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Therapy of Hyper-Lp(a)

  • Chapter
Atherosclerosis: Diet and Drugs

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 170))

Abstract

Lipoprotein (a) [Lp(a)] appears to be one of the most atherogenic lipoproteins. It consists of a low-density lipoprotein (LDL) core in addition to a covalently bound glycoprotein, apolipoprotein (a) [apo(a)]. Apo(a) exists in numerous polymorphic forms. The size polymorphism is mediated by the variable number of kringle-4 Type-II repeats found in apo(a). Plasma Lp(a) levels are determined to more than 90% by genetic factors. Plasma Lp(a) levels in healthy individuals correlate significantly high with apo(a) biosynthesis and not with its catabolism. There are several hormones known to have a strong impact on Lp(a) metabolism. In certain diseases, such as kidney disease, Lp(a) catabolism is impaired leading to up to fivefold elevations. Lp(a) levels rise with age but are otherwise influenced only little by diet and lifestyle. There is no safe and efficient way of treating individuals with elevated plasma Lp(a) concentrations. Most of the lipid-lowering drugs have either no significant influence on Lp(a) or exhibit a variable effect in patients with different forms of primary and secondary hyperlipoproteinemia. There is without doubt a strong need to concentrate on the development of specific medications to selectively target Lp(a) biosynthesis, Lp(a) assembly and Lp(a) catabolism. So far only anabolic steroids were found to drastically reduce Lp(a) plasma levels. This class of substance cannot, of course, be used for treatment of patients with hyper-Lp(a). We recommend that the mechanism of action of these drugs be studied in more detail and that the possibility of synthesizing derivatives which may have a more specific effect on Lp(a) without having any side effects be pursued. Other strategies that may be of use in the development of drugs for treatment of patients with hyper-Lp(a) are discussed in this review.

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Authors and Affiliations

  1. Research Wing Level 3, Princess Alexandra Hospital, O'Keefe Roads, 4102, Woolloongabba, Queensland, Australia

    K.M. Kostner

  2. Institute of Medical Biochemistry and Molecular Biology, Medical University of Graz, 8010, Graz, Austria

    G.M. Kostner

Authors
  1. K.M. Kostner
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  2. G.M. Kostner
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Editors and Affiliations

  1. Institute of Clinical Chemistry, University Hospital of Zurich, Rämistrasse 100, 8091, Zürich, Switzerland

    Arnold von Eckardstein

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Kostner, K., Kostner, G. (2005). Therapy of Hyper-Lp(a). In: von Eckardstein, A. (eds) Atherosclerosis: Diet and Drugs. Handbook of Experimental Pharmacology, vol 170. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-27661-0_19

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