Large High-density Lipoprotein Subfraction Research Articles

Associations between Serum Kallistatin Levels and Markers of Glucose Homeostasis, Inflammation, and Lipoprotein Metabolism in Patients with Type 2 Diabetes and Nondiabetic Obesity.

Kallistatin is an endogenous serine proteinase inhibitor with various functions, including antioxidative, anti-inflammatory, and anti-atherosclerotic properties. To date, associations between kallistatin and lipoprotein subfractions are poorly investigated. In this study, we enrolled 62 obese patients with type 2 diabetes (T2D), 106 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index, as well as 49 gender- and age-matched healthy, normal-weight controls. Serum kallistatin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint® (Quantimetrix Corp., Redondo Beach, CA, USA) gel electrophoresis. Kallistatin concentrations were significantly higher in T2D patients compared to NDO and control groups. We found significant positive correlations between very-low-density lipoprotein (VLDL), small high-density lipoprotein (HDL) subfractions, glucose, hemoglobin A1c (HbA1c), betatrophin, and kallistatin, while negative correlations were detected between mean low-density lipoprotein (LDL) size, large and intermediate HDL subfractions, and kallistatin in the whole study population. The best predictor of kallistatin was HbA1c in T2D patients, high-sensitivity C-reactive protein (hsCRP) and betatrophin in NDO patients, and hsCRP in controls. Our results indicate that kallistatin expression might be induced by persistent hyperglycemia in T2D, while in nondiabetic subjects, its production might be associated with systemic inflammation. The correlation of kallistatin with lipid subfractions may suggest its putative role in atherogenesis.

Gender-Dependent Associations between Serum Betatrophin Levels and Lipoprotein Subfractions in Diabetic and Nondiabetic Obese Patients.

Betatrophin, also known as angiopoietin-like protein 8 (ANGPTL8), mainly plays a role in lipid metabolism. To date, associations between betatrophin and lipoprotein subfractions are poorly investigated. For this study, 50 obese patients with type 2 diabetes (T2D) and 70 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index (BMI) as well as 49 gender- and age-matched healthy, normal-weight controls were enrolled. Serum betatrophin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint gel electrophoresis. Betatrophin concentrations were found to be significantly higher in the T2D and NDO groups compared to the controls in all subjects and in females, but not in males. We found significant positive correlations between triglyceride, very low density lipoprotein (VLDL), large LDL (low density lipoprotein), small LDL, high density lipoprotein (HDL) -6-10 subfractions, and betatrophin, while negative correlations were detected between betatrophin and IDL, mean LDL size, and HDL-1-5. Proportion of small HDL was the best predictor of betatrophin in all subjects. Small LDL and large HDL subfractions were found to be the best predictors in females, while in males, VLDL was found to be the best predictor of betatrophin. Our results underline the significance of serum betatrophin measurement in the cardiovascular risk assessment of obese patients with and without T2D, but gender differences might be taken into consideration.

Lipoprotein subfraction profiling in the search of new risk markers for myocardial infarction: The HUNT study.

Traditional biomarkers used to measure risk of myocardial infarction (MI) only explain a modest proportion of the incidence. Lipoprotein subfractions have the potential to improve risk prediction of MI. We aimed to identify lipoprotein subfractions that were associated with imminent MI risk. We identified apparently healthy participants with a predicted low 10-year risk of MI from The Trøndelag Health Survey 3 (HUNT3) that developed MI within 5 years after inclusion (cases, n = 50) and 100 matched controls. Lipoprotein subfractions were analyzed in serum by nuclear magnetic resonance spectroscopy at time of inclusion in HUNT3. Lipoprotein subfractions were compared between cases and controls in the full population (N = 150), and in subgroups of males (n = 90) and females (n = 60). In addition, a sub analysis was performed in participants that experienced MI within two years and their matched controls (n = 56). None of the lipoprotein subfractions were significantly associated with future MI when adjusting for multiple testing (p<0.002). At nominal significance level (p<0.05), the concentration of apolipoprotein A1 in the smallest high-density lipoprotein (HDL) subfractions was higher in cases compared to controls. Further, in sub analyses based on sex, male cases had lower lipid concentration within the large HDL subfractions and higher lipid concentration within the small HDL subfractions compared to male controls (p<0.05). No differences were found in lipoprotein subfractions between female cases and controls. In sub analysis of individuals suffering from MI within two years, triglycerides in low-density lipoprotein were higher among cases (p<0.05). None of the investigated lipoprotein subfractions were associated with future MI after adjustment for multiple testing. However, our findings suggests that HDL subfractions may be of interest in relation to risk prediction for MI, especially in males. This need to be further investigated in future studies.

Sphingosine 1-Phosphate and Apolipoprotein M Levels and Their Correlations with Inflammatory Biomarkers in Patients with Untreated Familial Hypercholesterolemia.

High-density lipoprotein (HDL)-bound apolipoprotein M/sphingosine 1-phosphate (ApoM/S1P) complex in cardiovascular diseases serves as a bridge between HDL and endothelial cells, maintaining a healthy endothelial barrier. To date, S1P and ApoM in patients with untreated heterozygous familial hypercholesterolemia (HeFH) have not been extensively studied. Eighty-one untreated patients with HeFH and 32 healthy control subjects were included in this study. Serum S1P, ApoM, sCD40L, sICAM-1, sVCAM-1, oxLDL, and TNFα concentrations were determined by ELISA. PON1 activities were measured spectrophotometrically. Lipoprotein subfractions were detected by Lipoprint. We diagnosed FH using the Dutch Lipid Clinic Network criteria. Significantly higher serum S1P and ApoM levels were found in HeFH patients compared to controls. S1P negatively correlated with large HDL and positively with small HDL subfractions in HeFH patients and the whole study population. S1P showed significant positive correlations with sCD40L and MMP-9 levels and PON1 arylesterase activity, while we found significant negative correlation between sVCAM-1 and S1P in HeFH patients. A backward stepwise multiple regression analysis showed that the best predictors of serum S1P were large HDL subfraction and arylesterase activity. Higher S1P and ApoM levels and their correlations with HDL subfractions and inflammatory markers in HeFH patients implied their possible role in endothelial protection.

Changes in serum pigment epithelium-derived factor levels after kidney transplantation in patients with end-stage renal disease

Background Pigment epithelium-derived factor (PEDF) is a serin protease inhibitor and a potent inhibitor of angiogenesis. Its serum level has significant associations with metabolic parameters. However, little is known about the association between PEDF levels and lipid parameters in renal transplanted (TX) patients. Therefore, our aim was to investigate the relationship between PEDF level and lipid parameters in TX patients. Methods Seventy TX patients (47 males, 23 females, mean age 51.7 ± 12.4 years) and 34 healthy controls were enrolled. We examined the serum creatinine, C-reactive protein, fasting glucose and lipid parameters right before, then 1 and 6 months after TX. High-density lipoprotein (HDL)-associated paraoxonase-1 (PON1) activities were measured spectrophotometrically. Lipoprotein subfractions were determined by Lipoprint. PEDF and oxidized low-density liporotein (oxLDL) levels were measured by ELISA. Results Before transplantation, patients had had a significantly higher PEDF level compared to control subjects (p < 0.001). One month after transplantation, their PEDF level decreased significantly reaching the healthy controls’ level, and this lower level was maintained during the 6 months follow-up period as well. The initial oxLDL level was significantly higher, while PON1 activities were significantly lower in the patient group compared to the control group. We found a significant positive correlation between PEDF and total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, oxLDL and small HDL subfraction; while negative correlations were found between PEDF and mean LDL size and large HDL subfraction during the entire follow-up period. Conclusion PEDF may play an important role in the increased oxidative stress and enhanced atherogenesis in renal transplant patients.

The impact of sleep apnea syndrome on the altered lipid metabolism and the redox balance

BackgroundObstructive sleep apnea (OSA) is a disorder with a significant risk for cardiovascular diseases. Dyslipidemia and redox imbalance belong to potential mechanisms linking OSA with the development of vascular diseases. The main aim of this study was the evaluation of the presence of lipid abnormalities in OSA patients, focusing on small dense low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions and determination of the redox imbalance by evaluating the marker of oxidative damage to plasma lipids - lipoperoxides.MethodsThe study included 15 male subjects with polysomnographically confirmed OSA and 16 male healthy controls. Plasma levels of total cholesterol, LDL and HDL and their subfractions, triacylglycerols and lipoperoxides were determined in all study individuals. Plasma LDL and HDL subfractions were separated by the Lipoprint system which is a polyacrylamide gel electrophoresis. Lipoperoxide levels were determined spectrophotometrically.ResultsOSA patients had significantly higher triacylglycerols, total cholesterol and LDL-cholesterol compared to healthy controls. HDL cholesterol was not significantly different. Of the LDL and HDL subfractions, OSA patients had significantly lower levels of atheroprotective LDL1 and large HDL subfractions and significantly higher levels of atherogenic small dense LDL3–7 and HDL8–10 subfractions. Lipoperoxide levels in patients with OSA were significantly elevated compared to healthy individuals.ConclusionThe lipoprotein pro-atherogenic phenotype was found in individuals with OSA characterized by increased levels of atherogenic lipoprotein subfractions and reduced levels of atheroprotective subfractions. In addition, a plasma redox imbalance was found in patients with OSA compared to controls by detecting higher oxidative damage to lipids. Abnormalities in lipoprotein levels in patients with OSA, as well as the redox imbalance, could lead to an acceleration of the atherosclerotic process in predisposed individuals and thus represent a significant risk factor for vasular diseases.

Low Levels of Serum Fetuin-A and Retinol-Binding Protein 4 Correlate with Lipoprotein Subfractions in Morbid Obese and Lean Non-Diabetic Subjects.

Background: Fetuin-A and retinol-binding protein 4 (RBP4) are secreted as both hepatokine and adipokine. These are involved in insulin resistance, obesity-related dyslipidemia, and atherosclerosis. To date, correlations of circulating fetuin-A and RBP4 with lipoprotein subfractions as well as high-density lipoprotein (HDL)-linked proteins have not been entirely investigated in morbid obese and lean non-diabetic subjects. Methods: One-hundred obese non-diabetic patients (body mass index, BMI: 42.5 ± 8.1 kg/m2) along with 32 gender and age-matched normal weight controls (BMI: 24.5 ± 2.5 kg/m2) were enrolled in our study. Serum fetuin-A and RBP4 were measured by ELISA. Lipoprotein subfractions were distributed by Lipoprint gelelectrophoresis. Results: Serum fetuin-A and RBP4 were unexpectedly lower in obese patients (p < 0.01 and p < 0.01, respectively) compared to controls and correlated with each other (r = 0.37; p < 0.001). Fetuin-A had positive correlations with HDL-C (r = 0.22; p = 0.02), apolipoprotein AI (apoAI) (r = 0.33; p < 0.001), very-low density lipoprotein (VLDL) subfraction (r = 0.18; p = 0.05), and large HDL subfraction levels (r = 0.3; p = 0.001) but did not show correlation with carbohydrate parameters in all subjects. RBP4 correlated positively with HDL-C (r = 0.2; p = 0.025), apoAI (r = 0.23; p = 0.01), VLDL subfraction (r = 0.37; p < 0.001), intermediate HDL subfraction (r = 0.23; p = 0.01), and small HDL subfraction (r = 0.21; p = 0.02) concentrations, as well as C-peptide levels in overall participants. Backward stepwise multiple regression analysis showed that serum fetuin-A concentration is best predicted by RBP4 and large HDL subfraction. In model 2, VLDL subfraction was the independent predictor of serum RBP4 level. Conclusions: Our data may indicate a potential role of fetuin-A and RBP4 in impaired lipoprotein metabolism associated with obesity.

Nonlinear optical responses of oxidized low-density lipoprotein: Cutoff point for z-scan peak-valley distance.

The development of new methods to assess biomarkers of cardiovascular disease is currently a subject of scientific research. This article broadens our view of nonlinear optical responses of oxidized low density lipoprotein (LDL) evaluated using the Z-scan peak-valley distance and proposes a cutoff point. We investigated the association of peak-valley distance and some cardiovascular risk factors related with sociodemographic, clinical and anthropometric profiles and plasma biomarkers such as lipid and glucose profile, apolipoprotein, lipoprotein subfractions and omega 3 fatty acids. Z-scan analysis was performed using isolated LDL after ultracentrifugation in human blood samples collected after fasting. Peak-valley distance is a parameter that decreases directly depending on the oxidizability of LDL. As peak-valley distance was associated with relevant biomarkers of cardiovascular risk, we tested cutoff points for categorization and the best results were obtained using percentile < 75 (Lowz-scan) and percentile ≥ 75 (Highz-scan). The regression logistic models tested after establishing the cutoff point for peak-valley distance showed that increased levels of plasma high-density lipoprotein cholesterol, apolipoprotein A-I, large high-density lipoprotein subfractions and docosahexaenoic acid are directly associated with HighZ-scan. Conversely, high levels of small LDL were associated with decreased odds of presenting HighZ-scan. In conclusion, the cutoff point for peak-valley distance was able to identify atherogenic characteristics of LDL and its relationship with some parameters of high-density lipoprotein functionality.

Relation of oxidized-low-density lipoprotein and high-density lipoprotein subfractions in non-treated patients with coronary artery disease

BackgroundOxidized-low-density lipoprotein (ox-LDL), as well as high-density lipoprotein (HDL) and its subfractions play important role in the development of coronary artery disease (CAD). MethodsA total of 1417 individuals who received selective coronary angiography (CAG) without lipids-lowering treatments were consecutively enrolled. Patients were divided into CAD (n = 942) and non-CAD group (n = 475). The severity of CAD was assessed by Gensini Scores (GS) system. The correlations of ox-LDL with HDL subfractions were analyzed. ResultsCompared with non-CAD subjects, CAD patients had higher ox-LDL but lower concentrations of HDL cholesterol (p = 0.002) and large HDL subfractions (p = 0.004). And ox-LDL was negatively correlated with large HDL subfractions in patients with severe CAD (p < 0.05). Moreover, ox-LDL was elevated and large HDL subfractions decreased with the increase of the number of stenotic coronary arteries and GS (p < 0.05, respectivelly). ConclusionsThe correlations between ox-LDL and cholesterol level of large HDL particles varied among CAD and non-CAD, and CAD with different severities of atherosclerosis.

Serum obestatin level strongly correlates with lipoprotein subfractions in non-diabetic obese patients

BackgroundObestatin is a ghrelin-associated peptide, derived from preproghrelin. Although many of its effects are unclear, accumulating evidence supports positive actions on both metabolism and cardiovascular function. To date, level of obestatin and its correlations to the lipid subfractions in non-diabetic obese (NDO) patients have not been investigated.MethodsFifty NDO patients (BMI: 41.96 ± 8.6 kg/m2) and thirty-two normal-weight, age- and gender-matched healthy controls (BMI: 24.16 ± 3.3 kg/m2) were enrolled into our study. Obestatin level was measured by ELISA. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions, intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) levels and mean LDL size were detected by nongradient polyacrylamide gel electrophoresis (Lipoprint).ResultsSerum level of obestatin was significantly lower in NDO patients compared to controls (3.01 ± 0.5 vs. 3.29 ± 0.6 μg/ml, p < 0.05). We found significant negative correlations between the level of obestatin and BMI (r = − 0.33; p < 0.001), level of serum glucose (r = − 0.27, p < 0.05), HbA1c (r = − 0.38; p < 0.001) and insulin (r = − 0.34; p < 0.05). Significant positive correlation was found between obestatin level and the levels of ApoA1 (r = 0.25; p < 0.05), large HDL subfraction ratio and level (r = 0.23; p < 0.05 and r = 0.24; p < 0.05), IDL (r = 0.25 p < 0.05) and mean LDL size (r = 0.25; p < 0.05). Serum VLDL ratio and level negatively correlated with obestatin (r = − 0.32; p < 0.01 and r = − 0.21; p = 0.05). In multiple regression analysis obestatin was predicted only by VLDL level.ConclusionsBased on our data, measurement of obestatin level in obesity may contribute to understand the interplay between gastrointestinal hormone secretion and metabolic alterations in obesity.

Bariatric surgery improves lipoprotein profile in morbidly obese patients by reducing LDL cholesterol, apoB, and SAA/PON1 ratio, increasing HDL cholesterol, but has no effect on cholesterol efflux capacity

Bariatric surgery has been shown to reduce cardiovascular events and cause-specific mortality for coronary artery disease in obese patients. Lipoprotein biomarkers relating to low-density lipoprotein (LDL), high-density lipoprotein (HDL), their subfractions, and macrophage cholesterol efflux have all been hypothesized to be of value in cardiovascular risk assessment. The objective of this study was to examine the effect of a lifestyle intervention followed by bariatric surgery on the lipid profile of morbidly obese patients. Thirty-four morbidly obese patients were evaluated before and after lifestyle changes and then 1 year after bariatric surgery. They were compared with 17 lean subjects. Several lipoprotein metrics, serum amyloid A (SAA), serum paraoxonase-1 (PON1), and macrophage cholesterol efflux capacity (CEC) were assessed. Average weight loss after the lifestyle intervention was 10.5% and 1 year after bariatric surgery was 33.9%. The lifestyle intervention significantly decreased triglycerides (TGs; -28.7mg/dL, P<.05), LDL cholesterol (LDL-C; -32.3mg/dL, P<.0001), and apolipoprotein B (apoB; -62.9μg/mL, P<.001). Bariatric surgery further reduced TGs (-36.7mg/dL, P<.05), increased HDL cholesterol (+12mg/dL, P<.0001), and reductions in LDL-C and apoB were sustained. Bariatric surgery reduced large, buoyant LDL (P<.0001), but had no effect on the small, dense LDL. The large HDL subfractions increased (P<.0001), but there was no effect on the smaller HDL subfractions. The ratio for SAA/PON1 was reduced after the lifestyle intervention (P<.01) and further reduced after bariatric surgery (P<.0001). Neither the lifestyle intervention nor bariatric surgery had any effect on CEC. Lifestyle intervention followed by bariatric surgery in 34 morbidly obese patients showed favorable effects on TGs, LDL-C, and apoB. HDL cholesterol and apoA1 was increased, apoB/apoA1 ratio as well as SAA/PON1 ratio reduced, but bariatric surgery did not influence CEC.

High density lipoprotein modulates osteocalcin expression in circulating monocytes: a potential protective mechanism for cardiovascular disease in type 1 diabetes

BackgroundCardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes (T1D). A pro-calcific drift of circulating monocytes has been linked to vascular calcification and is marked by the surface expression of osteocalcin (OCN). We studied OCN+ monocytes in a unique population with ≥50 years of T1D, the 50-Year Joslin Medalists (J50M).MethodsCD45 bright/CD14+/OCN+ cells in the circulating mononuclear blood cell fraction were quantified by flow cytometry and reported as percentage of CD45 bright cells. Mechanisms were studied by inducing OCN expression in human monocytes in vitro.ResultsSubjects without history of CVD (n = 16) showed lower levels of OCN+ monocytes than subjects with CVD (n = 14) (13.1 ± 8.4% vs 19.9 ± 6.4%, p = 0.02). OCN+ monocytes level was inversely related to total high density lipoprotein (HDL) cholesterol levels (r = −0.424, p = 0.02), large (r = −0.413, p = 0.02) and intermediate (r = −0.445, p = 0.01) HDL sub-fractions, but not to small HDL. In vitro, incubation with OxLDL significantly increased the number of OCN+ monocytes (p < 0.01). This action of OxLDL was significantly reduced by the addition of HDL in a concentration dependent manner (p < 0.001). Inhibition of the scavenger receptor B1 reduced the effects of both OxLDL and HDL (p < 0.05).ConclusionsLow OCN+ monocytes levels are associated with lack of CVD in people with long duration T1D. A possible mechanism for the increased OCN+ monocytes could be the elevated levels of oxidized lipids due to diabetes which may be inhibited by HDL. These findings suggest that circulating OCN+ monocytes could be a marker for vascular disease in diabetic patients and possibly modified by HDL elevation.

Elevated resting heart rate is associated with the severity of coronary artery disease in non-treated patients who underwent coronary angiography: potential role of lipoprotein subfractions

Objective: To assess the association between resting heart rate (RHR) and lipoprotein subfractions to provide potential evidence for the relationship between RHR and severity of CAD.Methods: A total of 1119 consecutive non-treated subjects scheduled for coronary angiography were enrolled. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) separation were performed by Lipoprint System. The link of RHR with lipoprotein subfractions was assessed.Results: Increased RHR was significantly associated with higher triglyceride, total cholesterol, non-HDL-cholesterol, and apolipoprotein B (all p < .01). Furthermore, data indicated that higher RHR was related to more severe CAD (all p < .05). In the following linear regression models, we observed that higher RHR (HRh bpm) was significantly associated with lower large HDL (β = –0.073, p = .024) and higher small LDL subfraction (β = 0.103, p = .005) after adjusting for potential confounders.Conclusions: Increased RHR was associated with more severe CAD, which may be partly due to the significant relation to atherogenic lipoprotein subfractions.

HDL subfractions and very early CAD: novel findings from untreated patients in a Chinese cohort.

Coronary artery disease (CAD) in very young individuals is a rare disease associated with poor prognosis. However, the role of specific lipoprotein subfractions in very young CAD patients (≤45 years) is not established yet. A total of 734 consecutive CAD subjects were enrolled and were classified as very early (n = 81, ≤45), early (n = 304, male: 45–55; female: 45–65), and late (n = 349, male: >55; female: >65) groups. Meanwhile, a group of non-CAD subjects were also enrolled as controls (n = 56, ≤45). The lipoprotein separation was performed using Lipoprint System. As a result, the very early CAD patients have lower large high-density lipoprotein (HDL) subfraction and higher small low-density lipoprotein (LDL) subfraction (p < 0.05). Although body mass index was inversely related to large HDL subfraction, overweight did not influence its association with very early CAD. In the logistic regression analysis, large HDL was inversely [OR 95% CI: 0.872 (0.825–0.922)] while small LDL was positively [1.038 (1.008–1.069)] related to very early CAD. However, after adjusting potential confounders, the association was only significant for large HDL [0.899 (0.848–0.954)]. This study firstly demonstrated that large HDL subfraction was negatively related to very early CAD suggestive of its important role in very early CAD incidence.

High density lipoprotein subfractions and paraoxonase 1 in children.

The Lipoprint system (Quantimetrix Corp., CA, USA), enables the determination of 10 high density lipoprotein (HDL) subfractions in contrast to the 5 HDL subfractions that can be determined by ultracentrifuge analysis. HDL subfractions, and their relationships to the arylesterase (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1), together with total-, very low density lipoprotein- and low density lipoprotein (LDL)-cholesterol and LDL subfractions were investigated in the serum of 27 mildly hypercholesterolemic children and 21 healthy controls. Our results suggest the antiatherogenity of large HDL (L-HDL) subfractions and the atherogenity of small HDL (S-HDL) subfractions in the study groups. However, the relationship between the intermediate HDL (I-HDL) subfractions with the LDL subfractions and other lipoproteins did not suggest that I-HDL subfractions are antiatherogenic. No significant association between PON1-A and the HDL subfractions was found. In contrast, PON1-L activity positively correlated with the antiatherogenic large HDL1 subfraction and negatively with intermediate HDL subfractions 4, 5 and 6. Our results contribute to the knowledge of the roles of total HDL and ten individual HDL subfractions in children and adolescents.

Large HDL Subfraction But Not HDL-C Is Closely Linked With Risk Factors, Coronary Severity and Outcomes in a Cohort of Nontreated Patients With Stable Coronary Artery Disease: A Prospective Observational Study.

High-density lipoprotein (HDL) is highly heterogeneous in its size and composition. Till now, the link of HDL subfractions to coronary risk is less clear. We aimed to investigate the associations of HDL subfractions with traditional risk factors (RFs), coronary severity, and outcomes in a cohort of nontreated patients with stable coronary artery disease (CAD).We prospectively enrolled 591 eligible patients. Baseline HDL subfractions were separated by Lipoprint system. HDL subfractions (large, medium, and small) and HDL-cholesterol (HDL-C) levels were dichotomized into low and high group according to the 50 percentile. Coronary severity was evaluated by SYNTAX, Gensini, and Jeopardy scoring systems. Patients were followed up annually for major adverse cardiovascular events (MACEs). Cox proportional hazards’ models were used to evaluate the risk of HDL subfractions on MACEs.Patients with high large HDL-C levels had a decreased number of RFs. Significantly, large HDL-C levels were negatively associated with coronary severity assessed by SYNTAX and Gensini score (both P < 0.05). New MACEs occurred in 67 (11.6%) patients during a median 17.0 months follow-up. Moreover, the log-rank test revealed that there was a significant difference between high and low large HDL-C groups in event-free survival analysis (P = 0.013), but no differences were observed in total HDL-C groups and medium or small HDL-C groups (both P > 0.05). In particular, the multivariate Cox-proportional hazards model revealed that high large HDL-C was associated with lower MACEs risk (hazard ratio [95% confidence interval] 0.531 [0.295–0.959]) independent of potential confounders.Higher large HDL-C but not medium, small, or total HDL-C is associated with lower cardiovascular risk, highlighting the potential beneficial of HDL subfractionation.

Distribution of High-Density Lipoprotein Subfractions and Hypertensive Status: A Cross-Sectional Study.

The exact mechanisms of hypertension contributing to atherosclerosis have not been fully elucidated. Although multiple studies have clarified the association with low-density lipoprotein (LDL) subfractions, uncertainty remains about its relationship with high-density lipoprotein (HDL) subfractions. Therefore, we aimed to comprehensively determine the relationship between distribution of HDL subfractions and hypertensive status.A total of 953 consecutive subjects without previous lipid-lowering drug treatment were enrolled and were categorized based on hypertension history (with hypertension [n = 550] or without hypertension [n = 403]). Baseline clinical and laboratory data were collected. HDL separation was performed using the Lipoprint System.Plasma large HDL-cholesterol (HDL-C) and large HDL percentage were dramatically lower whereas the small HDL-C and small HDL percentage were higher in patients with hypertension (all P < 0.05). The antihypertensive drug therapy was not associated with large or small HDL subfractions (on treatment vs not on treatment, P > 0.05; combination vs single drug therapy, P > 0.05). However, the blood pressure well-controlled patients have significantly lower small HDL subfraction (P < 0.05). Moreover, large HDL-C and percentage were inversely whereas small HDL percentage was positively associated with incident hypertension after adjusting potential confounders (all P < 0.05). In the multivariate model conducted in patients with and without hypertension separately, the cardio-protective value of large HDL-C was disappeared in patients with hypertension (OR 95%CI: 1.011 [0.974-1.049]).The distribution of HDL subfractions is closely associated with hypertensive status and hypertension may potentially impact the cardio-protective value of large HDL subfraction.

Analysis of Lipoprotein Subfractions in Chinese Han Patients with Stable Coronary Artery Disease

The relation of lipoprotein subfractions with stable coronary artery disease (CAD) has not been fully investigated in the Chinese Han population. Four-hundred-and-thirteen consecutive patients without any lipid-lowering drug treatment were investigated. Patients were classified into two groups according to the angiographic results: CAD group (n=293) and non-CAD group (n=120). The high-density lipoprotein (HDL) and low-density lipoprotein (LDL) subfractions were analysed using the Quantimetrix Lipoprint system. The data showed that the large HDL-cholesterol (HDL-C) level, large HDL subfraction percentage, and mean LDL particle size were significantly lower, while the small HDL-C level and HDL subfraction percentage, intermediate and small LDL-cholesterol (LDL-C) levels, and LDL subfraction percentages were higher in the CAD group compared with those in the non-CAD group. Interestingly, our results suggested that the small HDL-C level and HDL subfraction percentage as well as mean LDL particle size were independently associated with the presence of CAD assessed by logistic regression analysis (OR=1.136, 95%CI=1.018-1.268, p=0.022; OR=1.076, 95%CI=1.021-1.134, p=0.007; OR=0.946, 95%CI=0.898-0.997, p=0.040; respectively). Similar to previous Western population studies, our data suggested a clear association between the lipoprotein subfractions and stable CAD presented as higher small HDL subfraction and smaller mean LDL particle size in Chinese Han patients.

Effects of Hedan Tablet () on lipid profile, proprotein convertase subtilisin/kexin type 9 and high-density lipoprotein subfractions in patients with hyperlipidemia: A primary study.

To investigate the effects of Hedan Tablet () on serum lipid profile, proprotein convertase subtilisin/kexin type 9 (PSCK9) and high-density lipoprotein (HDL) subfractions in patients with hyperlipidemia. Thirty-seven patients with hyperlipidemia were randomized to treatment with Hedan Tablet 4.38 g/day as Hedan group (18 cases) or placebo (19 cases) as control group for 8 weeks. The lipid profile, PCSK9 and HDL subfractions were determined at day 0 and week 8 in both groups respectively. Hedan treatment for 8 weeks mildly decreased serum low-density lipoprotein cholesterol (LDL-C) levels, while no changes were found in total cholesterol (TC), triglycerides (TG) and PCSK9 concentrations. Furthermore, Hedan treatment increased the concentration of large high-density lipoprotein cholesterol (HDL-C) and the percentage of large HDL subfraction, while decreased the concentration of small HDL-C and the percentage of small HDL subfraction without changing serum HDL-C levels in patients with hyperlipidemia. Hedan treatment of 4.38 g per day for 8 weeks could confer a favorable effects on serum LDL-C concentration as well as HDL subfractions.

Altered lipid subfraction profile and impaired antioxidant defense of high-density lipoprotein in Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is a rare disease caused by biallelic mutation in the 7-dehydrocholesterol (7DHC) reductase gene. High oxidizability of 7DHC and the appearance of small-sized low-density lipoprotein (LDL) subfractions indicate increased endogenous oxidative stress that is counterbalanced by natural antioxidant defense mechanisms including the high-density lipoprotein (HDL)-associated paraoxonase-1 (PON1) enzyme. PON1 prevents lipoproteins from oxidative modifications; however, PON1 activity and the distribution of lipoprotein subfractions have not been studied in SLOS. 7DHC levels and PON1 arylesterase activities were measured spectrophotometrically in 11 SLOS patients and 10 healthy children. Lipoprotein subfractions were detected by polyacrylamide gel electrophoresis. Compared to controls, there was a shift towards the small-dense LDL subfraction and the large HDL subfraction in SLOS. PON1 arylesterase activity was significantly decreased in SLOS patients and correlated negatively with the proportion of small-dense LDL subfraction and the proportion of large HDL subfraction. Significant positive correlations were detected between PON1 arylesterase activity and the ratios of intermediate and small HDL subfractions. Decreased PON1 activity and the deleterious shift in the distribution of lipoprotein subfractions may contribute to the impaired antioxidant status observed in SLOS. Monitoring of serum PON1 arylesterase activity may be a complementary biomarker in SLOS.