by age. Subgroup analysis identified specific populations that warrant attention regarding HDL-2b and HDL-3.

Cholesterol Uptake Capacity in Cord Blood of Preterm Infants.

There is insufficient research on cholesterol uptake capacity (CUC) in preterm infants; therefore, the relationship between CUC and cholesterol transport in preterm infants is unclear. This study aimed to clarify the relationship between CUC and anthropometric measurements, high-density lipoprotein cholesterol (HDL-C) levels, and HDL-C subclasses in preterm infants. Fifty-eight preterm infants were divided into small-for-gestational age (n = 20) (SGA) and appropriate-for-gestational age (AGA) (n = 38). CUC was measured using a fully automated immunoassay system, HI-1000. HDL-C subclasses were measured using high-performance liquid chromatography. SGA showed significantly lower HDL-C and CUC levels than AGA. We found a positive correlation between CUC and birth weight, birth height, and birth head circumference in preterm infants. Moreover, CUC had a strong relationship with HDL-C and very large, large, and medium HDL-C in preterm infants. In preterm infants, CUC is associated with normal growth and may indicate the ability to transport cholesterol forward by large-or medium-size HDL.

Association of proportion of the HDL-cholesterol subclasses HDL-2b and HDL-3 and macrovascular events among patients undergoing hemodialysis

Altered high-density lipoprotein cholesterol (HDL-C) subclass distribution in hemodialysis (HD) patients is well documented. Aim of this study is to investigate the relationship between HDL-C subclass distribution and macrovascular events in patients undergoing HD. A total of 164 prevalent HD patients and 71 healthy individuals in one hospital-facilitated clinic were enrolled from May 2019 to July 2019 and individual HD patients was follow-up for one year. Macrovascular events (cerebral stroke, coronary heart disease) were recorded in the study period. The HDL-2b, HDL-3 proportions and biochemical parameters were measured. Pearson correlation test and logistic regression analysis were used to examine correlation and odds ratio (OR). 144 HD patients completed one-year follow-up. Cohort with macrovascular events revealed significantly lower HDL-2b and higher HDL-3 subclass proportions compared to those without events. By multivariable adjustment, HDL-3 subclass proportion revealed significantly increase risk for these events (OR 1.17, 95% CI 1.02–1.41, P = 0.044). HDL-2b subclass was significantly higher and HDL-3 subclass was significantly lower in the HD cohort under the hs-CRP level of < 3 mg/L compared to higher hs-CRP level. In conclusion, HDL-2b and HDL-3 subclasses distributions were associated with macrovascular events in HD patients. Proinflammatory status influences the distribution of HDL-2b and HDL-3 subclasses in HD patients.

A homogeneous assay to determine high-density lipoprotein subclass cholesterol in serum

Existing methods to measure high-density lipoprotein cholesterol (HDL-C) subclasses (HDL2-C and HDL3-C) are complex and require proficiency, and thus there is a need for a convenient, homogeneous assay to determine HDL-C subclasses in serum. Here, cholesterol reactivities in lipoprotein fractions [HDL2, HDL3, low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL)] toward polyethylene glycol (PEG)-modified enzymes were determined in the presence of varying concentrations of dextran sulfate and magnesium nitrate. Particle sizes formed in the lipoprotein fractions were measured by dynamic light scattering. We optimized the concentrations of dextran sulfate and magnesium nitrate before assay with PEG-modified enzymes to provide selectivity for HDL3-C. On addition of dextran sulfate and magnesium nitrate, the sizes of particles of HDL2, LDL, and VLDL increased, but the size of HDL3 fraction particles remained constant, allowing only HDL3-C to participate in coupled reactions with the PEG-modified enzymes. In serum from both healthy volunteers and patients with type 2 diabetes, a good correlation was observed between the proposed assay and ultracentrifugation in the determination of HDL-C subclasses. The assay proposed here enables convenient and accurate determination of HDL-C subclasses in serum on a general automatic analyzer and enables low-cost routine diagnosis without preprocessing.

Higher High Density Lipoprotein 2 (HDL2) to Total HDL Cholesterol Ratio Is Associated with a Lower Risk for Incident Hypertension.

BackgroundRecent studies have suggested that high density lipoprotein (HDL) cholesterol is inversely associated with the development of hypertension. We aimed to determine the association between different HDL cholesterol subclasses and risk of future hypertension.MethodsA total of 270 Japanese Americans (130 men, 140 women) without hypertension between the ages of 34 to 75 years were enrolled. Blood pressure was measured with a mercury sphygmomanometer, and average blood pressure was calculated. Incident hypertension was determined 5 to 6 and 10 to 11 years after enrollment. HDL2, HDL3, and total HDL cholesterol were measured at baseline.ResultsDuring 10 years of follow-up, the cumulative incidence of hypertension was 28.1% (76/270). In univariate analysis, age, diabetes, waist circumference, systolic and diastolic blood pressure, fasting glucose, insulin resistance index, total and low density lipoprotein cholesterol, and visceral adipose tissue were significant predictors for incident hypertension. Among the HDL cholesterol subclass, HDL2 cholesterol was inversely associated with hypertension incidence, but both total and HDL3 cholesterol were not. In addition, HDL2/HDL cholesterol was inversely associated with future hypertension risk. In multivariate analysis, age (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26 to 2.31; P=0.001), systolic blood pressure (OR, 1.83; 95% CI, 1.31 to 2.56; P<0.001), and HDL2/HDL cholesterol (OR, 0.71; 95% CI, 0.52 to 0.98; P=0.035), were associated with future development of hypertension.ConclusionA higher proportion of HDL2 cholesterol among total HDL cholesterol predicted a lower risk for incident hypertension. However, concentrations of total HDL, HDL2, and HDL3 cholesterol were not independent predictors of incident hypertension.

HDL cholesterol subclasses are associated with serum uric acid in Japanese men

HDL cholesterol subclasses are associated with serum uric acid in Japanese men

Relationship between serum levels of HDL cholesterol subclasses and carotid intima media thickness in patients with type 1 diabetes mellitus

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Different inverse association of large high-density lipoprotein subclasses with exacerbation of insulin resistance and incidence of type 2 diabetes: The Nagahama study.

In addition to its antiatherogenic action, high-density lipoprotein (HDL) may also have an antidiabetes function. Although the biological actions of small HDL (HDL3) and large HDL (HDL2) subclasses may be different, evidence in support of that hypothesis is lacking. The aim of this study was to clarify the difference in prognostic significance of HDL subclasses for exacerbation of insulin resistance and incidence of type 2 diabetes in the general population. Study participants included 8365 community residents 52±13years of age not taking lipid lowering drugs. Serum HDL cholesterol subclasses and low-density lipoprotein subclasses, were measured by a homogeneous assay. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR). Cross-sectional analysis adjusted for possible covariates found that HDL2 cholesterol (HDL2-C) levels were inversely associated with HOMA-IR (β=-0.169, p<0.001), whereas HDL3-C had the opposite association (β=0.054, p<0.001). Similar results were found in an analysis for type 2 diabetes (HDL2-C, odds ratio=0.96, p=0.001; HDL3-C, odds ratio=1.04, p=0.181). In a longitudinal analysis with 5.0years of follow-up, HDL2-C was inversely associated with exacerbation of insulin resistance (β=-0.163, p<0.001); HDL3-C had the opposite association (β=0.026, p=0.037). During follow-up, 205 individuals were newly diagnosed with diabetes, and HDL2-C level was associated with an inverse risk of type 2 diabetes incidence (odds ratio=0.98, p=0.006). HDL may have an antidiabetic function; the prognostic value of HDL2-C for diabetes and insulin resistance might be better than that of HDL3-C.

Serum Lipid Transfer Proteins in Hypothyreotic Patients Are Inversely Correlated with Thyroid-Stimulating Hormone (TSH) Levels.

BackgroundPlasma cholesteryl ester transfer protein (CETP) activity is often decreased in patients with hypothyroidism, whereas less is known about the phospholipid transfer protein (PLTP). We aimed to evaluate simultaneously serum CETP and PLTP activity in patients diagnosed with hypothyroidism.Material/MethodsThe selection criteria for control group members (without thyroid dysfunction) in this case to case study were levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides similar to those in study group patients (101 patients diagnosed with hypothyroidism). Serum CETP and PLTP activities were measured by homogenous fluorometric assays using synthetic donor particle substrates.ResultsSerum CETP and PLTP activities in hypothyreotic patients were lower (p<0.001) compared with those in healthy subjects. This lowering was associated with significant changes in HDL-C subclasses: decrease in HDL2- and increase in HDL3 cholesterol levels. Multiple linear regression analyses adjusted for age, sex, body mass index, smoking habits, and alcohol drinking showed a strong association between hypothyroidism and activity of lipid transfer proteins. A linear inverse relationship between thyroid-stimulating hormone (TSH) and CETP (r=−0.21; p<0.01) and between TSH and PLTP (r=−0.24; p<0.001) was shown. There also was a positive correlation (p<0.001) between CETP and HDL2 cholesterol (r=0.27) and between PLTP and HDL2 cholesterol (r=0.37). A negative correlation between CETP and HDL3 cholesterol (r=−0.22: p<0.01) and between PLTP and HDL3 cholesterol (r=−0.24; p<0.001) has been demonstrated as well.ConclusionsThe decreased HDL2 and increased HDL3 cholesterol levels in subjects with hypothyroidism are consequences of decreased activity of lipid transfer proteins. These changes are early symptoms of lipid disturbances in hypothyroidism.

Variant rs10911021 that associates with coronary heart disease in type 2 diabetes, is associated with lower concentrations of circulating HDL cholesterol and large HDL particles but not with amino acids.

AimsAn intergenic locus on chromosome 1 (lead SNP rs10911021) was previously associated with coronary heart disease (CHD) in type 2 diabetes (T2D). Using data from the UCLEB consortium we investigated the relationship between rs10911021 and CHD in T2D, whether rs10911021 was associated with levels of amino acids involved in the γ-glutamyl cycle or any conventional risk factors (CRFs) for CHD in the T2D participants.MethodsFour UCLEB studies (n = 6531) had rs10911021 imputation, CHD in T2D, CRF and metabolomics data determined using a nuclear magnetic resonance based platform.ResultsThe expected direction of effect between rs10911021 and CHD in T2D was observed (1377 no CHD/160 CHD; minor allele OR 0.80, 95 % CI 0.60–1.06) although this was not statistically significant (p = 0.13). No association between rs10911021 and CHD was seen in non-T2D participants (11218 no CHD/1274 CHD; minor allele OR 1.00 95 % CIs 0.92–1.10). In T2D participants, while no associations were observed between rs10911021 and the nine amino acids measured, rs10911021 was associated with HDL-cholesterol (p = 0.0005) but the minor “protective” allele was associated with lower levels (−0.034 mmol/l per allele). Focusing more closely on the HDL-cholesterol subclasses measured, we observed that rs10911021 was associated with six large HDL particle measures in T2D (all p < 0.001). No significant associations were seen in non-T2D subjects.ConclusionsOur findings are consistent with a true association between rs10911021 and CHD in T2D. The protective minor allele was associated with lower HDL-cholesterol and reductions in HDL particle traits. Our results indicate a complex relationship between rs10911021 and CHD in T2D.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0435-0) contains supplementary material, which is available to authorized users.

0157 : HDL cholesterol subclasses and platelet aggregation in acute myocardial infarction patients and controls

HDL cholesterol (HDL-C) is known to exert direct anti-thrombotic properties by inhibiting platelet aggregation. The failure of recent clinical trials on lipid-modifying drugs to increase HDL-C plasma levels suggests that the assessment of the function and the composition of HDL particles could be a better marker of cardiovascular risk. The aims of our study were to analyze the antithrombotic properties of HDL-C subclasses and their molecular mechanisms in patients with acute myocardial infarction (AMI) compared with controls. HDL subclasses were separated from plasma of AMI patients (n=30) and controls (n=30) by ultracentrifugation. Two major subclasses were isolated: small, dense (1.125-1.21 g/ml) HDL3 and larger, buoyant (1.063-1- 125 g/ml) HDL2. Human platelets obtained from healthy volunteers were incubated with 50 μg/ml HDL2 or HDL3 for 30 min. Platelet aggregation in response to various agonists were monitored by turbidimetry with a dualchannel aggregometer. Activation markers were analyzed by flow cytometry. We showed that HDL2 and HDL3 subclasses significantly decreased platelet aggregation. Surprisingly, both HDL subclasses from AMI patients had a greater effect than those of controls (51.5±5.2% of maximal aggregation vs 82.6±3.0%, p<0.001 for HDL2 and 59.0±5.7% vs 84.3±2.9%, p=0.0012 for HDL3), especially the HDL2 subclass (p=0.006). Experiments using Block Lipid Transport-1 revealed that lipid exchange was not implicated in this anti-thrombotic effect. Binding to Scavenger Receptor B type 1 (SR-B1) is required since pre-treatment of platelets with anti-SR-B1 blocking antibody abrogated the effect of HDL subclasses. Preliminary data showed an increase in VASP phosphorylation and suggested interference with Akt phosphorylation. Taken together, these data provide evidence for the anti-thrombotic properties of HDL2 and HDL3 subclasses on platelet aggregation which could be modulated by coronary heart disease. The author hereby declares no conflict of interest

Lipid phenotypes at the extremes of high-density lipoprotein cholesterol: The very large database of lipids-9

Low serum levels of high-density lipoprotein cholesterol (HDL-C) are an important risk factor for atherosclerotic disease. To date, therapeutically raising HDL-C has not been shown to impact risk for cardiovascular events. We aim to characterize lipid parameters at the extremes of HDL-C. We examined cholesterol profiles from 1,350,908 US adults and children from the Very Large Database of Lipids who were clinically referred for advanced lipoprotein testing from 2009 to 2011. We categorized patients into HDL-C percentile categories (<0.1th, 0.1th-<1st, 1st-5th, 25th-75th, 95th-99th, >99th-99.9th, and >99.9th). Within these groups, we examined HDL-C subclasses, low-density lipoprotein cholesterol (LDL-C), LDL and very-low density lipoprotein densities, non-HDL-C, triglycerides (TG), very-low density lipoprotein cholesterol, and remnant lipoprotein cholesterol (RLP-C), as well as prevalence of Fredrickson-Levy dyslipidemias. Extremely low HDL-C percentiles were associated with increased LDL density, TG, and especially RLP-C. Very high HDL-C levels (≥ 92 mg/dL) showed increasing HDL2-C/HDL3-C ratio and very low levels of RLP-C and triglyceride-rich lipoproteins. Type IV dyslipidemia had the highest prevalence among classical dyslipidemia and was the most frequent at extremely low HDL-C percentiles. These findings demonstrate a high prevalence of elevated triglyceride-rich lipoprotein levels and increased LDL density in patients with extremely low HDL-C levels. The relative contributions of these various changes in lipid profiles of patients with low HDL-C to cardiovascular risk need to be further scrutinized to more fully establish if low HDL-C is truly an independent risk factor for coronary heart disease or simply reflects detrimental shifts in the levels of atherogenic lipoproteins.

Frontiers in lipid research.

Lipoproteins are major mediators of atherosclerosis, myocardial infarction, and cardiovascular death. While lowering of LDLs has convincingly been shown to reduce cardiovascular events, the role of(HDLs as a therapeutic target is less clear. Indeed, HDL is much more heterogenous in its size and composition than LDL. This may at least in part explain why attempts to reduce cardiovascular events by pharmacologically increasing HDL plasma levels have failed.1–5 Even for LDL, particle size may matter. Furthermore, although statins are able to reduce LDL plasma levels and cardiovascular events successfully, there is considerable remaining risk. Thus, novel approaches to lower LDL levels further are of great interest. The current issue of the European Heart Journal addresses these important issues in four clinical and basic science papers. The first paper ‘ HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention: the Lipoprotein Investigators Collaborative ’ by Seth Shay Martin et al . from Johns Hopkins University School of Medicine in Baltimore,6 commented on in an Editorial by Jean-Claude Tardif from the Montreal Heart Institute,7 concerns the heterogeneity of HDL and the link of its subclasses to prognosis. The authors analysed data from two, complementary prospective cohorts: the TRIUMPH study of 2465 patients with acute myocardial infarction, and the IHCS study involving 2414 patients who underwent coronary angiography. All patients had baseline HDL subclassification by vertical-spin density gradient ultracentrifugation stratified by tertiles of HDL-cholesterol (HDL-C) and its two major subclasses …

Low concentrations of phospholipids and plasma HDL cholesterol subclasses in asymptomatic subjects with high coronary calcium scores

Objective: To determine whether HDL size distribution and HDL subclasses are associated with coronary calcium scores. Methods: We screened 677 apparently healthy individuals by coronary tomography. One hundred twenty subjects were then recruited for the study and grouped by coronary artery calcification scores (CAC). Forty asymptomatic patients with atherosclerosis with CAC scores ≥75th percentile for gender and age were placed in the first group. Forty patients with CAC scores ≤25th percentile and 40 matched controls (CAC = 0) made up the two remaining groups. HDL samples were separated via sequential ultracentrifugation, followed by electrophoresis: they were then enzymatically stained and densitometrically analyzed to determine the triglycerides (Tg), phospholipids (Ph), and plasma cholesterol (C) concentrations corresponding to each HDL subclass. Results: HDL size distribution, lipid and non-lipid risk factors for atherosclerosis were similar among the three groups: HDL-cholesterol and HDL-phospholipids were significantly lower in the CAC ≥75th percentile group, whereas HDL-lipids in the CAC ≤25th group were comparable to the controls. HDL2b- and HDL2a-cholesterol were decreased, whereas phospholipids were lower in patients constituting 4 of the 5 HDL subclasses. The Ph-to-Tg ratios of small HDL were higher in both experimental groups compared with the controls, suggesting that these lipoproteins had abnormal structures. In spite of the significant differences between the high-CAC score subjects and the controls, statistical analyses demonstrated no substantial relationship between CAC scores and HDL parameters: other lipid and non-lipid risk factors for atherosclerosis were not statistically linked to CAC scores. Only male gender and age contributed to CAC scores in our study population. Conclusions: Our results suggest that CAC scores and traditional lipid profiles are independent aspects of atherosclerosis and that only lipids may be biomarkers of coronary calcification during the asymptomatic stages of the disease; however, HDL subclasses do not contribute to CAC scores.

HDL cholesterol subclasses, myocardial infarction, and mortality in secondary prevention: the Lipoprotein Investigators Collaborative.

High-density lipoprotein (HDL) is highly heterogeneous and the link of its subclasses to prognosis remains controversial. We aimed to rigorously examine the associations of HDL subclasses with prognosis in secondary prevention. We collaboratively analysed data from two, complementary prospective cohorts: the TRIUMPH study of 2465 acute myocardial infarction patients, and the IHCS study of 2414 patients who underwent coronary angiography. All patients had baseline HDL subclassification by vertical-spin density gradient ultracentrifugation. Given non-linearity, we stratified by tertiles of HDL-C and its two major subclasses (HDL2-C, HDL3-C), then compared multivariable-adjusted hazard ratios for mortality and mortality/myocardial infarction. Patients were middle-aged to elderly (TRIUMPH: 58.2 ± 12.2 years; IHCS: 62.6 ± 12.6 years), and the majority were men (TRIUMPH: 68.0%; IHCS: 65.5%). IHCS had lower mean HDL-C levels (34.6 ± 10.1 mg/dL) compared with TRIUMPH (40 ± 10.6 mg/dL). HDL3-C accounted for >3/4 of HDL-C (mean HDL3-C/HDL-C 0.78 ± 0.05 in both cohorts). During 2 years of follow-up in TRIUMPH, 226 (9.2%) deaths occurred, while death/myocardial infarction occurred in 401 (16.6%) IHCS patients over 5 years. No independent associations with outcomes were observed for HDL-C or HDL2-C. In contrast, the lowest tertile of HDL3-C was independently associated with >50% higher risk in each cohort (TRIUMPH: with middle tertile as reference, fully adjusted HR for mortality of HDL3-C, 1.57; 95% CI, 1.13-2.18; IHCS: fully adjusted HR for mortality/myocardial infarction, 1.55; 95% CI, 1.20-2.00). In secondary prevention, increased risk for long-term hard clinical events is associated with low HDL3-C, but not HDL2-C or HDL-C, highlighting the potential value of subclassifying HDL-C.

High-density Lipoprotein Subclasses and Risk of Stroke and its Subtypes in Japanese Population

High-density lipoprotein (HDL) cholesterol is an established protective factor for ischemic stroke. However, the contribution of HDL subclasses to stroke risk and its subtypes is uncertain. A prospective nested case-control study of 40- to 85-year-old Japanese was undertaken using frozen serum samples collected from 5280 men and 7524 women. They participated in cardiovascular risk surveys from 1985 to 1999 (1 community) and 1989 to 1998 (2 communities) under Circulatory Risk in Communities Study. HDL cholesterol subclasses were classified by high-performance liquid chromatography into 3 subgroups: S-HDL (very small or small HDL), M-HDL (medium HDL), and L-HDL (large or very large HDL) cholesterol. One control subject per case was matched by sex, age, community, serum storage year, and fasting status. In 2005, we identified 241 strokes (155 ischemic and 86 hemorrhagic). S-HDL and M-HDL cholesterol levels were inversely associated with total stroke risk, ischemic stroke, specifically lacunar infarction, and hemorrhagic stroke. After adjustment for cardiovascular risk factors, these associations remained statistically significant. Multivariable conditional odds ratios (95% confidence interval) for 1 SD (0.12 mmol/L) increment of S-HDL cholesterol levels were 0.34 (0.23-0.52) for total stroke, 0.38 (0.23-0.63) for ischemic stroke, 0.33 (0.18-0.61) for lacunar infarction, 0.30 (0.14-0.65) for hemorrhagic stroke, and 0.30 (0.12-0.77) for intraparenchymal hemorrhage. The respective multivariable odds ratios for 1SD (0.10 mmol/L) increment of M-HDL cholesterol levels were 0.56 (0.41-0.75), 0.63 (0.45-0.88), 0.59 (0.40-0.87), 0.41 (0.21-0.80), and 0.38 (0.16-0.90). No associations were found between L-HDL cholesterol levels and risk of total stroke and its subtypes. Small- to medium-sized HDL, not large HDL, cholesterol levels were inversely associated with total stroke risk.

The Associations between Alcohol Intake and HDL Cholesterol Subclasses in Korean Population

The Associations between Alcohol Intake and HDL Cholesterol Subclasses in Korean Population Jung Eun Lim, Kim Jung Im, Sun Ju Lee, Jae Woong Sull, Myoungsook Lee, Sun Ha Jee Department of Epidemiology and Health Promotion, Institute for Health, Promotion, Graduate School of Public Health, Yonsei University, Seoul, Department of Food and Nutrition and Research Institute of Obesity Sciences, Sungshin Women’s University, Seoul, Department of Bio-Medical Laboratory Science, Eulji University, Gyeonggi-do, Korea

Lipid Abnormalities and Oxidized LDL in Chronic Kidney Disease Patients on Hemodialysis and Peritoneal Dialysis

Dyslipoproteinemia and oxidative modification of low-density lipoprotein (oxLDL) contribute to the development of oxidative stress and atherosclerosis in chronic kidney disease (CKD). On the contrary, high-density lipoprotein cholesterol (HDL-C), especially HDL3-C subtype, has protective effect against oxidative damage. There is limited evidence referring HDL-C subclass levels in patients on dialysis. This study was designed to compare lipid abnormalities and oxLDL levels in hemodialysis (HD) and peritoneal dialysis (PD) patients. Serum lipids, HDL subclasses, and oxLDL were measured in 55 patients with CKD-stage 5 (31 patients on HD and 24 patients on PD) and in 21 normal controls (NC). The results showed that in dialysis patients, triglycerides were higher than in controls (p < 0.0001) and HDL-C was significantly lower (p < 0.0001). The HDL2-C subclass concentration did not differ significantly between patients and controls, while HDL3-C was lower in patients (11 ± 0.5 mg/dL) than in NC (23 ± 1, p < 0.0001). oxLDL levels were markedly increased in patients (1.92 ± 0.29 mg/L) compared to NC (0.22 ± 0.05, p < 0.0001). Patients on PD had higher levels of cholesterol (p < 0.001) and apolipoprotein B (p < 0.05) than patients on HD. However, HDL-C, HDL-C subclasses, and oxLDL concentrations did not differ significantly between PD and HD patients. It is concluded that patients with CKD have a nearly 10-fold elevation of oxLDL compared with NC. Patients on PD have differences in the lipid profile compared with patients on HD; however, both modalities seem to possess similar potential to atherosclerosis development.

Serum Oxidized LDL Is Inversely Associated with HDL2-Cholesterol Subclass in Renal Failure Patients on Hemodialysis

Background:Dyslipoproteinemia and oxidative modification of LDL (oxLDL) are common symptoms in patients suffering from chronic renal failure on hemodialysis (HD), and contribute to the development of oxidative stress. High-density lipoprotein cholesterol (HDL-C) protects against atherosclerosis by inhibiting the oxidation of lipoproteins and by supporting reverse cholesterol transport. This study intends to examine the association of oxLDL with HDL2 and HDL3 subclasses of HDL-C in HD patients, in order to elucidate whether oxidative stress influences HDL-C composition. Methods: Thirty-four patients on HD and 21 age- and sex-matched controls were studied. HDL2 and HDL3-C subclasses were isolated from serum according to a single-step precipitation method following a homogenous HDL-C assay. oxLDL was measured by ELISA. Results: In HD patients, oxLDL concentration was higher compared to the controls (1.40 ± 0.47 vs. 0.21 ± 0.05 mg/l, p = 0.017) and was significantly associated to total cholesterol (r = 0.480, p = 0.044), LDL-C (r = 0.544, p = 0.019), HDL-C (r = –0.589, p = 0.027) and C-reactive protein (r = 0.578, p = 0.024). Comparing HDL-C subclasses, only HDL2-C was negatively correlated to oxLDL levels (r = –0.565, p = 0.035). Conclusions: In HD patients, high serum levels of oxLDL are associated with low HDL2-C subclass levels. This might suggest that oxidative stress affects the HDL subclass more related to the protecting activity of HDL-C, contributing to atherosclerosis development.

Lipoprotein abnormalities are associated with insulin resistance in South Asian Indian women

South Asian Indians are at increased risk of coronary heart disease (CHD), possibly related to dyslipidemia characterized by high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations. The importance of differences in insulin resistance as compared to abdominal obesity in the development of this atherogenic lipoprotein profile is not clear, and the current cross-sectional study was initiated to examine this issue. Consequently, we defined the relationship between differences in insulin-mediated glucose uptake (IMGU), abdominal obesity, and various measures of lipoprotein metabolism known to increase CHD risk in 52 apparently healthy women of South Asian Indian ancestry. IMGU was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test and abdominal obesity was assessed by measurement of waist circumference (WC), and the population was divided into tertiles on the basis of their SSPG results. Results indicated that although there were significant differences in SSPG, TG, and HDL-C values, there were no differences in age, blood pressure, total cholesterol, low-density lipoprotein cholesterol, body mass index, or WC between the highest and lowest tertiles. SSPG concentrations were significantly correlated with both log TG ( r = 0.44, P = .001) and HDL-C ( r = −0.44, P < .001) concentration, whereas TG and HDL-C concentrations were not significantly related to WC. Furthermore, the relationships between SSPG concentration and TG and HDL-C remained significant when adjusted for age and WC. Finally, a more extensive lipoprotein analysis indicated that the most insulin resistant tertile had higher TG concentrations, lower concentrations of HDL-C and HDL-C subclasses, and smaller and denser low-density lipoprotein particles than the most insulin sensitive tertile, despite the 2 groups not being different in age, BMI, or WC. These results indicate that a highly atherogenic lipoprotein profile seen in South Asian Indian women is significantly associated with insulin resistance independent of differences in WC.