Clinical Characteristics of Homozygous Familial Hypercholesterolemia in Japan: A Survey Using a National Database

Yasuaki Takeji; Hayato Tada; Masatsune Ogura; Atsushi Nohara; Masa-Aki Kawashiri; Shizuya Yamashita; Mariko Harada-Shiba; Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labor, and Welfare of Japan

doi:10.1016/j.jacasi.2023.07.011

Clinical Characteristics of Homozygous Familial Hypercholesterolemia in Japan: A Survey Using a National Database

JACC Asia. 2023 Sep 19;3(6):881-891. doi: 10.1016/j.jacasi.2023.07.011. eCollection 2023 Dec.

Authors

Yasuaki Takeji¹, Hayato Tada¹, Masatsune Ogura², Atsushi Nohara³, Masa-Aki Kawashiri⁴, Shizuya Yamashita⁵, Mariko Harada-Shiba⁶; Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labor, and Welfare of Japan

Collaborators

Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labor, and Welfare of Japan:
Mariko Harada-Shiba, Shun Ishibashi, Shinji Yokoyama, Hitoshi Shimano, Koutaro Yokote, Hideaki Bujo, Shizuya Yamashita, Kazuhisa Tsukamoto, Katsunori Ikewaki, Takanari Gotoda, Kazushige Dobashi, Misa Takegami, Yoshiki Sekijima, Yasushi Ishigaki, Hiroaki Okazaki, Atsushi Nohara, Shingo Koyama, Kyoko Inagaki, Koh Ono, Masahiro Koseki, Hiroyuki Daida, Manabu Takahashi, Kimitoshi Nakamura, Takashi Miida, Masa-Aki Kawashiri, Tetsuo Minamino, Sachiko Okazaki, Hayato Tada, Jun Wada, Masatsune Ogura, Hirotoshi Ohmura, Mika Hori, Kota Matsuki, Masashi Yamamoto, Yasuo Takeuchi, Atsuko Nakatsuka, Daisaku Masuda, Satoshi Hirayama, Masayuki Kuroda, Takashi Yamaguchi

Affiliations

¹ Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
² Department of Medical Laboratory Technology, Faculty of Medical Science, Juntendo University, Urayasu, Japan.
³ Department of Clinical Genetics, Ishikawa Prefectural Central Hospital, Kanazawa, Japan.
⁴ Department of Internal Medicine, Kaga Medical Center, Kaga, Japan.
⁵ Department of Cardiology, Rinku General Medical Center, Izumisano, Japan.
⁶ Cardiovascular Center, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.

Abstract

Background: The studies evaluating patients' characteristics and lipid-lowering therapy for patients with homozygous familial hypercholesterolemia (HoFH) are scarce.

Objectives: This study aims to evaluate the characteristics of and treatments for patients with HoFH.

Methods: This study included 201 patients who were diagnosed with definite or probable HoFH from the National Database of the Japanese Ministry of Health, Labour, and Welfare.

Results: The patients' median age at diagnosis was 27 years and exhibited a bimodal distribution. Approximately 70% of patients had coronary artery disease. Regarding genetic backgrounds, mutations in the low-density lipoprotein (LDL) receptor (LDLR) were identified in most of the patients, followed by proprotein convertase subtilisin/kexin type 9 (PCSK9) and double heterozygotes of LDLR. High-intensity statins were introduced to 74% of the patients, lipoprotein apheresis was performed in 21%, and PCSK9 inhibitors were administered to 50%. The mean of LDL cholesterol before and after treatment were 10.1 mmol/L and 3.9 mmol/L, respectively. Patients with coronary artery disease had significantly decreased LDL cholesterol. A quarter of the patients (n = 49, 24%) exhibited valvular diseases, particularly aortic valvular disease (n = 34, 61%).

Conclusions: The national epidemiological study of patients with HoFH showed patient's clinical and genetic characteristics and LDL-lowering therapy in Japan. There was considerable diversity in the severity of phenotypes, including LDL cholesterol levels, among patients with HoFH. In Japan, the management of LDL cholesterol in HoFH is still inadequate despite the availability of intensive lipid-lowering therapies.

Keywords: genetics; homozygous familial hypercholesterolemia; low-density lipoprotein cholesterol; low-density lipoprotein receptor; proprotein convertase subtilisin/kexin type 9.