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
2

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
Miyako Yuasa-Kawase Daisaku Masuda Taiji Yamashita Ryota Kawase Hajime Nakaoka Miwako Inagaki Kazuhiro Nakatani Kazumi Tsubakio-Yamamoto Tohru Ohama Akifumi Matsuyama Makoto Nishida Masato Ishigami Toshiharu Kawamoto Issei Komuro Shizuya Yamashita
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.19, no.3, pp.263-275, 2012 (Released:2012-03-26)
参考文献数
48
被引用文献数
9 17

Aim: The clustering of dyslipidemia, impaired glucose tolerance and hypertension increases the morbidity and mortality from cardiovascular events. A class B scavenger receptor, CD36, is a receptor for oxidized LDL and a transporter of long-chain fatty acids. Because of the impaired uptake of oxidized LDL in CD36-deficient macrophages and from the results of CD36 knockout mice, CD36 deficiency (CD36-D) was supposed to be associated with reduced risks for coronary artery disease (CAD); however, CD36-D patients are often accompanied by a clustering of coronary risk factors. The current study aimed to investigate the morbidity and severity of cardiovascular diseases in CD36-D patients.Methods: By screening for CD36 antigen on platelets and monocytes using FACS or the absent myocardial accumulation of 123I-BMIPP by scintigraphy, 40 patients with type I CD36-D were collected, the morbidity of CAD and their features of atherosclerotic cardiovascular diseases were observed. Screening for CD36-D in both CAD patients (n =319) and healthy subjects (n =1,239) were underwent.Results: The morbidity of CAD was significantly higher in CD36-D patients than in the general population; 50% of patients (20 out of 40) had CAD identified by BMIPP scintigraphy and 37.5% (3 out of 8) by FACS screening, respectively. Three representative CD36-D cases demonstrated severe CAD and atherosclerosis. The frequency of CD36-D was three times higher in CAD patients than in healthy subjects (0.9% vs 0.3%, p <0.0001).Conclusion: The morbidity of CAD is significantly higher in CD36-D patients suffering from severe atherosclerosis, implying that the status of CD36-D might be atherogenic.
著者
Atsushi Hirayama Narimon Honarpour Masayuki Yoshida Shizuya Yamashita Fannie Huang Scott M. Wasserman Tamio Teramoto
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-14-0130, (Released:2014-03-21)
参考文献数
38
被引用文献数
30 50 26

Background: YUKAWA is a 12-week, randomized, double-blind, placebocontrolled, phase 2 study evaluating the efficacy and safety of evolocumab (AMG 145) in statin-treated Japanese patients at high cardiovascular risk. Methods and Results: 310 eligible patients receiving stable statin (±ezetimibe) therapy were randomized to 1 of 6 treatments: placebo every 2 weeks (Q2W) or monthly (QM), evolocumab 70mg or 140mg Q2W, or evolocumab 280mg or 420mg QM. The primary endpoint was the percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) measured by preparative ultracentrifugation (UC). Secondary endpoints included percentage changes in other lipid parameters and the proportion of patients with LDL-C <1.8mmol/L. Mean (SD) age was 62 (10) years; 37% were female; and the mean (SD) baseline LDL-C was 3.7 (0.5) mmol/L (by UC). Mean (SE) changes vs. placebo in LDL-C were greatest in the high-dose groups: −68.6 (3.0) % and −63.9 (3.2) % with 140mg Q2W and 420mg QM dosing, respectively. Up to 96% of evolocumab-treated patients achieved LDL-C <1.8mmol/L. Adverse events (AEs) were more frequent in evolocumab (51%) vs. placebo (38%) patients; 4 patients taking evolocumab discontinued treatment because of an AE. There were no significant differences in AE rates based on dose or dose frequency. Conclusions: In Japanese patients at high cardiovascular risk with hypercholesterolemia on stable statin therapy, evolocumab significantly reduced LDL-C and was well tolerated during this 12-week study.