**2. Lp(a) metabolism**

The protein part of Lp(a) consists of two main components, apoB-100 and apo(a) [6]. ApoB-100, the main component of LDL, is biosynthesized in the liver and LDL is the end-product of VLDL catabolism. Yet, LDL also appears to be synthesized directly and secreted from the liver. Liver LDL, however, displays a different composition from VLDL-derived LDL. Apo(a) consists of 11 unique "kringle-IV's" (K-IV) that are highly homologous to kringle-4 of plasminogen. In addition, apo(a) has a variable number of so-called repetitive K-IVs, which is one of the main puzzles in the immunochemical quantification of Lp(a) (see below). In addition to the presence of K-IVs, apo(a) possesses one kringle-V and a nonactive protease domain; further details on the structure of apo(a) may be found in ref. [7]. The exact mode of the assembly of Lp(a) from LDL and apo(a) might be irrelevant for Lp(a) quantifications, yet it has important implications for the development of Lp(a)-lowering drugs and the interpretation of their mode of action. Mixing recombinant apo(a) with LDL in the test tube and incubation for a few minutes leads to the formation of an intact Lp(a) particle that is indistinguishable from native Lp(a). This led to the assumption that the assembly of Lp(a) takes part outside the liver in circulating blood. Turnover studies carried out in the laboratory of H. Dieplinger (Innsbruck), on the other hand, revealed that the synthesis rate of protein components of Lp(a), i.e. apoB-100 and apo(a), are identical but distinct from the synthesis rate of apoB-100 in LDL [8]. This appears to be a strong argument for the intracellular assembly of Lp(a).

It is well established that the black population has strikingly different plasma Lp(a) concen‐ trations compared with the white population (black individuals have the highest and Asians have the lowest plasma Lp(a) levels [9]). In addition to these ethnic differences, there are great differences of plasma Lp(a) levels in any ethnic group ranging from <1 mg/dl to >200 mg/dl. This heterogeneity is caused, on one hand, by numerous polymorphisms in the apo(a) promoter and on the other hand by the variable number of K-IV repeats: individuals with a high copy number of K-IV have lower plasma Lp(a) levels and those with a low number copy number have higher plasma Lp(a) levels.
