Vascular Health and Risk Management (Sep 2021)
Elevated Lipoprotein(a): Background, Current Insights and Future Potential Therapies
Abstract
Ahmed Handhle, 1 Adie Viljoen, 2 Anthony S Wierzbicki 3 1Department of Metabolic Medicine/Chemical Pathology, Addenbrookes Hospital, Cambridge, UK; 2Department of Metabolic Medicine/Chemical Pathology, North & East Hertfordshire Hospitals Trust, Lister Hospital, Hertfordshire, UK; 3Department of Metabolic Medicine/Chemical Pathology, Guy’s & St Thomas’, Hospitals, London, SE1 7EH, UKCorrespondence: Anthony S WierzbickiMetabolic Medicine/Chemical Pathology, St Thomas Hospital, Lambeth Palace Road, London, SE1 7EH, UKTel +44 207 188 1256Email [email protected]: 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
