Lipoprotein A

Excerpt

Lipoprotein(a), or Lp(a), is an established and genetically determined risk factor for atherosclerosis, coronary artery disease, stroke, thrombosis, and aortic stenosis. Structurally, it is a variant of low-density lipoprotein and features apolipoprotein(a), or apo(a), which is bound to apolipoprotein B-100, or apoB100. These 2 structures are assembled in the hepatocyte cell membranes and are bound by 1 disulfide bridge. The electrophoretic mobility of Lp(a) is typically pre-β but can vary between that of low-density lipoprotein (β) and albumin (pre-α).

Plasma concentrations of Lp(a) and the apo(a) isoform are inversely related. The variation in isoforms is induced by the number of kringle IV repeats in the LP(a) gene. The variation in kringle units leads to the variable levels of Lp(a) observed in the general population. In general, individuals with fewer kringle repeats tend to have smaller Lp(a) particles but higher serum levels. In addition, larger isoforms of apo(a) lead to an increased accumulation of its precursor intracellularly within the endoplasmic reticulum.

Lp(a) levels >50 mg/dL are associated with an increased risk of cardiovascular diseases. Internationally, there is a general disagreement on screening guidelines. Screening patients for elevated Lp(a) levels could help identify those who need more aggressive lipid therapy and cardiovascular disease risk management. The suggestion has been made that, for younger patients, coronary artery disease could be explained by Lp(a), with or without other risk factors.

No specific therapy exists for treating elevated Lp(a). Most generalized screening aims to identify elevated Lp(a) as an existing risk factor, followed by subsequent optimization of overall cardiac health as the primary treatment. While certain medications such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and niacin directly lower Lp(a) levels, there is no Food and Drug Administration (FDA)-approved medication for the treatment of elevated Lp(a). Further research will contribute to the improvement of both screening guidelines and treatment modalities.