著者

Hayato Tada Hirofumi Okada 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

vol.85, no.11, pp.2073-2078, 2021-10-25 (Released:2021-10-25)

参考文献数

23

被引用文献数

1 24

---

Background:Recent studies suggest that cumulative exposure to low-density lipoprotein-cholesterol (LDL-C) leads to the development of atherosclerotic cardiovascular disease (ASCVD). However, few studies have investigated whether this link extends to individuals with familial hypercholesterolemia (FH), a relevant patient population.Methods and Results:We retrospectively investigated the health records of 1,050 patients with clinical FH diagnosis between April 1990 and March 2019. We used Cox proportional hazards models adjusted for established ASCVD risk factors to assess the association between cholesterol-year-score and major adverse cardiovascular events (MACEs), including death from any cause or hospitalization due to ASCVD events. Cholesterol-year-score was calculated as LDL-C max × [age at diagnosis/statin initiation] + LDL-C at inclusion × [age at inclusion − age at diagnosis/statin initiation]. The median follow-up period for MACE evaluation was 12.3 (interquartile range, 9.1–17.5) years, and 177 patients experienced MACEs during the observation period. Cholesterol-year-score was significantly associated with MACEs (hazard ratio, 1.35; 95% confidence interval, 1.07–1.53; P=0.0034, per 1,000 mg-year/dL), independent of other traditional risk factors including age and LDL-C, based on cross-sectional assessment. Cholesterol-year-score improved the discrimination ability of other traditional risk factors for ASCVD events (C-index, 0.901 vs. 0.889; P=0.00473).Conclusions:Cumulative LDL-C exposure was strongly associated with MACEs in Japanese patients with FH, warranting early diagnosis and treatment initiation in these patients.

著者

Hayato Tada Hirofumi Okada Atsushi Nohara Ryuji Toh Amane Harada Katsuhiro Murakami Takuya Iino Manabu Nagao Tatsuro Ishida Ken-ichi Hirata 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-22-0560, (Released:2022-11-26)

参考文献数

33

被引用文献数

4

---

Background: Recently, the function of high-density lipoprotein (HDL), rather than the HDL cholesterol (HDL-C) level, has been attracting more attention in risk prediction for coronary artery disease (CAD).Methods and Results: Patients with clinically diagnosed familial hypercholesterolemia (FH; n=108; male/female, 51/57) were assessed cross-sectionally. Serum cholesterol uptake capacity (CUC) levels were determined using our original cell-free assay. Linear regression was used to determine associations between CUC and clinical variables, including low-density lipoprotein cholesterol and the carotid plaque score. Multivariable logistic regression analysis was used to test factors associated with the presence of CAD. Among the 108 FH patients, 30 had CAD. CUC levels were significantly lower among patients with than without CAD (median [interquartile range] 119 [92–139] vs. 142 [121–165] arbitrary units [AU]; P=0.0004). In addition, CUC was significantly lower in patients with Achilles tendon thickness ≥9.0 mm than in those without Achilles tendon thickening (133 [110–157] vs. 142 [123–174] AU; P=0.047). Serum CUC levels were negatively correlated with the carotid plaque score (Spearman’s r=0.37; P=0.00018). Serum CUC levels were significantly associated with CAD, after adjusting for other clinical variables (odds ratio=0.86, 95% CI=0.76–0.96, P=0.033), whereas HDL-C was not.Conclusions: HDL function, assessed by serum CUC level, rather than HDL-C level, adds risk stratification information among FH patients.

著者

Hayato Tada Masa-aki Kawashiri Masakazu Yamagishi

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-17-0586, (Released:2017-07-01)

参考文献数

11

被引用文献数

1

著者

Hayato Tada Hirofumi Okada Atsushi Nohara Ryuji Toh Amane Harada Katsuhiro Murakami Takuya Iino Manabu Nagao Tatsuro Ishida Ken-ichi Hirata 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.87, no.6, pp.806-812, 2023-05-25 (Released:2023-05-25)

参考文献数

33

被引用文献数

4

---

Background: Recently, the function of high-density lipoprotein (HDL), rather than the HDL cholesterol (HDL-C) level, has been attracting more attention in risk prediction for coronary artery disease (CAD).Methods and Results: Patients with clinically diagnosed familial hypercholesterolemia (FH; n=108; male/female, 51/57) were assessed cross-sectionally. Serum cholesterol uptake capacity (CUC) levels were determined using our original cell-free assay. Linear regression was used to determine associations between CUC and clinical variables, including low-density lipoprotein cholesterol and the carotid plaque score. Multivariable logistic regression analysis was used to test factors associated with the presence of CAD. Among the 108 FH patients, 30 had CAD. CUC levels were significantly lower among patients with than without CAD (median [interquartile range] 119 [92–139] vs. 142 [121–165] arbitrary units [AU]; P=0.0004). In addition, CUC was significantly lower in patients with Achilles tendon thickness ≥9.0 mm than in those without Achilles tendon thickening (133 [110–157] vs. 142 [123–174] AU; P=0.047). Serum CUC levels were negatively correlated with the carotid plaque score (Spearman’s r=0.37; P=0.00018). Serum CUC levels were significantly associated with CAD, after adjusting for other clinical variables (odds ratio=0.86, 95% CI=0.76–0.96, P=0.033), whereas HDL-C was not.Conclusions: HDL function, assessed by serum CUC level, rather than HDL-C level, adds risk stratification information among FH patients.

著者

Shohei Yoshida Hayato Tada Tetsuo Nishikawa Tamami Nakagawa-Kamiya Takuya Nakahashi Kenji Sakai Kenji Sakata Masa-aki Kawashiri Masahito Yamada Masayuki Takamura

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

pp.3870-19, (Released:2019-12-26)

参考文献数

11

---

Transcatheter aortic valve implantation (TAVI) is widely accepted as the treatment for patient with severe aortic stenosis (AS) whose prognosis may be over one year; however, there is no consensus concerning extremely high-risk patients whose prognosis may not exceed one year. We herein report a highly frail patient with severe AS complicated with transthyretin-type cardiac amyloidosis who had a very poor prognosis. Given his condition, we treated him by percutaneous antegrade balloon aortic valvuloplasty (A-BAV) instead of TAVI. A-BAV may be a beneficial option for treating extremely high-risk severe AS patients, including those with cardiac amyloidosis.

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

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 62

---

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

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

Toyonobu Tsuda Takeshi Kato Keisuke Usuda Takashi Kusayama Soichiro Usui Kenji Sakata Kenshi Hayashi Masa-aki Kawashiri Masakazu Yamagishi Masayuki Takamura Takayuki Otsuka Shinya Suzuki Akio Hirata Masato Murakami Mitsuru Takami Masaomi Kimura Hidehira Fukaya Shiro Nakahara Wataru Shimizu Yu-ki Iwasaki Hiroshi Hayashi Tomoo Harada Ikutaro Nakajima Ken Okumura Junjiroh Koyama Michifumi Tokuda Teiichi Yamane Yukihiko Momiyama Kojiro Tanimoto Kyoko Soejima Noriko Nonoguchi Koichiro Ejima Nobuhisa Hagiwara Masahide Harada Kazumasa Sonoda Masaru Inoue Koji Kumagai Hidemori Hayashi Kazuhiro Satomi Yoshinao Yazaki Yuji Watari Masaru Arai Ryuta Watanabe Katsuaki Yokoyama Naoya Matsumoto Koichi Nagashima Yasuo Okumura on behalf of the AF Ablation Frontier Registry and 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

vol.87, no.7, pp.939-946, 2023-06-23 (Released:2023-06-23)

参考文献数

36

被引用文献数

5

---

Background: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13–0.70; P=0.004) than the medical therapy group.Conclusions: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

著者

Hayato Tada Mika Hori Kota Matsuki Masatsune Ogura Atsushi Nohara Masa-aki Kawashiri Mariko Harada-Shiba

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.62869, (Released:2021-07-01)

参考文献数

25

被引用文献数

5 18

---

Aim: The 2017 Japan Atherosclerosis Society (JAS) familial hypercholesterolemia (FH) criteria adopt a cut-off value of ≥ 9 mm of Achilles tendon thickness (ATT) detected by X-ray as one of the three key items. This threshold was determined based on an old data evaluating the ATT of 36 non-FH individuals that was published in 1977. Although the specificity of these clinical criteria is extremely high due to a strict threshold, there are a significant number of patients with FH whose ATT <9 mm. We aimed to determine a cut-off value of ATT detected by X-ray to differentiate FH and non-FH based on genetic diagnosis. Methods: The individuals (male/female=486/501) with full assessments of genetic analyses for FH-genes (LDLR and PCSK9), serum lipids, and ATT detected by X-ray at the Kanazawa University Hospital and National Cerebral and Cardiovascular Center Research Institute were included in this study. Receiver operating characteristic (ROC) analyses were conducted to determine a better cut-off value of ATT that predicts the pathogenic mutation of FH. Results: The ROC analyses revealed that the best cut-off values of ATT are 7.6 mm for male and 7.0 mm for female, with the sensitivities/specificities of 0.83/0.83 for male and 0.86/0.85 for female, respectively. If the thresholds of ATT of 8.0/7.5 mm and 7.5/7.0 mm were applied to the diagnosis of male/female FH, the sensitivities/specificities predicting the pathogenic mutation of FH by the 2017 JAS FH clinical criteria would be 0.82/0.90 and 0.85/0.88, respectively. Conclusions: These results suggest that the cut-off value of ATT detected by X-ray is obviously lower than 9.0 mm, which was adopted by the 2017 JAS FH clinical criteria.

著者

Hayato Tada Mika Hori Kota Matsuki Masatsune Ogura Atsushi Nohara Masa-aki Kawashiri Mariko Harada-Shiba

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.29, no.6, pp.816-824, 2022-06-01 (Released:2022-06-01)

参考文献数

25

被引用文献数

5 18

---

Aim: The 2017 Japan Atherosclerosis Society (JAS) familial hypercholesterolemia (FH) criteria adopt a cut-off value of ≥ 9 mm of Achilles tendon thickness (ATT) detected by X-ray as one of the three key items. This threshold was determined based on an old data evaluating the ATT of 36 non-FH individuals that was published in 1977. Although the specificity of these clinical criteria is extremely high due to a strict threshold, there are a significant number of patients with FH whose ATT <9 mm. We aimed to determine a cut-off value of ATT detected by X-ray to differentiate FH and non-FH based on genetic diagnosis.Methods: The individuals (male/female=486/501) with full assessments of genetic analyses for FH-genes (LDLR and PCSK9), serum lipids, and ATT detected by X-ray at the Kanazawa University Hospital and National Cerebral and Cardiovascular Center Research Institute were included in this study. Receiver operating characteristic (ROC) analyses were conducted to determine a better cut-off value of ATT that predicts the pathogenic mutation of FH. Results: The ROC analyses revealed that the best cut-off values of ATT are 7.6 mm for male and 7.0 mm for female, with the sensitivities/specificities of 0.83/0.83 for male and 0.86/0.85 for female, respectively. If the thresholds of ATT of 8.0/7.5 mm and 7.5/7.0 mm were applied to the diagnosis of male/female FH, the sensitivities/specificities predicting the pathogenic mutation of FH by the 2017 JAS FH clinical criteria would be 0.82/0.90 and 0.85/0.88, respectively.Conclusions: These results suggest that the cut-off value of ATT detected by X-ray is obviously lower than 9.0 mm, which was adopted by the 2017 JAS FH clinical criteria.

著者

Toyonobu Tsuda Takeshi Kato Keisuke Usuda Takashi Kusayama Soichiro Usui Kenji Sakata Kenshi Hayashi Masa-aki Kawashiri Masakazu Yamagishi Masayuki Takamura Takayuki Otsuka Shinya Suzuki Akio Hirata Masato Murakami Mitsuru Takami Masaomi Kimura Hidehira Fukaya Shiro Nakahara Wataru Shimizu Yu-ki Iwasaki Hiroshi Hayashi Tomoo Harada Ikutaro Nakajima Ken Okumura Junjiroh Koyama Michifumi Tokuda Teiichi Yamane Yukihiko Momiyama Kojiro Tanimoto Kyoko Soejima Noriko Nonoguchi Koichiro Ejima Nobuhisa Hagiwara Masahide Harada Kazumasa Sonoda Masaru Inoue Koji Kumagai Hidemori Hayashi Kazuhiro Satomi Yoshinao Yazaki Yuji Watari Masaru Arai Ryuta Watanabe Katsuaki Yokoyama Naoya Matsumoto Koichi Nagashima Yasuo Okumura on behalf of the AF Ablation Frontier Registry and 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-22-0461, (Released:2022-12-02)

参考文献数

36

被引用文献数

5

---

Background: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13–0.70; P=0.004) than the medical therapy group.Conclusions: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

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

Keiji Matsunaga Asako Mizobuchi Hai Ying Fu Shohei Ishikawa Hayato Tada Masa-aki Kawashiri Ichiro Yokota Tsuyoshi Sasaki Shigeru Ito Jun Kunikata Takashi Iwase Tomohiro Hirao Katsunori Yokoyama Yoichi Hoshikawa Takuji Fujisawa Kazushige Dobashi Takashi Kusaka Tetsuo Minamino

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.29, no.6, pp.839-849, 2022-06-01 (Released:2022-06-01)

参考文献数

21

被引用文献数

6 20

---

Aim: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan.Method: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals.Results: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL.Conclusion: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.

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

Yoshihiro Tanaka Satoko Matsuyama Hayato Tada Kenshi Hayashi Masayuki Takamura Masa-aki Kawashiri Rod Passman Philip Greenland

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-21-0278, (Released:2021-07-03)

参考文献数

39

被引用文献数

4

---

Background:Because it is unclear whether lower urinary tract symptoms (LUTS) are associated with cardiovascular disease (CVD) in the Japanese population, we explored the association in general Japanese men aged 55–75 years.Methods and Results:The cross-sectional study included male participants who had both national health checkup data and the International Prostate Symptom Score (IPSS) in the same calendar year between 2009 and 2017. LUTS severity was evaluated by IPSS. A robust Poisson regression model was used to assess the association between LUTS severity and the composite CVD outcome [coronary artery disease (CAD), stroke, or atrial fibrillation (AF)] and each component of the composite outcome. Prevalence ratio (PR) was adjusted for conventional cardiovascular risk factors. Of 16,781 male participants (mean age, 67±5 years), mild LUTS were observed in 9,243 (55.1%); moderate, 6,445 (38.4%); and severe, 1,093 (6.5%). Compared with the mild LUTS group, moderate LUTS [PR 1.18, 95% confidence interval (CI) 1.10–1.25, P<0.001] and severe LUTS (PR 1.38, 95% CI 1.24–1.53, P<0.001) were significantly associated with a higher prevalence of CVD. LUTS severity was associated with higher prevalence of CAD and stroke, but not AF.Conclusions:The severity of LUTS was associated with a higher prevalence of CVD, especially CAD and stroke, independent of conventional CVD risk factors.

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

Noboru Fujino Kenshi Hayashi Kenji Sakata Akihiro Nomura Masa-aki Kawashiri

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.82, no.11, pp.2699-2700, 2018-10-25 (Released:2018-10-25)

参考文献数

12

被引用文献数

1

著者

Kenji Sakata Tadatsugu Gamou Hayato Tada Kenshi Hayashi Hidekazu Ino Masakazu Yamagishi Masa-aki Kawashiri behalf of the MILLION Study Group

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.44255, (Released:2018-09-21)

参考文献数

25

被引用文献数

3

---

Aim: The prospective, randomized, multicenter Myocardial Ischemia Treated with Percutaneous Coronary Intervention and Plaque Regression by Lipid Lowering & Blood Pressure Controlling assessed by Intravascular Ultrasonography (MILLION) study demonstrated that combined treatment with atorvastatin and amlodipine enhanced coronary artery plaque regression. Although the baseline high-sensitive C-reactive protein (hs-CRP) reportedly plays an important role in atherogenesis, few data exist regarding the relationship between hs-CRP and plaque regression in patients receiving a combined atorvastatin and amlodipine therapy.Methods: A total of 68 patients (male, 55; mean age, 64.2 years) with baseline and follow-up 3-dimensional intravascular ultrasound examinations in the MILLION study were stratified by baseline hs-CRP level quartiles. The serial measurements of lipid, blood pressure, and percentage changes in the plaque volume were compared between the groups, and the factors associated with the percentage change in the plaque volume were assessed.Results: There were no significant between-group differences in the extent of change in low-density lipoprotein cholesterol (LDL-C) or systolic and diastolic blood pressure after 18–24 months of treatment. The percentage change in the plaque volume showed a linear association with the baseline hs-CRP (p for trend <0.05); however, there was no correlation with changes in LDL-C or systolic and diastolic blood pressure. In the multiple regression analysis, the baseline hs-CRP level was independently associated with the percentage change in the plaque volume (β=0.29, p=0.022).Conclusions: Coronary plaque regression was associated with the baseline hs-CRP level in patients treated with a combined lipid- and blood pressure-lowering therapy.

著者

Hayato Tada Atsushi Nohara Akihiro Inazu Nagahiko Sakuma Hiroshi Mabuchi Masa-aki Kawashiri

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.RV17024, (Released:2018-07-20)

参考文献数

31

被引用文献数

87

---

Sitosterolemia is a rare inherited disease characterized by increased levels of plant sterols, such as sitosterol. The cause of this disease is ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively) gene mutations. Recent advances in genetics have revealed that the prevalence of subjects with deleterious mutations in ABCG5 and/or ABCG8 genes could be more than 1 in ~200,000 individuals among the general population. Furthermore, accumulated evidence, including infantile cases exhibiting progression/regression of systemic xanthomas associated with LDL cholesterol levels, have shown that the elevation of LDL cholesterol seems to be the major cause of development of atherosclerosis and not the elevation of sitosterol. Regarding therapies, LDL apheresis, as well as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, could be useful for sitosterolemia, in addition to ezetimibe and/or colestimide. In this study, we provide the current understanding and future perspectives of sitosterolemia, which is currently considered an extremely rare disorder but is expected to be much more prevalent in clinical settings.