Guidelines for the Management of Familial Hypercholesterolemia

Abstract

Familial hypercholesterolemia (FH) is a highly prevalent autosomal dominant hereditary disease, generally characterized by three major signs, hyper-low-density-lipoprotein (LDL) cholesterolemia, tendon/skin xanthomas and premature coronary artery disease (CAD). Because the risk of CAD is very high in these patients, they should be identified at an early stage of their lives and started on intensive treatment to control LDL-cholesterol. We here introduce a new guideline for the management of FH patients in Japan intending to achieve better control to prevent CAD. Diagnostic criteria for heterozygous FH are 2 or more of 1) LDL-cholesterol ≥ 180 mg/dL, 2) tendon/skin xanthoma(s), and 3) family history of FH or premature CAD within second degree relatives, for adults; and to have both 1) LDL-cholesterol ≥ 140 mg/dL and 2) family history of FH or premature CAD within second degree relatives, for children. For the treatment of adult heterozygous FH, intensive lipid control with statins and other drugs is necessary. Other risks of CAD, such as smoking, diabetes mellitus, hypertension etc., should also be controlled strictly. Atherosclerosis in coronary, carotid, or peripheral arteries, the aorta and aortic valve should be screened periodically. FH in children, pregnant women, and women who wish to bear a child should be referred to specialists. For homozygotes and severe heterozygotes resistant to drug therapies, LDL apheresis should be performed. The treatment cost of homozygous FH is authorized to be covered under the program of Research on Measures against Intractable Diseases by the Japanese Ministry of Health, Labour, and Welfare.

Familial Hypercholesterolemia in Asian Populations

“…In a Korean study, 31 patients with pathogenic mutations in the LDLR, APOB, and PCSK9 genes were found in 97 patients identified with LDL-C 190 mg/dL, combining with xanthoma or an FHcompatible family history 32) . Of the 31 patients, 27 had mutations in the LDLR gene, two had mutations Abbreviations: HeFH heterozygous familial hypercholesterolemia; HoFH homozygous familial hypercholesterolemia; CAD coronary artery disease; TC total cholesterol; LDL-C low-density lipoprotein cholesterol; TG triglyceride treatment of dyslipidemia 31) . China's 2007 guidelines for dyslipidemia lacked a separate section for FH and systematic recommendations for the diagnosis, detection, and treatment of FH 44) .…”

“…In Asia, Japan and China have developed their own diagnostic criteria 26,29,30) . The FH diagnostic criteria issued by Japanese scientists included three key diagnostic components: LDL-C level, tendon xanthoma or xanthoma tuberosum, and family history 31) . The clinical criteria developed by China can be found in the textbook Clinical Coronary Heart Disease, which included two key diagnostic components: TC/LDL-C level and patients or family members with tendon xanthoma 29) .…”

Modern Approaches to the Treatment of Homozygous Familial Hypercholesterolemia

“…Учитывая трудности в достижении целе-вого уровня холестерина ЛПНП, статины часто ком-бинируются с эзетролом -препаратом, препятству-ющим всасыванию липидов в кишечнике. Результаты большого клинического исследования с включением более 700 пациентов с семейной гиперхолестерине-мией показали, что комбинация симастатина с эзе-тролом позволяет дополнительно снизить уровень холестерина ЛПНП еще на 20% [26]. Препарат назна-чается с 10 лет, комбинируется со статинами, хорошо переносится [27].…”

“…При этом возможна регрессия ксантом, регресс атеросклеротического поражения сосудов и замедление прогрессирования атероскле-роза [6,26,[32][33][34]. Обычно процедура проводится 1 раз в 2 нед у детей старше 5 лет [6,26,32], хотя хо-рошие результаты были получены даже у детей бо-лее раннего возраста с массой тела более 13,5 кг [33]. К сожалению, в настоящее время эта процедура име-ет ограниченное применение в педиатрической прак-тике в России.…”

Translational Research for Improving the Care of Familial Hypercholesterolemia: The “Ten Countries Study” and Beyond

“…This provides an early foundation for the development of expert guidelines, essential services, and new models of care in Asian countries. Guidelines and diagnostic criteria for FH have hitherto been produced by Japan 17) and Australasia 18) ; Hong Kong 19) and South Korea 20) also recently communicated their experiences in managing FH. This is a good start to a long journey.…”