Volume 6, Issue 4

Lipoprotein(a), or Lp(a), is a low-density lipoprotein-like particle in which apolipoprotein B-100 is covalently linked to apolipoprotein(a). Its plasma concentration is determined largely by variation in the LPA gene, is stable throughout adult life, and is not substantially affected by diet or exercise. Evidence from large prospective cohorts and Mendelian randomization studies supports a causal role for Lp(a) in atherosclerotic cardiovascular disease and calcific aortic valve stenosis, with risk increasing continuously across the concentration range. About one in five people worldwide has a concentration high enough to raise risk meaningfully, and levels are higher on average in people of African ancestry and lower in those of East Asian ancestry. Recent consensus statements recommend measuring Lp(a) at least once in every adult, using isoform-insensitive assays reported in molar units, and using the result to refine risk estimates and intensify management of other modifiable risk factors. No therapy has yet been approved specifically to lower Lp(a) for the prevention of cardiovascular events. Statins do not lower it, PCSK9 inhibitors reduce it modestly, and lipoprotein apheresis is reserved for selected patients with progressive disease. Antisense oligonucleotides, small interfering RNAs, and an oral inhibitor of Lp(a) assembly reduce concentrations by 65% to more than 90%, and phase 3 outcome trials will determine whether these reductions prevent events. This review summarizes the biology, epidemiology, measurement, and management of Lp(a) and discusses how clinicians can use it in practice while outcome data are awaited.