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Klaus G. Parhofer - One of the best experts on this subject based on the ideXlab platform.

  • the potential of mipomersen an apob synthesis inhibitor to reduce necessity for LDL Apheresis in patients with heterozygous familial hypercholesterolemia and coronary artery disease
    Expert Opinion on Pharmacotherapy, 2013
    Co-Authors: Anja Vogt, Klaus G. Parhofer
    Abstract:

    Introduction: LDL-Apheresis is a treatment option for familial hypercholesterolemia (FH) with country-specific thresholds for LDL-cholesterol (LDL-C) for initiation. Apheresis also reduces lipoprotein(a) [Lp(a)] and may be used to lower Lp(a) in high-risk patients. Mipomersen, an apolipoproteinB-synthesis-inhibitor, reduces LDL-C and Lp(a). We hypothesized that mipomersen may prevent the necessity for Apheresis by reducing the both below thresholds. Methods: Data from a study in 123 patients with heterozygous FH and coronary artery disease on maximally tolerated lipid-lowering therapy were used to evaluate in what percentage adding mipomersen resulted in lipid-levels below Apheresis-thresholds. Different thresholds were tested: LDL-C ≥ 2.59 mmol/l, ≥ 3.36 mmol/l, ≥ 4.14 mmol/l, Lp(a) ≥ 60 mg/dl. Results: Mipomersen decreased LDL-C by 28% (baseline 153 mg/dl), Lp(a) by 21% (baseline 45 mg/dl) (placebo no effect). Mipomersen reduced the percentage of patients with LDL-C ≥ 4.14 mmol/l from 39 to 2%, with LDL...

  • severe hypercholesterolaemia therapeutic goals and eligibility criteria for LDL Apheresis in europe
    Current Opinion in Lipidology, 2010
    Co-Authors: G R Thompson, M Barbir, Alberico L Catapano, Samir Saheb, Marielle Atassidumont, Mats Eriksson, Bernhard Paulweber, Eric J G Sijbrands, Anton F H Stalenhoef, Klaus G. Parhofer
    Abstract:

    Purpose of review Despite the use of currently available lipid-lowering therapies, a significant proportion of patients with severe hypercholesterolaemia do not reach treatment goals and consequently remain at increased risk for cardiovascular disease (CVD). On the basis of clinical experience, these patients tend to have the most severe forms of familial hypercholesterolaemia or markedly elevated LDL cholesterol (LDL-C) levels but are unable to tolerate statin therapy. Recent findings LDL Apheresis is currently the best treatment option (or treatment rescue) to bring these patients closer to therapeutic LDL objectives, and has been shown to reduce the risk of CVD along with LDL-C levels. However, criteria for LDL Apheresis eligibility and the percentage of patients receiving treatment vary widely from country to country across Europe. Despite the proven benefits of LDL Apheresis, access to this procedure remains limited because of its high cost and low availability, reflecting inherent limitations of this treatment modality. Summary There is a need to both better define the patient population eligible for LDL Apheresis and to create unified European guidelines governing the use of Apheresis. In addition to improving access to Apheresis where appropriate, new therapies are needed to further decrease LDL-C and reduce the ongoing CVD risk in patients with severe hypercholesterolaemia.

  • long term LDL Apheresis does not stably improve hemorheology in hypercholesterolemic patients with coronary artery disease
    Clinical Hemorheology and Microcirculation, 2009
    Co-Authors: Thomas Pusl, Uli C. Broedl, Klaus G. Parhofer, C. Otto
    Abstract:

    : Hemorheological abnormalities are independent cardiovascular risk indicators and adversely affect the outcome of cardiovascular disease. Single LDL Apheresis treatment was shown to improve blood and plasma viscosity, red cell aggregation and deformability. However, the long-term effects of LDL Apheresis on hemorheology are still unknown. Therefore, we investigated hemorheological parameters in 23 patients (11 women, 12 men) with angiographically established coronary heart disease and drug-resistant hypercholesterolemia regularly treated with LDL Apheresis for 7.6+/-3.1 years. Hemorheological measurements (whole blood viscosity, plasma viscosity, red blood cell aggregation at stasis and low shear rate) were analyzed in all patients before and after the initial LDL Apheresis as well as before a current LDL Apheresis. Single LDL Apheresis resulted in significantly reduced plasma viscosity, whole blood viscosity and erythrocyte aggregation index. However, long-term Apheresis had no sustained effect on plasma and whole blood viscosity. Our data indicate that in contrast to its beneficial short-term effects, long-term LDL Apheresis does not stably improve hemorheology.

  • effects of two whole blood systems dali and liposorber d for LDL Apheresis on lipids and cardiovascular risk markers in severe hypercholesterolemia
    Journal of Clinical Apheresis, 2007
    Co-Authors: Carsten Otto, Jutta Berster, B Otto, Klaus G. Parhofer
    Abstract:

    LDL Apheresis is an extracorporal modality to lower the concentration of atherogenic lipoproteins, e.g., LDL cholesterol. We compared two recently introduced whole-blood LDL Apheresis systems inpatients with hypercholesterolemia in a randomized cross-over trial with respect to their effects on lipoproteins as well as on other cardiovascular risk markers. Six patients (4 women, 2 men, median age 62.5 years, median BMI 25.9 kg/m(2)) on regular LDL Apheresis were randomly assigned to receive six weekly treatments with either DALI (Fresenius) or Liposorber D (Kaneka). After 6 weeks, the patients were switched to the other device (again six weekly treatments). Blood was drawn before and immediately after LDL Apheresis at three time points (last regular Apheresis before the study; after six treatments with DALI and after six treatments with Liposorber D). LDL cholesterol concentration before the sixth Apheresis (DALI 129 mg/dL, Liposorber D 132 mg/dL) as well as LDL cholesterol reduction during the sixth Apheresis (DALI 68.3% and Liposorber D 68.4%) were similar with the two systems. CRP and fibrinogen concentrations were lower but interleukin-6, myeloperoxidase, and resistin concentrations were higher after the last Liposorber treatment compared with DALI (P < 0.05, respectively). No differences were observed concerning adiponectin, ghrelin, and PYY levels. In conclusion, both devices were highly effective in eliminating atherogenic lipoproteins. CRP and fibrinogen were better eliminated with Liposorber D. However, following Liposorber D, interleukin-6 levels were higher than after DALI possibly indicating an increased inflammatory activation.

  • effects of ezetimibe on plasma lipoproteins in severely hypercholesterolemic patients treated with regular LDL Apheresis and statins
    Atherosclerosis, 2005
    Co-Authors: H C Geiss, Carsten Otto, E Hundwissner, Klaus G. Parhofer
    Abstract:

    Abstract Ezetimibe, a cholesterol absorption inhibitor, can be combined with statins to lower LDL-cholesterol. We evaluated additional ezetimibe (10mg/day) in a placebo-controlled, double blind, randomized cross-over study in 20 patients (age 56±9 years, m:f 10:10, BMI 27.5±4.0kg/m 2 ) suffering from severe hypercholesterolemia and CHD who were treated by statins and regular LDL-Apheresis. Lipoproteins (cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol, VLDL-triglycerides, lipoprotein(a)) were determined twice (before and during ezetimibe/placebo, each given for 5 weeks), dietary behaviour was analyzed once (3-days-protocol) during each treatment period. During ezetimibe the mean (±S.D.) preApheresis LDL-cholesterol concentration decreased from 159±26mg/dl (4.11±0.67mmol/l) to 133±28mg/dl (3.44±0.72mmol/l) (−16±11%, P P P P Thus, in patients with severe LDL-hypercholesterolemia and CHD the addition of ezetimibe to intensive lipid lowering therapy (statins and LDL-Apheresis) resulted in a further, clinically significant decrease of LDL-cholesterol.

Eri Muso - One of the best experts on this subject based on the ideXlab platform.

  • Effects of LDL Apheresis on proteinuria in patients with diabetes mellitus, severe proteinuria, and dyslipidemia
    Clinical and Experimental Nephrology, 2020
    Co-Authors: Takashi Wada, Eri Muso, Akinori Hara, Shoichi Maruyama, Sawako Kato, Kengo Furuichi, Kenichi Yoshimura, Tadashi Toyama, Norihiko Sakai, Hiroyuki Suzuki
    Abstract:

    Background Patients with diabetes mellitus and severe proteinuria present with poor renal prognoses, despite improvements in diabetes and kidney disease therapies. In this study, we designed a low-density lipoprotein (LDL)-cholesterol Apheresis treatment for patients with diabetic nephropathy (DN)/diabetic kidney disease and severe proteinuria. This was a multicenter prospective LICENSE study to confirm the impact of LDL Apheresis on proteinuria that exhibited hyporesponsiveness to treatment. In addition, we sought to determine the efficacy and safety of LDL Apheresis by comparing the outcomes to those of historical controls in patients with diabetes, refractory hypercholesterolemia, and severe proteinuria. Methods This was a prospective, multicenter study, including 40 patients with diabetes, severe proteinuria, and dyslipidemia. LDL Apheresis was performed 6–12 times over a 12-week period. The primary endpoint was the proportion of patients with a decrease in proteinuria excretion of at least 30% in the 6 months after starting therapy. The secondary endpoints included serum creatinine levels and laboratory variables, which were evaluated 4, 6, 12, 18, and 24 months after therapy initiation. Results LDL Apheresis was performed on 40 registered patients with diabetes. The proportion of cases in which proteinuria decreased by 30% or more after 6 months of LDL Apheresis was 25%, which was similar to that of historical controls. The overall survival and end-stage kidney disease-free survival rates were significantly higher in the LICENSE group compared to those in historical controls. Conclusion Our results suggest that LDL Apheresis may be effective and safe for patients with diabetes, proteinuria, and dyslipidemia. Trial registration Trial registration number: jRCTs042180076.

  • rationale and study design of a clinical trial to assess the effects of LDL Apheresis on proteinuria in diabetic patients with severe proteinuria and dyslipidemia
    Clinical and Experimental Nephrology, 2018
    Co-Authors: Takashi Wada, Eri Muso, Akinori Hara, Shoichi Maruyama, Kengo Furuichi, Kenichi Yoshimura, Eiichi Sato, Mariko Miyazaki, Masanori Abe, Yugo Shibagaki
    Abstract:

    Diabetic nephropathy is a leading cause of end-stage kidney disease in the world. Although various types of treatment for diabetes, hypertension and dyslipidemia have improved prognosis and quality of life in patients with diabetic nephropathy, there still exist some diabetic patients with severe proteinuria showing poor prognosis. This clinical trial, LICENSE, aims to confirm the impact of LDL Apheresis on proteinuria exhibiting hyporesponsiveness to treatment. This ongoing trial is a multicenter, prospective study of diabetic patients with severe proteinuria. The objective is to examine the impact of LDL Apheresis on proteinuria in patients with diabetic nephropathy. The other subject is to investigate safety of LDL Apheresis in these patients. The subjects consist of diabetic patients with serum creatinine (Cr) levels below 2 mg/dL who present severe proteinuria above 3 g/g Cr or 3 g/day and LDL cholesterol above 120 mg/dL. The target number of registered patients will be 35 patients. Urinary protein excretion and renal function will be observed for 24 weeks after the treatment of LDL Apheresis. This study will determine the effectiveness and safety of LDL Apheresis for diabetic nephropathy patients with severe proteinuria and dyslipidemia.

  • a prospective observational survey on the long term effect of LDL Apheresis on drug resistant nephrotic syndrome
    Nephron extra, 2015
    Co-Authors: Eri Muso, Masatoshi Mune, Tsutomu Hirano, Motoshi Hattori, Kenjiro Kimura, Tsuyoshi Watanabe, Hitoshi Yokoyama, Hiroshi Sato, Shunya Uchida, Takashi Wada
    Abstract:

    Background/Aims: LDL Apheresis (LDL-A) is used for drug-resistant nephrotic syndrome (NS) as an alternative therapy to induce remission by improvement of hyperlip

  • beneficial effect of LDL Apheresis in refractory nephrotic syndrome
    Clinical and Experimental Nephrology, 2014
    Co-Authors: Eri Muso
    Abstract:

    LDL-Apheresis is a method to correct dyslipidemia rapidly. It is expected to alleviate the tissue toxicity of persistent dyslipidemia in not only primary, but also in secondary dyslipidemia associated with refractory nephrotic syndrome, and to have a protective effect against glomerular and tubular injury as expected in atherosclerosis. In addition, the effectiveness of LDL-Apheresis to promote the remission of nephrotic syndrome has been recognized. In Japan, LDL-A to control hyperlipidemia in patients with refractory nephrotic syndrome associated with focal segmental glomerulosclerosis is covered by national health insurance. Here, the hypothetical mechanism behind its effect and the evidence for its effectiveness over a long period are reviewed.

  • significantly rapid relief from steroid resistant nephrotic syndrome by LDL Apheresis compared with steroid monotherapy
    Nephron, 2001
    Co-Authors: Eri Muso, Masatoshi Mune, Yasuhiro Fujii, Enyu Imai, Naohiko Ueda, Kazuhiro Hatta, Akio Imada, Tsukasa Takemura, Shozo Miki, Takashi Kuwahara
    Abstract:

    Rapid amelioration of hypercholesterolemia by LDL Apheresis (LDL-A) was performed for long-standing nephrotic syndrome (NS) with hyperlipidemia due to focal segmental glomerulosclerosis (FGS) and the clinical data and prognosis were compared between LDL-A-treated and nontreated groups. Seventeen steroid-resistant NS patients treated with LDL-A (LDL-A group) and 10 NS patients treated with steroids only (steroid-monotherapy (SM) group) were compared. Serum cholesterol and phospholipid levels were significantly lowered only in the LDL-A group (p < 0.01, respectively). The LDL-A group showed a significant decrease of urinary protein (UP, p < 0.01) and increase of serum albumin (p < 0.05). Average time needed to achieve a decrease of UP to less than nephrotic range (< 3.5 g/day) was significantly shorter in the LDL-A group than in the SM group (p < 0.01). Although this is not a prospective study, it is highly expected that a rapid improvement of hypercholesterolemia by LDL-A in steroid-resistant NS will provide more rapid relief from NS than steroid therapy alone.

Claudia Stefanutti - One of the best experts on this subject based on the ideXlab platform.

  • cytokines profile in serum of homozygous familial hypercholesterolemia is changed by LDL Apheresis
    Cytokine, 2011
    Co-Authors: Claudia Stefanutti, A Vivenzio, S Di Giacomo, Pietro Manuel Ferraro
    Abstract:

    Abstract Objective The effects of LDL-Apheresis (LDLa) with dextran sulphate on plasma cytokines in 6 homozygous familial hypercholesterolemic (HozFH) patients, were evaluated. Methods Plasma IL-1α; IL-1ra; IL-4; IL-6; IL-10; IL-12(p40); IL-12(p70); TNF-α, sTNF-R, VEGF, VEGF-R1, E-Selectin (ESEL), and P-Selectin (PSEL) concentrations were measured before and after LDLa on three consecutive sessions for each patient. Results TNF-α was significantly reduced (−60%; P = 0.01), while TNF-R was only slightly increased (+15%), although not significantly. Plasma VEGF was significantly reduced (−57%; P = 1.87301E−05), while VEGF-R1 was significantly increased (+56%; P = 0.05). ESEL and PSEL were reduced but not to a statistically significant extent (−19%, −15%, respectively). IL-1α level was dramatically reduced (−87%; P = 0.0001). IL-1ra concentration was only slightly increased in plasma, but not significantly. IL-4 and IL-10 levels were significantly reduced in plasma after Apheresis (−50%; P = 0.03, and −55%; P = 0.004, respectively). On the contrary, IL-6 concentration showed a slight decrease (−8%). Plasma IL-12p40 was significantly increased (+47%; P = 0.0004). On the other hand, IL-12p70 was reduced, but the difference (−31%) was not statistically significant. Conclusions Plasma cytokines imbalance is associated with inflammation and atherogenesis. In this study LDLa changed several circulating cytokines inducing anti-inflammatory and anti-atherogenic changes in cytokines plasma profile in HozFH patients with/without pre-existing angiographically demonstrated coronary heart disease (CHD) and aortic valvular disease (AVD).

  • the 2009 2nd italian consensus conference on LDL Apheresis
    Nutrition Metabolism and Cardiovascular Diseases, 2010
    Co-Authors: Claudia Stefanutti
    Abstract:

    Abstract The ‘2009 2nd Italian Consensus Conference on LDL-Apheresis’ was held in Rome, Italy, 15 May 2009. The latest scientific evidence and the information processed in more than two decades of LDL-Apheresis application require new guidelines. Experts were invited by the Consensus Panel to give a scientific specific contribution in their clinical area of specialty. The experts of interdisciplinary affiliation participated in the extension of ‘The new guidelines and recommendations for the indications and the appropriate use of LDL-Apheresis’. The summary statement describing the frame and the lines of action of the scientific event and a supplementary document inherent to the Consensus available online at http://ees.elsevier.com/nmcd/ are reported.

  • treatment of symptomatic hyperlp a lipidemia with LDL Apheresis vs usual care
    Transfusion and Apheresis Science, 2010
    Co-Authors: Claudia Stefanutti, A Vivenzio, S Di Giacomo, B Mazzarella, Pietro Manuel Ferraro, S Abbolito
    Abstract:

    Background/aims: To assess LDL-Apheresis efficacy to lower Lp(a) and to compare the effects of Usual Medical Care (UMC) a 12-months study was carried out. The incidence of new coronary artery disease (CAD) events/need of revascularization, was also monitored. Methods: Twenty-one patients with hyperLp(a)lipidemia and angiographically documented CAD were randomly assigned to LDL-Apheresis every week, or the UMC. Results: LDL-Apheresis group, averaged an Lp(a) reduction of 57.8 ± 9.5% vs. basal values (P < 0.001). In the UMC group Lp(a) increased in 1 year to 14.7 ± 36.5% (P = 0.66). Stepwise multivariate regression analysis for predictors of Lp(a) including: type of treatment, smoking, hypertension, age, age at first cardiovascular event, initial Lp(a), LDL, and BMI values, was performed. Only the type of treatment was co-related (P < 0.001): Lp(a) variation (beta) = 0.863. The model has R2 adjusted relative risk of 0.725. Conclusion: LDL-Apheresis could be the first line treatment of isolated hyperLp(a)lipidemia when CAD is established. New CAD events/cardiac interventions were not observed.

  • treatment of symptomatic hyperlp a lipoproteinemia with LDL Apheresis a multicentre study
    Atherosclerosis Supplements, 2009
    Co-Authors: Claudia Stefanutti, A Vivenzio, G Dalessandri, G Russi, G De Silvestro, M G Zenti, Piero Marson, D Belotherkovsky, S Di Giacomo
    Abstract:

    Abstract LDL-Apheresis (LDLa) efficacy in the treatment of symptomatic HyperLp(a)lipoproteinemia -HyperLp(a)- has been studied in a multicentre trial. After 3.1±2.7 years of weekly and biweekly treatment, the data from 19 patients (males:12; females:7; aged 53.8±9.3 years; mean body mass index: 24.6±2.3 Kg/m 2 ) were evaluated. Data were collected using the same questionnaire shared by 5 participating centres. A total of 2331 procedures were performed. A mean of 3593.7±800.3 ml of plasma or 8115.3±2150.1 ml of blood, depending upon the technique used (H.E.L.P., D.A.LI., Dextransulphate, Lipocollect 200), was regularly treated on average every 10.1±2.6 days. Baseline mean Lp(a) levels were 172.3±153.8 mg/dL. The mean pre-/post-Apheresis Lp(a) levels decreased from 124.5±107.2 mg/dL (p

  • LDL Apheresis in a homozygous familial hypercholesterolemic child aged 4 5
    Artificial Organs, 2008
    Co-Authors: Claudia Stefanutti, A Notarbartolo, V Colloridi, A Nigri, A Vivenzio, S Bertolini, Giovanna Bosco, Andrea Berni, S Di Giacomo, B Matzarella
    Abstract:

    Preliminary experience with the efficacy and safety of dextran sulfate cellulose low-density lipoprotein (LDL) Apheresis for the treatment of a 4.5-year-old girl with homozygous familial hypercholesterolemia and coronary artery disease is reported. The decrease of the most atherogenic apolipoprotein B-containing lipoproteins, low-density lipoprotein (LDL) and lipoprotein(a) (Lp [a]), were in the ranges of 63.1-68.7%, and 52.5-58.6%, respectively. The child tolerated LDL Apheresis without any clinically significant complications. Therefore, she was submitted to a long-term program of treatment at intervals of 15 days. The experience suggests the possibility of an early beginning of extracorporeal treatment with LDL Apheresis in children severely affected by homozygous or double heterozygous familial hypercholesterolemia.

G Notohamiprodjo - One of the best experts on this subject based on the ideXlab platform.

  • improvement of coronary vasodilatation capacity through single LDL Apheresis
    Atherosclerosis, 1998
    Co-Authors: K P Mellwig, D Alle, U Gleichma, D Moll, S Etke, Reine Weise, G Notohamiprodjo
    Abstract:

    A concomitant phenomenon of hypercholesterolemia is reduced coronary vasodilatation capacity due to disturbed endothelial function. Endothelial function can be partially or completely normalized by reducing cholesterol levels through drug therapy, but it is still unclear how rapidly this desired effect is achieved. An interval of between weeks and months has been presumed. LDL Apheresis (LDL-A) is capable of achieving a high-degree LDL cholesterol reduction within hours. With positron emission tomography (PET), carried out immediately before and after LDL-A, changes in coronary reserve due to this abrupt LDL cholesterol reduction could be measured both quantitatively and non-invasively. In nine patients (six women, three men) with documented coronary artery disease and hypercholesterolemia, PET was carried out immediately before and 18‐20 h after LDL-A. A reduction in LDL cholesterol (from 1949 38 to 819 20 mg:dl), facilitated significant improvement in myocardial blood flow (MBF) (173963 versus 226979 ml:min per 100 g) after pharmacologic recruitment of coronary flow capacity (dipyridamole stress), coronary flow reserve (CFR) (1.919 0.68 versus 2.489 0.68) and minimum coronary resistance (MCR) (0.6190.18 versus 0.4390.16 mmHg:100 g per min per ml) within 24 h. Plasma viscosity was reduced slightly, by 6.6%. Probably for the first time, a 30% improvement in coronary vasodilatation capacity could be demonstrated quantitatively and non-invasively by PET after a single LDL-A within 24 h. © 1998 Elsevier Science Ireland Ltd. All rights reserved.

  • improvement of coronary vasodilatation capacity through single LDL Apheresis
    Atherosclerosis, 1998
    Co-Authors: K P Mellwig, D Moll, D Baller, U Gleichmann, S Betker, Reiner Weise, G Notohamiprodjo
    Abstract:

    A concomitant phenomenon of hypercholesterolemia is reduced coronary vasodilatation capacity due to disturbed endothelial function. Endothelial function can be partially or completely normalized by reducing cholesterol levels through drug therapy, but it is still unclear how rapidly this desired effect is achieved. An interval of between weeks and months has been presumed. LDL Apheresis (LDL-A) is capable of achieving a high-degree LDL cholesterol reduction within hours. With positron emission tomography (PET), carried out immediately before and after LDL-A, changes in coronary reserve due to this abrupt LDL cholesterol reduction could be measured both quantitatively and non-invasively. In nine patients (six women, three men) with documented coronary artery disease and hypercholesterolemia, PET was carried out immediately before and 18-20 h after LDL-A. A reduction in LDL cholesterol (from 194 +/- 38 to 81 +/- 20 mg/dl), facilitated significant improvement in myocardial blood flow (MBF) (173 +/- 63 versus 226 +/- 79 ml/min per 100 g) after pharmacologic recruitment of coronary flow capacity (dipyridamole stress), coronary flow reserve (CFR) (1.91 +/- 0.68 versus 2.48 +/- 0.68) and minimum coronary resistance (MCR) (0.61 +/- 0.18 versus 0.43 +/- 0.16 mmHg/100 g per min per ml) within 24 h. Plasma viscosity was reduced slightly, by 6.6%. Probably for the first time, a 30% improvement in coronary vasodilatation capacity could be demonstrated quantitatively and non-invasively by PET after a single LDL-A within 24 h.

U Julius - One of the best experts on this subject based on the ideXlab platform.

  • LDL Apheresis improves deranged cardiovagal modulation in hypercholesterolemic patients
    Atherosclerosis, 2010
    Co-Authors: Manja Reimann, U Julius, Kristin Haink, Birgit Lippold, S Tselmin, Stefan R Bornstein, H Reichmann, Heinz Rudiger, Tjalf Ziemssen
    Abstract:

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

  • retinal vessel analysis in hypercholesterolemic patients before and after LDL Apheresis
    Atherosclerosis Supplements, 2009
    Co-Authors: Manja Reimann, U Julius, Birgit Lippold, Stefan R Bornstein, H Reichmann, S Prieur, Tjalf Ziemssen
    Abstract:

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

  • the dresden Apheresis center experience with LDL Apheresis and immunoadsorption
    Atherosclerosis Supplements, 2009
    Co-Authors: U Julius, S Tselmin, S Fischer, Jens Passauer, Stefan R Bornstein
    Abstract:

    Abstract 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.

  • beyond lowering circulating LDL Apheresis induced changes of systemic oxidative stress markers by four different techniques
    Atherosclerosis Supplements, 2009
    Co-Authors: Steffi Kopprasch, Antje Frind, Ines Poberschin, S Tselmin, Stefan R Bornstein, Juergen Graessler, Peter Schwarz, U Julius
    Abstract:

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

  • comparison of different LDL Apheresis methods
    Expert Review of Cardiovascular Therapy, 2008
    Co-Authors: U Julius, Antje Frind, Sergej Tselmin, Steffi Kopprasch, Ines Poberschin, Gabriele Siegert
    Abstract:

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