Lipoprotein(a)—60 Years Later—What Do We Know?

Abstract

Lipoprotein(a) (Lp(a)) molecule includes two protein components: apolipoprotein(a) and apoB100. The molecule is the main transporter of oxidized phospholipids (OxPL) in plasma. The concentration of this strongly atherogenic lipoprotein is predominantly regulated by the LPA gene expression. Lp(a) is regarded as a risk factor for several cardiovascular diseases. Numerous epidemiological, clinical and in vitro studies showed a strong association between increased Lp(a) and atherosclerotic cardiovascular disease (ASCVD), calcific aortic valve disease/aortic stenosis (CAVD/AS), stroke, heart failure or peripheral arterial disease (PAD). Although there are acknowledged contributions of Lp(a) to the mentioned diseases, clinicians struggle with many inconveniences such as a lack of well-established treatment lowering Lp(a), and common guidelines for diagnosing or assessing cardiovascular risk among both adult and pediatric patients. Lp(a) levels are different with regard to a particular race or ethnicity and might fluctuate during childhood. Furthermore, the lack of standardization of assays is an additional impediment. The review presents the recent knowledge on Lp(a) based on clinical and scientific research, but also highlights relevant aspects of future study directions that would approach more suitable and effective managing risk associated with increased Lp(a), as well as control the Lp(a) levels.

Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Where Do We Stand?

“…However, the exact role and degree of involvement of each receptor remain uncertain [ 17 , 22 ]. ApoB100, apo(a), and oxidized phospholipids (OxPLs) on the surface of Lp(a) act as ligands for these receptors [ 23 ]. Intracellularly, LDL and apo(a) particles undergo lysosomal degradation, while approximately 30% of apo(a) molecules are recycled to contribute to the formation of new Lp(a) molecules [ 24 ].…”

Sex X Time Interactions in Lp(a) and LDL-C Response to Evolocumab

“…In the last decade, substantial evidence from epidemiological and experimental studies clearly showed that high levels of Lp(a) are an independent and genetically determined risk factor for the development of atherosclerosis and ASCVD, such as coronary artery disease (CAD), stroke and aortic stenosis [5,6]. Thus, the absence of available therapeutic options for effectively managing patients with hyperlipoproteinemia(a) means that identifying the genetic determinants of individual response variability to PCSK9 pharmacological inhibition is a critical issue [7].…”