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The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol (=total - HDL cholesterol) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDL cholesterol is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDL cholesterol shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a)-cholesterol is part of measured or calculated LDL cholesterol and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDL cholesterol decline poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDL cholesterol or apolipoprotein B, especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). Non-HDL cholesterol includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apolipoprotein B measurement can detect elevated LDL particle numbers often unidentified on the basis of LDL cholesterol alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20-100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Complications of atherosclerosis are the most common cause of death in Western societies. Among the many risk factors identified by epidemiological studies, only elevated levels of lipoproteins containing apolipoprotein (apo) B can drive the development of atherosclerosis in humans and experimental animals even in the absence of other risk factors. However, the mechanisms that lead to atherosclerosis are still poorly understood. We tested the hypothesis that the subendothelial retention of atherogenic apoB-containing lipoproteins is the initiating event in atherogenesis. The extracellular matrix of the subendothelium, particularly proteoglycans, is thought to play a major role in the retention of atherogenic lipoproteins. The interaction between atherogenic lipoproteins and proteoglycans involves an ionic interaction between basic amino acids in apoB100 and negatively charged sulphate groups on the proteoglycans. Here we present direct experimental evidence that the atherogenicity of apoB-containing low-density lipoproteins (LDL) is linked to their affinity for artery wall proteoglycans. Mice expressing proteoglycan-binding-defective LDL developed significantly less atherosclerosis than mice expressing wild-type control LDL. We conclude that subendothelial retention of apoB100-containing lipoprotein is an early step in atherogenesis.

Abdominal/visceral obesity is associated with blunted growth hormone (GH) secretion and an unfavourable lipoprotein pattern. In this study, the effect of GH treatment on LDL size and on serum lipoprotein concentrations was determined in abdominally obese men. Thirty men, aged 48-66 years, with a body mass index (BMI) of 25-35 kg/m(2)and a waist:hip ratio of >0.95, received treatment with GH (9. 5 microg/kg/day) or placebo for 9 months. Serum concentrations of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) were reduced (P<0.05, P<0.05 and P<0.001 vs placebo, respectively). Serum lipoprotein(a) [Lp(a)] concentration increased (P<0.05 vs. placebo). Mean low density lipoprotein (LDL) particle diameter was marginally increased by active treatment as compared with placebo (P =0.08). No changes were observed in the serum concentrations of high density lipoprotein-cholesterol (HDL-C), apolipoprotein A-I (apoA-I) and apolipoprotein E (apoE). In conclusion, 9 months of GH treatment in abdominally obese men beneficially reduced serum concentrations of TC, LDL-C and apoB, and marginally increased mean LDL diameter, while serum Lp(a) increased. The ultimate effect of GH therapy on the cardiovascular risk remains, however, to be determined., (Copyright 2000 Harcourt Publishers Ltd.)

Obesity is associated with blunted GH secretion and an unfavorable lipoprotein pattern. The objective of this study was to investigate the effects of treatment with the oral GH secretagogue MK-677 on lipoproteins in otherwise healthy obese males. The study was randomized, double blind, and parallel. Twenty-four obese males, aged 18-50 yr, with body mass index greater than 30 kg/m2 and waist/hip ratio above 0.95 were treated with 25 mg MK-677 (n = 12) or placebo (n = 12) daily for 8 weeks. MK-677 treatment did not significantly change serum lipoprotein(a) [Lp(a)] levels. Serum apolipoprotein A-I and E (apoA-I and apoE) were increased at 2 weeks (P < 0.001 and P < 0.01 vs. placebo, respectively), but were not changed at study end. Serum total cholesterol and low density lipoprotein (LDL) cholesterol (LDL-C) levels were not significantly changed by MK-677 treatment. Serum high density lipoprotein (HDL) cholesterol (HDL-C) was increased at 2 weeks of MK-677 treatment (P < 0.01 vs. placebo), but not at 8 weeks. The LDL-C/HDL-C ratio was reduced after 8 weeks of MK-677 treatment (P < 0.05 vs. placebo). Mean LDL particle diameter was decreased at 2 weeks (P < 0.05 vs. placebo), but was unchanged compared with baseline values at 8 weeks (P = NS vs. placebo). The level of serum triglycerides was increased at 2 (P < 0.05 vs. placebo), but not at 8, weeks. Lipoprotein lipase activity in abdominal and gluteal sc adipose tissue was not affected by active treatment. In conclusion, treatment with the oral GH secretagogue MK-677 affected circulating lipoproteins. The effects on serum apoA-1, apoE, triglycerides, and mean LDL particle diameter were transient. At study end, the LDL-C/HDL-C ratio was decreased. MK-677 treatment did not significantly affect serum Lp(a) concentrations at the present dose and administration protocol.

Retention of apo B-100 lipoproteins, low density lipoprotein (LDL) and probably lipoprotein(a), Lp(a), by intima proteoglycans (PGs) appears to increase the residence time needed for their structural, hydrolytic and oxidative modifications. If the rate of LDL entry exceeds the tissue capacity to eliminate the modified products, this process may be a contributor to atherogenesis and lesion advancement. LDL binds to PGs of the intima, by association of specific positive segments of the apo B-100 with the negatively-charged glycosaminoglycans (GAGs) made of chondroitin sulfate (CS), dermatan sulfate (DS) and probably heparan sulfate (HS). Small, dense LDL has a higher affinity for CS-PGs than large buoyant particles, probably because they expose more of the segments binding the GAGs than larger LDL. PGs cause irreversible structural alterations of LDL that potentiate hydrolytic and oxidative modifications. These alterations also increase LDL uptake by macrophages and smooth muscle cells. These in vitro data suggest that part of the atherogenicity of LDL may depend on its tendency to form complexes with arterial PGs in vivo. Ex vivo results support this hypothesis. Subjects with coronary heart disease have LDL with significantly higher affinity for arterial PGs. This is also a characteristic of subjects with the atherogenic lipoprotein phenotype, with high levels of small, dense LDL. The LDL-PG affinity, however can be modified by dietary or pharmacological interventions that change the composition and size of LDL. Lesion-prone intima contain PGs with a high affinity for LDL. Increased LDL entrapment at these sites may be a key step in a cyclic atherogenic process.

The insulin-dependent diabetic patient is at greatly increased risk of premature atherosclerosis. Oxidative damage to lipoproteins has been implicated as an important factor in the atherogenic process. Diabetic patients are exposed to excessive oxidative stress because of non-enzymatic glycation of proteins and a variety of defects in antioxidant systems. We have previously described an enhanced chemiluminescent method for measuring protective 'chain-breaking' antioxidant activity in plasma lipoprotein fractions. In this study we compare the lipid content and antioxidant activity of plasma lipoproteins in 22 young insulin-dependent diabetics without vascular complications and 20 age- and sex-matched controls. Mean levels of haemoglobin A 1c in the diabetic group were 8.8 +/- 0.2%. There were no significant differences in serum total cholesterol, apolipoprotein A, apolipoprotein B or lipoprotein(a) levels between the study groups. Serum total triglyceride levels (1.32 +/- 0.11 versus 1.01 +/- 0.08 mmol/l; P < 0.05) and LDL-associated triglyceride (0.28 +/- 0.04 versus 0.15 +/- 0.02 mmol/l; P < 0.05) were significantly elevated in the diabetic group. Total plasma antioxidant activity was significantly reduced in the diabetic group (272.0 +/- 15.4 versus 338.3 +/- 20.7 micromol/l; P < 0.05). Antioxidant activity measured in five lipoprotein fractions isolated by density gradient ultracentrifugation (VLDL1. VLDL2, LDL1, LDL2 and HDL) showed no significant differences between groups when corrected for protein, total lipid or cholesterol content. When corrected for triglyceride content significantly lower antioxidant values were found in the diabetic HDL fraction only. The results of this study imply that the susceptibility of the insulin-dependent diabetic to the development of premature atherosclerosis cannot be attributed to reduced antioxidant activity in circulating plasma lipoproteins.

A large proportion of a dense subfraction of LDL in plasma is coupled with an increased risk of coronary artery disease, CAD. This may reflect an increased inflow of such LDL subfractions into the intima, since the inflow of lipoproteins is supposed to be inversely related to the size of the particles. In order to evaluate this possibility we used an in vitro perfusion system for aortic intima-media from rabbits with experimental atherosclerosis. The uptake of human VLDL, LDL, HDL and subfractions of LDL (LDL1, 1.019-1.035 and LDL2, 1.035-1.063 g/ml) in lesions and non-involved areas was studied. Our results indicate that particle size is an important factor for the clearance of lipoproteins into the arterial tissue, both for plaques (VLDL 7.6, LDL 25, HDL 58 nl/mg wet wt./h) and in other areas (VLDL 3.8, LDL 4.1, HDL 12 nl/mg wet wt./h). Interestingly, the uptake of LDL2 was as much as 1.5-1.9 times higher than LDL1. This supports the view that an increased lipid load in the arterial wall may be one mechanism behind the association between denser LDL and CAD. Our data also suggest that the difference between LDL uptake in plaque (576 nl/mg wet wt.) and other areas (48 nl/mg wet wt.) not only reflects a rapid clearance but a large distribution volume of the intima (plaque > 60%, non-involved areas 5.7%).

Recombinant human growth hormone (GH) administered as daily subcutaneous (SC) injections has been shown to affect serum lipoproteins in GH-deficient subjects. However, the effects of continuous infusion of GH on serum lipoproteins have not been investigated in GH-deficient adults. The aim of the present study was to compare effects of daily injections and continuous infusion of GH on lipoprotein metabolism. Recombinant human GH (0.25 U/kg/wk) was administered to nine GH-deficient adult men during a period of 14 days in two different ways, ie, as a daily SC injection at 8:00 PM and as a continuous SC infusion, with 1 month of washout between the treatments. Blood samples and tests were performed in the morning after an overnight fast before the start of GH treatment (day 0) and on day 2 and day 14 of treatment. Abdominal SC adipose tissue lipoprotein lipase (LPL), postheparin plasma LPL, and hepatic lipase (HL) activity were measured 120 minutes after the intake of 100 g glucose. Adipose tissue LPL activity decreased and postheparin plasma HL activity increased after 14 days of GH treatment irrespective of the mode of GH administration, whereas GH treatment had no effect on postheparin plasma LPL activity. Serum triglyceride and very-low-density lipoprotein (VLDL) triglyceride concentrations increased during GH treatment. However, VLDL triglyceride concentrations increased to a greater degree during treatment with daily GH injections than during continuous infusion of GH. Serum apolipoprotein (apo) B and low-density lipoprotein (LDL) cholesterol concentrations decreased during treatment with daily GH injections, but were not significantly affected by continuous GH infusion. Thus, apo B and LDL cholesterol concentrations were lower after daily GH injections versus continuous GH infusion. Serum lipoprotein(a) [Lp(a)] and apo E concentrations increased during both modes of GH treatment. However, continuous infusion of GH resulted in a more marked increase in Lp(a) and apo E concentrations than daily GH injections. Minor effects were observed on serum apo A-I concentrations but high-density lipoprotein (HDL) cholesterol concentrations were not affected. In conclusion, GH treatment of GH-deficient men influenced adipose tissue LPL and postheparin plasma HL activity, as well as serum lipoprotein concentrations. Moreover, continuous GH infusion and daily GH injections differed with respect to the magnitude of effects on several lipoprotein fractions including VLDL triglycerides, LDL cholesterol, apo B, apo E, and Lp(a) concentrations.

We investigated the influence of gender and apoE and apo(a) phenotypes as well as the effect of the metabolic effects of growth hormone (GH) on the effect of GH therapy on serum lipoprotein concentrations in GH-deficient (GHD) adults. Forty-four consecutive patients, 30 men and 14 women aged 46.5 (range, 19 to 76) years with GHD due mainly to pituitary tumors, were treated with recombinant human GH for 12 months. Serum concentrations of lipoproteins, insulin, thyroxine, and insulin-like growth factor-I were determined, body composition was assessed by bioelectrical impedance, and apo(a) and apoE phenotypes were analyzed. Lipoprotein(a) [Lp(a)] concentrations in the GHD subjects were compared with a gender- and apo(a) phenotype-matched control group. After 12 months of GH treatment, the total cholesterol, LDL cholesterol, and apoB concentrations decreased, the HDL cholesterol and apoE concentrations increased, and the apoA-I and triglyceride concentrations were unchanged. Before treatment, the Lp(a) concentration was similar to that in the control group. However, after 12 months of treatment, the Lp(a) concentration had increased by 44% and 101% above baseline and the control group, respectively. Men and women responded differently to GH, with a more marked increase in Lp(a) concentration and fat-free mass and a more pronounced decrease in body-fat mass in men. Apo(a) phenotypes had no major influence on the effect of GH therapy. The only significant difference between apoE phenotypes was a higher baseline Lp(a) concentration among apoE4 heterozygotes.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: Acromegaly is a rare disorder characterized by over-secretion of GH, most often because of a pituitary adenoma. The disease is associated with disturbances in lipoprotein metabolism and an increased cardiovascular mortality. The aim of the present study was to investigate whether treatment of acromegaly results in changes in serum concentrations of lipids and apolipoproteins, including lipoprotein(a) (Lp(a))., Design: Fourteen patients with clinical features of acromegaly and increased GH secretion were studied 1-10 months before and 6-15 months after transsphenoidal adenomectomy in an open study., Patients: Three patients had diabetes mellitus before surgery and two of these patients had normalized serum glucose levels post-operatively. Mean and baseline plasma GH levels were determined from 24-hour GH profiles. Serum samples were taken in the morning after an overnight fast. All patients were normocholesterolaemic, and four patients were hypertriglyceridaemic before treatment., Results: Mean plasma GH levels decreased from 34.5 +/- 7.4 to 2.1 +/- 0.4 mU/l (mean +/- SEM). Serum IGF-I, insulin and free T3 levels decreased and serum SHBG concentrations increased post-operatively. There was no effect of treatment on serum cholesterol concentrations, but serum triglyceride concentrations decreased. Serum apolipoprotein (apo) B and apoE levels were unaffected by treatment. Serum apoA-I levels increased and Lp(a) levels decreased post-operatively., Conclusions: Successful treatment of acromegaly, resulting in normal mean GH values (< 5 mU/l) and/or normal responsiveness to TRH, have beneficial effects on serum lipoproteins with increased serum apoA-I levels and decreased serum levels of triglycerides and Lp(a). These effects seem to be independent of improvement in glucose tolerance, since patients with diabetes mellitus before surgery and normal fasting blood glucose levels post-operatively had similar lipoprotein responses to treatment as those with normal fasting blood glucose levels before surgery.

We describe a new assay for antioxidant activity (AOA) in lipoprotein solutions based upon their potential to quench light emission from a glowing horseradish peroxidase-catalyzed enhanced chemiluminescent reaction. By comparison with the quenching activity of the tocopherol-analogue trolox the AOA can be quantified. These measurements suggest that all lipoprotein fractions have significant AOA and that this has a non-linear relationship with lipoprotein concentration increasing significantly on a per particle basis at higher concentrations. Mean AOA in very low density, low density and high density lipoprotein fractions were 39.9 +/- 5.3, 20.3 +/- 4.0 and 5.3 +/- 1.0 mumol of trolox equivalents per litre, respectively, when measured at 1 mg protein/ml. Using known values for the protein content of the lipoprotein fractions, these values correspond to 79.8 +/- 10.7, 10.3 +/- 2.0 and 0.84 +/- 0.15 equivalents per particle. Parallel measurements of light emission and conjugated diene formation suggest that the oxidative stress imposed by the peroxidase-catalyzed reaction leads to lipid peroxidation but only after all AOA has been exhausted. AOA was significantly correlated with the alpha-tocopherol content in 30 lipoprotein samples (r = 0.764). This assay offers a rapid and simple method for investigating the effects of diseases, drugs or dietary manipulation on lipoprotein AOA.

A total of 46 patients, aged 39-71 years (mean 57.7), were studied. Forty-eight percent of the patients were hyperlipidemic and 63% had earlier suffered a myocardial infarction. Biopsies from aorta were obtained during coronary bypass surgery. Apo B was extracted from the intima by incubation of the tissue in buffer, followed by collagenase digestion. Intimal apo B was quantified in an immunoradiometric assay. There were significant correlations between total or collagenase-extractable apo B and serum cholesterol (rs = 0.39, P less than 0.01), serum triglycerides (rs = 0.33, P less than 0.05), LDL cholesterol (rs = 0.33, P less than 0.05) and serum apo B (rs = 0.37, P less than 0.05). The correlations were strongest for the collagenase-extractable apo B, while no correlations were observed for the buffer-extractable intimal apo B. No significant correlations were found between intimal apo B and serum HDL, apo A-I, smoking habits, history of hypertension or sustained myocardial infarction. Follow-up data were available for 42 of the patients, with a mean follow-up period of 35.1 months. The patients were classified according to symptoms of angina pectoris at the time of follow-up. There were significantly lower levels of serum apo A-I in the patients with poorer clinical prognosis. In a linear multiple stepwise regression analysis, apo A-I and serum LDL were significantly and independently related to clinical prognosis (R2 = 0.31).

Intimal lipid concentrations were determined in aortic biopsies obtained during coronary by-pass surgery. In addition serum lipoprotein and apolipoprotein levels were quantitated and their relationships to aortic intimal lipid concentrations were analysed. The possibility to use aortic intimal lipid and serum lipoprotein or apolipoprotein concentrations to predict clinical prognosis following the coronary by-pass operation was also evaluated. Intimal cholesterol, cholesterol ester, phosphatidylcholine and sphingomyelin were intercorrelated, whereas none of these lipid fractions correlated to aortic intimal triglyceride levels. Patients with hypertension had higher aortic intimal cholesterol ester levels than normotensive patients. There was a positive correlation between the number of stenosed coronary arteries and serum apo B or triglyceride levels. In addition there was a negative correlation between the number of stenosed arteries and HDL-cholesterol. Prognosis after the operation was inversely correlated to serum apo A-I levels. Our data do not, however, support the notion that aortic intimal lipid levels can be used to evaluate prognosis after coronary by-pass surgery.

The effects of metoprolol, propranolol and hydrochlorothiazide on lipoprotein metabolism were studied in three different but comparable groups of middle-aged men with previously untreated hypertension (n=10, n=10, and n=11, respectively). All three treatments were associated with an increase in serum triglyceride and VLDL-cholesterol levels. Propranolol treatment was associated with consistent and significant decreases in HDL-cholesterol, apoA-I and A-II levels, whereas these changes during the other treatments were neither significant nor consistent. An increase in adipose tissue LPL-activity and a decrease in serum free fatty acids were seen in the propranolol treatment group. Significant changes were not observed in glucose tolerance or catecholamine excretion. The blood pressure reduction was similar in the three groups. The design of the present study was in some important respects different from that of others. This may help to explain why we found a difference between the two beta-blockers in our study.

The relationship between apoB-100 and the membrane of the endoplasmic reticulum (ER) has been studied by a combination of pulse-chase methodology and subcellular fractionation. HepG2 cells were pulse-labeled with [35S]methionine for 3 min and chased with cold methionine for periods between 0 and 20 min. ApoB-100 and albumin, present in the membrane as well as in the luminal content of the ER vesicles, were isolated after each chase period. The results indicated that apoB-100 was cotranslationally bound to the membrane of the ER, and from this membrane-bound form, was transferred to the lumen after a delay of 10-15 min. Albumin was, as could be expected for a typical secretory protein, cotranslationally sequestered in the lumen of the ER. Apo-B-100-containing lipoproteins present in the microsomal lumen were analyzed by ultracentrifugation in a sucrose gradient. ApoB-100 occurred on rounded particles in three density regions: (i) d 1.1065-1.170 g/ml (Fraction I), (ii) d 1.011-1.045 g/ml (Fraction II), and (iii) d less than 1.011 g/ml (Fraction III). Fraction I, isolated from cells cultured in the absence of oleic acid, contained a homogenous population of particles with a mean diameter of approximately 200 A. Fraction I isolated from cells cultured in the presence of oleic acid was slightly more heterogeneous and had a mean diameter of approximately 250 A. Fractions II and III had mean diameters of 300 and 500 A, respectively. Cholesterol esters and triacylglycerol were the quantitatively dominating lipid constituents of all three fractions. Pulse-chase experiments indicated that Fraction I contained the newly assembled lipoproteins. With increasing chase time, the apoB-100 radioactivity was redistributed from Fraction I to Fractions II and III, indicating that Fraction I is converted into Fractions II and III during the intracellular transfer. Particles corresponding to Fractions II and III were by far the most abundant lipoproteins found in the medium. The results presented support the possibility of a sequential assembly of apoB-100-containing lipoproteins.

This publication is a summary of the presentations given at the First JIM Grand Round held at the Sahlgrenska University Hospital on 15 March 2006. The Grand Round was based on two case reports; a patient with type 2 diabetes and pronounced macrovascular disease and another patient with early microvascular disease combined with the macrovascular complications. The pathogenesis of the vascular complications and the current treatment regimens were discussed in relation to the history and examinations performed in these patients. [ABSTRACT FROM AUTHOR]

Objectives. The stability and inflammatory activity in atherosclerotic plaques may be modulated by lipids and lipoproteins as well as the pleiotropic effects of statins. The aim of this study was to analyse the effect of statin treatment as well as the relation of plasma lipids and lipoproteins to tissue composition in atherosclerotic plaques. Design. Patients with stable angina and coronary plaques suitable for directional coronary atherectomy (DCA) were randomized to atorvastatin (80 mg once daily) or placebo (29 randomized, 22 underwent DCA, 11/group). After an average treatment of 10 weeks, patients underwent DCA, tissue specimens were obtained, and the tissue composition was determined by immunohistochemistry. Results. Atorvastatin reduced the T-cell content, but did not change lipid, collagen, smooth muscle cell, or macrophage content. Plasma levels of apolipoprotein AI (apoAI) correlated positively with tissue collagen and inversely with metalloproteinase-9 and macrophage content. About half the specimens contained neutrophil granulocytes. Conclusions. Short-term atorvastatin treatment tended to reduce the T-cell content of atherosclerotic plaques, indicating modulation of cell-mediated immunity. High plasma levels of apoAI correlated with increased collagen content and reduced inflammation, supporting the notion that plasma apoAI stabilizes atherosclerotic plaques. The significance of neutrophils in the lesions merits further study. [ABSTRACT FROM AUTHOR]

Leinonen ES, Hiukka A, Hurt-Camejo E, Wiklund O, Sarna SS, Mattson Hultén L, Westerbacka J, Salonen RM, Salonen JT, Taskinen M-R (Division of Cardiology, University of Helsinki, Helsinki, Finland; Sahlgrenska University Hospital, Göteborg and AstraZeneca, R&D, Mölndal, Sweden; Department of Public Health, University of Helsinki, Helsinki; The Research Institute of Public Health, University of Kuopio, Kuopio and Inner Savo Health Center, Suonenjoki, Finland). Low-grade inflammation, endothelial activation and carotid intima-media thickness in type 2 diabetes. J Intern Med 2004; 256: 119–127. The objective of this study was to assess the relationship between inflammation, endothelial activation and incipient atherosclerosis in type 2 diabetes. Cross-sectional study. We studied 239 type 2 diabetic patients [71 with clinical cardiovascular disease (CVD)] and 78 healthy control subjects, aged 50–75 in a single research centre. Carotid intima-media thickness (IMT) was determined by ultrasound. Circulating intracellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, ultra-sensitive C-reactive protein, human serum amyloid A, interleukin-6, monocyte colony-stimulating factor, secretory nonpancreatic phospholipase A2 type IIA, glucose, HbA1c, and lipid/lipoprotein variables were measured. Carotid IMT was significantly thicker in diabetic patients than healthy controls across the whole age range. IMT was also thicker in diabetic patients with, than without, CVD, but this difference disappeared after controlling for confounding factors. Concentrations of the inflammatory and endothelial markers except IL-6 were significantly higher in the diabetic patients than in healthy controls, but comparable in diabetic patients with and without CVD. The main determinants of IMT in the diabetic patients were blood pressure, age and diabetes duration. Low-grade inflammation and endothelial activation are increased in diabetic patients but do not associate with IMT or clinical CVD. The inflammatory reaction seems to be rather a feature of the metabolic syndrome than a direct determinant of atherosclerosis. [ABSTRACT FROM AUTHOR]

Objective: The formation of foam cells from monocyte-derived macrophages involves the uptake of modified lipoproteins by scavenger receptors. Antioxidants inhibit lipoprotein oxidation and may also modulate gene expression. We investigated the effect of the antioxidant N-acetylcysteine on the expression of the class A scavenger receptor (SR-A) types I and II in human macrophages.Design: Monocytes and macrophages from healthy blood donors and plaque-derived macrophages from patients undergoing carotid endarterectomy were used for experiments. SR-A mRNA was analysed with quantitative and semiquantitative reverse transcription-polymerase chain reaction, and ligand binding and uptake were assessed with 125I-labelled acetylated low-density lipoprotein (LDL).Results: Incubation of monocytes and monocyte-derived macrophages with N-acetylcysteine decreased both SR-A I and II mRNA expression. N-Acetylcysteine also reduced SR-A mRNA in lesion-derived cells. Binding and uptake of 125I-acetylated LDL was decreased after brief incubation with N-acetylcysteine. After longer periods of incubation with N-acetylcysteine we observed an increased degradation of lipoproteins.Conclusions: Our results imply that N-acetylcysteine leads to a decrease in SR-A mRNA and initially also to an attenuated uptake of modified lipoproteins. This adds more to the knowledge about the cellular actions of this drug. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to study prognostic factors for death in patients with coronary heart disease (CHD), focusing on serum lipids and lipoproteins.Design and Subjects: The study subjects were 964 patients with angina pectoris who underwent coronary angiography between 1985 and 1987. Follow-up, including survival and cause of death, was carried out in April 1998.Results: A total of 363 patients died. Increasing age, diabetes and low levels of HDL cholesterol and of apolipoprotein (apo) AI were associated with increased risk of total mortality and cardiac mortality. In men, low levels of LDL cholesterol and of apoB were associated with increased risk of death, but not of cardiac death only; high levels of lipoprotein(a) [Lp(a)] were not associated with increased risk. In women, however, there was a trend towards increased risk with increasing Lp(a) levels (P = 0.054); the smallest isoform of apo(a) was associated with a twofold increase in risk. In women, but not in men, risk decreased with increasing molecular weight of the apo(a) isoforms.Conclusions: Amongst lipoprotein variables, low levels of HDL cholesterol and of apoAI and the presence of low-molecular weight isoforms of apo(a) are associated with increased risk of death in patients with CHD. Apo(a) isoforms and Lp(a) levels seem to be more important as risk factors amongst women. Low LDL cholesterol and apoB levels were associated with increased risk, but only in men. These findings demonstrate the importance of a gender-specific analysis of risk factors for CHD. [ABSTRACT FROM AUTHOR]

It appears that retention of lipoproteins rather than increased influx is the basis for lipoprotein deposition in arterial tissue during atherogenesis. Binding of lipoproteins to arterial proteoglycans is mediated by a peptide sequence considered to be involved in the interaction between the lipoproteins and the lipoprotein receptor. Consequently, in the presence of an excess of arterial proteoglycan, receptor-mediated cellular uptake of LDL is inhibited. However, LDL which has been precipitated by proteoglycan and subsequently resolubilized is taken up more avidly than native LDL, both in rnacrophages and in smooth muscle cells. This appears to be due to selection by the proteoglycans of a more reactive fraction of LDL. This fraction has a smaller molecular size and less surface phospholipids. As smaller LDL particles also have a higher transfer rate into the arterial tissue they may be particularly atherogenic. Low density lipoproteins appear to be taken up with higher affnity by arterial macrophages than by smooth muscle cells. The selective transfer of the LDL to macrophages can be inhibited by α-tocopherol, suggesting that oxidative modification may be involved in this process. The role of foam cells in atherogenesis is discussed in the context of the energy requirements of the arterial wall. [ABSTRACT FROM PUBLISHER]