A critical evaluation of the role of Lp(a) in cardiovascular disease: can Lp(a) be useful in risk assessment?

Lp(a) is a structurally complex particle which resembles LDL, but which also contains the distinctive glycoprotein apo(a). Apo(a) is characterized by a variable number of repeated kringle domains, which gives rise to differently-sized Lp(a) isoforms in the population. Although epidemiological studies indicate that elevated Lp(a) concentration and/or small apo(a) isoform sizes increase the risk of coronary heart disease (CHD), a causal role for Lp(a) in CHD remains unproven. This is largely due to the difficulty in establishing a relevant animal model to probe Lp(a) function, and the lack of intervention studies in which Lp(a) concentrations are lowered and outcomes followed. The accumulation of apo(a)/Lp(a) in arterial lesions has provided the rationale for numerous in vitro studies aimed at dissecting its function in this milieu. These studies have resulted in the proposal of numerous proatherogenic, prothrombotic and antifibrinolytic roles for both native and modified apo(a)/Lp(a). Although characterization of Lp(a) in the general population is not presently justified, Lp(a) analysis in patients at risk for CHD may be warranted.