Familial hypercholesterolemia and elevated lipoprotein(a) : double heritable risk and new therapeutic opportunities

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Vuorio , A , Watts , G F , Schneider , W J , Tsimikas , S & Kovanen , P T 2020 , ' Familial hypercholesterolemia and elevated lipoprotein(a) : double heritable risk and new therapeutic opportunities ' , Journal of internal medicine , vol. 287 , no. 1 , pp. 2-18 . https://doi.org/10.1111/joim.12981

Title: Familial hypercholesterolemia and elevated lipoprotein(a) : double heritable risk and new therapeutic opportunities
Author: Vuorio, A.; Watts, G. F.; Schneider, W. J.; Tsimikas, S.; Kovanen, P. T.
Contributor: University of Helsinki, Department of Forensic Medicine
University of Helsinki, Wihuri Research Institute
Date: 2020-01
Language: eng
Number of pages: 17
Belongs to series: Journal of internal medicine
ISSN: 0954-6820
URI: http://hdl.handle.net/10138/327064
Abstract: Vuorio A, Watts GF, Schneider WJ, Tsimikas S, Kovanen PT (Mehilainen Airport Health Centre, Vantaa; University of Helsinki, Helsinki, Finland; University of Western Australia, Perth, Australia; Royal Perth Hospital, Perth, Australia; Medical University of Vienna, Vienna, Austria; University of California San Diego, La Jolla, CA, USA; Wihuri Research Institute, Helsinki, Finland). Familial hypercholesterolemia and elevated lipoprotein(a): double heritable risk and new therapeutic opportunities (Review). J Intern Med 2020; 287: 2-18. There is compelling evidence that the elevated plasma lipoprotein(a) [Lp(a)] levels increase the risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. Like low-density lipoprotein (LDL) particles, Lp(a) particles contain cholesterol and promote atherosclerosis. In addition, Lp(a) particles contain strongly proinflammatory oxidized phospholipids and a unique apoprotein, apo(a), which promotes the growth of an arterial thrombus. At least one in 250 individuals worldwide suffer from the heterozygous form of familial hypercholesterolemia (HeFH), a condition in which LDL-cholesterol (LDL-C) is significantly elevated since birth. FH-causing mutations in the LDL receptor gene demonstrate a clear gene-dosage effect on Lp(a) plasma concentrations and elevated Lp(a) levels are present in 30-50% of patients with HeFH. The cumulative burden of two genetically determined pro-atherogenic lipoproteins, LDL and Lp(a), is a potent driver of ASCVD in HeFH patients. Statins are the cornerstone of treatment of HeFH, but they do not lower the plasma concentrations of Lp(a). Emerging therapies effectively lower Lp(a) by as much as 90% using RNA-based approaches that target the transcriptional product of the LPA gene. We are now approaching the dawn of an era, in which permanent and significant lowering of the high cholesterol burden of HeFH patients can be achieved. If outcome trials of novel Lp(a)-lowering therapies prove to be safe and cost-effective, they will provide additional risk reduction needed to effectively treat HeFH and potentially lower the CVD risk in these high-risk patients even more than currently achieved with LDL-C lowering alone.
Subject: atherosclerotic cardiovascular disease
burden
familial hypercholesterolemia
lipoprotein (a)
therapy
3121 General medicine, internal medicine and other clinical medicine
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