Ig-Therasorb immunoadsorption for selective removal of human immunoglobulins in diseases associated with pathogenic antibodies of all classes and IgG subclasses, immune complexes, and fragments of immunoglobulins.

Therasorb immunoadsorption (IA), by selectively eliminating pathogenic substances from the circulation, allows for successful therapy of previously insufficiently treatable diseases. Molecules (specific polyclonal sheep antibodies) coupled to a matrix (Sepharose CL 4B) selectively bind plasma components in extracorporeal circulation. This procedure has been established in the treatment of various diseases. Examples are familial hypercholesterolemia (LDL-Therasorb) and selected autoimmune diseases (Ig-Therasorb). Ig-Therasorb IA has been performed in a variety of clinical indications, primarily in the treatment of autoimmune diseases. In most cases, Ig-Therasorb IA has been applied in patients who have failed to respond to conventional therapy with a high rate of clinical improvement. In defined groups of patients with autoimmune diseases and alloantibodies, immunoadsorption can now be considered an established therapeutic means. The fast and efficient removal of immunoglobulins obviously exceeds the efficiency of conventional plasma exchange by far. Autoimmune diseases could be induced by balanced and nonbalanced immunity. The importance of autoantibodies remains unclear, but the efficacy of Ig-Therasorb IA suggests a key role for them. In addition to the established indications for removal of immunoglobulins, there may be a number of promising new indications.     

Evidence for maximal treatment of atherosclerosis: drastic reduction of cholesterol and fibrinogen restores vascular homeostasis.

This article summarizes the clinical and biochemical evidence for maximal treatment of atherosclerosis by a simultaneous 60% to 70% reduction of plasma low-density lipoprotein cholesterol (LDL cholesterol), fibrinogen, and lipoprotein a concentrations with heparin-mediated extracorporeal LDL/fibrinogen precipitation (HELP) apheresis and statins. Apheresis has proven efficient and safe in the treatment of more than 1,000 patients since 1984 and has been applied in children and adults for the treatment of homozygous and heterozygous familial hypercholesterolemia, coronary artery disease, ischemic cardiomyopathy, generalized atherosclerosis, or transplant-associated arteriosclerosis after cardiac transplantation. Simultaneous removal of the main atherogenic plasma compounds has an immediate impact on myocardial and peripheral vasomotion by increasing myocardial blood flow, coronary flow reserve, cerebral CO2-reactivity, and muscle oxygen tension. Removal of fibrinogen and cholesterol reduces plasma viscosity by 20% and erythrocyte aggregation by 60% which gives rise to applying the HELP apheresis in various microcirculatory disorders. Pilot studies on acute retinal ischemia, critical limb ischemia, and sudden hearing loss confirm this observation.     

First steps toward the establishment of a German low-density lipoprotein-apheresis registry: recommendations for the indication and for quality management.

New recommendations for the indication of treatment with selective extracorporeal plasma therapy low-density lipoprotein apheresis (LDL-apheresis) in the prevention of coronary heart disease are urgently needed. The following points are the first results of the ongoing discussion process for indications for LDL-apheresis in Germany: all patients with homozygous familial hypercholesterolemia with functional or genetically determined lack or dysfunction of LDL receptors and plasma LDL cholesterol levels >13.0 mmol/L (>500 mg/dL); patients with coronary heart disease (CHD) documented by clinical symptoms and imaging procedures in which over a period of at least 3 months the plasma LDL cholesterol levels cannot be lowered below 3.3 mmol/L (130 mg/dL) by a generally accepted, maximal drug-induced and documented therapy in combination with a cholesterol-lowering diet; and patients with progression of their CHD documented by clinical symptoms and imaging procedures and repeated plasma Lp(a) levels >60 mg/dL, even if the plasma LDL cholesterol levels are lower than 3.3 mmol/L (130 mg/dL). Respective goals for LDL cholesterol concentrations for high-risk patients have been recently defined by various international societies. To safely put into practice the recommendations for LDL-apheresis previously mentioned, standardized treatment guidelines for LDL-apheresis need to be established in Germany that should be supervised by an appropriate registry.     

Meaning of low-density lipoprotein-apheresis for hypercholesterolemic patients at high risk for recurrence of coronary heart disease.

The goal of cholesterol-lowering therapy in hypercholesterolemic patients at high risk for recurrence of coronary heart disease (CHD) is the prevention of acute coronary syndrome by stabilization of coronary atheromatous plaque. We often encounter patients in whom it is difficult to maintain the serum cholesterol level at a desirable level with dietary therapy and drug treatment, despite the development and use of statins. For secondary prevention in patients who are at high risk for the recurrence of CHD and whose cholesterol level cannot be controlled by drugs alone, low-density lipoprotein (LDL)-apheresis therapy, which involves removal of LDL through extracorporeal circulation, is now available. Many reports concerning improvement of vascular endothelial function, improvement of myocardial ischemia, regression of coronary atherosclerotic lesions, stabilization of coronary plaque, and reduction in the incidence of cardiac events as a result of LDL-apheresis treatment have been published in various countries. We believe that LDL-apheresis should be performed on hypercholesterolemic patients with existing CHD for whom diet and maximum cholesterol-lowering drug therapies have been ineffective or not tolerated and whose LDL cholesterol level is 160 mg/dL or higher.     

Application of a new LDL apheresis system using two dextran sulfate cellulose columns in combination with an automatic column-regenerating unit and a blood cell separator

Extracorporeal procedures for selective removal of low-density lipoproteins have become a promising new approach for treatment of severe familial hypercholesterolemia. We tested efficacy and safety of a new LDL apheresis system by using two dextran sulfate cellulose adsorbents (Liposorber LA 15TM from Kanegafuchi) under the control of an automatic column-regenerating unit for continuous alternate adsorption and desorption. Plasma was taken from a continuous-flow blood cell separator (model IBM/Cobe 2997) allowing an extracorporeal circuit from one cubital vein to another. A 57-year-old male with drug-resistant heterozygous familial hypercholesterolemia accompanied by moderate hypertriglyceridemia and severe coronary artery disease has been treated every 2 weeks for 3 months so far. Treatment of 4-5 liters of plasma resulted in a mean decrease of total cholesterol from 355 to 111 mg/dl (9.20 to 2.88 mmol/l), of LDL cholesterol from 272 to 49 mg/dl (7.05 to 1.53 mmol/l), and of apolipoprotein B from 175 to 44 mg/dl. HDL cholesterol, apolipoprotein A-I, and other plasma proteins did not substantially change apart from hemodilution. No side effects were seen. This new technique of LDL apheresis represents a very effective and safe method for treatment of drug-resistant familial hypercholesterolemia without or with concomitant hypertriglyceridemia.     

LDL-apheresis: clinical experience and indications in the treatment of severe hypercholesterolemia

LDL-cholesterol is the leading risk factor which influences the clinical outcome of patients with preexisting coronary heart disease. Clinical trials show that plasma LDL-cholesterol below 100 mg/dL decrease the rate of recurrent myocardial infarction and can induce regression in patients with coronary heart disease. However, in most cases of severe hypercholesterolemia with plasma LDL-cholesterol concentrations above 220 mg/dL LDL cannot be sufficiently decreased by maximal dietary and pharmacological therapy alone. Today this group of high risk CHD patients can be treated in addition with an extracorporeal procedure to eliminate LDL from the plasma circulation, the H.E.L.P.--LDL-apheresis. This method for selective removal of LDL, lipoprotein(a) and fibrinogen from plasma has been shown to be a clinically safe and very efficient method for the treatment of patients with homozygous familial hypercholesterolemia or CHD patients with severe hypercholesterolemia. Treatments with 1 week H.E.L.P. intervals revealed a mean reduction of minus 51% for LDL, of minus 45% for Lp(a) and of minus 46% for apo B, while HDL was increased by +12%. Fibrinogen was decreased by minus 46%. Besides the marked reduction of LDL and fibrinogen plasma concentrations the H.E.L.P. treatment significantly improves hemorheological parameters and increases the oxygen tension in the tissue. We have also investigated the efficiency of a combined therapy, using HMG-CoA reductase inhibitors together with the H.E.L.P.--apheresis. Under this combined treatment, a reduction of the interval LDL-cholesterol levels of 70-80% has been achieved, while Lp(a) and fibrinogen were not further affected. We now report about our long-term clinical experience with the H.E.L.P. system in treating patients with different lipoprotein disorders: (1) Homozygous form of familial hypercholesterolemia; (2) CHD patients with familial and non-familial hypercholesterolemia; (3) CHD patients with very high concentrations of lipoprotein(a); and (4) Hypercholesterolemic patients after heart transplantation. Based on present experience guidelines for secondary prevention of coronary heart disease indications for the H.E.L.P.--LDL-apheresis treatment are discussed.     

Treatment of hypercholesterolemia with heparin-induced extracorporeal low-density lipoprotein precipitation (HELP)

Familial hypercholesterolemia (FH) can cause early disability and death from premature atherosclerotic cardiovascular disease. Patients homozygous for the disease have very high plasma cholesterol, extensive xanthomatosis, and die from atherosclerosis in childhood or early adulthood. Past attempts to improve the prognosis included removal of cholesterol from the circulation by ileal bypass or biliary diversion. Neither treatment was successful. Direct removal by plasmapheresis of low-density lipoprotein (LDL), the primary carrier of cholesterol in plasma, was first performed on an FH homozygous patient in 1966. The treatment was well tolerated and led to rapid diminution of xanthomas. Other experimental treatments included selective LDL apheresis with monoclonal or polyclonal antibody affinity columns. A method for selective LDL apheresis was developed in 1983 by Armstrong, Seidel, and colleagues based on heparin precipitation of LDL at low pH. This method, called HELP, removes all apolipoprotein B-containing lipoproteins including LDL and lipoprotein (a), as well as some fibrinogen. LDL apheresis by HELP is well tolerated; the incidence of side effects is low, and the treatment has been associated with regression of cardiovascular disease. LDL apheresis, rather than liver transplantation, is the treatment of choice for patients with severe, life-threatening hypercholesterolemia which does not respond to diet and drug therapy. © 1996 Wiley-Liss, Inc.     

Effectiveness of cascade filtration plasmapheresis in two patients affected by familial hypercholesterolemia

Hypercholesterolemia has been recognised as a primary risk factor for coronary heart disease. Reduction of plasma levels of total and LDL cholesterol has been shown to decrease coronary atherosclerosis. Plasmapheresis represents an useful non-pharmacological tool to treat severe hypercholesterolemias. We have evaluated the effectiveness of a system of plasmapheresis using a cascade filtration method in two young male subjects (aged 16 and 26 years) with homozygous familial hypercholesterolemia. Both showed severe coronary atherosclerosis as determined by angiography. Procedures were performed at intervals of 7 days in each case. We observed a mean reduction of plasma levels of total cholesterol of 59.5% (range 31.0–75.5%); LDL-cholesterol, 61.6% (range 32.6–77.1%); triglycerides, 48.1%; HDL-cholesterol, 31.1%; apo A-I, 30.8%; and apo B, 57.6%. We also noted a reduction of other parameters, such as fibrinogen (49.9%) and Lp(a) (59.9%). At the end of each procedure about 8 g of cholesterol was removed from the total body pool. A decrease of total proteins (26.9%) and albumin (19.6%) was also observed, but this was completely restored before the next apheresis (1 week). These data show the effectiveness of the removal of LDL in a cascade filtration system, which obtains results not very different from other more selective methods. The lack of selectivity is not much of a problem, since it also reduces other risk factors such as Lp(a) and fibrinogen.     

Effects of low-density lipoprotein apheresis on coronary and carotid atherosclerosis and diabetic scleredema in patients with severe hypercholesterolemia.

Correlations between serum cholesterol levels and progression of coronary and peripheral atherosclerosis have been found in many recent studies. It has also been demonstrated that aggressive cholesterol-lowering therapy with low-density lipoprotein (LDL) apheresis, a method of LDL elimination by extracorporeal circulation, is effective not only for coronary artery disease, but also for systemic circulatory disturbance in severe hypercholesterolemic patients with familial hypercholesterolemia (FH) in particular. We found that LDL apheresis treatment with medical therapy improved coronary atherosclerotic lesions, based on coronary angiography evaluation and histopathological observation, suppressed progression of early carotid atherosclerotic lesions on annual B-mode ultrasonography, and improved diabetic scleredema in FH patients. This effectiveness of LDL apheresis appears to be due to recovery of vascular endothelial function and improvement of blood rheology. For diseases that are possibly due to circulation disturbance and that are intractable with drugs alone. LDL apheresis may be worth trying, particularly for patients complicated by hyperlipemia.     

Reduction of low-density lipoproteins with dextran sulfate in patients with familial hypercholesterolemia

A novel on-line system for the selective precipitation of low-density lipoprotein (LDL) using dextran sulfate has been devised and tested in four patients with heterozygous familial hypercholesterolemia (type II). The mean pretreatment serum cholesterol was 410 mg/dl. Plasma was generated by membrane filtration and LDL and VLDL (very-low-density lipoprotein) were completely precipitated with 10-35 mg% dextran sulfate (Mr 5,000) in the presence of 55 mM Ca2+. The precipitate was removed by filtration and the excess Ca2+ by dialysis. For 41 procedures the mean reduction of plasma solutes was LDL + VLDL 65%, HDL 23%, fibrinogen 19%, albumin 15%, IgG 20%, IgA 19%, IgM 24%. We conclude that dextran sulfate precipitation is an effective method for selective on-line removal of LDL from plasma.     

Efficacy and safety measures for low density lipoprotein apheresis treatment using dextran sulfate cellulose columns.

Long-term low density lipoprotein (LDL) apheresis using dextran sulfate cellulose (DSC) columns is a well tolerated treatment for drug refractory hypercholesterolemia with coronary heart disease (CHD). Hypercholesterolemic patients may benefit from LDL apheresis combined with cholesterol lowering drug therapy in terms of the prevention of the progression of atherosclerosis, stabilization of atheromatous plaque, and reduction of cardiac events. The major adverse reaction of LDL apheresis is temporal hypotension caused by hypovolemia or vasovagal reactions due to extracorporeal circulation. Anaphylactoid reactions in patients administered angiotensin converting enzyme inhibitors (ACE-I) are other dextran sulfate cellulose column related adverse reactions, which must be carefully prevented by ceasing the administration of ACE-I before LDL apheresis treatment. ACE-I must not be administered to patients undergoing LDL apheresis.     

Review: the oxidant/antioxidant balance during regular low density lipoprotein apheresis.

Low density lipoprotein (LDL) apheresis is a safe procedure to treat severe hypercholesterolemia in patients with chronic heart disease (CHD). However, both hypercholesterolemia and extracorporeal treatment have been associated with oxidative stress. Even though LDL lowering has been proven to reduce CHD, the oxidative modification of LDL has been suggested to render these lipoproteins more atherogenic. It is therefore important to know whether LDL apheresis is safe with respect to oxidative stress including LDL oxidation. The contact of living cells such as leukocytes with artificial surfaces during extracorporeal treatment induces the liberation of various chemokines and cytokines as well as oxygen-derived radicals also known as respiratory burst. These effects justify the consideration of leukocyte activation resulting from extracorporeal treatment as an inflammatory reaction. In extracorporeal circuits such as those used for hemodialysis, the release of oxygen radicals has been shown and depends on the fiber material used in the dialyzer membranes. Reactive oxygen radicals can interact with different cell components such as carbohydrates, DNA, proteins, and lipids. Antioxidants in the form of low molecular weight molecules such as glutathione or radical scavenging enzymes such as superoxide dismutase offer protection against the damaging effects of prooxidants. The disturbed balance between prooxidants and antioxidants is considered as oxidative stress. Therefore, either an increase in oxygen radical formation or a decrease of antioxidants will lead to oxidative stress. During LDL apheresis, a decrease of low molecular weight antioxidants has been reported. In contrast, we have observed an increase in plasma glutathione concentrations but no severe reduction in the activity of antioxidant enzymes in plasma, red cells, or granulocytes, which may explain the lack of plasma lipid peroxidation shown during this kind of extracorporeal treatment. In addition, LDL isolated at the end of apheresis procedures are more resistant to oxidation. These findings suggest that LDL apheresis is safe with respect to radical mediated injury.     

Efficacy of different low-density lipoprotein apheresis methods.

Low-density lipoprotein (LDL) apheresis is a treatment option in patients with coronary heart disease and drug resistant hypercholesterolemia. Various apheresis systems based on different elimination concepts are currently in use. We compared the efficacy of 4 different apheresis systems concerning the elimination of lipoproteins. The study included 7 patients treated by heparin extracorporeal LDL precipitation (HELP), 10 patients treated by immunoadsorption, 8 patients treated by dextran-sulfate adsorption, and 4 patients treated by cascade filtration. Ten subsequent aphereses were evaluated in patients undergoing regular apheresis for more than 6 months. Total cholesterol decreased by approximately 50% with all 4 systems. LDL cholesterol (LDL-C) (64-67%) and lipoprotein a [Lp(a)] (61-64%) were decreased more effectively by HELP, immunoadsorption, and dextran-sulfate apheresis than by the less specific cascade filtration system [LDL-C reduction 56%, Lp(a) reduction 53%]. Triglyceride concentrations were reduced by 40% (dextran-sulfate) to 49% (cascade filtration) and high-density lipoproteins (HDL) by 9% (dextran-sulfate) to 25% (cascade filtration). On the basis of plasma volume treated, HELP was the most efficient system (LDL-C reduction 25.0%/L plasma), followed by dextran-sulfate (21.0%/L plasma), cascade (19.4%/L plasma), and immunoadsorption (17.0%/L plasma). However, a maximal amount of 3 L plasma can be processed with HELP due to concomitant fibrinogen reduction while there is no such limitation with immunoadsorption. Therefore, the decision of which system should be used in a given patient must be individualized taking the pre-apheresis LDL concentration, concomitant pharmacotherapy, and fibrinogen concentration into account.     

Long-term effects of LDL apheresis in patients with severe hypercholesterolemia

Familial hypercholesterolemia (FH) is an inherited disorder of lipoprotein metabolism involving mutations in the LDL receptor (LDL-R). Patients with mutation in one (heterozygous) or both (homozygous) genes have markedly elevated LDL cholesterol and are at increased risk for coronary heart disease (CHD). Aggressive lipid lowering is required for homozygous and many heterozygous FH patients. This often involves LDL-apheresis, where LDL and other apo-B containing lipoproteins are selectively removed from the plasma. We have retrospectively studied 34 patients treated with biweekly LDL-apheresis at the Hospital of the University of Pennsylvania. In our patient population, adverse events were uncommon and rarely resulted in shortened treatment time. There was a dramatic decrease in the relative risk of cardiovascular events and cardiovascular interventions in patients treated with LDL-apheresis for an average of 2.5 years. Some but not all patients had long-term reduction in their LDL levels as a result of LDL-apheresis, suggesting that time-averaged reduction in LDL and/or LDL:HDL ratios were responsible for clinical improvement. These data support the use of LDL-apheresis in patients with FH, as well as medication-intolerant patients that have elevated LDL cholesterol despite maximal pharmacological treatment.     

Treatment of hypercholesterolemia by chemical adsorption of lipoproteins

Dextran sulfate (Mr 5,000) was covalently linked to porous cellulose beads, and the dissociation constant (Kd) and the maximum binding level (S) of the beads were calculated for the human plasma lipoproteins VLDL, LDL, and HDL. The S values for VLDL and LDL were 2 and 7 g cholesterol/liter of the wet beads and that for HDL was almost negligible, although the apparent Kd were all in the same order. In fact, LDL and VLDL were exclusively adsorbed by the beads from human plasma in vitro. Bound LDL was desorbed with 0.35 M NaCl. The beads were packed in a column (25-ml) and used with polysulfone hollow fibers in experimental LDL-apheresis for WHHL rabbits; LDL cholesterol was reduced from 500 to 200 mg/dl, while HDL, total plasma protein, and major blood cell counts did not change. For LDL apheresis of familial hypercholesterolemia, the sorbent column, 400-ml, was used with the polysulfone hollow fiber filter. The maximum removal of LDL + VLDL cholesterol was 6 to 8 g with a single column resulting in its reduction by 250 to 300 mg/dl after 3.5 liters plasma treatment. Adsorption was negligible with albumin, HDL, IgA, G, M, apoA-I, A-II, C-II, enzymes, and electrolytes. Activated complement fragments, C3a and C5a, were completely adsorbed. By periodic removal of LDL, an increase of HDL cholesterol was observed in some cases. In order to increase LDL removal in a single treatment and to reduce the extracorporeal circulation volume, two small columns (150 ml each) were used alternatively.(ABSTRACT TRUNCATED AT 250 WORDS)     

磺化塔拉胶选择清除血浆LDL／Fib的性能研究

该文研究磺化塔拉胶选择性清除血浆低密度脂蛋白（LDL）及纤维蛋白原（Fib）的性能.以塔拉胶为原料,以氯磺酸进行磺化,获得塔批胶磺化衍生物,红外光谱分析表明,该物质为酸性粘多糖,是一种类肝索物质.以磺化塔拉胶为净化剂,研究其选择清除血浆LDL/Fib的性能.结果 表明,当净化体系pH=5.10,净化剂浓度为750mg/L时,可使血浆总胆固醇（TC）平均下降53.4%,低密度脂蛋白和极低密度脂蛋白肌同醇平均下降60.7%,纤维蛋白原平均下降94.7%,而对高密度脂蛋白胆固醇（HDL-C）及血浆总蛋白（TP）水平影响较小.表明磺化塔拉胶是一种选择性良好的血浆LDL/Fib净化剂.     

Distinct effects of LDL apheresis by hemoperfusion (DALI) and heparin-induced extracorporeal precipitation (HELP) on leukocyte respiratory burst activity of patients with familial hypercholesterolemia

Hypercholesterolemia and oxidative stress are major risk factors in atherogenesis. In the last years, lipid apheresis has been established as an effective clinical therapy by lowering not only elevated plasma low-density lipoprotein (LDL) levels but also by reducing the incidence of cardiovascular events. The aim of the present study was to investigate peripheral leukocyte oxidant generation in patients with familial hypercholesterolemia (FH) undergoing regular LDL apheresis. The activity state of leukocytes was estimated prior to, immediately after, and 2 days after LDL apheresis carried out by two distinct techniques: hemoperfusion with the DALI system and heparin-induced extracorporeal LDL precipitation (HELP). Oxidant generating activity was measured by chemiluminescence (CL) in whole blood and isolated polymorphonuclear leukocytes (PMNL). The results of our study show increased baseline respiratory burst activities in FH patients as compared to healthy controls. Apheresis with the HELP system was followed by increases in leukocyte count, zymosan-induced whole blood CL, and plasma PMNL elastase levels. The DALI technique caused no changes in leukocyte count and elastase levels and decreased whole blood CL activity. Two days after lipid removal the observed changes returned to pre-apheresis levels. Leukocyte activity parameters before and after apheresis did not correlate with the corresponding plasma levels of triglycerides, total cholesterol, and LDL cholesterol, suggesting that different handling in the framework of both apheresis techniques rather than lipid profile changes during therapy accounted for leukocyte activity modulation.     

Effects of extracorporeal hemapheresis therapy on blood rheology

The blood flow property is one of the factors determining blood perfusion and oxygen supply. The viscosity of the blood is primarily related to the hematocrit, but also to the amount of fibrinogen and other macromolecules present in the blood. Patients with ischemic heart disease have shown a rapid and safe improvement in their hemorheological state when treated with heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP). In this study we used two extracorporeal hemapheresis methods, plasmapheresis (PP) and immunoadsorption (IA), in 15 patients (eight patients treated with PP and seven patients with IA) with various diseases. Hemorheological variables and plasma fibrinogen were measured before and after the first and before the third treatment performed at 3 consecutive days. The aim of our study was to investigate the immediate effects of these two treatment modalities on the flow properties of blood. Immediately after the first PP and IA session statistically significant declines in plasma fibrinogen concentration, plasma viscosity, whole blood viscosity, and erythrocyte aggregation tendency were found. These changes persisted before the third treatment session. The erythrocyte fluidity and hematocrit remained unchanged. We conclude that extracorporeal hemapheresis therapy, with plasmapheresis or immunoadsorption, affects the blood rheology by decreasing the plasma viscosity and erythrocyte aggregation tendency. The decrease in plasma fibrinogen is probably the main factor underlying that, but other factors such as a decrease in immunoglobulins may also be of importance. J. Clin. Apheresis 12:183–186, 1997. © 1997 Wiley-Liss, Inc.     

Lipoproteins and heart disease

Elevations of LDL and plasma cholesterol are established predictive risk factors for predisposing to early coronary heart disease. Conversely, HDL has a protective anti-atherogenic effect. The hyperlipidemias are classified according to a genetic basis (primary) and the result of other diseases (secondary). Diet is an important and modifiable determinant of the lipid concentration in plasma. Restricting saturated fat consumption, increasing intake of polyunsaturated fat and reducing dietary cholesterol are key to hyperlipidemias with elevated LDL. Weight reduction, decreased alcohol consumption, and in some individuals, restriction of simple sugar intake are the primary means for treating hyperlipidemias.     

Three low density lipoprotein apheresis techniques in treatment of patients with familial hypercholesterolemia: a long-term evaluation.

Low density lipoprotein (LDL) apheresis is a treatment option for patients with severe hypercholesterolemia not adequately responding to drug treatment who have developed coronary heart disease. We regularly treated 18 patients with immunoadsorption, 8 with heparin induced extracorporeal LDL precipitation (HELP) and 8 with dextran sulfate adsorption for a mean of 4.6 +/- 2.6 years. The effects on LDL cholesterol, high density lipoprotein (HDL) cholesterol, and lipoprotein (a) were comparable among all 3 techniques. Twelve patients were treated for longer than 5 years and 18 patients for longer than 3 years. The evaluation of coronary angiograms (23 patients) revealed a definite regression of coronary lesions in 3 patients; in all other patients, there was a halt in progression. Three patients suffered a sudden cardiac death and 1 patient a nonfatal myocardial infarction due to the occlusion of a coronary bypass. In 9 of 11 patients, no atherosclerotic lesions developed in the coronary bypasses. No severe side effect of either procedure was observed. In conclusion, aggressive lipid lowering by LDL apheresis can stabilize coronary atherosclerosis in most patients.