Update on lipoprotein(a) as a cardiovascular risk factor and mediator.

Recent genetic studies have put the spotlight back onto lipoprotein(a) [Lp(a)] as a causal risk factor for coronary heart disease. However, there remain significant gaps in our knowledge with respect to how the Lp(a) particle is assembled, the route of its catabolism, and the mechanism(s) of Lp(a) pathogenicity. It has long been speculated that the effects of Lp(a) in the vasculature can be attributed to both its low-density lipoprotein moiety and the unique apolipoprotein(a) component, which is strikingly similar to the kringle-containing fibrinolytic zymogen plasminogen. However, the ability of Lp(a) to modulate either purely thrombotic or purely atherothrombotic processes in vivo remains unclear. The presence of oxidized phospholipid on Lp(a) may underlie many of the proatherosclerotic effects of Lp(a) that have been identified both in cell models and in animal models, and provides a possible avenue for identifying therapeutics aimed at mitigating the effects of Lp(a) in the vasculature. However, the beneficial effects of targeted Lp(a) therapeutics, designed to either lower Lp(a) concentrations or interfere with its effects, on cardiovascular outcomes remains to be determined.