Proportion Of Low-density Lipoprotein Research Articles

The Biological and Chemical Ameliorative Effects of Bread Substituted with Dried Moringa Leaves

This study conducted to evaluate the effect of additional dried moringa leaves on bread and their effects on the chemical and biological of rats fed it. Wheat flour with dried moringa leaves powder (DMLB) is used at different levels (6 and 9%) to produce moringa bread. We performed a sensory evaluation of wheat bread substituted with dried moringa leaves, chemical properties (approximate composition and antioxidants), microbiology (total bacteria, spore-forming bacteria, fungi, and yeast) and biological analysis (Triglycerides, total cholesterol, HDL and LDL, ALT, AST, urea, creatinine). Therefore, histopathology examination for kidney and livers of male albino rats fed fortified bread with dried moringa leaves compared with the control sample. The results of the approximate analysis showed significant differences by adding moringa leaves and the percentage of ash, protein, fat, and fiber increased with the moisture content. Moreover, carbohydrates decreased from fortified bread with dried moringa leaves compared to the control sample. The best treatment was fortified bread with 6% dried moringa leaves for all sensory evaluations compared to the other samples and moringa bread (DMLB 9%) helped reduce the microbial load during storage. The effect of moringa bread on liver cirrhosis was evaluated in rats induced by carbon tetrachloride CCl 4 . We found out that the effect of moringa leaves on liver and kidney functions in a state of improvement, as for high-density lipoprotein (HDL) and low-density lipoprotein (LDL), the proportion of LDL was less than HDL compared to the control sample. At the same time, moringa leaves have a significant effect on reducing cholesterol, triglycerides, urea, and creatinine in the serum of rats, which may be attributed to the presence of biologically active plant components. It can be concluded that moringa leaves can improve biological and histological of rats feed it.

The nutritional and health value of beef lipids - fatty acid composition in grass-fed and grain-fed beef

Interest in meat fatty acid (FA) composition stems mainly from the need to find ways to produce healthier meat with a suitable ratio of polyunsaturated (PUFA) to saturated fatty acids (SFA) and a favourable balance between n-6 and n-3 PUFA. Studies of grass feeding versus grain feeding cattle have been conducted in different regions throughout the world and suggest that grass-based diets can significantly improve the fatty acid (FA) composition of beef. Compared with grain diets, grass diets contribute to a lower total fat content and more favourable SFA composition i.e. higher proportion of low density lipoprotein (LDL) and cholesterol-neutral stearic acid (C18:0). Feeding fresh grass compared to concentrates results in higher levels of n-3 PUFA in muscle lipids and a more favourable n-6/n-3 PUFA ratio that is within the nutritional recommendations for the human diet.

Association of glutathione-S-transferase gene polymorphism and lipoprotein subclasses in hemodialysis patients

ObjectivesEnd-stage renal disease (ESRD) is characterized by profound dyslipidemia and enhanced oxidative stress. The patients also show evidence of exhausted and/or deficient anti-oxidative defense enzymes, one of them being glutathione-S-transferase (GST). This study investigates relationship between GST gene polymorphism and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses in ESRD. Design and methodsGSTM1, T1, and P1 genotypes were determined by polymerase chain reaction–restriction fragment length polymorphism in 160 patients undergoing hemodialysis. LDL and HDL subclasses were separated by gradient gel electrophoresis and biochemical parameters were measured by routine laboratory methods. ResultsGSTM1-positive patients had higher proportion of small, dense LDL III particles than those with GSTM1-null genotype (P<0.05). Similarly, GSTP1-Ile/Ile patients had higher proportion of LDL III (P<0.05), but more HDL 2b and less HDL 3a particles than GSTP1-Ile/Val and Val/Val carriers (P<0.05). LDL subclass distribution in smokers with GSTM1-null genotype was shifted towards smaller particles, as compared to GSTM1-positive and GSTM1-null non-smokers. Smokers with GSTP1-Ile/Val and Val/Val genotypes had smaller LDL size than their non-smoking counterparts (P<0.05). Both smokers and non-smokers with GSTP1 Ile/Ile genotype had more LDL III particles than non-smokers carrying Val allele. Non-smokers with GSTP1 Ile/Ile genotype had more HDL 2b subclasses than non-smokers with GSTP1-Ile/Val and Val/Val (P<0.05), but less HDL 3a particles than smokers with GSTP1-Ile/Val and Val/Val genotypes (P<0.05). GSTT1 gene polymorphism had no effect on lipoprotein subclass distributions. ConclusionsOur results demonstrate significant associations between low activity GST genotypes and proatherogenic lipoprotein particles in hemodialysis patients which might further increase their cardiovascular disease risk.

Association between concentrations of serum magnesium and the short-term outcome of patients with acute ischemic stroke

To explore the relationship between the concentration of serum magnesium and the short-term outcome of patients with acute ischemic stroke, in order to provide evidence for improving the outcomes. Patients with acute ischemic stroke under study, were from four hospitals in Shandong province. Data on demographic characteristics, life style related risk factors, history of cardiovascular disease, blood pressure at admission and other clinical characteristics were collected for all the participants. The outcomes were defined as National Institutes of Health Stroke Scale (NIHSS) ≥ 10 or death. According to NIHSS, the subjects were divided into two groups: death/NIHSS ≥ 10 and NIHSS < 10. Concentrations of Mg(2+) were categorized into four levels according to the quartiles of serum magnesium. Cox proportion hazard regression analysis was used to evaluate the association between serum magnesium concentrations and the short-term outcome of acute ischemic stroke. In the death/NIHSS ≥ 10 group, concentrations of serum magnesium and the time from onset to admission were lower than that in the NIHSS < 10 group while the systolic blood pressure on admission, the proportion of low density lipoprotein abnormal, impaired fasting glucose and history of auricular fibrillation were all higher than that in the NIHSS < 10 group. Without the adjustment of multiple factors, when comparing to the lowest quartile of serum magnesium level, the fourth quartile (highest) seemed to have had a tendency of reducing the risk of death/NIHSS ≥ 10 (RR = 0.47, P < 0.05). When multiple factors were adjusted (adjust serum calcium, potassium level and other factors), the fourth and the third quartiles could both reduce the risk of death/NIHSS ≥ 10 (RR values were 0.39 and 0.54, P < 0.05, respectively). With or without the adjustment of multiple factors, there appeared a dose-response relationship between serum magnesium concentrations and the risk to death/NIHSS ≥ 10 (trend P < 0.05). Higher serum magnesium concentrations could reduce the risk to death/NIHSS ≥ 10, suggesting that there was a dose-response relationship between magnesium and the risk to death/NIHSS ≥ 10.

Changes in LDL and HDL Subclasses in Normal Pregnancy and Associations with Birth Weight, Birth Length and Head Circumference

Pregnancy is associated with alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, but the exact pattern of these variations remains controversial. This study investigates longitudinal changes of plasma LDL and HDL particles distributions during the course of normal pregnancy, as well as associations of maternal LDL and HDL subclasses distributions before delivery with parameters of newborn size. Blood samples were collected from 41 healthy pregnant women throughout entire pregnancy, before delivery and 7 weeks postpartum. LDL and HDL subclasses were determined by gradient gel electrophoresis, while other biochemical parameters were measured by standard laboratory methods. During gestation LDL size significantly decreased (P < 0.001), due to reduction in relative proportion of LDL I (P < 0.01) and increase of LDL II (P < 0.001) and IIIA (P < 0.05) subclasses. In the same time, HDL size and proportions of HDL 2a particles significantly decreased (P < 0.001), with concomitant increase of HDL 3b and 3c subclasses (P < 0.05). Observed alterations were associated with changes in serum triglyceride levels. Rearrangement in LDL subclasses distribution during gestation was transient, while postpartum HDL subclasses distribution remained shifted toward smaller particles. Higher proportion of LDL IVB in maternal plasma before delivery was an independent predictor of smaller birth weights and lengths, while higher proportions of LDL IVB and HDL 2a subclasses were independent determinants of newborns' smaller head circumferences. Routine gestational and prenatal care in otherwise normal pregnancy could be complemented with evaluation of LDL and HDL particles distribution in order to ensure an adequate size of the newborn.

Abstract P199: Mean Lipoprotein Levels and Composition in South Asian-Americans Compared to the US Population

Background South Asians have increased disk for cardiovascular disease (CVD) that is not captured by traditional risk factors, including TC and LDL-c. Low-density apolipoprotein-B (apoB) containing lipoproteins are heterogeneous in size and composition, and the particles with the greatest triglyceride content are thought to ultimately be the most atherogenic. Specific composition of low-density lipoproteins is not captured by common lipid measures (i.e. TC, LDL-c). A high proportion of triglyceride-rich low-density lipoproteins could be a mechanism for CVD risk in South Asians. Our objective was to compare mean TC, LDL-c, HDL-c, triglycerides, and apoB-triglyceride ratio (an estimate of low-density lipoprotein content) between South Asian-Americans and the US population. Methods We studied 2,876 South Asian adults living in the United States participating in a wellness program. Demographics were obtained by self-report. Lipoprotein levels were measured after 10-hour fast. US population means were calculated from NHANES (2007-2008, n = 5,113). Individuals on lipid-lowering therapy were excluded (780 (33%) South Asians, 1,194 (19%) NHANES). Results LDL-c (118mg/dL vs 116mg/dL, p&lt;0.05) and triglycerides (139mg/dL vs 131 mg/dL, p&lt;0.05) were higher in South Asians than the US population, whereas TC was lower (192mg/dL vs 197 mg/dL, p&lt;0.05). HDL-c was lower in South Asians (46mg/dL vs 52mg/dL, p&lt;0.05). ApoB was not statistically significantly different (93mg/dL vs 92mg/dL, p = 0.1), however the apoB/triglyceride ratio was lower in South Asians (0.8 vs 0.9, p&lt;0.05). After stratifying for age by decade and gender, we found that South Asians have lower HDL-c until the age of 50, and lower apoB/triglyceride ratio until the age of 60, with no substantial differences between men and women. Conclusions Mean TC, LDL-c, and triglycerides were normal in South Asians, however the apoB/triglyceride ratio was lower in South Asians than in the US population. This finding indicates that a higher proportion of low-density lipoproteins in South Asians are of the triglyceride-rich atherogenic type. This may portend non-HDL-c as a better indicator of CVD risk than LDL-c in South Asians. Further, low apoB/triglyceride ratio and low HDL-c occurs at a young age in South Asians, suggesting that onset of risk is early. The disappearance of these patterns after age 60 may be the result of sample bias (excluding individuals on lipid lowering therapy), and/or survival bias.

Effect of l-carnitine on the size of low-density lipoprotein particles in type 2 diabetes mellitus patients treated with simvastatin

Therapeutic modulation of low-density lipoprotein (LDL) size could be of benefit in reducing the risk of cardiovascular events in diabetic patients. This study evaluated the efficacy of l-carnitine on the size of LDL particles in type 2 diabetes mellitus patients treated with simvastatin. Eighty diabetic patients were randomly assigned to 1 of 2 treatment groups for 3 months. The 2 groups received either simvastatin monotherapy 20 mg (n = 40) or l-carnitine 2 g/d and simvastatin 20 mg (n = 40). The following variables were assessed at baseline; after washout; and at 1, 2, and 3 months of treatment: body mass index, fasting plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, LDL subclasses, LDL size, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-1, and apolipoprotein B-100. After 12 weeks, comparing the 2 groups, we observed a decrease in fasting plasma glucose (1.45 vs 0.61 mmol/L, P < .001) and an increase in glycosylated hemoglobin (0.2% vs 0.4%, P < .05). Moreover, there was a decrease in total cholesterol (2.07 vs 1.45 mmol/L, P < .001), LDL (1.65 vs 1.29 mmol/L, P < .001), triglycerides (1.36 vs 0.41 mmol/L, P < .001), apo B-100 (49 vs 9 g/L, P < .001), and small-sized LDL proportion (10.8% vs 4.9%, P < .001), whereas LDL particle size increased (6 vs 3 Å, P < .001) and HDL increased (0.2 vs 0.11 mmol/L, P < .001). We observed that patients treated with carnitine and simvastatin showed a reduction in small-sized LDL proportion and an increase in LDL particle size.

Electronegative low‐density lipoprotein subfraction from type 2 diabetic subjects is proatherogenic and unrelated to glycemic control

The physicochemical and biological characteristics of electronegative low-density lipoprotein (LDL) (LDL(-)) from type 2 diabetic patients (DM2), before and after insulin therapy, were studied. Total LDL was subfractionated in LDL(+) (native LDL) and LDL(-) by anion-exchange chromatography. The proportion of LDL(-) was increased in plasma from DM2 patients compared to control subjects (13.8 +/- 4.6% versus 6.1 +/- 2.5, P < 0.05) and was not modified after glycemic optimization (14.0 +/- 5.9%). LDL(-) from DM2 patients presented similar differential characteristics versus LDL(+) than LDL(-) from controls; that is, decreased apoB and oxidizability, and increased triglyceride, nonesterified fatty acids (NEFA), apoE, apoC-III, platelet-activating factor (PAF) acetylhydrolase activity and aggregability. No difference in particle size, antioxidants, malondialdehyde (MDA), fructosamine or glycated low-density lipoprotein (gLDL) was observed between LDL subfractions. Concerning differences between LDL subfractions isolated from DM2 and from control subjects, the former showed increased MDA, fructosamine and gLDL proportion and decreased LDL size and antioxidant content. The only effect of glycemic optimization was a decrease in fructosamine and gLDL in LDL(+) from DM2 subjects. LDL(-) from DM2 patients presented low binding affinity to the low-density lipoprotein receptor (LDLr) in cultured fibroblasts compared to LDL(+) and two- to threefold increased ability to release interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in endothelial cells. These results suggest that, although nonenzymatic glycosylation and oxidation are increased in type 2 diabetes, these features would not be directly involved in the generation of LDL(-). Moreover, LDL(-) properties suggest that the high proportion observed in plasma could promote accelerated atherosclerosis in DM2 patients through increased residence time in plasma and induction of inflammatory responses in artery wall cells.

The Triglyceride/High-Density Lipoprotein Cholesterol Ratio, the Small Dense Low-Density Lipoprotein Phenotype, and Ischemic Heart Disease Risk

This study investigated the relevance of using the plasma triglyceride to high-density lipoprotein cholesterol ratio (Log TG/HDL-C) for the prediction of the small dense lowdensity lipoprotein (LDL) phenotype and the risk of ischemic heart disease (IHD). Analyses were based on data from the Quebec Cardiovascular Study in a cohort of 2072 men free of IHD at baseline, among whom 262 had a first IHD event (coronary death, non fatal myocardial infarction and unstable angina) during a 13-year follow-up period. LDL particle size phenotype was characterized using 2-16% polyacrylamide gradient gel electrophoresis (PAGGE) of whole plasma. There were significant associations between the Log TG/HDL-C ratio and features of LDL size phenotype such as the proportion of LDL with a diameter <255A (r = 0.43, p < 0.001) and LDL peak particle size (r = -20.55, p < 0.001). However, the Log TG/HDL-C ratio brought no additional value (p â yen 0.1) in predicting the small dense LDL phenotype (area under the receiver operating curve (AUROC = 71.9%) compared to TG alone (AUROC = 71.2%) or to a combination of Log TG and HDL-C (AUROC = 72.4%) after multivariate adjustment for non lipid risk factors. Finally, elevations in the Log TG/HDL-C ratio did not improve the discrimination of incident IHD cases from non IHD cases compared to the use of plasma TG levels alone (p = 0.5) or a combination of the individual TG and HDL-C values (p = 0.5). The Log TG/HDL-C ratio does not improve our ability to identify individuals with the small dense LDL phenotype compared to plasma TG levels alone. The Log TG/HDLC is also not superior to plasma TG levels alone in predicting IHD risk in men of the QuA(c)bec Cardiovascular Study.

The Triglyceride/High-Density Lipoprotein Cholesterol Ratio, the Small Dense Low-Density Lipoprotein Phenotype, and Ischemic Heart Disease Risk

This study investigated the relevance of using the plasma triglyceride to high-density lipoprotein cholesterol ratio (Log TG/HDL-C) for the prediction of the small dense lowdensity lipoprotein (LDL) phenotype and the risk of ischemic heart disease (IHD). Analyses were based on data from the Quebec Cardiovascular Study in a cohort of 2072 men free of IHD at baseline, among whom 262 had a first IHD event (coronary death, non fatal myocardial infarction and unstable angina) during a 13-year follow-up period. LDL particle size phenotype was characterized using 2–16% polyacrylamide gradient gel electrophoresis (PAGGE) of whole plasma. There were significant associations between the Log TG/HDL-C ratio and features of LDL size phenotype such as the proportion of LDL with a diameter <255Å (r = 0.43, p < 0.001) and LDL peak particle size (r = -20.55, p < 0.001). However, the Log TG/HDL-C ratio brought no additional value (p ≥ 0.1) in predicting the small dense LDL phenotype (area under the receiver operating curve (AUROC = 71.9%) compared to TG alone (AUROC = 71.2%) or to a combination of Log TG and HDL-C (AUROC = 72.4%) after multivariate adjustment for non lipid risk factors. Finally, elevations in the Log TG/HDL-C ratio did not improve the discrimination of incident IHD cases from non IHD cases compared to the use of plasma TG levels alone (p = 0.5) or a combination of the individual TG and HDL-C values (p = 0.5). The Log TG/HDL-C ratio does not improve our ability to identify individuals with the small dense LDL phenotype compared to plasma TG levels alone. The Log TG/HDLC is also not superior to plasma TG levels alone in predicting IHD risk in men of the Québec Cardiovascular Study.

Low-density lipoprotein subclass and its correlating factors in diabetics

Objectives Small dense LDL, low density lipoprotein (LDL) particles with small size and high density, is regarded as a significant risk factor for cardiovascular diseases. Diabetes mellitus is one of the conditions accompanied by increased small dense LDL. We analyzed LDL subclass in type 2 diabetics and normal controls with LipoPrint LDL System to investigate the LDL heterogeneity in diabetics and factors affecting it. Design and methods We selected 40 normal controls and 40 type 2 diabetics with fasting blood glucose level over 7.0 mmol/L and HbA1c level over 7%. LDL subclass was determined with LipoPrint LDL System. LipoPrint LDL System fractionates LDL into seven parts (LDL1-7) by size and LDL3 to LDL7 are defined as small-sized LDL. In addition we estimated ‘the percent of small-sized LDL over whole LDL’ and defined it as ‘small-sized LDL proportion’. Results Mean small-sized LDL proportion was significantly higher in diabetics (23.4%) than in controls (11.8%) ( p < 0.001) and small-sized LDL proportion showed positive correlation with blood levels of glucose, HbA1c, total cholesterol, triglyceride, and oxidized LDL and negative correlation with HDL cholesterol level in univariate analysis ( p < 0.001). Of these parameters, triglyceride, HbA1c, oxidized LDL were statistically significant variables contributing to the small-sized LDL proportion in stepwise multiple regression analysis. Conclusions We analyzed small-sized LDL proportion in type 2 diabetics and found that it was significantly increased in diabetics than control subjects and it was independently correlated with triglyceride, HbA1c, oxidized LDL in descending order, which are reflecting lipid metabolism, glycation, and oxidative stress, respectively.

Pulsatile versus oscillatory shear stress regulates NADPH oxidase subunit expression: implication for native LDL oxidation.

Shear stress regulates endothelial nitric oxide and superoxide (O2-*) production, implicating the role of NADPH oxidase activity. It is unknown whether shear stress regulates the sources of reactive species production, consequent low-density lipoprotein (LDL) modification, and initiation of inflammatory events. Bovine aortic endothelial cells (BAECs) in the presence of 50 microg/mL of native LDL were exposed to (1) pulsatile flow with a mean shear stress (tau(ave)) of 25 dyne/cm2 and (2) oscillating flow at tau(ave) of 0. After 4 hours, aliquots of culture medium were collected for high-performance liquid chromatography analyses of electronegative LDL species, described as LDL- and LDL2-. In response to oscillatory shear stress, gp91phox mRNA expression was upregulated by 2.9+/-0.3-fold, and its homologue, Nox4, by 3.9+/-0.9-fold (P<0.05, n=4), with a corresponding increase in O2-* production rate. The proportion of LDL- and LDL2- relative to static conditions increased by 67+/-17% and 30+/-7%, respectively, with the concomitant upregulation of monocyte chemoattractant protein-1 expression and increase in monocyte/BAEC binding (P<0.05, n=5). In contrast, pulsatile flow downregulated both gp91phox and Nox4 mRNA expression (by 1.8+/-0.2-fold and 3.0+/-0.12-fold, respectively), with an accompanying reduction in O2-* production, reduction in the extent of LDL modification (51+/-12% for LDL- and 30+/-7% for LDL2-), and monocyte/BAEC binding. The flow-dependent LDL oxidation is determined in part by the NADPH oxidase activity. The formation of modified LDL via O2-* production may also affect the regulation of monocyte chemoattractant protein-1 expression and monocyte/BAEC binding.

Effect of Plasma C-Reactive Protein Levels in Modulating the Risk of Coronary Heart Disease AssociatedWith Small, Dense, Low-Density Lipoproteins in Men(The Quebec Cardiovascular Study)

This purpose of this study was to investigate how plasma C-reactive protein (CRP), a nonspecific acute-phase reactant, modulates the risk of coronary heart disease (CHD) associated with the small, dense, low-density lipoprotein (LDL) phenotype. LDL particle size and plasma CRP were measured in the Quebec Cardiovascular Study cohort of 2,025 men free of CHD at baseline, among whom 103 had a first CHD event during a 5-year follow-up period. Plasma CRP levels were measured using the Behring Latex-Enhanced (highly sensitive) CRP assay. LDL particle size phenotype was characterized using 2% to 16% polyacrylamide gradient gel electrophoresis. There were weak but significant associations between plasma CRP levels and features of LDL size, such as the proportion of LDL with a diameter <255 Å (r = 0.09, p <0.001) and LDL peak particle size (r = −0.09, p <0.001). Variations in plasma CRP levels modulated the risk of CHD associated with small LDL peak particle size (relative risk 4.3 vs 2.5 in men with high vs low plasma CRP levels, respectively) and with an elevated proportion of LDL <255 Å (relative risk 6.6 vs 3.0). Thus, increased plasma CRP levels further elevate the risk of CHD associated with having small, dense LDL particles.

Effect of Glycemic Optimization on Electronegative Low-Density Lipoprotein in Diabetes: Relation to Nonenzymatic Glycosylation and Oxidative Modification1

The effect of insulin therapy on low-density lipoprotein (LDL) oxidizability, proportion of electronegative LDL [LDL(-)] and LDL composition was studied in 33 type 2 diabetic patients. Before glycemic control improvement, type 2 diabetic subjects presented higher triglyceride and very low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol than 25 healthy matched subjects. Furthermore, their LDL was more susceptible to oxidation (lag phase 45.9 +/- 5.4 min vs. 49.7 +/- 7.6 min, P < 0.05), contained a higher proportion of LDL(-) (19.0 +/- 8.7% vs. 14.3 +/- 5.5%, P < 0.05), and was enriched in triglyceride and depleted in cholesterol and phopholipids. Lipoprotein profile improved after glycemic optimization but failed to change either LDL oxidizability (45.3 +/- 6.2 min) or LDL(-) (17.9 +/- 8.2%). These data suggest that oxidation rather than nonenzymatic glycosylation could be related to the high LDL(-) found in these patients and disagree with results obtained in a previous study of type 1 diabetic patients. A second study was conducted in 10 type 1 and 10 type 2 diabetic subjects under insulin therapy, and the proportions of glycated LDL (gLDL) and LDL(-) were determined. Basal gLDL (2.8 +/- 0.6%) and LDL(-) (20.7 +/- 6.1%) decreased in type 1 diabetics after glycemic optimization (1.9 +/- 0.6% and 15.4 +/- 3.4%, respectively; P < 0.05). In type 2 patients, even though gLDL decreased (from 2.2 +/- 0.6% to 1.6 +/- 0.6%, P < 0.05) no effect was observed on LDL(-) (from 17.3 +/- 2.9% to 16.0 +/- 4.3%). We conclude that nonenzymatic glycosylation, which appears as a determinant of the high proportion of LDL(-) in type 1 diabetes, does not play a major role in LDL(-) generation in type 2 diabetes.

Effect of physical exercise on lipoprotein(a) and low-density lipoprotein modifications in Type 1 and Type 2 diabetic patients

To evaluate the effect of physical exercise on blood pressure, the lipid profile, lipoprotein(a) (Lp(a)), and low-density lipoprotein (LDL) modifications in untrained diabetics, 27 diabetic patients (14 type 1 and 13 type 2) under acceptable and stable glycemic control were studied before and after a supervised 3-month physical exercise program. Anthropometric parameters, insulin requirements, blood pressure, the lipid profile, Lp(a), LDL composition, size, and susceptibility to oxidation, and the proportion of electronegative LDL (LDL(-)) were measured. After 3 months of physical exercise, physical fitness improved (maximal O2 consumption [VO2max], 29.6 +/- 6.8 v 33.0 +/- 8.4 mL/kg/min, P < .01). The body mass index (BMI) did not change, but the waist circumference (83.2 +/- 11.8 to 81.4 +/- 11.2 cm, P < .05) decreased significantly. An increase in the subscapular to triceps skinfold ratio (0.91 +/- 0.37 v 1.12 +/- 0.47 cm, P < .01) and midarm muscle circumference ([MMC], 23.1 +/- 3.4 v 24.4 +/- 3.7 cm, P < .001) were observed after exercise. Insulin requirements (0.40 +/- 0.18 v 0.31 +/- 0.19 U/kg/d, P < .05) and diastolic blood pressure (80.2 +/- 10 v 73.8 +/- 5 mm Hg, P < .01) decreased in type 2 diabetic patients. High-density lipoprotein cholesterol (HDL-C) increased in type 1 patients (1.48 +/- 0.45 v1.66 +/- 0.6 mmol/L, P < .05), while LDL cholesterol (LDL-C) decreased in type 2 patients (3.6 +/- 1.0 v3.4 +/- 0.9 mmol/L, P < .01). Although Lp(a) levels did not vary in the whole group, a significant decrease was noted in patients with baseline Lp(a) above 300 mg/L (mean decrease, -13%). A relationship between baseline Lp(a) and the change in Lp(a) (r = -.718, P < .0001) was also observed. After the exercise program, 3 of 4 patients with LDL phenotype B changed to LDL phenotype A, and the proportion of LDL(-) tended to decrease (16.5% +/- 7.4% v 14.0% +/- 5.1%, P = .06). No changes were observed for LDL composition or susceptibility to oxidation. In addition to its known beneficial effects on the classic cardiovascular risk factors, regular physical exercise may reduce the risk of cardiovascular disease in diabetic patients by reducing Lp(a) levels in those with elevated Lp(a) and producing favorable qualitative LDL modifications.

Identification and treatment of hypertriglyceridemia as a risk factor for coronary heart disease.

Recent publications, including new population-based studies and a meta-analysis of prospective, population-based studies, provide strong evidence for an elevated triglyceride level as an independent risk factor for coronary heart disease. Pathophysiologic relationships between elevated triglyceride levels and both reduced high-density lipoprotein levels and an increase in the proportion of low density lipoproteins that are small and dense support the epidemiologic data, and suggest that an elevated triglyceride level should constitute a target for lipid-lowering therapy. There are no clear recommendations for management of patients with hypertriglyceridemia available in the current treatment guidelines. Treatment options include life-style measures and, if drug therapy is required, nicotinic acid, fibrates, more potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), or combination therapy with statin plus fibrate or nicotinic acid.

Effect of simvastatin treatment on the electronegative low-density lipoprotein present in patients with heterozygous familial hypercholesterolemia

Most described modifications of low-density lipoprotein (LDL) cholesterol share an increase in its negative electric charge; in fact, an electronegative form of LDL can be identified and isolated from plasma. Although the exact nature of the chemical modification of electronegative LDL is still controversial, its toxicity on endothelial cells has been demonstrated. Statins have protective effects against cardiovascular disease that are independent of their lipid-lowering action and which could be due, at least in part, to the prevention of LDL modification. We evaluated the effect of 6 months of simvastatin therapy (40 mg/day) on electronegative LDL proportion and LDL susceptibility to in vitro induced oxidation in 21 patients with heterozygous familial hypercholesterolemia (FH). Eleven normolipemic subjects were analyzed as a control group. Total cholesterol as well as LDL and very low density lipoprotein cholesterol, triglycerides, and apoprotein B decreased 30% after the first month of therapy, with no further decreases thereafter. LDL susceptibility to oxidation was similar in FH patients and controls and did not change throughout the treatment. Electronegative LDL proportion was 35.1 ± 9.9% in FH patients and 9.1 ± 2.4% in control subjects (p <0.0001) but, in contrast to total LDL cholesterol and the rest of lipid parameters, it decreased to 28.6 ± 9.1% in the third month and to 21.2 ± 7.7% in the sixth month of therapy. The decrease in these cytotoxic particles may be a relevant mechanism by which simvastatin protects against cardiovascular disease.

Ascorbic acid inhibits the increase in low-density lipoprotein (LDL) susceptibility to oxidation and the proportion of electronegative LDL induced by intense aerobic exercise.

We have previously reported the finding of an acute increment in the susceptibility of low-density lipoprotein (LDL) to oxidation and in the proportion of electronegative LDL [LDL(-)] after intense exercise. We have now studied the effect of oral supplementation with 1 g ascorbic acid, immediately before a 4-h athletic race, on the susceptibility of LDL to oxidation, the proportion of LDL(-), and the alpha-tocopherol and lipid peroxides content in LDL, in order to inhibit such deleterious changes, and to confirm the oxidative nature of modifications of LDL induced by exercise. We studied seven highly trained runners who received a supplement of 1 g ascorbic acid and a control group of seven who did not receive the supplement. The susceptibility of LDL to oxidation was assessed by measurement of conjugated dienes after CuSO4-induced oxidation, the proportion of LDL(-) was determined by anion exchange chromatography, alpha-tocopherol was quantified by reverse-phase high performance liquid chromatography, and lipid peroxides were measured by the thiobarbituric acid-reactive substances (TBARS) method. After exercise, in the control group there was an increase in both the susceptibility of LDL to oxidation (change in lag phase from 51.4 +/- 4.7 min to 47.0 +/- 4.6 min, P < 0.05) and the proportion of LDL(-) (from 11.1 +/- 1.4% to 13.0 +/- 2.2%, P < 0.05), but these did not occur in the ascorbic acid group (change in lag phase from 49.7 +/- 2.3 min to 50.4 +/- 4.2 min, and in LDL(-) from 9.7 +/- 1.7% to 10.1 +/- 1.7%). No significant changes in the absolute amount of LDL alpha-tocopherol were observed after exercise (ascorbic acid group: 6.65 +/- 0.94 mol/mol apoB before the race, 7.13 +/- 0.88 mol/mol apoB after the race; control group: 7.34 +/-0.69 mol/mol apoB before the race, 7.06 +/- 0.69 mol/mol apoB after the race), but significant differences were found when increments or decrements of alpha-tocopherol were tested (alpha-tocopherol increased 9.9 +/- 11.5% in the ascorbic acid group, and decreased 0.6 +/- 7.3% in the control group; P < 0.018). TBARS did not change after exercise. We conclude that 1 g ascorbic acid inhibits the increase in LDL susceptibility to oxidation after exercise, preventing this acute pro-atherogenic effect. In addition, the observation that LDL(-) enhancement is prevented by ascorbic acid supports the hypothesis that at least some of the circulating LDL(-) originates from oxidative processes.

Differential effects of estrogen on low-density lipoprotein subclasses in healthy postmenopausal women

The use of estrogen by postmenopausal women decreases plasma low-density lipoprotein (LDL) cholesterol levels. To determine whether LDL subclass profiles influence this response, we studied 31 healthy postmenopausal women who were administered two doses (0.625 and 1.25 mg/d) of conjugated equine estrogen in a placebo-controlled double-blind crossover study. Lipid-stained gradient gels were used to categorize LDL subclass patterns. All women were classified as LDL subclass pattern A (predominant LDL peak ≥260 Å). Within the pattern A classification, there were 12 women during placebo treatment with LDL subclass I pattern (predominant LDL peak >271 Å) and 19 women with LDL subclass II pattern (predominant LDL peak ≤ 271 and ≥ 260 Å). Postmenopausal women with LDL subclass I on placebo treatment had significantly lower LDL cholesterol levels compared with women having LDL subclass II (126 ± 28 v 147 ± 23 mg/dL, P < .03). Postmenopausal women with LDL subclass I also had significantly ( P < .05) lower very-low-density lipoprotein (VLDL) cholesterol, VLDL triglyceride, and VLDL apo B levels and significantly higher ( P < .05) high-density lipoprotein 2 (HDL 2) cholesterol, HDL 3 cholesterol, and HDL 2 apo A-I levels. Estrogen replacement significantly ( P < .05) decreased LDL cholesterol levels and increased VLDL and LDL triglyceride, HDL 2 and HDL 3 cholesterol and apo A-I, and HDL 2 apo A-II levels to a similar extent in postmenopausal women with LDL I or II subclass patterns. Estrogen replacement at either dose in postmenopausal women with the LDL I subclass pattern decreased LDL I relative peak area and LDL II peak particle diameter from 55% ± 1.7% to 39% ± 2.3% (mean ± SEM, P < .001) and from 269 ± 0.5 to 267 ± 0.7 Å (mean ± SEM, P < .001), respectively. In postmenopausal women with the LDL II subclass pattern, no significant change in LDL subclass distribution or peak diameter was noted. The prevalence of pattern B (predominant LDL peak <260 Å) and the mean proportion of LDL subclass III particles (<260 Å, 12%) were unaffected by estrogen treatment. In summary, estrogen replacement therapy decreased the proportion of large LDL I particles and increased the proportion of intermediate-size LDL II particles in healthy postmenopausal women with a predominance of large LDL particles at baseline. However, estrogen treatment did not increase the proportion of small, dense LDL III particles or result in conversion to LDL pattern B, attributes of LDL that have been associated with increased coronary artery disease risk in men.

Regulation of low-density-lipoprotein metabolism in the rat

The mechanism of regulation of plasma low-density-lipoprotein (LDL) metabolism in the rat was studied under a number of experimental conditions. LDL clearance and uptake in the liver was measured after intravenous pulse injection of [14C]sucrose-labelled LDL alone or in combination with reductively methylated [3H]sucrose-labelled LDL. Hyperthyroid rats showed a significant increase in fractional catabolic rate (FCR) and the proportion of LDL degraded in the liver, whereas the synthetic rate of LDL increased by 50%. Receptor-mediated clearance increased 2-fold. Hypothyroid rats showed a significant increase in LDL concentration. The FCR and proportion of LDL degraded in the liver were decreased significantly. Receptor-mediated clearance was also reduced. Cholesterol feeding increased chylomicron, very-low-density-and intermediate-density-lipoprotein cholesterol concentrations, but there was no change in the LDL concentration, FCR or the synthetic rate of LDL. Cholestyramine feeding did not induce changes in the kinetic parameters. These results indicate that, in the rat, the hepatic LDL-receptor pathway is under hormonal control, whereas cholesterol and cholestyramine feeding have no demonstrated effect on LDL metabolism.