研究者詳細 - 平田　あや

論文 - 平田　あや

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Metabolomics profiles alterations in cigarette smokers and heated tobacco product users

Harada, S; Ohmomo, H; Matsumoto, M; Sata, M; Iida, M; Hirata, A; Miyagawa, N; Kuwabara, K; Kato, S; Toki, R; Edagawa, S; Sugiyama, D; Sato, A; Hirayama, A; Sugimoto, M; Soga, T; Tomita, M; Shimizu, A; Okamura, T; Takebayashi, T

Ｊｏｕｒｎａｌ　ｏｆ　Ｅｐｉｄｅｍｉｏｌｏｇｙ（日本疫学会） 34 （ 9 ） 403 - 410 2024年09月

ISSN 09175040

Background: Heated tobacco products (HTPs) have gained global popularity, but their health risks remain unclear. Therefore, the current study aimed to identify plasma metabolites associated with smoking and HTP use in a large Japanese population to improve health risk assessment.Methods: Metabolomics data from 9,922 baseline participants of the Tsuruoka Metabolomics Cohort Study (TMCS) were analyzed to determine the association between smoking habits and plasma metabolites. Moreover, alterations in smoking-related metabolites among HTP users were examined based on data obtained from 3,334 participants involved from April 2018 to June 2019 in a follow-up survey.Results: Our study revealed that cigarette smokers had metabolomics profiles distinct from never smokers, with 22 polar metabolites identified as candidate biomarkers for smoking. These biomarker profiles of HTP users were closer to those of cigarette smokers than those of never smokers. The concentration of glutamate was higher in cigarette smokers, and biomarkers involved in glutamate metabolism were also associated with cigarette smoking and HTP use. Network pathway analysis showed that smoking was associated with the glutamate pathway, which could lead to endothelial dysfunction and atherosclerosis of the vessels.Conclusion: Our study showed that the glutamate pathway is affected by habitual smoking. These changes in the glutamate pathway may partly explain the mechanism by which cigarette smoking causes cardiovascular disease. HTP use was also associated with glutamate metabolism, indicating that HTP use may contribute to the development of cardiovascular disease through mechanisms similar to those in cigarette use.

Risk Factors for Heart Failure and Coronary Artery Disease Mortality Based on the National Vital Statistics During a 25-Year Follow-up in Japan　― NIPPON DATA90 ―

Kubo Kota, Hirata Aya, Kadota Aya, Harada Akiko, Nakamura Yasuyuki, Hayakawa Takehito, Takashima Naoyuki, Fujiyoshi Akira, Okami Yukiko, Kita Yoshikuni, Okayama Akira, Miura Katsuyuki, Ueshima Hirotsugu, Okamura Tomonori, for the NIPPON DATA90 Research Group

Circulation Journal （一般社団法人日本循環器学会） 88 （ 9 ） 1478 - 1487 2024年08月

ISSN 13469843

Background: Prevention of heart failure (HF) is a public health issue. Using the National Vital Statistics, we explored risk factors for HF and coronary artery disease (CAD) mortality.Methods and Results: Altogether, 7,556 Japanese individuals aged ≥30 years in 1990 were followed over 25 years; of these, 139 and 154 died from HF and CAD, respectively. In multivariable Cox proportional hazard analysis, common risk factors for CAD and HF mortality were hypertension (hazard ratio [HR] 1.48 [95% confidence interval {CI} 1.00–2.20] and 2.31 [95% CI 1.48–3.61], respectively), diabetes (HR 2.52 [95% CI 1.63–3.90] and 2.07 [95% CI 1.23–3.50], respectively), and current smoking (HR 2.05 [95% CI 1.27–3.31) and 1.86 [95% CI 1.10–3.15], respectively). Specific risk factors for CAD were male sex, chronic kidney disease, history of cardiovascular disease, and both abnormal T and Q waves, with HRs (95% CIs) of 1.75 (1.05–2.92), 1.78 (1.19–2.66), 2.50 (1.62–3.88), and 11.4 (3.64–36.0), respectively. Specific factors for HF were current drinking (HR 0.43; 95% CI 0.24–0.78) and non-high-density lipoprotein cholesterol (non-HDL-C; HR 0.81; 95% CI 0.67–0.98). There was an inverse association between non-HDL-C and HF in those aged ≥65 years (HR 0.71; 95% CI 0.56–0.90), but not in those aged <65 years.Conclusions: We identified common risk factors for HF and CAD deaths; a history of cardiovascular disease was a specific risk for CAD.

お薬手帳と比較した自記式質問紙による服薬情報の妥当性研究

矢嶋里菜, 松元美奈子, 飯田美穂, 原田成, 澁木琢磨, 平田あや, 桑原和代, 宮川尚子, 中村智徳, 岡村智教, 武林亨

日本公衆衛生雑誌（日本公衆衛生学会） 71 （ 8 ） 430 - 437 2024年08月

ISSN 05461766

目的　疫学研究において服薬情報は自記式質問紙を用いて得ることが多いが，高齢者を対象に妥当性を検討した報告は希少である。本研究の目的は自己申告による服薬情報の妥当性をお薬手帳と比較して検討することである。方法　2019–2020年度に山形県鶴岡市の一般地域在住高齢者を対象として実施されたコホート研究の参加者370人において，自記式質問紙による薬剤情報をお薬手帳の薬剤情報と比較した。解析対象薬剤は降圧薬，脂質異常症用薬，抗心筋梗塞・抗狭心症薬，糖尿病用薬，抗リウマチ薬，骨粗鬆症・骨代謝改善薬，便秘薬，胃薬，抗不安・抗うつ薬，抗認知症薬，喘息治療薬，アレルギー治療薬，抗血栓薬，ステロイド，甲状腺疾患治療薬，解熱・鎮痛・抗炎症薬である。お薬手帳の薬剤情報を基準とし，調査日より前90日以内に服薬中で，28日以上処方されている内服薬，骨粗鬆症・骨代謝改善薬は注射薬も対象とした。ATCコード（解剖治療化学分類法）に基づいて薬効分類を行い，各薬剤の感度，特異度，カッパ係数を計算した。お薬手帳の持参がなかった者は「解析対象薬剤の使用なし」と定義し解析に組み込んだ。結果　男性146人，女性224人，平均年齢（標準偏差）は73.3（4.0）歳であった。各薬剤の感度と特異度は，降圧薬（0.97, 0.97），脂質異常症用薬（0.93, 0.98），抗心筋梗塞・抗狭心症薬（0.24, 0.99），糖尿病用薬（0.94, 1.00），抗リウマチ薬（1.00, 1.00），骨粗鬆症・骨代謝改善薬（0.82, 0.99），便秘薬（0.71, 0.98），胃薬（0.63, 0.97），抗不安薬・抗うつ薬（0.36, 1.00），抗認知症薬（0.67, 1.00），喘息治療薬（0.67, 0.98），アレルギー治療薬（0.57, 0.99），抗血栓薬（0.88, 0.98），副腎皮質ホルモン製剤（0.80, 0.99），甲状腺疾患治療薬（1.00, 1.00），解熱・鎮痛・抗炎症薬（0.75, 0.96）であった。結論　薬剤の種類により感度，特異度が異なっていた。とくに感度が8割を超える薬剤（降圧薬，脂質異常症用薬，糖尿病用薬，抗リウマチ薬，骨粗鬆症・骨代謝改善薬，抗血栓薬，副腎皮質ホルモン製剤，甲状腺疾患治療薬）では，高齢者においても自己申告による服薬情報の収集は有用であることが示唆された。

Study Profile of the Tsuruoka Metabolomics Cohort Study (TMCS)

Harada, S; Iida, M; Miyagawa, N; Hirata, A; Kuwabara, K; Matsumoto, M; Okamura, T; Edagawa, S; Kawada, Y; Miyake, A; Toki, R; Akiyama, M; Kawai, A; Sugiyama, D; Sato, Y; Takemura, R; Fukai, K; Ishibashi, Y; Kato, S; Kurihara, A; Sata, M; Shibuki, T; Takeuchi, A; Kohsaka, S; Sawano, M; Shoji, S; Izawa, Y; Katsumata, M; Oki, K; Takahashi, S; Takizawa, T; Maruya, H; Nishiwaki, Y; Kawasaki, R; Hirayama, A; Ishikawa, T; Saito, R; Sato, A; Soga, T; Sugimoto, M; Tomita, M; Komaki, S; Ohmomo, H; Ono, K; Otsuka-Yamasaki, Y; Shimizu, A; Sutoh, Y; Hozawa, A; Kinoshita, K; Koshiba, S; Kumada, K; Ogishima, S; Sakurai-Yageta, M; Tamiya, G; Takebayashi, T

Ｊｏｕｒｎａｌ　ｏｆ　Ｅｐｉｄｅｍｉｏｌｏｇｙ（日本疫学会） 34 （ 8 ） 393 - 401 2024年08月

ISSN 09175040

The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35–74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study uses an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants, and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability and functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women’s health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.

Evaluation of Medication Adherence Among Prevalent Users in Hypertension, Dyslipidemia, and Diabetes Using Health Insurance Claims: A Population-Based Cohort Study in Japan

Matsumoto, M; Harada, S; Ikuta, H; Iida, M; Kato, S; Sata, M; Shibuki, T; Ishibashi, Y; Miyagawa, N; Hisamatsu, M; Hirata, A; Kuwabara, K; Takeuchi, A; Sugiyama, D; Suzuki, S; Nakamura, T; Okamura, T; Takebayashi, T

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY 33 （ 8 ） 2024年08月

ISSN 1053-8569

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Clinical Practice for Acute Heart Failure in Japan From the Nationwide Registry

Hirata, A; Hirata, T

CIRCULATION JOURNAL （一般社団法人日本循環器学会） 88 （ 8 ） 1274 - 1275 2024年07月

ISSN 13469843

Association of Nonalcoholic Fatty Liver Disease with Arterial Stiffness and its Metabolomic Profiling in Japanese Community-Dwellers

Hirata, A; Harada, S; Iida, M; Kurihara, A; Fukai, K; Kuwabara, K; Kato, S; Matsumoto, M; Sata, M; Miyagawa, N; Toki, R; Edagawa, S; Sugiyama, D; Sato, A; Hirayama, A; Sugimoto, M; Soga, T; Tomita, M; Okamura, T; Takebayashi, T

Ｊｏｕｒｎａｌ　ｏｆ　Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ　ａｎｄ　Ｔｈｒｏｍｂｏｓｉｓ（一般社団法人日本動脈硬化学会） 31 （ 7 ） 1031 - 1047 2024年07月

ISSN 13403478

Aims: Nonalcoholic fatty liver disease (NAFLD) is known to be associated with atherosclerosis. This study focused on upstream changes in the process by which NAFLD leads to atherosclerosis. The study aimed to confirm the association between NAFLD and the cardio-ankle vascular index (CAVI), an indicator of subclinical atherosclerosis, and explore metabolites involved in both by assessing 94 plasma polar metabolites.Methods: A total of 928 Japanese community-dwellers (306 men and 622 women) were included in this study. The association between NAFLD and CAVI was examined using a multivariable regression model adjusted for confounders. Metabolites commonly associated with NAFLD and CAVI were investigated using linear mixed-effects models in which batch numbers of metabolite measurements were used as a random-effects variable, and false discovery rate-adjusted p-values were calculated. To determine the extent to which these metabolites mediated the association between NAFLD and CAVI, mediation analysis was conducted.Results: NAFLD was positively associated with CAVI (coefficients [95% Confidence intervals (CI)]=0.23 [0.09–0.37]; p=0.001). A total of 10 metabolites were involved in NAFLD and CAVI, namely, branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), aromatic amino acids (AAAs; tyrosine and tryptophan), alanine, proline, glutamic acid, glycerophosphorylcholine, and 4-methyl-2-oxopentanoate. Mediation analysis showed that BCAAs mediated more than 20% of the total effect in the association between NAFLD and CAVI.Conclusions: NAFLD was associated with a marker of atherosclerosis, and several metabolites related to insulin resistance, including BCAAs and AAAs, could be involved in the process by which NAFLD leads to atherosclerosis.

Is renal function the key to disease risk management in elevated homocysteine levels?

Hirata, A

HYPERTENSION RESEARCH 47 （ 7 ） 1976 - 1977 2024年07月

ISSN 0916-9636

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Smoking is associated with impaired long-term quality of life in elderly people: a 22-year cohort study in NIPPON-DATA 90.

Liu, YW; Okamura, T; Hirata, A; Sato, Y; Hayakawa, T; Kadota, A; Kondo, K; Ohkubo, T; Miura, K; Okayama, A; Ueshima, H

Ｊｏｕｒｎａｌ　ｏｆ　Ｅｐｉｄｅｍｉｏｌｏｇｙ（日本疫学会） 34 （ 6 ） 265 - 269 2024年06月

ISSN 09175040

Background: Whether smoking is associated with worse quality of life (QoL) or not is relatively controversial. The current study is to investigate the relationship between smoking and subjective QoL in a long cohort study.Methods: The NIPPON DATA 90 project collected 8,383 community residents in 300 randomly selected areas as baseline data in 1990, administered four follow-up QoL surveys, and evaluated mortality statistics. We conducted multinomial logistic regression analysis to compare past smokers and current smokers to never smokers, with impaired QoL and mortality as outcomes.Results: In four follow-ups, QoL data was collected from 2,035, 2,252, 2,522, and 3,280 participants in 1995, 2000, 2005, and 2012, respectively. In the 1995 follow-up, current smoking at baseline was not associated with worse QoL. In 2000 and 2005 follow-ups, smoking was significantly associated with worse QoL (odds ratio [OR] 2.1; 95% confidence interval [CI], 1.33–3.36 and OR 2.29; 95% CI, 1.38–3.80, respectively). In the 2012 follow-up, smoking was not associated with QoL. Sensitivity analysis did not change the result significantly.Conclusion: In this study we found that baseline smoking was associated with worse QoL in long-follow-up.

Reliability of Time-Series Plasma Metabolome Data over 6 Years in a Large-Scale Cohort Study

Miyake, A; Harada, S; Sugiyama, D; Matsumoto, M; Hirata, A; Miyagawa, N; Toki, R; Edagawa, S; Kuwabara, K; Okamura, T; Sato, A; Amano, K; Hirayama, A; Sugimoto, M; Soga, T; Tomita, M; Arakawa, K; Takebayashi, T; Iida, M

METABOLITES 14 （ 1 ） 2024年01月

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A population-based urinary and plasma metabolomics study of environmental exposure to cadmium

Ishibashi, Y; Harada, S; Eitaki, Y; Kurihara, A; Kato, S; Kuwabara, K; Iida, M; Hirata, A; Sata, M; Matsumoto, M; Shibuki, T; Okamura, T; Sugiyama, D; Sato, A; Amano, K; Hirayama, A; Sugimoto, M; Soga, T; Tomita, M; Takebayashi, T

ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE （一般社団法人日本衛生学会） 29 （ 0 ） 22 - 22 2024年

ISSN 1342078X

Background: The application of metabolomics-based profiles in environmental epidemiological studies is a promising approach to refine the process of health risk assessment. We aimed to identify potential metabolomics-based profiles in urine and plasma for the detection of relatively low-level cadmium (Cd) exposure in large population-based studies.Method: We analyzed 123 urinary metabolites and 94 plasma metabolites detected in fasting urine and plasma samples collected from 1,412 men and 2,022 women involved in the Tsuruoka Metabolomics Cohort Study. Regression analysis was performed for urinary N-acetyl-beta-D-glucosaminidase (NAG), plasma, and urinary metabolites as dependent variables, and urinary Cd (U-Cd, quartile) as an independent variable. The multivariable regression model included age, gender, systolic blood pressure, smoking, rice intake, BMI, glycated hemoglobin, low-density lipoprotein cholesterol, alcohol consumption, physical activity, educational history, dietary energy intake, urinary Na/K ratio, and uric acid. Pathway-network analysis was carried out to visualize the metabolite networks linked to Cd exposure.Result: Urinary NAG was positively associated with U-Cd, but not at lower concentrations (Q2). Among urinary metabolites in the total population, 45 metabolites showed associations with U-Cd in the unadjusted and adjusted models after adjusting for the multiplicity of comparison with FDR. There were 12 urinary metabolites which showed consistent associations between Cd exposure from Q2 to Q4. Among plasma metabolites, six cations and one anion were positively associated with U-Cd, whereas alanine, creatinine, and isoleucine were negatively associated with U-Cd. Our results were robust by statistical adjustment of various confounders. Pathway-network analysis revealed metabolites and upstream regulator changes associated with mitochondria (ACACB, UCP2, and metabolites related to the TCA cycle).Conclusion: These results suggested that U-Cd was associated with metabolites related to upstream mitochondrial dysfunction in a dose-dependent manner. Our data will help develop environmental Cd exposure profiles for human populations.

The association between sleep parameters and sarcopenia in Japanese community-dwelling older adults

Shibuki Takuma, Iida Miho, Harada Sei, Kato Suzuka, Kuwabara Kazuyo, Hirata Aya, Sata Mizuki, Matsumoto Minako, Osawa Yusuke, Okamura Tomonori, Sugiyama Daisuke, Takebayashi Toru

ARCHIVES OF GERONTOLOGY AND GERIATRICS 109 2023年06月

ISSN 0167-4943

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Quality Control of Targeted Plasma Lipids in a Large-Scale Cohort Study Using Liquid Chromatography-Tandem Mass Spectrometry

Hirayama, A; Ishikawa, T; Takahashi, H; Yamanaka, S; Ikeda, S; Hirata, A; Harada, S; Sugimoto, M; Soga, T; Tomita, M; Takebayashi, T

METABOLITES 13 （ 4 ） 2023年04月

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Optimal Cut-off Points of Triglycerides for Cardiovascular Disease Prediction in Japanese Population

Hirata Aya

Ｊｏｕｒｎａｌ　ｏｆ　Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ　ａｎｄ　Ｔｈｒｏｍｂｏｓｉｓ（一般社団法人日本動脈硬化学会） 30 （ 2 ） 105 - 106 2023年02月

ISSN 13403478

Fatty liver index predicts the development of hypertension in a Japanese general population with and without dysglycemia

Wu Dan, Hirata Aya, Hirata Takumi, Imai Yukiko, Kuwabara Kazuyo, Funamoto Mika, Sugiyama Daisuke, Okamura Tomonori

HYPERTENSION RESEARCH 2023年01月

ISSN 0916-9636

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都市部住民における塩味味覚閾値の規定要因に関する検討：神戸研究

若子みな美, 佐田みずき, 久保田芳美, 西田陽子, 久保佐智美, 東山綾, 平田匠, 門田文, 平田あや, 宮嵜潤二, 川原瑞希, 桑原和代, 杉山大典, 宮松直美, 宮本恵宏, 岡村智教

日本公衆衛生雑誌（日本公衆衛生学会） advpub （ 0 ） 2023年

ISSN 05461766

目的　塩味味覚閾値の高値は高血圧との関連が指摘されているが，その規定要因は明らかではない。都市部地域住民集団で塩味味覚閾値の規定要因を明らかにするとともに，複数の規定要因が同時に存在した場合の塩味味覚閾値との関連を明らかにすることを目的とした。方法　がんや循環器疾患の既往歴がなく，高血圧，糖尿病，脂質異常症の治療中ではない40～74歳の健康な都市部住民を対象としたコホート研究である神戸研究のベースライン調査参加者1,117人のうち，塩味味覚閾値検査を実施し，尿検査から推定一日食塩摂取量の結果が把握できる1,116人を対象者とした。塩味味覚閾値調査はソルセイブ®を用いて塩味味覚閾値0.6%を正常群，0.8%以上を高値群と定義した。塩味味覚閾値高値を目的変数，問診票から得られた生活状況，家族状況，教育歴，喫煙状況，飲酒状況，塩干物摂取状況，ストレス指標，推定一日食塩摂取量を説明変数として，二項ロジスティック回帰モデルにて検討した。さらに，説明変数を塩味味覚閾値に影響を与える要因，目的変数を塩味味覚閾値（正常/高値）として強制投入法を用いた多変量解析にて二項ロジスティック回帰分析を実施した。この分析では，推定一日食塩摂取量との多重共線性を考慮して，尿中ナトカリ比を除いて実施した。結果　平均年齢は男性60.9±9.0歳，女性58.0±8.7歳であった。塩味味覚閾値の正常群は80.9%（903人）（男性73.6%（251人），女性84.1%（652人）），高値群は19.1%（213人）（男性26.3%（90人），女性15.9%（123人））であった。多変量解析の結果，全対象者において現在喫煙習慣がある群は喫煙習慣が無い群と比較し，塩味味覚閾値高値となるオッズ比（95%信頼区間）が2.51（1.33-4.74）と有意な関連が認められた。また，推定一日食塩摂取量上位25%群では下位75%群と比較してオッズ比（95%信頼区間）が1.45（1.03-2.03）と塩味味覚閾値高値との有意な関連を認めた。男女別の解析では，男女ともに現在喫煙習慣と塩味味覚閾値高値との関連を認め，推定一日食塩摂取量は男性のみ関連を認めた。結論　健康な都市住民において，喫煙習慣と推定一日食塩摂取量の多さが塩味味覚閾値高値と関連していた。

Association between visceral fat accumulation and decline in the estimated glomerular filtration rate based on cystatin C in the Japanese urban population: the KOBE study

Tanabe Ayumi, Hirata Aya, Kuwabara Kazuyo, Kubo Sachimi, Higashiyama Aya, Hirata Takumi, Sugiyama Daisuke, Nishida Yoko, Kubota Yoshimi, Kadota Aya, Nishikawa Tomofumi, Miyamatsu Naomi, Miyamoto Yoshihiro, Okamura Tomonori

Endocrinologia Japonica （一般社団法人日本内分泌学会） 70 （ 1 ） 97 - 106 2023年

ISSN 09188959

Although metabolic syndrome, including visceral fat accumulation, causes kidney and cardiovascular diseases, the impact of visceral fat accumulation on mild decreased renal function remains unclear. This study examines the association between visceral fat area (VFA) measured by bioimpedance methods and the estimated glomerular filtration rate based on serum cystatin C (eGFRcys) in the Japanese urban population. This community-based cross-sectional study enrolled 952 individuals (287 men, 665 women) who participated in the second follow-up survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. We compared the multivariate-adjusted means of eGFRcys among VFA quartile groups by gender using the analysis of covariance. Models were adjusted for age, high blood pressure, hypercholesterolemia, glucose intolerance, smoking, and alcohol use, and further adjusted for body mass index (BMI). The highest VFA quartile group had lower eGFRcys than the lowest VFA quartile group after adjusted for cardiometabolic risk factors, except for BMI (93.1 [95% confidence interval (CI), 90.1–96.2] vs. 82.1 [95% CI, 79.1–85.0] in men and 95.8 [95% CI, 94.1–97.5] vs. 89.4 [95% CI, 87.8–90.9] in women). Moreover, further adjustment for BMI revealed a similar result in men (93.5 [95% CI, 89.8–97.2] vs. 81.6 [95% CI, 77.9–85.3]), while no significant association was found in women. This study suggests a significant association between increased VFA levels and lower eGFRcys levels independent of cardiometabolic risk factors, such as glucose intolerance and hypercholesterolemia in men and women, as well as independent of BMI in men.

Determinants of double product: a cross-sectional study of urban residents in Japan

Nakagoshi, N; Kubo, S; Nishida, Y; Kuwabara, K; Hirata, A; Sata, M; Higashiyama, A; Kubota, Y; Hirata, T; Tatsumi, Y; Kawamura, K; Miyazaki, J; Miyamatsu, N; Sugiyama, D; Miyamoto, Y; Okamura, T

ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE （一般社団法人日本衛生学会） 28 （ 0 ） 37 - 37 2023年

ISSN 1342078X

Background: The current study aimed to investigate the determinants of high double product (DP) by evaluating the association between resting DP, which is calculated as systolic blood pressure (SBP) multiplied by heart rate (HR), and blood test results and lifestyle factors.Methods: This research included 973 participants in the baseline survey of the KOBE study, which included a cohort of urban residents. The possible DP determinants were identified by examining the association between lifestyle factors and laboratory findings and DP by analyzing covariance adjusted for sex and age. Logistic regression analysis was performed with high DP (SBP × HR ≥ 9145 mmHg beats/min or quintile according to sex) as outcome and DP determinants as independent variables.Results: Age, hematocrit, and gamma-glutamyl transferase (log) level were positively associated with a high DP in both men and women. In addition, a high DP was positively associated with Homeostatic Model Assessment for Insulin Resistance score in women alone. Meanwhile, the amount of exercise was negatively associated with a high DP in men alone.Conclusions: High DP values at rest were associated with insulin resistance, gamma-glutamyl transferase, and the amount of exercise in participants without underlying disease.

Predicting habitual water intake from lifestyle questions

Tanaka, H; Mizuma, K; Nakamura, Y; Hirata, A; Miyazaki, J; Suzuki, K; Seta, H; Watanabe, H; Suzuki, T; Watanabe, R; Murayama, N; Okamura, T; Nakamura, S

EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES 27 （ 18 ） 8829 - 8841 2023年

ISSN 1128-3602

Effect of Chronic Kidney Disease or Anemia or Both on Cardiovascular Mortality in a 25-Year Follow-Up Study of Japanese General Population (From NIPPON DATA90)

Kubo Kota, Okamura Tomonori, Sugiyama Daisuke, Hisamatsu Takashi, Hirata Aya, Kadota Aya, Kondo Keiko, Hirata Takumi, Higashiyama Aya, Hayakawa Takehito, Miyamoto Yoshihiro, Okayama Akira, Miura Katsuyuki, Ueshima Hirotsugu

AMERICAN JOURNAL OF CARDIOLOGY 184 1 - 6 2022年12月

ISSN 0002-9149

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Impact of hypertension and diabetes on the onset of chronic kidney disease in a general Japanese population

Kaneyama Akira, Hirata Aya, Hirata Takumi, Imai Yukiko, Kuwabara Kazuyo, Funamoto Mika, Sugiyama Daisuke, Okamura Tomonori

HYPERTENSION RESEARCH 2022年09月

ISSN 0916-9636

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Association Between Clinical Backgrounds and Malignant Progression of Suspected Intraductal Papillary Mucinous Neoplasm

Fukushima Genki, Abe Kodai, Kitago Minoru, Iwasaki Eisuke, Hirata Aya, Takemura Ryo, Ishii Ryota, Yagi Hiroshi, Abe Yuta, Hasegawa Yasushi, Fukuhara Seiichiro, Hori Shutaro, Tanaka Masayuki, Nakano Yutaka, Yokose Takahiro, Shimane Gaku, Kitagawa Yuko

PANCREAS 51 （ 6 ） 617 - 623 2022年07月

ISSN 0885-3177

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Serum modified high-density lipoprotein and risk of atherosclerotic cardiovascular disease in a Japanese community-based nested case-control study

Sata Mizuki, Kakino Akemi, Hirata Aya, Iida Miho, Usami Yoko, Harada Sei, Fujita Yoshiko, Kohsaka Shun, Izawa Yoshikane, Sawano Mitsuaki, Oki Koichi, Sugiyama Daisuke, Takahashi Shinichi, Takebayashi Toru, Sawamura Tatsuya, Okamura Tomonori

EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY 29 （ 5 ） E193 - E195 2022年05月

ISSN 2047-4873

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Accumulated unhealthy behaviours and insomnia in Japanese dwellers with and without cardiovascular risk factors: a cross-sectional study

Kato Suzuka, Harada Sei, Iida Miho, Kuwabara Kazuyo, Sugiyama Daisuke, Takeuchi Ayano, Sata Mizuki, Matsumoto Minako, Kurihara Ayako, Hirata Aya, Okamura Tomonori, Takebayashi Toru

BMJ OPEN 12 （ 4 ） 2022年04月

ISSN 2044-6055

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Prediction of Lifetime Risk of Cardiovascular Disease Deaths Stratified by Sex in the Japanese Population

Imai Yukiko, Tanaka Sachiko Mizuno, Satoh Michihiro, Hirata Takumi, Murakami Yoshitaka, Miura Katsuyuki, Waki Takashi, Hirata Aya, Sairenchi Toshimi, Irie Fujiko, Sata Mizuki, Ninomiya Toshiharu, Ohkubo Takayoshi, Ishikawa Shizukiyo, Miyamoto Yoshihiro, Ohnishi Hirofumi, Saitoh Shigeyuki, Tamakoshi Akiko, Yamada Michiko, Kiyama Masahiko, Iso Hiroyasu, Sakata Kiyomi, Nakagawa Hideaki, Okayama Akira, Ueshima Hirotsugu, Okamura Tomonori

JOURNAL OF THE AMERICAN HEART ASSOCIATION 10 （ 23 ） 2021年12月

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Validity Assessment of Self-reported Medication Use for Hypertension, Diabetes, and Dyslipidemia in a Pharmacoepidemiologic Study by Comparison With Health Insurance Claims (vol 31, pg 495, 2021)

Matsumoto Minako, Harada Sei, Iida Miho, Kato Suzuka, Sata Mizuki, Hirata Aya, Kuwabara Kazuyo, Takeuchi Ayano, Sugiyama Daisuke, Okamura Tomonori, Takebayashi Toru

Ｊｏｕｒｎａｌ　ｏｆ　Ｅｐｉｄｅｍｉｏｌｏｇｙ（日本疫学会） 31 （ 9 ） 520 - 521 2021年09月

ISSN 09175040

Association between environmental cadmium exposure and plasma and urinary metabolite profiles in Japanese cohort study

Ishibashi Yoshiki, Harada Sei, Eitaki Yoko, Iida Miho, Kurihara Ayako, Hirata Aya, Shibuki Takuma, Okamura Tomonori, Hirayama Akiyoshi, Sugimoto Masahiro, Soga Tomoyoshi, Tomita Masaru, Takebayashi Toru

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY 50 2021年09月

ISSN 0300-5771

Change of smoking habits by introducing and spreading heated tobacco products in Japan

Harada Sei, Sata Mizuki, Matsumoto Minako, Takeuchi Ayano, Iida Miho, Kato Suzuka, Hirata Aya, Kuwabara Kazuyo, Sugiyama Daisuke, Okamura Tomonori, Takebayashi Toru

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY 50 93 - 93 2021年09月

ISSN 0300-5771

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SARS-CoV-2 Infection among Medical Institution Faculty and Healthcare Workers in Tokyo, Japan

Nishimura Tomoyasu, Uwamino Yoshifumi, Uno Shunsuke, Kashimura Shoko, Shiraki Toshikimi, Kurafuji Toshinobu, Morita Maasa, Noguchi Masayo, Azegami Tatsuhiko, Yamada-Goto Nobuko, Murai-Takeda Ayano, Yokoyama Hirokazu, Kuwabara Kazuyo, Kato Suzuka, Matsumoto Minako, Hirata Aya, Iida Miho, Harada Sei, Ishizaka Tamami, Misawa Kana, Murata Mitsuru, Saya Hideyuki, Amagai Masayuki, Kitagawa Yuko, Takeuchi Tsutomu, Mori Masaaki, Takebayashi Toru, Hasegawa Naoki

Japanese Journal of Medicine （一般社団法人日本内科学会） 60 （ 16 ） 2569 - 2575 2021年08月

ISSN 09182918

Objective To consider effective measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in medical institutions, this study estimated the SARS-CoV-2 infection rate among healthcare workers (HCWs) in Tokyo, Japan, and determined the specific findings for mild coronavirus disease 2019 (COVID-19) cases. Methods This study analyzed the results of serologic tests to detect immunoglobulin G antibodies against SARS-CoV-2 and evaluated the demographic and clinical characteristics of the faculty and HCWs at a Tokyo medical institution in August 2020. The demographic and clinical characteristics of participants with antibody-positive results were compared to those of participants with antibody-negative results. Materials This study recruited 2,341 faculty and HCWs at a Tokyo medical institution, 21 of whom had a COVID-19 history. Results Of the 2,320 participants without a COVID-19 history, 20 (0.862%) had positive serologic test results. A fever and dysgeusia or dysosmia occurred with greater frequency among the participants with positive test results than in those with negative results [odds ratio (OR), 5.475; 95% confidence interval (CI), 1.960-15.293 and OR, 24.158; 95% CI, 2.693-216.720, respectively]. No significant difference was observed in the positivity rate between HCWs providing medical care for COVID-19 patients using adequate protection and other HCWs (OR, 2.514; 95% CI, 0.959-6.588). Conclusion To reduce the risk of COVID-19 spread in medical institutions, faculty and HCWs should follow standard and necessary transmission-based precautions, and those with a fever and dysgeusia or dysosmia should excuse themselves from work as soon as possible.

Reliability of urinary charged metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry

Ishibashi Yoshiki, Harada Sei, Takeuchi Ayano, Iida Miho, Kurihara Ayako, Kato Suzuka, Kuwabara Kazuyo, Hirata Aya, Shibuki Takuma, Okamura Tomonori, Sugiyama Daisuke, Sato Asako, Amano Kaori, Hirayama Akiyoshi, Sugimoto Masahiro, Soga Tomoyoshi, Tomita Masaru, Takebayashi Toru

SCIENTIFIC REPORTS 11 （ 1 ） 2021年04月

ISSN 2045-2322

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Electrocardiographic Left Atrial Abnormality and B-Type Natriuretic Peptide in a General Japanese Population: NIPPON DATA2010

Shoji Satoshi, Kadota Aya, Ueshima Hirotsugu, Okayama Akira, Miura Katsuyuki, for the NIPPON DATA2010 Research Group, Kohsaka Shun, Sawano Mitsuaki, Okamura Tomonori, Hirata Aya, Sugiyama Daisuke, Ohkubo Takayoshi, Nakamura Yasuyuki, Watanabe Makoto

Ｊｏｕｒｎａｌ　ｏｆ　Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ　ａｎｄ　Ｔｈｒｏｍｂｏｓｉｓ（一般社団法人日本動脈硬化学会） 28 （ 1 ） 34 - 43 2021年

ISSN 1340-3478

Aims: P-wave terminal force in lead V1 (PTFV1) is an electrocardiogram marker of increased left atrial pressure and may be a noninvasive and early detectable marker for future cardiovascular events in the general population compared to serum B-type natriuretic peptide (BNP) concentration. The clinical significance of PTFV1 in the contemporary general population is an area of unmet need. We aimed to demonstrate the correlation between PTFV1 and BNP concentrations in a contemporary representative Japanese population. Methods: Among 2,898 adult men and women from 300 randomly selected districts throughout Japan (NIPPON DATA2010), we analyzed 2,556 participants without cardiovascular disease (stroke, myocardial infarction, and atrial fibrillation). Elevated BNP was defined as a value of ≥ 20 pg/mL based on the definition from the Japanese Circulation Society guidelines. Results: In total, 125 (4.9%) participants had PTFV1. Participants with PTFV1 were older with a higher prevalence of hypertension, major electrocardiographic findings, and elevated BNP concentrations (13.5 [6.9, 22.8] versus 7.8 [4.4, 14.5] pg/mL; P＜0.001). After adjustment for confounders, PTFV1 was correlated with elevated BNP (odds ratio, 1.66; 95% confidence interval, 1.05–2.62; P=0.030). This correlation was consistent among various subgroups and was particularly evident in those aged ＜65 years or those without a history of hypertension. Conclusions: In the contemporary general population cohort, PTFV1 was independently related to high BNP concentration. PTFV1 may be an alternative marker to BNP in identifying individuals at a higher risk of future cardiovascular events in the East Asian population.

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Changes in smoking habits and behaviors following the introduction and spread of heated tobacco products in Japan and its effect on FEV1 decline: a longitudinal cohort study

Harada Sei, Ishibashi Yoshiki, Sugiyama Daisuke, Okamura Tomonori, Takebayashi Toru, Sata Mizuki, Matsumoto Minako, Iida Miho, Takeuchi Ayano, Kato Suzuka, Hirata Aya, Kuwabara Kazuyo, Shibuki Takuma

Ｊｏｕｒｎａｌ　ｏｆ　Ｅｐｉｄｅｍｉｏｌｏｇｙ（日本疫学会） 2021年

ISSN 0917-5040

Background: Heated tobacco product (HTP) use in Japan has rapidly increased. Despite this rapid spread, little is known about the health effects of HTP use. We conducted a longitudinal cohort study to investigate the change in smoking habits following the spread of HTP use and its effect on forced expiratory volume in one second (FEV1) decline.Methods: Participants consisted of a resident population (n=2,612, aged 67.7) with FEV1 measurement in 2012-2014 and 2018-2019, and a worksite population (n=722, aged 49.3) without FEV1 data. Participants were categorized as never, past and combustible cigarette-only smokers, and HTP-only and dual users. The association between smoking group and the change in smoking consumption for 5.6 years was examined. Differences in annual FEV1 change between smoking groups were examined in the resident population.Results: Prevalence of HTP-only and dual users in 2018-2019 was 0.8% and 0.6% in the resident population, and 5.0% and 1.9% in the worksite population, respectively. The overall number of tobacco products smoked/used increased in dual users compared to baseline, but not in others. Annual FEV1 decline in dual users tended to be greater than that in cigarette-only smokers (16 mL/yr [95% CI: -34, 2] after full adjustment). Participants switching to HTP-only use 1.7 years before had a similar FEV1 decline as cigarette-only smokers.Conclusions: HTP use, including dual use, is prevalent even in a rural region of Japan. Dual users appear to smoke/use tobacco products more and have a greater FEV1 decline. Tobacco policy should consider dual use as high-risk.

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Relationship Between Non-fasting Triglycerides and Cardiovascular Disease Mortality in a 20-year Follow-up Study of a Japanese General Population: NIPPON DATA90

Hirata Aya, Kondo Keiko, Miura Katsuyuki, Okayama Akira, Ueshima Hirotsugu, Okamura Tomonori, Hirata Takumi, Sugiyama Daisuke, Ohkubo Takayoshi, Okuda Nagako, Kita Yoshikuni, Hayakawa Takehito, Kadota Aya

Ｊｏｕｒｎａｌ　ｏｆ　Ｅｐｉｄｅｍｉｏｌｏｇｙ（日本疫学会） 2021年

ISSN 0917-5040

Background: Non-fasting triglycerides (TG) are considered a better predictor of cardiovascular disease (CVD) than fasting TG. However, the effect of non-fasting TG on fatal CVD events remains unclear. In the present study, we aimed to explore the relationship between non-fasting TG and CVD mortality in a Japanese general population.Methods: A total of 6,831 participants without a history of CVD, in which those who had a blood sampling over 8 hours or more after a meal were excluded, were followed for 18.0 years. We divided participants into seven groups according to non-fasting TG levels: ≤59 mg/dL, 60–89 mg/dL, 90–119 mg/dL, 120–149 mg/dL, 150–179 mg/dL, 180–209 mg/dL, and ≥210 mg/dL, and estimated the multivariable-adjusted hazard ratios (HRs) of each TG group for CVD mortality after adjusting for potential confounders, including high density lipoprotein cholesterol. Additionally, we performed analysis stratified by age <65 and ≥65 years.Results: During the follow-up period, 433 deaths due to CVD were detected. Compared with a non-fasting TG of 150–179 mg/dL, non-fasting TG ≥210 mg/dL was significantly associated with increased risk for CVD mortality (HR 1.56: 95% CI, 1.01–2.41). Additionally, lower levels of non-fasting TG were also significantly associated with increased risk for fatal CVD. In participants aged ≥65 years, lower levels of non-fasting TG had a stronger impact on increased risk for CVD mortality, while higher levels of non-fasting TG had a stronger impact in those aged <65 years.Conclusion: In a general Japanese population, we observed a U-shaped association between non-fasting TG and fatal CVD events.

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Impact of resting heart rate on cardiovascular mortality according to serum albumin levels in a 24-year follow-up study on a general Japanese population: NIPPON DATA80

Liu Yiwei, Okayama Akira, Ueshima Hirotsugu, Hirata Aya, Okamura Tomonori, Sugiyama Daisuke, Hirata Takumi, Kadota Aya, Kondo Keiko, Ohkubo Takayoshi, Miura Katsuyuki

Ｊｏｕｒｎａｌ　ｏｆ　Ｅｐｉｄｅｍｉｏｌｏｇｙ（日本疫学会） 2021年

ISSN 0917-5040

BackgroundElevated resting heart rate (RHR) is associated with an increased risk for cardiovascular disease (CVD) and all-cause mortality. However, the findings of cohort studies differed. Thus, the impact of RHR on CVD mortality might be different according to the background of the population. Therefore, we examined the relationship of RHR and CVD mortality according to serum ALB levels in a Japanese general population.MethodsIn total, 8363 individuals without a history of CVD were followed-up for 24.0 years. The participants were divided into four groups according to the quartiles of RHR (Q1–Q4), and they were further classified into the high and low ALB groups based on a median value of 44 g/L. We estimated the multivariable-adjusted hazard ratios (HRs) of CVD mortality in each RHR group based on ALB levels, and the interaction between RHR and ALB groups on CVD mortality was evaluated.ResultsWe found no significant association between RHR and CVD mortality. However, the Q4 of RHR was significantly associated with an increased risk for CVD mortality (HR: 1.27 [95% confidence interval, CI: 1.02–1.57]) in participants with a low ALB level. Meanwhile, the Q4 of RHR was significantly correlated with a decreased risk for CVD morality in those with a high ALB level (HR: 0.61 [95% CI: 0.47–0.79]) after adjusting for covariates. A significant interaction between RHR and ALB for CVD mortality was shown (p<0.001).ConclusionsThe impact of RHR on CVD mortality differed according to ALB levels in a general Japanese population.

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Association of the Estimated Coronary Artery Incidence Risk According to the Japan Atherosclerosis Society Guidelines 2017 with Cardio-Ankle Vascular Index

Sata Mizuki, Matsumoto Minako, Kurihara Ayako, Takebayashi Toru, Okamura Tomonori, Harada Sei, Sugiyama Daisuke, Kuwabara Kazuyo, Hirata Aya, Takeuchi Ayano, Iida Miho, Kato Suzuka

Ｊｏｕｒｎａｌ　ｏｆ　Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ　ａｎｄ　Ｔｈｒｏｍｂｏｓｉｓ（一般社団法人日本動脈硬化学会） 2021年

ISSN 1340-3478

Aims: The categories in the comprehensive lipid and risk management guidelines were proposed by the Japan Atherosclerosis Society (JAS Guidelines 2017), which adopted the estimated 10 year absolute risk of coronary artery disease (CAD) incidence in the Suita score. We examined whether those categories were concordant with the degree of arterial stiffness. Methods: In 2014, the cardio-ankle vascular index (CAVI), an arterial stiffness parameter, was measured in 1,972 Japanese participants aged 35–74 years in Tsuruoka City, Yamagata Prefecture, Japan. We examined the mean CAVI and the proportion and odds ratios (ORs) of CAVI ≥ 9.0 on the basis of the following three management classifications using the analysis of variance and logistic regression: "Category I (Low risk)," "Category II (Middle risk)," and "Category III (High risk)." Results: The mean CAVI and proportion of CAVI ≥ 9.0 were 8.6 and 34.8% among males and 8.1 and 18.3% among females, respectively. The mean CAVI and proportion of CAVI ≥ 9.0 were associated with an estimated 10 year absolute risk for CAD among males and females, excluding High risk for females. These results were similar to the management classification by the guideline: the multivariable-adjusted ORs (95% confidence intervals) of CAVI ≥ 9.0 among Category II and Category III compared with those among Category I were 2.96 (1.61–5.43) and 7.33 (4.03–13.3) for males and 3.99 (2.55–6.24) and 3.34 (2.16–5.16) for females, respectively. Conclusions: The risk stratification, which was proposed in the JAS Guidelines 2017, is concordant with the arterial stiffness parameter.

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Control of a Nosocomial Outbreak of COVID-19 in a University Hospital

Harada Sei, Uno Shunsuke, Ando Takayuki, Iida Miho, Takano Yaoko, Ishibashi Yoshiki, Uwamino Yoshifumi, Nishimura Tomoyasu, Takeda Ayano, Uchida Sho, Hirata Aya, Sata Mizuki, Matsumoto Minako, Takeuchi Ayano, Obara Hideaki, Yokoyama Hirokazu, Fukunaga Koichi, Amagai Masayuki, Kitagawa Yuko, Takebayashi Toru, Hasegawa Naoki

OPEN FORUM INFECTIOUS DISEASES 7 （ 12 ） 2020年12月

ISSN 2328-8957

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The relationship between serum levels of LOX-1 ligand containing ApoAI as a novel marker of dysfunctional HDL and coronary artery calcification in middle-aged Japanese men

Hirata Aya, Kakino Akemi, Okamura Tomonori, Usami Yoko, Fujita Yoshiko, Kadota Aya, Fujiyoshi Akira, Hisamatsu Takashi, Kondo Keiko, Segawa Hiroyoshi, Sawamura Tatsuya, Miura Katsuyuki, Ueshima Hirotsugu

ATHEROSCLEROSIS 313 20 - 25 2020年11月

ISSN 0021-9150

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Estimated 24 h Urinary Sodium-to-Potassium Ratio Is Related to Renal Function Decline: A 6-Year Cohort Study of Japanese Urban Residents

Hattori Hiroko, Hirata Aya, Kubo Sachimi, Nishida Yoko, Nozawa Miki, Kawamura Kuniko, Hirata Takumi, Kubota Yoshimi, Sata Mizuki, Kuwabara Kazuyo, Higashiyama Aya, Kadota Aya, Sugiyama Daisuke, Miyamatsu Naomi, Miyamoto Yoshihiro, Okamura Tomonori

INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 17 （ 16 ） 2020年08月

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Validity Assessment of Self-reported Medication Use for Hypertension, Diabetes, and Dyslipidemia in a Pharmacoepidemiologic Study by Comparison With Health Insurance Claims

Matsumoto Minako, Okamura Tomonori, Takebayashi Toru, Harada Sei, Iida Miho, Kato Suzuka, Sata Mizuki, Hirata Aya, Kuwabara Kazuyo, Takeuchi Ayano, Sugiyama Daisuke

Ｊｏｕｒｎａｌ　ｏｆ　Ｅｐｉｄｅｍｉｏｌｏｇｙ（日本疫学会） 2020年

ISSN 0917-5040

Background: Although self-reported questionnaires are widely employed in epidemiologic studies, their validity has not been sufficiently assessed. The aim of this study was to evaluate the validity of a self-reported questionnaire on medication use by comparison with health insurance claims and to identify individual determinants of discordance in the Tsuruoka Metabolomics Cohort Study.Methods: Participants were 2,472 community-dwellers aged 37 to 78 years from the Tsuruoka Metabolomics Cohort Study. Information on lifestyle and medications was collected through a questionnaire. Sensitivity and specificity were determined using health insurance claims from November 2014 to March 2016, which were used as a standard. Potential determinants of discordance were assessed using multivariable logistic regression.Results: The self-reported questionnaire on medication use showed high validity. Sensitivity and specificity were 0.95 (95% CI, 0.93–0.96) and 0.97 (95% CI, 0.96–0.98) for antihypertensive medications, 0.94 (95% CI, 0.91–0.97) and 0.98 (95% CI, 0.98–0.99) for diabetes medications, and 0.84 (95% CI, 0.82–0.87) and 0.98 (95% CI, 0.97–0.99) for dyslipidemia medications, respectively. Males without high education and those who currently smoke cigarettes were found to be associated with discordant reporting which affected sensitivity, especially those with medication use for dyslipidemia.Conclusions: In this population-based cohort study, we found that the self-reported questionnaire on medication use was a valid measure to capture regular medication users. Sensitivity for dyslipidemia medications was lower than those for the other medications. Type of medication, sex, education years, and smoking status influenced discordance, which affected sensitivity in self-reporting.

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Physique at Birth and Cardiovascular Disease Risk Factors in Japanese Urban Residents: the KOBE Study

Umemoto Kaori, Kuwabara Kazuyo, Miyazaki Junji, Kadota Aya, Iida Miho, Sugiyama Daisuke, Miyamatsu Naomi, Miyamoto Yoshihiro, Okamura Tomonori, Kubo Sachimi, Nishida Yoko, Higashiyama Aya, Kawamura Kuniko, Kubota Yoshimi, Hirata Takumi, Hirata Aya, Sata Mizuki

Ｊｏｕｒｎａｌ　ｏｆ　Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ　ａｎｄ　Ｔｈｒｏｍｂｏｓｉｓ（一般社団法人日本動脈硬化学会） 2020年

ISSN 1340-3478

Aim: This study investigated the relationship between birth physique and cardiovascular risk factors in Japanese urban residents aged 40 years and more. Methods: A self-administered questionnaire on birth physique was performed among 624 individuals (165 men and 459 women) who participated in the KOBE study. We examined whether self-reported birth physique and available recorded birth weights matched for 72 participants. Then the association between birth physique and risk factors for all participants was examined by gender. Body size at birth in the questionnaire (large, medium, small) was set as an exposure and laboratory values from the baseline survey (2010-2011) were used as outcomes. Results: Mean (standard deviation) recorded birth weight of 72 participants was 3665 (318), 3051 (300), and 2653 (199) g, in the large, medium, and small group, respectively. In the analysis for all participants, odds ratio for having both hypertension and impaired glucose tolerance were significantly higher in the small versus large birth weight group, which was 7.42 (95% CI 1.75–31.50) for men and 4.44 (95% CI 1.14–17.30) for women after adjusting for age, body mass index, smoking/alcohol/exercise habits, and menstrual status in women. Similar results were observed in participants with recorded birth weight. Conclusions: The present study indicates that individuals with small physique at birth might be at higher risk for hypertension and impaired glucose tolerance in middle age compared to those with large birth weight.

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都市住民における非特異的ストレス指標K6の悪化予測因子の探索：神戸研究

田谷元, 久保田芳美, 門田文, 宮松直美, 西村邦宏, 宮本恵宏, 岡村智教, 桑原和代, 東山綾, 杉山大典, 平田あや, 佐田みずき, 平田匠, 西田陽子, 久保佐智美

日本公衆衛生雑誌（日本公衆衛生学会） 67 （ 8 ） 509 - 517 2020年

ISSN 0546-1766

目的　非特異的なストレス指標であるThe Kessler 6-Item Psychological Distress Scale（K6）スコアの将来的な悪化を予測できる健康関連要因を探索する。方法　がんや循環器疾患の既往歴がなく，高血圧，糖尿病，脂質異常症の治療中でない，健康な都市住民を対象としたコホート研究であるKobe Orthopedic and Biomedical Epidemiological study（KOBE study）のベースライン調査（2010～2011年度）に参加した1,117人にK6日本語版による質問紙調査を実施した。本研究ではK6≧5点をストレスあり群，K6<5点をストレスなし群と定義した。4年後の追跡調査が2014～2015年度に実施され，1,004人が参加した（追跡率90%）。欠損値がある39人，ベースライン調査時にK6≧5点であった185人を除く780人を本研究の解析対象とした。K6スコアのほかに性別，年齢，家族状況（単身/同居），運動・レクリエーションによる身体活動量，平均睡眠時間，screening version of the Hearing Handicap Inventory for Elderly（HHIE-S）日本語版，Oswestry Disability Index（ODI）日本語版を調査項目とした。4年後追跡調査時のK6≧5点を従属変数，ベースライン調査時の各因子を独立変数としたロジスティック回帰分析を行った。結果　解析対象者780人のうち，4年後追跡調査時にストレスあり（K6≧5点）となったのは132人（16.9%）であった。ロジスティック回帰分析の結果，年代（40歳代/70歳代）（オッズ比3.38, 95%信頼区間1.45-7.86），家族状況（単身/同居）（オッズ比1.98, 95%信頼区間1.07-3.68），ODIスコア（1%）（オッズ比1.05, 95%信頼区間1.01-1.09）の項目でストレスと有意な関連が見られた。結論　年齢，家族状況，腰痛・関節痛による機能障害の程度が将来的なストレスに関連していることが示唆された。

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Statin Intolerance Clinical Guide 2018.

Kajinami K, Tsukamoto K, Koba S, Inoue I, Yamakawa M, Suzuki S, Hamano T, Saito H, Saito Y, Masuda S, Nakayama T, Okamura T, Yamashita S, Kagawa T, Kaneyama J, Kuriyama A, Tanaka R, Hirata A, Statin Intolerance Clinical Guide Working Group; The Japan Society of Hepatology, Japanese Society of Neurology, Japan Atherosclerosis Society, The Japanese Society for the Study of Xenobiotics.

Journal of atherosclerosis and thrombosis 2019年10月

ISSN 1340-3478

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Higher serum uric acid level is inversely associated with renal function assessed by cystatin C in a Japanese general population without chronic kidney disease: The KOBE study

Kubo S, Nishida Y, Kubota Y, Higashiyama A, Sugiyama D, Hirata T, Miyamatsu N, Tanabe A, Hirata A, Tatsumi Y, Kadota A, Kuwabara K, Nishikawa T, Miyamoto Y, Okamura T

BMC Nephrology （BMC Nephrology） 20 （ 1 ） 117 2019年04月

研究論文（学術雑誌）, 査読有り

© 2019 The Author(s). Background: Although several epidemiological studies have suggested that high serum uric acid (SUA) levels are related to a decline in kidney function, only a few studies have investigated using cystatin C to calculate estimated glomerular filtration rate (eGFR). We aimed to clarify the relationship between SUA levels and kidney function assessed by cystatin C in a Japanese general community population without chronic kidney disease (CKD). Methods: We conducted a community-based cross-sectional study that included 1086 healthy participants, aged 40-74 years, without CKD and not undergoing treatment of hyperuricemia, who had participated in the baseline survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. The preconditions for participation in this study were no past histories of cardiovascular disease or cancer, and not undergoing treatment for diabetes, hypertension, or dyslipidemia. We classified the participants into quartiles stratified by sex according to their SUA level and then examined the relationship with eGFR. The odds ratios for having a low eGFR, defined as the lowest quartile of eGFR (i.e., ≤78.4 mL/min/1. 73m 2 ) was estimated according to SUA quartiles (men, Q1 ≤ 5.0, Q2 5.1-5.9, Q3 6.0-6.6, and Q4 ≥ 6.7; women, Q1 ≤ 3.8, Q2 3.9-4.3, Q3 4.4-4.9, and Q4 ≥ 5.0 mg/dL) after adjustment for age, body mass index, systolic blood pressure, HbA1c, high and low density lipoprotein cholesterol, and smoking and drinking habits. The adjusted mean of each quartile was also calculated. Results: Multivariable-adjusted means of eGFR showed a graded decrease in higher SUA quartiles (men, Q1 90.5, Q2 88.0, Q3 83.5, and Q4 82.0; women, Q1 95.7, Q2 91.3, Q3 89.2, and Q4 86.7). In addition, the multivariable-adjusted odds ratios for having a lower eGFR (95% confidence interval) for each SUA quartile compared with Q1 was Q2 2.29 (0.98, 5.35), Q3 4.94 (2.04, 11.97), and Q4 8.01 (3.20, 20.04) for men, and was Q2 2.20 (1.12, 4.32), Q3 2.68 (1.39, 5.20), and Q4 4.96 (2.62, 9.41) for women. Conclusions: There was a graded inverse relationship between mild elevations in SUA levels and eGFR assessed by cystatin C in an apparently healthy Japanese population without CKD. This association was similar in both men and women.

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Evaluation of the fatty liver index as an indicator of hepatic steatosis as assessed by the controlled attenuation parameter

Hirata A, Sugiyama D, Kuwabara K, Okamura T

Nihon Arukoru Yakubutsu Igakkai zasshi 54 （ 1 ） 15 - 24 2019年02月

研究論文（学術雑誌）, 査読有り, ISSN 1341-8963

Effects of sulfur dioxide on fractional exhaled nitric oxide concentration in the child residents of Miyakejima Island

Iwasawa S., Tsuboi T., Nakano M., Hirata A., Yoshioka N., Suzuki S., Tanaka S., Omae K.

Asian Journal of Atmospheric Environment （Asian Journal of Atmospheric Environment） 13 （ 2 ） 145 - 149 2019年

研究論文（学術雑誌）, 査読有り, ISSN 19766912

© 2019 by Asian Journal of Atmospheric Environment. The island of Miyakejima in Japan is subject to ongoing emissions of volcanic gases, including high concentrations of sulfur dioxide (SO2). Annual health checkups on the island, therefore, include the examination of respiratory system parameters. Here, we aimed to investigate the relationship between SO2 exposure and fractional exhaled nitric oxide (FeNO) concentration among children who received health checkups from 2008 to 2014. The subjects were 83 and 31 second-year junior high school students aged 13-14 years who resided on Miyakejima island and an SO2-free reference island, respectively. SO2 concentration in the air was measured at 6 fixed-point monitoring stations. FeNO was examined according to the American Thoracic Society guideline and European Respiratory Society recommendations for standardized procedures. Average concentrations of SO2 on Miyakejima over a period of 3 months prior to each health checkup from 2008 to 2014 were 22.2, 20.6, 8.9, 10.5, 10.7, 4.4 and 8.0 ppb, respectively. Among the Miyakejima students, geometric mean (GM) FeNO concentrations measured at each health checkup from 2008 to 2014 were 28.2, 18.2, 23.6, 35.5, 36.9, 28.1, and 32.1 ppb. The GM FeNO concentration measured from all Miyakejima students across the study period was 28.3 ppb. No clear dose-response relationship was observed. The GM FeNO concentration among the students from the reference island was 27.7 ppb in 2017. No significant difference was observed between the two populations, even when the data was stratified by sex and sensitivity. There was no clear significant difference in GM of FeNO concentration between Miyakejima and control students, when the average concentration of SO2 over a period of 3 months was 22 ppb or less.

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Association between dyslipidemia and plasma levels of branched-chain amino acids in the Japanese population without diabetes mellitus

Fukushima K., Harada S., Takeuchi A., Kurihara A., Iida M., Fukai K., Kuwabara K., Kato S., Matsumoto M., Hirata A., Akiyama M., Tomita M., Hirayama A., Sato A., Suzuki C., Sugimoto M., Soga T., Sugiyama D., Okamura T., Takebayashi T.

Journal of Clinical Lipidology （Journal of Clinical Lipidology） 2019年

ISSN 19332874

© 2019 National Lipid Association Background: Branched-chain amino acids (BCAAs) play a key role in energy homeostasis. Objective: We aimed to investigate the association between plasma BCAA levels and dyslipidemia in the Japanese population without diabetes mellitus. Methods: This cross-sectional study included 4952 participants without diabetes mellitus, enrolled in the Tsuruoka Metabolomic Cohort Study. Plasma BCAA levels were measured by capillary electrophoresis–mass spectrometry. Correlations between lipid and BCAA profiles were evaluated by sex-stratified multiple linear regression analyses, after adjusting for confounders. Logistic regression was used to identify associations between BCAAs and metabolic dyslipidemia (MD) defined as triglyceride levels ≥150 mg/dL, high-density lipoprotein cholesterol levels ≤40 mg/dL for men and ≤50 mg/dL for women, or low-density lipoprotein cholesterol (LDL-C) levels ≥140 mg/dL. Results: In both sexes, the levels of individual BCAAs and the total BCAA levels correlated positively with triglyceride levels and negatively with high-density lipoprotein cholesterol levels. Valine, leucine, and total BCAA levels were weakly and positively correlated with LDL-C levels. Increased BCAA levels showed positive associations with MD. However, associations between BCAAs and elevated LDL-C levels were unclear. Furthermore, the associations between BCAA levels and MD regardless of fasting blood sugar (FBS) levels (high or low). Although valine, leucine, and total BCAA levels were weakly associated with elevated LDL-C levels in the high-FBS group, no such association was observed in the low-FBS group. Conclusions: BCAAs might be associated with MD independently of the FBS level and might play an important role in lipid metabolism and dyslipidemia.

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Response to the letter entitled “Extremely high levels of high-density lipoprotein cholesterol and increased risk of cardiovascular mortality” by Dr Kawada

Hirata A., Okamura T.

Journal of Clinical Lipidology （Journal of Clinical Lipidology） 12 （ 6 ） 1551 2018年11月

ISSN 19332874

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Fatty liver index predicts incident diabetes in a Japanese general population with and without impaired fasting glucose

Hirata A, Sugiyama D, Kuwabara K, Hirata T, Tsutatani H, Funamoto M, Watanabe K, Miyamatsu N, Okamura T

Hepatology Research （Hepatology Research） 48 （ 9 ） 708 - 716 2018年08月

研究論文（学術雑誌）, 査読有り, ISSN 13866346

© 2018 The Japan Society of Hepatology Aim: Fatty liver is associated with the development of diabetes. However, to our knowledge, no study has examined the relationship between the fatty liver index (FLI), calculated scores of hepatic steatosis, and the development of diabetes among individuals without impaired fasting glucose (IFG). We aimed to examine whether FLI predicts the development of diabetes in individuals with and without IFG in a Japanese general population. Methods: We selected 1498 men and 2941 women who participated in Specific Health Checkups in Japan. We divided all participants into six groups according to tertiles of FLI (low, moderate, and high) and the presence or absence of IFG, by sex. We calculated hazard ratios for incident diabetes for each group using a Cox proportional hazard model, adjusting for potential confounders. Results: During a mean follow-up period of 3.0 years, 176 cases of diabetes in men and 320 cases in women were identified. Compared with the low FLI group without IFG, the high FLI group without IFG was significantly associated with incident diabetes in both men (hazard ratio, 1.90; 95% confidence interval, 1.08–3.36) and women (hazard ratio, 1.72; 95% confidence interval, 1.18–2.51). All IFG groups were significantly associated with incident diabetes regardless of FLI levels. Conclusions: Our results showed that FLI is associated with the development of diabetes regardless of sex and the presence or absence of IFG, and that it may be a useful predictor of future risk of incident diabetes even in individuals without IFG.

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Association of extremely high levels of high-density lipoprotein cholesterol with cardiovascular mortality in a pooled analysis of 9 cohort studies including 43,407 individuals: The EPOCH–JAPAN study

Hirata A, Sugiyama D, Watanabe M, Tamakoshi A, Iso H, Kotani K, Kiyama M, Yamada M, Ishikawa S, Murakami Y, Miura K, Ueshima H, Okamura T, Evidence for Cardiovascular Prevention from Observational Cohorts in Japan (EPOCH–JAPAN) Research Group.

Journal of Clinical Lipidology （Journal of Clinical Lipidology） 12 （ 3 ） 674 - 684 2018年05月

研究論文（学術雑誌）, 査読有り, ISSN 19332874

© 2018 National Lipid Association Background: The effect of very high or extremely high levels of high-density lipoprotein cholesterol (HDL-C) on cardiovascular disease (CVD) is not well described. Although a few recent studies have reported the adverse effects of extremely high levels of HDL-C on CVD events, these did not show a statistically significant association between extremely high levels of HDL-C and cause-specific CVD mortality. In addition, Asian populations have not been studied. Objective: We examine the impact of extremely high levels of HDL-C on cause-specific CVD mortality using pooled data of Japanese cohort studies. Methods: We performed a large-scale pooled analysis of 9 Japanese cohorts including 43,407 participants aged 40–89 years, dividing the participants into 5 groups by HDL-C levels, including extremely high levels of HDL-C ≥2.33 mmol/L (≥90 mg/dL). We estimated the adjusted hazard ratio of each HDL-C category for all-cause death and cause-specific deaths compared with HDL-C 1.04–1.55 mmol/L (40–59 mg/dL) using a cohort-stratified Cox proportional hazards model. Results: During a 12.1-year follow-up, 4995 all-cause deaths and 1280 deaths due to overall CVD were identified. Extremely high levels of HDL-C were significantly associated with increased risk of atherosclerotic CVD mortality (hazard ratio = 2.37, 95% confidence interval: 1.37–4.09 for total) and increased risk for coronary heart disease and ischemic stroke. In addition, the risk for extremely high HDL-C was more evident among current drinkers. Conclusion: We showed extremely high levels of HDL-C had an adverse effect on atherosclerotic CVD mortality in a pooled analysis of Japanese cohorts.

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Impacts of chronic kidney disease and diabetes on cardiovascular mortality in a general Japanese population: A 20-year follow-up of the NIPPON DATA90 study

Hirata A, Okamura T, Sugiyama D, Kuwabara K, Kadota A, Fujiyoshi A, Miura K, Okuda N, Ohkubo T, Okayama A, Ueshima H, NIPPON DATA90 and 2010 Research Group.

European Journal of Preventive Cardiology （European Journal of Preventive Cardiology） 24 （ 5 ） 505 - 513 2017年03月

研究論文（学術雑誌）, 査読有り, ISSN 20474873

© 2016 European Society of Cardiology. Background Studies have shown significant associations of chronic kidney disease (CKD) and diabetes mellitus (DM) with cardiovascular disease (CVD) mortality. The impact on the general population is an important public health issue. However, the population attributable fraction (PAF) of CVD because of CKD and/or DM in a general population is uncertain. Methods We followed 7229 participants (age: ≥30 years) with no history of CVD in a Japanese community. We divided participants into four categories according to CKD and/or DM and calculated hazard ratios (HRs) of CVD mortality for each category using a Cox proportional hazards model adjusted for age, dyslipidemia, smoking and alcohol consumption. In addition, PAFs of CVD were estimated among populations with CKD and/or DM. Results During 20-year follow-up, 488 participants died. HRs for CVD were 1.63 [95% confidence interval (CI): 1.16-2.30] with DM only, 1.42 (95% CI: 1.08-1.86) with CKD only and 2.37 (95% CI: 1.40-4.01) with CKD + DM. In men, the corresponding HRs for CVD were 1.88 (95% CI: 1.19-2.97), 1.71 (95% CI: 1.15-2.56) and 3.26 (95% CI: 1.69-6.30), respectively; the corresponding PAFs of CVD were 4.1%, 5.1% and 2.9%, respectively. PAFs for CVD among women were lower than those in men, 1.6% for DM only, 2.0% for CKD only and 0.7% for CKD + DM. Conclusions PAFs of CVD mortality due to CKD and/or DM were not so high in past 20 years; however, they might increase in the future because of recent increase in prevalence of these in Japanese population.

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Surveillance rates for hepatocellular carcinoma among patients with cirrhosis, chronic hepatitis B, and chronic hepatitis C based on Japanese claims database

Hirata A, Hirata T, Takahashi Y, Nakayama T

Hepatology Research （Hepatology Research） 47 （ 4 ） 283 - 292 2017年03月

研究論文（学術雑誌）, 査読有り, ISSN 13866346

© 2016 The Japan Society of Hepatology Aim: Surveillance is recommended for patients with risk of hepatocellular carcinoma (HCC) such as viral hepatitis and liver cirrhosis (LC). Although populations are at higher risk in Asia, surveillance rates have not been evaluated in those countries. Therefore, we aimed to examine surveillance rates for HCC and to compare predictors for surveillance among each type of liver disease in Japan. Methods: We carried out an observational study using the medical claims data of Japan. A total of 4713 patients who were diagnosed with LC, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection were followed for 12 months. We described surveillance rates in patients with HBV or HCV infection or non-viral LC and evaluated potential predictors for follow-up surveillance among them by using multivariable logistic regression analysis, in which we set explanatory variables as sex, age, medical facility, HBV or HCV infection, and LC. Results: The HCC surveillance rate during follow-up was 42.3% among patients with chronic viral hepatitis, 56.5% with viral cirrhosis and 26.0%, with non-viral LC. Significant predictors for follow-up surveillance were presence of LC and hospital visits. Hepatitis B virus-infected patients aged <50 years and HCV-infected patients aged ≥50 years were more likely to undergo exams, that is, different tendencies between HBV and HCV patients were shown. Conclusions: Follow-up surveillance for HCC was not adequately carried out among patients at risk for HCC in Japan, despite of recommendation in guidelines. In future, methodological research might be needed to increase surveillance rates for HCC in patients with chronic hepatitis or those who received treatment at a clinic.

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Impact of Flushing Response on the Relationship between Alcohol Consumption and Gamma-glutamyl Transpeptidase: the KOBE study.

Hirata T, Higashiyama A, Kubota Y, Sugiyama D, Kuwabara K, Tatsumi Y, Hirata A, Nishida Y, Kadota A, Imano H, Nishikawa T, Miyamatsu N, Miyamoto Y, Okamura T

Nihon Arukoru Yakubutsu Igakkai zasshi 51 （ 3 ） 173 - 183 2016年06月

研究論文（学術雑誌）, 査読有り, ISSN 1341-8963

The relationship between very high levels of serum high-density lipoprotein cholesterol and cause-specific mortality in a 20-year follow-up study of japanese general population

Hirata A, Okamura T, Sugiyama D, Kuwabara K, Kadota A, Fujiyoshi A, Miura K, Okuda N, Ohkubo T, Okayama A, Ueshima H, NIPPON DATA90 Research Group.

Journal of Atherosclerosis and Thrombosis （Journal of Atherosclerosis and Thrombosis） 23 （ 7 ） 800 - 809 2016年

研究論文（学術雑誌）, 査読有り, ISSN 13403478

© 2016, Japan Atherosclerosis Society. All rights reserved. Aims: There is no community-based cohort study to examine the effect of very high level of highdensity lipoprotein cholesterol (HDL-C) on coronary heart disease (CHD) and other cause-specific mortality. Therefore, we investigated the relationship between HDL-C including very high level and cause-specific mortality in a 20-year cohort study of the representative sample of Japanese. Methods: We followed 7,019 individuals from the Japanese general population (2,946 men and 4,073 women). We defined HDL-C levels as follow: low (HDL-C <1.04 mmol/L), reference (1.04-1.55 mmol/L), high (1.56- 2.06 mmol/L), very high (≥2.07 mmol/L). The multivariate adjusted hazard ratio (HR) for all-cause or cause-specific mortality was calculated using a Cox proportional hazards model adjusted for other traditional risk factors. Results: During follow-up, we observed 1,598 deaths. No significant association was observed between HDL-C and all-cause mortality. Serum HDL-C also showed no association with stroke. In contrast, the risk for CHD among high HDL-C was lower than reference, HRs were 0.51 [95% confidence interval (CI): 0.21-1.23] in men, 0.33 (95% CI: 0.11-0.95) in women, and 0.41 (95% CI: 0.21 -0.81) when men and women were combined. However, very high HDL-C did not show significant association with CHD and other cause-specific mortality. Conclusions: HDL-C was not associated with all-cause and stroke mortality. In contrast, high serum HDL-C levels, at least up to 2.06 mmol/L, were protective against CHD, although further high levels were not. However, sample size of cause-specific death in very high HDL-C group was not enough even in this 20-year follow-up of 7,019 Japanese; larger cohort studies should be warranted.

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