Mean Low-density Lipoprotein Size Research Articles

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.

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.

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.

Strong correlations between circulating chemerin levels and lipoprotein subfractions in nondiabetic obese and nonobese subjects

Chemerin is a recently described adipokine expressed primarily in the white adipose tissue. Compared with lean subjects, circulating chemerin levels are significantly elevated in obese individuals and correlate positively with the prevalence of various cardiovascular risk factors including altered lipoprotein levels. To date, the impact of chemerin on lipoprotein subfractions and its role in atherosclerotic processes are still unclear. Fifty nondiabetic obese (NDO) patients and 38 lean controls matched in age and gender were enrolled. Chemerin level was measured by ELISA. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were detected by nongradient polyacrylamide gel electrophoresis (Lipoprint). We detected significantly higher serum chemerin levels in NDO patients compared with healthy controls (590·1 ± 190·3 ng/ml vs 405 ± 127·1 ng/ml, P < 0·001). A significant positive correlation was found between chemerin and LDL cholesterol levels, while chemerin showed a significant negative correlation with the level of HDL cholesterol. Significant positive correlation was detected between chemerin and the ratio of small dense LDL, while chemerin correlated negatively with the mean LDL size. Also, a significant negative correlation was found between serum chemerin and the ratio of large HDL subfraction, while there were significant positive correlations between chemerin levels and intermediate and small HDL subfraction ratios, respectively. Chemerin may be involved in the regulation of lipoprotein metabolism in obese patients who do not show apparent abnormalities of glucose metabolism. Early changes in the distribution of the lipoprotein subfractions may contribute to the progression of atherosclerosis, leading to increased cardiovascular risk.

Atorvastatin effect on the distribution of high-density lipoprotein subfractions and human paraoxonase activity

Human serum paraoxonase-1 (PON1) protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low-density lipoprotein (LDL); therefore, it may protect against atherosclerosis. Changes in the ratio of high-density lipoprotein (HDL) subfractions may alter the stability and the antioxidant capacity of PON1. The aim of the study was to examine the effect of atorvastatin treatment on the distribution of HDL subfractions, LDL size, cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and PON1 activity. In all, 33 patients with type IIa and IIb hypercholesterolemia were involved in the study. LDL sizes and HDL subfractions were determined by gradient gel electrophoresis. CETP, LCAT, and PON1 activities were measured spectrophotometrically. Three months of treatment with atorvastatin 20 mg daily significantly increased the HDL3 (+8.13%) and decreased the HDL2a and HDL2b subfractions (-1.57% and -6.55%, respectively). The mean LDL size was significantly increased (+3.29%). The level of oxidized LDL was significantly decreased (-46.0%). The PON1 activity was augmented by the atorvastatin treatment (+5.0%). The CETP activity positively correlated with the HDL2b level and negatively correlated with the HDL3 and HDL2a levels. Atorvastatin alters the HDL subfractions, which may improve its antiatherogenic effect via enhancement of the PON1 activity.

Atherogenic lipid phenotype in a general group of subjects.

Abstract Context.—The atherogenic lipid phenotype is a major cardiovascular risk factor, but normal values do not exist derived from 1 analysis in a general study group. Objective.—To determine normal values of all of the atherogenic lipid phenotype parameters using subjects from a general study group. Design.—One hundred two general subjects were used to determine their atherogenic lipid phenotype using polyacrylamide gradient gels. Results.—Low-density lipoprotein (LDL) size revealed 24% of subjects express LDL phenotype B, defined as average LDL peak particle size 258 A or less; however, among the Chinese subjects, the expression of the B phenotype was higher at 44% (P = .02). For the total group, mean LDL size was 265 ± 11 A (1 SD); however, histograms were bimodal in both men and women. After excluding subjects expressing LDL phenotype B, because they are at increased cardiovascular risk and thus are not completely healthy, LDL histograms were unimodal and the mean LDL size was 270 ± 7 A. A small, de...

Atherogenic Lipid Phenotype in a General Group of Subjects

The atherogenic lipid phenotype is a major cardiovascular risk factor, but normal values do not exist derived from 1 analysis in a general study group. To determine normal values of all of the atherogenic lipid phenotype parameters using subjects from a general study group. One hundred two general subjects were used to determine their atherogenic lipid phenotype using polyacrylamide gradient gels. Low-density lipoprotein (LDL) size revealed 24% of subjects express LDL phenotype B, defined as average LDL peak particle size 258 A or less; however, among the Chinese subjects, the expression of the B phenotype was higher at 44% (P = .02). For the total group, mean LDL size was 265 +/- 11 A (1 SD); however, histograms were bimodal in both men and women. After excluding subjects expressing LDL phenotype B, because they are at increased cardiovascular risk and thus are not completely healthy, LDL histograms were unimodal and the mean LDL size was 270 +/- 7 A. A small, dense LDL concentration histogram (total group) revealed skewing; thus, phenotype B subjects were excluded, for the rationale described previously, and the mean value was 13 +/- 9 mg/dL (0.33 +/- 0.23 mmol/L). High-density lipoprotein (HDL) cholesterol histograms were bimodal in both sexes. After removing subjects as described previously or if HDL cholesterol levels were less than 45 mg/dL, histograms were unimodal and revealed a mean HDL cholesterol value of 61 +/- 12 mg/dL (1.56 +/- 0.31 mmol/L). HDL 2, HDL 2a, and HDL 2b were similarly evaluated. Approximate normal values for the atherogenic lipid phenotype, similar to those derived from cardiovascular endpoint trials, can be determined if those high proportions of subjects with dyslipidemic cardiovascular risk are excluded.

Lipoprotein(a) and LDL Particle Size Are Related to the Severity of Coronary Artery Disease

Background: The pathophysiological role and metabolic pathway of Lp(a) have not been clearly defined. An association between Lp(a) and oxidative low-density lipoprotein (LDL) were recently reported. And small dense LDL (sd-LDL) were associated with circulating malondialdehyde-modified LDL. We investigated the relationships between serum Lp(a) level and LDL particle size in coronary artery disease (CAD) patients. Further, we investigated the relationships of sd-LDL and Lp(a) with the extent and severity of CAD. Methods: A total of 490 patients (mean: 60.5 ± 11.5 years old) who underwent coronary angiography to evaluate chest pain were investigated. Patients were classified into two groups, a CAD group (n = 256), who had significant stenosis observed by coronary angiogram, and a control group (n = 234), who had normal, or minimal coronary arteries. CAD severity was measured by Gensini scores. The distribution of the LDL subfraction was analyzed using a Quantimetrix Lipoprint LDL System. Results: The serum Lp(a) concentration was correlated with the fraction of sd-LDL (r = 0.193, p < 0.001) and mean LDL size (r = 0.160, p = 0.003). The Lp(a) level and mean LDL particle size were significantly correlated with a high Gensini score. LDL particle size in the CAD group was smaller than in the control group (26.74 ± 0.64 vs. 26.43 ± 0.93 nm, p < 0.001). The Gensini score was significantly higher in small LDL with high Lp(a) level groups. Conclusion: The positive correlation of the level of Lp(a) and sd-LDL fraction were demonstrated. The mechanism of this association is not clearly defined; we can suggest that it may stem from the individual atherogenic condition that linked to increased oxidative stress. Both increased Lp(a) and sd-LDL fraction were correlated with the severity of CAD.

High Prevalence of Small Dense LDL as an Underestimated Component of Heart Transplantation–Induced Dyslipidemia: Potential Role in Graft Coronary Vasculopathy?

Heart transplantation–induced dyslipidemia is a recognized risk factor for cardiac allograft vasculopathy that affects survival prognosis. Beyond increased lipids, low-density lipoprotein (LDL) size and systemic factors, including glucose intolerance, oxidative stress, and inflammation, must be taken into account as components of the atherosclerotic risk. The aim of this study was to explore the atherogenic profile of heart transplant recipients (HTR) by assessing lipid parameters, glycemia, oxidative stress status, and inflammation in 59 transplant patients (follow-up of 6 ± 3 years) compared to 20 healthy volunteers. Classical hypercholesterolemia and hypertriglyceridemia were observed in HTR compared to controls, associated with increased apoCIII levels (0.13 ± 0.6 vs 0.07 ± 0.03 g/L, P < .01). Mean LDL size was reduced in HTR compared to controls (25.22 ± 0.72 vs 26.06 ± 0.54 nm, P < .001) with an abnormally high prevalence (69% vs 0%, P < .001) of small dense LDL (<25.5 nm). Hyperglycemia (7.3 ± 3 vs 5.4 ± 0.8 mmol/L, P < .05) and inflammation (high-sensitive CRP: 3.1 ± 3 vs 1.6 ± 0.9 mg/L, P < .001) were evidenced in HTR since no difference in oxidative stress parameters was observed. In conclusion, a high prevalence of small dense LDL is an important component of posttransplantation dyslipidemia.

Comparison of extended-release niacin and atorvastatin monotherapies and combination treatment of the atherogenic lipid profile in diabetes mellitus

• • • Fifty-three diabetic patients with either separate or combined abnormalities of the atherogenic lipid profile, defined by low-density lipoprotein (LDL) peak particle diameter 263 A and/or high-density lipoprotein (HDL) fraction-2 40% were recruited from the Diabetes Research Center. All subjects signed informed consent. This open-label, uncontrolled dosing and efficacy study used retrospective chart review analyses after aggressive antilipid treatment as previously reported in detail. The mean extended-release niacin dose was 2,819 821 mg/day, and atorvastatin was used at 80 mg/day. No patients received fibrates, bile acids, or thiazolidinediones during the observation period. Routine lipid, gel electrophoresis measurements of LDL and HDL species and hemoglobin A1c were performed as previously described in detail before and after 6 weeks of stable dosing. All data are presented as mean 1 SD. Paired and unpaired t tests were used to compare preand post-treatment results and differences between treatment groups, respectively. Table 1 shows the preand post-treatment results for the 3 treatment groups. To compare the 3 treatments, post-treatment lipid values were evaluated (Table 1). All pretreatment comparisons were similar among the groups (p NS), except where indicated. For subjects with abnormal LDL size, a combination therapy of atorvastatin and niaspan tended to be more effective than niaspan (p 0.08) or atorvastatin (p 0.05) monotherapy in lowering mean triglyceride values. Because of substantial baseline differences, an evaluation of the preand post-treatment changes showed combination treatment to be more effective than niaspan monotherapy for triglyceride lowering when percentage change (p 0.002) or delta change (p 0.05) was used. Atorvastatin monotherapy and the combination treatment reduced mean total LDL cholesterol levels substantially more than niaspan monotherapy (p 0.0001 and p 0.0002, respectively). Niaspan monotherapy increased mean LDL size more effectively than atorvastatin monotherapy (p 0.05), and combination treatment further improved size from atorvastatin monotherapy (p 0.03), but not niaspan monotherapy (p NS). Combination treatment reduced mean small, dense LDL cholesterol mass more effectively than niaspan monotherapy (p 0.001), and there was also a trend for atorvastatin monotherapy to be more effective than niaspan (p 0.07). The latter trend remained when preand post-treatment percentage changes were compared (p 0.04). Although mean levels of small, dense LDL cholesterol mass were not statistically different in the atorvastatin monotherapy group versus the combination treatment group because of baseline differences, preand post-treatment percentage change (p 0.05) and delta change (p 0.02) comparisons showed combination treatment to be more effective than atorvastatin monotherapy. Among patients with HDL-2 40%, combination therapy was more effective than atorvastatin monotherapy in reducing mean triglyceride levels (p 0.05). Combination therapy was also more effective than niaspan monotherapy in triglyceride lowering as shown by percentage change (p 0.003). Combination treatment was more effective than atorvastatin monotherapy in improving total HDL cholesterol values as shown by preand post-treatment percentage changes (p 0.001) and delta changes (p 0.002). Combination treatment was also more effective than atorvastatin in increasing HDL-2 cholesterol mass when comparing percentage changes (p 0.04) and delta changes (p 0.04). Niaspan monotherapy increased mean total HDL cholesterol (p 0.005) and HDL-2 cholesterol mass (p 0.03) more effectively than atorvastatin. HDL-2 levels across treatments were not statistically different for mean, percentage, or delta changes. Atorvastatin did not effectively treat lipoprotein(a) (Lp(a)) abnormalities (Lp(a) 25 mg/ dl) with mean preand post-treatment levels of 45 21 versus 44 6 mg/dl (n 4, p NS), whereas niaspan and combination decreased mean Lp(a) levels from 37 10 to 23 10 mg/dl (n 12, p 0.01) and from 54 19 to 35 6 mg/dl, respectively (n 4, p 0.06).

Doxazosin reduces prevalence of small dense low density lipoprotein and remnant-like particle cholesterol levels in nondiabetic and diabetic hypertensive patients

Small dense low density lipoprotein (LDL) and remnant lipoproteins are potent atherogenic lipoproteins, often elevated in the plasma of patients with type 2 diabetes. The α 1-blocker doxazosin has been reported to favorably affect the plasma lipid profile. We examined whether doxazosin could reduce these atherogenic lipoproteins in hypertensive subjects with and those without type 2 diabetes. Seventeen nondiabetic hypertensive patients and 33 hypertensive patients with type 2 diabetes were studied. Doxazosin (2 to 4 mg) was administered alone or with other previously received antihypertensive drugs for 6 months. Mean LDL size was measured by 2%∼16% gradient gel electrophoresis. Remnant-like particle (RLP)-cholesterol was measured with the use of an affinity column containing anti-apoA1 and B100 monoclonal antibodies. Doxazosin effectively decreased blood pressure (BP) without significantly affecting glucose, glycosylated hemoglobin (HbA 1c), or C-peptide levels in both nondiabetic and diabetic patients. Doxazosin significantly reduced triglyceride, apo CIII, and apo B, but did not alter total-, LDL- or HDL-cholesterol. Mean LDL particle diameter was significantly increased from 25.6 ± 0.6 nm to 25.9 ± 0.4 nm ( P < .001) by doxazosin treatment, regardless of the presence of diabetes. Consequently, the prevalence of small dense LDL (<25.5 nm) was halved in both groups. The increase in LDL size significantly correlated with decrease in triglyceride level (r = −0.798, P < .0001). Doxazosin significantly reduced RLP-cholesterol in both groups. These results suggest that doxazosin may help to prevent coronary artery disease by reducing atherogenic lipoproteins, including small dense LDL and remnant lipoproteins, in hypertensive patients, regardless of the presence of diabetes.

Dyslipoproteinaemia in postmenopausal women with a history of eclampsia.

To test the hypothesis that postmenopausal women with a history of eclampsia manifest a more high risk lipid profile than postmenopausal women with a history of normal pregnancy. The Department of Obstetrics and Gynaecology, National University Hospital, Reykjavik, Iceland, and the Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA. Thirty Icelandic women with a history of eclampsia, aged between 50 and 67 years at the time of re-examination (cases) were individually matched for current age, and for age and parity at index pregnancy, to 30 unrelated Icelandic women with a history of normal pregnancy (controls). The participating women completed a health and family history questionnaire and underwent a physical examination. Fasting plasma low density lipoprotein diameter, serum lipids, insulin, and glucose were measured. Mean low density lipoprotein size was significantly smaller and apolipoprotein B concentration was higher in women with prior eclampsia. The percentage of cases receiving blood pressure medication (33%) was significantly greater than controls (6.7%). Thirteen cases had had hypertensive complications in at least one other pregnancy (recurrent subgroup); postmenopausally, these women displayed significantly increased diastolic blood pressures, smaller-sized low density lipoprotein, increased apolipoprotein B, decreased high density lipoprotein2 (HDL2) cholesterol, and increased total cholesterol: HDL cholesterol ratio compared with their controls. Fourteen cases were normotensive in all other pregnancies (nonrecurrent); these showed no differences from their controls. Dyslipoproteinaemia is more prevalent among postmenopausal women with prior eclampsia, especially with recurrent hypertension in pregnancy, than in postmenopausal women with prior normal pregnancies.