Thematic Review Series: Lipoprotein (a): Coming of Age at Last Lipoprotein (a): a historical appraisal

Initially, lipoprotein (a) [Lp(a)] was believed to be a genetic variant of lipoprotein (Lp)-B. Because its lipid moiety is almost identical to LDL, Lp(a) has been deliberately considered to be highly atherogenic. Lp(a) was detected in 1963 by Kare Berg, and individuals who were positive for this factor were called Lpa(+). Lpa(+) individuals were found more frequently in patients with coronary heart disease than in controls. After the introduction of quantitative methods for monitoring of Lp(a), it became apparent that Lp(a), in fact, is present in all individuals, yet to a greatly variable extent. The genetics of Lp(a) had been a mystery for a long time until Gerd Utermann discovered that apo(a) is expressed by a variety of alleles, giving rise to a unique size heterogeneity. This size heterogeneity, as well as countless mutations, is responsible for the great variability in plasma Lp(a) concentrations. Initially, we proposed to evaluate the risk of myocardial infarction at a cut-off for Lp(a) of 30-50 mg/dl, a value that still is adopted in numerous epidemiological studies. Due to new therapies that lower Lp(a) levels, there is renewed interest and still rising research activity in Lp(a).(Jlr) Despite all these activities, numerous gaps exist in our knowledge, especially as far as the function and metabolism of this fascinating Lp are concerned.