Clinical Information

Lipoprotein (a) [Lp(a)] consists of a low-density lipoprotein (LDL) particle that is covalently bound to an additional protein, apolipoprotein (a) [Apo(a)]. Apo(a) has high sequence homology with the coagulation factor plasminogen, and like LDL, Lp(a) contains apolipoprotein B100 (ApoB). Thus, Lp(a) is both proatherogenic and prothrombotic.

Lp(a) is an independent risk factor for coronary heart disease (CHD), ischemic stroke, and aortic valve stenosis. Lp(a) has been referred to as "the most atherogenic lipoprotein". The mechanism of increased risk is unclear but most likely involves progression of atherosclerotic stenosis via intimal deposition of cholesterol and promotion of thrombosis via homology to plasminogen.

Accurate immunochemical measurement of Lp(a) is complicated by the heterogeneity of Lp(a) molecular size. Due to the large number of polymorphisms (varying number of kringle domain repeats in the Apo[a] protein) in the population, any given individual can have an Apo(a) protein between 240 to 800 kDa. This heterogeneity leads to inaccuracies in all immunoassays. In addition, the degree of atherogenicity of the Lp(a) particle may depend on the molecular size of the Lp(a)-specific protein. However, the measurement of Lp(a) using immunoassays calibrated to molar units is recommended to minimize assay inaccuracies caused by Apo(a) isoform size.

Serum concentrations of Lp(a) are related to genetic factors, specifically the expression of Apo(a), and are largely unaffected by diet, exercise, and lipid-lowering pharmaceuticals. However, in a patient with additional modifiable CHD risk factors, more aggressive therapy to normalize these factors may be indicated if the Lp(a) value is also increased. In cases of extremely elevated Lp(a), lipoprotein apheresis may be considered.