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• Lipoprotein(a) is an independent risk factor for cardiovascular disease and to understand the availability and application of Lp(a) measurement across UK lipid clinics, we undertook a national survey. • 60% of lipid clinics performed lipoprotein(a) testing once per patient and graded cardiovascular risk according to the lipoprotein(a) reference ranges recommended by HEART UK while cascade testing was performed on levels ≥200nmol/L. • Most lipid clinics reported lipoprotein(a) in mass units (mg/dL or mg/L) with no traceability to the WHO/IFCC reference material and only a third of lipid clinics used reagents that minimise sensitivity to the effect of lipoprotein(a) isoform size. • National effort is required to provide universal access to Lipoprotein(a) measurement and to harmonise the clinical application of this data. Lipoprotein(a) is an independent risk factor for cardiovascular disease and its use is recommended in national and international guidelines for cardiovascular disease risk stratification. We undertook a survey to understand the availability and application of lipoprotein(a) measurement across UK lipid clinics. Fifty-three out of an estimated 200 lipid clinics (27%) provided responses. Eighty-one percent of 53 clinics had access to lipoprotein(a) measurement. Twenty-seven clinics disclosed the number of lipoprotein(a) tests ordered annually with approximately half of the clinics (52%) requesting 0-250 tests per year. Sixty percent measured lipoprotein(a) once per patient and the leading indication was a personal or family history of premature history of cardiovascular disease in those <60 years old. Sixty-three percent of clinics that provided comments with lipoprotein(a) results graded cardiovascular risk as per the HEART UK consensus statement. Sixty percent of clinics performed family cascade testing on lipoprotein(a) results ≥200 nmol/L. Lipoprotein(a) was reported in nmol/L, mg/dL, or mg/L by 48%, 24%, and 28% of responding clinics, respectively. National effort is required to provide universal access to lipoprotein(a) measurement and to harmonise the clinical application of this data. [ABSTRACT FROM AUTHOR]

The article discusses outlook for clinical lipidology in the United Kingdom. Topics explored include the introduction of hospital outpatient lipid clinics that offer diagnostic, genetic testing, and therapeutic services, the development of several novel forms of lipid-lowering compounds, and the operations of medical associations that cater to lipidologists in the region such as HEART UK and the British Atherosclerosis Society (BAS).

Aims The strength of the relationship of triglyceride-rich lipoproteins (TRL) with risk of coronary heart disease (CHD) compared with low-density lipoprotein (LDL) is yet to be resolved. Methods and results Single-nucleotide polymorphisms (SNPs) associated with TRL/remnant cholesterol (TRL/remnant-C) and LDL cholesterol (LDL-C) were identified in the UK Biobank population. In a multivariable Mendelian randomization analysis, TRL/remnant-C was strongly and independently associated with CHD in a model adjusted for apolipoprotein B (apoB). Likewise, in a multivariable model, TRL/remnant-C and LDL-C also exhibited independent associations with CHD with odds ratios per 1 mmol/L higher cholesterol of 2.59 [95% confidence interval (CI): 1.99–3.36] and 1.37 [95% CI: 1.27–1.48], respectively. To examine the per-particle atherogenicity of TRL/remnants and LDL, SNPs were categorized into two clusters with differing effects on TRL/remnant-C and LDL-C. Cluster 1 contained SNPs in genes related to receptor-mediated lipoprotein removal that affected LDL-C more than TRL/remnant-C, whereas cluster 2 contained SNPs in genes related to lipolysis that had a much greater effect on TRL/remnant-C. The CHD odds ratio per standard deviation (Sd) higher apoB for cluster 2 (with the higher TRL/remnant to LDL ratio) was 1.76 (95% CI: 1.58–1.96), which was significantly greater than the CHD odds ratio per Sd higher apoB in cluster 1 [1.33 (95% CI: 1.26–1.40)]. A concordant result was obtained by using polygenic scores for each cluster to relate apoB to CHD risk. Conclusion Distinct SNP clusters appear to impact differentially on remnant particles and LDL. Our findings are consistent with TRL/remnants having a substantially greater atherogenicity per particle than LDL. [ABSTRACT FROM AUTHOR]

We aimed to examine the longitudinal associations of total cholesterol (TC), non–high-density lipoprotein cholesterol (non–HDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and low-density lipoprotein cholesterol (LDL-C) with carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT) progression. We studied 1779, 15-year-old participants from the Avon Longitudinal Study of Parents and Children, UK birth cohort, followed up for 9 years. Fasting TC, non–HDL-C, HDL-C, triglyceride, and LDL-C were measured at 15, 17, and 24 years and age-categorized as normal, elevated, and dyslipidemia based on National Heart, Lung, and Blood Institute lipid guidelines. cfPWV and cIMT were measured at 17 and 24 years. Associations were examined using linear mixed-effect models. To simulate the treatment of dyslipidemia we conducted temporal inverse allocation model analyses. Among 1779 [49.9% female] participants, mean lipid levels and proportions at elevated or dyslipidemia categories increased from ages 15 through 24 years. Persistently elevated TC: effect estimate 0.026 mm; [95% CI 0.004 to 0.049; p = 0.024], elevated non–HDL-C, and elevated LDL-C were cumulatively associated with cIMT progression. Persistent borderline-low HDL-C: −0.027 mm; [-0.050 to −0.005; p = 0.019] and very-low HDL-C −0.035 mm; [-0.057 to −0.013; p = 0.002] levels were associated with cIMT progression. A temporal inverse allocation of elevated and dyslipidemic levels with normal lipid levels at age 17 years attenuated the associations of cumulative elevated TC, non–HDL-C, LDL-C, and low HDL-C with cIMT progression. Cumulative elevated lipids or dyslipidemia were not associated with cfPWV progression. Late adolescence is key to preventing, halting, and reversing dyslipidemic-related preclinical atherosclerosis progression, warranting universal lipid screening in the general pediatric population. [Display omitted] • Elevated lipids and dyslipidemia are associated with subclinical atherosclerosis progression in asymptomatic adolescents. • Simulated treatment intervention at age 17 years neutralizes the effect of dyslipidemia on atherosclerosis progression. • Optimal timing for reversing dyslipidemia-related atherosclerosis progression in asymptomatic youths is late adolescence. • Total cholesterol, non-HDL-C and HDL-C may be the main targets of lipid intervention in asymptomatic youths, but not LDL-C. • A universal pediatric lipid screening is highly recommended for the primary prevention of subclinical atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating underlying mechanisms may shed light on disease mechanisms. In this study, we aimed to identify (1) epidemiological and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE., Methods: We used metabolomic data from 95 402 individuals in the UK Biobank, excluding individuals with prevalent cardiovascular disease. Cox proportional-hazards models estimated the associations of 249 metabolites with incident disease. Bidirectional 2-sample Mendelian randomization (MR) estimated the causal effects between metabolites and outcomes using genome-wide association summary statistics for metabolites (n=118 466 from the UK Biobank), CAD (n=184 305 from CARDIoGRAMplusC4D 2015), PAD (n=243 060 from the Million Veterans Project), and VTE (n=650 119 from the Million Veterans Project). Multivariable MR was performed in subsequent analyses., Results: We found that 196, 115, and 74 metabolites were associated ( P <0.001) with CAD, PAD, and VTE, respectively. Further interrogation of these metabolites with MR revealed 94, 34, and 9 metabolites with potentially causal effects on CAD, PAD, and VTE, respectively. There were 21 metabolites common to CAD and PAD and 4 common to PAD and VTE. Many putatively causal metabolites included lipoprotein traits with heterogeneity across different sizes and lipid subfractions. Small VLDL (very-low-density lipoprotein) particles increased the risk for CAD while large VLDL particles decreased the risk for VTE. We identified opposing directions of CAD and PAD effects for cholesterol and triglyceride concentrations within HDLs (high-density lipoproteins). Subsequent sensitivity analyses including multivariable MR revealed several metabolites with robust, potentially causal effects of VLDL particles on CAD., Conclusions: While common vascular conditions are associated with overlapping metabolomic profiles, MR prioritized the role of specific lipoprotein species for potential pharmacological targets to maximize benefits in both arterial and venous beds., Competing Interests: P. Natarajan reports research grants from Allelica, Amgen, Apple, Boston Scientific, Genentech/Roche, and Novartis; personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, Merck, and Novartis; scientific advisory board membership of Esperion Therapeutics, Preciseli, and TenSixteen Bio; being a scientific cofounder of TenSixteen Bio; equity in MyOme, Preciseli, and TenSixteen Bio; and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. The other authors report no conflicts.

Background: Atrial fibrillation (AF) is a cardiac arrhythmia associated with an elevated risk of stroke, heart failure, and mortality. However, preventative therapies are needed with ancillary benefits on its cardiovascular comorbidities. Lipoprotein(a) (Lp[a]) is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), which itself increases AF risk, but it remains unknown whether Lp(a) is a causal mediator of AF independent of ASCVD.Objectives: This study investigated the role of Lp(a) in AF and whether it is independent of ASCVD.Methods: Measured and genetically predicted Lp(a) levels were tested for association with 20,432 cases of incident AF in the UK Biobank (N = 435,579). Mendelian randomization analyses were performed by using summary-level data for AF from publicly available genome-wide association studies (N = 1,145,375).Results: In the UK Biobank, each 50 nmol/L (23 mg/dL) increase in Lp(a) was associated with an increased risk of incident AF using measured Lp(a) (HR: 1.03; 95% CI: 1.02-1.04 ; P = 1.65 × 10-8) and genetically predicted Lp(a) (OR: 1.03; 95% CI: 1.02-1.05; P = 1.33 × 10-5). Mendelian randomization analyses using independent data replicated the effect (OR: 1.04 per 50 nmol/L Lp[a] increase; 95% CI: 1.03-1.05 per 50 nmol/L Lp[a] increase; P = 9.23 × 10-10). There was no evidence of risk-conferring effect from low-density lipoprotein cholesterol or triglycerides, and only 39% (95% CI: 27%-73%) of Lp(a) risk was mediated through ASCVD, suggesting that Lp(a) partly influences AF independent of its known effects on ASCVD.Conclusions: Our findings implicate Lp(a) as a potential causal mediator in the development of AF which show that the effects of Lp(a) extend across myocardial tissues. Ongoing clinical trials for Lp(a)-lowering therapies should evaluate effects on AF prevention. [ABSTRACT FROM AUTHOR]

A previous study of 200,000 exome-sequenced UK Biobank participants investigating the association between rare coding variants and hyperlipidaemia had implicated four genes, LDLR, PCSK9, APOC3 and IFITM5, at exome-wide significance. In addition, a further 43 protein-coding genes were significant with an uncorrected p value of <0.001. Exome sequence data has become available for a further 270,000 participants and weighted burden analysis to test for association with hyperlipidaemia was carried out in this sample for the 47 genes highlighted by the previous study. There was no evidence to implicate IFITM5 but LDLR, PCSK9, APOC3, ANGPTL3, ABCG5 and NPC1L1 were all statistically significant after correction for multiple testing. These six genes were also all exome-wide significant in the combined sample of 470,000 participants. Variants impairing function of LDLR and ABCG5 were associated with increased risk whereas variants in the other genes were protective. Variant categories associated with large effect sizes are cumulatively very rare and the main benefit of this kind of study seems to be to throw light on the molecular mechanisms impacting hyperlipidaemia risk, hopefully supporting attempts to develop improved therapies., (© 2024. The Author(s).)

Background: Lipoprotein(a) (Lp(a)) concentrations are a major independent risk factor for coronary artery disease (CAD) and are mainly determined by variation in LPA. Up to 70% of the LPA coding sequence is located in the hypervariable kringle IV type 2 (KIV-2) region. It is hardly accessible by conventional technologies, but may contain functional variants.Objectives: This study sought to investigate the new, very frequent splicing variant KIV-2 4733G>A on Lp(a) and CAD.Methods: We genotyped 4733G>A in the GCKD (German Chronic Kidney Disease) study (n = 4,673) by allele-specific polymerase chain reaction, performed minigene assays, identified proxy single nucleotide polymorphisms and used them to characterize its effect on CAD by survival analysis in UK Biobank (n = 440,234). Frequencies in ethnic groups were assessed in the 1000 Genomes Project.Results: The 4733G>A variant (38.2% carrier frequency) was found in most isoform sizes. It reduces allelic expression without abolishing protein production, lowers Lp(a) by 13.6 mg/dL (95% CI: 12.5-14.7; P < 0.0001) and is the strongest variance-explaining factor after the smaller isoform. Splicing of minigenes was modified. Compound heterozygosity (4.6% of the population) for 4733G>A and 4925G>A, another KIV-2 splicing mutation, reduces Lp(a) by 31.8 mg/dL and most importantly narrows the interquartile range by 9-fold (from 42.1 to 4.6 mg/dL) when compared to the wild type. In UK Biobank 4733G>A alone and compound heterozygosity with 4925G>A reduced HR for CAD by 9% (95% CI: 7%-11%) and 12% (95% CI: 7%-16%) (both P < 0.001). Frequencies in ethnicities differ notably.Conclusions: Functional variants in the previously inaccessible LPA KIV-2 region cooperate in determining Lp(a) variance and CAD risk. Even a moderate but lifelong genetic Lp(a) reduction translates to a noticeable CAD risk reduction. [ABSTRACT FROM AUTHOR]

Background: Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear.Methods: We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in ∼30 000 adults and 4000 children across 10 UK and Finnish cohort studies.Results: In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids.Conclusions: Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Very rare loss-of-function mutations in the apolipoprotein C3 (APOC3) gene have been associated with low circulating apoC-III, low triglycerides, and reduced cardiovascular risk. We aimed to analyze the impact of common APOC3 variants on key parameters of lipid metabolism and coronary artery disease in the largest sample so far. Common variants in APOC3 were tested for associations with circulating apoC-III, lipids, and apolipoprotein B (apoB) in 3041 participants of the LUdwigshafen RIsk and Cardiovascular health study (LURIC). These variants were then tested for associations with coronary artery disease in a meta-analysis comprising up to 332,389 participants of the CARDIOGRAMplusC4D consortium and the UK Biobank. The mean (standard deviation) apoC-III concentration was 14.6 (5.1) mg/dl. Seven common variants in APOC3 (rs734104 , rs4520 , rs5142 , rs5141 , rs5130 , rs5128 , and rs4225) were associated with circulating apoC-III (all p < 0.05). The alleles that modestly raised apoC-III were also associated with markedly higher total triglycerides and very low density lipoprotein (VLDL) triglycerides and cholesterol (all p < 0.05), but not with low density lipoprotein (LDL) cholesterol and total apoB (all p > 0.05). These variants were not associated with coronary artery disease in the CARDIOGRAMplusC4D consortium and the UK Biobank (all p > 0.1). Modest, genetically caused elevations of apoC-III are associated with a marked increase of triglyceride-rich lipoproteins but not with an increase of LDL cholesterol, total apoB, and coronary artery disease. Whether effective inhibition of apoC-III production with antisense oligomers will be instrumental to reduce cardiovascular risk remains to be demonstrated. Image 1 • Common apolipoprotein C3 (APOC3) variants are associated with modest alterations of circulating apoC-III. • Common apoC-III raising alleles are associated with increased triglycerides, very low density lipoprotein (VLDL) triglycerides, and VLDL cholesterol. • Common apoC-III raising alleles are not associated with increased total apolipoprotein B and low density lipoprotein (LDL) cholesterol. • ApoC-III raising alleles are not associated with coronary artery disease in 332,389 participants of the CARDIOGRAMplusC4D consortium and the UK Biobank. [ABSTRACT FROM AUTHOR]

The relationship between genetically-driven liver fat and coronary heart disease (CHD) remains unclear. ApoB-containing lipoproteins are known causal factors for CHD and may explain this relationship. We conducted a genome-wide association study (GWAS) in the UK Biobank to identify genetic variants associated with liver fat. We then investigated the effects that these genetic variants had on both apoB-containing lipoproteins and CHD. Using Mendelian Randomization (MR) analyses, we examined if the relationship between genetically-driven liver fat and CHD could be attributed to its effect on apoB-containing lipoproteins. We found 25 independent liver-fat associated single-nucleotide polymorphisms (SNPs) with differing effects on lipoprotein metabolism. The SNPs were classified into three groups/clusters. The first cluster (N = 3 SNPs) displayed lipoprotein-raising effects. The second cluster (N = 12 SNPs) displayed neutral effects on lipoproteins and the third cluster (N = 10 SNPs) displayed lipoprotein-lowering effects. For every 1% higher liver fat, the first cluster showed an increased risk of CHD (OR = 1.157 [95% CI: 1.108–1.208]). The second cluster showed a non-significant effect on CHD (OR = 0.988 [95% CI: 0.965–1.012], whereas the third cluster showed a protective effect of increased liver fat on CHD (OR = 0.942 [95% CI: 0.897–0.989]). When adjusting for apoB, the risk for CHD became null. Here, we identify 25 liver-fat associated SNPs. We find that SNPs that increase, decrease or have neutral effects on apoB-containing lipoproteins show increased, decreased or neutral effects on CHD, respectively. Therefore, the relationship between genetically-driven liver fat and CHD is mediated by the causal effect of apoB. [Display omitted] • Liver fat-related genetic variants may or may not raise coronary heart disease risk. • Previous studies have shown different results using different genetic variants. • The effect on apoB-containing lipoproteins may explain previous results. • Here, we were able to directly account for the possible effect on plasma apoB. • We found that the effect on coronary heart disease risk is fully explained by apoB. [ABSTRACT FROM AUTHOR]

Background Associations of coronary heart disease (CHD) with plasma lipids are well described, but the associations with characteristics of lipoproteins (which transport lipids) remain unclear. Methods and Results UK Biobank is a prospective study of 0.5 million adults. Analyses were restricted to 89 422 participants with plasma lipoprotein and apolipoprotein measures from Nightingale nuclear magnetic resonance spectroscopy and without CHD at baseline. CHD risk was positively associated with concentrations of very-low-density lipoproteins, intermediate-density lipoproteins, and low-density lipoproteins (LDL), and inversely associated with high-density lipoproteins. Hazard ratios (99% CIs) per SD were 1.22 (1.17-1.28), 1.16 (1.11-1.21), 1.20 (1.15-1.25), and 0.90 (0.86-0.95), respectively. Larger subclasses of very-low-density lipoproteins were less strongly associated with CHD risk, but associations did not materially vary by size of LDL or high-density lipoprotein. Given lipoprotein particle concentrations, lipid composition (including cholesterol) was not strongly related to CHD risk, except for triglyceride in LDL particles. Apolipoprotein B was highly correlated with LDL concentration ( r =0.99), but after adjustment for apolipoprotein B, concentrations of very-low-density lipoprotein and high-density lipoprotein particles remained strongly related to CHD risk. Conclusions This large-scale study reliably quantifies the associations of nuclear magnetic resonance-defined lipoprotein characteristics with CHD risk. CHD risk was most strongly related to particle concentrations, and separate measurements of lipoprotein concentrations may be of greater value than the measurement by apolipoprotein B, which was largely determined by LDL concentration alone. Furthermore, there was strong evidence of positive association with mean triglyceride molecules per LDL particle but little evidence of associations with total triglycerides or other lipid and lipoprotein fractions after accounting for lipoprotein concentrations.

This consensus statement addresses the current three main modalities of treatment of homozygous familial hypercholesterolaemia (HoFH): pharmacotherapy, lipoprotein (Lp) apheresis and liver transplantation. HoFH may cause very premature atheromatous arterial disease and death, despite treatment with Lp apheresis combined with statin, ezetimibe and bile acid sequestrants. Two new classes of drug, effective in lowering cholesterol in HoFH, are now licensed in the United Kingdom. Lomitapide is restricted to use in HoFH but, may cause fatty liver and is very expensive. PCSK9 inhibitors are quite effective in receptor defective HoFH, are safe and are less expensive. Lower treatment targets for lipid lowering in HoFH, in line with those for the general FH population, have been proposed to improve cardiovascular outcomes. HEART UK presents a strategy combining Lp apheresis with pharmacological treatment to achieve these targets in the United Kingdom (UK). Improved provision of Lp apheresis by use of existing infrastructure for extracorporeal treatments such as renal dialysis is promoted. The clinical management of adults and children with HoFH including advice on pregnancy and contraception are addressed. A premise of the HEART UK strategy is that the risk of early use of drug treatments beyond their licensed age restriction may be balanced against risks of liver transplantation or ineffective treatment in severely affected patients. This may be of interest beyond the UK. [ABSTRACT FROM AUTHOR]

Background: Type III hyperlipidaemia (T3HL) is characterised by equimolar increases in plasma triglycerides (TG) and cholesterol in <10% of APOE22 carriers conveying high cardiovascular disease (CVD) risk. We investigate the role of a weighted triglyceride-raising polygenic score (TG.PS) precipitating T3HL., Methods: The TG.PS (restricted to genome-wide significance and weighted by published independent effect estimates) was applied to the Oxford Biobank (OBB, n = 6952) and the UK Biobank (UKB, n = 460,037), to analyse effects on plasma lipid phenotypes. Fasting plasma lipid, lipoprotein biochemistry and NMR lipoprotein profiles were analysed in OBB. CVD prevalence/incidence was examined in UKB., Results: One TG.PS standard-deviation (SD) was associated with 13.0% (95% confidence-interval 12.0-14.0%) greater TG in OBB and 15.2% (15.0-15.4%) in UKB. APOE22 carriers had 19.0% (1.0-39.0%) greater TG in UKB. Males were more susceptible to TG.PS effects (4.0% (2.0-6.0%) greater TG with 1 TG.PS SD in OBB, 1.6% (1.3-1.9%) in UKB) than females. There was no interaction between APOE22 and TG.PS, BMI, sex or age on TG. APOE22 carriers had lower apolipoprotein B (apoB) (OBB; -0.35 (-0.29 to -0.40)g/L, UKB; -0.41 (-0.405 to -0.42)g/L). NMR lipoprotein lipid concentrations were discordant to conventional biochemistry in APOE22 carriers. In APOE22 compared with APOE33, CVD was no more prevalent in similarly hypertriglyceridaemic participants (OR 0.97 95%CI 0.76-1.25), but was less prevalent in normolipidaemia (OR 0.81, 95%CI 0.69-0.95); no differences were observed in CVD incidence., Conclusions: TG.PS confers an additive risk for developing T3HL, that is of comparable effect size to conventional risk factors. The protective effect of APOE22 for prevalent CVD is consistent with lower apoB in APOE22 carriers., Competing Interests: Declaration of Competing Interest RWK has received consulting fees from Novo Nordisk. The Authors claim no other conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim To investigate the association between pulse pressure and risk of hospitalization for cardiovascular events among people with Type 2 diabetes. Methods A population-based case-control study was carried out using data from medical databases. A total of 588 people with Type 2 diabetes from 18 general practices in Cambridgeshire recorded a first hospitalization for a cardiovascular event between 2009 and 2011, and a total of 2920 age-matched, gender-matched and practice-matched control subjects with Type 2 diabetes were selected based on risk-set sampling. Pulse pressure was assessed before admission in 2008-2009. Further dose-response relationships between pulse pressure and risks were explored using spline models. Results There was a non-linear relationship between pulse pressure and the risk of hospitalization for a cardiovascular event ( P < 0.001 for linearity test). The pulse pressure associated with the lowest risk of hospitalization for a cardiovascular event was 61 (95% CI 57-63) mmHg. Conclusion In people with Type 2 diabetes, pulse pressure is a good predictor of risk of hospitalization for cardiovascular events. The risk is lowest with a pulse pressure of 57-63 mmHg. [ABSTRACT FROM AUTHOR]

What is already known about this subject Small, dense LDL is highly atherogenic and the prevalence is higher in obesity., Weight loss lowers the prevalence of small, dense LDL., What this study adds The important role of TG in lowering LDL peak particle density and the proportion of small, dense LDL particles., Waist or insulin resistance were not predictive of these important changes in LDL characteristics., Objective Small, dense low-density lipoprotein ( LDL) particles are highly atherogenic and strongly associated with obesity-related dyslipidemia. The metabolic inter-relationships between weight loss induced changes in waist circumference, triglycerides, insulin sensitivity and small-dense LDL particles in clinically obese children and adolescents have not been studied. Methods Seventy-five clinically obese boys and girls (standardized body mass index 3.07 ± 0.59, aged 8-18 years) were recruited. Anthropometric, body composition and cardiometabolic risk factors were measured pre- and post-weight loss. Results There were highly significant reductions in anthropometric, body composition and cardiometabolic risk factors. Triglyceride change was positively correlated with LDL peak particle density and percentage LDL pattern B changes (relative abundance of small, dense LDL particles). Multiple regression analyses showed that changes in triglyceride concentration accounted for between 24 and 18% of the variance in LDL peak particle density and percentage LDL pattern B change, respectively. Changes in waist circumference and insulin sensitivity did not predict these changes in LDL characteristics. Conclusion Acute and highly significant weight loss significantly decreased LDL peak particle density and percentage LDL pattern B. The change in triglycerides was a strong predictor of LDL peak particle density and percentage LDL pattern B change. [ABSTRACT FROM AUTHOR]

Aims Rising rates of obesity have led to an increasing prevalence of Type 2 diabetes mellitus in young people. Uncertainty exists over the utility of screening younger adults for Type 2 diabetes, as existing data sets have focused on mature (> 40 years) cohorts. The aim of this study was to determine the prevalence of impaired glucose metabolism in higher risk younger adults. Methods Overweight (with an additional risk factor) or obese adults (18-40 years) were recruited for the Sedentary Time And Diabetes ( STAND) randomized controlled trial. Measures included an oral glucose tolerance test, HbA1c, biochemical and anthropometric data. Results One hundred and ninety-three individuals (68% female; median age 33.8 years; median BMI 33.9 kg/m2) were recruited. Forty-three per cent had a first-degree family history of Type 2 diabetes. Previously undiagnosed Type 2 diabetes was present in 4.7% ( n = 9). Of participants, 18.1% ( n = 35) had impaired glucose metabolism: 4.7% ( n = 9) HbA1c ≥ 48 mmol/mol (6.5%); 9.3% ( n = 18) HbA1c 42-46 mmol/mol (6.0-6.4%); 3.1% ( n = 6) Type 2 diabetes on oral glucose tolerance test; 6.2% ( n = 12) isolated impaired glucose tolerance; 2.1% ( n = 4) isolated impaired fasting glucose; 1% ( n = 2) both impaired fasting glucose and impaired glucose tolerance. Of participants, 58.5% ( n = 113) had dyslipidaemia, 28.0% ( n = 54) had hypertension, 31.1% ( n = 60) were vitamin D deficient and 7.3% ( n = 14) had abnormal liver function. Conclusions This study identified a high prevalence of Type 2 diabetes and impaired glucose regulation in overweight and obese younger adults. These findings require confirmation in a larger, representative, population. [ABSTRACT FROM AUTHOR]

Aims To describe the proportion of people with Type 2 diabetes living in Scotland who meet eligibility criteria for inclusion in several large randomized controlled trials of glycaemic control to inform physicians and guideline developers about the generalizibility of trial results. Methods A literature review was performed to identify large trials assessing the impact of glycaemic control on risk of macrovascular disease. Inclusion and exclusion criteria from each trial were applied to data on the population of people with a diagnosis of Type 2 diabetes living in Scotland in 2008 ( n = 180 590) in a population-based cross-sectional study and the number and proportion of people eligible for each trial was determined. Results Seven trials were identified. The proportion of people with Type 2 diabetes who met the eligibility criteria for the trials ranged from 3.5 to 50.7%. Trial participants were younger at age of diagnosis of diabetes and at time of trial recruitment than in the Scottish study population. The application of upper age criteria excluded the largest proportion of patients, with up to 39% of people with Type 2 diabetes ineligible for a trial with the most stringent criteria based on age alone. Conclusions We found that many of the large trials of glycaemic control among people with Type 2 diabetes have limited external validity when applied to a population-based cohort of people with Type 2 diabetes. In particular, the age distribution of trial participants often does not reflect that of people with Type 2 diabetes in a contemporary British population. [ABSTRACT FROM AUTHOR]

Objectives To describe baseline characteristics of responders to insulin therapy (HbA1c targets < 58 mmol/mol, 7.5%) at 18 months among adults with newly diagnosed diabetes. Methods A retrospective UK study derived from 479 general practices electronic dataset. We included all adults (age > 18 years) with newly diagnosed diabetes who required insulin therapy within 6 months of diagnosis. The data comprised insulin regimen (long-acting only; premixed insulin only; basal bolus insulin regimen), gender, Townsend quintile, baseline and an 18-month measurement of clinical and biochemical variables. Multiple imputations were undertaken and logistic regression used to assess the effect of covariates. Results A total of 1492 patients (aged 19-93 years) were analysed. Means ( SD) baseline HbA1c and BMI were 10.3% (2.6%) and 29.6 (7.0%), respectively. Following multiple imputation for missing data, logistic regression analysis indicated important covariates to achieve HbA1c targets were baseline HbA1c, lipid lowering therapy, gender and age. Including all covariates, those treated with premixed insulin were 47% more likely to achieve target HbA1c at 18 months than those treated with a basal-bolus regimes (adjusted OR 1.47; 95% CI 1.12-1.92, P = 0.006)) and 32% more likely than those treated with long-acting insulin was (adjusted OR 1.32; 95% CI 1.01-1.74, P = 0.044). Those with a higher baseline HbA1c level, on lipid-lowering therapy, women and younger patients had a lower response rate. Mean weight gain ( SD) was 2.4 kg (8.5 kg) and was not influenced by treatment regimen. Conclusion The use of premixed insulin regimen among newly diagnosed patients with diabetes appears to be most effective in reaching HbA1c target values, independent of other confounders. The appropriate choice of insulin regimen at initiation should therefore take into account various metabolic and psychosocial factors. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated international differences in the association between obesity and physiological dysregulation in the U.S., England and Taiwan. Three nationally representative samples were used in the study, including the U.S. National Health and Nutrition Examination Survey. The researchers found higher physiological dysregulation among individuals with high waist.

Purpose: Why early puberty is associated with worse cardiovascular outcomes is unknown. The relationship between puberty and lipids is unclear. Our aim was to assess whether age at puberty was associated with triglyceride and total low-density lipoprotein and high-density lipoprotein cholesterol at age 53 years. Methods: Participants in a national birth cohort were examined at 15 years, when pubertal stage for boys was assessed and age at menarche reported by the girls'' mothers. At 53 years, 3035 were interviewed in their homes by research nurses, where blood was taken. Results: There was a significant inverse relationship in women but not men between age at puberty (in years) and triglycerides (regression coefficient −0.2.9, 95% confidence interval −5.5, to −0.04, p = .02), age at puberty, and age at puberty and adult body mass index (BMI; p < .001). Relationships between puberty and lipids were completely explained by BMI or waist circumference at 53 years. Conclusions: In both sexes earlier maturation was associated with greater BMI and waist circumference in later life, which resulted in greater triglycerides and cholesterol in women. We suggest that intervention after puberty to help avoid obesity in early maturing women may improve their later cardiovascular health. [Copyright &y& Elsevier]

Presents letters to the editor concerning topics in medicine. Confusion of the diagnosis of severe acute respiratory syndrome (SARS); Lymphopenia in SARS; Questions about the benefits of atorvastatin in the ASCOT-LLA trial; Lipoproteins and cardiovascular risk; Higher education and medical research in Great Britain; Introduction of selection bias by the informed consent process; Question of whether disabling cough is a habit disorder or tic syndrome; Clinical efficacy and toxicity of gefitinib in patients with lung cancer; Human telomerase RNA mutations and bone marrow failure; The death of George Edward Stanhope Molyneux Herbert, the fifth Earl of Carnarvon within weeks of the opening of the tomb of the Egyptian pharoah Tutankhamen, which lead to speculations of a curse.

Whether the protective effect of high density lipoprotein (HDL) on incident coronary heart disease (CHD) can be attributed to one or both HDL subfractions remains controversial. The associations of HDL2 and HDL3 cholesterol with the incidence of CHD in the 9-year follow-up of the Caerphilly study are described. A total of 2398 middle-aged British men were recruited from the general population between 1984 and 1988 and were followed, on average, for 9 years. Total and HDL3 cholesterol were measured by a two-step precipitation technique on fresh, fasting samples from 2225 men. HDL2 cholesterol was calculated by subtracting HDL3 from total HDL cholesterol. Relative odds and 95% confidence intervals (CI) for incident CHD were obtained by use of a logistic regression model. During follow-up, 282 (12%) men developed a major new CHD event. Total HDL and HDL3 cholesterol were significantly and inversely associated with the risk of incident CHD. When divided into fifths of the distributions of total HDL and HDL3 cholesterol, multivariate-adjusted relative odds were 1.00, 0.95, 0.72, 0.85, 0.38 and 1.00, 1.05, 0.92, 0.67, 0.39, respectively graded from the least to the most quintile, with the lowest quintile group as referent. Tests for trend were significant (P for trend 0.003 and 0.001, respectively). In a multivariate model, the contribution of HDL3 was significant (standardized relative odds, 0.76; 95% CI, 0.64–0.91), whereas HDL2 was not significant. No linear combination of the two subfractions was a better predictor of CHD than total HDL cholesterol alone. HDL3 cholesterol was an independent predictor of incident CHD and may be more closely related to the development of CHD than HDL2 cholesterol. The prediction of the risk of CHD from total HDL cholesterol alone could not be improved upon by measurement of the two HDL subfractions. In our view, the only way to improve our understanding of this situation is to measure both subfractions independently of each other and not to calculate one by subtraction. [Copyright &y& Elsevier]

Background: Effective targeted prevention of type 2 diabetes (T2D) depends on accurate prediction of disease risk. We assessed the role of metabolomic profiling in improving T2D risk prediction beyond conventional risk factors., Methods: Nuclear magnetic resonance (NMR) metabolomic profiling was undertaken on baseline plasma samples in 65,684 UK Biobank participants without diabetes and not taking lipid-lowering medication. Among a subset of 50,519 participants with data available on all relevant co-variates (sociodemographic characteristics, parental history of diabetes, lifestyle-including dietary-factors, anthropometric measures and fasting time), Cox regression yielded adjusted hazard ratios for the associations of 143 individual metabolic biomarkers (including lipids, lipoproteins, fatty acids, amino acids, ketone bodies and other low molecular weight metabolic biomarkers) and 11 metabolic biomarker principal components (PCs) (accounting for 90% of the total variance in individual biomarkers) with incident T2D. These 11 PCs were added to established models for T2D risk prediction among the full study population, and measures of risk discrimination (c-statistic) and reclassification (continuous net reclassification improvement [NRI], integrated discrimination index [IDI]) were assessed., Results: During median 11.9 (IQR 11.1-12.6) years' follow-up, after accounting for multiple testing, 90 metabolic biomarkers showed independent associations with T2D risk among 50,519 participants (1211 incident T2D cases) and 76 showed associations after additional adjustment for HbA1c (false discovery rate controlled p < 0.01). Overall, 8 metabolic biomarker PCs were independently associated with T2D. Among the full study population of 65,684 participants, of whom 1719 developed T2D, addition of PCs to an established risk prediction model, including age, sex, parental history of diabetes, body mass index and HbA1c, improved T2D risk prediction as assessed by the c-statistic (increased from 0.802 [95% CI 0.791-0.812] to 0.830 [0.822-0.841]), continuous NRI (0.44 [0.38-0.49]) and relative (15.0% [10.5-20.4%]) and absolute (1.5 [1.0-1.9]) IDI. More modest improvements were observed when metabolic biomarker PCs were added to a more comprehensive established T2D risk prediction model additionally including waist circumference, blood pressure and plasma lipid concentrations (c-statistic, 0.829 [0.819-0.838] to 0.837 [0.831-0.848]; continuous NRI, 0.22 [0.17-0.28]; relative IDI, 6.3% [4.1-9.8%]; absolute IDI, 0.7 [0.4-1.1])., Conclusions: When added to conventional risk factors, circulating NMR-based metabolic biomarkers modestly enhanced T2D risk prediction., (© 2022. The Author(s).)

Examines the concentrations of high density lipoprotein cholesterol and triglycerides in ischemic heart disease in Great Britain. Assessment on the roles of serum concentrations; Appraisal on the importance of the lipids; Effects of lipoprotein cholesterol on ischemic heart disease.

Examines the relation between alcohol consumption and cardiovascular risk factors in British women. Increase of lipoprotein cholesterol concentration; Role of insulin in hepatic synthesis of cholesterol; Effects of moderate alcohol consumption on cardiac activity.

The article highlights the meeting of the Forum on Lipids in Clinical Medicine that was held in Great Britain. Speaker D. N. Brindley presented a paper on hepatic lipid and lipoprotein metabolism. T. J. Peters of MRC Clinical Research Centre and his group provided an insight into the causes of fatty liver. J. Owen of Royal Free Hospital School discussed the surface composition of plasma lipoproteins.

Background: Lipoprotein-related traits have been consistently identified as risk factors for atherosclerotic cardiovascular disease, largely on the basis of studies of coronary artery disease (CAD). The relative contributions of specific lipoproteins to the risk of peripheral artery disease (PAD) have not been well defined. We leveraged large-scale genetic association data to investigate the effects of circulating lipoprotein-related traits on PAD risk., Methods: Genome-wide association study summary statistics for circulating lipoprotein-related traits were used in the mendelian randomization bayesian model averaging framework to prioritize the most likely causal major lipoprotein and subfraction risk factors for PAD and CAD. Mendelian randomization was used to estimate the effect of apolipoprotein B (ApoB) lowering on PAD risk using gene regions proxying lipid-lowering drug targets. Genes relevant to prioritized lipoprotein subfractions were identified with transcriptome-wide association studies., Results: ApoB was identified as the most likely causal lipoprotein-related risk factor for both PAD (marginal inclusion probability, 0.86; P =0.003) and CAD (marginal inclusion probability, 0.92; P =0.005). Genetic proxies for ApoB-lowering medications were associated with reduced risk of both PAD (odds ratio,0.87 per 1-SD decrease in ApoB [95% CI, 0.84-0.91]; P =9×10 -10 ) and CAD (odds ratio,0.66 [95% CI, 0.63-0.69]; P =4×10 -73 ), with a stronger predicted effect of ApoB lowering on CAD (ratio of effects, 3.09 [95% CI, 2.29-4.60]; P <1×10 -6 ). Extra-small very-low-density lipoprotein particle concentration was identified as the most likely subfraction associated with PAD risk (marginal inclusion probability, 0.91; P =2.3×10 -4 ), whereas large low-density lipoprotein particle concentration was the most likely subfraction associated with CAD risk (marginal inclusion probability, 0.95; P =0.011). Genes associated with extra-small very-low-density lipoprotein particle and large low-density lipoprotein particle concentration included canonical ApoB pathway components, although gene-specific effects were variable. Lipoprotein(a) was associated with increased risk of PAD independently of ApoB (odds ratio, 1.04 [95% CI, 1.03-1.04]; P =1.0×10 -33 )., Conclusions: ApoB was prioritized as the major lipoprotein fraction causally responsible for both PAD and CAD risk. However, ApoB-lowering drug targets and ApoB-containing lipoprotein subfractions had diverse associations with atherosclerotic cardiovascular disease, and distinct subfraction-associated genes suggest possible differences in the role of lipoproteins in the pathogenesis of PAD and CAD.

Highlights the conference of the Institute of Food Science and Technology Research Subject Interest Group and The Nutrition Society in Great Britain on March 27, 2001. Information on the contribution of genomics on disease etiology; Impact of genotype on lipoprotein metabolism; Role of inflammatory response in the development of chronic disease.

Background and Aims: There is some evidence of a cross-sectional, and possibly causal, relationship of lipid levels with leukocyte counts in mice and humans. This study investigates the cross-sectional and longitudinal relationship of blood lipid and lipoprotein levels with leukocyte counts in the UK Biobank cohort., Methods: The primary cross-sectional analysis included 417,132 participants with valid data on lipid measures and leukocyte counts. A subgroup analysis was performed in 333,668 participants with valid data on lipoprotein(a). The longitudinal analysis included 9058 participants with valid baseline and follow-up data on lipid and lipoprotein levels and leukocyte counts. The association of lipid and lipoprotein levels with leukocyte counts was analysed by multivariable linear regression., Results: Several relationships were significant in both cross-sectional and longitudinal analysis. After adjustment for demographic, socioeconomic and other confounding factors, a higher eosinophil count was associated with lower HDL cholesterol and apolipoprotein A-I concentration (p < 0.001). Higher triglycerides levels were associated with higher total leukocyte, basophil, eosinophil, monocyte and neutrophil counts (all p < 0.01). A higher lymphocyte count was associated with a higher apolipoprotein B level (p < 0.001). In the longitudinal analysis, lipoprotein(a) was inversely associated with basophil count in men but not women (p < 0.001)., Conclusions: Triglyceride levels demonstrate a robust positive association with total and differential leukocyte counts suggesting they may be directly involved in leukogenesis. However, unlike in murine models, the remainder of these relationships is modest, which suggests that cholesterol and lipoproteins are minimally involved in leukogenesis in humans., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) might play a role in aortic valve mineralization and is highly expressed in calcific aortic valve stenosis (CAVS). Whether Lp-PLA2 represents a biomarker or a causal risk factor for CAVS is unknown. Our objective was to test the association between plasma Lp-PLA2 activity vs. genetically determined plasma Lp-PLA2 mass/activity with CAVS risk in humans. Methods and Results: We measured plasma Lp-PLA2 activity in a case-control cohort of 890 patients undergoing cardiac surgery (476 patients undergoing aortic valve replacements for CAVS and 414 control patients with CAD undergoing coronary artery bypass grafting and without valvulopathy). After adjusting for age, sex, body mass index, diabetes, smoking and lipid-lowering therapy use, each standard deviation unit increment of Lp-PLA2 activity was associated with a higher CAVS risk (OR=1.23 [95%CI, 1.05-1.44]). In a combined analysis of the Quebec-CAVS cohort (1009 CAVS cases and 1017 controls) and the UK Biobank (1352 CAVS cases and 351,393 controls), we found no association between four single nucleotide polymorphisms at the PLA2G7 locus previously shown to be associated with Lp-PLA2 mass and/or activity and CAVS risk (OR=1.02 [95%CI, 0.95-1.11, p=0.48] for rs180517, 1.02 [95%CI, 0.95-1.11, p=0.56] for rs4498351, 0.98 [95%CI, 0.90-1.06, p=0.62] for rs7756935, and 0.95 [95%CI, 0.85-1.05, p=0.31] for rs1421368). Conclusion: Our study shows that higher Lp-PLA2 activity is significantly associated with the prevalence of CAVS in patients with heart disease, but the results of the genetic association analyses suggest that Lp-PLA2 is unlikely to represent a causal risk factor or therapeutic target for CAVS. [ABSTRACT FROM AUTHOR]

The article presents abstracts on Type 2 diabetes research award topics in Great Britain which include lipotoxicity in Type 2 diabetes deterioration, association between diabetics' body mass index and mortality risks, and interleukin 6 (IL-6) in older people with Type 2 diabetes' cognitive decline.

Individuals at increased cardio-metabolic (CM) risk have a greater chance of developing diabetes mellitus and suffering premature cardiovascular events. The metabolic syndrome (MetS) is a constellation of risk factors which confer increased CM risk. MetS was originally proposed by Reaven (1998) and the currently accepted definition was agreed by AHA/NHLBI,WH,IASIASO (Alberti et al., 2009). More recently, increased liver fat has been proposed as a marker of CM risk. The aims of this study were to evaluate the inter-relationships between percentage liver fat and established CM risk factors and identify those with MetS. This paper presents a secondary analysis of baseline data from a sample ( n = 37) (56 ± 5.32 years), of overweight men who were at increased CM risk but otherwise healthy,, and recruited into a randomised dietary intervention crossover study to investigate how dietary carbohydrate influences the metabolism of plasma lipoproteins in overweight volunteers with moderately high (>10% <20%) and low (<2%) levels of liver fat. Anthropometric and biochemistry measurements were obtained, and from a sub-sample, the percentage of liver fat by magnetic resonance imaging. The participants were also assigned a metabolic score based on the number of indicators of the MetS according to the AHA/NHLBI, WH, IASIASO definition (Alberti, 2009). Non-parametric statistical analyses was used, as not all variables were normally distributed, there were a number of outliers and a small sample size. Pearson Correlation Co-efficients were used to investigate relationships between continuous and categorical variables. The variables were not adjusted for age or BMI because of a small sample size. Statistical significance was set at P ≤ 0.05 and all analyses were carried out using SPSS 16.0. Fifty nine per cent of the participants had MetS ( n = 21). There was evidence of significant, positive associations between the metabolic score for MetS and total cholesterol:HDL-C ratio ( P = 0.030), and between percentage liver fat and plasma glucose and insulin ( P = 0.010 and P = 0.003 respectively). The percentage of liver fat was also notably higher than that reported in other studies (Yamada et al., 2010; Kotronen et al., 2007) and there was positive correlation between the liver enzyme alanine transaminase (ALT) and plasma insulin ( P = 0.012). The strong associations between established risk factors and liver fat suggest that the latter may be clinically useful as a marker for CM risk in MetS. Alberti, K., Eckel, R., Grundy, S. et al. (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation, 1640-1645. Kotronen, A., Westerbacka, A., Bergholm, R., Pietilainen, K.H. & Yki-Jarvinen, H. (2007) Liver fat in the metabolic syndrome. J. Clin. Endocrinol. Metab. , 3490-3497. Reaven, G. (1998) Insulin resistance and human disease: a short history. J. Basic Clin. Physiol. Pharmacol., 387-406. Yamada, T., Fukatsu, M., Suzuki, S. et al. (2010) Fatty liver predicts impaired fasting glucose and type 2 diabetes mellitus in Japanese undergoing a health checkup. J. Gastroenterol. Hepatol., 352-356. [ABSTRACT FROM AUTHOR]

Focuses on the brisk walking and plasma high density lipoprotein cholesterol concentration in sedentary women in Great Britain. Risk factors of coronary heart disease; Result of mean brisk walking pace; Percentage of predicted maximal oxygen uptake.

Evaluates the relationship between high density lipoprotein (HDL) cholesterol concentration and coronary heart disease in Great Britain. Participation of HDL in reverse cholesterol transport; Benefits of measuring the plasma HDL concentration in the assessment of vascular disease; Ratio of plasma concentration of low density lipoprotein to HDL.

The article presents information on a database developed by the Medical Research Council Laboratory of Molecular Biology in Cambridge in Great Britain. Bacteria rely on protein-lipid combinations known as lipoproteins to glom onto surfaces, sense their surroundings, slurp up nutrients, shuttle DNA to other cells, and perform other life tasks. Researchers can analyze more than 270 of the molecules at Dolop, a database from the Medical Research Council Laboratory of Molecular Biology in Cambridge in Great Britain. Entries describe each protein, indicate its size and function, and provide links to the Swiss-Prot database, where one can parse the molecule's sequence and structural features. The site also explains the synthesis of lipoproteins and describes the lipobox, a characteristic amino acid string to which lipids attach.