Lipoprotein(a) and Atherosclerosis

• Lipoprotein(a) [Lp(a)], a lipoprotein variant, was rel-egated for almost 25 years to the study of a few specialists. During the past 3 to 4 years, however, there has been a tremendous upsurge of interest in Lp(a), primarily because of multidisciplinary efforts in struc-tural and molecular biology. Findings emerging from these efforts include the following: Lp(a) represents a cholesteryl-ester, low-density-lipoprotein (LDL)-like particle with apolipoprotein (apo) B-100 linked to apo(a); apo(a) is a glycoprotein coded by a single gene locus on the long arm of chromosome 6, which has several alleles, accounting for its remarkable size poly-morphism (300 to 800 kD); apo(a) size polymorphism relates to plasma levels and density distribution of Lp(a); apo(a) is strikingly similar to plasminogen; and in vitro, Lp(a), in appropriate levels, competes for some physiologic functions of plasminogen in the coagula-tion and fibrinolytic cascade and may thus be throm-bogenic. The LDL-like properties of Lp(a) may also confer atherogenic potential, but the mechanisms un-derlying this atherogenicity remain to be defined. In epidemiologic studies, high plasma Lp(a) levels have been associated with an increased incidence of athero-sclerotic cardiovascular disease, especially in patients less than 60 years of age. Moreover, Lp(a) has been found as an intact particle in the arterial intima, partic-ularly in association with atherosclerotic plaque. This finding suggests that Lp(a) can traverse the endothe-lium, possibly by a non-receptor-mediated process, and, at the intimal level, acquire thrombogenic and atherogenic potentials. Current information justifies the need to determine plasma Lp(a) levels in patients with a history of atherosclerotic cardiovascular disease. Un-fortunately, the available techniques need to be stan-dardized. Apolipoprotein(a) exists in isoforms of dif-ferent sizes, and the importance of determining apo(a) phenotypes in clinical practice remains to be estab-lished