Efficacy of different low-density lipoprotein apheresis methods.

Low-density lipoprotein (LDL) apheresis is a treatment option in patients with coronary heart disease and drug resistant hypercholesterolemia. Various apheresis systems based on different elimination concepts are currently in use. We compared the efficacy of 4 different apheresis systems concerning the elimination of lipoproteins. The study included 7 patients treated by heparin extracorporeal LDL precipitation (HELP), 10 patients treated by immunoadsorption, 8 patients treated by dextran-sulfate adsorption, and 4 patients treated by cascade filtration. Ten subsequent aphereses were evaluated in patients undergoing regular apheresis for more than 6 months. Total cholesterol decreased by approximately 50% with all 4 systems. LDL cholesterol (LDL-C) (64-67%) and lipoprotein a [Lp(a)] (61-64%) were decreased more effectively by HELP, immunoadsorption, and dextran-sulfate apheresis than by the less specific cascade filtration system [LDL-C reduction 56%, Lp(a) reduction 53%]. Triglyceride concentrations were reduced by 40% (dextran-sulfate) to 49% (cascade filtration) and high-density lipoproteins (HDL) by 9% (dextran-sulfate) to 25% (cascade filtration). On the basis of plasma volume treated, HELP was the most efficient system (LDL-C reduction 25.0%/L plasma), followed by dextran-sulfate (21.0%/L plasma), cascade (19.4%/L plasma), and immunoadsorption (17.0%/L plasma). However, a maximal amount of 3 L plasma can be processed with HELP due to concomitant fibrinogen reduction while there is no such limitation with immunoadsorption. Therefore, the decision of which system should be used in a given patient must be individualized taking the pre-apheresis LDL concentration, concomitant pharmacotherapy, and fibrinogen concentration into account.     

Comparison of laboratory parameters as risk factors for the presence and the extent of coronary or carotid atherosclerosis: the significance of apolipoprotein B to apolipoprotein all ratio.

We compared several "new" risk factors (autoantibodies to oxidatively modified low density lipoprotein (LDL), sialic acid content of LDL, bilirubin and C-reactive protein) with "conventional" risk factors (apolipoprotein (apo) AI, AII and B, lipoprotein(a), triglycerides, and total, LDL and high density lipoprotein (HDL) cholesterol) for the presence and the extent of coronary or carotid atherosclerosis. Forty male patients with angiographically proven coronary atherosclerosis and 31 male patients with ultrasound-proven extracranial carotid atherosclerosis were compared to 40 age matched (53+/-5 years) healthy males as control subjects, with negative parental history of atherosclerosis, no clinical signs of systemic or organ-related ischemic disease and normal extracranial carotid arteries. The apo B/apo All ratio most powerfully indicated the presence and the extent of coronary or carotid atherosclerosis. Elevated lipoprotein(a) contributed significant additional information in the assessment of the atherosclerotic risk. Increase in C-reactive protein indicated the presence (but not the extent) of coronary or carotid atherosclerosis with a similar power as lipoprotein(a). Decreased values of total bilirubin indicated the presence of atherosclerosis only in smokers. Autoantibodies to oxidatively modified LDL additionally described the atherosclerotic process, but were less important than apolipoproteins, lipoprotein(a), C-reactive protein or bilirubin. Sialic acid content of LDL added no information to the parameters discussed above. We demonstrated that in male patients apolipoproteins, especially the apo B/apo All ratio, were better indicators of the presence and the extent of coronary or carotid atherosclerosis than C-reactive protein, bilirubin, autoantibodies to oxidatively modified LDL or sialic acid content of LDL.     

Hyperlipoprotein(a)aemia in nephrotic syndrome

The nephrotic syndrome is frequently associated with hyperlipidaemia and hyperfibrinogenaemia, leading to an increased coronary and thrombotic risk, which may be enhanced by high lipoprotein (a) [Lp(a)] concentrations. We followed the quantitative and qualitative pattern of plasma lipoproteins over 18 months in a patient with nephrotic syndrome suffering from premature coronary artery disease and with elevated level of Lp(a) (470 mg dL⁻¹). Analysis of kinetic parameters after heparin-induced extracorporeal plasma apheresis revealed a reduced fractional catabolic rate for both low-density lipoprotein (LDL) and Lp(a). After improvement of the nephrotic syndrome, Lp(a) decreased to 169 mg dL⁻¹ and LDL concentrations were normalized. The decrease of Lp(a) was associated with an increase in plasma albumin concentrations. Analysis of apo(a) isoforms in the patient showed the presence of isoform S2 (alleles 10 and 19). Consequently, the authors' present strategy is to normalize the elevated Lp(a) and fibrinogen levels. For this purpose heparin-mediated extracorporeal LDL precipitation (HELP) apheresis is a promising regimen, helping to reduce the thrombotic risk and prevent coronary and graft atherosclerosis as well as the progression of glomerulosclerosis in our patient.     

Apolipoproteins and lipoprotein particles in moroccan patients with previous myocardial infarction

We investigated for the first time in the Moroccan population the relationship between lipoprotein particles and the progression of coronary atherosclerosis. Plasma lipid variables, including total cholesterol, triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, apolipoproteins AI and B, Lp AI, Lp AI:AII, and Lp(a) were measured in 40 Moroccan adults who suffered a verified myocardial infarction before the age of 50 years. The results were compared with a healthy control group. Plasma total cholesterol, triglyceride, and Lp AI : AII levels of patients did not differ significantly from control subjects. Patients had lower plasma high-density lipoprotein-cholesterol (P<0.05), apo AI (P<0.05), and Lp AI (P<0.001 ) than control subjects, suggesting that the cholesterol reverse transport system is altered in patients with previous myocardial infarction. However, patients had higher plasma low-density lipoproteincholesterol (P<0.001), apo B (P<0.001), and Lp(a) (P<0.001). In all patients the best predictor of cardiovascular risk was the independent risk factor Lp(a) plasma level, and the Lp AI plasma level. In this study, the increased coronary atherosclerosis risk with elevated plasma levels of apo B and Lp(a), and with reduced Lp AI, was substantially modified by smoking habits, but not by family history of myocardial infarction.     

A monoclonal-antibody-based enzyme-linked immunosorbent assay of lipoprotein(a)

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL)-like lipoprotein particle recently described as a risk factor for premature coronary heart disease, stroke, and atherosclerosis. Structurally, Lp(a) is similar to LDL in that it has comparable lipid composition and contains apolipoprotein B-100 (apo B-100). In addition, Lp(a) contains the glycoprotein apolipoprotein(a) [apo(a)], which is disulfide-linked to apo B-100. The recent awareness of a striking correlation between atherosclerosis and concentrations of Lp(a) in plasma prompted our development of an accurate quantitative assay for plasma Lp(a), a monoclonal-antibody-based enzyme-linked immunosorbent assay for Lp(a) that is shown to be sensitive, precise, and highly specific. The response to several isoforms of Lp(a) is linear, and as many as 80 samples can be quantified on one plate. This easily performed assay is suitable for use in the clinical laboratory and for screening large populations.     

Current topics on low-density lipoprotein apheresis.

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lp[a]) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL-apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL-adsorption, and LDL-hemoperfusion. Despite substantial progress in diagnostics, drug therapy, and cardiosurgical procedures, atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia (HLP) therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, however, sometimes the goal of therapy cannot be reached. Mostly, the prognosis of patients suffering from severe HLP, sometimes combined with elevated Lp(a) levels and CHD refractory to diet and lipid-lowering drugs is poor. Hence, in such patients, treatment with LDL-apheresis can be useful. Regarding the different LDL-apheresis systems used, there were no significant differences with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein, or triglyceride concentrations. With respect to elevated Lp(a) levels, however, the immunoadsorption method seems to be the most effective. The published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.     

LDL-apheresis: clinical experience and indications in the treatment of severe hypercholesterolemia

LDL-cholesterol is the leading risk factor which influences the clinical outcome of patients with preexisting coronary heart disease. Clinical trials show that plasma LDL-cholesterol below 100 mg/dL decrease the rate of recurrent myocardial infarction and can induce regression in patients with coronary heart disease. However, in most cases of severe hypercholesterolemia with plasma LDL-cholesterol concentrations above 220 mg/dL LDL cannot be sufficiently decreased by maximal dietary and pharmacological therapy alone. Today this group of high risk CHD patients can be treated in addition with an extracorporeal procedure to eliminate LDL from the plasma circulation, the H.E.L.P.--LDL-apheresis. This method for selective removal of LDL, lipoprotein(a) and fibrinogen from plasma has been shown to be a clinically safe and very efficient method for the treatment of patients with homozygous familial hypercholesterolemia or CHD patients with severe hypercholesterolemia. Treatments with 1 week H.E.L.P. intervals revealed a mean reduction of minus 51% for LDL, of minus 45% for Lp(a) and of minus 46% for apo B, while HDL was increased by +12%. Fibrinogen was decreased by minus 46%. Besides the marked reduction of LDL and fibrinogen plasma concentrations the H.E.L.P. treatment significantly improves hemorheological parameters and increases the oxygen tension in the tissue. We have also investigated the efficiency of a combined therapy, using HMG-CoA reductase inhibitors together with the H.E.L.P.--apheresis. Under this combined treatment, a reduction of the interval LDL-cholesterol levels of 70-80% has been achieved, while Lp(a) and fibrinogen were not further affected. We now report about our long-term clinical experience with the H.E.L.P. system in treating patients with different lipoprotein disorders: (1) Homozygous form of familial hypercholesterolemia; (2) CHD patients with familial and non-familial hypercholesterolemia; (3) CHD patients with very high concentrations of lipoprotein(a); and (4) Hypercholesterolemic patients after heart transplantation. Based on present experience guidelines for secondary prevention of coronary heart disease indications for the H.E.L.P.--LDL-apheresis treatment are discussed.     

LDL-apheresis significantly reduces urinary apo(a) excretion

Abstract. Increased plasma Lp(a) is an established risk factor for atherosclerosis. We recently described the presence of apo(a) fragments in urine and the significant correlation between urinary apo(a) concentrations and plasma Lp(a). Here we investigated urinary apo(a) in patients suffering from familial hypercholesterolaemia (FH), treated with LDL apheresis. Before treatment, plasma Lp(a) levels and urinary apo(a) normalized to creatinine were >2-fold increased in FH patients (P <0.0001) as compared to controls. LDL-apheresis led to a reduction of plasma Lp(a) by 75% and a concommittant immediate reduction of urinary apo(a) by 45%. We conclude that a steady state condition for urinary apo(a) is rapidly achieved via LDL-apheresis.     

LDL-apheresis significantly reduces urinary apo(a) excretion

Abstract. Increased plasma Lp(a) is an established risk factor for atherosclerosis. We recently described the presence of apo(a) fragments in urine and the significant correlation between urinary apo(a) concentrations and plasma Lp(a). Here we investigated urinary apo(a) in patients suffering from familial hypercholesterolaemia (FH), treated with LDL apheresis. Before treatment, plasma Lp(a) levels and urinary apo(a) normalized to creatinine were >2-fold increased in FH patients ( P  <0.0001) as compared to controls. LDL-apheresis led to a reduction of plasma Lp(a) by 75% and a concommittant immediate reduction of urinary apo(a) by 45%. We conclude that a steady state condition for urinary apo(a) is rapidly achieved via LDL-apheresis.     

Apolipoprotein(a) phenotypes, Lp(a) concentration and plasma lipid levels in relation to coronary heart disease in a Chinese population: evidence for the role of the apo(a) gene in coronary heart disease.

Elevated lipoprotein(a) (Lp[a]) concentrations are associated with premature coronary heart disease (CHD). In the general population, Lp(a) levels are largely determined by alleles at the hypervariable apolipoprotein(a) (apo[a]) gene locus, but other genetic and environmental factors also affect plasma Lp(a) levels. In addition, Lp(a) has been hypothesized to be an acute phase protein. It is therefore unclear whether the association of Lp(a) concentrations with CHD is primary in nature. We have analyzed apo(a) phenotypes, Lp(a) levels, total cholesterol, and HDL-cholesterol in patients with CHD, and in controls from the general population. Both samples were Chinese individuals residing in Singapore. Lp(a) concentrations were significantly higher in the patients than in the population (mean 20.7 +/- 23.9 mg/dl vs 8.9 +/- 12.9 mg/dl). Apo(a) isoforms associated with high Lp(a) levels (B, S1, S2) were significantly more frequent in the CHD patients than in the population sample (15.9% vs 8.5%, P less than 0.01). Higher Lp(a) concentrations in the patients were in part explained by this difference in apo(a) allele frequencies. Results from stepwise logistic regression analysis indicate that apo(a) type was a significant predictor of CHD, independent of total cholesterol and HDL cholesterol, but not independent of Lp(a) levels. The data demonstrate that alleles at the apo(a) locus determine the risk for CHD through their effects on Lp(a) levels, and firmly establish the role of Lp(a) as a primary genetic risk factor for CHD.     

Plasma concentrations of apolipoprotein A-I containing particles in normolipidaemic young men

Low levels of plasma high-density lipoprotein (HDL)-cholesterol and apolipoprotein (apo)-A-I are associated with premature coronary heart disease. However, particles in the density range of HDL are heterogeneous. Two main types of apo A-I-containing particles can be identified, one species containing both apo A-I and apo A-II (Lp A-I:A-II) and the other apo A-I but no apo-A-II (Lp A-I). This study was designed to measure HDL cholesterol, apo A-I, and, using a new procedure, Lp A-I in 233 healthy normolipidaemic young men (cholesterol less than 250 mg dl-1 and triglycerides less than 200 mg dl-1). Among these subjects, the composition of HDL was very variable as indicated by the 10th and the 90th percentiles of the HDL-cholesterol/apo A-I ratios which were 0.32 and 0.49, respectively. The 10th and 90th percentiles of apo A-I and Lp A-I:A-II were 126 and 167 mg dl-1 and 83 and 116 mg dl-1, respectively. On the other hand, Lp A-I showed a much larger variation, the 10th and 90th percentiles being at 33 and 62 mg dl-1, respectively. The distribution of individual values of Lp A-I showed that this fraction of apo A-I-containing particles was very variable among subjects, the Lp A-I/apo A-I ratio extending from 0.18 to 0.58. Triglycerides, Lp A-I and Lp A-I:A-II were correlated with HDL cholesterol, but no correlation between apo A-I containing subfractions and plasma triglycerides was noticed. Since preliminary results from angiographic and clinical studies show that Lp A-I could exert a protective role for atherosclerosis, it would seem that the measurement of Lp A-I might help in the future to characterize better the individual's risk for atherosclerosis.     

Lipoprotein(a), apolipoprotein A-I and B serum levels in young families from Tallinn,Estonia. Relationships with other cardiovascular risk factors and nationality

Serum lipid, lipoprotein(a) (Lp(a)), apolipoprotein (apo) A-I and B concentrations were studied in young families of Tallinn: 157 husbands, 81 wives and 149 newborns participated in the study; 48% of subjects were Estonians, 39% Russians and 13% other nationalities. As previous studies among middle-aged men and school children of Estonia revealed clear national differences in serum lipoprotein profiles, our special interest was to study lipoprotein parameters in relation to ethnic origin. Body mass index (BMI), blood pressure (BP) and smoking habits were determined. In newborns, maturity by physical and neurological criteria and Apgar score after birth were assessed. At the age of 18-30 years, Estonian men had significantly higher serum total cholesterol, LDL cholesterol, triglyceride and Lp(a) levels than did Russian men. Estonian newborns had higher serum triglyceride concentration than Russian ones. Among women no national differences were recorded in the measured parameters. Lp(a) levels were not statistically correlated with age, BMI, BP or current smoking. Negative associations were revealed between Lp(a) and serum level of apo A-I (in men) or triglycerides (in newborns). Lp(a) concentrations correlated positively with LDL cholesterol (in women) and apo B (in newborns). Lp(a) levels of newborns were not associated with birthweight or health status, but correlated strongly with the sum of parental and fathers' Lp(a) concentrations, demonstrating that a genetic factor(s) is involved in the values of plasma Lp(a) levels.     

Relationship between apolipoprotein(a) phenotype, lipoprotein(a) concentration in plasma, and low density lipoprotein receptor function in a large kindred with familial hypercholesterolemia due to the pro664----leu mutation in the LDL receptor gene.

In a large kindred of 66 individuals, 22 were identified as heterozygous and 3 as homozygous for a mutation (pro664----leu) in the LDL-receptor gene that gives rise to familial hypercholesterolaemia (FH). All the heterozygotes had a raised level of plasma total cholesterol and low density lipoprotein cholesterol, but were remarkably free from premature coronary disease. Determination of apolipoprotein(a) (apo(a)) phenotype and lipoprotein(a) (Lp(a)) concentration in plasma revealed that in many instances, involving individuals with various apo(a) phenotypes, there was no difference in plasma Lp(a) concentration between an FH heterozygote and an unaffected sibling with the same apo(a) phenotype. No significant difference in Lp(a) concentration was observed between groups of FH and non-FH of the same apo(a) phenotype, although in each case the mean value for the FH group was greater than that for the non-FH group. There was also evidence for an inherited trait that markedly increased Lp(a) concentration, which did not segregate with apo(a) phenotype or the defective LDL-receptor allele. The data provide no evidence for a strong multiplicative interaction between the gene loci for apo(a) and the LDL receptor.     

Lipoprotein(a), apolipoprotein A-I and B serum levels in young families from Tallinn, Estonia. Relationships with other cardiovascular risk factors and nationality.

Serum lipid, lipoprotein(a) (Lp(a)), apolipoprotein (apo) A-I and B concentrations were studied in young families of Tallinn: 157 husbands, 81 wives and 149 newborns participated in the study; 48% of subjects were Estonians, 39% Russians and 13% other nationalities. As previous studies among middle-aged men and school children of Estonia revealed clear national differences in serum lipoprotein profiles, our special interest was to study lipoprotein parameters in relation to ethnic origin. Body mass index (BMI), blood pressure (BP) and smoking habits were determined. In newborns, maturity by physical and neurological criteria and Apgar score after birth were assessed. At the age of 18-30 years, Estonian men had significantly higher serum total cholesterol, LDL cholesterol, triglyceride and Lp(a) levels than did Russian men. Estonian newborns had higher serum triglyceride concentration than Russian ones. Among women no national differences were recorded in the measured parameters. Lp(a) levels were not statistically correlated with age, BMI, BP or current smoking. Negative associations were revealed between Lp(a) and serum level of apo A-I (in men) or triglycerides (in newborns). Lp(a) concentrations correlated positively with LDL cholesterol (in women) and apo B (in newborns). Lp(a) levels of newborns were not associated with birthweight or health status, but correlated strongly with the sum of parental and fathers' Lp(a) concentrations, demonstrating that a genetic factor(s) is involved in the values of plasma Lp(a) levels.     

Sialic acid content of LDL and lipoprotein metabolism in combined hyperlipidemia and primary moderate hypercholesterolemia.

Low density lipoprotein (LDL) with low sialic acid content has been shown to cause intracellular lipid accumulation and therefore is suggested to be atherogenic. We investigated the sialic acid content of total LDL and its subfractions, and their relations to lipoprotein kinetics in 22 subjects with primary moderate hypercholesterolemia (IIa) and in 21 subjects with combined hyperlipidemia (IIb) matched for age, sex, BMI and the frequency of coronary artery disease. Sialic acid to protein ratio decreased gradually from VLDL and IDL to light and dense LDL and HDL, but was high in very dense LDL probably due to presence of Lp(a). Sialic acid to apo B ratio was significantly lower in dense and very dense subfractions of IIb than IIa. The sialic acid/apo B ratios of dense and very dense LDL subfractions were interrelated and were negatively associated with their cholesterol and triglyceride concentrations, and with the transport rate (TR) for dense LDL apo B. The only metabolic variable differing between the groups was the TR for dense LDL apo B, which was significantly higher in IIb vs. IIa. In addition, the TR for dense LDL apo B was positively associated with the esterification percentage of LDL cholesterol. In conclusion, low sialic acid content in dense and very dense LDL subfractions was associated with enhanced TR for LDL apo B and type IIb dyslipidemia.     

Association of lipoprotein(a) and apolipoprotein(a) phenotypes with coronary and carotid atherosclerosis in CHD men

AIM: To evaluate in a case-control cross-sectional study whether lipoprotein(a) concentration and apo(a) phenotypes are associated with the presence and severity of coronary and carotid atherosclerosis. MATERIALS AND METHODS: We have examined 198 male CHD patients (mean age 53 +/- 8) years) with stenosis more than 50% at least in one main coronary artery or its major branches. Duplex scanning was performed in 168 patients to assess the degree of carotid atherosclerosis. Seventy six apparently healthy men (mean age 39 +/- 9 years) formed the control group. Lp(a) concentration was measured by ELISA, apo(a) phenotyping was performed by immunoblotting. RESULTS: Lp(a) level was significantly higher in cases compared to controls: 37 +/- 31 mg/dl vs. 18 +/- 27 mg/dl, p < 0.05. Patients had low-molecular weight apo(a) phenotypes more frequently than controls: 46% vs. 29%, p = 0.01. Patients aged 45 years and younger had low-molecular weight apo(a) phenotypes more frequently than older ones (65% vs. 42%, p < 0.05) and controls (65% vs. 29%, respectively, p = 0.001). High Lp(a) level and low-molecular weight apo(a) phenotypes correlated with presence and number of coronary occlusions. CONCLUSION: There was association between Lp(a) level, low-molecular weight apo(a) phenotypes and presence, severity, extension of carotid atherosclerosis. No differences in distribution of other CHD risk factors among all subgroups of patients were found.     

Increased levels of high-density lipoprotein cholesterol are ineffective in inhibiting the development of immune responses to oxidized low-density lipoprotein and atherosclerosis in transgenic rabbits expressing human apolipoprotein (apo) A-I with severe hypercholesterolaemia

High levels of high-density lipoprotein (HDL) cholesterol have been reported to protect against the development of atherosclerosis in humans by increasing reverse cholesterol transport and inhibiting the oxidation of low-density lipoprotein (LDL) due to the paraoxonase content of HDL. The purpose of the present study was to assess if there are any relationships between in vivo increases in serum levels of immunological LDL oxidation markers [autoantibodies against oxidized LDL, autoantibodies against malondialdehyde-modified LDL, LDL immune complexes and anti-cardiolipin autoantibodies], paraoxonase activity and the development of atherosclerosis in control rabbits and in transgenic rabbits expressing human apolipoprotein (apo) A-I. A total of 13 apo A-I transgenic rabbits and 18 non-transgenic littermates were fed on a cholesterol-rich diet (0.4%, w/w) for 14 weeks, and were monitored at weeks 0, 2, 6, 10 and 14. Aortic atherosclerotic lesions were measured at the end of this period. Human apo A-I transgenic rabbits with high HDL cholesterol levels were not protected against the development of atherosclerosis when they were fed on a cholesterol-rich diet which induced dramatic hypercholesterolaemia. Immunological markers of LDL oxidation increased and serum paraoxonase activity decreased similarly in control and transgenic rabbits. In conclusion, the present study demonstrates that high HDL cholesterol levels are ineffective in inhibiting increases in immunological markers of LDL oxidation and the development of atherosclerosis in a mammal with severe hypercholesterolaemia.     

Overexpression of human low density lipoprotein receptors leads to accelerated catabolism of Lp(a) lipoprotein in transgenic mice.

Lp(a) lipoprotein purified from human plasma bound with high affinity to isolated bovine LDL receptors on nitrocellulose blots and in a solid-phase assay. Lp(a) also competed with 125I-LDL for binding to human LDL receptors in intact fibroblasts. Binding led to cellular uptake of Lp(a) with subsequent stimulation of cholesterol esterification. After intravenous injection, human Lp(a) was cleared slowly from the plasma of normal mice. The clearance was markedly accelerated in transgenic mice that expressed large amounts of LDL receptors. We conclude that the covalent attachment of apo(a) to apo B-100 in Lp(a) does not interfere markedly with the ability of apo B-100 to bind to the LDL receptor and that this receptor has the potential to play a major role in clearance of Lp(a) from the circulation of intact humans.     

Serum lipids and apolipoproteins in patients with psoriasis.

Psoriasis is characterized by defects in the normal cycle of epidermal development that lead to epidermal hyperproliferation, altered maturation of skin cells, vascular changes and inflammation. Also, psoriasis has been associated with an abnormal plasma lipid metabolism. Changes in plasma lipid and lipoprotein composition in patients with psoriasis may be the reason for the increased risk of atherosclerosis in these patients. We determined serum concentrations of lipids, lipoproteins and apolipoprotein Al and B (apo A1 and apo B) in 72 patients with psoriasis and 30 age matched controls. Serum lipoprotein (a) (Lp(a)), apo A1 and apo B were measured by immunoprecipitation assays, and the lipids and other biochemical parameters by enzymatic methods. Serum Lp(a) and triglyceride (TG) were significantly higher in patients with psoriasis than in healthy control subjects (p<0.01 for both). Apo B was also found to be higher in the patient group, but the difference was not significant. The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apo A1 did not differ significantly from those of the controls. These observations imply that serum Lp(a) and TG concentrations may play a role as risk factors for atherosclerotic disease in patients with psoriasis.     

Atherogenic forms of dyslipidaemia in women with polycystic ovary syndrome

Objective: Dyslipidaemia is very common in patients with polycystic ovary syndrome (PCOS) but, beyond plasma lipids, atherogenic lipoprotein (Lp) and apolipoprotein (apo) alterations are still ill defined. Design: We measured concentrations of apoB, Lp(a) and small, dense low‐density lipoprotein (LDL) in 42 patients with PCOS [age: 28 ± 7 years, body mass index (BMI): 27 ± 5 kg/m²] vs. 37 age‐ and BMI‐matched healthy controls. Methods: Elevated Lp(a) levels considered were those > 30 mg/dl while elevated apoB concentrations were those > 100 g/l. Results: Polycystic ovary syndrome showed increased triglycerides levels (p = 0.0011) and lower high‐density lipoprotein (HDL)‐cholesterol concentrations (p = 0.0131) while total‐ and LDL cholesterol were similar. PCOS also showed smaller LDL size (p = 0.0005), higher levels of total small, dense LDL (p < 0.0001), higher concentrations of Lp(a), as considered as absolute values (p = 0.0143) and log‐transformed (p = 0.0014), while no differences were found in apoB levels. Elevated Lp(a) concentrations were found in 24% of PCOS, while elevated apoB levels were relatively uncommon (14%). Spearman correlation analysis revealed that Lp(a) concentrations were weakly correlated only with HDL‐cholesterol levels (r = ?0.378, p = 0.0431). In addition, 36% of patients with PCOS with normal plasma lipid profile showed elevated levels of Lp(a), apoB or small, dense LDL. Conclusions: Atherogenic Lp abnormalities may be found in one‐third of women with PCOS who have a normal lipid pattern. Future prospective studies are needed to test to which extent such atherogenic forms of dyslipidaemia may contribute to the increased cardiovascular risk in young women with PCOS.