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
3

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
Tamio Teramoto Masahiko Kobayashi Hiromi Tasaki Hiroaki Yagyu Toshinori Higashikata Yoshiharu Takagi Kiyoko Uno Marie T. Baccara-Dinet Atsushi Nohara
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-16-0387, (Released:2016-07-22)
参考文献数
30
被引用文献数
3 24

Background:The ODYSSEY Japan study was designed to demonstrate the reduction in low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on to existing lipid-lowering therapy in Japanese patients with heterozygous familial hypercholesterolemia (heFH) or non-FH at high cardiovascular risk who require additional pharmacological management to achieve their LDL-C treatment goal (<2.6 or <3.1 mmol/L, depending on risk category).Methods and Results:This randomized, double-blind, parallel-group, 52-week study was conducted in Japan. Patients (n=216) with heFH, non-FH at high cardiovascular risk with coronary disease, or classified as category III were enrolled. The prespecified safety analysis was done after the last patient completed 52 weeks. Patients were randomized (2:1, alirocumab:placebo) with stratification for heFH to s.c. alirocumab (75 mg every 2 weeks [Q2 W] with increase to 150 mg if week 8 LDL-C ≥2.6/3.1 mmol/L) or placebo for 52 weeks plus stable statin therapy. At week 24, mean±SE change in LDL-C from baseline was –62.5±1.3% in the alirocumab group and 1.6±1.8% in the placebo group (difference, –64.1±2.2%; P<0.0001); the reduction was sustained to week 52 (alirocumab, –62.5±1.4%; placebo, –3.6±1.9%). No patterns were evident between treatment groups for adverse events at 52 weeks.Conclusions:In high-risk Japanese patients with hypercholesterolemia on stable statin therapy, alirocumab markedly reduced LDL-C vs. placebo and was well tolerated over 52 weeks.
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

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
Kenshi Hayashi Toyonobu Tsuda Akihiro Nomura Noboru Fujino Atsushi Nohara Kenji Sakata Tetsuo Konno Chiaki Nakanishi Hayato Tada Yoji Nagata Ryota Teramoto Yoshihiro Tanaka Masa-aki Kawashiri Masakazu Yamagishi on behalf of the Hokuriku-Plus AF Registry Investigators
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-17-1085, (Released:2018-03-01)
参考文献数
22

Background:B-type natriuretic peptide (BNP) may be a predictor of stroke risk in patients with nonvalvular atrial fibrillation (NVAF); because heart failure is associated with the incidence of stroke in AF patients. However, limited data exist regarding the association between BNP at baseline and risks of thromboembolic events (TE) and death in NVAF patients.Methods and Results:We prospectively studied 1,013 NVAF patients (725 men, 72.8±9.7 years old) from the Hokuriku-plus AF Registry to determine the relationship between BNP at baseline and prognosis among Japanese NVAF patients. During the follow-up period (median, 751 days); 31 patients experienced TE and there were 81 cases of TE/all-cause death. For each endpoint we constructed receiver-operating characteristic curves that gave cutoff points of BNP for TE (170 pg/mL) and TE/all-cause death (147 pg/mL). Multivariate analysis with the Cox-proportional hazards model indicated that high BNP was significantly associated with risks of TE (hazard ratio [HR] 3.86; 95% confidence interval [CI] 1.83–8.67; P=0.0003) and TE/all-cause death (HR 2.27; 95% CI 1.45–3.56; P=0.0003). Based on the C-index and net reclassification improvement, the addition of BNP to CHA2DS2-VASc statistically improved the prediction of TE.Conclusions:In a real-world cohort of Japanese NVAF patients, high BNP was significantly associated with TE and death. Plasma BNP might be a useful biomarker for these adverse clinical events.
著者
Hayato Tada Masa-aki Kawashiri Taiji Yoshida Ryota Teramoto Atsushi Nohara Tetsuo Konno Akihiro Inazu Hiroshi Mabuchi Masakazu Yamagishi Kenshi Hayashi
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-15-0999, (Released:2015-12-02)
参考文献数
39
被引用文献数
7 24

Background:It has been shown that serum lipoprotein(a) [Lp(a)] is elevated in familial hypercholesterolemia (FH) with mutation(s) of the LDL receptor (LDLR) gene. However, few data exist regarding Lp(a) levels in FH with gain-of-function mutations of the PCSK9 gene.Methods and Results:We evaluated 42 mutation-determined heterozygous FH patients with aPCSK9gain-of-function mutation (FH-PCSK9, mean age 52, mean LDL-C 235 mg/dl), 198 mutation-determined heterozygous FH patients with aLDLRmutation (FH-LDLR, mean age 44, mean LDL-C 217 mg/dl), and 4,015 controls (CONTROL, mean age 56, mean LDL-C 109 mg/dl). We assessed their Lp(a), total cholesterol, triglycerides, HDL-C, LDL-C, use of statins, presence of hypertension, diabetes, chronic kidney disease, smoking, body mass index (BMI) and coronary artery disease (CAD). Multiple regression analysis showed that HDL-C, use of statins, presence of hypertension, smoking, BMI, and Lp(a) were independently associated with the presence of CAD. Under these conditions, the serum levels of Lp(a) in patients with FH were significantly higher than those of the CONTROL group regardless of their causative genes, among the groups propensity score-matched (median Lp(a) 12.6 mg/dl [IQR:9.4–33.9], 21.1 mg/dl [IQR:11.7–34.9], and 5.0 mg/dl [IQR:2.7–8.1] in the FH-LDLR, FH-PCSK9, and CONTROL groups, respectively, P=0.002 for FH-LDLR vs. CONTROL, P=0.002 for FH-PCSK9 vs. CONTROL).Conclusions:These data demonstrate that serum Lp(a) is elevated in patients with FH caused by PCSK9 gain-of-function mutations to the same level as that in FH caused by LDLR mutations.
著者
Shigetsugu Tsuji Atsushi Nohara Yoshiaki Hayashi Isao Yoshida Rie Oka Tadashi Moriuchi Tomomi Hagishita Susumu Miyamoto Ayako Suzuki Toshihide Okada Masakazu Yamagishi
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.25825, (Released:2014-10-23)
参考文献数
42

Aim: The role of gastrectomy in glycemic control has been established in the current era of bariatric surgery for obesity. Gastrectomy in obese patients is associated with increased levels of high-density lipoprotein cholesterol (HDL-C). However, limited data on the effects of gastrectomy in nonobese patients are available. We herein investigated the long-term plasma lipid changes in nonobese patients who had undergone gastrectomy. Methods: Patients were enrolled as part of routine healthcare examinations from 1984 to 2003. Preoperative and postoperative data from patients who had undergone curative gastrectomy were analyzed for up to 10 years postoperatively. Three age- and sex-matched controls were assigned to each case. Results: Sixty-four nonobese patients without diabetes mellitus or a history of having taken lipidlowering drugs who underwent curative gastrectomy during the study period were enrolled (60 subtotal gastrectomies, four total gastrectomies). The median follow-up period was 7.6 years. The mean body mass index was 9.6% lower one year after gastrectomy (p<0.01), then plateaued with a slight recovery. Intriguingly, the preoperative HDL-C level was 21% higher one year after gastrectomy (p<0.01), increased by another 30% six years after gastrectomy and remained at this level for the rest of the follow-up period. No significant changes in the HDL-C level were observed in the controls. The degree of HDL-C elevation was consistently significant, irrespective of the baseline triglyceride level, HDL-C level or body weight. Conclusions: Gastrectomy in nonobese patients was associated with consistent and distinct long-term HDL-C elevations and body mass index reductions.
著者
Akihiro Nomura Hayato Tada Atsushi Nohara Masa-aki Kawashiri Masakazu Yamagishi
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.42960, (Released:2018-01-20)
参考文献数
27
被引用文献数
2

Aim: Sitosterolemia is an extremely rare, autosomal recessive disease characterized by high plasma cholesterols and plant sterols because of increased absorption of dietary cholesterols and sterols from the intestine, and decreased excretion from biliary tract. Previous study indicated that sitosterolemic patients might be vulnerable to post-prandial hyperlipidemia, including high remnant-like lipoprotein particles (RLP) level. Here we evaluate whether a loading dietary fat increases a post-prandial RLP cholesterol level in sitosterolemic patients compared to heterozygous familial hypercholesterolemic patients (FH).Methods: We recruit total of 20 patients: 5 patients with homozygous sitosterolemia, 5 patients with heterozygous sitosterolemia, and 10 patients with heterozygous FH as controls from May 2015 to March 2018 at Kanazawa University Hospital, Japan. All patients receive Oral Fat Tolerance Test (OFTT) cream (50 g/body surface area square meter, orally only once, and the cream includes 34% of fat, 74 mg of cholesterol, and rich in palmitic and oleic acids. The primary endpoint is the change of a RLP cholesterol level after OFTT cream loading between sitosterolemia and FH. We measure them at baseline, and 2, 4, and 6 hours after the oral fat loading.Results: This is the first study to evaluate whether sitosterolemia patients have a higher post-prandial RLP cholesterol level compared to heterozygous FH patients.Conclusion: The result may become an additional evidence to restrict dietary cholesterols for sitosterolemia. This study is registered at University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN000020330).