Abstract
The purpose of this article is to discuss the pathophysiology, epidemiology, clinical assessment, and management of elevated lipoprotein(a) (Lp(a)) levels in atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS).
Lp(a) is a unique lipoprotein consisting of 2 components: a low-density lipoprotein (LDL) moiety and a single molecule of apolipoprotein(a) (apo(a)), which binds to apolipoprotein B in the LDL moiety. The cholesterol content of the LDL moiety promotes atherosclerosis while apo(a) confers additional atherogenic and inflammatory properties to Lp(a). Lp(a) is an independent and causal risk factor for ASCVD and CAVS as well as all-cause mortality. Elevations in Lp(a) levels are genetically determined with minimal reductions observed in response to nonpharmacological risk factor modification. Currently available lipid-lowering drugs produce minimal or only modest percent changes in Lp(a) levels. As a consequence, Lp(a) is rarely measured in clinical practice. Several investigational agents designed to specifically target Lp(a) reduce levels by 80% to 100%. These agents work by decreasing the synthesis of apo(a) or by inhibiting the binding of apo(a) to apolipoprotein B. Phase 3 ASCVD outcome trials for several of these agents have completed enrollment.
Elevated Lp(a) levels are a known risk factor for ASCVD and CAVS. Several investigational drugs produce 80% to 100% reductions in Lp(a) levels. However, until these therapies are proven to lead to favorable clinical outcomes, management of patients with elevated Lp(a) levels will continue to be limited to early and intensive ASCVD risk factor management.