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Background: Although lipid-lowering drugs, especially statins, and recently also PCSK9 inhibitors can reduce LDL cholesterol (LDL-C) and decrease the risk for cardiovascular disease (CVD) including coronary artery disease (CAD) events most efficiently, only 5-10% of high-risk cardiovascular patients reach the target values recommended by international guidelines. In patients who cannot be treated adequately by drugs it is possible to reduce increased LDL-C and/or lipoprotein(a) (Lp(a)) values by the use of lipoprotein apheresis (LA) with the potential to decrease severe CVD events in the range of 70%->80%. Even in Germany, a country with well-established reimbursement guidelines for LA, knowledge about this life-saving therapy is unsatisfactory in medical disciplines treating patients with CVD. Starting in 1996 our aim was to offer LA treatment following current guidelines for all patients in the entire region of our clinic as standard of care., Methods: Based on the experience of our large apheresis competence center overlooking now nearly 80,000 LA treatments in the last two decades, we depict the necessary structure for identification of patients, defining indication, referral, implementation and standardisation of therapy as well as for reimbursement. LA is unfamiliar for most patients and even for many practitioners and consultants. Therefore nephrologists performing more than 90% of LA in Germany have to form a network for referral and ongoing medical education, comprising all regional care-givers, general practitioners as well as the respective specialists and insurances or other cost bearing parties for offering a scientifically approved therapeutic regimen and comprehensive care. The German Lipid Association (Lipid-Liga) has implemented the certification of a lipidological competence center as an appropriate way to realize such a network structure., Results: Working as a lipidological and apheresis competence center in a region of 400,000 to 500,000 inhabitants, today we treat 160 patients in the chronic LA program. In spite of the availability of PCSK9 inhibitors since 2015, LA has remained as an indispensable therapeutic option for targeted lipid lowering treatment. An analysis of nearly 37,000 LA treatments in our own center documented a >80% reduction of cardiovascular events in patients treated by regular LA when comparing with the situation before the start of the LA therapy. We have implemented the concept of an apheresis competence center characterised by ongoing medical education with a focus on lipidological and cardiovascular aspects, interdisciplinary networking and referral., Conclusions: Incidence and prevalence of LA patients in our region demonstrate that based on our ongoing patient-centered approach the access of patients in need to LA is substantially above the German average, thus contributing to an extraordinary reduction of cardiovascular events in the population we in particular feel responsible for., (Copyright © 2019. Published by Elsevier B.V.)

Lipoprotein(a) (Lp(a)) is an internationally accepted independent atherogenic risk factor. Details about its synthesis, many aspects of composition and clearance from the bloodstream are still unknown. LDL receptor (LDLR) (and probably other receptors) play a role in the elimination of Lp(a) particles. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors increase the number of available LDLRs and in this way very effectively reduce the LDL cholesterol (LDL-C) concentrations. As shown in controlled studies using PCSK9 inhibitors, Lp(a) levels are decreased by 20 to 30%, though in some patients no effect was observed. So far, it has not been clarified whether this decrease is associated with an effect on the incidence of cardiovascular events (CVEs). In two recently published well-performed secondary prevention studies (FOURIER with evolocumab, ODYSSEY OUTCOMES with alirocumab) baseline Lp(a) levels were shown to have an impact on CVEs independently of baseline LDL-C concentrations. The rather modest PCSK9 inhibitor-induced decrease of Lp(a) was associated with a reduction of CVEs in both studies, even after adjusting (ODYSSEY OUTCOMES) for demographic variables (age, sex, race, region), baseline Lp(a), baseline LDL-C, change in LDL-C, and clinical variables (time from acute coronary syndrome, body mass index, diabetes, smoking history). The largest decrease of CVEs was seen in patients with relatively low concentrations of both LDL-C and Lp(a) (FOURIER). These findings will probably have an influence on the use of PCSK9 inhibitors in patients with high Lp(a) concentrations.

Background and Aims: Familial hypercholesterolemia (FH) is amongst the most common genetic disorders encountered in primary care. Yet, only a minority of affected patients is diagnosed and treated. This interim analysis of the CaRe High Registry aims at examining the state of treatment and attainment of lipid goals in German FH patients., Methods: The CaRe High registry includes FH patients from lipid clinics and private practices. Data have been collected using questionnaires filled in by the recruiting physicians and by interviewing the participating patients., Results: We examined 512 F H patients diagnosed according to clinical criteria. Median age at the time of the first FH diagnosis was 39 (25th and 75th percentile: 27-50) years, median treatment naïve LDL cholesterol (LDL-C) was 239.4 mg/dl (6.19 mmol/l), 25th to 75th percentile 191.8-342.5 mg/dl (4.96-8.86 mmol/l). 27% of the participants did not receive lipid-lowering drugs. Among the patients treated with lipid-lowering drugs, 19% received a PCSK9 inhibitor (PCSK9i) in combination with a statin, 9% were treated with a PCSK9i alone and 3% were treated with a combination of PCSK9i and a non-statin drug. Patients with pre-existing CVD were more likely to be treated with lipid-lowering drugs and more likely to receive a PCSK9i, but LDL-C targets were only achieved by a minority of patients (<20%). Gap to target LDL-C was lowest and the median achieved LDL-C reduction was 1.4 times higher with PCSK9i treatment than with (oral) lipid-lowering therapy without PCSK9i., Conclusions: The Care High registry has included patients with the typical clinical features of familial hypercholesterolemia. PCSK9i treatment in addition to standard therapy allows attainment of target values in many patients with initially very high LDL-C., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Lipoprotein apheresis (LA) has been the last-resort therapeutic option in patients suffering from limited pharmaceutical options to lower highly elevated low density lipoprotein cholesterol (LDL-C) levels. Facing the introduction of the proprotein convertase subtilisin/kexine type 9 (PCSK-9) inhibitors, it has been speculated that they might replace LA to a large extend. Given an efficacy of approx. 55-65% to lower LDL-C it is important to analyze whether this might be realistic i) for potential candidates in apheresis sites and ii) for the future structures of the sites themselves. We performed a review of our own single center, one of the largest apheresis centers in Germany to answer these questions. Therefore we analyzed all actively treated apheresis patients and identified those with the primary indication of LDL-C elevation. In a next step we used pre-apheresis LDL-C values to calculate expected LDL-C under three given models of PCSK9 inhibitor efficacy. Including other aspects such as the accompanying presence of elevated lipoprotein(a), we identified 11-17 patients among 29 patients undergoing treatment for insufficiently treated LDL-C (38-58%). In the total cohort of 112 patients this reflects 10-15% of all patients that might potentially stop apheresis therapy due to the availability of PCSK9 inhibitor therapy, which is in clear contrast to speculations on the future perspective of apheresis therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: In recent years the Federal Joint Committee (G-BA), a paramount decision-making body of the German health care system required a reassessment of the approval of chronic lipoprotein apheresis therapy for regular reimbursement. Since 2005 an interdisciplinary German apheresis working group has been established by members of both German Societies of Nephrology. In 2009 the working group completed the indication for lipoprotein apheresis with respect to current cardiovascular guidelines and current scientific knowledge for the registry. In 2011 the German Lipoprotein Apheresis Registry (GLAR) was launched and data acquired over nearly 5 years can now be reported., Methods and Results: All data were collected and analyzed during the time period 2012-2015. Over this time interval, 68 German apheresis centers collected retrospective and prospective observational data of 1.283 patients undergoing lipoprotein apheresis (LA) treatment of high LDL-cholesterol (LDL-C) levels and/or high lipoprotein(a) (Lp(a)) levels suffering from progressive cardiovascular disease (CVD). A total of 15,167 documented LA treatments were investigated. All patients treated by LA exhibited a median LDL-C reduction rate of 68.6%, and a median Lp(a) reduction rate of 70.4%. Analogue to the Pro(a)LiFe pattern, patient data were analyzed and compared with respect to the incidence rate of coronary events (MACE) 1 and 2 years before the start of LA treatment (y-2 and y-1) and prospectively one year on LA treatment (y+1). During the first year of LA treatment a MACE reduction of 97% was be observed. In the years considered, LA treatment side effects occurred at a low rate (ca. 5%) and mainly comprised puncture problems., Conclusions: For the first time data generated by the GLAR shows that LA lowers the incidence rate of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive CVD and maximally tolerated lipid lowering medication. In addition LA treatments were found to be safe, exhibiting a low rate of side effects., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In recent years statins have become an established option in lipid-lowering pharmacotherapy despite the fact that statin intolerance is fairly common. When muscle pains and/or an elevation of the creatine kinase appear, the dose must be lowered in patients with slight symptoms or stopped altogether if the symptoms are more severe. When the symptoms are alleviated and creatine kinase is normalized, re-exposition can be considered. If symptoms recur, treatment with another statin should be attempted - in these cases pravastatin or fluvastatin are recommended, although they are less effective in reducing LDL cholesterol. As a rule, at least 3 statins should be tested. In some patients an intake of atorvastatin or rosuvastatin twice weekly may be tolerated and effective. Alternative drugs for patients who cannot tolerate any of the statins are ezetimibe and/or bile acid sequestrants. If LDL cholesterol targets are not reached, PCSK9 inhibitors may be used. In high-risk patients with multiple cardio-vascular events and sub-optimal LDL cholesterol despite lipid-lowering drug therapy a lipoprotein apheresis should be started. In this context, we present the history of a patient, who also had high lipoprotein(a) levels, for whom lipoprotein apheresis therapy was indicated., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Familial hypercholesterolemia (FH) is an inherited disorder of the LDL metabolism, leading to cardiovascular disease, even at young age. This risk can be significantly lowered by early diagnosis and treatment. About 270,000 patients affected in Germany are not diagnosed correctly and only a small number is treated properly. To improve FH diagnosis in the general population a cascade screening and registry data is warranted, yet missing in Germany. This project aims to fill this gap., Methods: Study assistants approach physicians and lipid clinics to introduce the cascade screening and registry. The physicians identify potential FH patients and include them in the study. Patient data is acquired via questionnaires about medical history. Patients meeting at least two inclusion criteria (LDL-C >190 mg/dl or total cholesterol >290 mg/dl; tendon xanthomas; family history of hypercholesterolemia or early myocardial infarction) are included in the registry. Family members will be contacted and physicians get feedback about diagnosis and treatment options. Ethical approvals for all German states have been collected., Results: So far physicians, lipid clinics and patients within the Rhein-Neckar region, the Saarland, North-Rhine-Westphalia, Upper Bavaria, Bremen, Saxonia and Berlin have joined the study. We expect to include more than 3000 patients during the next two years., Conclusion: After initial patient and data collection the project aims to improve FH-diagnosis and treatment. Utilizing registry data might advance diagnostic criteria and improve detection of FH and thus prevent CVD in this population., (Copyright © 2017. Published by Elsevier B.V.)

According to current European guidelines, lipid lowering therapy for progressive cardiovascular disease including cardiovascular events has to be focused on a target level for LDL-C. In contrast for Lp(a) a threshold has to be defined with respect to the method of measurement. However, due to new lipid lowering drug developments like PCSK9-inhibitors (PCSK-9-I) a therapeutic algorithm for patients with severe hypercholesterolemia or isolated Lipoprotein(a)-hyperlipoproteinemia with progressive cardiovascular disease may be necessary to manage the use of PCSK9-I, lipoprotein apheresis (LA) or both. The therapeutic approach for patients with homozygous familial hypercholesterolemia is unambiguous: In addition to LA, in order to improve LDL-C reduction, PCSK9-I could be applied. In patients with heterozygous familial hypercholesterolemia, PCSK9-I is to be applied first. If in addition to a pronounced LDL-C elevation, cardiovascular complications exist or if imaging techniques documented atherosclerotic changes pre-disposing for a cardiovascular event while LDL-C reduction is insufficiently reduced (LDL-C > 100 mg/dl (2.6 mmol/l)), LA treatment should then be applied as last resort. In patients with elevated Lp(a) concentrations (Lp(a) > 60 mg/dl (>120 nmol/l)) and established cardiovascular disease, therapy should rely primarily on LA methods. If in addition to high Lp(a) levels insufficiently treated LDL-C concentrations (LDL-C > 100 mg/dl (2.6 mmol/l)) exist, in rare cases PCSK9-I can supplement the lipid lowering concept., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Lipoprotein apheresis (LA) therapy is effective in eliminating atherogenic lipoproteins and reducing the rate of cardiovascular events (CVE) in patients suffering from severe hypercholesterolemia or increased lipoprotein(a) (Lp(a)) levels despite maximal tolerated lipid lowering therapy., Methods: We examined the rate of CVE in 116 patients (63% males) with an isolated increase of LDL-cholesterol (LDL-C) (Group 1), an isolated increase of Lp(a) (Group 2), a combined increase of LDL-C and Lp(a) (Group 3) and patients who were referred for LA, but never started (Group 4)., Results: Patients with increased Lp(a) (Groups 2 and 3) showed a higher prevalence of advanced atherosclerotic changes, defined as involvement of 3 or 4 vascular territories, including the abdominal aorta and leg arteries, and an involvement of more coronary vessels compared to patients in group 1. Prior to initiation of LA, on average patients suffered 4.4 (range: 0-14) CVE during a period of 7.2 (range: 0-41) years. Group 1 patients suffered fewer CVE per patient-year compared to the other groups (Group 1: 0.75, Group 2: 1.7, Groups 3 and 4: 1.4). 55-63% of patients applying for LA experienced a CVE within the last year (on average 1.3 CVE per patient in the last year). Among patients referred to LA there is a high rate of intolerance to nicotinic acid (42% of patients in Group 3) and statins (58% of patients in Group 1)., Conclusion: Patients referred to LA represent a high risk population for CVE in all vascular territories. Increased Lp(a) levels cause a higher percentage of patients with advanced atherosclerosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) increases LDL cholesterol (LDL-C) levels by stimulating the degradation of Low Density Lipoprotein receptors (LDL-r). This protein is now of high interest because antibodies which inhibit its effect on LDL-r are being developed. A severe hypercholesterolemia and / or an elevation of lipoprotein(a) can be treated with lipoprotein apheresis (LA) in high-risk patients., Methods: We measured serum PCSK9 levels in patients eligible for the extracorporeal treatment: in 40 patients (Cohort I) who were treated with different systems before and after apheresis sessions and in the intervals between sessions. 10 patients (Cohort II) who were eligible but did not start LA yet served as controls., Results: Patients' baseline serum PCSK9 levels were elevated relative to healthy volunteers and LA sessions acutely reduced the mean PCSK9 concentrations by 51%. Comparison of the effectiveness of the different LA methods demonstrated the DSA and HELP were more effective than the DALI system. After 24 h PCSK9 levels had returned to baseline compared to 8 days for the LDL-C concentrations to return to its pre-apheresis levels. In Cohort II baseline PCSK9 levels were similar to those in Cohort I., Conclusion: The acute reductions of PCSK9 by apheresis may be beneficial with respect to increasing the effectiveness of lipid-lowering drugs and with respect to an anti-atherosclerotic effect. In the future, antagonists to PCSK9 will probably be combined with or possibly replace LA in patients with a very high cardiovascular risk., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

We describe our experience with the performance of six lipoprotein apheresis methods (HELP, TheraSorb LDL, DALI, lipidfiltration, Liposorber D, MONET) which have been used in 68 patients. Thirty-four of them have been treated with more than one method. The calculations presented in this paper are based on laboratory data measured at the last three available apheresis sessions before the switch to another method and at the end of the observation period, respectively. With respect to the reduction of low-density lipoprotein (LDL) cholesterol, DALI and Liposorber D appeared to be the most effective lipoprotein apheresis methods, for reduction of lipoprotein(a), Liposorber D. Data on the influence of these lipoprotein apheresis methods on parameters of the coagulation system (prothrombin time, international normalized ratio, activated partial thromboplastin time, fibrinogen) are also reported. The histories of three patients who have been switched to several lipoprotein apheresis methods are given as examples. The major reason for switching was the low efficiency of a given lipoprotein apheresis method with respect to lowering of LDL cholesterol; the reason for this phenomenon was not clear in each case. In three patients who took an oral anticoagulant and were treated with HELP, the influence on the coagulation system is reported; they were submitted to another apheresis method. In two patients we observed an allergy to heparin-they were then treated with a heparin-free apheresis method. In conclusion, we point out that there are several reasons why an apheresis center should offer more than one lipoprotein apheresis method., (© 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.)

Aim: To investigate the effect of low-density lipoprotein (LDL) apheresis on ocular microcirculation in patients with hypercholesterolaemia., Methods: Six patients with hypercholesterolaemia were included in this study. The diameter of retinal vessels was measured continuously with the retinal vessel analyser before and after LDL apheresis. After baseline assessment a monochromatic luminance flicker was applied to evoke retinal vasodilation. Flicker response was then analysed 50, 70 and 120 s after baseline measurement. In addition, cholesterol, high-density lipoprotein, LDL and triglyceride levels were obtained to find a possible correlation between changes in retinal vessel diameter and lipid metabolism before and after apheresis., Results: The mean diameter of the arterioles at baseline was 107.6±2.1 μm and the mean diameter of the venules at baseline was 132.8±3.2 μm. The diameter of the arterioles after apheresis increased to 111.2±2.3 μm after 50 s, 113.2±2.6 μm after 70 s and 113.7±2.6 μm after 120 s, showing a trend to statistical significance at all time points (p=0.046, p=0.028 and p=0.028, respectively). The mean diameter of the venules after apheresis increased to 138.8±5.9 μm after 50 s, 139.8±6.3 μm after 70 s and 141.2±6.0 μm after 120 s, showing a trend to statistical significance at all time points (all p=0.028)., Conclusions: Changes in retinal vascular diameter seem to be associated with the systemic effect of a single LDL apheresis. Vasodilatation of the arterioles and the venules improved after LDL apheresis, indicating an improvement of ocular perfusion in patients with hypercholesterolaemia.

Objective: Hypotensive episodes are relatively frequent adverse effects during LDL apheresis. To evaluate the impact of LDL apheresis on autonomic cardiovascular control we investigated hypercholesterolemic patients before and after a single LDL apheresis in comparison to an age-matched control group., Methods: We continuously recorded systemic arterial blood pressure, electrocardiogram and respiration in 21 hypercholesterolemic patients (57 ± 15 years) on regular LDL apheresis treatment and 22 healthy control subjects (56 ± 4 years) during cardiovascular autonomic testing (metronomic breathing, Valsalva manoeuvre, head-up tilt). Baroreflex sensitivity and frequency spectra of R-R intervals and systolic blood pressure were evaluated by trigonometric regressive spectral analysis., Results: Hypercholesterolemic patients had reduced resting baroreflex sensitivity and high-frequency power of heart rate variability compared to controls. Consequently, there was a sympathetic predominance of heart rate modulation reflected by increased ratio of low-to-high frequency power of R-R intervals. Cardiovascular stimulation failed to adequately activate baroreflex mechanisms before LDL apheresis. After LDL apheresis, the parasympathetic response to cardiovascular stimulation improved and sympathetic outflow to peripheral vasculature was reduced. Baroreflex sensitivity remained low., Conclusion: Hypercholesterolemic patients on regular LDL apheresis treatment have significant autonomic dysfunction. A single LDL apheresis does not evoke sympathetic overactivation but improved deranged cardiovagal heart rate modulation in hypercholesterolemia., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective and Methods: Dyslipidemia and oxidative stress are causally related to atherogenesis and cardiovascular disease. We assessed acute changes of systemic oxidative stress biomarkers in thirty-two patients undergoing regular apheresis using four different techniques: heparin-induced extracorporeal LDL precipitation (HELP), direct adsorption of lipoproteins (DALI), lipidfiltration (LF), and immunoadsorption of lipoproteins (IA)., Results: All apheresis procedures were similarly effective in lowering LDL cholesterol (-2.5+/-0.2 mmoL/L), oxidized LDL (-52.4+/-4.4 U/L), and levels of antioxLDL antibodies (-59.5+/-15.1 U/L). Among the LDL-apheresis methods investigated, only the DALI technique without prior separation of blood plasma led to a decline in leukocyte count (p=0.01 vs. LF post apheresis) and to decreased phagocyte oxidant-generating activity as evaluated by chemiluminescence. Moreover, DALI was followed by a smaller decrease of blood total antioxidant capacity than the other techniques (p<0.01 vs. HELP post apheresis)., Conclusion: Together, our data suggest that compared with other common techniques, the DALI apheresis system is accompanied by the lowest systemic oxidative burden evoked by a single apheresis treatment., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

The first apheresis center in former German Democratic Republic was established in Dresden November 1990 following the reunification of Germany. We here summarize the activities of this center to date. From the center's establishment until the end of July 2009 13,291 sessions of therapeutic apheresis have been performed. Four LDL apheresis methods, namely DALI, Therasorb LDL, HELP and lipidfiltration, are available and several comparative studies of these methods have been published. In addition, we have established the Therasorb IG method and two rheophoresis methods (Rheofilter SR 20; TheraSorb-Rheo Adsorber). Currently we treat 53 high-risk patients with LDL apheresis, including 6 post- heart transplant patients and 5 patients with immunoadsorption. Since November 1990 we have seen a marked reduction in the number of new cardiovascular events by apheresis intervention, but they could not be totally prevented and 2 patients died despite LDL apheresis treatment. In our clinical experience all 4 LDL apheresis methods appear equally effective. However, it is an advantage to have the ability to switch methods in patients in whom one method was less effective or less well tolerated. We also successfully treated patients suffering from Evans' syndrome, pemphigus, urticaria vasculitis with monoclonal gammopathy IgM Type Kappa, lichen myxoedematosus or lupus erythematodes with immunoadsorption. The rheophoresis approach has been used in patients with age-dependent degeneration of the macula, sudden hearing loss, leg ulcers, and diabetic foot syndrome., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Objective: Changes in the microcirculation per se may precede macrovascular changes, hence, may present a good surrogate for monitoring vascular changes during treatment. Using retinal vascular imaging techniques, we attempted to investigate the microvascular benefit of a single LDL apheresis in hypercholesterolemia., Methods: Twenty-one hypercholesterolemic patients (57+/-15 years) on regular LDL apheresis treatment, seven women and 14 men, were examined for retinal endothelial function before and after a single LDL apheresis. The Dynamic Vessel Analyzer was applied for static and dynamic retinal vessel analysis. Retinal vessel diameter was measured at rest and during flicker light stimulation. Changes in vasodilation are expressed as percent changes over baseline., Results: Cholesterol fractions and triglycerides were reduced by 21-74 % by the LDL apheresis procedure. In hypercholesterolemic patients, flicker-induced vasodilation was diminished in both retinal arterioles and venules, but had significantly improved in retinal venules after a single LDL apheresis (p = 0.013). This increase in vasodilatory capacity of retinal venules was linked to a wider basal retinal venular caliber (p = 0.031), but was unrelated to changes in serum lipids (p > 0.05)., Conclusion: In hypercholesterolemia, abnormal retinal autoregulation is improved by a single LDL apheresis. Our findings suggest that venules represent a dynamic component, which is highly responsive to metabolic changes in the microcirculation., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

This article presents the generally accepted indications for LDL apheresis treatment. The available LDL apheresis methods differ with respect to acute relative reductions of LDL cholesterol; mean values after the LDL apheresis treatments are not different. Serum triglycerides, HDL-cholesterol, and lipoprotein(a) are also acutely reduced. Available LDL apheresis methods differ with respect to their impact on the coagulation system, on C-reactive protein and on leukocyte count. Cardiovascular events are clearly reduced by the LDL apheresis methods. There is an urgent need to prospectively compare the different LDL apheresis methods taking into account hard end points. The lower target values for LDL cholesterol suggested by international guidelines for high-risk patients will certainly require a more widespread use of LDL apheresis.

Background: Small dense low-density lipoprotein (LDL) particles are known to be especially atherogenic. Several mechanisms are involved in this atherogenicity., Aims: We wanted to look for the presence of small dense LDL particles depending on gender, metabolic syndrome (MS) and different degrees of glucose intolerance. Moreover, we looked for anthropometric factors and factors of lipid and carbohydrate metabolism that are associated with changes in the LDL size., Results: We studied 752 persons (330 males, 422 females; age 40 +/- 17 years). LDL particle size was estimated with polyacrylamide gel electrophoresis. Males had smaller LDL particles than females. Probands with the MS had smaller LDL particles than those without this syndrome. With rising plasma triglyceride (TG) levels more small dense LDL particles were seen. The highest proportion of these small dense LDL particles was observed in the subgroup of type 2 diabetic patients. In the whole material, the mean LDL diameter was correlated negatively with plasma TG and very low-density lipoprotein components (TG, cholesterol and proteins) and positively with high-density lipoprotein cholesterol. In a linear stepwise regression analysis different significant factors influencing the LDL size were found in the whole population, in normoglycaemic probands, in persons with impaired glucose tolerance, in type 2 diabetic patients and in type 2 diabetic patients injecting insulin., Conclusions: Our data point to different mechanisms of the formation of small dense LDL particles in dependence on the degree of glucose intolerance. Moreover, the target values for plasma TG should be set lower.

The patient introduced in the case history had a myocardial infarction in 2001 and a coronary two-vessel disease (extensive subtotal proximal stenosis of the left anterior descending [LAD] and proximal subtotal stenosis of the right coronary artery) which was diagnosed via coronary angiography at the age of 39 years. Besides smoking and obesity an important coronary risk factor was hyperlipoproteinemia with an especially massive increase in lipoprotein (a) level. The lipoprotein (a) level in January 2002 was massively elevated with 273.7 mg/dl (2 737 mg/l; Table 1). Despite invasive therapy with percutaneous transluminal coronary angioplasty (PTCA) and stent implantation in LAD and immediate therapy with atorvastatin, a restenosis in LAD was detected in April 2002 (Figure 1). Re-PTCA and intracoronary brachytherapy were performed (Figure 2). After presentation of unstable angina pectoris symptoms in November 2003, again a new in-stent restenosis in LAD could be detected via coronary angiography (Figure 3a), so that a single-bypass operation became necessary (Figure 3b). Since December 2001, an intensified treatment in a specialized polyclinic for lipid metabolism has been carried out, in which LDL-C values of 104 mg/dl (2.7 mmol/l) were targeted under aggressive lipid-lowering therapy with atorvastatin 80 mg/d and ezetimibe 10 mg/d (Table 1). Since 1998, the patient has quitted smoking. Blood pressure values are now in the therapeutic range, but the obesity could not be overcome.A distinctly elevated lipoprotein (a) level is an important risk factor for an early-onset and badly progressive arteriosclerosis. Thus, once in lifetime in the scope of risk factor management one should measure the lipoprotein (a) level. In case of elevated values the crucial treatment options include a very good management of all other risk factors, whereas an LDL-C level < 100 mg/dl (< 2.6 mmol/l), optionally < 70 mg/dl (< 1.8 mmol/l), is of vital importance. Nicotinic acid derivatives lower lipoprotein (a) levels by about 20-30%. All other risk factors, e.g., diabetes or hypertension, should be strictly managed as well. Cardiologic and angiologic examinations have to be an integral part of the treatment of these patients.

For many years dextran sulfate adsorption (DSA) treatment of separated plasma has been an established technology for low-density lipoprotein (LDL)-elimination. Recently a system for the treatment of whole blood based on DSA was introduced into clinical practice. To further characterize DSA treatment of whole blood, the performance characteristics of both DSA modalities were compared at two investigational sites with two alternative LDL apheresis systems being already in routine clinical use. In prospective cross-over design, DSA whole blood treatment was compared with a whole blood polyacrylate LDL adsorption system (DALI) in one study group. DSA for plasma treatment was compared with Lipidfiltration in cross-over design in a second study group. In total, 12 patients on chronic LDL apheresis received 169 treatments. Six patients were treated twice with whole blood polyacrylate adsorption and twice with whole blood DSA. LDL-cholesterol (74.9-78.0%) and lipoprotein (a) (72.1-73.3%) were reduced by both with equal efficacy. DSA achieved a significantly higher reduction rate of fibrinogen. Another six patients were treated eight times with DSA plasma adsorption followed by 16 Lipidfiltration treatments. LDL-cholesterol (67.0-70.2%) and lipoprotein (a) (69.2-73.7%) were reduced by both with equal efficacy. Fibrinogen was eliminated more efficiently by Lipidfiltration (50.2 vs. 38.5%). DSA proved to be a safe and effective in both treatment modes, for plasma as well as for whole blood. At the discretion of the apheresis specialist, depending upon the status of national approval, DSA of whole blood complements the armamentarium of powerful modalities for extracorporeal elimination of atherosclerotic lipoproteins to meet specific individual, medical, or logistic needs., ((c) 2007 Wiley-Liss, Inc.)

Low density lipoprotein (LDL) apheresis is an effective treatment option for patients with severe hypercholesterolemia not adequately responding to diet and drug therapy. Membrane differential filtration (MDF), synonymous with double filtration plasmapheresis (DFPP), here named Lipidfiltration, and heparin-induced extracorporeal LDL-precipitation (HELP) are two of the five methods available for extracorporeal LDL apheresis. In this prospective investigation 6 patients with severe LDL-hypercholesterolemia and CAD were treated in a cross-over design with Lipidfiltration at two stages of technical development and HELP to compare the efficacy of these two LDL apheresis methods with respect to lowering and modifying plasma lipids and rheologically relevant plasma proteins, especially fibrinogen. In total, 44 LDL apheresis sessions were investigated. In weekly intervals, patients were treated with consecutive LDL apheresis sessions with either Lipidfiltration and HELP, treating identical plasma volumes. In one part of the investigation Lipidfiltration was performed with the novel Lipidfilter EC-50, combined with a newly developed blood and plasma therapy machine allowing optimized plasma heating. The results showed that the reduction rates of LDL-cholesterol, lipoprotein(a) and triglycerides were essentially identical for both methods. Also pretreatment levels of total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol were not significantly different in both treatment groups. Both methods lead to a significant reduction of serum lipoproteins, especially for LDL-cholesterol, which was decreased by 61.4% with Lipidfiltration (treated plasma volume: 2998 ml) and 61.3% with HELP (treated plasma volume: 3013 ml). With respect to Lipidfiltration LDL-cholesterol reduction was more efficient with the novel Lipidfilter EC-50. Mean pretreatment HDL cholesterol concentrations remained unchanged. Comparing Cascadeflo AC-1770 with the novel Lipidfilter EC-50 reduction rates of HDL-cholesterol (17.4% versus 6.4%) and total protein (17.9% versus 7.8%) were significantly reduced. Lipidfiltration and HELP both resulted in a reduction of plasma viscosity and hemorheologically relevant plasma proteins, like fibrinogen.

We performed an intraindividual comparison of the effect on the coagulation system of two selective apheresis procedures: Direct Adsorption of Lipoproteins (DALI) and Heparin-induced Lipoprotein Fibrinogen Precipitation (HELP). Six patients suffering from heterozygous familial hypercholesterolemia have been treated with 2 sessions of each procedure. Anticoagulation was carried out according to usual recommendations. Blood samples were taken before, immediately after and on the second day after the sessions. We assessed global coagulation tests (prothrombin time, activated partial thromboplastin time), fibrinogen, prothrombin fragment F 1 + 2 and a variety of factors (Factors II, V, VII, XIII, IX, X, XI, XII, XIIa; von Willebrand Factor; collagen-binding activity, prekallikrein, high-molecular weight kininogen) and antagonists (antithrombin III, protein S activity, free protein S). In fact, all parameters measured have been influenced by the apheresis treatment. Fibrinogen is lowered more by HELP which also has a more definite impact on factors belonging to the prothrombin complex (II, VII, X). In contrast, the major effects of the DALI system have been seen on the intrinsic pathway of the coagulation system (IX, XI, prekallikrein, high-molecular-weight kininogen). With both systems, no increases in activated Factor XII or in prothrombin fragment F 1 + 2 have been observed. These data provide a solid basis for individual adaptations of anticoagulant doses.