Low Density Lipoprotein Subfraction Profile Research Articles

Distinct effects of fixed combinations of valsartan with either amlodipine or hydrochlorothiazide on lipoprotein subfraction profile in patients with hypertension

The effect of antihypertensive drugs on lipoprotein subfraction profile is still under investigation. In this study the effects of fixed combination of valsartan with either amlodipine (V-A) or hydrochlorothiazide (V-H) on low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) subfraction profile of patients with stage 2 or 3 hypertension were assessed. A total of 60 drug-naive patients were randomized to either V-A (160/5 mg, n=30) or V-H (160/12.5 mg, n=30). At baseline as well as 16 weeks post-treatment analysis of the LDL and HDL subfraction profile was conducted by using LDL Lipoprint System. Both V-A and V-H effectively reduced blood pressure (BP) to similar levels. An increase in the cholesterol concentration of small-dense LDL subfractions (by 18.2%, P<0.05) was observed in the V-H group, whereas this parameter remained unchanged in the V-A group. Therefore, mean LDL particle size was decreased in the V-H group (from 267 ± 5 to 266 ± 5Å, P<0.05). HDL-Cholesterol (HDL-C) levels were reduced by 4.7% (P<0.05) in the V-H group, mirrored by a reduction in the cholesterol mass of small and intermediate HDL particles. In conclusion, despite similar reductions in BP, V-H combination may adversely affect serum lipids as well as LDL and HDL subfraction profile as compared with V-A.

Serum adipokines and low density lipoprotein subfraction profile in hypopituitary patients with growth hormone deficiency

The aim was to evaluate the concentrations of lipid subfractions in relation to adipokines and metabolic parameters in adult growth hormone (GH)-deficient hypopituitary patients on conventional replacement therapy. The study included 21 GH deficient-hypopituitary patients (age: 36.0 ± 15.1 years, male/female: 7/14) on conventional replacement therapy other than GH and 20 comparable controls (age: 37.3 ± 14.0 years, male/female: 6/14). Lipid subfractions (Lipoprint system), serum adipokine (leptin, adiponectin, resistin) concentrations, body composition, a surrogate marker for insulin resistance (HOMA) and conventional lipid profile were evaluated. No statistically significant difference was found with respect to HOMA, adipokine concentrations and anthropometric parameters between patients and controls except for significantly increased waist-to-hip ratio in hypopituitary group. Total and LDL cholesterol concentrations were significantly higher in the patients. LDL particle size (268.88 ± 3.16 vs. 271.31 ± 3.11 Å, P = 0.151) and small-dense LDL subfraction did not differ significantly. According to logistic regression analysis, triglyceride concentrations ≥1.69 mmol/L was the sole parameter significantly and independently predicted small (<268 Å) LDL particle size (P = 0.019) in the whole group. Increased triglyceride concentrations affect LDL particle size in GH-deficient hypopituitary patients. Small dense LDL seems not directly contribute to atherogenic potential in hypopituitarism.

Baseline triglyceride levels and insulin sensitivity are major determinants of the increase of LDL particle size and buoyancy induced by rosuvastatin treatment in patients with primary hyperlipidemia

The influence of various statins on low-density-lipoprotein (LDL)-particle phenotype has been reportedly trivial or moderate. We assessed the effect of rosuvastatin (the newest statin available) on the LDL subfraction profile in patients with primary hyperlipidemia. One hundred and twenty patients with primary hyperlipidemia without evidence of cardiovascular disease were randomized to therapeutic lifestyle modification (‘control’ group, N = 60) or therapeutic lifestyle modification plus rosuvastatin 20 mg/day ( N = 60). Laboratory evaluation was performed at baseline and 12 weeks post-treatment. LDL subfraction analysis was carried out electrophoretically using of high-resolution 3% polyacrylamide gel tubes and the Lipoprint LDL System. Rosuvastatin induced a redistribution of LDL-cholesterol from small-dense LDL particles to large-buoyant ones and increased the mean LDL particle size. This beneficial effect was observed only in patients with baseline triglyceride levels ≥ 150 mg/dl (mean LDL particle size 255 ± 7 Ǻ vs 260 ± 5 Ǻ, P < 0.01), whereas the LDL subfraction profile was not altered in those with triglyceride levels < 150 mg/dl. Stepwise multivariate linear regression analysis revealed that baseline triglyceride levels ( R 2 = 0.29, P = 0.001) followed by baseline insulin resistance as assessed by the HOmeostasis Model Assessment (HOMA) ( R 2 = 0.25, P = 0.001) were independently associated with the rosuvastatin-induced increase in the mean LDL particle size. In conclusion, rosuvastatin at 20 mg/day favorably modified the relative distribution of LDL-cholesterol distribution on LDL subfractions as well as on the mean LDL particle size in patients treated for primary dyslipidemia. Baseline triglyceride levels as well as baseline HOMA-index were found to be the major predictors of this beneficial action of rosuvastatin.

Low-Density Lipoprotein Sub-Fraction Profiles in Obese Children Before and After Attending a Residential Weight Loss Intervention

Small dense LDL particles are associated with an increased risk of coronary heart disease and are prevalent in obesity related dyslipidaemia. This study evaluated the effect of weight loss in nine children (BMI 33.4 +/- 8.4 kg.m(-2) and age 15.1 +/- 2.9 years) on LDL peak particle size, and cholesterol concentrations within particular LDL sub-fractions. Each child undertook fun based physical activity, dietary restriction and modification and lifestyle education classes in a residential summer weight loss intervention. Blood was drawn before and after intervention and LDL heterogeneity measured by ultracentrifugation. The mean change in body weight were -6.8 +/- 4.9 kg, BMI units -2.5 +/- 1.4 kg.m(-2), and waist circumference -6.3 +/- 6.3 cm (all p < 0.01). Absolute LDL-c concentration reduced from 106.2 mg/dL to 88.3 mg/dL (p < 0.01). The cholesterol contained within the small dense LDL sub-fraction (LDL-c III) reduced from 54.1 mg/dL to 40.4 mg/dL (p < 0.01). Peak particle density decreased from 1.041g/mL to 1.035g/mL (p < 0.01). At pre intervention 50.9% of absolute cholesterol was within LDL-c III particles, changing to 46.2%. Mean weight loss of -6.8 +/- 4.9 kg lowers absolute LDL-c and the cholesterol specifically within LDL-c III particles. LDL peak particle size increased and a degree of LDL particle remodelling occurred. These favourable adaptations, accrued in a matter of 4 weeks, maybe associated with a reduction in CHD risk.

Associations of apolipoprotein E polymorphism with low-density lipoprotein size and subfraction profiles in Arab patients with coronary heart disease

The APOE gene locus has 3 major alleles, E3, E4 and E2, which variably influence coronary heart disease (CHD) risk. Plasma low-density lipoprotein (LDL) profile, another major CHD risk factor, is characterized on the basis of size and density into 2 main patterns: large buoyant LDL and small dense LDL. The latter has also been linked with increased CHD risk. This study investigates associations of specific APOE allelic patterns with LDL size and subfraction profiles in patients with CHD and healthy control subjects. We recruited 2 groups of male subjects: (A) 65 apparently healthy control subjects, median age, 39.0 years (range, 25.0-60.0 years); (B) 50 patients with CHD, median age, 54.0 years (range, 40.0-76.0 years). APOE genotypes were determined by validated polymerase chain reaction-restriction fragment length polymorphism methods, and LDL size and subfractions were assessed by a high-resolution, nongradient polyacrylamide gel electrophoresis technique (LIPOPRINT, Quantimetrix, Redondo Beach, CA). Lipid and other biochemical analyses were done by autoanalyzer techniques. The associations of specific APOE alleles and genotypes with LDL size and subfraction patterns were then assessed. As expected, patients with CHD had a worse atherogenic lipoprotein profile (waist-hip ratio, LDL, uric acid, and apolipoprotein B) than the controls. APOE genotype and allele frequencies were similar for both groups. In either group, median percent large buoyant LDL (pattern A) was greater in controls (51.0% vs 46.5%, P < .001) and percent small dense LDL (pattern B) was greater with CHD (9.0% vs 3.0%, P < .001). The latter also had smaller median particle size (26.5 vs 26.9 nm, P < .001). In controls, percent LDL pattern B was significantly lower with APOE2 than with APO non-E2 (4.0% vs 0.0%, P < .05); in patients with CHD, E2 patients had smaller particle size, and pattern B was significantly lower with non-E2 than with E2 (15.0 vs 8.0, P < .05). With respect to E4, control non-E4 had a smaller median percent LDL pattern B than E4; otherwise, there were no significant findings in relation to APOE type and LDL size and subfractions in both subject groups. These results confirm observations in other populations of increased levels of small dense LDL in patients with CHD. Although the APOE allelic pattern, especially APOE2, could be related to LDL subfraction profiles in control subjects, such associations could not be demonstrated in those with CHD.

Effect of aging and obesity on the expression of dyslipidaemia in children from families with familial combined hyperlipidaemia

The aim of the present study was to delineate the mechanism(s) responsible for the increased secretion of VLDL (very-low-density lipoprotein) particles in patients with FCH (familial combined hyperlipidaemia). In 194 young adults (<25 years of age) recruited from families with FCH, we investigated how plasma lipids, (apo)lipoproteins and BMI (body mass index) varied with age. Furthermore, we performed a 5-year follow-up study of clinical and biochemical characteristics of a subset of this population (n=85) stratified by apoB (apolipoprotein B) levels (below or above the 75th percentile adjusted for age and gender). Plasma apoB concentration (r=0.45, P<0.0001), triacylglycerol (triglyceride) concentration (r=0.45, P<0.0001), LDL (low-density lipoprotein) subfraction profile (r=-0.46, P<0.0001) and BMI (r=0.51, P<0.0001) were significantly associated with age. Plasma apoB concentration in the hyperapoB group was already elevated at a young age, whereas other characteristics of FCH, as observed in adults, including triacylglycerol levels >1.5 mmol/l and/or small-dense LDL, were observed only sporadically. After the 5-year follow-up, BMI increased in both groups, and this increase was associated with changes in apoB (r=0.27, P<0.05), triacylglycerol (r=0.30, P<0.01), VLDL cholesterol (r=0.22, P<0.05), VLDL triacylglycerol (r=0.25, P<0.05) and high-density lipoprotein cholesterol (r=-0.27, P<0.05). In conclusion, we have found indirect evidence of a primary, presumably genetically determined, increase in plasma apoB concentration occurring early in life of offspring from families with FCH. However, aging-related post-maturation increases in adipose tissue mass also appear to contribute to an aggravation and/or modulation of this genetically determined apoB overproduction.

Effects of Atorvastatin and Simvastatin on Low-Density Lipoprotein Subtraction Profile, Low-Density Lipoprotein Oxidizability, and Antibodies to Oxidized Low-Density Lipoprotein in Relation to Carotid Intima Media Thickness in Familial Hypercholesterolemia

BackgroundLittle is known about the effects of statins on the quality of circulating low-density lipoprotein (LDL) in relation to atherosclerosis progression.MethodsIn a double-blind, randomized trial of 325 patients with familial...

Effects of Atorvastatin and Simvastatin on Low-Density Lipoprotein Subfraction Profile, Low-Density Lipoprotein Oxidizability, and Antibodies to Oxidized Low-Density Lipoprotein in Relation to Carotid Intima Media Thickness in Familial Hypercholesterolemia

Effects of Atorvastatin and Simvastatin on Low-Density Lipoprotein Subfraction Profile, Low-Density Lipoprotein Oxidizability, and Antibodies to Oxidized Low-Density Lipoprotein in Relation to Carotid Intima Media Thickness in Familial Hypercholesterolemia

Oxidative stress and normal pregnancy.

To determine whether, in normal pregnancies, there is evidence of oxidative stress that is related to the lipid changes observed in pregnancy. Longitudinal study of healthy women having a normal pregnancy. Samples were obtained towards the end of each trimester and after 8 weeks postpartum. Seventeen healthy women during a normal singleton pregnancy were compared with 12 healthy, non-pregnant women. Oxidative stress was determined by measuring total antioxidant capacity (TAC), uric acid and lipid hydroperoxides (LHP). Lipid status was evaluated by measuring total and high-density lipoprotein cholesterol, triglycerides and low-density lipoprotein (LDL) subfractions. Pregnancy was associated with decreased TAC and uric acid in the first trimester, which gradually increased during pregnancy, reaching normal values during the postpartum period. LHP significantly increased towards the end of pregnancy. The changes observed in LHP were significantly correlated with increases in LDL subfraction profile. Late pregnancy was associated with the formation of susceptible, oxidisable particles (high LDL score) and an increase in oxidative damage. These biochemical changes may be relevant for the long-term cardiovascular health of women, especially those of high parity or those who are at high risk for cardiovascular disease (e.g. women with diabetes).

HMG-CoA reductase inhibitor decreases small dense low-density lipoprotein and remnant-like particle cholesterol in patients with type-2 diabetes

Patients with type 2 diabetes are known to have abnormalities in their remnant metabolism and low density lipoprotein (LDL) subfraction pattern, with a preponderance of small dense LDL. The effects of pitavastatin, a newly synthesized 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, on lipoprotein profiles in patients with type 2 diabetes were determined. Thirty-three patients were treated with pitavastatin with a daily dose of 2 mg for 8 weeks. After treatment, triglyceride, total and LDL cholesterol were significantly reduced by 28.7 ± 36.7%, 25.2 ± 14.3% and 36.1 ± 14.3%, respectively. Remnant-like particle cholesterol (RLP-C), an independent risk factor for CAD which is known to be elevated in diabetic patients, was also significantly reduced (−30.9 ± 30.5%) by the treatment and this decrease correlated well with the decrease in triglyceride level. The proportion of small dense LDL, which is known for its atherogenisity, decreased from 29.9 ± 26.2% to 19.7 ± 22.7% and the mean LDL particle size significantly increased from 26.36 ± 1.13 nm to 27.10 ± 1.36 nm. Pitavastatin, which is known to improve triglyceride levels and cholesterol levels, also improves RLP-C level and LDL subfraction profiles, and this in turn may reduce the cardiovascular risk in patients with type 2 diabetes and dyslipidemia.

Abnormal low-density lipoprotein subfraction profile in patients with untreated hypertension.

Low-density lipoprotein (LDL) consists of a heterogeneous group of particles of varying size and electrophoretic mobility. A predominance of small, more mobile particles is a risk factor for cardiovascular disease. To investigate the hypothesis that untreated patients with essential hypertension in the absence of vascular disease may exhibit abnormalities of LDL subfractions. Specialist hypertension clinic. Cross-sectional study. Following disc polyacrylamide gel electrophoresis, the mean (LDL locus) and heterogeneity (LDL spread) of mobility was recorded in 41 patients (mean age 52.6 years, 24 men) presenting with untreated essential hypertension (in the absence of vascular disease or diabetes mellitus) and in 45 healthy controls (age 56.9 years, 22 men) recruited from primary-care lists. Although there were no significant differences in total, low- or high-density lipoprotein cholesterol concentrations, LDL locus was significantly greater in the hypertensive group: mean (95%CI) 36.7 (35.7-37.6) vs. 34.8 (34.1-35.5), p=0.002. LDL locus was significantly elevated even in hypertensives with triglyceride concentrations below the median (<1.25 mmol/l). LDL spread was also greater in the hypertensive group, but not significantly: 5.6 (5.2-6.0) vs. 5.5 (5.3-5.8), p=0.10. Hypertensive patients have a preponderance of smaller LDL subfractions. This dyslipidaemia is not readily detected by conventional lipid assays.

Dyslipidaemia in patients with malignant-phase hypertension.

Low-density lipoprotein (LDL) consists of a heterogeneous group of particles of differing size, density and electrophoretic mobility, smaller particles being more atherogenic. A high proportion of small LDL particles is an independent risk factor for cardiovascular disease. We hypothesized that patients with malignant phase hypertension (MHT), the most severe form of hypertension, would demonstrate a more atherogenic LDL subfraction profile than either non-malignant hypertension (NMHT) or normotensive controls. We compared 16 patients with MHT to 41 patients with untreated NMHT and 45 normotensive controls. LDL subfraction profile was measured by disc polyacrylamide gel electrophoresis using a validated scoring system to calculate the mean size (locus) and heterogeneity (spread) of LDL subfraction mobilities. A higher LDL locus indicates a greater proportion of small LDL subfractions. LDL cholesterol levels were similar in all three groups (p=0.23). High-density lipoprotein cholesterol (HDL-C) levels were significantly lower (p<0.001) and serum triglyceride concentrations significantly higher (p=0.02) in the MHT group, compared to normotensive controls. LDL locus was greater in the NMHT group than in the normotensive controls and intermediate in the MHT group (p=0.008). There was no significant difference in LDL spread (p=0.26). Serum triglyceride concentrations were not significantly higher after adjusting for confounding variables. MHT is associated with an abnormal lipid profile, characterized by low HDL-cholesterol concentration. This dyslipidaemia may be partly responsible for the vascular complications and the poor prognosis of these patients.

Effects of Peritoneal Dialysis with an Overnight Icodextrin Dwell on Parameters of Glucose and LIPID Metabolism

To examine whether a reduced daily glucose load by overnight application of the less-absorbed glucose polymer icodextrin would have favorable effects on lipid profiles of continuous ambulatory peritoneal dialysis (CAPD) patients. Randomized crossover study with two subsequent periods of 6 weeks. Home PD unit of a secondary-care hospital. Twenty-one nondiabetic CAPD patients (15 male, 6 female; mean age 50.3+/-11.8 years). Participants were randomly assigned to receive an overnight dwell with either standard glucose solution or with a 7.5% icodextrin-containing solution. Relation between reduction in the total amount of intraperitoneal infused glucose and parameters of glucose (plasma glucose, insulin, and HbA1C) and lipid metabolism [free fatty acids, plasma lipids, lipoproteins, and low density lipoprotein (LDL) subfraction profile]. After the icodextrin dwells, a reduction of plasma total cholesterol (from 5.43+/-0.85 to 4.86+/-0.70 mmol/L, p < 0.001) and LDL cholesterol (from 3.38+/-0.87 to 2.93+/-0.73 mmol/L, p = 0.001) was observed. Also, high density lipoprotein (HDL) cholesterol (from 0.95+/-0.27 to 0.90+/-0.24 mmol/L, p = 0.029) was reduced, but the plasma total cholesterol-to-HDL ratio remained similar. Plasma free fatty acids and triglyceride levels tended to decrease (from 0.16+/-0.10 to 0.13+/-0.08 mmol/L, p= 0.06, and from 2.14+/-1.96 to 1.92+/-1.03 mmol/L, respectively). Evaluation of LDL subfraction profiles after ultracentrifugation showed a more buoyant LDL subfraction profile with fewer dense LDL particles in 6 patients and no changes in 14 patients after icodextrin. The effects on lipids were not accompanied by a decrease in fasting plasma glucose (from 5.76+/-1.29 to 5.86+/-0.80 mmol/L) or insulin levels (from 19.5+/-14.4 to 20.3+/-13.0 mU/L). These results suggest a beneficial effect on lipid profiles of CAPD patients with the use of an overnight dwell with icodextrin.

The effect of concentrated n-3 fatty acids versus gemfibrozil on plasma lipoproteins, low density lipoprotein heterogeneity and oxidizability in patients with hypertrygliceridemia

We evaluated in a double-blind randomized trial with a double-dummy design in 28 patients with primary hypertriglyceridemia, the effect of gemfibrozil (1200 mg/day) versus Omacor (4 g/day), a drug containing the n-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), on lipid and lipoprotein levels, low density lipoprotein (LDL) subfraction profile and LDL oxidizability. Both Omacor and gemfibrozil therapy resulted in a similar significant decrease in serum triglyceride (TG), very low density lipoprotein (VLDL) triglyceride and VLDL cholesterol concentrations and an increase in high density lipoprotein (HDL) and LDL cholesterol concentrations. The increase in LDL cholesterol was due to a significant increase in cholesterol content of the relatively buoyant LDL subfractions LDL1, LDL2 and LDL3, whereas the relative contribution of the dense LDL subfractions LDL4 and LDL5 to total LDL tended to decrease. So, both therapies resulted in a more buoyant LDL subfraction profile, reflected by a significant increase of the value of parameter K (+10.3% on Omacor vs +26.5% on gemfibrozil therapy, gemfibrozil vs Omacor P>0.05). Cu 2+-induced oxidation of LDL was measured by continuous monitoring of conjugated dienes. After 12 weeks of Omacor treatment LDL appeared more prone to oxidative modification in vitro than LDL after gemfibrozil treatment, as measured by the significantly decreased lag time, preceding the onset of the lipid peroxidation. In both groups the rate of oxidation did not change with therapy. The amount of dienes formed during oxidation increased significantly on Omacor treatment, but not on gemfibrozil treatment. Plasma thiobarbituric acid reactive substances were higher after Omacor and lower after gemfibrozil treatment, although not significantly. We conclude that both Omacor and gemfibrozil have favorable effects on lipid and lipoprotein concentrations and the LDL subfraction profile. However, Omacor increased the susceptibility of LDL to oxidation, whereas gemfibrozil did not affect the resistance of LDL to oxidative modification in vitro. The clinical relevance of these changes remains to be established in the light of other postulated favorable effects of n-3 fatty acids on the course of cardiovascular disease.

Malignant phase hypertension is associated with abnormalities of low density lipoprotein subfraction profiles

Elevated levels of low density lipoprotein (LDL) are an independent risk factor for cardiovascular disease. LDL however is not a single entity but consists of a heterogeneous group of particles with smaller dense particles being the most atherogenic. To test the hypothesis that malignant hypertension (MHT), the most severe form of hypertension, is associated with an abnormal lipid profile, and that this may contribute to the complications of MHT, we studied 18 patients presenting with this condition (49.4 (11.4) years; 16 male; 236/141). LDL subfraction profile was measured by disc polyacrylamide gel electrophoresis using a validated scoring system to calculate the mean (locus) and standard deviation (spread) mobility of LDL. Results were compared with 41 patients with non-malignant, untreated hypertension (mean age 53.9 years; 24 male systolic/diastolic blood pressure 173/100) and 45 normotensive patients with normal coronary angiograms (58 (10.6) years; 22 male; 136/80).

LDL particle size: an important drug target?

Low density lipoprotein (LDL) is the main carrier of plasma cholesterol and a major component of atherosclerotic plaque [1]. Lowering LDL cholesterol reduces coronary events and mortality from coronary artery disease (CAD) [2–4], however, the relation between LDL cholesterol concentration and (CAD) is complex. Many patients with CAD have plasma LDL cholesterol concentrations in the normal rangefor the general population [5]. Thus, it could be that coronary risk goes beyond LDL cholesterol concentration to the characteristics of the LDL particles themselves. The purpose of this communication is to address the issue of whether LDL particle size and density influences its atherogenecity and how this might be modified by drug therapy.

Influence of 4 weeks' intervention by exercise and diet on low-density lipoprotein subfractions in obese men with type 2 diabetes

Insulin resistance is associated with dyslipoproteinemia characterized by increased serum triglycerides, reduced high-density lipoprotein 2 (HDL 2) cholesterol, and increased small, dense low-density lipoprotein (LDL) subfraction particles. Physical activity and weight reduction are known to improve insulin resistance and dyslipoproteinemia, but their influence on LDL subfractions in diabetic patients is unknown. Therefore, we investigated the effect of a 4-week intervention program of exercise (2,200 kcal/wk) and diet (1,000 kcal/d: 50% carbohydrate, 25% protein, and 25% fat; polyunsaturated/saturated fat ratio, 1.0) on glycemic control and HDL and LDL subfractions in 34 obese patients with non—insulin-dependent diabetes (age, 49 ± 9 years; body mass index [BMI], 33.1 ± 5.1 kg/m 2). Reductions in body weight ( P < .001) and improvements in fasting blood glucose, insulin, fructosamine ( P < .001), and free fatty acids ( P < .01) by intervention were associated with reductions in serum cholesterol and apolipoprotein B (apo B) concentrations in very—low-density lipoprotein (VLDL) ( P < .01), intermediate-density lipoprotein (IDL), and small, dense (> 1.040 g/mL) LDL particles ( P < .001). These data underlie the positive influence of weight reduction induced by exercise and diet on insulin resistance and lipoprotein metabolism in obese diabetic patients, particularly showing improvements of the LDL subfraction profile with a decrease of small, dense LDL particles. This is of particular importance, as these particles have been shown to be associated with coronary artery disease.

Influence of mild to moderately elevated triglyceride’s on low density lipoprotein subfraction concentration and composition in healthy men with low high density lipoprotein cholesterol levels

Epidemiologic studies have shown that a dyslipoproteinemia with low concentrations of high density lipoprotein (HDL) cholesterol and elevated serum triglycerides (TG) is associated with a particularly high incidence of coronary artery disease. This lipid profile is associated with increased concentrations of small, dense low density lipoprotein (LDL) particles. To evaluate the role of mild to moderately elevated TG on the LDL subfraction profile in patients with low HDL cholesterol, concentration and composition of six LDL subfractions was determined by density gradient ultracentrifugation in 41 healthy men (31±9 years, body mass index (BMI) 25.1±3.9 kg/m 2) with equally low HDL cholesterol levels <0.91 mmol/l but different TG levels: TG<1.13 mmol/l, n=16; TG=1.13–2.26 mmol/l, n=13; TG=2.26–3.39 mmol/l, n=12. Those men with moderately elevated TG levels between 2.26 and 3.39 mmol/l had significantly higher concentrations of very low density lipoprotein (VLDL), intermediate low density lipoprotein (IDL), and small, dense LDL apoB and cholesterol than men with TG <1.13 mmol/l. With increasing serum TG, the TG content per particle also increased in VLDL, IDL as well as total LDL particles while the cholesterol and phospholipid (PL) content decreased in VLDL and IDL, but not in LDL particles. LDL subfraction analysis revealed that only large, more buoyant LDL particles ( d<1.044 g/ml) but not the smaller, more dense LDL, were enriched in TG. Small, dense LDL particles were depleted of free cholesterol (FC) and PL. This study has shown that in men with low HDL cholesterol levels mild to moderately elevated serum TG strongly suggest the presence of other metabolic cardiovascular risk factors and in particular of a more atherogenic LDL subfraction profile of increased concentration of small, dense LDL particles that are depleted in surface lipids.

Low-density lipoprotein subfraction profiles in chronic renal failure.

Small low-density lipoprotein (LDL) particle size, a newly recognized risk factor for cardiovascular disease in the general population, is frequently associated with hypertriglyceridaemia, the predominant plasma lipid abnormality present in uraemia. Plasma lipids and LDL subfraction profiles were examined in 33 non-dialysed patients with chronic renal failure (predial), 40 patients on continuous ambulatory peritoneal dialysis (CAPD), 42 haemodialysis patients (HD), 47 renal transplant recipients (RTR), and 44 controls. LDL subfractions separated by gel electrophoresis were scored by densitometric analysis (higher scores indicate profiles comprising smaller particles). All groups with renal failure had significantly elevated (mean+/-SD) LDL scores (predial 1.36+/-0.6, CAPD 1.71+/-0.9, HD 1.68+/-0.9, RTR 1.92+0.8 vs control 0.87+0.4, all P<0.001), this being the only lipid abnormality detected in the predialysis patients. In CAPD and HD patients, LDL scores were associated with serum triglyceride (r=0.81, P<0.001 and r=0.70, P<0.001 respectively), cholesterol (r=0.55, P<0.001 and r=0.49, P<0.01) and HDL-cholesterol (r= -0.43, P<0.01 and r= -0.51, P<0.01), whilst no such relationship was seen in the predialysis and RTR groups, suggesting that other factors were important. The presence of small LDL particles appears to be an early and unexplained feature of the uraemic dyslipidaemia. This abnormality persists after renal transplantation and may represent an important atherogenic risk factor.

Lipoprotein subfraction changes in normal pregnancy: threshold effect of plasma triglyceride on appearance of small, dense low density lipoprotein.

A detailed longitudinal examination of plasma lipoprotein subfraction concentrations and compositions in pregnancy was performed with the objective of discovering the pattern of change in lipoprotein subfractions. Plasma triglyceride, cholesterol, very low density lipoprotein (VLDL1), very low density lipoprotein (VLDL2), intermediate density lipoprotein (IDL), low density lipoprotein (LDL) and its subfractions (LDL-I, LDL-II, LDL-III), and high density lipoprotein-cholesterol (HDL cholesterol) were quantified in 10 normal pregnant women from 10 weeks of gestation and at 5 weekly intervals thereafter, until 35 weeks of gestation, together with circulating hepatic lipase (at 10 and 35 weeks) and serum estradiol concentration. Median concentrations of VLDL1 (19-109 mg/dL), VLDL2 (17-103 mg/dL) and IDL (26-124 mg/dL) increased in parallel (maximum increase around 5-fold) as plasma triglyceride increased with advancing gestation. This contrasts with observations in the normal non-pregnant female, where higher concentrations of plasma triglyceride are associated with preferentially higher VLDL1 concentrations. The rise in IDL was also remarkable as this does not normally accompany changes in plasma triglyceride. LDL mass increased by 70% (200-353 mg/dL) between 10 and 35 weeks, and in 6 of the 10 women studied, the LDL subfraction pattern was modified towards a smaller denser pattern in a manner suggestive of a "threshold" transition, with the proportion of LDL-III increasing at the expense of LDL-II, whereas in the other 4 women, LDL subfraction profile remained unchanged throughout pregnancy. Interestingly, this "threshold" transition, if it occurred, did so at varying gestational ages and triglyceride concentrations for different women. The likelihood of LDL subfraction change and the final concentration of small, dense. LDL-III were related to the 10-week triglyceride concentration (R2 = 36.7%, P = 0.063) and to the rate of change in triglyceride for a given increment in estrogen (R2 = 48.6%, P = 0.025). In addition, VLDL1 mass exceeded 100 mg/dL during pregnancy only in those individuals in whom LDL profile perturbation was evident (chi 2, P < 0.001). LDL profile change was evident at the lowest triglyceride concentrations in the 2 individuals with the highest increments in triglyceride corrected for estrogen. On the basis of these longitudinal observations, we conclude the following: 1) as plasma triglyceride increases in pregnancy, there are parallel rises in median concentrations of VLDL1, VLDL2 and IDL, around 5-fold; 2) as a result of this progressive increase in plasma triglyceride, in particular in VLDL1, the LDL profile is altered in some individuals towards smaller, dense particles; 3) in general, the higher the initial (booking) fasting plasma triglyceride concentration or the larger the rate of change in triglyceride for a given increment in estradiol, the greater the probability of change in LDL profile towards smaller denser species; 4) significantly, LDL subclass perturbation towards smaller denser species occurs not in a gradual and progressive manner but exhibits "threshold" behavior; and finally, 5) this threshold is achieved at differing gestational ages and triglyceride concentrations for different women.