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Here the impact of APOE genotype on CHD risk in UK adults is reported, along with an analysis of APOE genotype × BMI/age/sex interactions. APOE genotype had a significant impact on fasting total:LDL-cholesterol (TC:LDL-C) ratio, triglycerides, % HDL3, and the Framingham 10-year CVD risk score (P<0.05), with an overall trend towards lower and higher risk in E2- and E4-carriers, respectively, relative to the wild-type E3/E3 genotype. A greater impact of genotype on TC:HDL-C was observed in females, which explained 16% of the variability in this outcome versus 6% in males. APOE genotype was also associated with plasma C-reactive protein and adhesion molecule concentrations (P<0.05), with significant genotype × BMI interactions observed. Our observations indicate that the association between the APOE genotype and CHD risk is unlikely to be homogenous and highlights the risk of inaccurate estimations of genotype-phenotype associations in population subgroups without appropriate stratification for sex and adiposity., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an inflammatory biomarker that circulates mainly bound to LDL. We evaluated the association of Lp-PLA(2) with vascular events in the elderly where the importance of LDL is diminished as a risk factor for coronary disease., Methods: Mass and activity of Lp-PLA(2) were related to risk over 3.2 years for vascular events (definite or suspected death from CHD, non-fatal MI, fatal or non-fatal stroke) in the 2804 men and 3000 women age 70-82 years in the Prospective Study of Pravastatin in the Elderly (PROSPER)., Results: Lp-PLA(2) showed a moderate, positive association with risk of a vascular event with hazard ratios of 1.25 (confidence interval (CI) 1.02-1.54) for mass and 1.39 (CI 1.14-1.70) for activity for top versus bottom quartile. Risk associations were attenuated when classical risk factors, lipids and inflammatory markers - C-reactive protein and white cell count - were included in the models. Lp-PLA(2) was unrelated to stroke risk. Inclusion of all three inflammatory markers in multivariate models negated the association of HDL cholesterol with risk (hazard ratio 0.98; CI 0.88-1.10) and increased prediction of coronary events; the C statistic rose from 63.2% to 64.4% (P<0.001)., Conclusion: In elderly people Lp-PLA(2), alongside other inflammatory indices, is a potential biomarker for vascular events, particularly CHD., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To investigate the impact of apolipoprotein E (apoE) genotype on the response of the plasma lipoprotein profile to eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) intervention in humans., Methods and Results: 38 healthy normolipidaemic males, prospectively recruited on the basis of apoE genotype (n=20 E3/E3 and n=18 E3/E4), completed a double-blind placebo-controlled cross-over trial, consisting of 3 x 4 week intervention arms of either control oil, EPA-rich oil (ERO, 3.3g EPA/day) or DHA-rich oil (DRO, 3.7g DHA/day) in random order, separated by 10 week wash-out periods. A significant genotype-independent 28% and 19% reduction in plasma triglycerides in response to ERO and DRO was observed. For total cholesterol (TC), no significant treatment effects were evident; however a significant genotype by treatment interaction emerged (P=0.045), with a differential response to ERO and DRO in E4 carriers. Although the genotype x treatment interaction for LDL-cholesterol (P=0.089) did not reach significance, within DRO treatment analysis indicated a 10% increase in LDL (P=0.029) in E4 carriers with a non-significant 4% reduction in E3/E3 individuals. A genotype-independent increase in LDL mass was observed following DRO intervention (P=0.018). Competitive uptake studies in HepG2 cells using plasma very low density lipoproteins (VLDL) from the human trial, indicated that following DRO treatment, VLDL(2) fractions obtained from E3/E4 individuals resulted in a significant 32% (P=0.002) reduction in LDL uptake relative to the control., Conclusions: High dose DHA supplementation is associated with increases in total cholesterol in E4 carriers, which appears to be due to an increase in LDL-C and may in part negate the cardioprotective action of DHA in this population subgroup.

Background: Patients with nephrotic range proteinuria have a marked increase in the risk of cardiovascular disease. Qualitative and quantitative changes in lipids and lipoproteins contribute to this increased risk with an abundance of atherogenic triglyceride (TG) rich apolipoprotein B containing lipoproteins. TG rich lipoproteins predominate postprandially and are associated with increased risk of coronary heart disease (CHD). Omega-3 fatty acids derived from fish oils have been shown to have beneficial effects on lipids and lipoproteins in patients without proteinuria., Methods: 17 patients with nephrotic range proteinuria and 17 age and sex matched controls were studied. Postprandial lipaemia was assessed in patients and controls, before and after 8 weeks treatment with 4 g daily of omega-3 fatty acids (Omacor). A standard fat load (90 g) was administered and blood sampling was performed in the fasting state and at 2, 4, 6 and 8h after the fat load. Chylomicrons and VLDL(1) density fraction was isolated from plasma by density ultracentrifugation. Postprandial chylomicron and VLDL(1) triglyceride concentrations were measured and quantified using the incremental area under the curve (AUC) method., Results: Baseline postprandial chylomicron TG AUC was greater in patients compared with controls: median 18.5 mmol/lh (interquartile range 8.9-32.6) vs 9.3 mmol/lh (4.8-14.4) p=0.05. Following treatment patient chylomicron AUC fell [mean reduction 6.8 mmol/lh (95% CI 0.1-13.6) p=0.05]. No significant reduction in chylomicron AUC was observed in the controls [mean reduction 3.9 mmol/lh (95% CI -3.6 to 11.5)]. As a result, following 8 weeks treatment with omega-3 fatty acids, patient and control chylomicron AUC were no longer significantly different [patients 13.5 mmol/lh (7.4-22.9), controls 7.2 mmol/lh (4.6-14.5) both median and IQR, p=nsd]. VLDL(1) TG AUC did not differ at baseline between patients and controls. Furthermore, there was no significant effect on VLDL(1) AUC following treatment in either group., Conclusions: We have shown that there is an excess of postprandial chylomicron density fraction in patients with nephrotic range proteinuria, which is reduced by treatment with omega-3 fatty acids. We suggest that this would be an ideal therapy in combination with statins for this high risk group of patients.

In the West of Scotland Coronary Prevention Study (WOSCOPS), treatment of hypercholesterolemic men with pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, reduced their likelihood to progress to diabetes mellitus by 30%. However, the mechanism of this effect of pravastatin has not been investigated. In the current study, we examined the effect of pravastatin on the development of diabetes in obese diabetic mice, and on the insulin-induced glucose uptake and adiponectin production. Pravastatin treatment attenuated the development of diabetes in db/db and high fat/high sucrose diet-fed C57BL/6J mice. An in vivo glucose transport assay showed that pravastatin upregulated glucose uptake in adipose tissue. Insulin-stimulated glucose uptake was enhanced in primary adipocytes isolated from pravastatin-treated mice. Pravastatin treatment increased adiponectin production in 3T3-L1 adipocytes. Plasma adiponectin levels were significantly increased in pravastatin-treated mice. Analyses of plasma samples from the WOSCOPS biobank indicated a significant increase of plasma adiponectin levels with pravastatin treatment (placebo -0.28+/-0.34 microg/ml versus pravastatin +1.47+/-0.33 microg/ml, p=0.0003). Taken together, our findings suggest that pravastatin may have beneficial effects on adipose tissue, which may partly explain the reduction of the development of diabetes by pravastatin treatment.

IDL is considered an atherogenic lipoprotein but little progress has been made on methods to subfractionate this density class. Furthermore, previous work suggests that lipoproteins retained by the arterial wall, of which chondoitin sulphate is the major arterial wall proteoglycan, are potentially atherogenic. The aim of this study was to assess the subfractionation of IDL particles using chondroitin sulphate (CS). Forty healthy subjects were recruited from laboratory staff and/or their partners. Fasted plasma samples were obtained and IDL (1.006 g/ml

Unlabelled: Prior moderate exercise has been shown consistently to reduce postprandial triglyceride (TG) concentrations in non-diabetic adults, but its effects in men with type 2 diabetes are not known. This study aimed to determine the effect of moderate exercise on postprandial metabolism in men with type 2 diabetes. Ten middle-aged men with type 2 diabetes underwent two oral fat tolerance tests (blood taken fasting and for 8 h after a meal containing 80 g fat, 70 g carbohydrate) in random order. On the afternoon before one test, participants performed a 90-min treadmill walk (Exercise); no exercise was performed before the CONTROL test. Exercise significantly reduced fasting glucose (, Control: 9.08+/-0.75 mmol l(-1), Exercise: 8.40+/-0.72 mmol l(-1), p=0.033) and insulin (, Control: 8.01+/-0.98 microU ml(-1), Exercise: 6.81+/-0.93 microU ml(-1), p=0.046) and increased fasting 3-hydroxybutyrate (, Control: 87.1+/-19.2 micromol l(-1), Exercise: 134.3+/-28.4 micromol l(-1), p=0.011); reduced postprandial insulin by 11.0% (p=0.04) and increased postprandial 3-hydroxybutyrate by 31.8% (p=0.03); but did not significantly change fasting or postprandial triglyceride or NEFA concentrations. However, the exercise-induced change in postprandial triglyceride concentration ranged from -32.3 to +28.3% and the exercise-induced change in fasting 3-hydroxybutyrate concentration (a marker of hepatic fatty acid oxidation) was highly correlated with the exercise-induced changes in fasting and postprandial triglyceride (r=0.68, p=0.03 for both). Thus, inter-individual variation in propensity to increase hepatic fatty acid oxidation following exercise may account for the considerable heterogeneity in triglyceride responses to moderate exercise observed in men with type 2 diabetes.

Aim: The present clinical study tested the hypothesis that oil-rich fish consumption improves CHD risk factors., Methods: Forty-eight (16 men) non-obese, healthy adults aged 20-55, consumed 125 g/day of salmon for a 4-week period followed by a 4-week period with no-fish (41 completers). Subjects were instructed to maintain dietary and physical activity patterns during the period of study. Blood pressure, anthropometric, body composition and dietary information with fasting blood samples to determine traditional and novel CHD risk markers and plasma fatty acids were obtained before and after each period., Results: Compared to no-fish, eating salmon significantly decreased systolic, diastolic and mean arterial blood pressure by 4%, triglycerides by 15%, and LDL-cholesterol by 7%, and significantly increased HDL-cholesterol by 5% (P<0.05). The changes in blood pressure and lipids alone with salmon intake predict around a 25% reduction in CHD risk based on the PROCAM risk calculator. Plasma adiponectin demonstrated a trend towards improvement (8.39 micromol/L with salmon and 7.52 with no-fish; P=0.086) but no significant changes were found either in plasma leptin, glucose or insulin after salmon consumption., Conclusions: Daily consumption of salmon improves traditional risk predictors of CHD in non-obese subjects. Adiponectin may be involved but the impact on novel risk factors needs study in high-risk subjects.

Prior moderate exercise reduces postprandial triglyceride concentrations. Its effects on the concentrations, compositions and potential atherogenicity of lipoprotein subfractions were investigated in the present study. Twenty normoglycaemic middle-aged men each underwent two fat tolerance tests (blood taken fasting and for 8 h after a meal containing 80 g fat and 70 g carbohydrate). On the afternoon before one test, subjects performed a 90-min treadmill walk (exercise); no exercise was performed before the control test. Prior exercise significantly reduced postprandial concentrations of chylomicrons (Sf >400) by 28.6% (absolute reduction 14.6 mg dl(-1)), of large VLDL1 (Sf 60-400) by 34.4% (39.7 mg dl(-1)) and of small VLDL2 (Sf 20-60) by 23.0% (9.6 mg dl(-1)). Over 95% of VLDL1 and VLDL2 comprised apolipoprotein (apo) B100-containing particles. Exercise also reduced postprandial remnant-like lipoprotein cholesterol (by 35%) and triglyceride concentrations (by 29%). Postprandial apo CIII/apo B and apo E/apo B ratios in VLDL1 were lower following exercise. Postprandial cholesteryl ester/triglyceride ratios were lower in VLDL1 and VLDL2 and higher in HDL2 following exercise. These data suggest that the effect of prior moderate exercise on VLDL1 is quantitatively greater than its effect on chylomicrons and that, in addition to reducing lipoprotein concentrations, exercise induces compositional changes to lipoprotein species which are likely to influence their metabolism and atherogenicity.

Introduction: Glutathione S transferases (GST) are enzymes responsible for the metabolism of numerous xenobiotics and play a major cellular antioxidant role. Our aim was firstly, to examine the association between the GST M1/GST mu-1 (GSTM1) and GST T1/GST theta-1 (GSTT1) gene variants with markers of oxidative stress and inflammation in diabetic patients, and secondly to examine the association and potential interaction between these variants and cigarette smoking., Methods: Seven hundred and seventy-three Caucasian subjects with diabetes and 2592 Caucasian non-diabetic subjects were successfully genotyped. Plasma total antioxidant status, C-reactive protein (CRP), oxidized-LDL (Ox-LDL) and LDL-mean/peak particle diameter were recorded in the diabetes sample., Results: No association was seen between genotype and cardiovascular disease (CVD) risk. In the diabetic subjects, GSTT1-1 compared to GSTT1-0 subjects had significantly higher CRP (p=0.001), Ox-LDL (p=0.004) and smaller LDL particles (p=0.01). In subjects without CVD, there was a significant interaction between the GSTT1-1 variant and smoking in determining Ox-LDL (p=0.04). Furthermore, CVD risk was higher in smokers compared to non-smokers with GSTT1-1. No significant associations were observed by GSTM1. Within the non-diabetic sample, no association was observed between genotype and prospective coronary heart disease (CHD) risk. Of note, the frequency of the GSTT1-1 variant was significantly lower in the diabetes subjects compared to the non-diabetic sample (p=0.01)., Conclusions: This study demonstrates an association between the GSTT1-1 variant and markers of inflammation and lipid peroxidation. Furthermore this variant interacts with smoking to increase lipid peroxidation.

Familial combined hyperlipidaemia (FCHL) is a complex genetic disorder of unknown aetiology. Study of this human condition over many decades has been hampered by likely genetic heterogeneity. In order to find better phenotypic markers, we have characterised the structures of VLDL, IDL and LDL in the St. Thomas' Mixed Hyperlipidaemic (SMHL) rabbit--an animal model of FCHL in which the hyperlipidaemia is caused primarily by an increased production rate of apolipoprotein B (apoB)--containing lipoproteins-and compared them with those in the Watanabe Heritable Hyperlipidaemic (WHHL) rabbit, in which hyperlipidaemia is caused mainly by a defect in lipoprotein clearance, and those in the normolipidaemic New Zealand White (NZW) animal. All three rabbit strains were fed a cholesterol-enriched (0.08%, w/w) diet for at least 3 months prior to blood sampling. Both SMHL and WHHL rabbits showed combined hyperlipidaemia as evidenced by significantly increased levels of plasma cholesterol and triglycerides. Raised plasma lipids in the SMHL rabbit were attributable mainly to an overabundance of lipoprotein particles with the same lipid composition as those in NZW rabbits. VLDL and IDL in the SMHL rabbit showed a significantly increased sphingomyelin to phosphatidyl choline ratio. In the WHHL rabbit there was a high concentration of particles that were significantly enriched in cholesteryl esters and depleted in triglycerides. Phospholipids in all lipoprotein fractions from WHHL rabbits contained significantly more sphingomyelin and less phosphatidyl choline resulting in a significantly increased sphingomyelin to phosphatidyl choline ratio. We found that the VLDL of SMHL rabbits could be distinguished from that of NZW rabbits on the basis of the cholesterol:apoB and the sphingomyelin:phosphatidylcholine ratios, and from that of WHHL rabbits by the sphingomyelin:triglyceride ratio. Extrapolating these findings to the human condition, an assessment of particle core composition, together with the proportion of sphingomyelin in phospholipids especially in VLDL might help in the differentiation of the combined hyperlipidaemia of FCHL into disorders of lipoprotein overproduction versus decreased clearance.

The aim of our work was to evaluate changes in levels of oxidised low-density lipoprotein (Ox-LDL) during pregnancy and how they correlate with changes in LDL size and serum total antioxidant status (TAS). LDL peak and mean particle diameter (LDL-PPD and LDL-MPD, respectively) and the relative proportion of 3 LDL subfractions were quantified. We evaluated plasma levels of Ox-LDL and serum levels of TAS, total cholesterol (Chol), triglycerides (TG), apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), HDL-cholesterol (HDLc) and LDL-cholesterol (LDLc). A longitudinal study was performed in the three trimesters (T1-T3) of pregnancy in normal pregnant women (n = 23) and a non-pregnant group (n = 18) was used as control. TG levels were significantly elevated whereas LDL-MPD and LDL-PPD were significantly reduced in T1 compared to controls. Ox-LDL, TG, Chol, apo B and LDLc rose markedly throughout pregnancy with significant changes between each trimester; LDL-PPD, LDL-MPD and TAS levels decreased significantly from T1 to T3. Changes in LDL size and in Ox-LDL and TAS levels were more pronounced between T1 and T2 than between T2 and T3. HDLc and apo A-I reached peak concentration in T2 but decreased in T3. TG concentrations correlated inversely with LDL size and positively with Ox-LDL; Ox-LDL was positively and strongly correlated with LDLc. Moreover, relative changes in the levels of Ox-LDL correlated inversely with relative changes in LDL size and TAS between trimesters. In conclusion, during human gestation the change in LDL profile towards smaller species and the decrease in serum TAS are closely associated with increased levels of Ox-LDL. The exact physiological role of the increments in Ox-LDL during pregnancy remains to be clarified.

Insulin resistance is probably the defining feature of the metabolic syndrome and is an important determinant of plasma triglyceride (TG) concentrations. We sought to investigate whether insulin resistance influenced the metabolism of VLDL1 (Sf 60-400) and VLDL2 (Sf 20-60). Sixteen (eight men, eight women) middle-aged, normoglycaemic subjects participated. VLDL1and VLDL2 apolipoprotein (apo) B metabolism was followed using a deuterated leucine tracer and insulin resistance was estimated using homeostasis model assessment (HOMA). HOMA-estimated insulin resistance (HOMAIR) significantly and strongly correlated with the VLDL1 production rate (r = 0.69, P < 0.01) and VLDL1 apo B pool size (r = 0.59, P = 0.02), but these relationships were not evident for VLDL2. Conversely, HOMAIR was not significantly related to the fractional rate of transfer of VLDL1 to VLDL2 but was significantly related to the fractional rate of transfer from VLDL2 to IDL (r = 0.61, P = 0.01). HOMAIR was not significantly related to the fractional rate of direct catabolism for either VLDL1 or VLDL2. These results suggest a role for insulin resistance in the determination of hepatic VLDL1 production and highlight the independent regulation of VLDL1 and VLDL2 metabolism.

This randomised, double-blind, placebo-controlled crossover study evaluated the effects of rosuvastatin (40 mg/day for 8 weeks) on atherogenic apolipoprotein B-containing lipoprotein subfractions. Subjects, recruited based on raised plasma triglyceride (TG) or low-density lipoprotein cholesterol (LDL-C), were divided into normotriglyceridaemic (NTG, n = 13; TG < 2.0 mmol/l) and hypertriglyceridaemic (HTG, n = 16; TG > or = 2.0 mmol/l) groups. Similar reductions on rosuvastatin were observed for both groups in LDL-C (NTG -60%; HTG -56%), apoB (both -49%), intermediate-density lipoprotein (NTG -57%; HTG -54%) and LDL circulating mass (NTG -52%, HTG -58%) (all P < 0.001 versus placebo), i.e., these changes were phenotype independent. Phenotype dependency in response was observed in HTG relative to NTG in concentration of small dense LDL (LDL-III) (NTG -44%, P = NS; HTG -69%, P < 0.001), very-low-density lipoprotein1 (NTG -18%, P = NS; HTG 46%, P < 0.01), and remnant-like particle cholesterol (NTG -31%, P = NS; HTG -48%, P < 0.05). Rosuvastatin reduced cholesteryl ester transfer protein (CETP) by 33% in NTG and 37% in HTG (both P < 0.001); a reduction in cholesteryl ester transfer activity (-59%, P < 0.001) was observed in HTG only. Rosuvastatin therefore, in addition to lowering LDL and apoB-concentrations, largely corrected the TG and LDL abnormalities in subjects who had the propensity to develop the atherogenic lipoprotein phenotype., (Copyright 2003 Elsevier Ireland Ltd.)

Subjects with moderate combined hyperlipidemia (n=11) were assessed in an investigation of the effects of atorvastatin and simvastatin (both 40 mg per day) on apolipoprotein B (apoB) metabolism. The objective of the study was to examine the mechanism by which statins lower plasma triglyceride levels. Patients were studied on three occasions, in the basal state, after 8 weeks on atorvastatin or simvastatin and then again on the alternate treatment. Atorvastatin produced significantly greater reductions than simvastatin in low density lipoprotein (LDL) cholesterol (49.7 vs. 44.1% decrease on simvastatin) and plasma triglyceride (46.4 vs. 39.4% decrease on simvastatin). ApoB metabolism was followed using a tracer of deuterated leucine. Both drugs stimulated direct catabolism of large very low density lipoprotein (VLDL(1)) apoB (4.52+/-3.06 pools per day on atorvastatin; 5.48+/-4.76 pools per day on simvastatin versus 2.26+/-1.65 pools per day at baseline (both P<0.05)) and this was the basis of the 50% reduction in plasma VLDL(1) concentration; apoB production in this fraction was not significantly altered. On atorvastatin and simvastatin the fractional transfer rates (FTR) of VLDL(1) to VLDL(2) and of VLDL(2) to intermediate density lipoprotein (IDL) were increased significantly, in the latter instance nearly twofold. IDL apoB direct catabolism rose from 0.54+/-0.30 pools per day at baseline to 1.17+/-0.87 pools per day on atorvastatin and to 0.95+/-0.43 pools per day on simvastatin (both P<0.05). Similarly the fractional transfer rate for IDL to LDL conversion was enhanced 58-84% by statin treatment (P<0.01) LDL apoB fractional catabolic rate (FCR) which was low at baseline in these subjects (0.22+/-0.04 pools per day) increased to 0.44+/-0.11 pools per day on atorvastatin and 0.38+/-0.11 pools per day on simvastatin (both P<0.01). ApoB-containing lipoproteins were more triglyceride-rich and contained less free cholesterol and cholesteryl ester on statin therapy. Further, patients on both treatments showed marked decreases in all LDL subfractions. In particular the concentration of small dense LDL (LDL-III) fell 64% on atorvastatin and 45% on simvastatin. We conclude that in patients with moderate combined hyperlipidemia who initially have a low FCR for VLDL and LDL apoB, the principal action of atorvastatin and simvastatin is to stimulate receptor-mediated catabolism across the spectrum of apoB-containing lipoproteins. This leads to a substantial, and approximately equivalent, percentage reduction in plasma triglyceride and LDL cholesterol.

Small dense LDL is now emerging as an important risk factor for coronary artery disease. The amount of the LDL III has been reported to differ between ethnic groups. To investigate differences in the distribution of LDL subfractions between Korean and Scottish populations, we measured the plasma concentration and percent distribution of three major LDL subfractions in age-and sex-matched, middle aged, healthy 124 Korean and Scottish subjects (32 Korean men vs. 32 Scottish men; 30 Korean women vs. 30 Scottish women). Body mass index and waist circumference did not differ between the two ethnic groups. Total cholesterol and LDL cholesterol concentrations were higher in Scottish men compared with Korean men (P<0.01), while plasma triglyceride concentration was higher in Korean men and women (P<0.01 in men, P<0.05 in women). HDL cholesterol concentrations in both Korean men and women were lower than that of their Scottish counterparts (P<0.05 in men; P<0.001 in women). Korean men had lower concentrations of total LDL (242+/-65 vs. 325+/-122 mg/dl, P<0.01), LDL I (24+/-18 vs. 60+/-36 mg/dl, P<0.001) and LDL II (110+/-56 vs. 196+/-78 mg/dl, P<0.001). In contrast, LDL III concentration was markedly higher in Korean men (108+/-75 vs. 70+/-65 mg/dl, P<0.05). Likewise, the percent of LDL I (10.0+/-7.3 vs. 19.1+/-10.1%, P<0.001) and LDL II (47.2+/-20.7 vs. 60.1+/-10.9%, P<0.01) were lower in Korean men, while that of LDL III was higher (42.8+/-24.9 vs. 20.8+/-15.0%, P<0.001). In the female population, there were no differences in total LDL and LDL I concentrations between Korean and Scottish. LDL II concentration was lower in Korean women (106+/-53 vs. 151+/-57 mg/dl, P<0.01). Korean women showed a higher percent of LDL III (24.8+/-24.7 vs. 14.2+/-5.9%, P<0.05) and a lower LDL II (47.8+/-19.1 vs. 61.0+/-10.0%, P<0.01). Multiple linear regression revealed that plasma triglyceride concentration was the most important determinant of the LDL III subfraction concentration in Korean men and women and in Scottish men. In Korean men, the LDL III concentration rose linearly through the whole range of plasma triglyceride concentration, whereas in Scottish men, there was a threshold at 108 mg/dl triglyceride above which there was a positive association. Korean women showed the same pattern as Scottish men. We suggest that LDL concentrations and LDL subfraction distributions are regulated differently in these two ethnic groups. The different relationships between triglyceride and LDL III subfraction in Koreans versus Scots suggest that other factors, such as hepatic lipase or cholesteryl ester transfer protein may additionally play a role determining the LDL subfraction profile.

The aim of this study was to evaluate changes in lipids, apolipoproteins and lipoproteins in Portuguese pregnant women and their potential involvement in the pathophysiology of preeclampsia. A cross-sectional study was performed by collecting blood samples in the first (n=64), second (n=48) and third (n=67) trimesters and puerperium (n=32) of normal pregnancies. Samples from preeclamptic women were obtained in the third trimester (n=51) and in puerperium (n=26). As normal pregnancy progressed and triglyceride (TG) levels rose there was a decrease in low density lipoprotein (LDL) size, as measured by peak and mean particle diameter (MPD), with an increased proportion of atherogenic small dense LDL. Preeclamptic women exhibited, in the third trimester and puerperium, higher mean serum TG concentration and lower high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) levels compared with healthy pregnant women. In the third trimester, LDL-mean particle diameter (LDL-MPD) and LDL cholesterol-apolipoprotein B (LDLc-apo B) ratio were also significantly reduced in the pathologic group. We conclude that human gestation is associated with an 'atherogenic' lipid profile that is further enhanced in preeclampsia and that this profile may be a potential contributor to endothelial cell dysfunction.

Both defective LDL receptors (familial hypercholesterolaemia, FH) and mutations in apolipoprotein B (apoB) on LDL (familial defective apoB, FDB) give rise to a phenotype of elevated LDL cholesterol. We sought to compare the metabolic basis of the two conditions by examining apoB turnover in FDB and FH subjects. A group comprising three heterozygous and one homozygous FDB subjects were compared with five FH heterozygotes and 17 control subjects using a deuterated leucine tracer. Kinetic parameters were derived by multicompartmental modelling. FH heterozygotes had a reduced delipidation rate for VLDL, which led to a moderate increase in plasma triglyceride. Compared with controls and FH, the FDB subjects converted 44% less IDL to LDL. The LDL FCR was reduced to a similar extent in FDB and FH. In all subjects LDL plasma levels appeared to be regulated by the LDL FCR and the rate of production of small VLDL. We conclude that disturbances in IDL metabolism provide the basis for understanding why FDB is less severe than FH. Our findings suggest that an apoB-LDL receptor interaction is important in the IDL to LDL conversion.