著者
Mariko Harada-Shiba Takao Ohta Akira Ohtake Masatsune Ogura Kazushige Dobashi Atsushi Nohara Shizuya Yamashita Koutaro Yokote Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.CR002, (Released:2018-02-06)
参考文献数
49
被引用文献数
4

This paper describes consensus statement by Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia (FH) in order to improve prognosis of FH.FH is a common genetic disease caused by mutations in genes related to low density lipoprotein (LDL) receptor pathway. Because patients with FH have high LDL cholesterol (LDL-C) levels from the birth, atherosclerosis begins and develops during childhood which determines the prognosis. Therefore, in order to reduce their lifetime risk for cardiovascular disease, patients with FH need to be diagnosed as early as possible and appropriate treatment should be started.Diagnosis of pediatric heterozygous FH patients is made by LDL-C ≥140 mg/dL, and family history of FH or premature CAD. When the diagnosis is made, they need to improve their lifestyle including diet and exercise which sometimes are not enough to reduce LDL-C levels. For pediatric FH aged ≥10 years, pharmacotherapy needs to be considered if the LDL-C level is persistently above 180 mg/dL. Statins are the first line drugs starting from the lowest dose and are increased if necessary. The target LDL-C level should ideally be <140 mg/dL. Assessment of atherosclerosis is mainly performed by noninvasive methods such as ultrasound.For homozygous FH patients, the diagnosis is made by existence of skin xanthomas or tendon xanthomas from infancy, and untreated LDL-C levels are approximately twice those of heterozygous FH parents. The responsiveness to pharmacotherapy should be ascertained promptly and if the effect of treatment is not enough, LDL apheresis needs to be immediately initiated.
著者
Mariko Harada-Shiba Hidenori Arai Yasushi Ishigaki Shun Ishibashi Tomonori Okamura Masatsune Ogura Kazushige Dobashi Atsushi Nohara Hideaki Bujo Katsumi Miyauchi Shizuya Yamashita Koutaro Yokote Working Group by Japan Atherosclerosis Society for Making Guidance of Familial Hypercholesterolemia
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.CR003, (Released:2018-06-07)
参考文献数
74
被引用文献数
1

Statement1. Familial hypercholesterolemia (FH) is an autosomal hereditary disease with the 3 major clinical features of hyper-LDL-cholesterolemia, premature coronary artery disease and tendon and skin xanthomas. As there is a considerably high risk of coronary artery disease, in addition to early diagnosis and intensive treatment, family screening (cascade screening) is required (Recommendation level A)2.For a diagnosis of FH, at least 2 of the following criteria should be satisfied:① LDL-C ≥180 mg/dL, ② Tendon/skin xanthomas, ③ History of FH or premature coronary artery disease (CAD) within 2nd degree blood relatives (Recommendation level A)3. Intensive lipid-lowering therapy is necessary for the treatment of FH. First-line drug should be statin. (Recommendation level A, evidence level 3)4.Screening for coronary artery disease as well as asymptomatic atherosclerosis should be conducted periodically in FH patients. (Recommendation level A)5. For homozygous FH, consider LDL apheresis and treatment with PCSK9 inhibitors or MTP inhibitors. (Recommendation level A)6.For severe forms of heterozygous FH who have resistant to drug therapy, consider PCSK9 inhibitors and LDL apheresis. (Recommendation level A)7.Refer FH homozygotes as well as heterozygotes who are resistant to drug therapy, who are children or are pregnant or have the desire to bear children to a specialist. (Recommendation level A)
著者
Mariko Harada-Shiba John J.P. Kastelein G. Kees Hovingh Kausik K. Ray Akira Ohtake Osamu Arisaka Takao Ohta Tomoo Okada Hideki Suganami Albert Wiegman
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.42242, (Released:2017-11-29)
参考文献数
24

Aim: Children with Familial Hypercholesterolemia (FH) are widely prescribed statins, and it has been suggested that the effects of statins differ among ethnicities. We compared the efficacy and safety of pitavastatin in children and adolescents with FH in clinical trials conducted in Japan and Europe.
著者
Yoshitsune Miyagi Mariko Harada-Shiba Takao Ohta
出版者
一般社団法人 日本動脈硬化学会
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.31666, (Released:2015-10-27)
参考文献数
18
被引用文献数
2

Familial hypercholesterolemia (FH) is characterized by a high level of low-density lipoprotein cholesterol (LDL-C) and is inherited as an autosomal dominant trait. We report 4-year-old dichorionic diamniotic twins (boy and girl) with FH who presented with multiple xanthomas on the face, both knees, both feet, and buttocks. Family history revealed vertical transmission of hypercholesterolemia from father to patients, thereby suggesting dominant inheritance. Lipid data of their mother did not match the criteria of FH. However, lipid data of maternal grandmother and maternal sister matched the criteria of FH. LDL receptor gene analysis of the family revealed that their father was heterozygous for a missense mutation, L547V, their mother was heterozygous for a nonsense mutation, C675X, and patients were compound heterozygous for L547V and C675X. After 10 months of treatment with pitavastatin (2 mg/day) and ezetimibe (10 mg/day), LDL-C decreased from 595 mg/dL to 267 mg/dL in the boy and from 530 mg/dL to 182 mg/dL in the girl. These findings suggest that lipid-lowering therapy with statin may be considered in pediatric patients with compound heterozygous FH (hetero FH) before inducing LDL apheresis, and gene analysis for true diagnosis in pediatric patients with multiple xanthomas should be considered, though they appear to be hetero FH from the family history and lipid data of parents.
著者
Mariko Harada-Shiba Osamu Arisaka Akira Ohtake Tomoo Okada Hideki Suganami NK-104-PH 01 study registration group
出版者
一般社団法人 日本動脈硬化学会
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
vol.23, no.1, pp.48-55, 2016-01-06 (Released:2016-01-06)
参考文献数
14
被引用文献数
2 5 2

Aim: The purpose of this study was to evaluate the efficacy and safety of LIVALO® tablets (pitavastatin) in Japanese male children with heterozygous familial hypercholesterolemia (FH).Methods: A multicenter, randomized, double-blind, parallel study was conducted in 14 male children 10-15 years of age with heterozygous FH. Pitavastatin (1 mg/day or 2 mg/day) was administered orally for 52 weeks.The primary endpoint was the percent change in the LDL-cholesterol (LDL-C) concentrations from baseline to endpoint (repeated measures ANCOVA at Weeks 8 and 12). Secondary endpoints included the percentage of patients who achieved the target LDL-C concentration and percent changes in the levels of lipoprotein and lipid parameters at the visit performed at 52 weeks.Results: The percent change in LDL-C from baseline (mean 258 mg/dL for all patients) to the endpoint was -27.3% (95%CI; -34.0, -20.5) and -34.3% (95%CI; -41.0, -27.5) in the patients receiving 1 mg and 2 mg of pitavastatin, respectively. Stable reductions in the total cholesterol (TC), non-HDL cholesterol (non-HDL-C), apolipoprotein B (Apo-B) and LDL-C levels and non-HDL-C/HDL-C and Apo-B/Apo-A1 ratios were observed up to 52 weeks in both groups. One patient in each dose group (14%) reached the treatment target level of 130 mg/dL.Adverse events were observed in seven (100%) patients receiving 1 mg and five (71%) patients receiving 2 mg of pitavastatin, although none were considered related to the study treatment. One patient in the 1 mg group reported a musculoskeletal AE; however, it was attributed to recent excessive exercise.Conclusions: Pitavastatin significantly reduced the LDL-C levels and was well tolerated when administered at usual adult doses in 14 male children 10-15 years of age with heterozygous FH. Pitavastatin is a promising therapeutic agent for pediatric dyslipidemia with few safety concerns.