Dyslipoproteinemia therapy with lipoprotein-apheresis and/or human monoclonal antibodies

Abstract

The prognosis of patients suffering from severe dyslipoproteinemia, sometimes combined with elevated lipoprotein (a) (Lp(a)), and coronary artery disease (CAD) refractory to diet and lipid-lowering drugs has been improved by the introduction of the lipoprotein-apheresis, and the human monoclonal antibodies (HMA) in different studies. All severe forms of dyslipoproteinemia can be treated successfully with these methods alone or in combination. Different lipoprotein-apheresis systems are available which reduce LDL cholesterol, Lp(a), triglycerides and others: cascade filtration or lipoproteinfiltration, immunoadsorption, heparin-induced LDL precipitation, dextran sulfate LDL adsorption, LDL hemoperfusion, and/or different HMA. There is a strong correlation between dyslipoproteinemia and atherosclerosis. Besides the elimination of other risk factors in severe dyslipoproteinemia therapeutic strategies focus on a drastic reduction of serum lipoproteins. In such patients in whom the maximum drug therapy failed, lipoprotein-apheresis (LA) is indicated. Technical and clinical aspects of these different lipoproteinapheresis methods and results of the application of HMA are shown here. The published data clearly demonstrate that treatment with lipoprotein-apheresis in patients suffering from severe dyslipoproteinemia refractory to conservative therapy are effective and safe in long application. A disadvantage is the high costs and the expensive technologies of the different lipoprotein-apheresis methods. The costs of the therapy with HMA are lower than the costs of the lipoprotein-apheresis but larger studies are necessary to show what method could be preferred.

LDL Apheresis And/or Human Monoclonal Antibodies as Treatment in Se-vere Dyslipoproteinemia

“…High concentration of circulating LDL is usually combined with an increase in VLDL, which leads to a development of atherosclerosis, and in particular to CAD. Heterogenous FH has a frequency of 1: 500 may be closer to 1: 250 and the homozygous form a frequency of 1: 1,000,000 [2]. Genetic assessment helps to identify patients at risk for developing dyslipoprotenemia and for treatment decision based on "risk allele" profiles [3].…”

“…The largest endocrine, paracrine, and autocrine participant in the regulation of numerous homeostatic vascular functions is the vascular endothelium [2,4]. Changes in hemodynamic forces such as pressure and shear stress as well as circulating and locally formed vasoactive substances released by blood cells are sensed by endothelial cells.…”

“…These endothelial cells synthesize and release biologically active substances such as nitride oxide (NO), prostacyclin, endothelium-derived hyperpolarizing factor, endothelin, prostaglandin H2, thromboxane A2, heparin sulfate, transforming growth factor, vascular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor, tissue plasminogen activator, plasminogen activator inhibitor-1, oxygen free radical, etc. [2]. All these factors together modulate vascular tone.…”

“…Hypertriglyceridemia is prevalent in 18.6 % of men and 4.2 % of women between the age of 16 and 65 and a positive correlation between elevated triglycerides (TG) blood levels and heart attacks has been established [2]. Increased TG are often accompanied by low HDL-cholesterol blood levels.…”

“…A cumulative insult to the vasculature resulting in more severe disease which occurs at an earlier age in large and small vessels as well as capillaries is caused in dyslipoproteinemia and hyperglycemias on endothelial function [5]. Lipoprotein (a), which is very similar to LDL is a further important atherogenic substance, and contains also Apo (a), which is very similar to plasminogen, enabling Lp(a) to bind to fibrin clots and become plague compounds in the walls of the arteries [2]. High Lp(a) concentrations are associated with an early occurrence of CAD and apoplectic insult [6].…”