Lipoprotein(a)

Lipoprotein(a), Lp(a), a complex between a low-density lipoprotein (LDL)-like lipid moiety containing one copy of apolipoprotein (apo) B, and apo(a), a plasminogen-derived, carbohydrate-rich, hydrophilic protein, is a genetically regulated cardiovascular risk factor. While La(a) levels are stable within an individual, Lp(a) levels have a skewed distribution in the population and are strongly impacted by a size polymorphism of theLPAgene, resulting in a variable number of kringle IV (KIV) units, a key motif of apolipoprotein(a). The variation in KIV units is a strong predictor of plasma Lp(a) levels and has been associated with cardiovascular risk, as recently confirmed by Mendelian randomization studies. In view of a number of recent, large studies firmly documenting Lp(a) as a cardiovascular risk factor, the European Atherosclerosis Society has issued screening and treatment guidelines. To date, there is only limited experience from Lp(a)-reducing therapy, and apart from nicotinic acid, Lp(a) levels are not impacted by conventional lipid-lowering therapy. Recent studies using novel therapeutic approaches show promise, as apoB antisense inhibitors and proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors have been shown to decrease Lp(a) levels, opening possibilities for intervention as well as mechanistic studies.