Low density lipoprotein apheresis in treatment of hyperlipidemia: experience with four different technologies.

The prognosis of patients suffering from severe hyperlipidaemia (HLP), sometimes combined with elevated lipoprotein (a) levels, and coronary heart disease (CHD) refractory to diet and lipid lowering drugs is poor. A new therapeutic option for such patients is regular treatment with low density lipoprotein (LDL) apheresis. In total 33 patients (16 males, 17 female, aged 43.8+/-14.3 years), suffering from severe HLP resistant to diet and lipid lowering drugs, were treated for 62.3+/-21.3 (range, 1-113) months with LDL-apheresis. Four different LDL-apheresis systems were used: the dextran sulfate adsorption for 28 of 33 (Liposorber, Kaneka, Japan), immunoadsorption for 2 of 33 (Therasorb, Baxter, Germany), LDL-hemoperfusion for 2 of 33 (Dali, Fresenius, Germany), and the immunoadsorption system with special antilipoprotein (a) columns for 1 of 33 patients (Lipopak, Pocard, Russia). Before applying LDL-apheresis, 27 of 33 patients suffered from CHD with severe angina pectoris symptoms, a history of myocardial infarction or coronary artery venous bypass (CAVB). With LDL-apheresis, reductions (p < 0.05) of 46% for total cholesterol, 49% for LDL, 28% for Lp(a), and 38% for triglycerides were reached. Severe side-effects, such as shock or allergic reactions, were very rare (0.5%). In the course of treatment an improvement in general well-being and increased performance were experienced in 29 of 33 patients. In 23 of 27 patients suffering from CHD, a reduction of 60 to 100% of nitrate medication was observed. Regarding the different apheresis systems used, there were no significant differences with respect to the clinical outcome and concerning total cholesterol, LDL, HDL, and triglyceride concentrations. But, in respect to elevated lipoprotein (a) levels, the immunoadsorption method using special anti-lipoprotein (a) columns seems to be the most effective (-57% versus -25% [Kaneka, p < 0.05] or -23% [Baxter, p < 0.05]). The present data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe HLP, refractory to maximum conservative therapy, is effective and safe in long-term application.     

The role of low density lipoprotein apheresis in the treatment of familial hypercholesterolemia.

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.     

Low-density lipoprotein-apheresis in two patients with extremely elevated lipoprotein (a) levels

Two male caucasian patients (36 and 42 years old) with heterozygous familial hypercholesterolemia and extremely elevated lipoprotein Lp(a) concentrations, resistant to diet and lipid-lowering drugs, were treated with low-density lipoprotein (LDL)-apheresis for 55 months (liposorber system, Kaneka®, Japan) and 15 months (immunoadsorption system, special Lp(a) columns. Lipopak®, Pocard, Russia). Lp(a) dropped on average by 50%, total cholesterol by 27%, LDL-cholesterol by 42%, triglycerides by 43%, and the fibrinogen concentration by 16%. © 1996 Wiley-Liss, Inc.     

Comparison of different treatment regimens in a case of homozygous familial hypercholesterolemia.

The laboratory results of five periods of different treatment regimens were compared in a 19-year-old girl with homozygous familial hypercholesterolemia (FH): weekly low-density lipoprotein (LDL) apheresis sessions with dextran sulfate columns (LA 15, Kaneka Corporation, Osaka, Japan) without statin administration; weekly LDL apheresis with polyacrylate columns (DALI, Fresenius Adsorber Technology, Bad Homburg, Germany) without statin; LDL apheresis as in Period 2 with 40 mg atorvastatin daily; LDL apheresis as in Period 2 with 80 mg atorvastatin daily; and fortnightly LDL apheresis sessions with polyacrilate and administration of 80 mg atorvastatin daily. The five treatments were given in the above order, and each lasted at least 2 months. To compare the effectiveness of the different methods, the blood levels of total cholesterol, LDL-cholesterol and high-density lipoprotein (HDL)-cholesterol were measured before each session, and the percentage decreases in the blood levels of total cholesterol and LDL-cholesterol were recorded during sessions in Periods 1 and 2. In Periods 1 and 2, the biological effectiveness of LDL apheresis was comparable. Atorvastatin (40 mg daily) improved the blood levels of total cholesterol and LDL-cholesterol, but lowered HDL-cholesterol values. Increasing the daily dose of atorvastatin from 40 mg to 80 mg did not significantly improve LDL-cholesterol levels. When the time between two sessions was longer (Period 5), the total cholesterol and LDL-cholesterol values worsened and were comparable to those of Period 2 during which there was no atorvastatin treatment. In this case of homozygous FH, weekly sessions of LDL apheresis in association with atorvastatin at dose of 40 mg per day gave the best results.     

Clinical application and effectiveness of low-density lipoprotein apheresis in the treatment of coronary artery disease.

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 > or = 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.     

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.     

Three different LDL apheresis columns efficiently and equally reduce lipoprotein(a) concentrations in patients with familial hypercholesterolemia and small apolipoprotein(a) particles

Introduction

High levels of lipoprotein(a) [Lp(a)] and apolipoprotein(a) [apo(a)] are associated with cardiovascular disease. In this study we determined apo(a) particle size and compared the Lp(a) reducing efficacy of three different LDL apheresis columns; DL-75, LA-15 and EC-50W in patients with familial hypercholesterolemia (FH).

Results

Average Lp(a) concentration was reduced by 70%, 74% and 75% (all p < 0.0001) for DL-75, LA-15 and EC-50W, respectively. No significant changes in the relative proportion of the isoforms of 14 and 32 K 4 domains were observed after apheresis.

Conclusion

Three different LDL apheresis columns reduced Lp(a) efficiently with preserved ratio between apo(a) isoforms.     

Current topics on low-density lipoprotein apheresis.

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lp[a]) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL-apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL-adsorption, and LDL-hemoperfusion. Despite substantial progress in diagnostics, drug therapy, and cardiosurgical procedures, atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia (HLP) therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, however, sometimes the goal of therapy cannot be reached. Mostly, the prognosis of patients suffering from severe HLP, sometimes combined with elevated Lp(a) levels and CHD refractory to diet and lipid-lowering drugs is poor. Hence, in such patients, treatment with LDL-apheresis can be useful. Regarding the different LDL-apheresis systems used, there were no significant differences with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein, or triglyceride concentrations. With respect to elevated Lp(a) levels, however, the immunoadsorption method seems to be the most effective. The published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.     

Short-term and long-term effects of low-density lipoprotein (LDL) apheresis on restenosis after percutaneous transluminal coronary angioplasty (PTCA): is lowering Lp(a) by LDL apheresis effective on restenosis after PTCA?

It has been reported that serum lipoprotein(a) (Lp[a]) levels in patients with restenosis after percutaneous transluminal coronary angioplasty (PTCA) were significantly higher than in patients without restenosis. In this study, we evaluated the preventive effect of LDL apheresis on restenosis after PTCA in patients with hypercholesterolemia. For 10 patients who had shown a serum cholesterol level of more than 220 mg/dl despite treatment with antihypercholesterolemic drugs, LDL apheresis was conducted every 2 weeks after a successful PTCA until restenosis could be checked. In 4 patients, LDL apheresis was conducted for 2 years. LDL apheresis significantly reduced serum cholesterol from 248 +/- 22 mg/dl to 135 +/- 26 mg/dl and Lp(a) from 42 +/- 34 mg/dl to 21 +/- 16 mg/dl. The average degree of stenosis in the 11 lesions undergoing PTCA was 92 +/- 6% before PTCA, 35 +/- 10% immediately after PTCA, and 38 +/- 19% at 3 to 4 months after PTCA. Restenosis was observed in only 1 lesion. In 4 patients who received LDL apheresis for 2 years, restenosis did not occur in any of the 4 lesions treated. We concluded that LDL apheresis was an efficacious therapy to prevent restenosis after PTCA in patients with hypercholesterolemia.     

DALI low-density lipoprotein apheresis in homozygous and heterozygous familial hypercholesterolemic patients using low-dose citrate anticoagulation.

The purpose of this study was to clarify the efficacy and safety of direct adsorption of lipoprotein low-density lipoprotein apheresis (DALI LDL apheresis) in patients with severe homozygous and heterozygous familial hypercholesterolemia who showed minor adverse effects during treatment with the usual DALI configuration (AC 1:20) through the use of a new system with low-dose citrate anticoagulation (AC 1:40) developed in order to minimize citrate-related adverse effects. Serum total cholesterol and LDL-cholesterol (LDL-C) showed a decrease of 57% to 61%, and 62% to 67%, respectively, in the 2 patients. Serum lipoprotein (a) (Lp[a]) was higher in the homozygous patient (Patient 1: MD) and within the normal range in the heterozygous patient (Patient 2: ES). In the former, Lp(a) was reduced by 52%. Serum high-density lipoprotein cholesterol (HDL-C) showed a statistically insignificant acute reduction: 15% to 19%. The observed reduction is mainly related to the well-known effect of hemodilution. The cardiovascular risk (total cholesterol/HDL-C) was reduced in both patients (46% to 54%) as expected. Serum triglycerides were reduced by 33% to 49%. The mean blood volume processed per session was 7,600 ml. Fifteen treatments for each patient have successfully been completed without the appearance of any clinically significant subjective and objective symptoms related to treatment with the new system.     

Lipoprotein(a), Cardiovascular Disease,and Contemporary Management

Elevated lipoprotein(a) (Lp[a]) is a causal genetic risk factor for cardiovascular disease. To determine if current evidence supports both screening and treatment for elevated Lp(a) in high-risk patients, an English-language search of PubMed and MEDLINE was conducted. In population studies, there is a continuous association between Lp(a) concentrations and cardiovascular risk, with synergistic effects when low-density lipoprotein (LDL) is also elevated. Candidates for Lp(a) screening include patients with a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, recurrent cardiovascular events, or inadequate LDL cholesterol (LDL-C) responses to statins. Given the comparative strength of clinical evidence, reducing LDL-C to the lowest attainable value with a high-potency statin should be the primary focus of lipid-modifying therapies. If the Lp(a) level is 30 mg/dL or higher in a patient who has the aforementioned characteristics plus residual LDL-C elevations (≥70-100 mg/dL) despite maximum-potency statins or combination statin therapy, the clinician may consider adding niacin (up to 2 g/d). If, after these interventions, the patient has progressive coronary heart disease (CHD) or LDL-C levels of 160-200 mg/dL or higher, LDL apheresis should be contemplated. Although Lp(a) is a major causal risk factor for CHD, no currently available controlled studies have suggested that lowering it through either pharmacotherapy or LDL apheresis specifically and significantly reduces coronary risk. Further research is needed to (1) optimize management in order to reduce CHD risk associated with elevated Lp(a) and (2) determine what other intermediate- or high-risk groups might benefit from Lp(a) screening.     

Low-density lipoprotein apheresis for prevention and regression of atherosclerosis: clinical results.

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 LA-15 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 extracorporeal 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.     

LDL-apheresis in treatment of two patients with heterozygous familial hypercholesterolemia and extremely elevated lipoprotein (a) levels

In hyperlipidemia and, in particular, elevated lipoprotein (a) [Lp(a)] levels there appears to be pronounced linkage between the development and progression of atherosclerosis. Our study concerned two Caucasian male patients with heterozygous forms of familial hypercholesterolemia and extremely high Lp(a) concentrations. Maximal diet regimens and the use of lipid lowering drugs achieved a serum total-, LDL-cholesterol and triglyceride reduction of up to 30%, but no reduction of the Lp(a) level was discernible. Both patients suffered three myocardial infarctions and several coronary angiographies with percutaneous transluminal angioplasties (PTCA) were necessary. In 1989, we commenced treatment with LDL-apheresis. At present, after 78 LDL-aphereses in the case of the 41-year-old patient (48 months, dextran sulfate adsorption, KANEKA, Japan) and 38 aphereses in the case of the 35-year old patient (8 months, immunoadsorption, special Lp[a] columns, LIPOPAK, POCARD, Russia), the Lp(a) has dropped an average of 53%, total cholesterol 31%, LDL-cholesterol 40% and triglycerides 42%. During this period neither mycardial infarctions nor cardiac complaints were observed. In the course of treatment, both patients experienced an improvement in general well-being and increased performance. These results are very encouraging: LDL-apheresis may be effective in the treatment of patients, the only risk factor for premature atherosclerosis being an extremely high Lp(a) concentration.     

Low density lipoprotein hemoperfusion by direct adsorption of lipoproteins from whole blood (DALI apheresis): clinical experience from a single center.

The elimination of low density lipoprotein (LDL) and lipoprotein (a) (Lp[a]) by conventional LDL apheresis techniques can only be achieved in a cell-free medium and thus requires the initial separation of plasma from the blood cells. The present paper describes the first LDL hemoperfusion system which is able to adsorb LDL and Lp(a) directly from whole blood. This simplifies the procedure substantially. The adsorber consists of polyacrylate ligands linked to a modified polyacrylamide matrix. These negatively charged polyacrylate ligands interact with the positively charged apoprotein B moiety of LDL and Lp(a), which results in selective adsorption of these lipoproteins onto the column. Three hypercholesterolemic patients suffering from overt atherosclerotic complications were treated weekly by direct adsorption of lipoproteins (DALI) (n = 20 sessions each). All patients were on the highest tolerated dose of cholesterol synthesis enzyme (CSE) inhibitors. About 1.3 patient blood volumes were treated per session. The anticoagulation was performed with acid citrate dextrose (ACD-A). The following acute reductions were achieved: LDL: 66%; Lp(a): 63%; and triglycerides: 29%. High density lipoprotein (HDL) (-13%) and fibrinogen (-16%) were not substantially reduced. The sessions were essentially uneventful. Due to a low ACD-A infusion rate, no hypocalcemic episodes were registered. One patient on enalapril was treated without complications when this angiotensin converting enzyme (ACE) inhibitor was withdrawn 2 days prior to apheresis. In summary, in our hands, DALI apheresis proved to be a simple, safe, and efficient method of lipid apheresis in hypercholesterolemic patients refractory to conservative lipid lowering therapy.     

Lipoprotein particles in homozygous familial hypercholesterolemic patients treated with portacaval shunt and LDL apheresis

Lipoprotein particles containing apolipoproteins (Apo) were studied by enzyme-linked-immunosorbent assay in two homozygous familial hypercholesterolemic patients (1 male and 1 female) with portacaval shunts, and in controls. Total Apo B, total cholesterol and LDL cholesterol were increased in both patients while complex Apo B containing particles, Lp CIII: B, were not increased in these FH patients. The dextran-sulfate cellulose columns (Liposorber LA-40) had an excellent adsorption selectivity and adsorption capacity for lipoprotein particles containing Apo B and a minimum adsorption capacity in Apo AI and Apo AII-containing particles. This apheresis technique selectively depleted plasma of atherogenic Apo B-containing particles with a minimal loss of antiatherogenic Apo AI-containing particles.     

Different inflammatory responses induced by three LDL‐lowering apheresis columns

Low‐density lipoprotein (LDL) apheresis is well‐established in selected patients with uncontrolled LDL levels. As such treatment affects biomarkers important in atherosclerosis and acute coronary syndromes, we systematically compared the inflammatory response induced by three LDL apheresis columns. Three patients with heterozygous familial hypercholesterolemia participated in a cross‐over study with six consecutive treatments with three different LDL apheresis columns: DL‐75 (whole blood adsorption), LA‐15 (plasma adsorption), and EC‐50W (plasma filtration). Biochemical parameters and inflammatory biomarkers, including complement activation products and 27 cytokines, chemokines, and growth factors were measured before and after treatment. Complement was activated through the alternative pathway. The final end product sC5b‐9 increased significantly (P < 0.01) and equally with all devices, whereas the anaphylatoxins C3a and C5a were lower by use of the adsorption columns. Hs‐CRP was reduced by 77% (DL‐75), 72% (LA‐15), and 43% (EC‐50W). The cytokines were consistently either increased (IL‐1ra, IP‐10, MCP‐1), decreased (IFN‐γ, TNF‐α, RANTES, PDGF, VEGF), or hardly changed (including IL‐6, IL8, MIP‐1αβ) during treatment. The changes were in general less pronounced with the adsorption columns. All columns reduced LDL significantly and to the same extent. In conclusion, three LDL‐apheresis devices with equal cholesterol‐lowering effect differed significantly with respect to the inflammatory response. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Low-density lipoprotein apheresis for the treatment of refractory hyperlipidemia

The advent of treatment with 3-hydroxy-3-methylglutaryl coenzyme A inhibitors has meant that, with a combination of diet and drug therapy, adequate control of serum cholesterol concentrations can be achieved in most patients with hypercholesterolemia. However, some patients, primarily those with familial hypercholesterolemia (FH), may require additional therapy to lower their cholesterol levels. In recent years, low-density lipoprotein (LDL) apheresis has emerged as an effective method of treatment in these patients. The criteria for commencement of LDL apheresis are LDL cholesterol levels of 500 mg/dL or higher for homozygous FH patients, 300 mg/dL or higher for heterozygous FH patients in whom medical therapy has failed, and 200 mg/dL or higher for heterozygous FH patients with documented coronary disease and in whom medical therapy has failed. In addition to cholesterol lowering in patients with FH, other indications for LDL apheresis are emerging. These include its use in the treatment of graft vascular disease in patients receiving cardiac transplants as well as in the treatment of certain glomerulonephritides. This review examines the role of LDL apheresis in the management of lipid disorders and the evidence available to support its use in clinical practice.     

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.     

Short- and long-term effects of LDL-apheresis on lipoprotein (a) serum levels

The effect of two extracorporeal elimination procedures for LDL on lipoprotein (a) concentrations in serum was studied in patients with heterozygous familial hypercholesterolemia. During a single apheresis serum lipoprotein (a) levels fell by 45% and 58%. Over a long-term period with weekly elimination lipoprotein (a) concentrations were lowered significantly by 43% (after 10-50 treatments) and 30% (after 51-99 treatments) compared to pre-treatment values. The rise during the week following apheresis was comparable to the corresponding reincrease of LDL-cholesterol and apolipoprotein B. We conclude that both apheresis techniques are very effective in reducing lipoprotein (a) serum levels.     

Low density lipoprotein immunoapheresis does not increase plasma lipid peroxidation products in vivo.

Extracorporeal elimination of low density lipoprotein (LDL) is frequently used in drug-resistant hypercholesterolemia. LDL-immunoapheresis selectively removes LDL and lipoprotein(a) [Lp(a)] from plasma. Lipid peroxidation is one unwanted side effect, that occurs during extracorporeal plasma treatment. The purpose of this study was to investigate the effect of LDL immunoapheresis on lipid peroxidation. Before and after a single LDL-immunoapheresis treatment, plasma concentrations of lipid hydroperoxides, determined with two different spectophotometric assays, thiobarbituric acid-reacting substances (TBARS), determined spectrophotometrically and malondialdehyde (MDA), determined by an MDA-TBA/HPLC method, were measured in 13 hypercholesterolemic patients. In addition MDA was also determined in the eluate of the apheresis column. Before treatment, plasma cholesterol and LDL cholesterol concentrations were significantly higher in patients than in healthy control subjects, as were the lipid peroxidation products. LDL-immunoapheresis treatment of the patients led to significant decreases in total cholesterol (69+/-8%), LDL-cholesterol (79+/-7%), HDL-cholesterol (35+/-17%), triglycerides (38+/-21%), apolipoprotein-B (77+/-6%), apolipoprotein-A1 (25+/-5%) and Lp(a) concentrations (76+/-10%). Changes in plasma lipid peroxide concentrations (17+/-8 nmol/l before vs. 14+/-5 nmol/l after treatment) were not significant, neither were those in TBARS (3. 0+/-2.6 micromol/l vs. 2.3+/-1.3 micromol/l) or MDA concentrations (1.03+/-0.17 micromol/l vs. 1.0+/-0.20 micromol/l). Patients with high baseline values showed a decrease, whereas others did not. MDA was present (0.57+/-0.13 micromol/l) in the eluate of the apheresis column, suggesting that, along with LDL, lipid peroxidation products are also removed. From these results we conclude that a single LDL-immunoapheresis treatment effectively reduces LDL and Lp(a) in the absence of increases in plasma lipid peroxidation products.