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U Julius - One of the best experts on this subject based on the ideXlab platform.
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Lipoprotein Apheresis: YESTERDAY, TODAY, TOMORROW. REVIEW
'Silicea - Poligraf LLC', 2018Co-Authors: U Julius, S. Tselmin, S. R. BornsteinAbstract:The first attempts to treat patients with homozygous familial hypercholesterolemia (HCH) were performed in the 60ies and 70ies using a total plasma exchange. Later on, more specific Lipoprotein Apheresis (LA) methods have been developed – the replacement with foreign proteins was no longer necessary. It could be demonstrated that LA is life-saving in these patients, lipid-lowering drugs were shown to be much less effective than in other HCH patients. A severe HCH became an accepted indication for LA when cardiovascular events appeared. An elevation of Lipoprotein(a) (Lp(a)) is an internationally accepted independent atherogenic risk factor. Thus, an increasing number of patients with high Lp(a) concentrations suffering from life-threatening cardiovascular events like a myocardial infarction or a stroke started to be treated extracorporeally. Russian specific PocardR anti-Lp(a) columns are produced, their position within the LA methods is discussed. In the future, an antisense oligonucleotide against apoLipoprotein(a) will represent another therapeutic option
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toward an international consensus integrating Lipoprotein Apheresis and new lipid lowering drugs
Journal of Clinical Lipidology, 2017Co-Authors: Claudia Stefanutti, Mariko Haradashiba, U Julius, Gerald F Watts, Maria Laura Cossu, V J J Schettler, Giustina De Silvestro, Handrean Soran, Jeanine Roeters E Van Lennep, Livia PisciottaAbstract:Background Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein Apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic Lipoproteins including low-density Lipoprotein cholesterol and Lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Sources of material This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density Lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. Abstract of findings Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. Conclusion Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for HemApheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk.
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Lipoprotein Apheresis for Lipoprotein a associated cardiovascular disease prospective 5 years of follow up and apoLipoprotein a characterization
Arteriosclerosis Thrombosis and Vascular Biology, 2016Co-Authors: Eberhard Roeseler, Franz Heigl, Josef Leebmann, U Julius, Ralf Spitthoever, Dennis Heutling, Paul Breitenberger, Walter Lehmacher, Pia R Kamstrup, Borge G NordestgaardAbstract: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.
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adverse events of Lipoprotein Apheresis and immunoadsorption at the Apheresis center at the university hospital dresden
Atherosclerosis Supplements, 2015Co-Authors: J Dittrichriediger, Ulrike Schatz, Bernd Hohenstein, U JuliusAbstract:Abstract Background Lipoprotein Apheresis and immunoadsorption methods have a firm place among therapeutic approaches in order to treat disorders of Lipoprotein metabolism or anti-body induced diseases. The extracorporeal treatment is associated with adverse effects, we wanted to report the Dresden experience. Methods In this study we retrospectively analyzed the adverse events of several Lipoprotein Apheresis and immunoadsorption methods at the Apheresis Center in Dresden (Germany). We carefully looked into all available documents. The first extracorporeal Lipoprotein Apheresis was performed in 1990 and the first extracorporeal immunoadsorption was executed in 1995. Throughout the 23 years study period, 10 different methods were employed in treating 268 patients for a total of 25,293 treatments. Results Adverse events of varying severity occurred in 1948 of the treatments (7.7%). We subdivided them into mild (61.3% no treatment was necessary), moderate (37.0% oral medication or infusion was given) and severe (1.7% emergency hospitalization was necessary). Therapy had to be stopped prematurely in 1.5% of the treatments. We compared adverse events profiles among the different methods and evaluated for differences by gender. Females were found to have a significantly higher risk of adverse events than male patients. In males, the rate of adverse events ranged from 3.3% (Liposorber ® D) to 11% (Therasorb™ Ig); in females the minimum rate was 7.8% (DALI) and the maximum 30% (rheopheresis). Adverse events were evenly distributed between the ages of 30–69, the age range at which most of the therapies were performed. We also found that all methods had a higher rate of adverse events during the first year of treatment. Puncture problems and hypotension were the most common adverse events. Conclusion It can be stressed that in general the extracorporeal methods used can be regarded as safe.
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increasing plasma lysophosphatidylcholine levels in patients with regular dextran sulfate Lipoprotein Apheresis
Atherosclerosis Supplements, 2015Co-Authors: Juergen Graessler, Steffi Kopprasch, Stefan R Bornstein, Bernd Hohenstein, Kai Schuhmann, Andrej Shevchenko, Ryan Ban, S Bergmann, U JuliusAbstract:Abstract Objectives Previously we found a highly significant increase of phosphatidylethanolamines (PE) in response to acute Lipoprotein Apheresis (LA) with whole blood dextran sulfate adsorption (DSA) in contrast to the overall tendency of reduction of lipid metabolites of all lipid classes in post-Apheresis plasma. Therefore, the aim of the present study was to analyze long-term modifications of the plasma lipidomic profile in patients with repeated DSA Apheresis. Methods Nine patients weekly treated with DSA were followed for 40 weeks. Pre- and post-Apheresis levels of routine lipid parameters and lipidomic profiles of five Apheresis sessions were assessed. Results The main finding of the present study was a progressive increase of pre- and post-Apheresis plasma lysophosphatidylcholine (LPC) levels, which doubled in concentration at the end of the 40 week observation period. LPC metabolites which mainly contributed to this increase were LPC 20:4 > 18:0 > 18:1 > 16:0 > 20:3 > 18:2. Conclusion These data indicate that long-term application of DSA technology may be associated with a continuous increase in LPC levels. Possible pro- or anti-atherogenic consequences should be elucidated in further studies.
Nicola Ferri - One of the best experts on this subject based on the ideXlab platform.
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from Lipoprotein Apheresis to proprotein convertase subtilisin kexin type 9 inhibitors impact on low density Lipoprotein cholesterol and c reactive protein levels in cardiovascular disease patients
European Journal of Preventive Cardiology, 2018Co-Authors: M G Zenti, Anna Altomari, Maria Giovanna Lupo, Margherita Botta, Enzo Bonora, Alberto Corsini, Massimiliano Ruscica, Nicola FerriAbstract:In this observational study, we compared the effect of Lipoprotein Apheresis and evolocumab or alirocumab on levels of Lipoprotein cholesterol, triglycerides and inflammatory markers (C reactive protein and interleukin 6) in cardiovascular patients ( n = 9). Patients were monitored during the last year of Lipoprotein Apheresis followed by six months of treatment with proprotein convertase subtilisin/kexin type 9 inhibitors. The biochemical parameters were determined pre- and post- every Apheresis procedure for 12 months and then after one, three and six months of treatment with evolocumab (140 mg every two weeks [Q2W]) or alirocumab (75 mg or 150 mg every two weeks [Q2W]). Lipoprotein Apheresis significantly reduced low-density Lipoprotein cholesterol levels from 138 ± 32 mg/dl to 46 ± 16 mg/dl ( p < 0.001), with an inter-Apheresis level of 114 ± 26 mg/dl. Lipoprotein(a) was also reduced from a median of 42 mg/dl to 17 mg/dl ( p < 0.01). Upon anti-proprotein convertase subtilisin/kexin type 9 therapy, low-density Lipoprotein cholesterol levels were similar to post-Apheresis (59 ± 25, 41 ± 22 and 42 ± 21mg/dl at one, three and six months, respectively) as well as those of Lipoprotein(a) (18 mg/dl). However, an opposite effect was observed on high-density Lipoprotein cholesterol levels: -16.0% from pre- to post-Apheresis and +34.0% between pre-Apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors. Apheresis significantly reduced high-sensitivity C-reactive protein levels (1.5 ± 1.2 mg/l pre-Apheresis to 0.6 ± 0.6 mg/l post-Apheresis), while no changes were found upon proprotein convertase subtilisin/kexin type 9 mAbs administration. In conclusion, our study demonstrated that, by switching from Lipoprotein Apheresis to anti-proprotein convertase subtilisin/kexin type 9 therapies, patients reached similar low-density Lipoprotein cholesterol and Lipoprotein(a) levels, increased those of high-density Lipoprotein cholesterol, and showed no changes on high-sensitivity C-reactive protein.
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From Lipoprotein Apheresis to proprotein convertase subtilisin/kexin type 9 inhibitors: Impact on low-density Lipoprotein cholesterol and C-reactive protein levels in cardiovascular disease patients.
European journal of preventive cardiology, 2018Co-Authors: M G Zenti, Anna Altomari, Maria Giovanna Lupo, Margherita Botta, Enzo Bonora, Alberto Corsini, Massimiliano Ruscica, Nicola FerriAbstract:In this observational study, we compared the effect of Lipoprotein Apheresis and evolocumab or alirocumab on levels of Lipoprotein cholesterol, triglycerides and inflammatory markers (C reactive protein and interleukin 6) in cardiovascular patients ( n = 9). Patients were monitored during the last year of Lipoprotein Apheresis followed by six months of treatment with proprotein convertase subtilisin/kexin type 9 inhibitors. The biochemical parameters were determined pre- and post- every Apheresis procedure for 12 months and then after one, three and six months of treatment with evolocumab (140 mg every two weeks [Q2W]) or alirocumab (75 mg or 150 mg every two weeks [Q2W]). Lipoprotein Apheresis significantly reduced low-density Lipoprotein cholesterol levels from 138 ± 32 mg/dl to 46 ± 16 mg/dl ( p
Stefanutti Claudia - One of the best experts on this subject based on the ideXlab platform.
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A complicated pregnancy in homozygous familial hypercholesterolaemia treated with Lipoprotein Apheresis: A case report
'Elsevier BV', 2019Co-Authors: Perrone Seila, Morozzi Claudia, Di Giacomo Serafina, Perrone Giuseppina, Brunelli Roberto, Galoppi Paola, Flammini Guendalina, Stefanutti ClaudiaAbstract:BACKGROUND AND AIMS: During pregnancy total cholesterol (TC) and low density Lipoprotein cholesterol (LDL-C) levels increase significantly and Lipoprotein Apheresis (LA) is considered the most effective therapy in homozygous familial hypercholesterolaemia (HoFH) for modulating lipid and Lipoprotein levels and reducing maternal and foetal complications. CLINICAL CASE: A primigravida 28 years old Caucasian female patient, previously diagnosed as to be HoFH, was admitted at our outpatient service at the beginning of pregnancy. METHODS: The patient was continuously submitted to LA every two weeks without foetal complication. During pregnancy two methods have been utilised: selective Apheresis, and later plasma exchange. At 33 weeks gestational age the patient developed progressively hypertension, associated to LDL-C levels increase. Weekly LA was favoured. RESULTS: At 34 weeks +5 days patient suddenly experienced acute chest pain and abnormal electrocardiogram heart tracing and cardiac enzymes increase. An emergency caesarean section was performed without complications and the foetus was healthy. The patient was immediately transferred to Coronary Intensive Care Unit, where she was diagnosed non-ST elevation myocardial infarction (NSTEMI). Notwithstanding the patient improved in few days and was quickly discharged in fair clinical condition. CONCLUSIONS: LA is a safe and effective tool in HoFH subjects even in pregnancy. Evidence based guidelines for the management of these patients during pregnancy are still lacking.
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Familial hypercholesterolaemia: the influence of Lipoprotein Apheresis on choroid and retina. an oct and octa retrospective study
Investigative Ophthalmology & Visual Science, 2019Co-Authors: Pacella Elena, Pannarale Luigi, Pacella Fernanda, Trovato Battagliola Edoardo, Forastiere Michele, Stefanutti ClaudiaAbstract:Purpose: High cholesterol levels in untreated familial hypercholesterolemia (FH) can significantly compromise retinal microvasculature. This type of dyslipidemia is commonly treated with combination drug therapy and Lipoprotein Apheresis (LA). We conducted a retrospective observational study by means of optical coherence tomography (OCT) and optical coherence tomography-angiography (OCTA) on patients affected by familial hypercholesterolemia (FH) treated by LA and healthy controls. Methods: A group of 20 patients (40 eyes; 8 males and 12 females; mean age±SD: 50, 05±13, 68) with FH were compared to a group of 20 matched healthy controls (CT group). Inclusion criteria: genetically-confirmed diagnosis of FH, treatment with combination drug therapy and LA for at least 2 years, spherical equivalent (SE)-3 to+ 3 diopters. Exclusion criteria: pre-existent retinal or choroidal damage (including macula
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Toward an international consensus—Integrating Lipoprotein Apheresis and new lipid-lowering drugs
'Elsevier BV', 2017Co-Authors: Stefanutti Claudia, Harada-shiba Mariko, Julius Ulrich, Watts, Gerald F., Cossu Maria, Schettler, Volker J., De Silvestro Giustina, Soran Handrean, Van Lennep, Jeanine Roeters, Pisciotta LiviaAbstract:BACKGROUND: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein Apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic Lipoproteins including low-density Lipoprotein cholesterol and Lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. SOURCES OF MATERIAL: This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density Lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. ABSTRACT OF FINDINGS: Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. CONCLUSION: Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for HemApheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk
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Toward an international consensus-Integrating Lipoprotein Apheresis and new lipid-lowering drugs
2016Co-Authors: Stefanutti Claudia, Harada-shiba Mariko, Schettler, Volker J., Van Lennep, Jeanine Roeters, Julius U., Watts Gerald, Cossu M., De Silvestro G., Soran H., Pisciotta L.Abstract:textabstractBackground: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein Apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic Lipoproteins including low-density Lipoprotein cholesterol and Lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Sources of material: This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density Lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. Abstract of findings: Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. Conclusion: Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for HemApheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk
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Management of homozygous familial hypercholesterolemia in real-world clinical practice: A report of 7 Italian patients treated in Rome with lomitapide and Lipoprotein Apheresis
'Elsevier BV', 2016Co-Authors: Stefanutti Claudia, Morozzi Claudia, Di Giacomo Serafina, Sovrano Barbara, Mesce Dario, Grossi AlbertoAbstract:Homozygous familial hypercholesterolemia (HoFH) is a rare, genetically determined condition of highly elevated low-density Lipoprotein cholesterol (LDLC) levels. If untreated, patients do not typically survive beyond the second decade of life. Traditional lipid-lowering therapies (statins and ezetimibe) are largely ineffective in HoFH patients, and extracorporeal Lipoprotein Apheresis (LA) forms the mainstay of treatment. Lomitapide is a microsomal triglyceride transfer protein inhibitor approved for the treatment of HoFH as an adjunct to LA. We undertook to examine the efficacy and safety of lomitapide in 7 HoFH patients treated with LA in the Lipid Clinic and Therapeutic Apheresis Unit in Rome, Italy outside a clinical trial setting
Josef Leebmann - One of the best experts on this subject based on the ideXlab platform.
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alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing Lipoprotein Apheresis the odyssey escape trial
European Heart Journal, 2016Co-Authors: Patrick M. Moriarty, Klaus G. Parhofer, Wolfgang Ramlow, Stephan P Babirak, Marcandre Cornier, Barton P Duell, Bernd Hohenstein, Josef Leebmann, Volker Schettler, Vinaya SimhaAbstract:Aim To evaluate the effect of alirocumab on frequency of standard Apheresis treatments [weekly or every 2 weeks (Q2W)] in heterozygous familial hypercholesterolaemia (HeFH). Methods and results ODYSSEY ESCAPE ([NCT02326220][1]) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W Lipoprotein Apheresis. Patients were randomly assigned (2:1, respectively) to receive alirocumab 150 mg ( n = 41) or placebo ( n = 21) Q2W subcutaneously for 18 weeks. From day 1 to week 6, Apheresis rate was fixed according to the patient’s established schedule; from weeks 7 to 18, Apheresis rate was adjusted based on the patient’s low-density Lipoprotein cholesterol (LDL-C) response in a blinded fashion. Apheresis was not performed when the LDL-C value was ≥30% lower than the baseline (pre-Apheresis) value. The primary efficacy endpoint was the rate of Apheresis treatments over 12 weeks (weeks 7–18), standardized to number of planned treatments. In the alirocumab group the least square (LS) mean ± SE (95% confidence interval [CI]) per cent change in pre-Apheresis LDL-C from baseline at week 6 was − 53.7 ± 2.3 (−58.2 to − 49.2) compared with 1.6 ± 3.1 (–4.7 to 7.9) in the placebo group. The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab (Hodges–Lehmann median estimate of treatment difference: 0.75; 95% CI 0.67–0.83; P < 0.0001). Therefore, alirocumab-treated patients had a 0.75 (75%) additional reduction in the standardized rate of Apheresis treatments vs. placebo-treated patients. During this period, 63.4% of patients on alirocumab avoided all and 92.7% avoided at least half of the Apheresis treatments. Adverse event rates were similar (75.6% of patients on alirocumab vs. 76.2% on placebo). Conclusions Lipoprotein Apheresis was discontinued in 63.4% of patients on alirocumab who were previously undergoing regular Apheresis, and the rate was at least halved in 92.7% of patients. Alirocumab was generally safe and well tolerated. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02326220&atom=%2Fehj%2Fearly%2F2016%2F09%2F08%2Feurheartj.ehw388.atom
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Lipoprotein Apheresis for Lipoprotein a associated cardiovascular disease prospective 5 years of follow up and apoLipoprotein a characterization
Arteriosclerosis Thrombosis and Vascular Biology, 2016Co-Authors: Eberhard Roeseler, Franz Heigl, Josef Leebmann, U Julius, Ralf Spitthoever, Dennis Heutling, Paul Breitenberger, Walter Lehmacher, Pia R Kamstrup, Borge G NordestgaardAbstract: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.
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Lipoprotein Apheresis in patients with maximally tolerated lipid lowering therapy Lipoprotein a hyperLipoproteinemia and progressive cardiovascular disease prospective observational multicenter study
Circulation, 2013Co-Authors: Josef Leebmann, Franz Heigl, U Julius, Eberhard Roeseler, Ralf Spitthoever, Dennis Heutling, Paul Breitenberger, Winfried Maerz, Walter Lehmacher, Andreas HeibgesAbstract: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.
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Lipoprotein Apheresis in patients with maximally tolerated lipid lowering therapy Lipoprotein a hyperLipoproteinemia and progressive cardiovascular disease prospective observational multicenter study
Circulation, 2013Co-Authors: Josef Leebmann, Franz Heigl, U Julius, Eberhard Roeseler, Ralf Spitthoever, Dennis Heutling, Paul Breitenberger, Winfried Maerz, Walter Lehmacher, Andreas HeibgesAbstract: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: . Unique identifier: DRKS00003119. # Clinical Perspective {#article-title-17}
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Lipoprotein Apheresis in patients with maximally tolerated lipid lowering therapy Lipoprotein a hyperLipoproteinemia and progressive cardiovascular disease
Circulation, 2013Co-Authors: Josef Leebmann, Franz Heigl, U Julius, Eberhard Roeseler, Ralf Spitthoever, Dennis Heutling, Paul Breitenberger, Winfried Maerz, Walter Lehmacher, Andreas HeibgesAbstract: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 chol...
Andreas Heibges - One of the best experts on this subject based on the ideXlab platform.
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prevention of cardiovascular complications in patients with lp a hyperLipoproteinemia and progressive cardiovascular disease by long term Lipoprotein Apheresis according to german national guidelines
Clinical Research in Cardiology Supplements, 2017Co-Authors: Reinhard Klingel, Andreas Heibges, Cordula FassbenderAbstract:Lipoprotein(a) (Lp(a)) is an independent cardiovascular risk factor playing a causal role for atherosclerotic cardiovascular disease (CVD). Lipoprotein Apheresis (LA) is a safe well-tolerated outpatient treatment to lower LDL-C and Lp(a) by 60–70%, and is the ultimate escalating therapeutic option in patients with hyperLipoproteinemias (HLP) involving LDL particles. Major therapeutic effect of LA is preventing cardiovascular events. Lp(a)-HLP associated with progressive CVD has been approved as indication for regular LA in Germany since 2008. The Pro(a)LiFe-study investigated with a prospective multicenter design the long-term preventive effect of LA on incidence rates of cardiovascular events prospectively over a period of 5 years in 170 consecutive patients who commenced regular LA. During a median period of 4.7 years of the pre-LA period, Lp(a) associated progressive CVD became apparent. ApoLipoprotein(a) (apo(a)) isoforms and polymorphisms at the apo(a) gene (LPA) were analyzed to assess hypothetical clinical correlations. 154 patients (90.6%) completed 5‑years follow-up. Significant decline of the mean annual major adverse cardiac event (MACE) rate was observed from 0.41 ± 0.45 two years prior to regular LA to 0.06 ± 0.11 during 5 years with regular LA (p < 0.0001). 95.3% of patients expressed at least one small apo(a) isoform. Calculation of isoform specific concentrations allowed to confirm the equivalence of 60 mg/dl or 120 nmol/l as Lp(a) thresholds of the German LA guideline. Results of 5 years prospective follow-up confirmed that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP and afore progressive CVD.
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Lipoprotein Apheresis for lp a hyperLipoproteinemia with progressive cardiovascular disease additional particular aspects of the pro a life multicenter trial
Atherosclerosis Supplements, 2015Co-Authors: Reinhard Klingel, Andreas Heibges, Cordula FassbenderAbstract:Lipoprotein Apheresis (LA) can lower LDL-cholesterol and Lp(a) by 60%-70% and is the final escalating option in patients with hyperLipoproteinemias involving LDL or Lp(a) particles. Major therapeutic effect of LA is preventing cardiovascular events. In Germany since 2008 a reimbursement guideline has been implemented accepting to establish the indication for LA not only for familial or severe forms of hypercholesterolemia but also based on Lp(a)-hyperLipoproteinemia associated with a progressive course of cardiovascular disease, that persists despite effective treatment of other concomitant cardiovascular risk factors. The Pro(a)LiFe-study confirmed with a prospective multicenter design that LA can be regarded as an important therapeutic approach to effectively reduce Lp(a) plasma levels and prevent cardiovascular events in this particular high-risk patient group. Results support that Lp(a) may be a major causal factor for precipitating mechanisms of accelerated progression of cardiovascular disease (CVD). Indication for LA based on measurement of Lp(a) as part of risk assessment is supported by the following conditions: progressive CVD as assessed clinically and with imaging techniques, established maximally tolerated lipid lowering drug treatment, recent cardiovascular events despite efficient drug treatment, out of the ordinary frequency of cardiovascular events, early CVD, or positive family history of early CVD. Still existing difficulties with Lp(a) laboratory measurement require a practical approach to establish the indication for LA considering the 60 mg/dl threshold of German guidelines with selecting an Lp(a) assay which has been calibrated for mass.
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Lipoprotein Apheresis in patients with maximally tolerated lipid lowering therapy Lipoprotein a hyperLipoproteinemia and progressive cardiovascular disease prospective observational multicenter study
Circulation, 2013Co-Authors: Josef Leebmann, Franz Heigl, U Julius, Eberhard Roeseler, Ralf Spitthoever, Dennis Heutling, Paul Breitenberger, Winfried Maerz, Walter Lehmacher, Andreas HeibgesAbstract: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.
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Lipoprotein Apheresis in patients with maximally tolerated lipid lowering therapy Lipoprotein a hyperLipoproteinemia and progressive cardiovascular disease prospective observational multicenter study
Circulation, 2013Co-Authors: Josef Leebmann, Franz Heigl, U Julius, Eberhard Roeseler, Ralf Spitthoever, Dennis Heutling, Paul Breitenberger, Winfried Maerz, Walter Lehmacher, Andreas HeibgesAbstract: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: . Unique identifier: DRKS00003119. # Clinical Perspective {#article-title-17}
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Lipoprotein Apheresis in patients with maximally tolerated lipid lowering therapy Lipoprotein a hyperLipoproteinemia and progressive cardiovascular disease
Circulation, 2013Co-Authors: Josef Leebmann, Franz Heigl, U Julius, Eberhard Roeseler, Ralf Spitthoever, Dennis Heutling, Paul Breitenberger, Winfried Maerz, Walter Lehmacher, Andreas HeibgesAbstract: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 chol...