New research project aims to set standardized approach to lipoprotein(a) management

March 27th, 2023

Figure. Lp(a) structure, properties, regulation, and relation to disease. Lipoprotein(a) [Lp(a)] consists of a lipid-rich domain, primarily cholesteryl esters, and apolipoprotein(a) [apo(a)]. Apo(a) binds to apolipoprotein B100 (apoB) via a single disulfide bond (a) at a location close the low-density lipoprotein receptor binding site of apoB (b). Apo(a) contains repeated kringle (K) structures (KIV and KV), comparable with those in plasminogen. There are 10 different subtypes of apo(a) KIV, where type 2 is present in multiple copies, resulting in a highly variable molecular mass (300–800 kDa). Apo(a) is compositionally unique among apolipoproteins with a high carbohydrate content (≈28%). Proinflammatory and proatherogenic oxidized phospholipids bind to apo(a) KIV type 10 (c) and can also be found in the lipid phase. Apo(a) contains a protease domain (d) that lacks enzymatic activity. The Lp(a) concentration is heterogeneous and, to a major extent, controlled by genetics, inversely related to the copy number variation in the LPA gene. Other factors such as ethnicity and race and medical and environmental conditions also play roles in Lp(a) regulation. Lp(a) has been associated with increased risks of atherosclerosis, thrombosis, and aortic valve calcification. Credit: Arteriosclerosis, Thrombosis, and Vascular Biology (2021). DOI: 10.1161/ATV.0000000000000147

High levels of lipoprotein(a) [Lp(a)] are an independent, predominantly inherited and causal risk factor for cardiovascular disease, the leading cause of death and disability worldwide, according to a recent American Heart Association scientific statement. It is estimated that 1 in 5 Americans have high Lp(a) levels.

Studies have shown that elevated Lp(a)—a low-density lipoprotein variant containing a protein called apolipoprotein(a)—is a risk factor for atherosclerosis (buildup of fatty material in artery walls) and related diseases, such as coronary heart disease and stroke. However, there are no standard management approaches for diagnosis or risk assessment, nor any targeted treatments available to lower Lp(a).

Today, national Lp(a) Awareness Day, the American Heart Association launched a new project to better understand the genetic and biological basis for variation in Lp(a) levels and its relationship to disease. The Lp(a) Discovery Project, supported by Novartis Pharmaceuticals Corporation, aims to determine clinical standards for optimal patient care through a new screening measure and quality improvement interventions for those with elevated Lp(a).

The Lp(a) Discovery Project will use an integrated, patient-centered approach to launch an Lp(a) screening measure and, using the Association's current Integrated ASCVD Management Initiative infrastructure, track and test it nationally. The new effort will engage the six health systems currently involved in the ASCVD initiative, as well as an additional 10 new sites, to test and pilot specific Lp(a) quality improvement interventions.

In addition, the Association will launch a data challenge inviting the world's best researchers to apply novel data science techniques with large clinical and genetic datasets to better understand how Lp(a) levels impact cardiovascular and stroke risk.

"Scientific discovery has determined that Lp(a) plays a role in the development of cardiovascular disease, however many questions still remain," said Mariell Jessup, M.D., FAHA, chief science and medical officer of the American Heart Association. "This project is an important step to fill in knowledge gaps around Lp(a) and encourage better, more targeted treatments to reduce cardiovascular risk."

The three-year project will culminate with nationally released education and insights to improve patient care, as well as Lp(a) enhancements to the Association's Get With The Guidelines platform, such as additional data collection.

Provided by American Heart Association