Lipoprotein(A): physiologic function, association with atherosclerosis, and effects of lipid-lowering drug therapy

OBJECTIVE: To review the structure and physiologic function of lipoprotein(a) [Lp(a)], review the association of Lp(a) with the development of atherosclerosis, and to critically evaluate the current literature regarding the effects of lipid-lowering drug therapy on Lp(a) serum concentrations. DATA SOURCES: English language clinical and animal studies, abstracts, and review articles pertaining to Lp(a). STUDY SELECTION AND DATA EXTRACTION: Relevant human and animal studies examining Lp(a)'s role in atherosclerosis and the effect of drug therapy on Lp(a) serum concentrations. DATA SYNTHESIS: Possible physiologic functions and potential atherogenic mechanisms of Lp(a) are discussed. Evidence supporting the association of Lp(a) with atherosclerosis is presented. Studies evaluating the effects of lipid-lowering drug therapy on Lp(a) concentrations are reviewed and critiqued. CONCLUSIONS: Lp(a) concentrations are correlated with the risk of atherosclerotic vascular disease (AVD) in both animals models and human studies. Drug therapies that have produced a consistent reduction in Lp(a) concentration include niacin alone or in combination with a bile acid sequestrant or neomycin. However, additional, larger studies are needed to evaluate the ability of drug therapies to specifically reduce elevated Lp(a) concentrations. Preliminary information suggests that reduction in Lp(a) concentrations may be associated with atherosclerotic plaque regression. Although drugs are available to lower Lp(a), one cannot conclude that lowering of Lp(a) is warranted until clinical trials demonstrating beneficial effects have been published.