PCSK9 inhibitors are currently the most effective approved option for lowering Lp(a), but measurement itself lacks a reference standard, a review with practical recommendations (Heart 2022)

Original title: Lipoprotein(a): a risk factor for atherosclerosis and an emerging therapeutic target

Heart · 13 December 2022 · 5

Di Fusco SA, Arca M, Scicchitano P, Alonzo A, Perone F, Gulizia MM, Gabrielli D, Oliva F, Imperoli G, Colivicchi F

This review examines Lp(a) as both a cardiovascular risk factor and an emerging therapeutic target. Beyond cholesterol accumulation in the arterial wall, Lp(a) atherogenic effects are attributed partly to proinflammatory oxidised phospholipids, and multiple studies support a causal, independent relationship between Lp(a) and both cardiovascular risk and calcific aortic valve stenosis. Among currently available therapies, PCSK9 inhibitors are the most effective at lowering Lp(a), while more potent LPA-targeted treatments remain in development. Lp(a) measurement is complicated by the lack of a definitive reference method and inconsistent reporting in molar (nmol/L) versus mass (mg/dL) units across assays. The authors recommend Lp(a) measurement to refine risk in patients with family history of premature ASCVD, unexplained ASCVD, or recurrent events despite optimal risk factor management, with more intensive treatment of other modifiable risk factors in those found to have high Lp(a).

Original abstract

Lipoprotein(a) (Lp(a)) is a complex circulating lipoprotein, and increasing evidence has demonstrated its role as a risk factor for atherosclerotic cardiovascular disease (ASCVD) and as a possible therapeutic target. Lp(a) atherogenic effects are attributed to several potential mechanisms in addition to cholesterol accumulation in the arterial wall, including proinflammatory effects mainly mediated by oxidised phospholipids. Several studies have found a causal and independent relationship between Lp(a) levels and cardiovascular risk. Furthermore, several studies also suggest a causal association between Lp(a) levels and calcific aortic valve stenosis. Available lipid-lowering agents have at best moderate impact on Lp(a) levels. Among available therapies, antibody proprotein convertase subtilisin/kexin type 9 inhibitors are the most effective in reducing Lp(a). Potent Lp(a)-lowering treatments that target LPA expression are under development. Lp(a) level measurement poses some challenges due to the absence of a definitive reference method and the reporting of Lp(a) values as molar (nanomoles per litre (nmol/L)) or mass concentrations (milligrams per decilitre (mg/dL)) by different assays. Currently, Lp(a) measurement is recommended to refine cardiovascular risk in specific clinical settings, that is, in individuals with a family history of premature ASCVD, in patients with ASCVD not explained by standard risk factors or in those with recurrent events despite optimal management of traditional risk factors. Patients with high Lp(a) levels should be managed with more intensive approaches to treat other modifiable cardiovascular risk factors. Overall, this review focuses on Lp(a) as an ASCVD risk factor and therapeutic target. Furthermore, it reports practical recommendations for Lp(a) measurement and interpretation and updated evidence on Lp(a)-lowering approaches.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.