Lipoprotein(a) as a novel therapeutic target for preventing cardiovascular disease: A whiter shade of pale?

Research on the importance of lipoprotein(a) [Lp(a)] gained new momentum when it became a potential therapeutic target. Our understanding of this mysterious circulating lipoprotein particle has undergone advances and setbacks since its discovery in 1963 by Kåre Berg’s group. Lp(a) is composed of liver-derived apolipoprotein A and apolipoprotein B-100, and has a similar structure to both low-density lipoprotein cholesterol (LDL-C) and plasminogen. Lp(a) thus has a proatherogenic and a prothrombotic component, and is associated with the pathogenesis of cardiovascular disease (CVD). Findings from epidemiological, genetic and clinical studies have provided compelling evidence establishing Lp(a) as a marker of increased CVD risk in both primary and secondary prevention, including myocardial infarction (MI), stroke, and calcific aortic valve disease (CAVD). However, significant gaps in knowledge remain about the biology and pathophysiology of Lp(a). To address these gaps, a National Heart, Lung, and Blood Institute working group identified several challenges to fully understand the role of Lp(a) in CVD/CAVD. These include its metabolism and pathophysiological mechanisms, how to measure it, current