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
被引用文献数
30

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
Toyonobu Tsuda Kenshi Hayashi Takeshi Kato Takashi Kusayama Yoichiro Nakagawa Akihiro Nomura Hayato Tada Soichiro Usui Kenji Sakata Masa-aki Kawashiri Noboru Fujino Masakazu Yamagishi Masayuki Takamura 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-23-0418, (Released:2023-10-20)
参考文献数
37
被引用文献数
1

Background: The prognostic effect of concomitant hypertrophic cardiomyopathy (HCM) on adverse events in patients with atrial fibrillation (AF) has not been evaluated in a multicenter prospective cohort study in Japan.Methods and Results: Using the Hokuriku-Plus AF Registry, 1,396 patients with nonvalvular AF (1,018 men, 72.3±9.7 years old) were assessed prospectively; 72 (5.2%) had concomitant HCM. During a median follow-up of 5.0 years (interquartile range 3.5–5.3 years), 79 cases of thromboembolism (1.3 per 100 person-years) and 192 of heart failure (HF) (3.2 per 100 person-years) occurred. Kaplan-Meier analysis revealed that the HCM group had a significantly greater incidence of thromboembolism (P=0.002 by log-rank test) and HF (P<0.0001 by a log-rank test) than the non-HCM group. The Cox proportional hazards model demonstrated that persistent AF (adjusted hazard ratio 2.98, 95% confidence interval 1.56–6.21), the CHA2DS2-VASc score (1.35, 1.18–1.54), and concomitant HCM (2.48, 1.16–4.79) were significantly associated with thromboembolism. Conversely, concomitant HCM (2.81, 1.72–4.43), older age (1.07, 1.05–1.10), lower body mass index (0.95, 0.91–0.99), a history of HF (2.49, 1.77–3.52), and lower left ventricular ejection fraction (0.98, 0.97–0.99) were significantly associated with the development of HF.Conclusions: Concomitant HCM predicts the incidence of thromboembolism and HF in AF patients.
著者
Hayato Tada Akihiro Nomura Masatsune Ogura Katsunori Ikewaki Yasushi Ishigaki Kyoko Inagaki Kazuhisa Tsukamoto Kazushige Dobashi Kimitoshi Nakamura Mika Hori Kota Matsuki Shizuya Yamashita Shinji Yokoyama Masa-aki Kawashiri Mariko Harada-Shiba on behalf of the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Desease of the Ministry of Health Labour and Welfare of Japan
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
pp.RV17052, (Released:2021-04-28)
参考文献数
56
被引用文献数
36

Sitosterolemia is an inherited metabolic disorder characterized by increased levels of plant sterols, such as sitosterol. This disease is caused by loss-of-function genetic mutations in ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively), both of which play important roles in selective excretion of plant sterols from the liver and intestine, leading to failure to prevent absorption of food plant sterols. This disorder has been considered to be extremely rare. However, accumulated clinical data as well as genetics suggest the possibility of a much higher prevalence. Its clinical manifestations resemble those observed in patients with familial hypercholesterolemia (FH), including tendon xanthomas, hyper LDL-cholesterolemia, and premature coronary atherosclerosis. We provide an overview of this recessive genetic disease, diagnostic as well as therapeutic tips, and the latest diagnostic criteria in Japan.
著者
Hayato Tada Hirofumi Okada Akihiro Nomura Satoshi Yashiro Atsushi Nohara Yasushi Ishigaki Masayuki Takamura Masa-aki Kawashiri
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.83, no.9, pp.1917-1924, 2019-08-23 (Released:2019-08-23)
参考文献数
21
被引用文献数
55 55

Background:A substantial proportion of patients clinically diagnosed as having familial hypercholesterolemia (FH) do not manifest causative mutation(s) in the FH genes such asLDLR,APOB, andPCSK9. We aimed to evaluate the effect of rare and deleterious mutation(s) inABCG5/ABCG8on hyper-low-density lipoprotein (LDL) cholesterolemia in individuals who meet the clinical criteria for FH.Methods and Results:We compared the LDL cholesterol (LDL-C) values among 487 subjects with FH; the subjects were grouped according to the presence of mutation(s) in FH andABCG5/ABCG8genes. We identified 276 individuals with a deleterious mutation in 1 FH gene (57%, monogenic FH), but found no causative mutations in 156 individuals (32%, mutation-negative). A total of 37 individuals had deleterious mutations inABCG5orABCG8, but not in FH genes (8%,ABCG5/ABCG8mutation carriers). Among these, 3 individuals had sitosterolemia (0.6%) with double mutations. We also identified 18 individuals with deleterious mutations in an FH gene andABCG5orABCG8(4%,ABCG5/ABCG8-oligogenic FH). Subjects without mutations had significantly higher polygenic scores than those in any other groups. LDL-C levels in oligogenic FH subjects were significantly higher than in the monogenic FH subjects. Moreover, sitosterol/lathosterol levels were significantly affected by those mutations.Conclusions:The results suggested that rare and deleterious mutations inABCG5/ABCG8contribute substantially to mimicking and exacerbation of the FH phenotype.
著者
Hayato Tada Hirofumi Okada Akihiro Nomura Soichiro Usui Kenji Sakata Atsushi Nohara Masakazu Yamagishi Masayuki Takamura Masa-aki Kawashiri
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-20-0901, (Released:2020-12-03)
参考文献数
21
被引用文献数
11

Background:This study is aimed to compare the efficacy of the 2017 Japan Atherosclerosis Society (JAS) familial hypercholesterolemia (FH) criteria, which focuses on only 3 essential clinical manifestations, with that of Dutch Lipid Clinic Network (DLCN) FH criteria, which adopts a scoring system of multiple elements.Methods and Results:A total of 680 Japanese dyslipidemic participants (51% men) were enrolled between 2006 and 2018, all of whom had full evaluations of low-density lipoprotein (LDL) cholesterol, Achilles tendon X-rays, family history records, and genetic analysis of FH-associated genes (LDLR,APOB, andPCSK9). Predictive values for the existence of FH mutations by both clinical criteria were evaluated. Overall, 173 FH patients were clinically diagnosed by using the 2017 JAS criteria and 100, 57, 156, and 367 subjects were also diagnosed as having definite, probable, possible, and unlikely FH by the DLCN FH criteria, respectively. The positive and negative likelihood ratio predicting the presence of FH mutations by using the 2017 JAS FH criteria were 19.8 and 0.143, respectively; whereas, using the DLCN criteria of definite, probable, and possible FH, the ratios were 29.2 and 0.489, 9.70 and 0.332, and 3.43 and 0.040, respectively.Conclusions:Among Japanese patients, the JAS 2017 FH criteria is considered superior to diagnose FH mutation-positive patients and simultaneously rule out FH mutation-negative patients compared with the DLCN FH criteria.
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
7

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).