Search

Background: Atherosclerosis is considered a chronic inflammation of arterial vessels with the involvement of several immune cells causing severe cardiovascular diseases. Lipoprotein apheresis (LA) improves cardiovascular conditions of patients with severely disturbed lipid metabolism. In this context, little is known about the impact of LA on various immune cell populations, especially over time., Methods: Immune cells of 18 LA-naïve patients starting weekly LA treatment were analyzed before and after four apheresis cycles over the course of 24 weeks by flow cytometry., Results and Conclusions: An acute lowering effect of LA on T cell and natural killer (NK) cell subpopulations expressing CD69 was observed. The non-classical and intermediate monocyte subsets as well as HLA-DR + 6-sulfo LacNAc + monocytes were significantly reduced during the apheresis procedure. We conclude that LA has the capacity to alter various immune cell subsets. However, LA has mainly short-term effects than long-term consequences on proportions of immune cells., (© 2022 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis and Japanese Society for Apheresis.)

Methods: Three hundred thirty-nine patients (230 men, 109 women) treated with lipoprotein apheresis in Saxony, Germany, in 2018 are described in terms of age, lipid pattern, risk factors, cardiovascular events, medication, and number of new admissions since 2014, and the data are compared with figures from 2010 to 2013., Results: Patients were treated by 45.5 physicians in 16 lipoprotein apheresis centers. With about 10 patients per 100 000 inhabitants, the number of patients treated with lipoprotein apheresis in Saxony is twice as high as in Germany as a whole. The median treatment time was 3 years. Almost all patients had hypertension; type 2 diabetes mellitus was seen significantly more often in patients with low Lipoprotein(a). Cardiovascular events occurred in almost all patients before initiation of lipoprotein apheresis, under apheresis therapy the cardiovascular events rate was very low in this high-risk group. For some cardiovascular regions even no events could be observed., Conclusions: The importance of lipoprotein apheresis in Saxony had been increasing from 2010 to 2018., (© 2022 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis and Japanese Society for Apheresis.)

Familial hypercholesterolemia (FH) is the most common, but poorly diagnosed autosomal-dominant genetic disease which increases the cardio-vascular risk., Aim: To evaluate the experience of FH registry conducted in Karelia Republic., Methods: FH registry in Karelia is existing from 2004, it includes 350 patients with heterozygous FH (110 with definite FH), the mean age is 48 ± 2.3 years. The genetic study was performed in 102 patients (29.1%)., Result: The creation of the registry has contributed to the active identification of FH, and now the estimated frequency of FH occurrence in Karelia may be 1:300, in patients with cardiovascular disease 1:10. We also analyzed genetic features of FH in our republic and found that the LDL-C level, above which the probability of LDL receptor mutation increases in Karelia, is 6.5 mmol/L. We analyzed risk factors of ischemic heart disease and the prognosis in FH., Conclusion: The creation and maintenance of a registry is an effective way of organizing timely diagnosis and adequate treatment of FH patients., (© 2022 International Society for Apheresis and Japanese Society for Apheresis.)

During 2012-2020, 89 German apheresis centers collected retrospective and prospective observational data of 2028 patients undergoing regular lipoprotein apheresis (LA) for the German Lipoprotein Apheresis Registry (GLAR). More than 47 500 LA sessions are documented in GLAR. In 2020, all patients treated with LA showed a high immediate median reduction rate of LDL-C (68.2%, n = 1055) and Lp(a) (72.4%, n = 994). Patient data were analyzed for the incidence rate of major coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y-1) and prospectively up to 7 years on LA (y + 1 to y + 7). During the first 2 years of LA (y + 1 and y + 2), a MACE reduction of 78% was observed. Current analysis of GLAR data shows very low incidence rates of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive ASCVD, and maximally tolerated lipid lowering medication regular by LA results., (© 2022 International Society for Apheresis and Japanese Society for Apheresis.)

Lipoprotein apheresis (LA) is currently the most powerful intervention possible to reach a maximal reduction of lipids in patients with familial hypercholesterolemia and lipoprotein(a) hyperlipidemia. Although LA is an invasive method, it has few side effects and the best results in preventing further major cardiovascular events. It has been suggested that the highly significant reduction of cardiovascular complications in patients with severe lipid disorders achieved by LA is mediated not only by the potent reduction of lipid levels but also by the removal of other proinflammatory and proatherogenic factors. Here we performed a comprehensive proteomic analysis of patients on LA treatment using intra-individually a set of differently sized apheresis filters with the INUSpheresis system. This study revealed that proteomic analysis correlates well with routine clinical chemistry in these patients. The method is eminently suited to discover new biomarkers and risk factors for cardiovascular disease in these patients. Different filters achieve reduction and removal of proatherogenic proteins in different quantities. This includes not only apolipoproteins, C-reactive protein, fibrinogen, and plasminogen but also proteins like complement factor B (CFAB), protein AMBP, afamin, and the low affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa) among others that have been described as atherosclerosis and metabolic vascular diseases promoting factors. We therefore conclude that future trials should be designed to develop an individualized therapy approach for patients on LA based on their metabolic and vascular risk profile. Furthermore, the power of such cascade filter treatment protocols may improve the prevention of cardiometabolic disease and its complications., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Patients who have achieved very low low-density lipoprotein CH (LDL-C) levels in clinical trials have shown the lowest cardio-vascular risk. The current clinical guidelines set such a concentration for LDL-C as < 1.4 mmol/L. However, the question of minimum permissible target values of the lipids remains unresolved. A number of experimental and clinical studies showed some unfavorable consequences of low LDL-C levels At the same time, the modern arsenal of lipid lowering drugs allows reducing LDL-C levels to extremely low values. This review presents an analysis of literature about the safety of low lipid spectrum parameters., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.)

Objectives: Despite improved treatment, premature cardiovascular (CV) events remain a major health problem. Aim of this study was to evaluate the patterns of risk factors in patients with premature CV events., Methods: CV risk factors (CVRF) were evaluated in 130 patients with a history of CV events (myocardial infarction, stroke, limb ischemia, stent and bypass intervention in any vessel bed) under 50 years of age attending our lipid clinic. Patients were also stratified according to their Lp(a) concentrations: group 1: 0-45 nmol/l (<18 mg/dl); group 2: >45-120 nmol/l (>18-50 mg/dl); group 3: >120 nmol/l (>50 mg/dl)., Results: The most common risk factors in our patients were male sex (75%), current (61%) and previous smoking (9%), arterial hypertension (70%), and a positive family history of early CV events (54%) and hyperlipidemia (69%). Only 27% had a BMI >30 kg/m 2 and 14% had diabetes mellitus. 69% of patients with premature CV disease (CVD) showed Lp(a) levels > 120 nmol/l (>50 mg/dl). Patients with the highest Lp(a) showed a tendency of more frequent positive family histories of hyperlipidemia. They had experienced their first CV event on average 3 years earlier than those with low Lp(a). CV events predominantly involved coronary arteries. 85% of patients experienced at least one coronary event., Conclusion: In patients with premature CV disease male sex, smoking, hypertension, a positive family history and elevated Lp(a) are the most important CV risk factors. Lp(a) should be considered in the management of young patients with CV disease., (Copyright © 2019. Published by Elsevier B.V.)

An elevation of lipoprotein(a) (Lp(a)) is an internationally recognized atherogenic risk factor, documented in epidemiological studies, in studies with Mendelian randomization and in genome-wide association studies (GWAS). At present, no drug is available to effectively reduce its concentration. In Germany, an elevation of Lp(a) associated with progressive cardiovascular diseases is officially recognized as an indication for a lipoprotein apheresis (LA). The number of patients who were treated with LA with this abnormality was steadily increasing in the years 2013-2016 - the official data are reported. In all new patients, who started to be treated at our LA center in 2017 (n = 20) the increased Lp(a) was a main indication for extracorporeal therapy, though some of them also showed clearly elevated LDL cholesterol (LDL-C) concentrations despite being treated with a maximal tolerated lipid-lowering drug therapy. A diabetes mellitus was seen in 5 patients. The higher was the Lp(a) level before the first LA session, the higher was the cardiovascular risk. Lp(a) concentrations measured before LA sessions were usually about 20% lower than those before the start of the LA therapy. Acutely, Lp(a) levels were reduced by about 70%. Following LA sessions the Lp(a) levels increased and in the majority reach pre-session concentrations after one week. Thus a weekly interval is best for the patients, but a few may need two sessions per week to stop the progress of atherosclerosis. The interval mean values were about 39% lower than previous levels. Several papers had been published showing a higher efficiency of LA therapy on the incidence of cardiovascular events in patients with high Lp(a) values when comparing with hypercholesterolemic patients with normal Lp(a) concentrations. Russian specific anti-Lp(a) columns positively affected coronary atherosclerosis. PCSK9 inhibitors reduce Lp(a) concentrations in many patients and in this way have a positive impact on cardiovascular outcomes. In the future, an antisense oligonucleotide against apolipoprotein(a) may be an alternative therapeutic option, provided a clear-cut reduction of cardiovascular events will be demonstrated., (Copyright © 2019. Published by Elsevier B.V.)

Lipoprotein(a) (Lp(a)) consists of an LDL particle whose apolipoprotein B (apoB) is covalently bound to apolipoprotein(a) (apo[a]). An increased Lp(a) concentration is a causal, independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and a predictor of incident or recurrent cardiovascular events. Although Lp(a) was first described as early as 1963, only the more recent results of epidemiological, molecular, and genetic studies have led to this unequivocal conclusion. More than 20% of Western populations have elevated Lp(a) values. Lp(a) concentrations should be always part of the lipid profile when ASCVD risk is assessed. However, presence of other risk factors, laboratory findings, medical history and family history must be considered to conclude on its clinical relevance in an individual patient. Early or progressive ASCVD or a familial predisposition are key findings which can be associated with elevated Lp(a). The cholesterol portion contained in Lp(a) is also included in the various methods of LDL-C measurement. To assess proximity to the cardiovascular risk related target value for LDL-C, appropriate correction should be applied when high Lp(a) values are obtained to estimate the LDL-C that can actually be treated by lipid lowering drugs. Initial study data show that antisense oligonucleotides, which selectively decrease apolipoprotein(a), are promising as future treatment options. Currently, lipoprotein apheresis, which has a reimbursement guideline in Germany, is the therapy of choice for patients with Lp(a)-associated progressive ASCVD, with the aim of sustained prevention of further cardiovascular events., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Lipoprotein(a) (Lp(a)) is an internationally recognized atherogenic risk factor which is inherited and not changed by nutrition or physical activity. At present, only proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may modestly decrease its concentration (but not in all patients)-leading to a certain decrease in cardiovascular events (CVE) in controlled studies. However, at present an elevation of Lp(a) is not a generally accepted indication for their use. More effective is lipoprotein apheresis (LA) therapy with respect to both lowering Lp(a) levels and reduction of CVE. In the future, an antisense oligonucleotide against apolipoprotein(a) will probably be available. Atherosclerosis in patients with an elevation of Lp(a) may affect several vessel regions (carotids, aorta, coronaries, leg arteries). Thus, Lp(a) should be measured in high-risk patients. These patients are usually cared for by their family doctors and by other specialists who should closely cooperate. Lipidologists should decide whether costly therapies like PCSK9 inhibitors or LA should be started. The main aim of current therapy is to optimize all other risk factors (LDL cholesterol, hypertension, diabetes mellitus, body weight, renal insufficiency). Patients should be regularly monitored (lab data, heart, arteries). This paper describes the duties of physicians of different specialties when caring for patients with high Lp(a) concentrations.

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: Lipoprotein(a) (Lp(a)) is a genetic risk factor for cardiovascular disease (CVD) and is associated with the induction and sustaining of atherosclerotic cardiovascular diseases (ASCVD). Since 2008 Lp(a) along with progressive CVD has been approved as an indication for regular lipoprotein apheresis (LA) in Germany. The German Lipoprotein Apheresis Registry (GLAR) has been initiated to provide statistical evidence for the assessment of extracorporeal procedures to treat dyslipidemia for both LDL-cholesterol (LDL-C) and Lp(a). The GLAR now allows prospective investigations over a 5-year period about annual incidence rates of cardiovascular events. Here Lp(a) patients (LDL-C < 100 mg/dl; Lp(a) > 60 mg/dl or >120 nmol/l) showed the same reduction of major coronary (83%) and non-coronary events (63%) as had been formerly shown in the Pro(a)LiFe study. However, Lp(a) is not only an apolipoprotein(a) (apo(a)) and LDL-C containing particle, which is covalently bound to a LDL-C core by a disulphide bridge. The composition of this particle, inter alia containing oxidized phospholipids, gives pro-atherosclerotic, pro-inflammatory, and pro-thrombotic properties, inducing atherosclerotic processes mainly in the arterial wall. However, recent investigations have shown that a reduction of inflammatory settings without LDL-C or Lp(a) reduction may reduce ASCVD events. Lipoprotein apheresis (LA) could not only reduce LDL-C and Lp(a) in parallel, but also different inflammatory and coagulation parameters. In summary lipoprotein apheresis is not only anti-atherosclerotic, but also anti-inflammatory and anti-thrombotic and therefore an ideal treatment option with respect to the shown reduction of major adverse coronary events (MACE) and major adverse non-coronary events (MANCE) by reducing Lp(a) levels.

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.)

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.)

Objectives: Lipoprotein(a) (Lp(a)) is an independent cardiovascular (CV) risk factor, predisposing to premature and progressive CV events. Lipoproteinapheresis (LA) is the only efficacious therapy for reducing Lp(a). Data comparing the clinical efficacy of LA with respect to reduction of CV events in subjects with elevated Lp(a) versus LDL-C versus both disorders is scarce. We aimed to perform this comparison in a multicenter observational study., Methods: 113 LA patients from 8 apheresis centers were included (mean age 56.3 years). They were divided into 3 groups: Group I: Lp(a) < 600 mg/l, LDL-C > 2.6 mmol/l, Group II: Lp(a) > 600 mg/l, LDL-C < 2.6 mmol/l, and Group III: Lp(a) > 600 mg/l, LDL-C > 2.6 mmol/l. CV events were documented 2 years before versus 2 years after LA start., Results: Before start of LA Group II showed the highest CV event rate (p 0.001). Group III had a higher CV event rate than Group I (p 0.03). During LA there was a significant reduction of CV events/patient in all vessel beds (1.22 ± 1.16 versus 0.33 ± 0.75, p < 0.001). The highest CV event rate during LA was seen in coronaries followed by peripheral arteries, cerebrovascular events were least common. Greater CV event reduction rates were achieved in patients with isolated Lp(a) elevation (-77%, p < 0.001) and in patients with Lp(a) and LDL-C elevation (-74%, p < 0.001) than in subjects with isolated hypercholesterolemia (-53%, p 0.06)., Conclusion: This study demonstrates that patients with Lp(a) elevation benefit most from LA treatment. Prospective trials to confirm these data are warranted., (Copyright © 2017. Published by Elsevier B.V.)

Background: Since 2005 an interdisciplinary German apheresis working group has been established by members of both German Societies of Nephrology and of Lipidologists and completed the data set for the registry according to the current guidelines and the German indication guideline for apheresis in 2009. In 2011 the German Lipoprotein Apheresis Registry (GLAR) was launched and data are available over nearly 5 years now., Methods and Results: During the time period 2012-2016, 71 German apheresis centers collected retrospective and prospective observational data of 1435 patients undergoing lipoprotein apheresis (LA) treatment of high LDL-C levels and/or high Lp (a) levels suffering from cardiovascular disease (CVD) or progressive CVD. A total of 15,527 completely documented LA treatments were entered into the database. All patients treated by LA showed a median LDL-C reduction rate of 67.5%, and a median Lp (a) reduction rate of 71.1%. Analog to the Pro(a)LiFe pattern, patient data were analyzed to the incidence rate of coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y‑1) and prospectively two years on LA treatment (y + 1 and y + 2). During two years of LA treatment a MACE reduction of 78% was observed. In the years considered, side effects of LA treatment were low (5.9%) and mainly comprised puncture problems., Conclusions: The 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 with a low rate of side effects.

Objective: Lipoprotein(a)-hyperlipoproteinemia (Lp(a)-HLP) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis (LA) in Germany since 2008. We aimed to study the long-term preventive effect of LA and to assess hypothetical clinical correlations of apolipoprotein(a) (apo(a)) by analyzing genotypes and phenotypes., Approach and Results: This prospective observational multicenter study included 170 patients with Lp(a)-HLP and progressive cardiovascular disease (48.9 years median age at diagnosis) despite other cardiovascular risk factors, including low-density lipoprotein cholesterol had maximally been treated (mean baseline low-density lipoprotein cholesterol: measured, 2.56 mmol/L [98.9 mg/dL] and corrected, 1.72 mmol/L [66.3 mg/dL]). Patients were prospectively investigated during a 5-year period about annual incidence rates of cardiovascular events. In addition, apo(a) isoforms and polymorphisms at the apo(a) gene (LPA) were characterized. One hundred fifty-four patients (90.6%) completed 5 years of follow-up. Mean Lp(a) concentration before commencing regular LA was 108.1 mg/dL. This was reduced by a single LA treatment by 68.1% on average. Significant decline of the mean annual cardiovascular event rate was observed from 0.58±0.53 2 years before regular LA to 0.11±0.15 thereafter (P<0.0001); 95.3% of patients expressed at least 1 small apo(a) isoform. Small apo(a) isoform (35.2%) carrying phenotypes were not tagged by single-nucleotide polymorphisms rs10455872 or rs3798220., Conclusions: Results of 5 years of prospective follow-up confirm that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP. Patients clinically selected by progressive cardiovascular disease were characterized by a highly frequent expression of small apo(a) isoforms. Only Lp(a) concentration seemed to comprehensively reflect Lp(a)-associated cardiovascular risk, however., (© 2016 American Heart Association, Inc.)

Introduction: The causal association of elevated lipoprotein(a) (Lp(a)) plasma levels with the increased cardiovascular risk is still controversial and presently there are no standard recommendations on managing of hyperLp(a)emia. Our retrospective analysis is aimed to explore the Lp(a) thresholds, the magnitude of various cardiovascular risk factors and their combinations., Methods: The files of 544 outpatients from our Outpatient Department of Lipid Disorders were divided into quintiles with respect to Lp(a) levels and reviewed regarding age, gender, Body Mass Index, dyslipidemias, arterial hypertension, diabetes mellitus, smoking and incidence of vascular events in coronaries, carotids and lower extremities. Furthermore we built 15 small quantiles to identify the Lp(a) threshold more precisely., Results: The incidence odds ratio for cardiovascular events rose from 2.65 in the 2nd quintile with Lp(a) 483-821 mg/L to 6.36 in the 5th quintile (Lp(a) ≥ 1495 mg/L). The relative risk of cardiovascular events was 0.08 in subjects with a Lp(a) level under 232 mg/l and 3.6 at Lp(a) ≥ 315 mg/L. The magnitude of the combination of elevated Lp (a) with arterial hypertension factor exceeded that of gender, age and combination of arterial hypertension with smoking., Conclusions: A Lp(a) plasma level of higher than about 300 mg/L seems to be a threshold for occurring of cardiovascular events. The combination of raised Lp(a) with arterial hypertension was found to be the most important cardiovascular risk factor. Lp(a) levels under 232 mg/L appeared to be a marker for good prognosis., (Copyright © 2015 Elsevier Ireland Ltd. 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.)

The MightyMedic (Multidisciplinary International Group for Hemapheresis TherapY and MEtabolic DIsturbances Contrast) Working Group has been founded in 2013. The leading idea was to establish an international network of interdisciplinary nature aimed at working to cross national borders research projects, clinical trials, educational initiatives (meetings, workshops, summer schools) in the field of metabolic diseases, namely hyperlipidemias, and diabetes, preventive cardiology, and atherosclerosis. Therapeutic apheresis, its indications and techniques, is a parallel field of investigation. The first on-line survey of the Group has been completed in the first half of 2014. The survey included # 24 Centers in Italy, Germany, Greece, UK, Sweden, Japan and USA. Relevant data have been collected on current practice in diagnosis, therapy and follow-up of dyslipidemias. 240 subjects with hyperlipidemia and treated with lipoprotein apheresis have been reported in the survey, but a large percentage of patients (35%) who could benefit from this therapeutic option are still treated by conventional drug approach. Genetic molecular diagnosis is performed in only 33% of patients while Lipoprotein(a) (Lp(a)) is included in cardiovascular disease risk assessment in 71% of participating Centers. New detailed investigations and prospective multicenter studies are needed to evaluate changes induced by the impact of updated indications and strategies, as well as new treatment options, targeting standardization of therapeutic and diagnostic approaches., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Lipoprotein apheresis (LA) is an officially accepted therapeutic approach in Germany. Reliable population-based data on the patients are scarce. It is of special interest to learn what are the main indications for this extracorporeal treatment and how many new patients started over the last years., Methods: This paper is a summary of the situation of the treatment of high-risk patients via LA in the federal state of Saxony, Germany. The documentation of all patients who agreed to be included into this study have been evaluated. Patients were treated at the University Hospital Dresden (UHD) and in private practices of nephrologists. This evaluation aimed at the characterization of patients treated with LA in Saxony with respect to age, gender, lipid pattern, to the number of new patients per year and the development of the ratio of patients to the Saxon population between 2010 and 2013. The obtained data were compared with the official statistics published by the National Association of Statutory Health Insurance Physicians for whole Germany., Results: In 2013, 181 patients, primarily males, were treated in 15 LA centers by 32 doctors. Still, the number of apheresis doctors per 1 million inhabitants is under the average in Germany (Saxony: 7.7/1 million inhabitants, average: 12/1 million inhabitants). The usage of LA is 45 per 1 million inhabitants in Saxony; in comparison to 2010, this is an increase of 16 per 1 million inhabitants. The number of new patients in 2013 with an isolated elevation of Lipoprotein(a) (Lp(a)) is twice as high than it was in 2011. The mean duration of all patients being treated with LA, most on a weekly basis, was 5.75 years (UHD: 6.2 years, range: 1 month to 23.1 years; other centers: 5.3 years, range: 1 month to 19.2 years). About 19.3% of all patients suffered from elevated triglyceride (TG) levels (>5 mmol/L). Non-high- density lipoprotein cholesterol (Non-HDL-C) was calculated, which is also acutely reduced by LA sessions. The following data were reported for those patients who are treated outside the UHD: risk factors such as hypertension and familial predisposition could be seen in almost every patient, and several others such as type 2 diabetes mellitus, genetic defects and obesity were also present. Almost all patients had suffered from cardiovascular events (CVE) occurring before the start of apheresis treatment. LA therapy led to a reduction in occurrence of CVE during LA therapy. In particular, patients with an isolated increased Lp(a) had the highest reduction when comparing CVE before and during apheresis therapy. In the official statistics published by the National Association of Statutory Health Insurance Physicians the number of LA patients with homozygous familial hypercholesterolemia (HoFH) is clearly too high. Moreover, these statistics do not include patients who are treated at hospitals like the UHD., Conclusion: All in all it can be shown that the extracorporeal therapy is performed effectively in Saxony, and that more centers than 2010 (additional 5) were conducting this therapy when lipid-lowering medication was not sufficiently effective. It is certain that the number of patients requiring LA will increase in the future., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Lipoprotein(a) (Lp(a)) is a low density lipoprotein-like particle to which apolipoprotein(a) is bound. It is recognized as an atherosclerosis-inducing risk factor. Up to now a detailed description of the effect of Lipoprotein apheresis (LA) on Lp(a) levels in the long run is lacking., Methods: We studied 59 patients with elevated Lp(a) levels who were treated with LA at the Lipoprotein Apheresis Center at the University Hospital Dresden. We analyzed Lp(a) concentrations before the start of the LA treatment and during this extracorporeal therapy., Results: Comparing the Lp(a) levels before the start of LA therapy and pre-apheresis (measured before the LA sessions) Lp(a) levels, we observed a reduction of the Lp(a) levels of about 22.8% in all patients. Lp(a) levels were acutely (comparing post-apheresis with pre-apheresis concentrations) reduced by all 6 available LA methods (by about 70%). A linear regression analysis was performed to differentiate the long term course of pre-apheresis Lp(a) levels. In 30 patients we saw an increase of the pre-apheresis Lp(a) levels over the time, in 15 patients a constancy and in 14 patients a decrease. Patients with a decrease of pre-apheresis Lp(a) levels over the time had significantly higher initial (before the start of the extracorporeal treatment) and pre-apheresis values and they were significantly older. These patients had significantly more severe peripheral arterial disease as well as cardiac valve and carotid stenosis. The patients with the lowest initial Lp(a) levels and an increase of the pre-apheresis Lp(a) levels over the time had the highest percentage of intake of Tredaptive(®)/Niaspan(®) though after stopping the intake of these nicotinic acid preparations no clear increase of Lp(a) concentrations was observed. The applied LA systems did not seem to have a significant influence on the course of pre-apheresis Lp(a) levels. In all patients there was a high variability of Lp(a) concentrations between LA sessions which may in part be due to the inaccuracy of the method used to measure Lp(a) concentrations., Conclusion: Pre-apheresis Lp(a) levels (before the LA sessions) are lower than those before the start of a LA treatment but they behave differently among patients during LA treatment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Lipoprotein(a) (Lp(a)) hyperlipoproteinemia is a major risk factor for cardiovascular disease, which is not affected by treatment of other cardiovascular risk factors. This study sought to assess the effect of chronic lipoprotein apheresis (LA) on the incidence of cardiovascular events in patients with progressive cardiovascular disease receiving maximally tolerated lipid-lowering treatment., Methods and Results: In a prospective observational multicenter study, 170 patients were investigated who commenced LA because of Lp(a)-hyperlipoproteinemia and progressive cardiovascular disease. Patients were characterized regarding plasma lipid status, lipid-lowering drug treatment, and variants at the LPA gene locus. The incidence rates of cardiovascular events 2 years before (y-2 and y-1) and prospectively 2 years during LA treatment (y+1, y+2) were compared. The mean age of patients was 51 years at the first cardiovascular event and 57 years at the first LA. Before LA, mean low-density lipoprotein cholesterol and Lp(a) were 2.56±1.04 mmol·L(-1) (99.0±40.1 mg·dL(-1)) and Lp(a) 3.74±1.63 µmol·L(-1) (104.9±45.7 mg·dL(-1)), respectively. Mean annual rates for major adverse coronary events declined from 0.41 for 2 years before LA to 0.09 for 2 years during LA (P<0.0001). Event rates including all vascular beds declined from 0.61 to 0.16 (P<0.0001). Analysis of single years revealed increasing major adverse coronary event rates from 0.30 to 0.54 (P=0.001) for y-2 to y-1 before LA, decline to 0.14 from y-1 to y+1 (P<0.0001) and to 0.05 from y+1 to y+2 (P=0.014)., Conclusions: In patients with Lp(a)-hyperlipoproteinemia, progressive cardiovascular disease, and maximally tolerated lipid-lowering medication, LA effectively lowered the incidence rate of cardiovascular events., Clinical Trial Registration Url: https://drks-neu.uniklinik-freiburg.de. Unique identifier: DRKS00003119.

This paper summarizes the situation pertinent to treatment via lipoprotein apheresis in the federal state of Saxony, Germany in 2010. In total, 119 predominately male patients were treated in 10 centers; the majority of the patients was older than the mean age of the general population. Several risk factors were present, particularly a familial predisposition and hypertension. All patients had experienced cardiovascular events and the majority was taking statins. Patient data from the University Hospital Carl Gustav Carus in Dresden concurred with data derived from patients treated at nephrological practices. In the mean, patients attended the centers for about 6 years, the majority weekly. LDL cholesterol concentrations prior to apheresis were clearly higher than target levels; apheresis sessions decreased LDL cholesterol by 69%. Lipoprotein(a) levels could be measured in 75 patients and were effectively reduced by lipoprotein apheresis. In Saxony, 29 patients per 1 million inhabitants received lipoprotein apheresis, which is higher than the proportion of patients treated in Germany as a whole. The need for this extracorporeal treatment seems to be much greater than its current utilization. Among the patients only one homozygous patient with familial hypercholesterolemia was observed. Physicians should be actively informed about this therapeutic possibility to reduce the cardiovascular risk efficiently. The introduction of new drugs may alter the position of lipoprotein apheresis within the therapeutic spectrum., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Lipoprotein apheresis is indicated in patients at high risk for cardiovascular disease due to severe hyperlipoproteinemia, which is not adequately controlled by diet and medication. This extracorporeal therapy reduces the event rate, although it does not completely abolish new events. We compared atherogenic risk factors in patients who were treated in 2009 and 2010 with lipoprotein apheresis and who suffered events (n 20) with patients who did not (n 44). Among the 45 cardiovascular events that occurred four were strokes, one was myocardial infarction, and two were bypass operations (one coronary and one peripheral). The following risk factors were found to be associated with events: male gender, coexisting diabetes/glucose intolerance and elevation of Lp(a) concentrations. In addition, the history of previous cardiovascular events, the efficiency of the lipoprotein apheresis therapy as judged by the reduction rates of LDL-C and of Lp(a), and the duration of the extracorporeal treatment (patients with events had started treatment with lipoprotein apheresis more recently) may play a role. We did not observe any influence of family history, of the underlying lipid disorder or lipid levels, of arterial hypertension or of smoking habits. Evidently, apheresis therapy of longer duration (more than two years) stabilizes the cardiovascular situation of the patients. Patients on apheresis therapy should be regularly assessed with respect to their risk factor and vascular situation. Lipoprotein apheresis therapy is important for the reduction of cardiovascular events, but optimization of additional modifiable risk factors should also be undertaken., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Lipid apheresis is an efficient method for reducing cholesterol and triglyceride serum levels, but its effect on other lipid species has not been investigated. This study explored the effect of LDL apheresis on the serum lipidome in hyperlipidemic patients with cardiovascular complications. Lipid analysis was performed before and immediately after a single apheresis procedure in serum samples of six patients treated with different apheresis methods. Conventional lipid parameters (TC, LDL-C, HDL-C, TG) were determined by standard enzymatic methods. Phosphatidylcholines (PC), sphingomyelins (SM), phosphatidylethanolamines (PE), PE-based plasmalogens (PE&#95;pl), lysophosphatidylcholines (LPC), ceramides (Cer), free cholesterol (FC) and cholesterol ester (CE) were detected with electrospray ionization tandem mass spectrometry. LDL apheresis induced a mean reduction of LDL-C by 68% and of HDL-C by 14%, respectively. CE, FC, SM, and Cer revealed an apheresis-induced decrease of about 47%, which was not statistically different from LDL-C reduction. In contrast, the decline of PC (31%), LPC (26%), PE (2%), and PE&#95;pl (37%) after apheresis was significantly lower in comparison to LDL-C reduction, but not statistically different from HDL-C decrease. While the group of PC-species declined uniformly during apheresis, changes in particular LPC-, Cer-, and SM-species revealed significant differences, reflecting their differential distribution in lipoprotein particles and blood cells. We conclude that the acute effect of lipid apheresis on serum lipidome could be predominantly attributed to lipoprotein changes, while blood cell damages during this procedure caused additional, less pronounced changes. The importance of specific changes in particular lipid species remains to be established., (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.)

Introduction: The role of lipoprotein (a) (Lp(a)) in atherogenesis has been previously demonstrated in several trials reporting various and sometimes contradictory findings. Our retrospective study analyzed the incidence of cardiovascular events in patients with Lp(a) plasma level of more than 250 mg/l, which has been defined as a threshold in previous publications., Methods: The files of 303 patients with Lp(a) of more than 250 mg/l were divided into 5 groups categorized by Lp(a) level increase and reviewed regarding age, sex, BMI, dyslipidemias, arterial hypertension, diabetes mellitus, family history of cardiovascular events, fatty liver and incidence of vascular events in coronaries, carotids and lower extremities., Results: No significant differences were observed with respect to sex, age, BMI, dyslipidemias, diabetes mellitus, arterial hypertension and hepatic steatosis. The likely occurrence of at least one event was 2.77 times more in the fourth (Lp(a) 1235 +/- 82 mg/l) and 6.2 times more in the fifth (Lp(a) 2068 +/- 471 mg/l) than in the first group (Lp(a) 322 +/- 48 mg/l). The 5 groups differed with respect to average "events per patient" (p < 0.001). The magnitude of increased Lp (a) exceeded that of other risk factors., Conclusion: A substantially (more than 1100 mg/l) elevated Lp(a) plasma level seems to be an important predictor for the occurrence of cardiovascular events. It makes sense in clinical practice to consider patients exhibiting this elevation as having a high cardiovascular risk. In case of progression of atherosclerotic complications the patients should be assigned for lipid apheresis., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Abstract: Background: Lipid apheresis (LA) is instituted to increase life expectancy in patients with previous cardiovascular events and severe and otherwise untreatable hypercholesterolemia. Studies have demonstrated that even a single LA markedly improves endothelial and micro-vascular function in patients. It is unknown whether these changes also impact pulse wave reflection and established parameters of arterial stiffness. Methods: In 20 patients on regular LA (8 treated by immunoadsorption, 7 by lipid filtration, 5 by direct adsorption of lipids) we measured peripheral blood pressure, heart rate, central systolic pressure (CSP), central pulse pressure (CPP), augmentation index (AIX) and pulse wave velocity by applanation tonometry (SphygmoCor, Atcor Medical) before and after a single treatment. Results: Peripheral blood pressure and heart rate were comparable pre- and post treatment. CSP, CPP, AIX and PWV did not significantly change during LA independent of treatment modality although LDL-cholesterol levels were markedly reduced (in average from 3.5±0.9 to 0.9±0.3 mmol/L). Conclusion: The well-documented effects of a single LA on microvascular function are not associated with measurable changes in pulse wave reflection. Future studies are required in order to evaluate long-term effects of LA in this context. [Copyright &y& Elsevier]