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Review
. 2019 Nov 27;8(12):2073.
doi: 10.3390/jcm8122073.

Molecular, Population, and Clinical Aspects of Lipoprotein(a): A Bridge Too Far?

Natalie C Ward  1   2 , Karam M Kostner  3   4 , David R Sullivan  5   6   7 , Paul Nestel  8   9 , Gerald F Watts  2   10
Affiliations
Review

Molecular, Population, and Clinical Aspects of Lipoprotein(a): A Bridge Too Far?

Natalie C Ward et al. J Clin Med. .

Abstract

There is now significant evidence to support an independent causal role for lipoprotein(a) (Lp(a)) as a risk factor for atherosclerotic cardiovascular disease. Plasma Lp(a) concentrations are predominantly determined by genetic factors. However, research into Lp(a) has been hampered by incomplete understanding of its metabolism and proatherogeneic properties and by a lack of suitable animal models. Furthermore, a lack of standardized assays to measure Lp(a) and no universal consensus on optimal plasma levels remain significant obstacles. In addition, there are currently no approved specific therapies that target and lower elevated plasma Lp(a), although there are recent but limited clinical outcome data suggesting benefits of such reduction. Despite this, international guidelines now recognize elevated Lp(a) as a risk enhancing factor for risk reclassification. This review summarises the current literature on Lp(a), including its discovery and recognition as an atherosclerotic cardiovascular disease risk factor, attempts to standardise analytical measurement, interpopulation studies, and emerging therapies for lowering elevated Lp(a) levels.

Keywords: atherosclerotic cardiovascular disease; calcific aortic valve disease; lipoprotein(a).

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Conflict of interest statement

N.C.W.: none. K.M.K.: honoraria from Amgen, MSD, Sanofi, Pfizer, Astra Zeneka, Novartis and Bayer. D.R.S.: research support from Amgen, Sanofi, Arrowhead, Novartis and Regeneron. P.N.: honorarium support from Amgen and Sanofi. G.F.W.: research support and honoraria for advisory panels for Sanofi, Amgen, Gemphire, Regeneron and Kowa.

Figures

Figure 1
Figure 1
Structure lipoprotein(a). ApoB = apolipoprotein B, apo(a) = apolipoprotein a and KIV = kringle repeat.
Figure 2
Figure 2
Association between lipoprotein(a) concencentration and isoform size (Reproduced from Reference [21]). Apo(a) = apolipoprotein (a), Lp(a) = lipoprotein (a), LMW = low molecular weight, HMW = high molecular weight, KIV = kringle number repeats.
Figure 3
Figure 3
Proposed algorithm for the management of elevated lipoprotein(a). Lp(a) = lipoprotein (a), ASCVD = atherosclerotic cardiovascular disease, CAD = coronary artery disease, APOA = apolipoprotein (a) gene, PCSK9 = proprotein convertase subtilisin/kexin type 9.
See this image and copyright information in PMC

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