The Familial Hypercholesterolemia Regression Study: A Randomized Comparison of Therapeutic Reduction of Both Low-Density Lipoprotein and Lipoprotein(a) Versus Low-Density Lipoprotein Alone

Abstract: Lipoprotein (a) [Lp (a)] is a risk factor for coronary heart disease (CHD), especially in the presence of a raised low-density lipoprotein (LDL)-cholesterol (LDL-C). To ascertain whether reduction of both LDL and Lp(a) is more advantageous than reduction of LDL alone, patients with heterozygous FH and CHD were selected randomly to receive either LDL apheresis fortnightly plus simvastatin 40 mg/day or colestipol 20 g plus simvastatin 40 mg/day. Quantitative coronary angiography was undertaken before and after 2.1 years. Changes in serum lipids were similar in both groups except for the greater reduction of LDL-C and Lp(a) by apheresis. There were no significant differences in primary angiographic endpoints, and none of the angiographic changes correlated with Lp(a). Although LDL apheresis plus simvastatin was more effective than colestipol plus simvastatin in reducing LDL-C and Lp(a), it was not more beneficial in influencing coronary atherosclerosis. Decreasing Lp(a) seems unnecessary if LDL-C is reduced below 130 mg/dl.—     

Lipoprotein (a) Immunapheresis in the Treatment of Familial Lipoprotein (a) Hyperlipoproteinemia in a Patient with Coronary Heart Disease

Abstract: This paper reports 2 years' experience with lipoprotein (a) (Lp[a]) immunapheresis which was successfully handled on a now 40-year-old patient with familial Lp(a) hyperlipoproteinemia inducing severe coronary heart disease with 2 myocardial infarctions and diffuse coronary sclerosis. Continued treatment by Lp(a) immun-absorption with specific sheep antibodies reduced stenosis in coronary vessels more than 50% and stopped the progression of coronary heart disease. A special apheresis technique and the results of continued absorption effects are described.     

Low‐Density Lipoprotein Apheresis and Changes in Plasma Components

Abstract: Several different techniques of low‐density lipoprotein (LDL) apheresis are available for management of severe hypercholesterolemia. Among them, the adsorption system with a dextran‐sulfate cellulose (DSC) column is most widely used. In addition to adsorption of LDL, DSC adsorbs plasma constituents that have the following characteristics: proteins containing apolipoprotein B (Lp[a]); proteins involved in the initial contact phase of the intrinsic coagulation pathway (coagulation factor XII, high‐molecular‐weight kininogen and prekallikrein); factors with lipophilic characteristics (coagulation factor VII, coagulation factor VIII, and vitamin E); and proteins with adhesive or other characteristics (von Willebrand factor, fibronectin, serum amyloid P component, hepatocyte growth factor). The adsorption of these proteins seems to ameliorate prevention or regression of atherosclerosis. Moreover, plasma treatment by the DSC column may be useful for treatment of inexorable diseases, such as amyloidosis. On the other hand, the DSC column generates bradykinin by activation of the initial contact phase of the intrinsic coagulation pathway. Bradykinin generation may explain the functional improvement in the circulatory system, as well as hypotension during LDL apheresis, which is observed in patients taking ACE inhibitors.     

The Effect of Selective Low-Density Lipoprotein Apheresis on Plasma Lipoperoxides and Antioxidant Vitamins in Familial Hypercholesterolemic Patients

Abstract: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by a lifelong elevation in the concentration of low-density lipoprotein (LDL) bound cholesterol in blood by cholesterol deposits and by early coronary artery disease. The LDL apheresis technique has been introduced with the goal of reducing LDL cholesterol levels, thereby preventing the development of atherosclerosis. The literature on LDL apheresis reports 2 different facets, the therapeutic aspect associated with the lessening of LDL concentration and the initiation of a peroxidation process associated with the biocompatibility of the artificial membrane. Lipid and protein peroxidation gives rise to toxic and atherogenic hydroperoxide, mostly lipid hydroperoxides, and derivative compounds, which may offset the benefit of the procedure. In this paper, plasma hydroperoxide levels are determined along with the elevation of the serum and LDL antioxidant status in hypercholesterolemic patients before and following repeated LDL apheresis sessions. Hydroperoxide concentration has been expressed both in terms of plasma volume and LDL concentration. A highly significant increase in LDL lipid hydroperoxides is demonstrated when expressed in terms of LDL concentration and is associated with the LDL apheresis procedure. The usefulness of antioxidant supplementation in LDL apheresis is discussed.     

Heparin‐Induced Extracorporeal Low‐Density Lipoprotein Precipitation Futura,a New Modification of HELP Apheresis: Technique and First Clinical Results

Abstract: Heparin extracorporeal low‐density lipoprotein precipitation (HELP) Futura is a new development in the standard HELP Secura system that has been in clinical practice for more than 15 years. Based on this experience, a HELP Upgrading system was first evaluated in a clinical trial to confirm the same clinical results as in the standard system. The upgraded procedure worked with industrially prepared sterile dialysis solutions instead of the reverse osmosis device. The conclusion of the study was that the reductions of low‐density lipoprotein, lipoprotein (a), and fibrinogen and the correction of the acid‐base balance were comparable with the results of the standard system. As a second step, the HELP Futura system was evaluated in a clinical acceptance test and in a field test in the daily routine. After approximately 2,000 treatments on 35 patients, we can conclude that the HELP Futura procedure has reached a mature phase with a high degree of clinical safety and flexibility.     

Apheresis Technology for Prevention and Regression of Atherosclerosis: An Overview

Abstract: Low density lipoprotein (LDL) apheresis is at present one method of treatment in homozygous cases of familial hypercholesterolemia (FH). It is also effective in the prevention of the development of coronary atherosclerosis in patients with heterozygous FH and other types of mild hypercholesterolemia, leading to the regression of the stenosing lesions. In this paper, an overview is presented on the development of the devices for LDL apheresis and its short-and long-term effects on FH mainly based upon experience with the Liposorber system. LDL apheresis has served to protect the lives of patients from life threatening diseases like myocardial infarction although observations for more than 10 years in some laboratories have shown that the progression of atherosclerosis has taken place in many patients, and more importantly, the involvement of the aortic valve with calcification has developed. especially in patients who had homozygous FH, making this the most obstinate complication of FH. Therefore, more aggressive treatment or the combination of LDL apheresis with other therapies is required in the future. LDL apheresis has also been approved for the treatment of glomerulosclerosis and arteriosclerosis obliterans.     

Relation of Serum Lipoprotein(a) Levels to Lipoprotein and Apolipoprotein Profiles and Atherosclerotic Diseases in Japanese Patients with Heterozygous Familial Hypercholesterolemia: Familial Hypercholesterolemia Expert Forum (FAME) Study

Aims: Lipoprotein(a) [Lp(a)] is a plasma lipoprotein consisting of a low-density lipoprotein (LDL)–like particle with apolipoprotein (Apo)(a), attached via a disulfide bond to Apo B100. Previous studies have shown that high Lp(a) levels are associated with an increased risk of cardiovascular disease in patients with familial hypercholesterolemia (FH). To date, limited data are available as to distribution of Lp(a) in FH and associations of Lp(a) with other lipid profiles and cardiovascular disease. Our study aimed to investigate serum Lp(a) levels in relation to other lipid profiles and clinical conditions in the national largest-ever cohort of Japanese FH patients. Methods: This study is a secondary analysis of the Familial Hypercholesterolemia Expert Forum (FAME) Study that includes a Japanese nationwide cohort of FH patients. In 399 patients under treatment for heterozygous FH who had a baseline measurement of serum Lp(a), the present study examined the distribution of Lp(a) levels and associations of Lp(a) with other lipid profiles and clinical conditions including coronary artery disease (CAD). Results: The distribution of Lp(a) was skewed to the right with a median of 20.8 mg/dL, showing a log-normal distribution. Serum Apo B and Apo E levels were positively associated with Lp(a) levels. Age-adjusted mean of Apo B was 8.77 mg/dL higher and that of Apo E was 0.39 mg/dL higher in the highest category (40+ mg/dL) of Lp(a) than in the lowest category (＜20 mg/dL). LDL-C levels did not show such an association with Lp(a) levels. A tendency towards a positive relationship between Lp(a) and prevalent CAD was observed in men. Conclusion: Our study demonstrated a distribution pattern of Lp(a) in Japanese FH patients and positive relationships of Lp(a) with Apo B and Apo E levels.     

Apheresis in coronary heart disease with elevated Lp (a): a review of Lp (a) as a risk factor and its management

Lipoprotein (a) (Lp (a)) increases global cardiovascular risk, especially when LDL cholesterol is concomitantly elevated. Epidemiologic data show that Lp (a) concentration in plasma can be used to predict the risk of early atherogenesis in a dose-dependent manner and late stages of atherosclerosis are accelerated by elevated Lp (a). Therapeutic means to lower Lp (a) are limited. The most effective method to reduce plasma Lp (a) concentration significantly is therapeutic apheresis. Because apheresis is laborious and expensive, patients considered for this procedure should suffer from high Lp (a) concentrations, well beyond 50 mg/dL, and have manifested and progressive coronary heart disease despite maximal drug therapy. Experimental data and therapeutic results will be discussed in the present paper.     

Clinical Application and Effectiveness of Low-Density Lipoprotein Apheresis in the Treatment of Coronary Artery Disease

Abstract: The Low-Density Lipoprotein Apheresis Coronary Atherosclerosis Prospective Study (L-CAPS) examined whether or not combined low-density lipoprotein (LDL) apheresis and drug therapy apheresis could induce the regression of coronary atherosclerotic lesions in patients with familial hypercholesterolemia. Twenty-eight patients treated with LDL apheresis and drugs and 11 patients treated with drugs alone underwent sequential coronary angiography 2.5 years apart. The frequency of cases with regression or no change was significantly higher for the apheresis group than for the control group (p = 0.004). The LDL apheresis Angioplasty Restenosis Trial (LART) investigated the hypothesis that high plasma lipoprotein (a) (Lp[a]) levels were associated with increased incidences of restenosis after coronary angioplasty. Two days before and 5 days after angioplasty, 66 patients underwent LDL apheresis. The restenosis rates were 21% in the 42 patients whose Lp(a) levels were reduced 50% and 50% in the 24 patients whose Lp(a) levels were reduced < 50% (p < 0.05). LDL apheresis is effective in the prevention of the progression of coronary atherosclerosis. Its potential application in restenosis prevention should be further investigated.     

Single Lipoprotein Apheresis Session Improves Cardiac Microvascular Function in Patients With Elevated Lipoprotein(a): Detection by Stress/Rest Perfusion Magnetic Resonance Imaging

The aim of this study was to explore the effects of a single lipoprotein apheresis session on myocardial stress/rest (S/R) perfusion in patients with elevated lipoprotein(a) (Lp(a)) and coronary artery disease using cardiac magnetic resonance imaging. Twenty patients with Lp(a) > 60 mg/dL and coronary artery disease were randomized into a control or a treatment group. Both groups underwent cardiac magnetic resonance imaging with assessment of left ventricular function, perfusion and viability, and the treatment group underwent lipoprotein apheresis immediately afterwards. Repeat magnetic resonance imaging was performed at 24 h for both groups and at 96 h for just the treatment group. The transmyocardial perfusion gradient (i.e. endo-epi ratio [EER]) was determined and a comprehensive parameter of resting and adenosine-induced stress perfusion was derived (EER-S/R). While the hematocrit remained unchanged, apheresis reduced lipoproteins and rheological parameters: Lp(a) − 55.1%, total cholesterol − 34.5%, low density lipoprotein (LDL) − 54.6%, Lp(a)-corrected LDL − 54.3%, high density lipoprotein − 17.4%, apolipoprotein B − 39.2%, plasma viscosity − 10.7%, and fibrinogen − 30.6% at 24 h (P < 0.05 for all). At 96 h these parameters, except for plasma viscosity, apolipoprotein B and Lp(a)-corrected LDL, recovered but did not reach baseline values (P < 0.05 for all). The EER-S/R at 24 h was lowered by therapy (ΔEER-S/R 5%; P < 0.03), whereas this effect disappeared at 96 h. The ejection fraction (EF) was slightly improved at 24 h (67.07 ± 6.28% vs. 64.89 ± 6.39%; ΔEF 2.2%, P < 0.05) and returned to baseline at 96 h. In the control group no corresponding changes were detected. In conclusion, cardiac magnetic resonance imaging detects subtle treatment-related changes in regional myocardial perfusion in patients with elevated Lp(a) and coronary artery disease undergoing lipoprotein apheresis.     

Comparison of Different Low Density Lipoprotein Apheresis Machines on Brain Natriuretic Peptide Levels in Patients With Familial Hypercholesterolemia

B-type natriuretic peptide (BNP) is a hormone released from cardiac ventricles during episodes of hemodynamic overload. Low density lipoprotein (LDL) apheresis, a procedure for patients with familial hypercholesterolemia (FH) and coronary artery disease (CAD), lowers plasma cholesterol and immediately reduces blood viscosity and coronary vascular resistance while improving myocardial blood flow and microvascular perfusion. Previous studies have demonstrated the ability of LDL apheresis to reduce BNP chronically. We undertook this study to evaluate the difference in reduction of BNP levels following a single treatment with two dissimilar LDL apheresis devices. We conducted a prospective trial involving 27 patients (19 F; age = 59 ± 9 years) with FH who received at least 6 months of bi-weekly LDL apheresis therapy with either the Secura heparin extracorporeal LDL precipitation (HELP) system (N = 17 patients, B. Braun, Inc., Melsungen, Germany) or the Liposorber LA-15 dextran sulfate absorber (DSA) system (N = 10 patients, Kaneka, Inc., Osaka, Japan). We measured BNP levels immediately before and after one treatment of LDL apheresis. Following LDL apheresis, BNP levels were reduced by an average of 40 ± 17% (P < 0.001). Despite treating equal amounts of plasma, the HELP system reduced BNP (45 ± 18%) significantly more than the DSA system (31 ± 11%, P = 0.031). In conclusion, LDL apheresis therapy, possibly through its immediate improvement of vascular flow and/or removal of the peptide from plasma, results in a significant reduction of BNP levels. The increased reduction of BNP by HELP may result from its superior acute alterations of rheological markers.     

The Role of Low Density Lipoprotein Apheresis in the Treatment of Familial Hypercholesterolemia

Abstract: The chief indication for low density lipoprotein (LDL) apheresis is the treatment of homozygous familial hypercholesterolemia (FH), a potentially fatal condition that responds poorly to conventional therapy. Dextran sulfate/cellulose adsorption columns (Kaneka) and on-line heparin precipitation (HELP) are the most popular systems used in LDL apheresis. Weekly or biweekly procedures plus concomitant drug therapy enable LDL cholesterol to be maintained at 30–50% of its untreated level, with regression of xanthomas, arrest of progression of coronary atherosclerosis, and improved life expectancy. However, aortic stenosis may progress despite apheresis and necessitate valve replacement. Better control of hypercholesterolemia results from combining apheresis with a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, atorvastatin. LDL apheresis can also be useful in treating drug-resistant FH heterozygotes with coronary disease. However, the FH Regression Study showed no evidence that reduction by apheresis of both LDL and lipoprotein(a), was more advantageous than reduction by combination drug therapy of LDL alone.     

Influence of Single Low‐Density Lipoprotein Apheresis on the Adhesion Molecules Soluble Vascular Cellular Adhesion Molecule‐1, Soluble Intercellular Adhesion Molecule‐1, and P‐Selectin

Abstract: The aim of our study was to investigate the influence of single low‐density lipoprotein apheresis (heparin extracorporeal low‐density lipoprotein precipitation [HELP]procedure) on plasma concentrations of soluble adhesion molecules (sAMs) such as soluble vascular cellular adhesion molecule‐1 (sVCAM‐1), soluble intercellular adhesion molecule‐1 (sICAM‐1), and P‐selectin in patients with familial heterozygous hypercholesterolemia and documented coronary artery disease enrolled in a chronic weekly HELP apheresis. Before HELP apheresis, the mean plasma concentration of sVCAM‐1 was 515 ± 119 ng/ml, 204 ± 58 ng/ml for sICAM‐1, and 112 ± 45 ng/ml for P‐selectin. After single HELP apheresis, plasma concentrations of sAM declined significantly by 32 ± 7%, 18 ± 15%, and 33 ± 25% for sVCAM‐ 1,sICAM‐1 and P‐selectin, respectively. After a 1 week interval, sAM concentrations rose to approximately the initial values. The concentrations of all sAMs studied were significantly lower in the plasma leaving than entering the filter. Due to filtration, the decline in plasma level of sVCAM‐1, sICAM‐1, and P‐selectin was 62 ± 19%, 51 ± 39%, and 67 ± 22%, respectively. In addition to lipid reduction, single HELP apheresis significantly lowers plasma concentrations of sVCAM‐1, sICAM‐1, and P‐selectin.     

Low-Density Lipoprotein Apheresis for Prevention and Regression of Atherosclerosis: Clinical Results

Abstract: Hypercholesterolemia can be adequately controlled by appropriate diet and maximum lipid lowering drug therapy in most patients. Nevertheless, there exists a group of patients, including those with familial hypercholesterolemia (FH), who remain at high risk for the development or progression of premature coronary heart disease (CHD). For these patients additional measures such as surgery and low-density lipoprotein (LDL) apheresis have to be considered. The objective of this multicenter trial, which included 30 clinical centers (28 in Germany and one each in Scotland and Luxembourg), was to determine if repeated LDL apheresis using the Liposorber LAIS system (Kaneka Corporation, Osaka, Japan) could lead to an additional acute and time averaged lowering of total cholesterol (TC) and LDL-cholesterol (LDL-C) in severely hypercholesterolemic patients whose cholesterol levels could not be controlled by appropriate diet and maximum drug therapy. A total of 6,798 treatments were performed on 120 patients, including 8 with homozygous FH, 75 with heterozygous FH, and 37 with unclassified FH or other hyperlipidemias from 1988 through 1994. The mean TC and mean LDL-C levels at baseline were 410.0 mg/dl and 333.9 mg/dl, respectively. LDL apheresis was performed once a week or at least once every 2 weeks in all patients. During treatment with the Liposorber system the mean acute percentage reduction was 52.6% for TC and 63.1% for LDL-C. Very low density lipoprotein cholesterol (VLDL-C) and triglycerides (TG) were also substantially reduced to 60.6% and 47.5%, respectively. Fibrinogen, a potential risk factor for CHD, was reduced by 26.2%. In contrast, the mean acute reduction of high density lipoprotein (HDL) was only 3.4%. During the course of the treatment, the time averaged levels of TC and LDL-C were reduced by approximately 39% and 50%, respectively, compared to baseline levels. The adverse events (AEs) were those generally associated with extra-corporeal treatments. The most common AE was hypotension, with 69 episodes corresponding to 1 % of all treatments reported in 44 of the 120 patients treated. All other kinds of AEs occurred in less than 0.2% of the treatments. The treatment with the Liposorber LA-15 system was overall well tolerated. It should be noted, however, that a more severe type of hypotensive reaction associated with flush, bradycardia, and dyspnea was reported in patients taking concomitant angiotensin converting enzyme (ACE) inhibitor medication. Except for such anaphylactoid-like reactions associated with the intake of ACE inhibitors, the Liposorber LA-15 system represents a safe and effective therapeutic option for patients suffering from severe hypercholesterolemia that could not be adequately controlled by diet and maximum drug therapy.     

Low-Density Lipoprotein Apheresis by Membrane Differential Filtration (Cascade Filtration) via Arteriovenous Fistula Performed in Children With Familial Hypercholesterolemia

Membrane differential filtration (cascade filtration) is an apheresis technique by which atherogenic lipoproteins can be eliminated from plasma on the basis of particle size. In this study, we aim to discuss the efficacy of low-density lipoprotein (LDL) apheresis performed by providing alternative vascular routes in two siblings with familial hypercholesterolemia who did not respond to medical treatment and diet. Of the two siblings, one was nine years old and the other one was three-and-a-half years old. Of the total of 78 apheresis processes performed, 24 were done via a permanent subclavian catheter, 36 were done via a subsequently provided arteriovenous fistula, and 18 were done via an arteriovenous graft. We observed a mean reduction in the plasma levels of total cholesterol (61.6%), LDL cholesterol (65.5%), and high-density lipoprotein cholesterol (38.6%). We noted that cascade filtration apheresis was effective in decreasing the LDL cholesterol in plasma, and no serious complications were noted. The success of the apheresis program depends on well-functioning blood access. An arteriovenous fistula may be the best route for the long-term treatment of familial hypercholesterolemia, which requires complication-free apheresis treatments.     

Apheresis Technology for Prevention and Regression of Atherosclerosis

Abstract: Familial hypercholesterolemia (FH) is a congenital disorder of cholesterol metabolism, which is due to a deficiency in low‐density lipoprotein (LDL) receptors. The homozygous form of FH is especially liable to coronary artery disease (CAD) in youth because of the very high LDL‐cholesterol levels. It is resistant to drug therapy, and LDL‐apheresis is the only practical way of treatment for these patients. Some patients with heterozygous FH also have high LDL‐cholesterol levels that cannot be brought down into the optimum range by any combination drug therapy. We have treated or are treating 10 homozygous and 28 heterozygous FH patients in our hospital or in affiliated hospitals expert in blood purification. Among the 10 homozygous patients, 2 died of myocardial infarction. Only one young female patient is still free of symptoms, and the other patients have been suffering from regurgitation through the aortic valve although they have not experienced myocardial infarction. Rapid rebound of LDL‐cholesterol after each apheresis treatment limits the period during which LDL‐cholesterol is in the optimum range. The use of atorvastatin at a high dose (40 mg/day) was attempted to suppress this rebound. In contrast with good results in receptor‐defective‐type patients, receptor‐negative‐type patients did not show a response in LDL‐cholesterol levels to the statin therapy although there was a slight increase in high‐density lipoprotein (HDL)‐cholesterol with a decrease in very‐low‐density lipoprotein‐triglyceride and ‐cholesterol. Follow‐up study of the patients with heterozygous FH revealed that LDL‐apheresis was effective in lengthening the life expectancy of the patients with pre‐existing CAD, especially those who had received intervention coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA). It was also shown that the use of probucol in combination with LDL‐apheresis was effective in reducing coronary events as shown by the necessity of CABG or PTCA. Clinical data on the effect of LDL‐apheresis, recently reported from some other institutions in Japan, will also be reviewed.     

Why an Apheresis Center Should Offer More Than One Lipoprotein Apheresis Method

We describe our experience with the performance of six lipoprotein apheresis methods (HELP, TheraSorb LDL, DALI, lipidfiltration, Liposorber D, MONET) which have been used in 68 patients. Thirty‐four of them have been treated with more than one method. The calculations presented in this paper are based on laboratory data measured at the last three available apheresis sessions before the switch to another method and at the end of the observation period, respectively. With respect to the reduction of low‐density lipoprotein (LDL) cholesterol, DALI and Liposorber D appeared to be the most effective lipoprotein apheresis methods, for reduction of lipoprotein(a), Liposorber D. Data on the influence of these lipoprotein apheresis methods on parameters of the coagulation system (prothrombin time, international normalized ratio, activated partial thromboplastin time, fibrinogen) are also reported. The histories of three patients who have been switched to several lipoprotein apheresis methods are given as examples. The major reason for switching was the low efficiency of a given lipoprotein apheresis method with respect to lowering of LDL cholesterol; the reason for this phenomenon was not clear in each case. In three patients who took an oral anticoagulant and were treated with HELP, the influence on the coagulation system is reported; they were submitted to another apheresis method. In two patients we observed an allergy to heparin—they were then treated with a heparin‐free apheresis method. In conclusion, we point out that there are several reasons why an apheresis center should offer more than one lipoprotein apheresis method.     

Low-Density Lipoprotein Apheresis Using the Liposorber System: Features of the System and Clinical Benefits

Abstract: LDL apheresis using the Liposorber system is indicated for use to remove selectively LDL from the plasma of hypercholesterolemic patients for whom diet and maximum cholesterol-lowering drug therapy have been ineffective or not tolerated. The dextran sulfate immobilized to porous cellulose beads is contained in the adsorption column as the adsorbent. The dextran sulfate has a structure similar to that of the LDL receptor and seems to act as a type of pseudoreceptor for LDL. There have been reported a number of clinical benefits using the Liposorber system for drug refractory hypercholesterolemic patients. Among them, the improvement of endothelial cell function of coronary and brachial arteries by a single treatment is the focus of the world's attention. Moreover, it is also noteworthy that LDL apheresis reduced the incidence of the cardiac events by 70% compared to drug therapy alone. In addition to the clinical benefits of the Liposorber system on familial hypercholesterolemia (FH), the preliminary data suggest that LDL apheresis may improve arteriosclerosis obliterans (ASO) of the lower extremities and focal glomerular sclerosis (FGS).