Treatment of Severe Hyperlipidemia: Six Years' Experience with Low–Density Lipoprotein Apheresis

Abstract: In total, 30 patients suffering from familial hypercholesterolemia, resistant to diet and lipid–lowering drugs, were treated for up to 6 years (3.6 ± 1.6; range, 0.2–6.8 years) with low–density lipoprotein (LDL) apheresis. Three different systems were used; the dextran sulfate adsorption system (Kaneka) for 27 of 30 patients, the immunoadsorption system from Baxter for 2 of 30 patients, and the immunoadsorption system with special li–poprotein(a) (Lp[a]) columns from Lipopak for one patient. Prior to the LDL apheresis, 23 of 30 patients suffered from coronary heart disease. Twenty of 23 patients suffered intermittently from symptoms of angina, excertional dyspnea, and claudication. With LDL apheresis, reductions of 47% for total cholesterol, 49% for LDL, 26% for Lp(a), and 40% for triglycerides were reached. Severe side effects such as shock or allergic reactions were very rare (0.55%). In the course of treatment with LDL apheresis, an improvement in general well–being and increased performance were experienced in 27 of 30 patients. A reduction of nitrate medication between 60 and 100% was observed in 17 of 23 patients. The present data clearly demonstrate that treatment with LDL apheresis in patients suffering from severe familial hyperlipidemia, resistant to maximum conservative therapy, is very effective and safe even over long periods of time.     

Evaluation of Double Filtration Plasmapheresis, Thermofiltration, and Low–Density Lipoprotein Adsorptive Methods by Crossover Test in the Treatment of Familial Hypercholesterolemia Patients

Abstract: A comparative assessment has been made regarding efficacy and safety of the double filtration plasmapheresis (DFPP), thermofiltration (TFPP), and low–density lipoprotein (LDL) adsorptive (PA) methods by making a crossover test on heterozygous familial hypercholesterolemia patients. Treatments by DFPP, TFPP (secondary membrane Evalux 5A), and PA (Liposorber LA–40) were carried out 5 times each, with a 2–week interval, in 5 patients with heterozygous familial hypercholesterolemia. The same plasma separator (Plasmacure PS–60, polysulfone) was used in all cases, and the volume of plasma processed was set at 4 L. High removal rates were obtained of total cholesterol, LDL cholesterol, triglycerides TG, and apolipoprotein B (apoB) by all three methods, and no differences were observed. Lipoprotein (a), apoA–2, apoC–3, fibrinogen, and immunoglobulin M (IgM) showed significantly high removal rates by the DFPP and TFPP methods compared with the PA method.
The sieving coefficient of albumin and high–density lipoprotein (HDL) cholesterol at 2 and 4 L of plasma processed exhibited high permeabilities using all three methods. Supplementing albumin was not necessary. An increase of the transmembrane pressure was observed in 1 case treated by DFPP but was not observed when using the TFPP or PA method. No changes were observed in serum interleukin 1β (IL–lβ) or tumor necrosis factor–a (TNF–α) before and after treatment by any of the three methods. No remarkable side effects were observed using either the DFPP or TFPP method. The DFPP and TFPP methods showed efficacy and safety that was not inferior to the PA method in conventional LDL apheresis, and the dead–end method of the filter operation without the discarding of plasma was shown to be possible.     

Low–Density Lipoprotein Adsorption for Arteriosclerotic Patients

Abstract: A wide variety of treatments is now available for arteriosclerosis obliterans (ASO) patients, not very successful in some cases. Low—density lipoprotein (LDL) apheresis using an extracorporeal adsorption column containing dextran sulfate cellulose beads was applied to control lipid levels intensively in ASO patients with accompanying drug—resistant hyperlipidemia. A series of the apheresis procedures had a remarkable impact on clinical symptoms and physiological findings with improvement in intermittent claudication observed in more than 80% of the patients. Improvements in plethysmogram and thermogram readings suggested an increased circulation in lower extremities in more than 80% of patients. In addition, the treatment improved blood rheology, as evidenced by a reduction in blood viscosity. In a follow—up study made by sending a questionnaire to previously treated patients, it was revealed that improvements in clinical symptoms were well maintained even after cessation of the treatment. In conclusion, LDL apheresis proved to be a useful therapeutic tool in ASO patients having elevated lipid levels     

Heparin–Induced Extracorporeal Low–Density Lipoprotein Precipitation and Low–Density Lipoprotein Chemoadsorption onto Dextran Sulfate: A Comparison

Abstract: Both heparin–induced extracorporeal low–density lipoprotein precipitation (HELP) and dextran sulfate (DS) apheresis are potent tools for acute and long–term risk factor reduction in the secondary prevention treatment of coronary patients suffering from recalcitrant hypercholesterolemia. They combine high efficacy and selectivity of risk factor removal. Whereas LDL cholesterol and lipoprotein (a) adsorption onto DS offers the advantage of an unlimited treatable plasma volume and somewhat easier handling, HELP reduces fibrinogen more effectively and does not interfere with angiotension converting enzyme (ACE) inhibitors. Both systems can improve blood rheology and induce regression or stabilize coronary lesions. In an uncontrolled trial, HELP reduced the incidence of myocardial infarction. To date, no controlled prospective trials have been performed comparing the two systems with respect to their long–term risk factor reduction and their effect on coronary lesions, morbidity, and mortality.     

Low–Density Lipoprotein Apheresis Versus Lipid Lowering Drugs in the Treatment of Severe Hypercholesterolemia: Four Years' Experience

Abstract: Elevated lipoprotein concentrations seem to be linked strongly in a dose dependent manner to an increased incidence of atherosclerosis. A total of 47 patients suffering from severe hyperlipidemia were matched to treatment with LDL apheresis (Baxter, Kaneka, Li–popak; 24 patients, aged 50.2 ±11.5 years), diet, and/or lipid–lowering drugs or with diet and lipid–lowering drugs only (23 patients, aged 48.8 ±11.8 years). After treatment periods of 49.8 ±13.4 months (apheresis group, 2,396 treatment sessions) and 38.6 ± 15.1 months (drug group), the ensuing results revealed significant differences (p <0.0001): –47.3% versus –12.1% for total cholesterol, –46.9% versus –21.8% for LDL, +8.4% versus +0.9% for HDL, –52.0% versus – 13.1% for the LDL/HDL ratio, –36.4% versus –16.2% for triglycerides, and –25.9% versus + 1.5% for lipoprotein (a). In the apheresis group, one patient died of myocardial infarction; in the drug group, there was one nonfatal myocardial infarction and the manifestation of coronary heart disease in 3 cases. There were no severe side effects in either group. All patients in the apheresis group responded to therapy. The present trial suggests that a continuing reduction in serum lipid concentrations may lower, in a dose dependent manner, the risk for development and progression of coronary heart disease. Regarding clinical and laboratory results, LDL apheresis seems to be safe, effective therapy for treatment of severe hyperlipidemia.     

Low–Density Lipoprotein Apheresis in the Treatment of Two Patients with Coronary Heart Disease and Extremely Elevated Lipoprotein (a) Levels

Abstract: Hyperlipidemia and elevated lipoprotein (a) (Lp[a]) levels have been linked to the development and progression of premature atherosclerosis. Our study concerned 2 white male patients (aged 36 and 42 years) with heterozygous familial hypercholesterolemia and extremely elevated Lp(a) concentrations that were resistant to diet regimens and lipid–lowering drugs. The patients were treated with low–density lipoprotein (LDL) apheresis for 59 months (Liposorber system, Kaneka, Japan) and 19 months (immunoadsorption system, special Lp(a) columns; Lipopak; Pocard, Russia), respectively. The concentration of Lp(a) decreased on average by 50%, total cholesterol by 27%, LDL cholesterol by 41%, triglycerides by 43%, and fibrinogen by 16%. High–density lipoprotein (HDL) cholesterol increased by approximately 4%. Before treatment with LDL apheresis, each patient had suffered 3 myocardial infarctions, and had had 4 and 6 coronary angiographies with 2 and 4 percutaneous transluminal angioplasties (PTCAs), respectively. Since treatment with LDL apheresis, no myocardial infarctions or cardiac complaints were observed. In the course of treatment, both patients reported an increased performance. Available data suggest that LDL apheresis may be effective in the treatment of patients, the only risk factor for premature atherosclerosis being extremely elevated Lp(a) concentrations.     

Low–Density Lipoprotein Hemoperfusion Using a Modified Polyacrylate Adsorber: In Vitro, Ex Vivo, and First Clinical Results

Abstract: Current lipid apheresis techniques can remove low–density lipoprotein (LDL) cholesterol only from plasma, i.e., a primary cell–plasma separation step is mandatory. This article describes in vitro, ex vivo, and clinical results using a new LDL adsorber compatible with human whole blood. It consists of modified polyacrylate, the negative charges of which can interact with the positively charged protein B moiety of LDL, thus retaining these particles on the surface of the adsorber. After the efficacy and selectivity of LDL removal had been demonstrated in vitro and ex vivo, a clinical pilot study corroborated these results. Thus, treating 60 ml of blood per kilogram of body weight in a single session, LDL hemoperfusion reduced LDL cholesterol by 50%, lipoprotein (a) by 17%, and triglycerides by 19% in 6 hy–percholesterolemic patients. High–density lipoprotein cholesterol recovery amounted to 97%. In conclusion, LDL hemoperfusion holds great promise for the future.     

Influence of Dialysis Membranes on Interleukin-1β and Interleukin-1 Receptor Antagonist Production by Peripheral Blood Mononuclear Cells

Abstract: We investigated the production of interleukin (1L)-1β and IL-1 receptor antagonist (Ra) by peripheral blood mononuclear cell (PBMC) in vitro during hemodialysis of 7 dialysis patients using 4 differential dialysis membranes (regenerated cellulose [RC], polyamide [PA], polysulfone [PSI and AN-69). Blood sampling was performed before dialysis (0 min), 15 min after starting dialysis, and after dialysis (240 min) during the last session of each treatment. The cellular content of fresh cells and the production of IL-1β and IL-1Ra with and without lipopolysaccharide (LPS) stimulation of the cells were evaluated and measured by enzyme-linked immunosorbent assay (ELISA). The level of IL-1β with LPS stimulation using RC, PA, and PS membranes was significantly reduced at 15 min and was not changed at 240 min as compared with the level at 0 min. On the other hand, the level of IL-1β with LPS stimulation using an AN-69 membrane at 15 and 240 min was not significantly different from that at 0 min. Neither initial cellular content nor spontaneous production of IL-1β were detected at 0, 15, or 240 min in any of the membranes. The spontaneous production of IL-1Ra at 15 and 240 min was not significantly different from that at 0 min in any of the membranes. The cellular content of IL-1Ra using the RC membrane was significantly lower at 15 min and did not differ at 240 min from the level at 0 min. The cellular content of IL-1Ra using PA, PS, and AN-69 membranes was not significantly different at 15 and 240 min from that at 0 min. However, the IL-1Ra level with LPS stimulation using RC and PA membranes was significantly reduced from that at 0 min, but the level using PS and AN-69 membranes was not different from that at 0 min. Because IL-1β and IL-1Ra levels 15 min after starting dialysis using bioincompatible dialysis membranes were reduced from the levels at 0 min, the findings suggest that measurement of cytokines during dialysis treatment at an early stage is a useful marker for evaluating the biocompatibility of a dialysis membrane.