[Opinion of the Czech Atherosclerosis Society's committee (CSAT) on the ESC/EAS guidelines related to the diagnostics and treatment of dyslipidemias issued in 2011]. / Stanovisko výboru CSAT k doporucením ESC/EAS pro diagnostiku a lécbu dyslipidemií z roku 2011.

This position statement of the Executive Committee of the Czech Society for Atherosclerosis (CSAT) summarizes the most important aspects and novelties of the latest European guidelines for the management of dyslipidemia. In particular the position statement comments on: cardiovascular risk stratification, indications for plasma lipid and lipoprotein levels assessment as well as target lipid values, evaluation of current options for both lifestyle and pharmacological treatment of lipid metabolism disorders and, also, recommendation for laboratory monitoring of patients treated with lipid lowering agents. The statement deals with actual concepts of management of dyslipiemia in everyday practice, e.g. therapy of dyslipidemia in special patients´ groups. This statement does not replace the latest guidelines but focuses on the changes from the former guidelines for dyslipidemia management, published by CSAT in 2007.

[Current guidelines on the care of tunelized vascular catheters in patients on home parenteral nutrition]. / Péce o tunelizované zilní katétry u nemocných na domácí parenterální výzive podle soucasných doporucení

Home parenteral nutrition is the only option to provide nutrition in a number of patients. Care of venous entry, its management and treatment of complications resulting from its use importantly affect patient survival. Appropriate care of the catheter and the use of current knowledge may prolong the lifespan of the catheter, reduce patient morbidity and mortality and thus increase quality of life of patients who are dependent on home parenteral nutrition. The present paper summarizes recommendations for the care of long-term venous catheters.

RHEOPHERESIS IN THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Evaluation of the long-term effect of rheopheresis treatment of dry form of age-related macular degeneration (AMD). MATERIALS AND METHODS: The treatment group consisted of 65 patients and 55 patients in the control group, with a minimum follow-up period of 60 months. The basic treatment consisted of 8 rheopheresis procedures, and the additional treatment (booster therapy) of 2 rheopheresis procedures 1.5-2 years after the basic treatment. We evaluated changes in best corrected visual acuity, anatomical effect, electrical activity of the retina, haematological, biochemical and immunological parameters. RESULTS: Rheopheresis treatment contributed significantly: 1) to stabilisation of best corrected visual acuity of the treated patients, which initially showed an insignificant increased during the 2-years follow-up period, and then slightly decreased. By contrast, visual acuity decreased in the control group, to an insignificant degree up to 4 years, then statistically significantly. 2) to an improvement of the morphological findings in 62.4% of treated patients compared to 7.5% in the control group, while disease progression to stage 3 (neovascular form of the disease or geographic atrophy) with a significant decrease of visual acuity occurred in only 7.1% of treated patients, versus 37.0% in the control group. 3) to regression, even to the attachment of drusenoid pigment epithelial detachment (DPED). To a reduction of the area of DPED in 80.4% of treated patients, in contrast with an steaincrease in the area of DPED in 47.1% of patients in the control group, and the development of new DPED in only 2 eyes of treated patients compared with 16 eyes of patients in the control group. 4) to a preservation of the integrity of the ellipsoid layer in the fovea in 68.2% of the treated patients, while by contrast we found a damaged ellipsoid layer in the fovea in 66.6% of the control patients. 5) to a stabilisation of the activity of ganglion cells, the pineal system and the activity of the central area of the retina, with eccentricity between 1.8° and 30° in the treated patients, compared to alteration in the control group manifested mainly after 3.5 years of the follow-up period. 6) to a statistically significant improvement in rheological parameters, thereby increasing flow in microcirculation and positively influencing the metabolism in the retina. Also to a positive effect on the classical, alternative and lectin pathway of complement activation, a reduction in the level of proprotein convertase subtilisin kexin 9 (PCSK9), and thus also the level of LDLcholesterol, and 7) Additional treatment with 2 RHF procedures (so-called "booster therapy") seems to be a safe and suitable method of prolonging the stabilisation phase, or even improving visual acuity, anatomical and functional findings. CONCLUSION: We demonstrated positive changes in anatomical, functional and humoral parameters upon rheopheresis treatment of AMD. Their correlation provides a real possibility to identify patients at risk and to manage an individualised regime of rheopheresis therapy. This method of treatment is effective and safe, with a low percentage of non-serious adverse effects.

Use of ultra high performance liquid chromatography-tandem mass spectrometry to demonstrate decreased serum statin levels after extracorporeal LDL-cholesterol elimination.

BACKGROUND: Using our statin analysis method, it was possible to uncover a significant drop in statin levels (atorvastatin, simvastatin, and metabolites) after extracorporeal LDL-cholesterol elimination (EE) in severe familial hypercholesterolemia (FH). The purpose of this work was to identify the mechanism underlying this drop and its clinical significance as well as to propose measures to optimize a pharmacotherapeutical regimen that can prevent the loss of statins. METHODS: Ultra High Performance Liquid Chromatography (UHPLC) connected to the triple quadrupole MS/MS system was used. Patients. A group of long-term treated patients (3-12 years of treatment) with severe FH (12 patients) and treated regularly by LDL-apheresis (immunoadsorption) or haemorheopheresis (cascade filtration) were included in this study. RESULTS: After EE, the level of statins and their metabolites decreased (atorvastatin before/after LDL-apheresis: 8.83/3.46 nmol/l; before/after haemorheopheresis: 37.02/18.94 nmol/l). A specific loss was found (concentration of atorvastatin for LDL-apheresis/haemorheopheresis: 0.28/3.04 nmol/l in washing fluids; 11.07 nmol/l in filters). To prevent substantial loss of statin concentrations, a pharmacotherapeutic regimen with a longer time interval between the dose of statins and EE is recommended (15 hours). CONCLUSIONS: A specific loss of statins was found in adsorbent columns and filters. The decrease can be prevented by the suggested dosage scheme.

Monitoring of up to 15 years effects of lipoprotein apheresis on lipids, biomarkers of inflammation, and soluble endoglin in familial hypercholesterolemia patients.

BACKGROUND: Lipoprotein apheresis (LA) is considered as an add-on therapy for patients with familial hypercholesterolemia (FH). We aimed to analyze the data collected in the last 15 years from FH patients treated with LA, to elucidate the benefit of this procedure with respect to plasma lipids, biomarkers of inflammation, and endothelial dysfunction and soluble endoglin. RESULTS: 14 patients (10 heterozygous FH patients (HeFH), 4 homozygous FH patients (HoFH)) were treated by long-term lipoprotein apheresis. Lipid levels were examined, and ELISA detected biomarkers of inflammation and soluble endoglin. Paired tests were used for intergroup comparisons, and a linear regression model served to estimate the influence of the number of days patients were treated with LA on the studied parameters. LA treatment was associated with a significant decrease of total cholesterol (TC), LDL-C, HDL-C, and apoB, in both HeFH and HoFH patients, after single apheresis and in a long-term period during the monitored interval of 15 years. Biomarkers of inflammation and endothelial dysfunction were reduced for soluble endoglin, hsCRP, and MCP-1, and sP-selectin after each procedure in some HeFH and HoFH patients. CONCLUSIONS: LA treatment up to 15 years, reduced cholesterol levels, levels of biomarkers related to endothelial dysfunction, and inflammation not only after each procedure but also in the long-term evaluation in FH patients. We propose that long-term LA treatment improves lipid profile and endothelial dysfunction in familial hypercholesterolemia patients, suggesting a promising improvement in cardiovascular prognosis in most FH patients.

Extracorporeal immunoglobulin elimination for the treatment of severe myasthenia gravis.

Myasthenia gravis (MG) is a neuromuscular disorder leading to fluctuating muscle weakness and fatigue. Rarely, long-term stabilization is not possible through the use of thymectomy or any known drug therapy. We present our experience with extracorporeal immunoglobulin (Ig) elimination by immunoadsorption (adsorbers with human Ig antibodies). Acetylcholine receptor antibodies (AChRAs) were measured during long-term monitoring (4.7 +/- 2.9 years; range 1.1-8.0). A total of 474 samples (232 pairs) were analyzed, and a drop in AChRA levels was observed (P = .025). The clinical status of patients improved and stabilized. Roughly 6.8% of patients experienced clinically irrelevant side effects. The method of Ig elimination by extracorporeal immunoadsorption (IA) is a clinical application of the recent biotechnological advances. It offers an effective and safe therapy for severe MG even when the disease is resistant to standard therapy.

Prediction of long-term prognosis of age-related macular degeneration treated by hemorheologic therapy using baseline laboratory indicators - Experimental-clinical model.

BACKGROUND + OBJECTIVE:Age-related macular degeneration (AMD) is the most common cause of practical blindness in people over 60 years of age in industrialised countries. We formulated a hypothesis that a group of initial laboratory parameters would be suitable for prediction of prognosis of AMD, allowing for individual modifications in treatment intensity. PATIENTS AND METHODS: 66 patients with dry form of AMD were treated using rheohaemapheresis with an individual follow-up period of more than 5 years. The patients' initial laboratory data was split in two subgroups based on treatment success and analysed using discriminant analysis (analysis of the linear and quadratic models using the automated and interactive step-wise approach) by means of the Systat 13 software. RESULTS: Prediction of prognosis based on the initial laboratory parameters was correct in 79% of unsuccessfully treated patients, allowing for early detection of high-risk patients. With the use of a quadratic model, the prediction was correct in 100% of unsuccessfully treated patients and in 75% of successfully treated patients. CONCLUSION: Implementation of discriminant analysis is a promising method for prediction of prognosis, especially when the patient is at risk of AMD progression, which allows for early and more intensive monitoring and treatment.

The importance of rheological parameters in the therapy of microcirculatory disorders.

Rheological conditions basically influence tissue perfusion, oxygen and nutrient supply, tissue regeneration and in its consequence the course of pathological processes, especially in microcirculation and partially even in macrocirculation. Haemorheotherapy has shown to be successful in several indications (critical disorders in microcirculation) when other methods of therapy have failed. In this study we describe the changes of effectivity indicators in haemorheopheresis treatment and their clinical importance in cases of eye microcirculation, statoacoustic apparatus and disorders of the lower extremities. We treated with haemorheopheresis (separator Cobe.Spetra + Evaflux filter) 24 patients (16 patients with age related macular degeneration, 5 with critical peripheral arterial foot disease, and 3 with acute hearing loss). After the procedures alpha2-macroglobulin decreases by about 58%, fibrinogen by about 69%, IgM by about 61%, LDL-cholesterol by about 77%, apolipoprotein B by about 76% and lipoprotein(a) by about 63%. It corresponds with a decrease in blood and plasma viscosity and clinical improvement in the observed patients, i.e. visual improvement, acceleration of tissue defect healing and improvement in hearing. We noticed 7.1% clinically insignificant side-effects. The method of haemorheopheresis was safe. It led to improvement in patients' clinical condition in the above mentioned indications when other methods of treatment failed.

[Hypolipidemic drugs and diabetes mellitus]. / Hypolipidemika a diabetes mellitus.

Diabetes mellitus associates with high cardiovascular risk. The absolute values of cardiovascular risk tend to be even higher than as calculated from the SCORE tables. Recent randomized clinical trials have shown evidence of benefit and safety of more intensive LDL-cholesterol lowering in patients with diabetes and established cardiovascular disease supporting guidelines for a more intensive LDL goal of therapy. A recent meta-analysis has confirmed benefit on major coronary events and ischaemic stroke in many diabetic patient subgroups, including those with type 1 disease. The pathological combination of several lipoprotein metabolism abnormalities and the need to reach lipoprotein goals need combination therapy of hypolipidemic drugs with different mechanisms of action. Despite statin treatment, cardiovascular disease residual risk remains high. After LDL the next lipoprotein goal is to increase HDL. Although there has been disappointment with the first cholesteryl-ester-transfer-protein-inhibitor, there is encouraging evidence that increasing HDL with the peroxisome-proliferator-activator-receptor (PPAR) gamma agonist, pioglitazone and nicotinic acid derivatives may contribute beyond statin therapy.

[Peritonitides caused by gastrointestinal perforations--analysis of an elderly patient group]. / Peritonitidy zpusobené perforací trávicí trubice--analýza gerontologické skupiny pacientu.

AIM: The aim of this study was to assess causes of peritonitides resulting from acute abdominal perforations in a group of elderly patients and to evaluate the yield of common classification systems in predicting the risks of postoperative complications, in particular of postoperative death rates. PATIENTS AND METHODS: The retrospective analysis included 123 patients aged 70 y.o.a. and over (65 males, 58 females, the mean age was 78.7 y.o.a.), who underwent surgical revision for signs of peritonitis due to urgent GIT perforation, over a five-year period. The patients were assigned to groups based on their baseline diagnosis and on the procedure performed. The PSS (Peritonitis Severity Score) and MPI (Mannheim Peritonitis Index) classification systems factors were assessed. Statistical significance of the classification systems was evaluated, as well as their relation. RESULTS: Overall death rate of the studied group was 30% (37 patients). The highest death rate related to the baseline diagnosis was observed in the GIT ischemia group (67%). Based on the procedure, the highest death rate was observed in the enterostomy group (75%). Overall morbidity related to a known wound infection was 24% (29 patients). Significant correlation between the both classification systems was demonstrated (Spearman's correlation coefficient 0.86). Of the all studied factors creating classification schemes, the following proved statistically most significant: ASA IV, peritonitis Hinchey grade III-IV, existing immunosuppression and signs of organ failure (p < 0.0001). CONCLUSION: Perforation peritonitis remains a high risk condition, considering the postoperative morbidity rates, as well as the death rates. Perforation of the sigmoid diverticle was the commonest cause of GIT perforations in the elderly. The highest death rate was observed in those with ischemic ethiology. The PSS and MPI scoring systems are of high prediction value in the assessment of the risk of postoperative death.

High-dose chemotherapy followed by autologous stem cell transplantation changes prognosis of IgD multiple myeloma.

Immunoglobulin D (IgD) multiple myeloma (MM) is a rare plasma cell disorder constituting less than 2% of all MM cases. Survival of patients with IgD MM is generally shorter than that of patients with other types of monoclonal (M-) protein. We have retrospectively analyzed patients with IgD MM participating in clinical trials of the Czech Myeloma Group. Twenty-six IgD MM patients treated between 1996 and 2006 were identified, 14 (54%) men and 12 (46%) women. The median age was 61 years (range: 37-79 years). Ten of 26 patients (39%) were treated with first-line high-dose chemotherapy (HDCT) using melphalan 200 mg/m(2) followed by autologous stem cell transplantation (ASCT). Thirteen of 26 patients (50%) received conventional chemotherapy (CHT), mostly melphalan and prednisone or a vincristine/doxorubicin/dexamethasone (VAD) regimen. Treatment responses were evaluable for 23 of 26 (89%) patients. All HDCT patients had treatment responses, including seven patients (70%) with complete responses and three patients (30%) with partial responses. The median progression-free survival was 18 months for HDCT patients and 20 months for CHT patients. The median overall survival (OS) for all patients was 34 months. The median OS for the HDCT group has not yet been reached (70% of the patients are still alive). In contrast, the median OS for CHT patients was only 16 months. The difference in OS between the two groups was statistically significant (P=0.005). In conclusion, the overall response rate for patients with IgD MM aged 65 years or less treated with HDCT and ASCT is similar to that seen in other MM types.

[Nutrition for the diabetic patient with kidney disease]. / Výziva diabetika s onemocnením ledvin.

Malnutrition is a major problem in chronically ill patients. The combination of diabetes and renal insufficiency increases the risk of malnutrition, also due to dietary interventions associated with the two diseases. Resulting malnutrition intensifies inflammatory activity and further compromises nutrition intake. This results in a vicious circle which significantly reduces the quality of life of the affected patients and increases their mortality. Proper nutritional care for such patients is an integral part of their treatment.

Isotype class switching after transplantation in multiple myeloma.

Switching of the paraprotein isotype or transient presence of oligoclonal bands detectable by serum immunofixation electrophoresis has been reported following not only transplantations, but also after intensive chemotherapy for leukemia. Retrospective analysis of 72 transplanted myeloma patients was carried out to determine the frequency and clinical significance of the appearance of abnormal proteins bands (APB) distinct from the original paraprotein. APB presence was observed in 31 patients (43%) already after the first autotransplant, the median interval from transplant was 2 months (range, 1 to 6 months). The most frequent occurrence of APB was observed after allogeneic transplantation. In the group of patients with APB presence more patients achieved complete remission (32.2% versus 17.1%), statistically significant differences were also established when we compared the percentage of surviving patients and overall survival, to the present date, among both groups of patients (p=0.03). All relapsed patients with previous isotype class switching had disease characterized by the same type of paraprotein as that detected at diagnosis. The development of APB is likely related to the recovery of impaired immunoglobulin production after transplantation. We confirmed favourable prognostic significance of this finding in transplanted myeloma patients.

[The MIAC (malnutrition, inflammation, atherosclerosis, calcification) syndrome]. / Syndróm MIAC (malnutrition, inflammation, atherosclerosis, calcification).

The number of patients with chronic renal failure is on the rise; these patients have a 10 to 20 times higher risk of development and progression of cardiovascular diseases. Higher cardiovascular risk in such patients cannot be satisfactorily explained by traditional risk factors defined in the Framingham study. On the contrary, a concept of reverse epidemiology has been brought forward, designating a situation in which the incidence of obesity and hyperlipoproteinemia is associated with a higher survival rate of the patients concerned. Higher risk is today explained by the "MIAC (malnutrition, inflammation, atherosclerosis, calcification) syndrome", which is present in patients with chronic kidney disease. New evidence has been recently obtained of different circulating molecules associated with atherosclerosis, the plasmatic levels of which are decreased or increased in such patients and which are in a way linked with the MIAC syndrome and the progression of atherosclerosis. Clinical management of the syndrome could increase survival in the future, and reduce morbidity and the number of hospitalisations. Circulating molecules could serve as markers evidencing the presence of the syndrome and its severity, as well as the success of treatment.

[Changes in lipid metabolism in patients in the active phase of Crohn's disease]. / Zmeny metabolizmu lipidu u pacientu v aktivní fázi Crohnovy choroby.

INTRODUCTION: Crohn's disease (CD) in its active period is accompanied by a decreased food intake and deterioration in water, mineral and metabolic balance. Lipid metabolism is known to be altered in many acute diseases, and hypocholesterolemia is a serious negative prognostic indicator. The causes of decreased serum cholesterol concentration are multiple. Simultaneous affection of both cholesterol synthesis and absorption has been reported in many sources. The changes in both the above processes can be quantified with the use of specific indicators of synthesis (cholesterol level) and absorption (sitosterol and campesterol levels). OBJECTIVE: The objective of the study was to demonstrate changes in lipid metabolism in patients with active Crohn's disease, and to find out to what extent the above phenomenon is influenced by the affection of the process of cholesterol synthesis and/or absorption in the case of detected hypocholesterolemia. MATERIAL AND METHODS: Total serum cholesterol, LDL- and HDL-cholesterol and triglyceride levels were measured on the 3rd, 14th and 28th day from admission in addition to admission analyses in 24 patients with acute manifestation of CD (CDAI - Cohn's disease activity index - over 150). Also measured were the concentrations ofsqualene, lathosterol, sitosterol and campesterol. The results were compared with a control sample of 100 voluntary blood donors. The obtained data was processed using the Sigma-stat 3.1 statistical software. RESULTS: Decreased levels of all basic lipid metabolism parameters were detected. At the same time, a statistically significant decrease in the levels of lathosterol and camposterol was recorded. The decrease in sitosterol levels was insignificant and the level of squalene was higher than in the controls. CONCLUSION: Significant changes in lipid metabolism were demonstrated in the study in patients in active phase of Crohn's disease. Also detected was statistically significant hypocholesterolemia, with altered process of cholesterol synthesis and absorption.

[The effect of treatment with fenofibrate on the risk profile of patients with metabolic syndrome and mixed dyslipidemia treated on an outpatient basis]. / VIiv lécby fenofibrátem na rizikový profil nemocných s metabolickým syndromem a smísenou dyslipidemií lécených ambulantne.

The study has shown that patients with metabolic syndrome and typical dyslipidemia treated on an outpatient basis by general practitioners or specialists are those whose anamneses include IHD or diabetes and who are very often indicated for combined statin-fibrate therapy. Fenofibrate therapy combined with a single lifestyle intervention in the form of individual interview resulted in the following improvement of the risk profile of the above patients: significant decrease in body weight and waist circumference, decrease in blood pressure and fasting glycemia; improvement of typical dyslipidemia in 90% of patients, however, only 30% of patients achieved the target TG levels below 1.7 mmol/l and the HDL-cholesterol levels above 1.3 mmol/l and 1 mmol/l in women and men, respectively. A total of 60% of patients no longer met the criteria for MS after 6 months of therapy. However, LDL-cholesterol and total cholesterol levels in patients with IHD or with diabetes were very unsatisfactory; only 6% of patients had achieved the recommended level of target LDL-cholesterol below 2.5 mmol/l before the intervention, i.e. 94% of the patient sample was indicated for statin therapy. 86% of patients with LDL-cholesterol above 2.5 mmol/l remained in our patient sample after non-pharmacological and pharmacological fibrate therapy. The results show that combined statin--fibrate therapy would be the best therapy for patients with IHD or diabetes who meet the MS criteria and whose typical dyslipidemia is expressed.

Familial hypercholesterolemia in the Czech Republic: more than 17 years of systematic screening within the MedPed project.

Familial hypercholesterolemia (FH) is the most common autosomal dominant disorder. It is characterized by a decrease in LDL cholesterol catabolism and an early clinical manifestation of atherosclerotic vessel damage. The aim of the MedPed (Make early diagnosis to Prevent early deaths) project is an early diagnosis of FH patients in order to profit from early treatment and prevent cardiovascular events. Till November 30, 2016 The Czech National MedPed Database has registered 7,001 FH patients from 5,223 different families that is 17.4 % of expected patients in the Czech Republic considering 1:250 FH prevalence. The improvement in diagnostic accuracy, patient cooperation and above all familial cascade screening is enabled by FH mutation detection using the modern technology of next-generation sequencing. FH still remain undiagnosed even though the Czech Republic is one of the most successful countries with respect to FH detection. The opportunities of international collaboration and experience sharing within international programs (e.g. EAS FHSC, ScreenPro FH etc.) will improve the detection of FH patients in the future and enable even more accessible and accurate genetic diagnostics.

Antioxidant defense system in familial hypercholesterolemia and the effects of lipoprotein apheresis.

Oxidative stress is thought to play an important role in the pathogenesis of disorders associated with atherosclerosis. Alpha-tocopherol is considered to be an effective lipophilic antioxidant, which protects lipid membranes against peroxidation and thus prevents cell damage by reaction with free radicals. However, measurement of alpha-tocopherol concentration in serum does not reflect the content of α-tocopherol in membranes whereas erythrocyte alpha-tocopherol may be good indicator of antioxidative status. Therefore a simple isocratic reversed phase HPLC method has been developed and validated for the determination of alpha-tocopherol in human erythrocytes in a clinical setting. The content of alpha-tocopherol in human erythrocyte membrane and lipoperoxidation were studied in patients with severe hypercholesterolemia treated by lipoprotein apheresis. The group of hypercholesterolemic patients (n = 14) treated by lipoprotein apheresis was compared to healthy adult normolipidemic controls. After lipoprotein apheresis, the content of in membrane alpha-tocopherol did not change significantly despite decreased tocopherol in serum and lipoprotein fractions. We observed significantly decreased lipoperoxidation as revealed by serum TBARS, representing end products of lipid peroxidation, which increased from third day afterwards and remained significantly higher in comparison to controls until the next LDL-apheresis. We conclude that aggressive lipid lowering procedure with lipoprotein apheresis was associated with favorable transient decrease of lipoperoxidation. Simultaneously the cell membrane bound antioxidative defense mechanisms as reflected by the content of alpha-tocopherol in human erythrocyte membrane where not depressed in spite of its decreased plasma lipid carrier. Another variables involved remain to be investigated.

Lipoprotein apheresis in the treatment of dyslipidaemia - the Czech Republic experience.

In 1984, we started using therapeutic plasmapheresis (plasma exchange) as a method of extracorporeal lipoprotein elimination for the treatment of hypercholesterolemic patients. We evaluated the results of long-term therapy in 14 patients, 8 men and 6 women. The average age was 55.6+/-13.2 (range 28-70), median 59.5 years. 14 patients were diagnosed with familial hypercholesterolemia (FH): 5 homozygous, 9 heterozygous. Ten patients in the group were treated using immunoadsorption lipoprotein apheresis and 4 using hemorheopheresis. Immunoapheretic interventions decreased LDL-cholesterol (82+/-1 %), ApoB (73+/-13 %) and even Lp(a) by 82+/-19 %, respectively. Selected non-invasive methods are important for long-term and repeated follow-up. Carotid intima-media thickness showed improvement or stagnation in 75 % of the patients. Biomarkers of endothelial dysfunction such as endoglin (in the control group: 3.85+/-1.25 microg/l, in lipoprotein apheresis-treated hypercholesterolemic individuals 5.74+/-1.47 microg/l), CD40 ligand (before lipoprotein apheresis: 6498+/-2529 ng/l, after lipoprotein apheresis: 4057+/-2560 ng/l) and neopterin (before lipoprotein apheresis: 5.7+/-1.1 nmol/l, after lipoprotein apheresis: 5.5+/-1.3 nmol/l) related to the course of atherosclerosis, but did not reflect the actual activity of the disease nor facilitate the prediction or planning of therapy. Hemorheopheresis may improve blood flow in microcirculation in familial hypercholesterolemia and also in some other microcirculation disorders via significantly decreased activity of thrombomodulin (p<0.0001), tissue factor (p<0.0001), aggregation of thrombocytes (p<0.0001) and plasma and whole blood viscosity (p<0.0001). In conclusion, lipoprotein apheresis and hemorheopheresis substantially lowered LDL-cholesterol in severe hypercholesterolemia. Our experience with long-term therapy also shows good tolerance and a small number of complications (6.26 % non-serious clinical complications).