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2nd Congress of the European Group – International Society for Apheresis

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03/23/2018 - Foyer | 10:30am - 11:15am 
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Poster session 2 (P-11–P-22): Lp-apheresis

Chairs: B. Jäger (Mühlheim a.d. Ruhr, Germany), A. Vogt (Munich, Germany)

P-11 Removal of Xanthomas and Xanthelasmas by LDL-Apheresis in a Case of severe Familial Hypercholesterolemia (FH)
*Jürgen Otto1, Doris Handschel1, Gabriele Maniera1
1 Deutsches Hämapherese Zentrum gGmbH, , Köln, Germany
Abstract text :

History: The female patient was born in Tunesia in 1983 (34 Y). At the age of nine FH was diagnosed and treatment with Colestyramine and Rosuvastatin was started. When she moved to Germany in 2011, she presented with distinct xanthomas and xanthelasmas (X X). Clinical or diagnostic signs of cardiovascular disease (CVD) are not traceable until today. The underlying mutation was identified as missense-mutation in exon 10 of the LDL receptor  gene and deletion in exon 2-6. Total cholesterol was 512 mg/dl (13.24 mmol/l), LDL-C 463 mg/dl (11.97 mmol/l) and HDL-C 31 mg/dl (0.8 mmol/l). Maximum oral medication did not lower the serum LDL-C below 250 mg/dl (6.47 mmol/l).


Apheresis: Since May 2014 the patient is treated in our hemapheresis center in Cologne with Spectra Optia/ADAsorb and specific LDL-adsorber-columns (Lipocollect 200, medicollect®, Rimbach). Relative treated plasma volumes were between 1,55 and 1,85 (mean 1,60). The apheresis was performed weekly or biweekly (gaps due to pregnancy and holidays). Additionally the patient takes 80 mg of atorvastatin.


Results: The LDL-C is thereby reduced by up to 80% (pre/post apheresis) and we usually achieve our post-apheresis target of 50 mg/dl (1.29 mmol/l). However complete removal of X X until today is an impressive result of the apheresis.


PCSK9-antibody treatment: In 2015 a trial with Alirocumab 75 mg and Atorvastatin 80 mg without apheresis was undertaken. This could drop the LDL-C-level to 187 mg/dl (4.84 mmol/l). In 2017 150 mg of Alirocumab were combined with LDL-apheresis and Atorvastatin 80 mg, but the pre-apheresis levels were not lower than with LDL-apheresis and Atorvastatin alone (lowest pre-apheresis LDL-C 167 mg/dl (4.32 mmol/l).


Conclusion: The rapid removal of Xanthomas and Xanthelasmas by LDL-apheresis in severe FH makes it very probable, that cardiovascular deposits are removed too. This could not be shown in this case due to absence of obvious CVD. Additionally, the literature confirms a favourable long-term outcome of homozygous FH by LDL-apheresis. Though the data are still preliminary, in this case additional administration of Alirocumab did not result in lower pre-apheresis LDL-C than apheresis and atorvastatin alone.



P-12 Direct Adsorption of Lipoproteins (DALI®) Apheresis for Elevated Lipoprotein(a) During Pregnancy – A Case Report
*Monika Chocholous1, Ammon Handisurya2
1 Medical University of Vienna, Department of Pediatric and Adolescent Medicine, Vienna, Austria
2 Medical University of Vienna, Department of Medicine III, Vienna, Austria
Abstract text :

 


Background


Due to its atherogenic and thrombogenic potential Lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. Additionally, elevated Lp(a) levels confer a significantly increased risk for placenta-mediated pregnancy complications including pre-eclampsia and stillbirth. To the best of our knowledge no data on pregnancy outcomes in women undergoing Direct Adsorption of Lipoproteins (DALI®) for elevated Lp(a) have been published to date.


Case description


A 32-years old woman with positive family history for premature ischemic heart disease, clinically manifest atherosclerosis and/or dyslipidemia for three generations became pregnant in March 2016. Lipoprotein apheresis using the DALI® adsorbers (Fresenius HemoCare Adsorber Technology, St. Wendel, Germany) was initiated 17 months prior to pregnancy due to Lp(a) levels of up to >500nm/L, significant progression of intima media thickness and clinical deterioration with severe asymmetric manifestation of a secondary Raynaud phenomenon, unexplained syncopes and a central vertigo with nystagmus and ataxia.


During pregnancy, lipoprotein apheresis was continued once weekly using the DALI® 1000 adsorbers via a veno-venous access. Compared to the three months before conception the mean pre-apheresis Lp(a) levels were significantly higher during pregnancy (274.8±61.7 vs. 338.4±58.2nmol/L, p=0.001). Especially during the first trimester Lp(a) increased significantly by 29% (354.5±72.3nmol/L, p=0.006). Despite the subsequent increase of the processed blood volume from 10 to 12 liters per apheresis session, the mean Lp(a)-reduction per session was significantly attenuated in pregnancy (74.0±2.7 vs. 67.0±5.8%, p=0.030) probably due to expanded plasma volume. LDL-cholesterol also increased significantly late in pregnancy (73.5 vs. 90.8mg/dL, p=0.004).


Fetal monitoring as well as Doppler ultrasound of the placenta and maternal / fetal vessels were performed in close meshed intervals with no abnormalities detected. The ratio of SFLT1/PLGF as angiogenic marker for the prediction of pre-eclampsia was repeatedly within normal range and glucose monitoring was negative for gestational diabetes mellitus. A healthy female infant weighing 2500g was delivered by primary Caesarean section at 35 weeks´ gestation.


Conclusion


Clinically and technically, the apheresis sessions were completely uneventful during the whole pregnancy and resulted in the delivery of a healthy girl. Therefore, DALI® apheresis for elevated Lp(a) during pregnancy seems to be safe and effective.



P-13 Lipoprotein(a), PCSK9 and complex Lp(a)-PCSK9 plasma levels in hypercholesterolemia patients.
Olga Afanasieva1, Oxana Razova1, Marat Ezhov 2, Elena Utkina1, Marina Afanasieva1, *Sergei Pokrovsky1
1 National Medical Research Center of Cardiology, Ministry of Health of Russian Federation, Institute of Experimental Cardiology, Moscow, Russian Federation
2 National Medical Research Center of Cardiology, Ministry of Health of Russian Federation, Institute of Clinical Cardiology, Moscow, Russian Federation
Abstract text :

Question. Previously we have shown that the association of protein convertase subtilisin-kexin type 9 (PCSK9) and lipoprotein(a) [Lp(a)] concentrations depends on the apolipoprotein(a) phenotype. The aim of this study was to investigate the relationship between the concentrations of Lp(a), PCSK9 and Lp(a)-PCSK9 complex in hypercholesterolemic patients.


Methods. The study included 80 (34% males) patients with TC>7.5 mmol/L and LDL-C>4.9 mmol/L aged 18 - 75 years. All patients were free of CHD and were statin-naive. We measured lipids, Lp(a), PCSK9 and complex Lp(a)-PCSK9 plasma levels by ELISA, apo(a) phenotype by immunoblotting. Lipoprotein subfractions were determined by «Lipoprint® System» (Quantimetrix, USA). Depending on the phenotype of apo(a) all patients were divided into two subgroups: the low-molecular weight (LMW) apo(a) (n=33) and the high-molecular weight (HMW) apo(a) (n=47).


Results. The groups were comparable by all clinical characteristics and lipids. The mean PCSK9 level did not differ between the subgroups 342±109 and 343±89 ng/mL. The median plasma Lp(a) level was significantly higher in patients with LMW apo(a) phenotype than in HMW apo(a) subgroups (median[25%-75%]) 69[28-98] mg/dL vs 22 [14-42] mg/dL, p<0.05. Lp(a)-PCSK9 complex was comparable in HMW and LMW subgroups. There was a weak relationship between the concentration of Lp(a) and PCSK9 (r=0.22, p<0.05) in the whole group, which was enhanced in the LMW apo(a) subgroup (r=0.37, p<0.05) and disappeared in HMW apo(a). There was no correlation between Lp(a)-PCSK9 and Lp(a) or PCSK9 levels in the whole group and all subgroups. But we found a significant relationship of plasma concentrations of Lp(a)-PCSK9 complex with total cholesterol (TC) (r=0.40, p<0.005), and large subfractions of intermediate density lipoproteins (IDL-C) (r=0.30, p<0.05) and low density lipoproteins (LDL-1) r=0.30, p<0.05. The same of Lp(a) and PCSK9, the correlation of Lp(a)-PCSK9 complex with large LDL-1 and IDL-C concentrations was significant only in LMW apo(a) subgroup (r=0.59, p<0.005 and r=0.40, p<0.05, respectively).


Conclusion. A positive relationships between concentrations of Lp(a) and PCSK9 as well as between Lp(a)-PCSK9 complex and large apoB100-containing lipoprotein subfractions was observed only in hypercholesterolemia patients with LMW apo(a) phenotype. These facts illustrate the difference in metabolism and pathophysiological properties of Lp(a) with small and large apo(a) isoforms.




P-14 Effects of a newly established lipid apheresis for a young homozygous familial hypercholesterolemia population at the Department of Pediatrics and Adolescent Medicine in Vienna
*Nina-Katharina Walleczek1, Klaus Arbeiter1, Pinky Rose Espina1, Thomas Hörtenhuber1, Alexandra Kreissl1,2, Susanne Greber-Platzer1
1 Medical University of Vienna, Austria, Division of Pediatric Pulmology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Vienna, Austria
2 Medical University of Vienna, Austria, , Vienna, Austria
Abstract text :

Introduction: Homozygous familial hypercholesterolemia (HoFH) is a rare but severe disorder of lipoprotein metabolism. HoFH prevalence is about 1 per 160 000 to 300 000. Children with HoFH present with highly elevated LDL-Cholesterol (LDL-C) plasma levels (> 500mg/dl / > 130 mmol), early xanthomas or xanthelasms and a high risk of premature cardiovascular events during childhood. Early diagnosis and treatment by strict fat reduced diet and medication of statins, ezetimibe and bile acid sequestrants are essential. Nevertheless therapy is mostly inefficient and therefore lipid apheresis has to be performed biweekly or weekly to reduce LDL-C.


 


Aim of this study was to describe the effect of lipid apheresis in pediatric HoFH patients aged < 7 years at the pediatric dialysis center of the Department of Pediatrics and Adolescent Medicine in Vienna.


 


Objectives and Methods: Lipid apheresis started biweekly in 4 children with hoFH aged 4-6 years (1 boy and 3 girls) in 2016.  For this long-lasting central venous catheters were implanted. Data were analysed for the time period October 2016 until December 2017.


For lipid apheresis a Therasorb column by Miltenyi Biotec was used with a plasma Adasorb filled with 5% albumin and a volume of 100 ml. For the treatment volume the patients" plasma volume was taken twice times and filled up to 250 ml per cycle and  6 to 8 treatment cycles were performed. The patients did not need any additional fluid prior to apheresis and no cardiovascular instability was observed. Systemic anticoagulation consisted of bolus administration of citrate and heparin, followed by a continuous citrate/heparin infusion.


 


Results: In total, the four children received regularly lipid apheresis. Total Cholesterol (T-C) decreased significantly by 65% (p<0.001), LDL-C by 68% (p<0.001), HDL Cholesterol by 37% (p<0.001), and triglycerides by 30% (p<0.001) [Table 1]. Severe side effects of the long-lasting central venous catheters were catheter infections by staphylococcus and plesiomonas spp.


 


Discussion: Biweekly lipid apheresis seems to be very successful in young aged children with HoFH by significant reduction of LDL-C of 68% and quick completion of the procedure.


Venous punction is difficult in young aged children, because of small venous diameters and severe anxiety. Long-lasting central venous catheters seem to be acceptable alternatives.


The most frequent complications were catheter-associated infections by staphylococcus aureus. So two patients (2 girls) acquired a central venous catheter sepsis shortly after the implementation. Another patient (boy) needed two times catheter replacement because of tunnel infection and finally received an arteriovenous shunt on his forearm. At least one of the girls had repeated catheter-associated infections and needed intravenous administration of antibiotics and finally the catheter was removed.


Another side effect of lipid apheresis in childhood was anaemia which occurred in all 4 children and was successfully treated by intravenous iron infusions weekly or biweekly.


 


Conclusion: Lipid apheresis is a very effective method to reduce T-C and LDL-C also in young children with HoFH. Long-lasting central venous catheters seem to operate acceptable, but severe infections are a major problem. Therefore other alternatives like arteriovenous shunts or venous punctions should be planned as early as possible.



P-15 Left ventricular ejection fraction after 1 year Lipoprotein apheresis
*Aura Giurgea1, Elodie Karkutli1, Helmut Sinzinger2
1 Athos Institute, , Vienna, Austria
2 Isotopix Institute, , Vienna, Austria
Abstract text :

Purpose
Left ventricular ejection fraction (LVEF) is a valuable measure to assess left ventricular function and pumping efficiency. Lipid lowering by statins has been shown to increase LVEF already after a 6 months treatment, a higher dose of statins has been claimed to be more effective as compared to a conventional one and even a difference between lipophilic and hydrophilic compounds has been reported.


Methods
In order to elucidate whether this beneficial effect is due to the lowering of lipoproteins (Lp) or maybe a substance specific effect of the respective statin, we examined patients before initiation and after one year of ongoing Lp-apheresis. In total, 18 patients were examined. 13 (11 males, 2 females, mean age 58.3 a, groups A) were since more than a year on stable, unchanged statin treatment (atorvastatin 40 mg , simvastatin 40 mg, rosuvastatin 20 mg /- ezetimibe), the other 5 patients (3 males, 2 females, mean age 57.1 a, group B) were intolerant to statins being either on micronized fenofibrate /- resorption inhibitors. All patients had a Lp(a) < 30 mg/dl. As part of the usual follow-up monitoring, LVEF was determined by means of radionuclide ventriculography after application of 550 MBq 99mTc-pertechnetate.


Results
The investigation was repeated at a mean of 48.7 weeks in group A and 51.2 in group B. Except in 1 patient (46,8 % before vs. 45,2 % after Lp- apheresis initiation) in group A , in all the patients in both groups we noted a significant increase in LVEF.


The mean LVEF in group A increased from (42.7 /- 8.1  à 46.5 /- 7.5 %) (p < 0.001) and from (41.9 /- 8.4  à 46.5 /- 6.3 %) (p < 0.01) to a comparable extent (mean increase in group A 9.6%, in group B 9.7%). Even considering the smaller number of statin intolerant patients in group B the difference (p < 0.01) was significant.


Conclusion
These findings indicate that regular long-term Lp-apheresis treatment apparently increases LVEF, independent on whether the patient was statin naive due to intolerance or on a stable at least one year statin treatment. This implies a role of lowering of atherogenic lipoproteins as underlying mechanism.


A prospective study should clarify the relative extent of LVEF improvement induced by Lp-apheresis vs. the one by statins.



P-16 Lipoprotein-Apheresis with the Spectra Optia Apheresis System
*Anne Klink1, Agnieszka Hilge1, Sabine Volkholz1, Katrin Maier1, Heike Jütte1, Silke Rummler1
1 University Hospital Jena, Institute of Transfusion Medicine, Jena, Germany
Abstract text :

Question: The Spectra Optia® Apheresis System is an automatic blood component separator used to perform various therapeutic apheresis procedures, cell collections and cell processing procedures. Data of the Spectra Optia® in combination with the plasma filter Monet® for the treatment of hyperlipoproteinemia (a) (Lpa) are only marginally known so far. The secondary plasma device (SPD) is the procedure to be used.


Methods: We report a retrospective monocentric analysis of 139 lipoprotein apheresis between XI/ 2015 and XII/ 2017. Only patients (pts) with Lpa elevation and transplant vasculopathy after heart transplantation (n=4), or pts with coronary heart disease (n=2) and one patient with atherosclerosis and multiple cerebellar infarction received lipoprotein apheresis at our center. The treatment frequency was 15 days (range, 4 - 28). In 57% of the pts a peripheral venous access was used and otherwise an AV fistula (n=3, all male pts). For anticoagulation (AC) ACD-A was solely used in a whole blood: ACD-A-Ratio of 12:1. The target plasma volume (PV) was standardized set as 1.1-fold PV. The blood flow/plasma rate was adjusted depending on the patient"s condition and filter pressure limit of 200 mmHg. The median treatment time per session was 183 minutes (range, 69 - 226). All pts received prophylactically calcium gluconate.


Results: LP(a) could be reduced on average by 67% (range, 38 - 76) compared with baseline. Moreover, the reduction of the macro-molecules under this procedure should be noted. Fibrinogen and factor XIII were reduced significantly to 1,8 g/l (range, 0.7 - 2.4) and to 45% (range, 39 - 75). Severe adverse events did not occur. Also no bleedings, no embolic events and no infections were registered. Technical alarms were documented at all in 19% of apheresis procedures. No alarms led to premature termination of the lipoprotein apheresis.


Conclusions: Advantage of the Spectra Optia appears to be the effective plasma extraction efficiency with low blood flow rates, allowing the use of peripheral venous access. The procedure seems to be feasible and effective and deserves a prospective multicenter investigation.



P-17 Changes in some pro- and antioxidant parameters after selective LDL apheresis
Viktória Evelin Varga1, Hajnalka Lőrincz1, Anita Szentpéteri1, Lilla Juhász1, Ildikó Seres1, József Balla1, György Paragh1, *Mariann Harangi1
1 University of Debrecen, Faculty of Medicine, Department of Internal Medicine, Debrecen, Hungary
Abstract text :

Background: Beyond its lipid lowering efficacy, LDL apheresis affects several pro- and anti-oxidant factors involved in the pathophysiology of human atherosclerosis.


Methods: We aimed to measure the serum level of oxidized LDL by enzyme-linked immunosorbent assay in six severe heterozygous FH patients before and after their first LDL apheresis treatments. We also investigated the changes in HDL subfractions and ApoA1, α- and γ-tocopherol levels during the LDL apheresis treatment. HDL subfractions were detected by an electrophoretic method on polyacrylamide gel (Lipoprint). Serum α- and γ-tocopherol levels were detected by gas chromatography-mass spectrometry.


Results: The first treatment sessions decreased the total cholesterol, LDL-C, HDL-C and ApoA1 levels by 52.6; 61.8; 10.5 and 14.1%, respectively. We found that α- and γ-tocopherol levels markedly decreased (by 34.1 and 32.9%, respectively), while α- tocopherol/cholesterol and γ-tocopherol/cholesterol ratios significantly increased (by 41.4 and 40.3%, respectively). Furthermore, oxidized LDL levels significantly decreased and there was a shift towards the larger HDL subfractions.


Conclusion: Despite the overall reduction in vitamin E level beneficial changes in vitamin E/cholesterol ratios, oxidized LDL levels and HDL subfraction distribution were detected after LDL apheresis. These additional effects of LDL apheresis may result in further cardiovascular risk reduction in FH patients.



P-18 Intensified treatment regimen of regular lipoprotein apheresis in patients with elevated lipoprotein(a) and clinically progressive atherosclerotic disease: two case reports
*Theresa Berent1, Mirnesa Halilovic1, Robert Berent2, Helmut Sinzinger1,3
1 Athos Institute, Institute for Diagnosis and Treatment of Lipid Disorders, Vienna, Austria
2 HerzReha Bad Ischl, Center for Cardiovascular Rehabilitation, Bad Ischl, Austria
3 Sigmund Freud University, Department of Lipid Metabolism, Vienna, Austria
Abstract text :

Introduction: Lipoprotein (Lp-) apheresis is a life-long therapy, usually performed in weekly intervals. Lp-apheresis lowers the incidence rate of cardiovascular events effectively. In some cases, however, atherosclerotic disease progresses despite weekly Lp-apheresis and maximal lipid lowering medication. Therefore, we thought about a temporarily shortening of treatment intervals to improve the clinical outcome of these patients. The intensified treatment protocol included three sessions in two weeks for a duration of one year. The following cases illustrate the effect (benefit) of an intensified treatment regimen in secondary prevention with elevated lipoprotein(a) and further progression of coronary atherosclerosis despite weekly Lp-apheresis and maximal lipid lowering medication.


Case 1: Weekly Lp-apheresis was started in a 40-year-old male patient with elevated Lp(a) (> 150 mg/dl) after his first myocardial infarction and implantation of three coronary stents in May 2011. In 2013, elective coronary angiography showed progression of atherosclerosis and two in-stent restenoses without any clinical symptoms. Therefore, an intensified Lp-apheresis treatment regimen was started in January 2014. After a year with a total of 68 Lp-apheresis sessions in 52 weeks (1,31 sessions per week), control coronary angiography revealed an excellent long-term result and a decrease in the extent of coronary atherosclerotic lesions. Since then the patient was on weekly treatment again and experienced no further clinical symptoms or angiographic progression.


Case 2: Based on this experience, we started an intensified treatment regimen in August 2017 in a 78-year-old woman with elevated Lp(a) (> 140 mg/dl). Initially weekly Lp-apheresis was started in September 2013 due to generalized atherosclerosis. Aortocoronary bypass surgery, multiple coronary stenting, as well as thrombendarteriectomy in terms of peripheral artery disease was performed over the years. In 2016 the patient experienced angina pectoris. Coronary angiography showed progression of coronary atherosclerosis and three in-stent restenoses in 2016 and one in-stent restenosis in 2017. Percutaneous coronary angioplasty was successfully performed. After 7 months with 42 Lp-apheresis sessions in 31 weeks (1,35 therapies per week), the patient reported an increase in exercise capacity due to a decrease of angina pectoris. Coronary angiography showed one in-stent restenosis, a percutaneous coronary angioplasty and a stent-in-stent implantation was successfully performed.


Conclusion: Temporarily shortening of treatment intervals for a duration of one year resulted in an improvement in clinical symptoms and no further progression of atherosclerosis. In contrast, an improvement of atherosclerotic disease could be proven by coronary angiography. We conclude that shorter therapeutic Lp-apheresis intervals should be considered in patients who suffer from clinical and/or angiographic progression of atherosclerosis despite maximal lipid lowering medication and weekly Lp-apheresis sessions.



P-19 Affinity sorbents based on tryptamine and tyramine for practical use in medicine and biotechnology
Ekaterina Ovchinnikova1, Irina Adamova2, *Elena Utkina2, Pavel Levashov3, Sergei Pokrovsky2
1 National Medical Research Center of Cardiology, Ministry of Health of Russian Federation, Moscow, Russia, Institute of Experimental Cardiology, Moscow, Russian Federation
2 National Medical Research Center of Cardiology, Ministry of Health of Russian Federation, Moscow, Russia, Institute of Experimental Cardiology, Moscow, Russian Federation
3 Moscow State University, , Moscow , Russian Federation
Abstract text :

Question. Affinity sorbents which can bind different components of human plasma are widely used in medicine and biotechnology. As ligands, animal and bacterial proteins are usually used. Natural aromatic amines, tyramine and tryptamine are small structurally simple hydrophobic molecules that are potentially capable of interacting with various components of human plasma. We propose to create sorbents based on these synthetic ligands which can replace expensive sorbents with protein ligands.


Methods. We have developed a simple new technique for immobilizing these ligands on a polysaccharide matrix. Sorption characteristics of the sorbents have been studied.


Results. It has been shown that sorbents with tyramine and tryptamine can bind: IgG and IgA; atherogenic lipoproteins like lipoprotein(a) [Lp (a)] and low density lipoproteins (LDL) from human plasma. The sorption capacity (mg per mL of gel) was: for IgG - 9 and 4, for IgA - 4 and 2, for Lp(a) - 3 and 5, for LDL - 5 and 7 for tyramine-agarose and tryptamine-agarose respectively. We have investigated eluates from the sorbents by electrophoresis under denaturing conditions and exclusion chromatography. In one from 3 samples of patient"s plasma a part of their IgG binds with Lp(a), which can confirm the existence of Lp(a) and IgG complexes. These results correspond to literature data about existence of antibodies against apoB100-containing lipoproteins.


Conclusions. We proved that sorbents based on tyramine and tryptamine, bind IgG and atherogenic lipoproteins. New sorbents will be able to find application in clinical practice and in solving biotechnological problems.



P-20 Effect of LDL/Lp(a) apheresis treatment on plasma levels of miRNAs in patients with high Lp(a), a follow-up study
*Dana Dlouha1, Jan Pitha1, Zuzana Eretova2, Jaroslav Hubacek1, Alena Parikova2, Ondrej Viklicky2
1 Institute for Clinical and Experimental Medicine, Centre for Experimental Medicine, Prague, Czech Republic
2 Institute for Clinical and Experimental Medicine, Clinic of nephrology, Prague, Czech Republic
Abstract text :

Background: LDL/Lp(a) apheresis therapy is the well-established method for an aggressive lowering of LDL and Lp(a). Recently discussed markers of vascular status including atherosclerosis are miRNAs, which inhibit post-translational processes through RNA duplex formation resulting in gene silencing. The aim of our study was to analyze the effect of LDL/Lp(a) apheresis on circulating miRNAs related to cardiac diseases.


Materials and methods: We measured a profile of 180 plasma circulating miRNAs using pre-defined Serum/Plasma Focus panels in two women with the diagnosis of high levels of Lp(a) and repeated re-occlusions of coronary arteries who underwent 3 years therapy of LDL/Lp(a) apheresis. We compared miRNAs plasma levels at the start of therapy and one year after.


Results: Lower levels of circulating miR1260a; miR505-3p; miR132-3p; miR421; miR365a-3p; (all P<0.05) implicated in lipid metabolism and vascular integrity, were detected in samples one year after LDL/Lp(a) therapy. We found also differences between patients: levels of plasma miR22-3p (P<0.007); miR185-5p (P<0.01); miR484 (P<0.02) associated with cardiac remodeling and mir125a-5p; miR335-5p and miR27a-3p, (all P<0.03) implicated in regulating triglyceride and cholesterol metabolism, showed differently plasma levels.


Conclusions: LDL/Lp(a) apheresis has a significant impact on miRNAs associated with vascular integrity and impaired angiogenesis. Divergence in plasma miRNAs levels between women could probably reflect their different clinical condition. Results should be verified in a larger study.


Supported by Ministry of Health of the Czech Republic, grant nr. 17-28882A. All rights reserved."



P-21 Lipoprotein Apheresis Administration Experience in Estonia: Case Report
*Julia Piel1, Kadri Lilienthal1
1 The North Estonia Medical Centre, Nephrology, Tallinn, Estonia
Abstract text :

A 69-year-old female patient with acute angina pectoris and myocardial infarction (STEMI; in anterior wall) was hospitalized into ICU unit in March 2014. The patient had a history of hypertension with cardiac insufficiency as well as dyslipidemia and obesity. She was a daily smoker. The parents of the patient died of heart attack at the ages of 65 and 67. She was allergic to fluvastatin, aspirin and paracetamol. Selective coronarography showed occlusion of LAD (left anterior descending) coronary artery OM (obtus marginalis) 80% stenosis of ACD (right coronary artery), the last one non-dominant. It was not possible to reopen LAD during coronaroplasty. EF (exit fraction) was 30 %.


Despite several angioplasty procedures in 2014 and 2015 there were still complaints of angina pectoris in November 2016 and the levels of LDL and TG were constantly high despite treatment with ezetimib. Treatment with several statins was not tolerated due to adverse effects. This study was commenced to assess the suitability of lipopheresis for treatment of dyslipidemia by decreasing blood cholesterol and LDL levels.


An arterio-venous fistula was created into patient"s right hand brachial region and on 09.01.2017 lipopheresis treatment was started on a weekly basis to decrease LDL, TG and Lp(a). For that, a pair of multiple use Lipocollect adsorbers (Medicollect, Germany) were used for the adsorption of lipids from blood plasma. The adsorption was controlled using the Adasorb monitor (Medicap, Germany) together with the Spectra Optia plasma exchange device (Terumo BCT, USA).


Blood tests performed the same day before and after the procedure revealed a consistent decrease in lipid concentrations: (on average) Chol - 57%, LDL - 63%, HDL - 20%, TG - 36%, Lp(a) - 67%


During the study period there were no complaints of angina pectoris. The patient"s physical capacity rose substantially immediately after each procedure. One year into treatment the EF stays at 35-40 %.


Considering the cardiac status and morphological changes of patient"s heart (MRI, SPECT study, echocardiography), allergic reactions to statins and lack of effect of ezetimib as well as coexisting diseases, (dyslipidemia, diabetes mellitus, hypertension with coexisting heart failure) the weekly lipopheresis has been efficient in improving patient"s health status and quality of life.



P-22 Risk factor constellation in patients with premature cardiovascular events
*Ulrike Schatz1, Sabine Fischer1, Sergey Tselmin1, Gisela Müller1, Ulrich Julius1, Stefan Richtard Bornstein1
1 Universitätsklinikum Dresden, Mk3, Dresden, Germany
Abstract text :

Introduction


Lipoprotein(a) (Lp(a)) is recognized as an independent and severe cardiovascular (CV) risk factor. Several studies showed raised CV risk in patients with increased Lp(a). There is data demonstrating a significant reduction of CV events in patients undergoing lipoprotein apheresis (LA). Aim of this study was to evaluate main risk factors of patients with premature (< 50 years) CV events.


Material and Methods


130 patients of our Lipidology Outpatients Specialist Clinics were included in the analysis (97 males, 33 females) with ≥ 1 CV event at the age of ≤ 50 years (myocardial infarction, PTCA and Stent Implantation in coronary arteries or carotid arteries or peripheral arteries, bypass graft operation in coronaries or peripheral arteries, TIA, stroke, carotid TEA). All CV risk factors were assessed. Since all patients had a CV event they were all on lipid lowering drugs at their first consultation in our specialty outpatients unit. LDL-C and Lp(a) levels before the CV event are hence unknown. Patients were divided into three groups depending on their Lp(a) level: Group 1 (n = 29): Lp(a) 0-45 nmol/l, Group 2 (n = 11) : Lp(a) 46-120 nmol/l and Group 3 (n = 90) Lp(a)> 120 nmol/l.


Results


69.2% of patients with premature CV events ≤ 50 years in this analysis had Lp(a) levels > 120 nmol/l (Group 3). There was no significant difference between the three groups regarding body mass index, age, LDL-C, HDL-C, triglycerides, HbA1c, creatinine/eGFR. Mean age at first CV event did not differ between the three groups: Group 1: 37.9 years, Group 2: 38.7 years, Group 3: 40.6 years. Most CV events were observed in Group 3. The majority of patients with premature CV events were smokers (61%), 9% were ex-smokers, 30% were non-smokers. In Group 3 highest rates of a positive family history regarding hyperlipoproteinemia (Group 1: 58.6%, Group 2: 54.2%, Group 3: 71.1%) and premature CV events (Group 1: 45%, Group 2: 46%, Group 3: 56%) were documented. Premature CV events occurred predominantly in coronary arteries (60%) in all three groups, followed by PAOD. Cerebrovascular disease was least common.


Conclusions


Our data show that most of the included patients with premature CV events had a Lp(a) > 120 nmol/l and most events were observed in coronary arteries. This demonstrates that Lp(a) > 120 nmol/l is an important risk factor for premature CV events.