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Background: Current lipid guidelines suggest measurement of Lp(a) (lipoprotein[a]) and ApoB (apolipoprotein B) for atherosclerotic cardiovascular disease risk assessment. Polygenic risk scores (PRSs) for Lp(a) and ApoB may identify individuals unlikely to have elevated Lp(a) or ApoB and thus reduce such suggested testing. Methods: PRSs were developed using least absolute shrinkage and selection operator regression among 273 222 and 356 958 UK Biobank participants of white British ancestry for Lp(a) and ApoB, respectively, and validated in separate sets of 60 771 UK Biobank and 15 050 European Prospective Investigation into Cancer and Nutrition-Norfolk participants. We then assessed the proportion of participants who, based on these PRSs, were unlikely to benefit from Lp(a) or ApoB measurements, according to current lipid guidelines. Results: In the UK Biobank and European Prospective Investigation into Cancer and Nutrition-Norfolk cohorts, the area under the receiver operating curve for the PRS-predicted Lp(a) and ApoB to identify individuals with elevated Lp(a) and ApoB was at least 0.91 (95% CI, 0.90–0.92) and 0.74 (95% CI, 0.73–0.75), respectively. The Lp(a) PRS and measured Lp(a) showed comparable association with atherosclerotic cardiovascular disease incidence, whereas the ApoB PRS was in general less predictive of atherosclerotic cardiovascular disease risk than measured ApoB. In the context of the European Society of Cardiology/European Atherosclerosis Society lipid guidelines, at a 95% sensitivity to identify individuals with elevated Lp(a) and ApoB levels, at least 54% of Lp(a) and 24% of ApoB testing could be reduced by prescreening with a PRS while maintaining a low false-negative rate. Conclusions: A substantial proportion of suggested testing for elevated Lp(a) and a modest proportion of testing for elevated ApoB could potentially be reduced by prescreening individuals with PRSs.

Background: Lp(a) (lipoprotein [a]) levels are higher in individuals of African ancestry (AA) than in individuals of European ancestry (EA). We examined associations of genetically predicted Lp(a) levels with (1) atherosclerotic cardiovascular disease subtypes: coronary heart disease, cerebrovascular disease, peripheral artery disease, and abdominal aortic aneurysm and (2) nonatherosclerotic cardiovascular disease phenotypes, stratified by ancestry. Methods: We performed (1) Mendelian randomization analyses for previously reported cardiovascular associations and (2) Mendelian randomization–phenome-wide association analyses for novel associations. Analyses were stratified by ancestry in electronic Medical Records and Genomics, United Kingdom Biobank, and Million Veteran Program cohorts separately and in a combined cohort of 804 507 EA and 103 580 AA participants. Results: In Mendelian randomization analyses using the combined cohort, a 1-SD genetic increase in Lp(a) level was associated with atherosclerotic cardiovascular disease subtypes in EA—odds ratio and 95% CI for coronary heart disease 1.28 (1.16–1.41); cerebrovascular disease 1.14 (1.07–1.21); peripheral artery disease 1.22 (1.11–1.34); abdominal aortic aneurysm 1.28 (1.17–1.40); in AA, the effect estimate was lower than in EA and nonsignificant for coronary heart disease 1.11 (0.99–1.24) and cerebrovascular disease 1.06 (0.99–1.14) but similar for peripheral artery disease 1.16 (1.01–1.33) and abdominal aortic aneurysm 1.34 (1.11–1.62). In EA, a 1-SD genetic increase in Lp(a) level was associated with aortic valve disorders 1.34 (1.10–1.62), mitral valve disorders 1.18 (1.09–1.27), congestive heart failure 1.12 (1.05–1.19), and chronic kidney disease 1.07 (1.01–1.14). In AA, no significant associations were noted for aortic valve disorders 1.08 (0.94–1.25), mitral valve disorders 1.02 (0.89–1.16), congestive heart failure 1.02 (0.95–1.10), or chronic kidney disease 1.05 (0.99–1.12). Mendelian randomization–phenome-wide association analyses identified novel associations in EA with arterial thromboembolic disease, nonaortic aneurysmal disease, atrial fibrillation, cardiac conduction disorders, and hypertension. Conclusions: Many cardiovascular associations of genetically increased Lp(a) that were significant in EA were not significant in AA. Lp(a) was associated with atherosclerotic cardiovascular disease in four major arterial beds in EA but only with peripheral artery disease and abdominal aortic aneurysm in AA. Additionally, novel cardiovascular associations were detected in EA.

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER). Some lipoprotein disorders related to the residual risk of premature cardiovascular disease (PCVD) are not detected by the conventional lipid profile. In this case-control study, the predictive power of PCVD of serum sdLDL-C, measured using a lipoprotein precipitation method, and of the physicochemical properties of serum lipoproteins, analyzed by nuclear magnetic resonance (NMR) techniques, were evaluated. We studied a group of patients with a first PCVD event (n = 125) and a group of control subjects (n = 190). Conventional lipid profile, the size and number of Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipopro-teins (HDL) particles, and the number of particles of their subclasses (large, medium, and small) were measured. Compared to controls, PCVD patients had lower concentrations of all LDL parti-cles, and smaller and larger diameter of LDL and HDL particles, respectively. PCVD patients also showed higher concentrations of small dense LDL-cholesterol (sdLDL), and triglycerides (Tg) in LDL and HDL particles (HDL-Tg), and higher concentrations of large VLDL particles. Multivariate logistic regression showed that sdLDL-C, HDL-Tg, and large concentrations of LDL particles were the most powerful predictors of PCVD. A strong relationship was observed between increased HDL-Tg concentrations and PCVD. This study demonstrates that beyond the conventional lipid profile, PCVD patients have other atherogenic lipoprotein alterations that are detected by magnetic resonance imaging (MRI) analysis.

Objective— Lp(a) [lipoprotein(a)] levels vary by race/ethnicity and were recently found to be associated with risk of heart failure (HF). We aimed to determine whether Lp(a)-related risk of HF is similar across different races and whether Lp(a) may further be related to HF with reduced ejection fraction or HF with preserved ejection fraction (HFpEF). Approach and Results— In 6809 participants of the MESA (Multi-Ethnic Study of Atherosclerosis), aged 45 to 84 years and free of cardiovascular disease, 308 incident HF events occurred during a median 13-year follow-up. Baseline Lp(a) concentrations were determined by immunoassay. Incident HF was adjudicated, distinguishing HF with reduced ejection fraction (ejection fraction, P =0.02); Lp(a) ≥30 mg/dL (HR, 1.69; P =0.01), Lp(a) ≥50 mg/dL (HR, 1.87; P =0.006). No significant relations were found in black, Hispanic, or Chinese participants, and significant race interactions were observed. Lp(a) was additionally related to greater risk of HFpEF in white participants: per log unit Lp(a) (HR, 1.48; P =0.001), Lp(a) ≥30 mg/dL (HR, 2.15; P =0.01), Lp(a) ≥50 mg/dL (HR, 2.60; P =0.004). Lp(a)-related risk of HF and HFpEF in whites was independent of aortic valve disease. Conclusions— In a multiethnic sample, Lp(a)-related risks of HF and HFpEF were only evident in white participants. If confirmed, these findings have implications in further Lp(a) research and clinical practice.

Lipoprotein (a) [Lp(a)] is a lipoprotein defined by presenting a specific apolipoprotein, ApoA, linked to the ApoB-100 by different types of chemical bonds, including a disulfide bridge. Despite their atherogenic mechanism is not fully understood, its importance has been demonstrated in the development of premature aterosclerosis. Multiple studies have shown its role as a cardiovascular risk factor associated with heart disease and stroke. We report the case of a patient with a diagnosis of Takayasu arteritis in which a massive elevation of Lp(a) was detected. We emphasize its diagnostic and therapeutic implications.

Lipoprotein apheresis involves the extracorporeal removal of low-density lipoprotein cholesterol and other atherogenic lipoproteins from the blood. It is a lifesaving treatment for patients with very high low-density lipoprotein levels which cannot be sufficiently lowered by lipid-lowering drugs and diet. However, it is an invasive, repetitive and chronic treatment under taken at fortnightly intervals on an outpatient basis, meaning that patients need considerable commitment to undertake the treatment. The Lipoprotein Apheresis Unit at University Hospital Llandough is one of only eight centres in the UK, and has undertaken patient research to evaluate the service, so that changes can be implemented to ensure the service meets the needs and expectations of patients. The survey showed that patients consider apheresis treatment to be an important and beneficial part of their health care. The majority of patients (68%) reported that their general health had improved since starting lipoprotein apheresis treatment and the other 32% reported that their general health remained the same.

Background: Lipoprotein particle sizes and concentrations are characteristically altered in patients with insulin resistance (IR) or type 2 diabetes mellitus (T2DM). This study assessed the ability of an IR score, based on nuclear magnetic resonance (NMR)-derived lipoprotein information, to detect IR in otherwise healthy individuals.Lipoprotein subclass and size information were evaluated for strength of association with IR, as measured by homeostasis model assessment of insulin resistance (HOMA-IR) in the Multi-Ethnic Study of Atherosclerosis (MESA). To increase the likelihood of identifying subjects with IR, six lipoprotein measures were combined into a single algorithm. The resulting assay [Lipoprotein Insulin Resistance Index (LP-IR)] was developed using HOMA-IR in 4972 nondiabetic subjects from MESA and verified independently using glucose disposal rates (GDRs) measured during hyperinsulinemic-euglycemic clamps in 56 insulin-sensitive, 46 insulin-resistant, and 46 untreated subjects with T2DM.LP-IR exhibited stronger associations with HOMA-IR (r=0.51) and GDR (r=-0.53) than each of the individual lipoprotein parameters as well as the triglycerides/high-density lipoprotein cholesterol (TGs/HDL-C) ratio (r=0.41 and -0.44, respectively). In MESA, associations between the LP-IR score and HOMA-IR were strong in men (r=0.51), women (r=0.52), European Americans (r=0.58), African Americans (r=0.48), Chinese Americans (r=0.49), and Hispanic Americans (r=0.45). When LP-IR was categorized by HOMA-IR and either body mass index (BMI) or fasting plasma glucose (FPG), subgroups were revealed whose LP-IR scores were high (≥ 50), despite having normal BMIs (24 kg/m(2)) or FPG (100 mg/dL).LP-IR scores had strong associations with multiple measures, HOMA-IR, and GDR, the former being more reflective of hepatic and the latter of peripheral insulin sensitivity, and may represent a simple means to identify individuals with IR.

In high-risk patients who are already on a maximal lipid-lowering therapy, a lipoprotein apheresis is an important therapeutic option in preventing further progress of vascular complications as it may decrease both LDL-cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) levels. We looked at the occurrence of cardiovascular events before apheresis and during apheresis in three groups defined by their lipid patterns at the start of an apheresis treatment: Group 1 (LDL-C ≥ 3.4 mmol/l and Lp(a) ≤ 600 mg/l; n = 35), Group 2 (LDL-C ≤ 3.4 mmol/l and Lp(a) ≥ 600 mg/l n = 37) and Group 3 (LDL-C ≥ 3.4 mmol/l and Lp(a) ≥ 600 mg/l; n = 15). Group 2 shows a time period of about 10 years from the first event until the start of apheresis treatment (compared to 2–6 years in the other two groups). Before the start of apheresis treatment 2.1 events per patient had occurred in Group 1, 3.4 events per patient in Group 2 and 1.8 events per patient in Group 3. Under apheresis therapy just 0.9 events per patient occurred in Group 1, 0.5 in Group 2 and 0.5 in Group 3. When comparing the two years before the start of apheresis treatment with the first two years under apheresis we saw the following reduction rates of cardiovascular events: Group 1–54%; Group 2–83%; Group 3–83.5%. Our results show that the reduction of cardiovascular events due to lipoprotein apheresis is especially high in patients with elevated levels of Lp(a) compared to patients with elevated LDL-C only indicating that physicians should be more focused on the risk factor elevated Lp(a).

A very strong association between phenotype Lp(a +) and presence of pre-β1-lipoprotein has been observed in two series of healthy young adults. The data are in agreement with the view that pre-β1-lipoprotein is identical to the lipoprotein carrying the Lp(a) antigen: the Lp(a) lipoprotein. Lp(a) antigen/pre-β1-lipoprotein occurred more frequently in persons with a positive than with a negative family history of coronary heart disease, though this trend was not statistically significant. Occurrence of Lp(a) antigen/pre-β1-rlipoprotein was not correlated with smoking or with the use of contraceptive pills.

Previous studies have shown that a slow-moving pre-beta-lipoprotein fraction, named the pre-beta1-lipoprotein, occurred significantly more frequently among subjects with coronary heart disease (CHD) than among healthy individuals. This lipoprotein is closely related to, and probably identical with, the Lp(a) lipoprotein. Immunological tests likewise showed that Lp(a) lipoprotein was significantly more common among patients with CHD than among controls. Mean cholesterol and triglyceride levels were higher in pre-beta1-lipoprotein positive than in pre-beta1-lipoprotein negative individuals. Lp(a+) individuals tended to have higher serum cholesterol values than did Lp(a-) persons but there was no difference in the mean triglyceride value. This apparent discrepancy seems to be due to the presence in occasional sera of lipoprotein fractions with pre-beta1-mobility, usually of a VLDL nature. These lipoproteins are not associated with the Lp(a) lipoprotein.

A small number of recent studies have reportedly failed to detect the well-established association between a high Lp(a) lipoprotein level and coronary heart disease (CHD). This has made some workers question the importance of a high Lp(a) lipoprotein level as a CHD risk factor. However, serious problems with some of the commercially available test kits, inadequate test techniques or failure to consider the lability of the Lp(a) lipoprotein particle are more plausible explanations of the confounding results. The problems with some of the commercially available test kits include lack of standardization and validation; risk of cross-reactivity with plasminogen or other serum proteins; failure to consider potential problems when measuring samples with varying length of the Lp(a) polypeptide chain (i.e. failure to cope with the isoform variation); non-divulgence of contents of test reagents; and pretreatments of samples that drastically change the Lp(a) lipoprotein particles from their native state. Any test system should be validated at the scientific level before it is assumed to provide correct measurements of Lp(a) lipoprotein level in serum. New test kits should be safely anchored in validation in one of the research laboratories active in the area, before they are put on the market. As new batches are produced, the quality of every new batch of test kits should be monitored on a long-term basis in collaboration with a research laboratory.

The effects of cholesterol on droplet size distribution and rheological properties of cholesterol-reduced egg yolk-stabilized emulsions were determined. Oil-in-water emulsions were prepared by using spray-dried eggs submitted to different levels of cholesterol reduction (14–81 wt% of cholesterol removed). Cholesterol was extracted in a modified Jennings apparatus with subcritical CO2 (9°C and 4.66·106 Pa). Oscillatory and steady flow tests, as well as droplet size distribution measurements, were carried out on the cholesterol-reduced egg yolk-stabilized emulsions. The rheological parameters increased with the level of cholesterol reduction up to 40–80 wt% for emulsions having the same total amount of egg yolk. Opposite results, however, were obtined with some emulsions stabilized by a highly cholesterol-reduced (≈80 wt%) egg yolk. These results were explained by taking into account two opposite phenomena: an increase in the concentration of surface-active agents as cholesterol content decreased, and a lipoprotein structural rearrangement induced by cholesterol removal.

Background: The conformation and assembly of lipoproteins, proteins containing large amounts of noncovalently bound lipid, is poorly understood. Lipoproteins present an unusual challenge as they often contain varying loads of lipid and are not readily crystallized. Lipovitellin is a large crystallizable oocyte protein of approximately 1300 residues that contains about 16% w/w lipid. Lipovitellin contains two large domains that appear to be conserved in both microsomal triglyceride transfer protein and apolipoprotein B-100. To gain insight into the conformation of a lipoprotein and the potential modes of binding of both neutral and phospholipid, the crystal structure of lamprey lipovitellin has been determined. Results: We report here the refined crystal structure of lipovitellin at 2.8 a resolution. The structure contains 1129 amino acid residues located on five peptide chains, one 40-atom phosphatidylcholine, and one 13-atom hydrocarbon chain. The protein contains a funnel-shaped cavity formed primarily by two β sheets and lined predominantly by hydrophobic residues. Conclusions: Using the crystal structure as a template, a model for the bound lipid is proposed. The lipid-binding cavity is formed primarily by a single-thickness β -sheet structure which is stabilized by bound lipid. This cavity appears to be flexible, allowing lipid to be loaded or unloaded.

Summary The genetically determined Lp(a) lipoprotein whose specific apoprotein evolved from plasminogen exhibits association with atherosclerotic/thrombotic diseases including coronary heart disease (CHD). People with an Lp(a) lipoprotein concentration corresponding to the top quartile in the healthy population have a significantly increased CHD risk compared with those with a lower value, and the risk in the top decile appears to be particularly high. However, a very low Lp(a) lipoprotein level may also cause disadvantage with respect to CHD and longevity. Lp(a) lipoprotein may compromise thrombolytic processes through molecular mimicry and in vitro it stimulates vascular cells to cell division. The normal function of Lp(a) lipoprotein is unknown. It could be related to repair processes. Preliminary evidence suggests that Lp(a) lipoprotein may be involved in vascular processes in the placenta. It has been reported that Lp(a) lipoprotein increases following myocardial infarction in a way suggesting that it could possess characteristics of an acute phase reactant. In view of the strikingly high heritability of Lp(a) lipoprotein, this would a priori be unlikely. We have not been able to confirm a significant increase in Lp(a) lipoprotein following myocardial infarction. Several commercially available test kits are of a doudtful quality. At present, a highly needed, international effort at standardizing Lp(a) lipoprotein measurements is taking place.

Two hundred and ninety four pairs of Swedish twins reared apart and twins reared together were used to evaluate the importance of genetic and environmental influences on lipoprotein(a) (Lp(a)) levels. Lp(a) levels ranged from10 mg/l to 926 mg/l with 7.9% of the sample having undetectable Lp(a) levels (i.e.10 mg/l). A substantial genetic component in Lp(a) variation was indicated by a heritability estimate of approximately 90%. No difference in heritability was found across age groups. Quantitative genetic analyses also suggest correlated environmental effects most likely composed of maternal, neonatal and postnatal environmental influences. However, these effects did not reach statistical significance, partly due to a lack of power. Results from analyses of co-twin differences in Lp(a) levels for monozygotic twins indicate that sex hormone use may be of importance for Lp(a) variation in women. There was no evidence of potential influences of alcohol consumption, beta-blocker and diuretic administration on Lp(a) levels in either men or women.

Abstract To determine the facets of lipoprotein metabolism associated with variation in lipoprotein(a) [Lp(a)] density, we examined by density gradient ultracentrifugation 246 plasma samples exhibiting single apo(a) isoform band phenotypes. Estimated molecular weights of apo(a) isoforms ranged from 488 to 874 kD, and they accounted for approximately 80% of variation in Lp(a) density. After adjustment for variation in the protein composition, we found in univariate analyses that variation in residual Lp(a) density was associated with 10 different measures of lipoprotein size and concentration. Residual Lp(a) density was positively correlated with measures of apoB-containing lipoproteins and negatively correlated with measures of HDL. HDL size phenotypes were based on nondenaturing gradient gel electrophoresis fractions after staining for esterified cholesterol with Sudan black B and for apoA-I with immunoblotting methods. The HDL size variables in each case had higher correlations with residual Lp(a) density than did the HDL concentration measures. Stepwise regression analyses selected two lipoprotein variables (LDL density and HDL size) that were significantly correlated with residual Lp(a) density, and they accounted for approximately 35% of variation in density. The densities of LDL and Lp(a) were highly correlated, and additional stepwise regression analyses showed that they were similarly correlated with triglyceride concentration and with a measure of HDL size. Thus, with respect to residual Lp(a) density, the results show that small, dense Lp(a) particles are found under conditions leading also to small, dense LDL particles and to small, dense HDLs.

The serum levels of Lp(a) lipoprotein (Lp(a)) were determined preoperatively in 601 patients with coronary artery disease, undergoing bypass operations. Compared with a reference group of 99 apparently healthy individuals, the Lp(a) levels were higher in the patient group (7.7 mg dl-1 vs. 5.1 mg dl-1, p = 0.012). In the patient group, there was a weak, but significant negative correlation between the Lp(a) levels and age (r = -0.10, p = 0.017), and in both groups the women had higher Lp(a) levels than the men. In the patients we found no significant correlations between Lp(a) and other serum lipids or lipoproteins, nor between Lp(a) and variables in the fibrinolytic system. We investigated the long-term effects of supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) on the Lp(a) concentrations. Postoperatively, in a randomized fashion, 280 of the patients received 4 g of an n-3 PUFA concentrate (containing85% of long-chain n-3 PUFAs) per day, whereas 269 patients comprised the control group. The fatty acids in serum phospholipids were monitored, and a significant increase in the phospholipid n-3 fatty acids was noted in the n-3 PUFA group, as opposed to the virtually unchanged amounts in the control group. The Lp(a) levels were determined again after 6 months, and, compared with the control group, n-3 PUFA supplementation had no overall effect on the serum Lp(a) levels.

The study of lipoproteins, natural nanoparticles comprised of lipids and apolipoproteins that transport fats throughout the body, is of key importance to better understand, treat, and prevent cardiovascular disease. In the current study, we have developed a lipoprotein-based nanoparticle that consists of a quantum dot (QD) core and Cy5.5 labeled lipidic coating. The methodology allows judicious tuning of the QD/Cy5.5 ratio, which enabled us to optimize Förster resonance energy transfer (FRET) between the QD core and the Cy5.5-labeled coating. This phenomenon allowed us to study lipoprotein-lipoprotein interactions, lipid exchange dynamics, and the influence of apolipoproteins on these processes. Moreover, we were able to study HDL-cell interactions and exploit FRET to visualize HDL association with live macrophage cells

In a 3-year follow-up study of 761 elderly men and 983 elderly women, total plasma cholesterol levels predicted fatal coronary heart disease (CHD) in men but not women. Low-density lipoprotein level was no better a predictor of fatal CHD than total cholesterol in either sex. Women had higher levels of high-density lipoprotein than men, which explains most of their usual higher total cholesterol levels. These data suggest that cholesterol screening of elderly women would have little value without a lipoprotein evaluation.

We thank Dr Ala-Korpela and colleagues for their interest and their thoughtful comments on our study.1 We agree that different uses may be made of the nuclear magnetic resonance (NMR) spectroscopy signals that arise from the lipids carried in plasma by lipoprotein subclass particles of varying size. In our study, subclass signal amplitudes were converted to particle concentrations using calculations that account for the amount of lipid that fits into a lipoprotein particle …

Serum lipoprotein(a) [Lp(a)] was determined in 205 patients (71 ± 10 years; mean age ± SD) with acute stroke and in 204 nonhospitalized referent subjects in the 60- to 80-year age range. Lp(a) levels

Recently, Hashimoto et al. ([1][1]) reported that lipoteichoic acid (LTA) extracted from a lipoprotein diacylglycerol transferase deletion (Δ lgt ) mutant of Staphylococcus aureus is immunologically inactive and concluded that the activity of LTA preparations generally lies in lipoprotein

In this article, we demonstrate the analytical power of linking density gradient ultracentrifugation with affinity separations. Here we address some of the analytical challenges in the study of lipoprotein(a), (Lp(a)). The mean density distribution of Lp(a) was determined by a differential density lipoprotein profile (DDLP). For DDLP, the lipoprotein density distribution of a serum sample with elevated Lp(a) levels was determined by ultracentrifugation using a BiEDTA complex as a density gradient. Lp(a) was removed from a second aliquot of the same serum sample by carbohydrate affinity using wheat germ agglutinin (WGA). WGA was demonstrated to have high specificity for Lp(a) in a serum sample. This sample was ultracentrifuged to obtain a lipoprotein density distribution in the absence of Lp(a). A DDLP was obtained after subtracting the Lp(a)-depleted lipoprotein density profile from the untreated lipoprotein density profile. The DDLP methodology reported herein gives relevant information of the lipoproteins in serum such as density, isoform, and subclass characteristics. Lp(a) was quantitatively isolated from serum with a recovery efficiency of 82%. Lp(a) was purified by ultracentrifugation. Lp(a) retained its inherent density (1.086 g/mL) and immunoreactivity. The major outcome of this research was the effectiveness of using affinity separations coupled with density ultracentrifugation for the isolation of pure Lp(a) from serum and its isoform characterization based on density by DDLP.

Objective to evaluate the association between Lp(a) lipoprotein levels, other serum lipids and the presence of lower limb atherosclerotic occlusive disease. Materials and methods angiographic findings in 36 patients were related to serum Lp(a). Total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol and Lp(a) levels were compared with those of 73 age- and sex-matched healthy controls. Results atheromatous lesions were localised in the femoropopliteal (≈60%) and aortoiliac (≈40%) segments. The number of stenosed arteries was ≥2 and the range of stenosis severity was between 40% and 100%. There was a significant increase in serum Lp(a) ( p = 0.000001) and a decrease in serum HDL ( p = 0.000009) levels in patients compared to controls. No difference was observed in total cholesterol, LDL-cholesterol or triglyceride. However, the ratio of total cholesterol/HDL-cholesterol was significantly higher ( p = 0.005) in patients. Conclusion a dyslipidaemic serum profile, characterised by increased Lp(a) levels and decreased HDL-cholesterol levels, is associated with atherosclerotic occlusive disease of the lower extremities.

This is the third year of competition for ATVB New Investigator Awards. The Awards recognize papers published in ATVB in 2007 that were submitted by new investigators and judged to be the most outstanding in the Atherosclerosis/Lipoprotein, Thrombosis, and Vascular Biology sections of the journal. The three awards are named for Dr Daniel Steinberg, who devised a method to determine the site of degradation of the proteins and lipids of a lipoprotein, which led to the concept of selective uptake of cholesterol and apoprotein that characterizes the reverse cholesterol transport pathway; Dr …

Cultured hepatocytes of silver eel actively secreted only chylomicron-like lipoprotein. The rate of secretion per mg cellular protein per 24 hr was 2.2 times higher compared with that by yellow eel hepatocytes. Silver eel hepatocytes secreted lipids 2.5 times higher through the lipoprotein than yellow eel hepatocytes. Main lipid was triacylglycerol in either secreted lipoprotein and composition of apolipoproteins of both secreted lipoproteins was the same. The incorporation of 3H-leucine into the lipoprotein secreted by silver eel hepatocytes was 2.4 times higher, but that of 14C-acetate was not significantly different. Protein and lipids composition of plasma lipoproteins of silver eel was significantly higher and lower compared with those of yellow eel, respectively. We suggest that the secreted lipoprotein of silver eel hepatocytes transport much more lipids to other tissues than that of yellow eel hepatocytes.

Publisher Summary Lipoprotein (Lp) [a] is a lipoprotein whose plasma concentration is highly correlated with cardiovascular disease. Electrophoretic methods have been used widely for many years for qualitative detection and quantitative measurement of plasma lipoproteins, especially Lp[a]. The movement of a lipoprotein or apoprotein in an electrophoretic field is determined by several physiochemical properties, such as charge, size, shape, and composition. When electrophoretic migration is used with immunochemical reaction, the combined properties can be used for positive identification of specific migrating species. However, migration and immunoreactivity may be significantly altered by variations in specific structural features. In case of apolipoprotein (apo) [a], variations in the number of kringle repeats, carbohydrate content, and disulfide pairing can have profound effects. For Lp[a], lipid content and association with other apoB-containing lipoproreins can be important determinants of migratory and immunoreactive behavior. In this chapter, the topic of electrophoretic methods for quantification has been expanded beyond concentration determination to include other properties of apo[a] or Lp[a] amenable to measurement. These include apo[a] polymorph classification and phenotyping for individual and population analyses, molecular weight (Mr) determination of apo[a] polymorphs, and calculation of relative electrophoretic mobility. Investigations that combine various aspects of these analytical electrophoretic methods expand the opportunities for assessing structure and function relationships. Some of the features of apo[a] and Lp[a] and how these impact on the determinations are briefly discussed in this chapter.

In the present work we have tested a new immunoturbidometric (IT) lipoprotein(a) (Lp(a)) assay and compared it with two other Lp(a) assay systems (IRMA and ELISA) commonly used in clinical chemistry laboratories. In addition, we have examined the effects of long-term storage and plasminogen on the results of Lp(a). Intra-assay and inter-assay coefficients of variation of the IT method were from 1.6 to 5.5% and from 2.8 to 10.7% depending on the concentration of Lp(a). The correlations between methods were 0.957 (IRMA vs. IT), 0.969 (IRMA vs. ELISA) and 0.956 (IT vs. ELISA) and the regression curves were IRMA = 1.07*IT + 11, IRMA = 1.84*ELISA + 2 and IT = 1.62*ELISA + 17, respectively. Storage of the samples for 5 years at -70 degrees C did not affect serum Lp(a) levels. There was a slight increasing effect of high concentrations of plasminogen on the Lp(a) results, but on physiological serum levels of plasminogen the effect was not significant. We conclude that the IT method provides a simple way to screen serum Lp(a) levels.

In persons who are fasting, lipids circulate in the plasma as constituents of lipoprotein particles that are defined on the basis of their density as very-low-, intermediate-, low-, and high-densit...

As part of a longitudinal study--the Kristianstad Survey--we measured plasma cholesterol, HDL- and LDL-cholesterol, triglycerides and lipoprotein (a) in a reference group consisting of 203 men and women aged 20-80, randomly sampled from a well-defined area in the southernmost part of Sweden. The selection of reference individuals and the collection of specimens for assay of the constituents were performed in accordance with current recommendations. The results were subjected to statistical analyses both with and without application of exclusion criteria. Application of the theoretical exclusion criteria resulted in the exclusion of 22% of the participants; however, this procedure had a remarkably weak impact on the results: the mean values and the standard deviations were almost unaltered. The mean (standard deviation) for cholesterol was 5.9 (1.3) mmol l-1, for HDL-C 1.1 (0.3) mmol l-1, and for LDL-C 4.3 (1.2) mmol l-1. Women had higher values than men. Plasma triglycerides were positively skewed; their median and Q3-Q1-values were 1.0 and 0.5 mmol l-1 respectively, men higher than women. There was an increase with age for cholesterol and LDL-C in both sexes and for triglycerides in women. The steepest increase of cholesterol values with age in women coincided with menopause, which have a more clear-cut separation between high and low cholesterol values than did any age limit.

The Lp(a) lipoprotein, a distinct class of serum lipoproteins, was detected in 1962. It consists of an LDL particle to which a long polypeptide chain is attached by a disulfide bridge. The level of Lp(a) lipoprotein is genetically determined. Single locus control was suggested already in the very first report, and this has been conclusively confirmed by the demonstration of absolute genetic linkage to the plasminogen gene, from which the LPA gene is likely to have evolved. The detection in 1974 of an association between Lp(a) lipoprotein and coronary heart disease has been confirmed in numerous studies. The Lp(a) lipoprotein may have atherogenic as well as thrombogenic properties and thus form the bridge between atherogenesis and thrombogenesis. Genes determining a moderate level of Lp(a) lipoprotein may be longevity genes, and it seems possible that Lp(a) lipoprotein, because of its affinity to vessel walls, may also influence placental function. Lp(a) lipoprotein measurements should be included in the diagnostic work-up of people with premature coronary heart disease or with such disease in close relatives.

The development of a method to mask bitter taste is required in the fields of food and pharmaceutical sciences, and would be welcomed in the field of receptor physiology. A specific inhibitor for bitter taste would be most useful for this purpose, but, thus for, no such inhibitor has been available. In this study, we found that a lipoprotein, PA-LG, made of phosphatidic acid (PA) and β-lactoglobulin (LG) completely suppressed taste responses in the frog and taste sensation in humans to all bitter substances examined, without affecting responses to other taste stimuli [1]. Both PA and LG originate from foods, being prepared from soybeans and milk, respectively. Hence PA-LG can be safely used to mask bitter taste in foods and drugs.

The Lp(a) lipoprotein1 is a distinct class of serum lipoprotein particles which was detected because of its immunological properties. It consists of a low density lipoprotein (LDL) particle to which a long polypeptide chain has been attached (the Lp(a) polypeptide chain, the Lp(a) apolipoprotein or apolipoprotein(a)). It is the Lp(a) polypeptide chain that confers the unique antigenic properties to the Lp(a) lipoprotein particle.

SUMMARY The interest in Lp(a) lipoprotein [Lp(a)] has increased dramatically during the last few years due to the documented strong association between high Lp(a) levels and early atherosclerosis and its sequelae and the probable additional thrombogenic effect of inherited high Lp(a) levels. However, some paradoxes still remain to be solved in Lp(a) research. This pilot study was performed to test whether some criteria could be found for an association between Lp(a) levels, HLA genotype, and early coronary heart disease. If so, it could help to explain why some individuals with high Lp(a) levels get atherosclerosis while others with comparable lipid levels do not. It would also indicate that immunological processes could be involved in Lp(a) associated atherosclerosis. In this case-control study the HLA-DR genotypes 13 or 17 were significantly more frequently encountered in 30 male patients with early coronary heart disease than in 30 sex and age matched healthy controls (P = 0.012). These HLA-DR specificities were especially frequent in male patients with high Lp(a) levels. The same HLA-DR genotype pattern was not seen in 30 female patients, although there was a trend towards more frequent 13a genotype.

Lipoprotein(a), or Lp(a), is a lipoprotein having lipid composition similar to that of LDL, but a protein moiety consisting of ApoB 100 linked by disulfide bridge to apo(a), a glycoprotein with structural similarity to plasminogen. Lp(a) can be both atherogenic and thrombogenic. These two actions are likely to be mutually operative, a fact that on a molar basis makes Lp(a) more of a cardiovascular pathogen than LDL.

Lipoprotein [a] or Lp [a] represents a class of lipoprotein particles associated with an increased prevalence of atherosclerotic cardiovascular disease (ASGVD) (Utermann 1989; Scanu and Fless 1990; Berg 1990). At this time this notion rests predominantly on epidemiological data although emerging experimental evidence is now permitting to formulate hypotheses on the possible mechanism(s) of this pathogenicity. This experimental evidence will be reviewed and correlated with the current understanding of the structural properties of Lp[a].

Sixty years ago Michel Macheboeuf published his Doctor of Science Thesis and a year later his first paper on the isolation of a lipoprotein from horse serum. His outstanding studies1 showed for the first time that a lipoprotein of constant composition was obtained by repeated precipitation from an aqueous solution. Shortly after Macheboeuf’s work appeared, Sorensen2 questioned whether isolated lipoproteins truly represented the molecular complexes found in serum. Sorensen was most concerned with the association and dissociation of solutes during lipoprotein isolation but his paper, as Chargaff3 has noted, identified the problem of true lipoprotein composition in vivo. Some twenty years later, Oncley and Gurd4 reported that isolated serum low density lipoproteins (LDL) were highly unstable complexes readily susceptible to chemical modification by processes such as oxidation (LDLOXID). Lipoprotein instability raised again the question first posed by Sorensen that purified lipoproteins might be significantly different from native lipoproteins.

This is the second year of competition for ATVB New Investigator Awards. The Awards recognize papers published in ATVB in 2006 that were submitted by new investigators and judged to be the most outstanding in the Atherosclerosis/Lipoprotein, Thrombosis, and Vascular Biology sections of the journal. The three awards are named for Dr Daniel Steinberg, who devised a method to determine the site of degradation of the proteins and lipids of a lipoprotein, which …

As compared with what is known about predictors of vascular events in middle-aged persons, less is known about these events in the elderly. Lp(a) lipoprotein, which plays an important part in atherothrombogenesis, has been associated with an increased risk of vascular disease. We investigated this relation among older U.S. adults.In a prospective study of 5888 community-dwelling older adults (65 years of age or older) in the United States, 2375 women and 1597 men who were free of vascular disease provided base-line serum samples for analysis for levels of Lp(a) lipoprotein. These 3972 subjects were followed for a median of 7.4 years to evaluate the development of stroke and to track deaths from vascular causes and all causes. The men and women were divided into quintile groups according to the Lp(a) lipoprotein level at base line.Using Cox proportional-hazards models, we determined the risk associated with each quintile level of Lp(a) lipoprotein, with the lowest quintile serving as the reference group. As compared with those in the lowest quintile, men in the highest quintile had three times the unadjusted risk of stroke (relative risk, 3.00; 95 percent confidence interval, 1.59 to 5.65), almost three times the risk of death associated with vascular events (relative risk, 2.54; 95 percent confidence interval, 1.59 to 4.08), and nearly twice the risk of death from all causes (relative risk, 1.76; 95 percent confidence interval, 1.31 to 2.36). Adjustment for age; sex; the levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides; carotid-wall thickness; smoking status; the presence or absence of diabetes and systolic and diastolic hypertension; body-mass index; and other traditional risk factors had little effect on the final assessments. Similar analyses for women, which also included adjustment for estrogen use or nonuse, revealed no such relation.Among older adults in the United States, an elevated level of Lp(a) lipoprotein is an independent predictor of stroke, death from vascular disease, and death from any cause in men but not in women. These data support the use of Lp(a) lipoprotein levels in predicting the risk of these events in older men.

Evidence supports the involvement of 2 common dyslipidemias-low high-density lipoprotein disorders and Lp(a) lipoprotein excess—in coronary heart disease. Until clinical trials determine whether specific therapeutic interventions can prevent the occurrence and recurrence of coronary heart disease in patients with these dyslipidemias, the implementation of cholesterol-lowering guidelines can provide a reasonable way to manage low highdensity lipoprotein disorders and to identify specific categories of patients who may be at particularly high risk for premature coronary heart disease. Empiric treatment guidelines are suggested for low high-density lipoprotein disorders and Lp(a) lipoprotein excess in order to foster further discussion and validation by clinical trial data. (Arch Intern Med. 1996;156:1278-1284)

To the Editor. —The results of clinical studies correlating lipoprotein levels with risk for thrombotic events like myocardial infarction are inconsistent and not sensitive indicators of risk. 1 One may assume that these thrombotic events are causally related to hypercoagulability and that protection from these events is associated with relative hypocoagulability. Regrettably, there is no coagulation test to detect a prothrombotic (high-risk) state or antithrombotic (low-risk) state as a marker of the effects of lipoproteins. We here describe the utilization of a modified recalcification time (MRT) test to document the adverse coagulation-accelerating effect of low-density lipoproteins (LDLs) and the beneficial coagulation-retarding property of high-density lipoproteins (HDLs). This test was described in detail in a recent article. 2 Unlike other tests, by using whole blood, the MRT incorporates the role of both cellular and chemical participants in coagulation. Also, incubating blood with an activator like a lipoprotein induces the monocyte to

EDITOR, - M Farrer and colleagues recently investigated the association between impaired glucose tolerance and Lp(a) lipoprotein concentration in relation to coronary artery disease.1 Although the subject was reasonable to investigate, we were disturbed by the statistical methods they used and by the conclusions they drew. In particular, the study design did not directly address the specific objectiveof assessing the relation …

Objective: Lp(a) lipoprotein is a distinct lipoprotein particle that recently has been found to be associated with cardiovascular disease. A study was conducted to assess the influence of cardiovascular disease risk factors on levels of Lp(a) and to evaluate the effects of age, exercise, and estrogen on these levels. Study Design: Two studies, a cross-sectional study of older men ( n = 105) and women ( n = 75) (mean age 76 years) and a prospective study of younger postmenopausal women (mean age 48 years), were carried out. Lp(a) and other lipoproteins were measured in the two studies and differences were sought by statistical analysis. Results: In the cross-sectional study, serum Lp(a) was similar in men and women and was not influenced by age. Lp(a) levels in men and women were higher when there was more than one cardiovascular disease risk factor present ( p p = 0.08). The decrease in Lp(a) with oral estrogen was associated with increases in triglycerides ( p p Conclusion: These data confirm that elevated Lp(a) levels are an independent risk factor for cardiovascular disease. Lp(a) levels are primarily influenced by genetic factors and it appears estrogen may have a minor influence on its hepatic synthesis.

The sedimentation at low speed centrifugation of a lipoprotein recombined from the lipids, and the strongly bound proteins of the human erythrocyte membrane depends on pH : between 4.5 and 6.0, most of the liproprotein sediments, whereas at pH 7.0 - 8.5, up to 90% remains in the supernatant. Precipitation of the lipoprotein can be reversed by increasing the pH, followed by a brief sonication. The mobility of spin-labelled protein groups in the lipoprotein increases with increasing pH. This mobility increase is also reversible and is of equal magnitude in precipitated and nonprecipitated recombinates. It is concluded that, because of these reversibilities, determination of the yield of liproprotein formation in recombination experiments must include analysis of both precipitated and nonprecipitated lipoproteins.

1. 1. Lipoproteins staining with Sudan Black were isolated from the haemolymph of several desert arthropods. 2. 2. Millipedes and centipedes possess a lipoprotein structurally similar to insect lipophorin. 3. 3. Isopods utilize a different lipoprotein which is closely related to that of marine crustaceans. 4. 4. The haemolymph of most arachnids however contains lipophorin-like lipoproteins. 5. 5. With the exception of Crustacea, lipophorins seem to be universal throughout the phylum Arthropoda.

A method is described for the chromatographic separation of mixtures of egg-yolk proteins of low solubility by using a hydrophobic column (phenyl-Sepharose) and eluting with increasing concentrations of aqueous urea at low pH. The resolving power of the method was established by tests on proteins and protein fragments of known sequence. The theoretical basis for the method remains, however, unclear. Factors such as the aggregation of the protein often appeared to be more important than its hydrophobicity in determining the urea concentration needed for elution. The method was applied to the mixture of apoproteins from the low-density lipoprotein (density about 0.95 g/ml) of avian egg yolk. For the previously studied apoproteins from egg yolk of the hen (Gallus domesticus), hydrophobic chromatography provided a new and convenient method for isolating the main apoproteins (hen apovitellenins I-VI). For the hitherto unexplored apoproteins from egg yolk of the duck (Anas platyrhynchos) the method has now been used to isolate three new proteins, two of which were not readily separated by methods based on molecular size. The elution pattern obtained with duck egg-yolk apoproteins is not the same as that of the hen egg-yolk apoproteins, although we suggest a relationship for the three new apoproteins based on their amino acid compositions and other properties. Possible roles for the apoproteins in avian egg yolk are described.

Lp(a) lipoprotein is thought to be an addi- tional risk factor for coronary heart disease [l-3]. Papers published up to now have been concerned with its electrophoretical mobility [4,5], its chemical com- position [6,7] and its physiological role [l-3]. Con- cerning the size of the particle, only disagreeing information has been reported [8]. Serum concentra- tion of that lipoprotein differs from man to man, and Harvie and Schultz were the first to demonstrate that Lp(a) is expressed by a quantitative genetic trait [9,10]. A diet enriched by cholesterol did not influence the serum Lp(a) level, while LDL increased markedly [11,12]. As pointed out [13,14] Lp(a) reacts very sensitively on addition of Ca2+. The aim of this work was to provide for this lipo- protein the values for molecular weight (a,) diffu- sion coefficient (D), radius of gyration Cs;) and hydrodynamic radius

The amylose precipitating factor from Neurospora is a lipoprotein of 53,800 mw. The lipid component, which is responsible for the amylose precipitating activity, is mainly polar lipid and constitutes 14.5% of the lipoprotein molecule. The binding of amylose to the amylose precipitating factor possibly results in the conversion of the amylose molecule from a random coil to an interrupted helix configuration.