Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Nov 2;78(18):1831-1843.
doi: 10.1016/j.jacc.2021.09.004.

Familial Hypercholesterolemia: JACC Focus Seminar 4/4

Julia Brandts  1 , Kausik K Ray  2
Affiliations
Review

Familial Hypercholesterolemia: JACC Focus Seminar 4/4

Julia Brandts et al. J Am Coll Cardiol. .

Abstract

Detecting familial hypercholesterolemia (FH) early and "normalizing" low-density lipoprotein (LDL) cholesterol values are the 2 pillars for effective cardiovascular disease prevention in FH. Combining lipid-lowering therapies targeting synergistic/complementary metabolic pathways makes this feasible, even among severe phenotypes. For LDL receptor-dependent treatments, PCSK9 remains the main target for adjunctive therapy to statins and ezetimibe through a variety of approaches. These include protein inhibition (adnectins), inhibition of translation at mRNA level (antisense oligonucleotides or small interfering RNA), and creation of loss-of-function mutations through base-pair editing. For patients with little LDL receptor function, LDL receptor-independent treatment targeting ANGPTL3 through monoclonal therapies are now available, or in the future, antisense/small interfering RNA-based approaches offer alternative approaches. Finally, first-in-human studies are ongoing, testing adenovirus-mediated gene therapy transducing healthy LDLR DNA in patients with HoFH. Further development of the CRISPR cas technology, which has shown promising results in vivo on introducing PCSK9 loss-of-function mutations, will move a single-dose, curative treatment for FH closer.

Keywords: LDL cholesterol; familial hypercholesterolemia; lipid-lowering therapies.

PubMed Disclaimer

Conflict of interest statement

Funding Support and Author Disclosures Dr Brandts has received research grant support from AstraZeneca; and has received speaker honoraria from Amgen. Dr Ray has received support from the National Institute for Health Research Imperial Biomedical Research Centre and additional support from the National Institute for Health Research ARC for northwest London; has received grants from Amgen during the conduct of the study; has received grants and personal fees from Amgen, Sanofi/Regeneron, Pfizer, Merck Sharp & Dohme, Daiichi-Sankyo; has received personal fees from Aegerion, AstraZeneca, Cerenis, Akcea, The Medicines Company, Kowa, Novartis, Cipla, Lilly, Algorithm, Takeda, Boehringer Ingelheim, Abbvie, Silence Therapeutics, Dr Reddys, Bayer, Esperion, Abbvie, Zuelling Pharma, and Silence Therapeutics outside of the submitted work.

MeSH terms