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Background: Targets for cholesterol reduction are part of the Quality Outcomes Framework and general practitioners have to meet these targets to fulfil their remuneration package. By contrast, there are no targets for the accuracy of cholesterol or other lipid measurements and no recent surveys on performance of these assays. We have assessed the performance of lipid measurement of the available methods in the UK., Methods: Serum samples collected from individual donors attending the national blood service were distributed after values were obtained from a secondary reference laboratory. Samples were sent to participant laboratories to assess different methods' analytical performance on single donation specimens, on routine external quality assessment pooled specimens, on specimens subjected to a range of freeze-thaw cycles and on frozen-stored specimens., Results: Differences in measured cholesterol were found that were method-dependent and related to triglyceride content. HDL-cholesterol (HDL-C) showed significant positive bias in all assays. Individual donor specimens showed no significant changes with differing numbers of freeze-thaw cycles. Pooled serum was stable for up to six months., Conclusions: Most cholesterol measurements are accurate but some methods are affected by triglyceride interference. HDL-C methods show significant positive bias. Although there are potential matrix effects introduced as a result of specimen preparation, additional work is needed to show if these effects are present in fresh patient samples.

Background: New dietary strategies to reduce cardiovascular disease (CVD) risk include the addition of fiber to the diet. The effect of soluble-fiber consumption derived from Plantago ovata husk on lipid risk factors in patients with CVD is unknown., Objective: We compared the effects of soluble fiber (P. ovata husk) with those of insoluble fiber (P. ovata seeds) on plasma lipid, lipoprotein, and apolipoprotein (apo) concentrations within a CVD secondary prevention program., Design: In a randomized, crossover, controlled, single-blind design, 28 men with CVD (myocardial infarction or stable angina) and an LDL-cholesterol concentration

Objectives: To evaluate the association of apolipoprotein (apo) E polymorphism and a cholesteryl ester transfer protein (CETP) polymorphism (CETP/TaqIB) with preeclampsia and with lipid/lipoprotein profile in pregnancy., Materials and Methods: A group of 144 normal pregnant women (67 in the third trimester) were compared with 51 cases of preeclampsia in the third trimester of gestation. Apo E and CETP genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Serum lipids, lipoproteins and apolipoproteins were evaluated using commercially available kits. LDL size was assessed by gradient gel electrophoresis., Results: No differences were found in the distribution of subjects with respect to genotypes, in the apo E and CETP polymorphisms, between control and pathologic groups. In the third trimester of gestation (both control and case groups considered), apo E polymorphism, but not CETP polymorphism, was associated with different lipid and lipoprotein levels. Patients carrying the E2 allele (E2+) presented with significantly lower values of LDL cholesterol (LDLc) compared with carriers of E4 (E4+) and E3/3 individuals. E2+ also presented with the highest triglyceride (TG) level, although this was not statistically significant. On the other hand, HDL cholesterol (HDLc) and apo A-I levels were significantly reduced in E4+, compared with E3/3. Furthermore, E4+ presented with the highest total cholesterol and LDL and therefore LDLc/HDLc and apo B/apo A-I ratios were significantly higher in this group compared with the other two., Conclusions: Neither of our candidate genes showed association with preeclampsia. However, apo E genotype was associated with changes in lipid and lipoprotein profiles in pregnant women.

The article focuses on a study to asses various emerging lipid-related markers for prediction of initial cardiovascular events. The objective behind the study was to determine whether adding information on apolipoprotein B and apolipoprotein A-I, lipoprotein (a), or lipoprotein-associated phospholipids A2 to total cholesterol and high-density lipoprotein cholesterol (HDL-C) improves cardiovascular disease (CVD) risk prediction. Results of the study showed that addition of information on various lipid-related markers to total cholesterol, HDL-C, and other conventional risk factors yielded improvement in the model's discrimination. The study concluded that the addition of information led to slight improvement in CVD prediction.

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. [Copyright &y& Elsevier]

Abstract: 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 &y& Elsevier]

Abstract: 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 4g daily of omega-3 fatty acids (Omacor). A standard fat load (90g) was administered and blood sampling was performed in the fasting state and at 2, 4, 6 and 8h after the fat load. Chylomicrons and VLDL1 density fraction was isolated from plasma by density ultracentrifugation. Postprandial chylomicron and VLDL1 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 18.5mmol/lh (interquartile range 8.9–32.6) vs 9.3mmol/lh (4.8–14.4) p =0.05. Following treatment patient chylomicron AUC fell [mean reduction 6.8mmol/lh (95% CI 0.1–13.6) p =0.05]. No significant reduction in chylomicron AUC was observed in the controls [mean reduction 3.9mmol/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 13.5mmol/lh (7.4–22.9), controls 7.2mmol/lh (4.6–14.5) both median and IQR, p =nsd]. VLDL1 TG AUC did not differ at baseline between patients and controls. Furthermore, there was no significant effect on VLDL1 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. [Copyright &y& Elsevier]

Abstract: 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 (1.006g/ml< d <1.030g/ml) was isolated. Approximately 1mg protein of IDL was allowed to interact with CS. The unbound and bound IDL particles were eluted using a low salt and high salt buffer, respectively. On average 70% of IDL bound to CS ranging from 56 to 92%. Total, unbound and bound IDL particles were analysed for lipid composition and particle size. The unbound IDL particles were larger (32nm) and triglyceride rich (40% versus 33%, P <0.01), whereas the bound IDL particles were smaller (26–28nm) and cholesterol rich (21% versus 14%, P <0.01). The unbound particles contain at least double the amount of apo C-II and apo C-III per IDL particle compared with the bound IDL particles. There are specific IDL particles that bind to CS in vitro, these being the cholesterol rich IDL particles. It remains to be determined if these cholesterol rich IDL particles are potentially more atherogenic than the triglyceride rich IDL particles. [Copyright &y& Elsevier]