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What Do We Know About the Role of Lipoprotein(a) in Atherogenesis 57 Years After its Discovery?

Cybulska, B, Kłosiewicz-Latoszek, L, Penson, P and Banach, M What Do We Know About the Role of Lipoprotein(a) in Atherogenesis 57 Years After its Discovery? Progress in Cardiovascular Diseases. ISSN 0033-0620 (Accepted)

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Abstract

Elevated circulating concentrations of lipoprotein(a) [Lp(a)] is strongly associated with increased risk of atherosclerotic cardiovascular disease (CVD) and degenerative aortic stenosis. This relationship was first observed in prospective observational studies, and the causal relationship was confirmed in genetic studies. Everybody should have their Lp(a) concentration measured once in their lifetime. CVD risk is elevated when Lp(a) concentrations are high i.e >50 mg/dL (≥100 mmol/L). Extremely high Lp(a) levels >180 mg/dL (≥430 mmol/L) are associated with CVD risk similar to that conferred by familial hypercholesterolemia. Elevated Lp(a) level was previously treated with niacin, which exerts a potent Lp(a)-lowering effect. However, niacin is currently not recommended because, despite the improvement in lipid profile, no improvements on clinical outcomes have been observed. Furthermore, niacin use has been associated with severe adverse effects. Post hoc analyses of clinical trials with proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors have shown that these drugs exert clinical benefits by lowering Lp(a), independent of their potent reduction of low-density lipoprotein cholesterol (LDL-C). It is not yet known whether PCSK9 inhibitors will be of clinical use in patients with elevated Lp(a). Apheresis is a very effective approach to Lp(a) reduction, which reduces CVD risk but is invasive and time-consuming and is thus reserved for patients with very high Lp(a) levels and progressive CVD. Studies are ongoing on the practical application of genetic approaches to therapy, including antisense oligonucleotides against apolipoprotein(a) and small interfering RNA (siRNA) technology, to reduce the synthesis of Lp(a).

Item Type: Article
Uncontrolled Keywords: 1102 Cardiorespiratory Medicine and Haematology
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier
Date Deposited: 23 Mar 2020 12:28
Last Modified: 23 Mar 2020 12:28
URI: http://researchonline.ljmu.ac.uk/id/eprint/12582

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