Letter to the Editor
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Dec 20, 2024; 14(4): 99968
Published online Dec 20, 2024. doi: 10.5493/wjem.v14.i4.99968
Familial hypercholesterolemia: Current limitations and future breakthroughs
Ze Xiang, Jia-Rui Li, Wei-Min Wan, Shu-Hui Li, Jian Wu
Ze Xiang, Jia-Rui Li, Shu-Hui Li, School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang Province, China
Wei-Min Wan, Jian Wu, Department of Clinical Laboratory, Suzhou Municipal Hospital, Suzhou 215008, Jiangsu Province, China
Co-first authors: Ze Xiang and Jia-Rui Li.
Author contributions: Wu J designed study and revised the manuscript; Xiang Z and Li JR wrote the paper; Wan WM and Li SH searched the literature; All authors reviewed and approved the final version; Xiang Z and Li JR contributed equally to this work.
Supported by National Key Research and Development Program of China, No. 2022YFE0209900.
Conflict-of-interest statement: The authors declare that there are no competing interests associated with this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jian Wu, MD, PhD, Professor, Department of Clinical Laboratory, Suzhou Municipal Hospital, No. 242 Guangji Road, Suzhou 215008, Jiangsu Province, China. wujianglinxing@163.com
Received: August 4, 2024
Revised: October 2, 2024
Accepted: October 16, 2024
Published online: December 20, 2024
Processing time: 88 Days and 0.4 Hours
Abstract

Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol levels due to genetic mutations, presenting with xanthomas, corneal arch, and severe cardiovascular diseases. Early identification, diagnosis, and treatment are crucial to prevent severe complications like acute myocardial infarction. Statins are the primary treatment, supplemented by Ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, though their effectiveness can be limited in severe cases. Over 90% of FH cases remain undiagnosed, and current treatments are often inadequate, underscoring the need for improved diagnostic and management systems. Future strategies include advancements in gene testing, precision medicine, and novel drugs, along with gene therapy approaches like AAV-mediated gene therapy and clustered regularly interspaced short palindromic repeats. Lifestyle modifications, including health education, dietary control, and regular exercise, are essential for managing FH and preventing related diseases. Research into FH-related gene mutations, especially LDLR, is critical for accurate diagnosis and effective treatment.

Keywords: Familial hypercholesterolemia; Genetic mutations; Treatment; Limitations; Breakthroughs

Core Tip: Familial hypercholesterolemia (FH) is a genetic disorder characterized by significantly elevated levels of plasma low-density lipoprotein cholesterol, often leading to severe cardiovascular conditions such as acute myocardial infarction. Early detection, diagnosis, and treatment are crucial for improving patient outcomes. Despite growing awareness, over 90% of the estimated 30 million global FH cases remain undiagnosed, and many patients lack adequate treatment. Current management primarily involves statins, with additional therapies like Ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, though effectiveness varies, particularly in homozygous FH cases. Advancements in gene testing and precision medicine are essential for better understanding and treating FH. Future strategies include gene therapy and novel lipid-lowering drugs, alongside lifestyle modifications and genetic diagnosis for early intervention and improved prognosis.