2.5. Lipoprotein(a)

Lp(a) was first discovered in human plasma by Berg (Berg & Mohr 1963). Lipoprotein(a) is synthesised by the liver (Edelstein et al. 1994), it consists of an LDL particle covalently attached to apolipoprotein(a) (apo(a)), and it can also contain apo AI and apo E (Blanco-Vaca et al. 1994). Apo (a) is highly homologous to plasminogen, and the size variation of apo (a) is due to the number of kringle 4 type 2 copies present in the molecule (Gaw & Hobbs 1994). The plasma concentrations of Lp(a) are about 90 % genetically determined (Utermann et al. 1987, Sandholzer et al. 1991, Austin et al. 1992, Snyder et al. 1994, Keesler et al. 1994, Rainwater 1995), being inversely related to the number (12-51) of kringle 4 type 2 repeats (Lackner et al. 1991) and the size of the apo (a) protein (Utermann et al. 1987). The catabolism of Lp(a) is less well known. Lp(a) can be degraded by the LDL receptor, but the affinity of Lp(a) for the receptor is low (Snyder et al. 1994). A receptor for Lp(a) has been characterised on human macrophages (Keesler et al. 1994).

High plasma levels of lipoprotein(a) have been positively associated with atherosclerosis (Frick et al. 1978, Dahlén et al. 1986, Armstrong 1986), myocardial infarction (Dahlén et al. 1975, Rhoads et al. 1986, Murai et al. 1986) and stroke (Murai et al. 1986, Woo et al. 1991) in numerous cross-sectional studies. The atherogenity of Lp(a) is at least partly associated with an elevated concentration of LDL cholesterol (Maher & Brown 1995), and a reduction of LDL cholesterol without a change in the Lp(a) concentration associates with slowing down of CAD progression (Thompson et al. 1995). The plasma Lp(a) concentration is higher in individuals with than those without the apo E 4 allele (Ukkola et al. 1993a, de Andrade et al. 1995). Diet has no effect on the serum concentrations of Lp(a), and so far, neomycin and nicotinic acid are the only hypocholesterolemic drugs with an Lp(a) lowering effect (Gurakar et al. 1985, Carlson et al. 1989, Angelin 1997).