Lipoprotein(a) and Cardiovascular Disease Prevention across Diverse Populations
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REVIEW
Lipoprotein(a) and Cardiovascular Disease Prevention across Diverse Populations Keon Pearson . Fatima Rodriguez
Received: April 20, 2020 The Author(s) 2020
ABSTRACT Lipoprotein(a) (Lp(a)) is a highly proatherogenic lipid fraction that is genetically determined and minimally responsive to lifestyle or behavior changes. Mendelian randomization studies have suggested a causal link between elevated Lp(a) and heart disease, stroke, and aortic stenosis. There is substantial inter-ethnic variation in Lp(a) levels, with persons of African descent having the highest median values. Monitoring of Lp(a) has historically been limited by lack of standardization of assays. With the advent of novel therapeutic modalities to lower Lp(a) levels including proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors and targeted antisense oligonucleotides, it is increasingly important to screen patients who have family or personal history of atherosclerotic cardiovascular disease for elevations in Lp(a). Further study is needed to establish a causal relationship between elevated Lp(a) and cardiovascular disease across diverse ethnic populations.
Digital features To view digital features for this article go to https://doi.org/10.6084/m9.figshare.12290483. K. Pearson F. Rodriguez (&) Division of Cardiovascular Medicine and the Cardiovascular Institute, Stanford University, Stanford, USA e-mail: [email protected]
Keywords: Antisense oligonucleotide; Aortic stenosis; Coronary artery disease; Ethnic disparities; Lipoprotein(a); PCSK9 inhibitor; Plasma lipid apheresis; Stroke Key Summary Points Lp(a) is a highly atherogenic lipid fraction with numerous studies showing a strong association between elevated Lp(a) and coronary artery disease stroke and aortic stenosis. The expression of Lp(a) is largely determined by autosomal dominant inheritance with behavioral factors having minimal influence over serum levels. Persons of African and South Asian descent have significantly higher mean Lp(a) levels than persons of European Latin American or East Asian descent. Novel therapies including PCSK-9 inhibitors and antisense oligonucleotides significantly reduce Lp(a) levels independently of LDL reductions. Further studies on the role of Lp(a) reduction in primary cardiovascular disease prevention are needed.
Cardiol Ther
INTRODUCTION What is Lipoprotein(a)? Lipoprotein(a) [Lp(a)] is a low-density lipoprotein(LDL)-like lipid fraction consisting of two subunits: a single apolipoprotein a [Apo(a)] molecule, which is a lipid-rich fraction produced by the liver; and apolipoprotein B-100 (ApoB100), which has an LDL receptor and is also a constituent of very low density lipoprotein(VLDL), intermediate density lipoprotein(IDL), and LDL [1]. Apo(a) consists of 11 different kringle domains, which are subdomains of the protein with a structure that resembles the folded Danish pastry of the same name. While most kringle domains are expressed exactly once in the final Apo(a) quaternary structure, the primary constituent by mass is the kring
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