Elevated Lipoprotein(a): Background, Current Insights and Future Potential Therapies

Abstract

Lipoprotein(a) forms a subfraction of the lipid profile and is characterized by the addition of apolipprotein(a) (apo(a)) to apoB100 derived particles. Its levels are mostly genetically determined inversely related to the number of protein domain (kringle) repeats in apo(a). In epidemiological studies, it shows consistent association with cardiovascular disease (CVD) and most recently with extent of aortic stenosis. Issues with standardizing the measurement of Lp(a) are being resolved and consensus statements favor its measurement in patients at high risk of, or with family histories of CVD events. Major lipid-lowering therapies such as statin, fibrates, and ezetimibe have little effect on Lp(a) levels. Therapies such as niacin or cholesterol ester transfer protein (CETP) inhibitors lower Lp(a) as well as reducing other lipid-related risk factors but have failed to clearly reduce CVD events. Proprotein convertase subtilisin kexin-9 (PCSK9) inhibitors reduce cholesterol and Lp(a) as well as reducing CVD events. New antisense therapies specifically targeting apo(a) and hence Lp(a) have greater and more specific effects and will help clarify the extent to which intervention in Lp(a) levels will reduce CVD events.

Keywords:

• lipoprotein (a)
• cardiovascular disease
• aortic stenosis
• apheresis
• genetics
• lipoprotein turnover
• statin
• PCSK9
• antisense therapy

Disclosure

Dr Adie Viljoen reports personal fees, non-financial support from Novo Nordisk, personal fees from Novartis, non-financial support from Lilly, personal fees from Boehringer Ingelheim, grants, personal fees from Sanofi, personal fees from Napp, personal fees from Novartis, personal fees from Pfizer, personal fees, non-financial support from Astra Zeneca, outside the submitted work. Professor Anthony S Wierzbicki is: Site clinical trial investigator: volanesorsen for Akcea, Site clinical trial investigator: Evinacumab for Regeneron, Site clinical trial investigator: Evolocumab for Amgen, outside the submitted work. The authors report no other conflicts in this work.