研究者詳細 - 宮川　尚子

論文 - 宮川　尚子

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Genome-wide association study of plasma amino acids and Mendelian randomization for cardiometabolic traits

Toki R., Fushiki S., Kojima S., Sutoh Y., Otsuka-Yamasaki Y., Harada S., Iida M., Hirata A., Miyagawa N., Matsumoto M., Edagawa S., Miyake A., Kuwabara K., Hirayama A., Sugimoto M., Sato A., Amano K., Soga T., Tomita M., Arakawa K., Kinoshita K., Sakurai-Yageta M., Tamiya G., Ohmomo H., Shimizu A., Okamura T., Takebayashi T.

Scientific Reports 15 （ 1 ） 14569 2025年12月

Plasma amino acids (AAs) have emerged as promising biomarkers for metabolic disorders, yet their causality remains unclear. We aimed to investigate the genetic determinants of AA levels in a cohort of 10,333 individuals and their causal effects on cardiometabolic traits using Mendelian randomization (MR). Plasma levels of 20 AAs were quantified using capillary electrophoresis mass spectrometry. Genome-wide association studies were conducted using BOLT-LMM and heritability estimation via LDSC analysis. Causal effects of AAs on 11 cardiometabolic traits were examined using two-sample MR analyses. We identified 85 locus-metabolite associations across 43 genes for 18 AAs, including 44 novel loci linked to metabolic genes. Heritability for AAs was estimated at 16%. MR analysis demonstrated cystine to positively associate with systolic blood pressure (SBP) (β = 0.056, SE = 0.010), while serine indicated protective effects on SBP (β = − 0.040, SE = 0.011), diastolic BP (β = − 0.044, SE = 0.010), and coronary artery disease (odds ratio 0.888, SE = 0.028). We identified potentially novel genetic loci associated with AA levels and demonstrated robust causal associations between several AAs and cardiometabolic traits. These findings reinforce the importance of AAs as potential biomarkers and therapeutic targets in cardiometabolic health.

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Causal relationship between body mass index and insulin resistance: Linear and nonlinear Mendelian randomization study in a Japanese population.

Ishida N, Harada S, Toki R, Hirata A, Matsumoto M, Miyagawa N, Iida M, Edagawa S, Miyake A, Kuwabara K, Shibuki T, Kato S, Arakawa K, Kinoshita K, Sakurai-Yageta M, Tamiya G, Nagashima K, Muraoka H, Sato Y, Takebayashi T

Journal of diabetes investigation 2025年04月

ISSN 2040-1116

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Dairy Intake and All-Cause, Cancer, and Cardiovascular Disease Mortality Risk in A Large Japanese Population: A 12-Year Follow-Up of the J-MICC Study.

Miyagawa N, Takashima N, Harada A, Kadota A, Kondo K, Miura K, Imaeda N, Goto C, Otonari J, Ikezaki H, Tanaka K, Shimanoe C, Nagayoshi M, Tamura T, Kubo Y, Kato Y, Koyanagi YN, Ito H, Michihata N, Nakamura Y, Tanoue S, Ibusuki R, Suzuki S, Nishiyama T, Ozaki E, Watanabe I, Kuriki K, Watanabe T, Ishizu M, Hishida A, Kita Y, Wakai K, Matsuo K, J-MICC Study Group

Journal of atherosclerosis and thrombosis （一般社団法人日本動脈硬化学会） advpub （ 0 ） 596 - 607 2024年11月

ISSN 1340-3478

AIM: We examined the association between dairy intake and all-cause, cancer, and cardiovascular disease mortality in a cohort of the general population followed up for 12 years across Japan. METHODS: We conducted a longitudinal cohort study of 79,715 participants from the Japan Multi-Institutional Collaborative Cohort study (57.2% women, mean age 54.7 years old). The amount of dairy (milk and yogurt) intake was determined using a validated short-food frequency questionnaire. The hazard ratio for mortality according to sex-specific tertile of dairy intake was calculated using Cox proportional hazards regression models with adjustment for potential confounding factors and dietary factors by sex. RESULTS: During the follow-up period (932,738 person-years), 3,723 participants died, including 2,088 cancer and 530 cardiovascular disease deaths. The highest tertile of total dairy intake (versus the lowest tertile) was associated with a 19% lower all-cause mortality risk (hazard ratio=0.81, 95% confidence interval: 0.70-0.92; P for trend=0.001) in women. Similarly, we observed inverse associations between milk intake and all-cause and cancer mortality risk in women, yogurt intake and cardiovascular disease risk in women, and yogurt intake and all-cause mortality risk in both sexes. CONCLUSION: A higher total dairy and milk intakes in women and yogurt intake in both sexes were associated with a reduced risk of all-cause mortality in the general population across Japan during the 12-year follow-up period.

Food group intakes and high-sensitivity C-reactive protein among community-dwelling Japanese adults: a cross-sectional study

Matsunaga T., Wakai K., Imaeda N., Goto C., Tamada Y., Kato Y., Kubo Y., Okada R., Nagayoshi M., Tamura T., Hishida A., Ikezaki H., Otonari J., Takashima N., Miyagawa N., Matsuo K.

Public Health Nutrition 27 （ 1 ） e212 2024年10月

ISSN 13689800

Objective: Healthy dietary patterns have been linked to lower levels of chronic inflammation. The present study aimed to investigate the associations between food group intakes and high-sensitivity C-reactive protein (hsCRP) among community-dwelling adults. Design: Cross-sectional. Setting: Three areas in Japan (Shiga, Fukuoka, or Kyushu and Okinawa). Participants: The present analysis included 13 648 participants (5126 males and 8522 females; age range, 35-69 years) who had been enrolled in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Food group intakes were estimated using a FFQ. Multiple linear regression was used to examine associations between the quartiles of each energy-adjusted food group intake and log-transformed hsCRP. Results: The following concentration ratios of hsCRP after comparing the highest and lowest quartiles of food group intake were significant: in males, 1.12 (95 % CI 1.02, 1.22) for processed meat, 1.13 (95 % CI 1.03, 1.24) for fish and 0.83 (95 % CI 0.76, 0.90) for nuts; in females, 0.89 (95 % CI 0.81, 0.97) for bread, 1.11 (95 % CI 1.03, 1.19) for processed meat, 0.86 (95 % CI 0.80, 0.92) for vegetables, 1.19 (95 % CI 1.11, 1.29) for fruit, 0.90 (95 % CI 0.84, 0.97) for nuts and 0.88 (95 % CI 0.82, 0.95) for green tea. Conclusions: Processed meat and nut intakes were associated with higher and lower hsCRP levels, respectively, in both sexes. However, for several food groups, including fish and fruit, previous findings from dietary pattern analyses were not supported by the present analyses at the food group level.

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[Validity assessment of self-reported medication use in a pharmacoepidemiologic study by comparison with prescription record review].

Yajima R, Matsumoto M, Iida M, Harada S, Shibuki T, Hirata A, Kuwabara K, Miyagawa N, Nakamura T, Okamura T, Takebayashi T

[Nihon koshu eisei zasshi] Japanese journal of public health （日本公衆衛生学会） 71 （ 8 ） 430 - 437 2024年08月

ISSN 0546-1766

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。

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 0546-1766

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。(著者抄録)

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 ） e5855 2024年08月

ISSN 10538569

Purpose: Hypertension (HT), dyslipidemia (DL), and diabetes mellitus (DM) are major risk factors for cardiovascular diseases. Despite the wide availability of medications to reduce this risk, poor adherence to medications remains an issue. The aim of this study is to evaluate medication adherence of prevalent users in these disease medications (HT, DL, DM) using claims data. Factors associated with non-adherence were also examined. Methods: Of 7538 participants of the Tsuruoka Metabolomics Cohort Study, 3693 (HT: 2702, DL: 2112, DM: 661) were identified as prevalent users of these disease medications. Information on lifestyle was collected through a questionnaire. Adherence was assessed by a proportion of days covered (PDC) and participants with PDC ≥0.8 were defined as adherent. Predictors of non-adherence were determined by performing multivariable logistic regression. Results: Medication adherence differed by treatment status. Among those without comorbidities, those with HT-only showed the highest adherence (90.2%), followed by those with DM-only (81.2%) and those with DL-only (80.8%). Factors associated with non-adherence in each medication group were skipping breakfast and poor understanding of medications among those with HT medications, females, having comorbidities, having a history of heart disease, and drinking habit among those with DL medications, and good sleep quality and skipping breakfast among those with DM medications. Conclusion: While participants showed high medication adherence, differences were observed across medication groups. The identified predictors of non-adherence could help target those in need of adherence support.

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Association between consumption of small fish and all-cause mortality among Japanese: the Japan Multi-Institutional Collaborative Cohort Study

Kasahara C., Tamura T., Wakai K., Tamada Y., Kato Y., Kubo Y., Okada R., Nagayoshi M., Hishida A., Imaeda N., Goto C., Otonari J., Ikezaki H., Nishida Y., Shimanoe C., Oze I., Koyanagi Y.N., Nakamura Y., Kusakabe M., Nishimoto D., Shimoshikiryo I., Suzuki S., Watanabe M., Ozaki E., Omichi C., Kuriki K., Takashima N., Miyagawa N., Arisawa K., Katsuura-Kamano S., Takeuchi K., Matsuo K.

Public Health Nutrition 27 （ 1 ） e135 - 40 2024年05月

ISSN 13689800

Objective: Although small fish are an important source of micronutrients, the relationship between their intake and mortality remains unclear. This study aimed to clarify the association between intake of small fish and all-cause and cause-specific mortality. Design: We used the data from a cohort study in Japan. The frequency of the intake of small fish was assessed using a validated FFQ. The hazard ratio (HR) and 95 % confidence interval (CI) for all-cause and cause-specific mortality according to the frequency of the intake of small fish by sex were estimated using a Cox proportional hazard model with adjustments for covariates. Setting: The Japan Multi-Institutional Collaborative Cohort Study. Participants: A total of 80 802 participants (34 555 males and 46 247 females), aged 35-69 years. Results: During a mean follow-up of 9·0 years, we identified 2482 deaths including 1495 cancer-related deaths. The intake of small fish was statistically significantly and inversely associated with the risk of all-cause and cancer mortality in females. The multivariable-adjusted HR (95 % CI) in females for all-cause mortality according to the intake were 0·68 (0·55, 0·85) for intakes 1-3 times/month, 0·72 (0·57, 0·90) for 1-2 times/week and 0·69 (0·54, 0·88) for ≥ 3 times/week, compared with the rare intake. The corresponding HR (95 % CI) in females for cancer mortality were 0·72 (0·54, 0·96), 0·71 (0·53, 0·96) and 0·64 (0·46, 0·89), respectively. No statistically significant association was observed in males. Conclusions: Intake of small fish may reduce the risk of all-cause and cancer mortality in Japanese females.

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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） advpub （ 0 ） 1031 - 1047 2024年02月

ISSN 1340-3478

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.

スポット尿中のナトリウム・カリウム排泄状況と栄養素等摂取量・食品群摂取量の関連

中川夕美, 由田克士, 宮川尚子, 岡見雪子, 大久保孝義, 岡村智教, 三浦克之, NIPPON DATA2010研究グループ

栄養学雑誌（特定非営利活動法人日本栄養改善学会） 82 （ 1 ） 13 - 23 2024年02月

ISSN 00215147

【目的】スポット尿から推定した24時間尿中のナトリウム (Na)・カリウム (K) 排泄量と食事記録法により求められた栄養素等摂取量および食品群摂取量の関連を検討する。【方法】平成22年国民健康・栄養調査およびNIPPON DATA2010の参加者から，重篤な循環器疾患，腎臓病または腎機能低下と指摘された者および高血圧，糖尿病，脂質異常症の治療中の者を除いた男性581人，女性923人を対象とした。性別に推定24時間尿中のNaとKの排泄量の中央値で多／少を組み合わせた4群間 (尿中K多Na少群，尿中K多Na多群，尿中K少Na少群，尿中K少Na多群) で栄養素等摂取量と食品群別摂取量を比較した。【結果】尿中へのK排泄量が多くNa排泄量も多い群（尿中K多Na多群）は男女ともK摂取量が尿中K少群より多く，女性においてNaおよび漬け物の摂取量が尿中Na少群より多く，野菜類摂取量が尿中K少群より多かった。尿中K少Na少群は男女ともK摂取量が尿中K多群より少なかった。尿中K少Na多群は食事中Na/K比が女性で最も高かった。尿中K多Na少群は，食事中Na/K比が女性で最も低く，男女ともK摂取量，乳類の摂取量が尿中K少群より多かった。【結論】集団レベルにおいて，スポット尿から推定した24時間尿中のNaとKの排泄量は，NaやKの摂取状況，およびKの寄与率が高い食品群の摂取量と関連している可能性が示唆された。

スポット尿中のナトリウム・カリウム排泄状況と栄養素等摂取量・食品群摂取量の関連　NIPPON DATA2010

中川夕美, 由田克士, 宮川尚子, 岡見雪子, 大久保孝義, 岡村智教, 三浦克之

栄養学雑誌（(NPO)日本栄養改善学会） 82 （ 1 ） 13 - 23 2024年02月

ISSN 0021-5147

【目的】スポット尿から推定した24時間尿中のナトリウム(Na)・カリウム(K)排泄量と食事記録法により求められた栄養素等摂取量および食品群摂取量の関連を検討する。【方法】平成22年国民健康・栄養調査およびNIPPON DATA2010の参加者から,重篤な循環器疾患,腎臓病または腎機能低下と指摘された者および高血圧,糖尿病,脂質異常症の治療中の者を除いた男性581人,女性923人を対象とした。性別に推定24時間尿中のNaとKの排泄量の中央値で多/少を組み合わせた4群間(尿中K多Na少群,尿中K多Na多群,尿中K少Na少群,尿中K少Na多群)で栄養素等摂取量と食品群別摂取量を比較した。【結果】尿中へのK排泄量が多くNa排泄量も多い群(尿中K多Na多群)は男女ともK摂取量が尿中K少群より多く,女性においてNaおよび漬け物の摂取量が尿中Na少群より多く,野菜類摂取量が尿中K少群より多かった。尿中K少Na少群は男女ともK摂取量が尿中K多群より少なかった。尿中K少Na多群は食事中Na/K比が女性で最も高かった。尿中K多Na少群は,食事中Na/K比が女性で最も低く,男女ともK摂取量,乳類の摂取量が尿中K少群より多かった。【結論】集団レベルにおいて,スポット尿から推定した24時間尿中のNaとKの排泄量は,NaやKの摂取状況,およびKの寄与率が高い食品群の摂取量と関連している可能性が示唆された。(著者抄録)

Seven-plus hours of daily sedentary time and the subsequent risk of breast cancer: Japan Multi-Institutional Collaborative Cohort Study

Tomida S., Koyama T., Ozaki E., Takashima N., Morita M., Sakaguchi K., Naoi Y., Nishida Y., Hara M., Hishida A., Tamura T., Okada R., Kubo Y., Otonari J., Ikezaki H., Nakamura Y., Kusakabe M., Tanoue S., Koriyama C., Koyanagi Y.N., Ito H., Suzuki S., Otani T., Miyagawa N., Okami Y., Arisawa K., Watanabe T., Kuriki K., Wakai K., Matsuo K.

Cancer Science （Cancer Science） 115 （ 2 ） 611 - 622 2024年02月

ISSN 13479032

This study aimed to investigate the association between daily sedentary time and the risk of breast cancer (BC) in a large Japanese population. The participants were 36,023 women aged 35–69 years from the Japan Multi-Institutional Collaborative Cohort Study. Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for BC incidence in relation to time spent sedentarily (categorical variables: <7 and ≥7 hours/day [h/d]). Additionally, the associations of BC incidence to the joint effect of sedentary time with each component of physical activity, such as leisure-time metabolic equivalents (METs), frequency of leisure-time physical activity, and daily walking time, were examined. During 315,189 person-years of follow-up, 554 incident cases of BC were identified. When compared to participants who spent <7 h/d sedentary, those who spent ≥7 h/d sedentary have a significantly higher risk of BC (HR, 1.36; 95% CI, 1.07–1.71). The corresponding HRs among participants who spent ≥7 h/d sedentary with more physical activity, such as ≥1 h/d for leisure-time METs, ≥3 days/week of leisure-time physical activity, and ≥1 h/d of daily walking were 1.58 (95% CI, 1.11–2.25), 1.77 (95% CI, 1.20–2.61), and 1.42 (95% CI, 1.10–1.83), respectively, compared with those who spent <7 h/d sedentary. This study found that spending ≥7 h/d of sedentary time is associated with the risk of BC. Neither leisure-time physical activity nor walking had a BC-preventive effect in those with ≥7 h/d of sedentary time.

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Association of step counts with cognitive function in apparently healthy middle-aged and older Japanese men

Shibukawa T., Fujiyoshi A., Moniruzzaman M., Miyagawa N., Kadota A., Kondo K., Saito Y., Kadowaki S., Hisamatsu T., Yano Y., Arima H., Tooyama I., Ueshima H., Miura K.

Preventive Medicine Reports （Preventive Medicine Reports） 38 102615 - 102615 2024年02月

ISSN 2211-3355

Background: Increasing physical activity may prevent cognitive decline. Previous studies primarily focused on older adults and used self-reported questionnaires to assess physical activity. We examined the relationship between step count, an objective measure of physical activity, and cognitive function in community-based middle-aged and older Japanese men. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis randomly recruited community-dwelling healthy men aged 40–79 years from Shiga, Japan, and measured their step counts over 7 consecutive days using a pedometer at baseline (2006–2008). Among men who returned for follow-up (2009–2014), we assessed their cognitive function using the Cognitive Abilities Screening Instrument (CASI) score. We restricted our analyses to those with valid 7-day average step counts at baseline and those who remained free of stroke at follow-up (n = 676). Using analysis of covariance, we calculated the adjusted means of the CASI score according to the quartiles of the average step counts. Results: The mean (standard deviation) of age and unadjusted CASI score were 63.8 (9.1) years and 90.8 (5.8), respectively. The CASI score was elevated in higher quartiles of step counts (90.2, 90.4, 90.6, and 91.8 from the lowest to the highest quartile, respectively, [p for trend = 0.004]) in a model adjusted for age and education. Further adjustment for smoking, drinking, and other cardiovascular risk factors resulted in a similar pattern of association (p for trend = 0.005). Conclusion: In apparently healthy middle-aged and older Japanese men, a greater 7-day average step count at baseline was associated with significantly higher cognitive function score.

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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） advpub （ 0 ） 393 - 401 2024年01月

ISSN 0917-5040

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.

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 （Metabolites） 14 （ 1 ） 2024年01月

ISSN 2218-1989

Studies examining long-term longitudinal metabolomic data and their reliability in large-scale populations are limited. Therefore, we aimed to evaluate the reliability of repeated measurements of plasma metabolites in a prospective cohort setting and to explore intra-individual concentration changes at three time points over a 6-year period. The study participants included 2999 individuals (1317 men and 1682 women) from the Tsuruoka Metabolomics Cohort Study, who participated in all three surveys—at baseline, 3 years, and 6 years. In each survey, 94 plasma metabolites were quantified for each individual and quality control (QC) sample. The coefficients of variation of QC, intraclass correlation coefficients, and change rates of QC were calculated for each metabolite, and their reliability was classified into three categories: excellent, fair to good, and poor. Seventy-six percent (71/94) of metabolites were classified as fair to good or better. Of the 39 metabolites grouped as excellent, 29 (74%) in men and 26 (67%) in women showed significant intra-individual changes over 6 years. Overall, our study demonstrated a high degree of reliability for repeated metabolome measurements. Many highly reliable metabolites showed significant changes over the 6-year period, suggesting that repeated longitudinal metabolome measurements are useful for epidemiological studies.

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Association between awareness of limiting food intake and all-cause mortality: A cohort study in Japan.

Nishimoto D, Ibusuki R, Shimoshikiryo I, Shibuya K, Tanoue S, Koriyama C, Takezaki T, Oze I, Ito H, Hishida A, Tamura T, Kato Y, Tamada Y, Nishida Y, Shimanoe C, Suzuki S, Nishiyama T, Ozaki E, Tomida S, Kuriki K, Miyagawa N, Kondo K, Arisawa K, Watanabe T, Ikezaki H, Otonari J, Wakai K, Matsuo K

Journal of epidemiology （日本疫学会） advpub （ 0 ） 286 - 294 2023年11月

ISSN 0917-5040

Background: Improving diets requires an awareness of the need to limit foods for which excessive consumption is a health problem. Since there are limited reports on the link between this awareness and mortality risk, we examined the association between awareness of limiting food intake (energy, fat, and sweets) and all-cause mortality in a Japanese cohort study. Methods: Participants comprised 58,772 residents (27,294 men; 31,478 women) aged 35–69 years who completed baseline surveys of the Japan Multi-Institutional Collaborative Cohort Study from 2004 to 2014. Hazard ratios (HRs) for all-cause mortality and 95% confidence intervals (CIs) were estimated by sex using a Cox proportional hazard model, with adjustment for related factors. Mediation analysis with fat intake as a mediator was also conducted. Results: The mean follow-up period was 11 years, and 2,516 people died. Estimated energy and fat intakes according to the Food Frequency Questionnaire were lower in those with awareness of limiting food intake than in those without this awareness. Women with awareness of limiting fat intake showed a significant decrease in mortality risk (HR 0.73; 95% CI, 0.55–0.94). Mediation analysis revealed that this association was due to the direct effect of the awareness of limiting fat intake and that the total effect was not mediated by actual fat intake. Awareness of limiting energy or sweets intake was not related to mortality risk reduction. Conclusion: Awareness of limiting food intake had a limited effect on reducing all-cause mortality risk.

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） advpub （ 0 ） 403 - 410 2023年11月

ISSN 0917-5040

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.

Association of Arterial Stiffness and Atherosclerotic Burden With Brain Structural Changes Among Japanese Men.

Azahar NM, Yano Y, Kadota A, Shiino A, Syaifullah AH, Miyagawa N, Kondo K, Moniruzzaman M, Torii S, Segawa H, Hisamatsu T, Fujiyoshi A, Nozaki K, Tooyama I, Ueshima H, Miura K, SESSA Research Group

Journal of the American Heart Association （Journal of the American Heart Association） 12 （ 11 ） e028586 2023年06月

BACKGROUND: Little is known regarding whether arterial stiffness and atherosclerotic burden are each independently associated with brain structural changes. Simultaneous assessments of both arterial stiffness and atherosclerotic burden in associations with brain could provide insights into the mechanisms of brain structural changes. METHODS AND RESULTS: Using data from the SESSA (Shiga Epidemiological Study of Subclinical Atherosclerosis), we analyzed data among 686 Japanese men (mean [SD] age, 67.9 [8.4] years; range, 46–83 years) free from history of stroke and myo-cardial infarction. Brachial-ankle pulse wave velocity and coronary artery calcification on computed tomography scans were measured between March 2010 and August 2014. Brain volumes (total brain volume, gray matter, Alzheimer disease signature and prefrontal) and brain vascular damage (white matter hyperintensities) were quantified using brain magnetic resonance imaging from January 2012 through February 2015. In multivariable adjustment models including mean arterial pressure, when brachial-ankle pulse wave velocity and coronary artery calcification were entered into the same models, the β (95% CI) for Alzheimer disease signature volume for each 1-SD increase in brachial-ankle pulse wave velocity was −0.33 (−0.64 to −0.02), and the unstandardized β (95% CI) for white matter hyperintensities for each 1-unit increase in coronary artery calcification was 0.68 (0.05–1.32). Brachial-ankle pulse wave velocity and coronary artery calcification were not statistically significantly associated with total brain and gray matter volumes. CONCLUSIONS: Among Japanese men, higher arterial stiffness was associated with lower Alzheimer disease signature vol-umes, whereas higher atherosclerotic burden was associated with brain vascular damage. Arterial stiffness and atheroscle-rotic burden may be independently associated with brain structural changes via different pathways.

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Circulating plasma phospholipid fatty acid levels as a biomarker of habitual dietary fat intake: The INTERMAP/INTERLIPID Study

Miyagawa N., Sekikawa A., Miura K., Evans R.W., Okuda N., Fujiyoshi A., Yoshita K., Chan Q., Okami Y., Kadota A., Willcox B., Masaki K., Rodriguez B., Sakata K., Nakagawa H., Saitoh S., Okayama A., Kuller L.H., Elliott P., Stamler J., Ueshima H.

Journal of Clinical Lipidology （Journal of Clinical Lipidology） 17 （ 1 ） 131 - 141 2023年

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り, ISSN 19332874

Background: Accurate assessment of fat intake is essential to examine relationships between diet and disease risk. However, estimating individual intakes of fat quantity by dietary assessment is difficult. Objective: We assessed the association of plasma phospholipid fatty acid levels with dietary intake of fatty acids in the INTERMAP/INTERLIPID study, conducted with a standardized protocol. Methods: The study participants were 1339 men and women ages 40–59 years from five Japanese populations one from Hawaii; four from Japan. Fatty acid intake was estimated from four standardized 24-hour dietary recalls. Plasma phospholipid fatty acid composition was analyzed by gas chromatography. We illustrated the relationship between intake and circulating fatty acid levels using Spearman's rank-correlation coefficients, mean, and median values. Results: Spearman's rank-correlation coefficients between intake (g/d) and circulating fatty acid levels (µg/ml) were -0.03 to 0.21 for saturated fatty acids and monounsaturated fatty acids and -0.04 to 0.32 for trans fatty acids. The coefficients for essential n-3 and n-6 fatty acids were moderate to high, especially for eicosapentaenoic acid (EPA), 0.60; docosahexaenoic acid (DHA), 0.41; and EPA+DHA, 0.51. The circulating levels and intake of marine-derived n-3 fatty acids showed a linear association, at least for the intake of EPA+DHA up to 2.1 g/d. Conclusion: We observed high correlation between intake and circulating levels of marine-derived n-3 fatty acids in participants from Japanese and Japanese-American populations with high and low fish intake. Plasma phospholipid marine-derived n-3 fatty acid measurements are a simple and reliable biomarker for assessing dietary intake.

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Coffee and metabolic phenotypes: A cross-sectional analysis of the Japan multi-institutional collaborative cohort (J-MICC) study

Watanabe T., Arisawa K., Nguyen T.V., Ishizu M., Katsuura-Kamano S., Hishida A., Tamura T., Kato Y., Okada R., Ibusuki R., Koriyama C., Suzuki S., Otani T., Koyama T., Tomida S., Kuriki K., Takashima N., Miyagawa N., Wakai K., Matsuo K.

Nutrition, Metabolism and Cardiovascular Diseases （Nutrition, Metabolism and Cardiovascular Diseases） 33 （ 3 ） 620 - 630 2022年12月

ISSN 0939-4753

Background and aims: To date, the relationship between coffee consumption and metabolic phenotypes has hardly been investigated and remains controversial. Therefore, the aim of this cross-sectional study is to examine the associations between coffee consumption and metabolic phenotypes in a Japanese population. Methods and results: We analyzed the data of 26,363 subjects (aged 35–69 years) in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Coffee consumption was assessed using a questionnaire. Metabolic Syndrome (MetS) was defined according to the Joint Interim Statement Criteria of 2009, using body mass index (BMI) instead of waist circumference. Subjects stratified by the presence or absence of obesity (normal weight: BMI <25 kg/m2; obesity: BMI ≥25 kg/m2) were classified by the number of MetS components (metabolically healthy: no components; metabolically unhealthy: one or more components) other than BMI. In multiple logistic regression analyses adjusted for sex, age, and other potential confounders, high coffee consumption (≥3 cups/day) was associated with a lower prevalence of MetS and metabolically unhealthy phenotypes both in normal weight (OR 0.83, 95% CI 0.76–0.90) and obese subjects (OR 0.83, 95% CI 0.69–0.99). Filtered/instant coffee consumption was inversely associated with the prevalence of MetS and metabolically unhealthy phenotypes, whereas canned/bottled/packed coffee consumption was not. Conclusion: The present results suggest that high coffee consumption, particularly filtered/instant coffee, is inversely associated with the prevalence of metabolically unhealthy phenotypes in both normal weight and obese Japanese adults.

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Relationship between Serum Irisin Levels and MRI-Measured Cerebral Small Vessel Disease in Japanese Men.

Moniruzzaman M, Kadota A, Hisamatsu T, Segawa H, Kondo K, Torii S, Miyagawa N, Fujiyoshi A, Yano Y, Watanabe Y, Shiino A, Nozaki K, Ueshima H, Miura K, SESSA Research Group

Journal of atherosclerosis and thrombosis （一般社団法人日本動脈硬化学会） advpub （ 0 ） 1045 - 1056 2022年11月

ISSN 1340-3478

Aim: Irisin, an exercise-induced myokine, is a potential neurotrophic factor; however, its relationship with cerebral small vessel disease (CSVD) remains unknown. Therefore, we investigated whether serum irisin levels are associated with CSVD in healthy Japanese men. Methods: We analyzed data from 720 men free of stroke and participated in this observational study. Serum irisin levels were measured by enzyme-linked immunosorbent assay. CSVD was assessed on deep and subcortical white matter hyperintensities (DSWMHs), periventricular hyperintensities (PVHs), lacunar infarcts (LIs), and cerebral microbleeds (CMBs) on brain magnetic resonance imaging. We calculated the total CSVD score (ranges 0–4) to express the total CSVD burden. We computed the adjusted odds ratios (ORs), with 95% confidence intervals (CIs), of the total CSVD score and individual CSVD features using logistic regression models according to the quartiles of irisin (reference: Q1). Results: Serum irisin levels were associated with lower ORs of higher (vs. zero or lower score) total CSVD score, with the lowest risk (OR, 0.63; 95% CI, 0.41–0.97) being observed in Q3 compared to Q1 after adjustment of potential covariates. Similar results were obtained for younger adults (＜65 years). Among individual CSVD features, irisin was associated with a reduced risk of LIs in the total sample and PVHs, LIs, and CMBs in younger adults. No relationship was observed in older adults (≥ 65 years). Conclusions: Serum irisin levels were associated with less burden of total CSVD in healthy Japanese men. Serum irisin levels were also related with a reduced risk of PVHs, LIs, and CMBs, but not DSWMHs.

Small High-Density Lipoprotein and Omega-3 Fatty Acid Intake Differentiates Japanese and Japanese-Americans: The INTERLIPID Study.

Okami Y, Chan Q, Miura K, Kadota A, Elliott P, Masaki K, Okayama A, Okuda N, Yoshita K, Miyagawa N, Okamura T, Sakata K, Saitoh S, Sakurai M, Nakagawa H, Stamler J, Ueshima H, INTERMAP and INTERLIPID Research Groups

Journal of atherosclerosis and thrombosis （一般社団法人日本動脈硬化学会） advpub （ 0 ） 884 - 906 2022年11月

ISSN 1340-3478

Aim: To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii, in the absence of possible genetic confounders, and cross-sectionally examine the associated modifiable lifestyle factors. Methods: Overall, 1,241 (aged 40–59 years) Japanese living in Japan and Japanese-Americans in Hawaii were included. We quantified 130 serum lipid profiles (VLDL 1-5, IDL, LDL 1-6, high-density lipoprotein [HDL] 1-4, and their subfractions) using Bruker’s1H-nuclear magnetic resonance spectrometer for the primary outcome. Modifiable lifestyle factors included body mass index (BMI), physical activity, alcohol and smoking habits, and 70 nutrient parameters. We evaluated the different lipids between the groups using partial least squares-discriminant analysis and association between extracted lipids and lifestyle factors using multivariable linear regression analysis. Results: Concentrations of HDL4, HDL with the smallest particle size, were lower in Japanese than in Japanese-Americans of both sexes. Higher fish-derived omega-3 fatty acid intake and lower alcohol intake were associated with lower HDL4 concentrations. A 1% higher kcal intake of total omega-3 fatty acids was associated with a 9.8-mg/dL lower HDL4. Fish-derived docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid intake were inversely associated with HDL4 concentration. There was no relationship between country, sex, age, or BMI. Conclusions: Japanese and Japanese-Americans can be differentiated based on HDL4 concentration. High fish intake among the Japanese may contribute to their lower HDL4 concentration. Thus, HDL particle size may be an important clinical marker for coronary artery diseases or a fish consumption biomarker.

Inverse association of seafood intake with becoming overweight among survivors of the Great East Japan Earthquake

Tsuboyama-Kasaoka N., Ueda S., Miyagawa N., Nishi N., Shimoda H., Sakata K., Ogawa A., Kobayashi S.

International Journal of Disaster Risk Reduction （International Journal of Disaster Risk Reduction） 79 2022年09月

ISSN 22124209

Obesity is a major health issue after disaster. However, the types of food associated with obesity that increases in response to prolonged evacuation are unknown. Therefore, this study aimed to clarify the association between seafood intake following the Great East Japan Earthquake of 2011 and becoming overweight within 2 years after that baseline. We followed 4410 Japanese survivors aged ≥18 years (mean age 62.3 years) who were not overweight at baseline. In 2011, all participants completed a self-administered questionnaire regarding food intake and lifestyle and had a subsequent follow-up in 2013. Multiple logistic regression analysis was performed. During the 2-year follow-up, 296 participants became overweight. Frequency of fish and shellfish intake in men was significantly and inversely associated with becoming overweight after adjusting for confounding factors. The multivariable-adjusted odds ratios for becoming overweight in men was lower in the group with the highest intake of fish and shellfish (odds ratio 0.24; 95% confidence interval, 0.06–0.90) than in the group with the lowest intake in Model 1, and the trend was statistically significant in all models. This significant association was observed in temporary housing but not in non-temporary housing. We showed that consuming seafood may have an obesity-suppressing effect in men who suffered from disaster and lived in temporary housing. Seafood might be a key factor in reducing overweight/obesity not only after a disaster but also during a pandemic and in regions with low seafood intake.

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Effect of diabetes and prediabetes on the development of disability and mortality among middle-aged adult Japanese: a 22-year follow-up of NIPPON DATA90.

Tran Ngoc Hoang P, Kadota A, Yuichiro Y, Akiko H, Takehito H, Shohei O, Miyagawa N, Kondo K, Nagako O, Kita Y, Okayama A, Yukihiro F, Maegawa H, Miura K, Okamura T, Ueshima H, NIPPON DATA90 Research Group.

Journal of diabetes investigation （Journal of Diabetes Investigation） 13 （ 11 ） 1897 - 1904 2022年06月

ISSN 2040-1116

Aims/Introduction: To examine the association between diabetes and prediabetes at baseline, and disability, mortality over a 22-year period among middle-aged Japanese adults. Materials and Methods: Participants consisted of 1,788 adults aged 45–64 years at baseline from the cohort study National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged 1990 (NIPPON DATA90). Disability, defined as having a decline in activities of daily living (ADL), was assessed by a modified Katz questionnaire at four time points. Disability and death without disability for 22-year follow up were used as outcomes to test the association with a diagnosis of diabetes or prediabetes at baseline, using multinomial logistic regression. Adjusted odds ratios (ORs) were obtained from four models that contained appropriate adjustment factors, such as age, sex, smoking status, drinking status, body mass index and cardiovascular risk factors (hypertension, hypercholesterolemia, triglycerides, low serum high-density lipoprotein), at baseline. Results: In the present study, 334 participants (18.7%) reported at least one disability, and 350 (19.6%) were reported dead without observation of disability during follow up. Adjusting sex and other risk factors, participants with diabetes and prediabetes had a higher risk for disability (OR 1.43, 95% confidence interval [CI] 1.07–1.91 and OR 1.66, 95% CI 1.10–2.50, respectively) and for mortality (OR 1.56, 95% CI 1.16–2.08 and OR 1.77, 95% CI 1.18–2.65, respectively) than individuals with normal glucose tolerance. Conclusions: In middle-aged Japanese adults, individuals with diabetes and prediabetes were more likely to be associated with disability and mortality. Our findings suggest that prediabetes and diabetes in middle-aged adults should be paid more attention, and requires more intervention to prevent disability and mortality in later life.

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Association between C-Reactive Protein Levels and Functional Disability in the General Older-Population: The Takashima Study.

Takashima N, Nakamura Y, Miyagawa N, Kadota A, Saito Y, Matsui K, Miura K, Ueshima H, Kita Y

Journal of atherosclerosis and thrombosis （一般社団法人日本動脈硬化学会） advpub （ 0 ） 56 - 65 2022年03月

ISSN 1340-3478

Aims: High-sensitivity C-reactive protein (hsCRP) associates with atherosclerotic diseases such as stroke. However, previous results on the association between hsCRP levels and functional disability were controversial. Methods: We analyzed 2,610 men and women who did not exhibit functional disability or death within the first 3 years of the baseline survey and those aged 65 years or older at the end of follow-up. The levels of hsCRP were assessed using latex agglutination assay at baseline survey from 2006 to 2014. Functional disability was followed up using the long-term care insurance (LTCI) program until November 1, 2019. Functional disability was defined as a new LTCI program certification. Cox proportional hazards model with competing risk analysis for death was used to evaluate the association between hsCRP levels and future functional disability. Results: During a 9-year follow-up period, we observed 328 cases of functional disability and 67 deaths without prior functional disability incidence. The multivariable-adjusted hazard ratio (HR, 95% confidence interval [CI]) of functional disability in log-transferred hsCRP levels was 1.43 (1.22–1.67) in men and 0.97 (0.81–1.15) in women. When hsCRP level was analyzed as a categorical variable, low hsCRP levels (＜1.0 mg/l) as the reference, the multivariable-adjusted HR (95% CI) of functional disability in high hsCRP levels (≥ 3.0 mg/l) was 2.37 (1.56–3.62). Similar results were observed when stratified by sex, but it was not significant in women. Conclusions: This study demonstrates that low-grade systemic inflammation to assess hsCRP might predict the future incidence of functional disability, especially in men.

Dietary Patterns and Their Associations with Intermediate Age-Related Macular Degeneration in a Japanese Population

Sasaki M., Miyagawa N., Harada S., Tsubota K., Takebayashi T., Nishiwaki Y., Kawasaki R.

Journal of Clinical Medicine （Journal of Clinical Medicine） 11 （ 6 ） 2022年03月

ISSN 2077-0383

This population-based cross-sectional study investigated the influence of dietary patterns on age-related macular degeneration (AMD) in a Japanese population. The Tsuruoka Metabolomics Cohort Study enrolled a general population aged 35–74 years from among participants in annual health check-up programs in Tsuruoka City, Japan. Eating habits were assessed using a food frequency questionnaire. Principal component analysis was used to identify dietary patterns among food items. The association between quartiles of scores for each dietary pattern and intermediate AMD was assessed using multivariate logistic regression models. Of 3433 participants, 415 had intermediate AMD. We identified four principal components comprising the Vegetable-rich pattern, Varied staple food pattern, Animal-rich pattern, and Seafood-rich pattern. After adjusting for potential confounders, higher Varied staple food diet scores were associated with a lower prevalence of intermediate AMD (fourth vs. first quartile) (OR, 0.63; 95% confidence interval [CI], 0.46–0.86). A significant trend of decreasing ORs for intermediate AMD associated with increasing Varied staple food diet scores was noted (p for trend = 0.002). There was no significant association between the other dietary patterns and intermediate AMD. In a Japanese population, individuals with a dietary pattern score high in the Varied staple food pattern had a lower prevalence of intermediate AMD.

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高血圧の指摘や治療の継続状況と野菜摂取量の関連　NIPPON DATA2010

中川夕美, 由田克士, 荒井裕介, 尾島俊之, 藤吉朗, 中川秀昭, 奥田奈賀子, 宮川尚子, 門田文, 近藤慶子, 岡村智教, 大久保孝義, 西信雄, 上島弘嗣, 岡山明, 三浦克之

日本循環器病予防学会誌（(一社)日本循環器病予防学会） 57 （ 1 ） 42 - 54 2022年03月

ISSN 1346-6267

【目的】高血圧者に対する食事指導等の介入によって野菜摂取量の増加が認められたとする報告はこれまでにもあるが、高血圧を指摘されることそれ自体や治療の継続状況と野菜摂取量の関連を検討した報告はない。そこで本研究では、高血圧の指摘や治療の継続状況が、実際の野菜摂取量に影響を与えるのか検討した。【方法】平成22年国民健康・栄養調査及びNIPPON DATA2010の20歳以上の参加者を対象とした。このうち、これまでに医療機関や健康診査で脳卒中、心筋梗塞、腎臓病または腎機能低下と指摘されたことはないが、高血圧の指摘を受けている者もしくは高血圧、糖尿病、脂質異常症のいずれの指摘も受けたことはないが、国民健康・栄養調査の血圧測定値が高血圧(収縮期血圧140mmHg以上または拡張期血圧90mmHg以上の者と定義)であった高値血圧者の男女1,004人を解析対象とした。野菜摂取量が多いこと(1日350g以上)をアウトカムとして、高血圧を指摘されることやその後の治療の継続状況(治療継続、治療中断、未治療)との関連をロジスティック回帰分析にて検討した。【結果】野菜摂取量が多いことと高血圧を指摘されることは男女とも有意な関連はなく、野菜を積極的に摂取しようと心がけることとのオッズ比が男性1.72(95%CI:1.17-2.53)、女性1.51(95%CI:1.04-2.21)と有意な正の関連が認められた。野菜摂取量が多いことと高血圧者における治療の継続状況では、野菜を積極的に摂取しようと心がけることとのオッズ比が男性1.69(95%CI:1.07-2.68)と有意な正の関連、「治療中断」の女性でオッズ比0.37(95%CI:0.15-0.90)と有意な負の関連がみられた。【結論】男女とも野菜の摂取量と高血圧の指摘自体との関連は認められなかったが、女性では治療中断と負の関連が示唆された。(著者抄録)

A genome-wide association study on adherence to low-carbohydrate diets in Japanese.

Nakamura Y, Tamura T, Narita A, Shimizu A, Sutoh Y, Takashima N, Matsui K, Miyagawa N, Kadota A, Miura K, Otonari J, Ikezaki H, Hishida A, Nagayoshi M, Okada R, Kubo Y, Tanaka K, Shimanoe C, Ibusuki R, Nishimoto D, Oze I, Ito H, Ozaki E, Matsui D, Mikami H, Kusakabe M, Suzuki S, Watanabe M, Arisawa K, Katsuura-Kamano S, Kuriki K, Nakatochi M, Momozawa Y, Kubo M, Takeuchi K, Wakai K, J-MICC Research Group Consortium.

European journal of clinical nutrition （European Journal of Clinical Nutrition） 76 （ 8 ） 1103 - 1110 2022年02月

研究論文（学術雑誌）, 共著, ISSN 0954-3007

Background/objectives: Low-carbohydrate diets (LCD) are useful for weight reduction, and 50–55% carbohydrate consumption is associated with minimal risk. Genetic differences were related to nutritional consumption, food preferences, and dietary patterns, but whether particular genetic differences in individuals influence LCD adherence is unknown. Subjects/methods: We conducted a GWAS on adherence to LCD utilizing 14,076 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a previously validated semiquantitative food frequency questionnaire to estimate food consumption. Association of the imputed variants with the LCD score by Halton et al. we used linear regression analysis adjusting for sex, age, total dietary energy consumption, and components 1 to 10 by principal component analysis. We repeated the analysis with adjustment for alcohol consumption (g/day) in addition to the above-described variables. Results: Men and women combined analysis without adjustment for alcohol consumption; we found 395 variants on chromosome 12 associated with the LCD score having P values <5 × 10−8. A conditional analysis with the addition of the dosage data of rs671 on chromosome 12 as a covariate, P values for all 395 SNPs on chromosome 12 turned out to be insignificant. In the analysis with additional adjustment for alcohol consumption, we did not identify any SNPs associated with the LCD score. Conclusion: We found rs671 was inversely associated with adherence to LCD, but that was strongly confounded by alcohol consumption.

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Predictors of lower limb fractures in general Japanese: NIPPON DATA90

Saito Y., Miura K., Arima H., Hayakawa T., Takashima N., Kita Y., Okuda N., Fujiyoshi A., Iwahori T., Miyagawa N., Kondo K., Torii S., Kadota A., Ohkubo T., Okayama A., Okamura T., Ueshima H.

PLoS ONE （PLoS ONE） 17 （ 2 February ） e0261716 2022年02月

ISSN 1932-6203

Objective This study aimed to investigate the incidence rates and predictors of lower limb fractures in a general Japanese population. Methods NIPPON DATA is a nationwide, long-term, prospective cohort study of individuals who participated in the National Cardiovascular Survey Japan and the National Nutrition Survey in 1990. Overall, 3,134 individuals (1,827 women, 1,307 men) who participated in follow-up assessments in 1995, 2000, and/or 2006 were included in the present analysis. The outcomes of this study were lower limb fractures (including proximal femur fractures). Results The mean age at baseline was 63.8 years in women and 63.1 years in men. The average body mass index (BMI) was 23.3 kg/m2 in women and 22.9 kg/m2 in men. During a mean follow- up of 12.1 years, 271 total lower limb fractures were observed. In women, older age, lower BMI, and less intake of vegetables were associated with increased risks of proximal femur fractures. With regard to the outcome of total lower limb fractures, less intake of vegetables and regular exercise were significant predictors in women. Calcium intake was not significantly associated with proximal femur or total lower limb fractures. There were no significant predictors of proximal femur or total lower limb fractures in men, except for age. Conclusions Aging was a significant risk factor for proximal femur and total lower limb fractures in both men and women. With regard to modifiable risk factors, low BMI and low intake of vegetables were associated with increased risks of proximal femur and/or total lower limb fractures in the general population of Japanese women.

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Seven-year incidence of new-onset hypertension by frequency of dairy intake among survivors of the Great East Japan Earthquake

Miyagawa N., Tsubota-Utsugi M., Tsuboyama-Kasaoka N., Nishi N., Shimoda H., Sakata K., Ogawa A., Kobayashi S.

Hypertension Research （Hypertension Research） 45 （ 9 ） 1459 - 1467 2022年

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り, ISSN 09169636

Survivors of natural disasters are at a high risk of cardiovascular disease. Behavioral risk factors, including modifiable diet, need to be identified. Thus far, the association between dairy intake and new-onset hypertension among these survivors is unknown. Therefore, we investigated this relationship. We conducted a longitudinal cohort study of 4475 survivors of the Great East Japan Earthquake in 2011 who participated in a 7-year follow-up survey. New-onset hypertension was assessed using annual health checkup data. Information on the frequency of dairy intake was obtained using a self-report questionnaire. The hazard ratio for developing hypertension according to the frequency of dairy intake was calculated using Cox proportional hazards regression models. The total number of person-years observed was 20,042, with a median follow-up of 5.4 years. During the observation period, 1554 individuals developed hypertension. The multivariable-adjusted hazard ratios of new-onset hypertension were significantly lower in those who consumed dairy products once per day (0.82, 95% confidence interval 0.71–0.94) and twice or more times per day (0.84, 95% confidence interval 0.71–0.99) than in nonconsumers; the inverse linear trend was marginally significant (P = 0.083). This association was not affected by lipid metabolism and was consistent across subgroups by sex, age, behavioral factors, cardiometabolic factors, and housing type due to the disaster. A higher frequency of dairy intake was associated with a lower risk of new-onset hypertension in community-dwelling survivors of earthquakes and tsunamis. Dietary guidance involving dairy intake could reduce the risk of developing hypertension among these survivors.

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Differential Association of Serum n-3 Polyunsaturated Fatty Acids with Various Cerebrovascular Lesions in Japanese Men

Kondo K., Arima H., Fujiyoshi A., Sekikawa A., Kadota A., Hisamatsu T., Torii S., Shiino A., Morino K., Miyagawa N., Segawa H., Watanabe Y., Maegawa H., Nozaki K., Miura K., Ueshima H.

Cerebrovascular Diseases （Cerebrovascular Diseases） 51 （ 6 ） 1 - 7 2022年

ISSN 10159770

Background: An association between a high intake of marine-derived n-3 polyunsaturated fatty acids (n-3 PUFAs) with a lower risk of coronary heart disease was previously reported. However, the association between n-3 PUFAs and cerebrovascular lesions remains unclear. We evaluated this association in a general-population-based sample of Japanese men. Methods: Participants were community-dwelling men (40-79 years old) living in Kusatsu City, Shiga, Japan. Serum concentrations of n-3 PUFAs, defined as the sum of eicosapentaenoic and docosahexaenoic acids, were measured via gas-liquid chromatography between 2006 and 2008. Magnetic resonance imaging was used to assess cerebrovascular lesions (including intracerebral large-artery stenosis, lacunar infarction, and microbleeds) and white matter lesions between 2012 and 2015. Logistic regression adjusting for conventional cardiovascular risk factors was used to estimate the odds ratio of prevalent cerebrovascular lesions per 1 standard deviation higher serum concentration of n-3 PUFAs. Results: Of a total of 739 men, the numbers (crude prevalence in %) of prevalent cerebral large-artery stenoses, lacunar infarctions, microbleeds, and white matter lesions were 222 (30.0), 162 (21.9), 103 (13.9), and 164 (22.2), respectively. A 1 standard deviation higher concentration of n-3 PUFAs (30.5 μmol/L) was independently associated with lower odds of cerebral large-artery stenosis (multivariable-adjusted odds ratio, 0.80; 95% confidential interval, 0.67-0.97). There were no significant associations of n-3 PUFAs with the other types of lesions. Conclusions: n-3 PUFAs may have protective effects against large-artery stenosis, but not small vessel lesions, in the brain.

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Reproducibility and validity of food group intake in a short food frequency questionnaire for the middle-aged Japanese population

Imaeda N., Goto C., Sasakabe T., Mikami H., Oze I., Hosono A., Naito M., Miyagawa N., Ozaki E., Ikezaki H., Nanri H., Nakahata N.T., Kamano S.K., Kuriki K., Yaguchi Y.T., Kayama T., Kurihara A., Harada S., Wakai K.

Environmental Health and Preventive Medicine （Environmental Health and Preventive Medicine） 26 （ 1 ） 28 - 28 2021年12月

研究論文（学術雑誌）, 共著, ISSN 1342078X

Purpose: The purpose of this study was to evaluate the reproducibility and validity of a short food frequency questionnaire (FFQ) for food group intake in Japan, the reproducibility and partial validity of which were previously confirmed for nutrients. Methods: A total of 288 middle-aged healthy volunteers from 11 different areas of Japan provided nonconsecutive 3-day weighed dietary records (DRs) at 3-month intervals over four seasons. We evaluated reproducibility based on the first (FFQ1) and second (FFQ2) questionnaires and their validity against the DRs by comparing the intake of 20 food groups. Spearman’s rank correlation coefficients (SRs) were calculated between energy-adjusted intake from the FFQs and that from the DRs. Results: The intake of 20 food groups estimated from the two FFQs was mostly equivalent. The median energy-adjusted SRs between the FFQ1 and FFQ2 were 0.61 (range 0.38–0.86) for men and 0.66 (0.45–0.84) for women. For validity, the median de-attenuated SRs between DRs and the FFQ1 were 0.51 (0.17–0.76) for men and 0.47 (0.23–0.77) for women. Compared with the DRs, the proportion of cross-classification into exact plus adjacent quintiles with the FFQ1 ranged from 58 to 86% in men and from 57 to 86% in women. According to the robust Z scores and the Bland–Altman plot graphs, the underestimation errors in the FFQ1 tended to be greater in individuals with high mean levels of consumption for meat for men and for other vegetables for both men and women. Conclusion: The FFQ demonstrated high reproducibility and reasonable validity for food group intake. This questionnaire is short and remains appropriate for identifying associations between diet and health/disease among adults in Japan.

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Association between socioeconomic status and prolonged television viewing time in a general Japanese population: NIPPON DATA2010

Sumimoto Y., Yanagita M., Miyamatsu N., Okuda N., Nishi N., Nakamura Y., Nakamura K., Miyagawa N., Miyachi M., Kadota A., Ohkubo T., Okamura T., Ueshima H., Okayama A., Miura K.

Environmental Health and Preventive Medicine （Environmental Health and Preventive Medicine） 26 （ 1 ） 57 - 57 2021年12月

研究論文（学術雑誌）, 共著, ISSN 1342078X

Background: It has been pointed out that prolonged television (TV) viewing is one of the sedentary behaviors that is harmful to health; however, the association between socioeconomic status (SES) and prolonged TV viewing time has not been sufficiently investigated in Japan. Methods: The study population are the participants of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey 2010 in Japan. They were residents in 300 randomly selected areas across Japan. This study included 2752 adults. SES was classified according to the employment status, educational attainment, living status, and equivalent household expenditure (EHE). Prolonged TV viewing time was defined as more than or equal to 4 h of TV viewing per day. Multivariable logistic regression analyses were conducted to examine the association of SES with prolonged TV viewing time. Results: The mean TV viewing time was 2.92 h in all participants. Of 2752 participants, 809 (29.4%) prolonged TV viewing, and the mean TV viewing time of them was 5.61 h. The mean TV viewing time in participants without prolonged TV viewing time was 1.81 h. The mean TV viewing time was prolonged as age classes increased and significantly longer in aged ≥60 years. Prolonged TV viewing time was associated with not working for all age classes and sexes. Only among women, education attainment and living status were also associated with prolonged TV viewing time. For education attainment, the lower the received years of education, the higher odds ratios (OR) of prolonged TV viewing time. For living status, in women aged <60 years, living with others had a significantly higher OR compared to living with spouse. On the other hand, in women aged ≥60 years, living alone had a significantly higher OR. EHE did not have any significant associations with prolonged TV viewing time. Conclusions: In a general Japanese population, it should be noted that the association between SES and prolonged TV viewing time differed by age and sex. Particularly, it must draw attention to the prolonged TV viewing in elderly. The intervention in order to shorten TV viewing time needs to consider these attributes.

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Association of skipping breakfast and short sleep duration with the prevalence of metabolic syndrome in the general Japanese population: Baseline data from the Japan Multi-Institutional Collaborative cohort study

Katsuura-Kamano S., Arisawa K., Uemura H., Van Nguyen T., Takezaki T., Ibusuki R., Suzuki S., Otani T., Okada R., Kubo Y., Tamura T., Hishida A., Koyama T., Matsui D., Kuriki K., Takashima N., Miyagawa N., Ikezaki H., Matsumoto Y., Nishida Y., Shimanoe C., Oze I., Matsuo K., Mikami H., Kusakabe M., Takeuchi K., Wakai K.

Preventive Medicine Reports （Preventive Medicine Reports） 24 101613 - 101613 2021年12月

ISSN 2211-3355

The purpose of the study was to investigate sex-specific associations of skipping breakfast and short sleep duration with metabolic syndrome (MetS) and their interaction. We analyzed baseline data of 14,907 men and 14,873 women aged 35–69 years, who participated in the Japan Multi-Institutional Collaborative Cohort Study from 2005. MetS was diagnosed using a modification of the National Cholesterol Education Program Adult Treatment Panel III revised definition (NCEP-R 2005), using body mass index instead of waist circumference. Breakfast consumption was classified into two categories: ≥6 days/week (consumers) or <6 days/week (skippers). Sleep duration was classified into three categories: <6h, 6 to <8 h, and ≥8 h/day. Multivariate logistic regression analysis was performed to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) and examine the presence of interaction. In men, skipping breakfast and short sleep duration were independently associated with an increased prevalence of MetS (OR 1.26, 95%CI 1.12–1.42 and OR 1.28, 95%CI 1.12–1.45, respectively), obesity, and components of MetS. However, no significant interaction was observed between skipping breakfast and short sleep duration. In women, skipping breakfast and short sleep duration were associated with an increased prevalence of obesity, but not with MetS. These findings indicate that breakfast consumption and moderate sleep duration may be associated with a lower risk of MetS, particularly in men.

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Association between Stress-Coping Strategy and Functional Disability in the General Older Adult Population: The Takashima Study.

Takashima N, Nakamura Y, Miyagawa N, Kadota A, Tanaka-Mizuno S, Matsui K, Miura K, Ueshima H, Kita Y, Takashima Study Group.

Gerontology （Gerontology） 68 （ 6 ） 1 - 8 2021年09月

研究論文（学術雑誌）, 共著, ISSN 0304-324X

Background: Both physical and psychological factors have been associated with functional disability. However, the associations between stress-coping strategies and future functional disability remain unclear. Methods: We analyzed 2,924 participants who did not have incidence of functional disability or death within the first 3 years of the baseline survey and were aged 65 years or more at the end of follow-up. Stress-coping strategies were assessed via a self-administered questionnaire (emotional expression, emotional support seeking, positive thought, problem-solving, and disengagement) in a baseline survey from 2006 to 2014. Levels of coping strategies were classified as low, middle, and high based of frequency. Functional disability decline was followed up using the long-term-care insurance program until November 1, 2019. Functional disability decline was defined as a new long-term-care insurance program certification. Cox proportional hazards model with competing risk analysis for death was used to evaluate associations between coping strategy levels and functional disability. Results: During the follow-up period, we observed 341 cases of functional disability and 73 deaths without previous incidence of functional disability. A significant inverse association between "positive thought"and "problem-solving"and future functional disability was observed. Multivariable adjusted hazard ratios (95% confidence interval) for functional disability were 0.68 (0.51-0.92) for high levels of "positive thought"and 0.73 (0.55-0.95) for high levels of "problem-solving,"compared with low levels of the coping strategies. The inverse association was stronger in men. Conclusions: Some subcomponents of stress-coping strategies might be associated with future incidence of functional disability among older adults.

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Population-Based Impact of Smoking, Drinking, and Genetic Factors on HDL-Cholesterol Levels in J-MICC Study Participants.

Nindita Y, Nakatochi M, Ibusuki R, Shimoshikiryo I, Nishimoto D, Shimatani K, Takezaki T, Ikezaki H, Murata M, Hara M, Nishida Y, Tamura T, Hishida A, Nagayoshi M, Okada R, Matsuo K, Ito H, Mikami H, Nakamura Y, Otani T, Suzuki S, Koyama T, Ozaki E, Kuriki K, Takashima N, Miyagawa N, Arisawa K, Katsuura-Kamao S, Momozawa Y, Kubo M, Takeuchi K, Wakai K

Journal of epidemiology （日本疫学会） advpub （ 0 ） 193 - 200 2021年08月

研究論文（学術雑誌）, 共著, ISSN 0917-5040

BACKGROUND: Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. METHODS: Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10-8) were selected from the GWAS catalog, and seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF). RESULTS: We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. CONCLUSIONS: The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.

Association between lifestyle changes and at-home hours during and after the state of emergency due to the COVID-19 pandemic in Japan

Nishijima C., Miyagawa N., Tsuboyama-Kasaoka N., Chiba T., Miyachi M.

Nutrients （Nutrients） 13 （ 8 ） 2021年08月

研究論文（学術雑誌）, 共著

Lifestyle changes during the coronavirus disease (COVID-19) lockdown have been previously examined, but there is limited understanding about changes after such restrictions were lifted. This study examines changes in lifestyle habits and body weight among the Japanese population with regard to the length of at-home hours both during (April to May) and after (September) the na-tionwide stay-at-home request compared to those before the COVID-19 pandemic (January 2020). An online survey was conducted in September 2020 involving 10,000 Japanese survey monitors, selected according to population distribution. During the stay-at-home request, 34% participants extended their at-home hours. More respondents in the group with extended at-home hours experienced an increase or decrease in total physical activity, snacking, food intake, alcohol drinking, and body weight than those in the group with nonextended at-home hours. Some of these changes had a trend according to age. The prevalence of most of these changes decreased when at-home hours returned to normal after the stay-at-home request period; however, increased alcohol consumption and increased or decreased body weight persisted. Our findings suggest that close monitoring for further health outcomes and age-appropriate measures to encourage favorable health behaviors is needed.

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Association between socioeconomic status and physical inactivity in a general Japanese population: NIPPON DATA2010

Sumimoto Y., Yanagita M., Miyamatsu N., Okuda N., Nishi N., Nakamura Y., Nakamura K., Miyagawa N., Miyachi M., Kadota A., Ohkubo T., Okamura T., Ueshima H., Okayama A., Miura K.

PLoS ONE （PLoS ONE） 16 （ 7 July ） e0254706 2021年07月

研究論文（学術雑誌）, 共著, ISSN 1932-6203

Background: Lower socioeconomic status (SES) may be related to inactivity lifestyle; however, the association between SES and physical inactivity has not been sufficiently investigated in Japan. Methods: The study population is the participants of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey 2010 in Japan. They were residents in 300 randomly selected areas across Japan. This study included 2,609 adults. Physical activity was assessed by physical activity index (PAI) calculated from activity intensity and time. The lowest tertile of PAI for each 10-year age class and sex was defined as physical inactivity. Multivariable logistic regression analyses were conducted to examine the association of SES (employment status, educational attainment, living status, and equivalent household expenditure (EHE)) with physical inactivity. Results: In the distribution of PAI by age classes and sex, the highest median PAI was aged 30-39 years among men (median 38.6), aged 40-49 years among women (38.0), and median PAI was decreased with increasing age. Multivariable-adjusted model shows that not working was significantly associated with physical inactivity after adjustment for age in all age groups and sexes. Not living with spouse for adult women and elderly men was significantly associated with physical inactivity compared to those who living with spouse. However, neither educational attainment nor EHE had any significant associations with physical inactivity. Conclusions: The result indicated that physical inactivity was associated with SES in a general Japanese population. SES of individuals need to be considered in order to prevent inactivity lifestyle.

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Alcohol drinking and brain morphometry in apparently healthy community-dwelling Japanese men

Syaifullah A.H., Shiino A., Fujiyoshi A., Kadota A., Kondo K., Ito T., Segawa H., Moniruzzaman M., Waki T., Miyagawa N., Tooyama I., Ueshima H., Miura K., Horie M., Nakagawa Y., Yamamoto T., Nakano Y., Ogawa E., Maegawa H., Morino K., Miyazawa I., Watanabe Y., Nozaki K., Andoh A., Tsuru T., Ogita H., Miyamatsu N., Nakamura Y., Torii S., Kadowaki T., Kadowaki S., Suzuki S., Kunimura A., Higashiyama A., Okamura T., Azuma K., Sawamura T., Igase M., Tabara Y., Sekikawa A., Barinas-Mitchell E.J.M., Edmundowicz D., Ohkubo T., Hozawa A., Murakami Y., Okuda N., Arima H., Satoh A., Kita Y., Hisamatsu T., Yanagita M., Abbott R.D., Ohno S., Takashima N., Zaid M., Saito Y.

Alcohol （Alcohol） 90 57 - 65 2021年02月

研究論文（学術雑誌）, 共著, ISSN 07418329

The clinical implications of alcohol consumption have been extensively examined; however, its effects on brain structures in apparently healthy community-dwellers remain unclear. Therefore, we investigated the relationship between alcohol consumption and brain gray matter volume (GMV) in community-dwelling Japanese men using voxel-based morphometry (VBM). We recruited cognitively intact Japanese men, aged 40–79 years, from a population-based cohort in Shiga, Japan. Brain magnetic resonance imaging was performed, on average, 2 years after demographic and medical information was obtained in 2010–2014. A multivariable linear regression analysis of 639 men was conducted to elucidate the relationship between the amount of alcohol consumed and GMV. VBM statistics were analyzed by threshold-free cluster enhancement with a family-wise error rate of <0.05. The results obtained demonstrated that the amount of alcohol consumed was associated with lower GMV. The VBM analysis showed lower GMV within the parahippocampal, entorhinal, cingulate, insular, temporal, and frontal cortices and cerebellum in very heavy drinkers (≥42 ethanol g/day) than in non-drinkers. Furthermore, alcohol consumption was associated with a higher white matter lesion volume. These results suggest subclinical structural changes similar to alcohol-related neurological diseases.

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Seven-Day Pedometer-Assessed Step Counts and Brain Volume: A Population-Based Observational Study

Moniruzzaman M., Kadota A., Shiino A., Fujiyoshi A., Ito T., Syaifullah A.H., Miyagawa N., Kondo K., Hisamatsu T., Segawa H., Tooyama I., Ueshima H., Miura K.

Journal of Physical Activity and Health （Journal of Physical Activity and Health） 18 （ 2 ） 157 - 164 2021年

研究論文（学術雑誌）, 共著, ISSN 15433080

Background: To investigate the association between step counts and brain volumes (BVs)—global and 6 a priori selected cognition-related regions of interest—in Japanese men aged 40–79 years. Methods: The authors analyzed data from 680 cognitively intact participants of the Shiga Epidemiological Study of Subclinical Atherosclerosis—a population-based observational study. Using multivariable linear regression, the authors assessed cross-sectional associations between 7-day step counts at baseline (2006–2008) and BVs at follow-up (2012–2015) for age-stratified groups (<60 y and ≥60 y). Results: In the older adults ≥60 years, step counts at baseline (per 1000 steps) were associated with total BV at follow-up (β = 1.42, P = .022) while adjusted for potential covariates. Regions of interest-based analyses yielded an association of step counts with both prefrontal cortexes (P < .05) in older adults, while the left entorhinal cortex showed marginally significant association (P = .05). No association was observed with hippocampus, parahippocampal, cingulum, and cerebellum. No association was observed in younger adults (<60 y). Conclusions: The authors found a positive association between 7-day step counts and BVs, including prefrontal cortexes, and left entorhinal cortex in apparently healthy Japanese men.

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Association between the prevalence of hypertension and dairy consumption by housing type among survivors of the Great East Japan Earthquake

Miyagawa N., Tsuboyama-Kasaoka N., Nishi N., Tsubota-Utsugi M., Shimoda H., Sakata K., Ogawa A., Kobayashi S.

Journal of Human Hypertension （Journal of Human Hypertension） 36 （ 3 ） 299 - 307 2021年

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り, ISSN 09509240

Survivors of the Great East Japan Earthquake in 2011 had higher risks of cardiovascular diseases and hypertension, particularly residents of heavy flooding areas and evacuees. Thus far, the association between the prevalence of hypertension and dairy consumption remains unknown among these evacuees. We investigated this association by housing type after the Great East Japan Earthquake. In this cross-sectional study, we conducted a baseline survey among 9569 survivors of the earthquake, aged ≥18 years, between September 2011 and February 2012. Hypertension was defined as a systolic/diastolic blood pressure ≥140/90 mmHg or as persons undergoing treatment for high blood pressure. The frequency of dairy consumption was determined using a questionnaire. Participants living in prefabricated housing and emergency shelters were regarded as residents of temporary housing. Hypertension was prevalent among 43.8% and 44.7% of the participants in temporary and non-temporary housing, respectively. A logistic regression analysis of the prevalence of hypertension by daily dairy consumption showed that the magnitude of multivariable-adjusted odds ratios differed according to housing type (odds ratio, 0.64; 95% confidence interval, 0.51–0.80 in temporary housing; odds ratio, 0.85; 95% confidence interval, 0.73–0.995 in non-temporary housing; P for interaction = 0.0501). These associations were consistent across subgroups according to sex, age, behavioral factors, obesity, disorders of lipid metabolism, and economic status. A higher frequency of dairy consumption was associated with a lower prevalence of hypertension among community-dwelling survivors of earthquakes and tsunamis, particularly those living in temporary housing. Therefore, dietary therapy involving dairy consumption could help prevent hypertension among evacuees.

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Factors Associated with Lower Cognitive Performance Scores among Older Japanese Men in Hawaii and Japan

Miyagawa N., Ohkubo T., Fujiyoshi A., Shiino A., Chen R., Ross G.W., Willcox B., Miura K., Ueshima H., Masaki K., Polidori M.C.

Journal of Alzheimer's Disease （Journal of Alzheimer's Disease） 81 （ 1 ） 403 - 412 2021年

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り, ISSN 13872877

Background: Few studies have compared factors related to cognitive function among people with similar genetic backgrounds but different lifestyles. Objective: We aimed to identify factors related to lower cognitive scores among older Japanese men in two genetically similar cohorts exposed to different lifestyle factors. Methods: This cross-sectional study of community-dwelling Japanese men aged 71-81 years included 2,628 men enrolled in the Kuakini Honolulu-Asia Aging Study based in Hawaii and 349 men in the Shiga Epidemiological Study of Subclinical Atherosclerosis based in Japan. We compared participant performance through Cognitive Abilities Screening Instrument (CASI) assessment in Hawaii (1991-1993) and Japan (2009-2014). Factors related to low cognitive scores (history of cardiovascular disease, cardiometabolic factors, and lifestyle factors) were identified with questionnaires and measurements. Multivariable logistic regression analysis was used to calculate the adjusted odds ratios (ORs) of a low (<82) CASI score based on different factors. Results: CASI scores were lower in Hawaii than in Japan [21.2%(n=556) versus 12.3%(n=43), p<0.001], though this was not significant when adjusted for age and educational attainment (Hawaii 20.3%versus Japan 17.9%, p=0.328). History of stroke (OR=1.65, 95%confidence interval=1.19-2.29) was positively associated with low cognitive scores in Hawaii. Body mass index =25kg/m2 tended to be associated with low cognitive scores in Japan; there was a significant interaction between the cohorts. Conclusion: Cognitive scores differences between cohorts were mostly explained by differences in educational attainment. Conversely, cardiovascular diseases and cardiometabolic factors differentially impacted cognitive scores among genetically similar older men exposed to different lifestyle factors.

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Relationship between calcium intake and impaired activities of daily living in a japanese population: Nippon data90

Kogure M., Tsuchiya N., Narita A., Hirata T., Nakaya N., Nakamura T., Hozawa A., Hayakawa T., Okuda N., Miyagawa N., Kadota A., Ohkubo T., Murakami Y., Sakata K., Miura K., Okayama A., Okamura T., Ueshima H.

Journal of Epidemiology （Journal of Epidemiology） 31 （ 1 ） 119 - 124 2021年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 09175040

Background: Major reasons for long-term care insurance certification in Japan are stroke, dementia, and fracture. These diseases are reported to be associated with calcium intake. This study examined the association between calcium intake and impaired activities of daily living (ADL) using the data from NIPPON DATA90, consisting of representative sample of the Japanese population. Methods: A population-based nested case-control study was performed. A baseline survey was conducted in 1990, followed by ADL surveys of individuals ≥65 years old in 2000. Individuals with impaired ADL and selected age-and sex-matched controls were then identified. We obtained 132 pairs. Calcium intake was energy-adjusted using the residual method. The association between calcium intake and impaired ADL was examined using conditional logistic regression models. To assess the accuracy of the estimates, we conducted bootstrap analyses. Results: The adjusted odds ratios (ORs) for impaired ADL compared with the group with a calcium intake of <476 mg/day were 0.72 (95% confidence interval [CI], 0.37–1.40) for the 476–606 mg/day group and 0.44 (95% CI, 0.21–0.94) for the ≥607 mg/ day group in 2000 (P for linear trend = 0.03). After the bootstrap analyses, the inverse relationship unchanged (median OR per 100-mg rise in calcium intake, 0.87 [1,000 resamplings]; 95% CI, 0.76–0.97). Conclusions: After bootstrap analyses, calcium intake was inversely associated with impaired ADL 10 years after the baseline survey.

Relationships of alcohol consumption with coronary risk factors and macro-and micro-nutrient intake in Japanese people: The interlipid study

Matsumoto-Yamauchi H., Kondo K., Miura K., Tanaka-Mizuno S., Segawa H., Ohno S., Miyagawa N., Zaid M., Okami Y., Okuda N., Nakagawa H., Sakata K., Saitoh S., Okayama A., Yoshita K., Chan Q., Masaki K., Elliott P., Stamler J., Ueshima H.

Journal of Nutritional Science and Vitaminology （Journal of Nutritional Science and Vitaminology） 67 （ 1 ） 28 - 38 2021年

研究論文（学術雑誌）, 共著, ISSN 03014800

Several studies have reported a J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk. However, the mechanisms of this relationship remain unclear. This study aimed to evaluate the relationships of alcohol consumption with established CHD risk factors and with macro-/micro-nutrient intake among Japanese people. Participants were 1,090 Japanese men and women aged 40–59 y enrolled in the INTERLIPID study, excluding former drinkers. Based on two 7-d alcohol records, participants were classified as non-drinkers (0 g/wk), light-drinkers (<100 g/wk), moder-ate-drinkers (100–299 g/wk), or heavy-drinkers (≥300 g/wk). Detailed macro-/micro-nu-trient intake was evaluated using four in-depth 24-h dietary recalls and adjusted for total energy intake excluding alcohol. We analyzed the associations of CHD risk factors and nutrient intake with alcohol consumption. Serum high-density lipoprotein cholesterol and blood pressure were higher and low-density lipoprotein cholesterol was lower among those with higher alcohol consumption. J-shaped relationships with alcohol consumption were observed for the proportion of current smokers, number of cigarettes smoked, and prevalence of hypertension; these risk factors were lowest among light-drinkers. Carbohydrate and total fiber intakes were lower and protein and dietary cholesterol intakes were higher among those with higher alcohol consumption. These associations were similar for men and women. Alcohol consumption was related to nutrient intake as well as established CHD risk factors. Non-drinkers were higher on some CHD risk factors than were light-drinkers. These findings may influence the J-shaped relationship between alcohol consumption and CHD risk.

自然災害後の栄養問題と改善の取り組みに関連する要因のレビュー

宮川尚子, 笠岡 (坪山) 宜代, 原田萌香, 西信雄

栄養学雑誌（特定非営利活動法人日本栄養改善学会） 78 （ Supplement ） S111 - S120 2020年12月

ISSN 00215147

【目的】このレビューの目的は，避難所での食事と栄養問題の改善方法と，日本における自然災害後の健康と栄養を改善するためのさまざまな取り組みを明らかにすることである。【方法】世界の避難所における栄養問題の改善方法を明らかにするため，PubMedおよびJ-STAGEにて，「災害」および「避難所ORキャンプ」AND「栄養OR食品OR食事」をキーワードとして文献検索した。活動報告，レビュー，方法のない記事，英語と日本語以外の言語で書かれた論文は，本レビューから除外した。また，日本の政府，専門機関，学術研究機関による自然災害後の健康と栄養改善の取り組みに関する情報を整理した。【結果】条件に合致した7編の論文から，自然災害後の避難所における栄養問題の改善に関連する4つの主要な要素，1）避難所のサイズと設備，2）避難所での食事の提供方法と内容，3）専門家との共同作業，4）避難所間の協力，が抽出された。また，東日本大震災以降に日本で開始された自然災害後の健康・栄養問題改善のための取り組みとして，国の研究機関への災害栄養に特化した部署の設置，災害食の備蓄の推奨や認証制度，人材の開発育成，災害時の栄養基準などがあった。【結論】本レビューにより，緊急時の避難所における栄養問題の改善に関連する要因と日本における自然災害に伴う栄養と健康の問題を軽減するための様々な取り組みを明らかにした。

Association of red meat intake with the risk of cardiovascular mortality in general japanese stratified by kidney function: Nippon data80

Segawa H., Kondo K., Kadota A., Yamauchi H., Ohno S., Tanaka-Mizuno S., Okuda N., Miyagawa N., Arima H., Okamura T., Miura K., Okayama A., Ueshima H.

Nutrients （Nutrients） 12 （ 12 ） 1 - 10 2020年12月

研究論文（学術雑誌）, 共著

The consumption of red meat has been recommended for individuals with reduced kidney function. However, red meat intake was recently suspected to increase cardiovascular disease (CVD) risk. We evaluated the association of red meat intake with CVD mortality risk in Japanese with/without reduced kidney function. Overall, 9112 participants of a Japanese national survey in 1980, aged ≥30 years, were followed for 29 years. Red meat intake was assessed using weighed dietary record. Cox proportional hazards models were used to estimate the hazard ratio (HR) of CVD mortality according to sex-specific tertiles of red meat intake. We also performed stratified analyses with/without reduced kidney function defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m2. Red meat intake was not associated with CVD mortality risk in men and women. In stratified analyses, the HR of the highest compared with the lowest tertile of red meat intake was lower only in women with reduced kidney function (0.67, 95% confidence interval 0.46–0.98). In conclusion, there were no clear associations between red meat intake and CVD mortality risk in Japanese population; however, a higher intake of red meat was associated with lower risk of future CVD mortality in women with reduced kidney function.

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Alcohol consumption and cognitive function in elderly Japanese men

Siddiquee A.T., Kadota A., Fujiyoshi A., Miyagawa N., Saito Y., Suzuki H., Kondo K., Yamauchi H., Ito T., Segawa H., Tooyama I., Miura K., Ueshima H.

Alcohol （Alcohol） 85 145 - 152 2020年06月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 07418329

Although heavy alcohol consumption has been identified as a risk factor for adverse cognitive functioning, it currently remains unclear whether moderate alcohol consumption exerts similar effects. Observational studies previously reported the potential benefits of moderate alcohol consumption on cognition, particularly in the elderly; however, these effects have not yet been demonstrated in Asian populations. The aim of the present study was to investigate the relationship between alcohol consumption levels and global and domain-specific cognitive functions in cognitively intact elderly Japanese men. Cross-sectional data from the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA), an ongoing prospective, population-based study in Shiga, Japan, were used to examine the relationship between alcohol consumption and cognitive function. Men (n = 585) aged ≥65 years provided information on their weekly consumption of alcohol, and the data obtained were used to construct categories of never, ex- (quit before interview), very light (<14 g/day), light (14–23 g/day), moderate (>23–46 g/day), and heavy (>46 g/day) drinkers. Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI). A fractional logistic regression model adjusted for age, education, body mass index, smoking, exercise, hypertension, diabetes, and dyslipidemia showed that the CASI scores for global and domain-specific cognitive functions were not significantly different between all subgroups of current drinkers and never-drinkers. However, the CASI score of ex-drinkers (multivariable adjusted mean CASI score [SD]) was significantly lower than that of never-drinkers in the global [never vs. ex: 90.16 (2.21) vs. 88.26 (2.58)] and abstraction and judgment domain [never vs. ex: 9.48 (0.46) vs. 8.61 (0.57)]). The present results do not suggest any beneficial or adverse relationship between current alcohol consumption levels and cognitive functioning (both global and domain specific) in elderly Japanese men; however, low cognitive function among ex-drinkers warrants future investigations to identify the factors causing drinkers to quit.

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Food sources of dietary potassium in the adult Japanese population: The international study of macro-/micronutrients and blood pressure (INTERMAP)

Okuda N., Okayama A., Miura K., Yoshita K., Miyagawa N., Saitoh S., Nakagawa H., Sakata K., Chan Q., Elliott P., Ueshima H., Stamler J.

Nutrients （Nutrients） 12 （ 3 ） 2020年03月

研究論文（学術雑誌）, 共著, 査読有り

A lower-than-recommended potassium intake is a well-established risk factor for increased blood pressure. Although the Japanese diet is associated with higher sodium intake and lower potassium intake, few studies have examined the source foods quantitatively. Studies on dietary patterns in association with potassium intake will be useful to provide dietary advice to increase potassium intake. Twenty-four-hour (hr) dietary recall data and 24-hr urinary potassium excretion data from Japanese participants (574 men and 571 women) in the International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were used to calculate food sources of potassium and compare food consumption patterns among quartiles of participants categorized according to 24-hr urinary potassium excretion per unit of body weight (UK/BW). The average potassium intake was 2791 mg/day per participant, and the major sources were vegetables and fruits (1262 mg/day), fish (333 mg/day), coffee and tea (206 mg/day), and milk and dairy products (200 mg/day). Participants in the higher UK/BW quartile consumed significantly more vegetables and fruits, fish, and milk and dairy products, and ate less rice and noodles. Conclusion: Advice to increase the intake of vegetables and fruits, fish, and milk may be useful to increase potassium intake in Japan.

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Relationship of household salt intake level with long-term all-cause and cardiovascular disease mortality in Japan: NIPPON DATA80

Shima A., Miyamatsu N., Miura K., Miyagawa N., Okuda N., Yoshita K., Kadota A., Suzuki H., Kondo K., Okamura T., Okayama A., Ueshima H., Saitoh S., Sakata K., Hozawa A., Hayakawa T., Nakamura Y., Nishi N., Ohkubo T., Kasagi F., Murakami Y., Izumi T., Matsumura Y., Ojima T., Tamakoshi K., Nakagawa H., Kita Y., Fujiyoshi A., Nakamura Y., Miyamoto Y., Kodama K., Kiyohara Y.

Hypertension Research （Hypertension Research） 43 （ 2 ） 132 - 139 2020年02月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 09169636

In Asian countries, a major source of salt intake is from seasoning or table salt added at home. However, little is known about the adverse effects of salt intake evaluated according to household unit. We investigated the relationship between household salt intake level and mortality from all-cause and cardiovascular diseases (CVDs). Participants included 8702 individuals (56% women) who were living with someone else and who were aged 30–79 years and enrolled in the National Nutritional Survey of Japan in 1980 with a 24-year follow-up. Household nutrient intake was evaluated using a 3-day weighing record method in which all foods and beverages consumed by any of the household members were recorded. The household salt intake level was defined as the amount of salt consumed (g) per 1000 kcal of total energy intake in each household, and its average was 6.25 (2.02) g/1000 kcal. During the follow-up, there were 2360 deaths (787 CVD, 168 coronary heart disease [CHD], and 361 stroke). Cox proportional hazard ratios (HRs) for an increment of 2 g/1000 kcal in household salt intake were calculated and adjusting for sex, age, body mass index, smoking status, alcohol consumption status, self-reported work exertion level, household potassium intake, household saturated fatty acid intake, and household long-chain n-3 polyunsaturated fatty acid intake. The HRs (95% confidence intervals) were 1.07 (1.02, 1.12) for all-cause mortality, 1.11 (1.03, 1.19) for CVD, 1.25 (1.08, 1.44) for CHD, and 1.12 (1.00, 1.25) for stroke. The household salt intake level was significantly associated with long-term risk of all-cause, CVD, CHD, and stroke mortality in a representative Japanese population.

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Relationship between carbohydrate and dietary fibre intake and the risk of cardiovascular disease mortality in Japanese: 24-year follow-up of NIPPON DATA80

Miyazawa I., Miura K., Miyagawa N., Kondo K., Kadota A., Okuda N., Fujiyoshi A., Chihara I., Nakamura Y., Hozawa A., Nakamura Y., Kita Y., Yoshita K., Okamura T., Okayama A., Ueshima H.

European Journal of Clinical Nutrition （European Journal of Clinical Nutrition） 74 （ 1 ） 67 - 76 2020年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 09543007

Background/Objectives: The association between carbohydrate intake and cardiovascular disease (CVD) risk has been investigated, but whether the quality of carbohydrate is more important than its amount is not known. We examined the associations between intake of dietary fibre (DF), carbohydrate, available carbohydrate, and starch with long-term CVD mortality in a Japanese population. Subjects/Methods: We prospectively followed 8925 participants (3916 men and 5009 women) aged 30–79 years without CVD at baseline who participated in the National Nutrition Survey in Japan. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for CVD mortality by quartiles of exposure variables. Results: During 24 years of follow-up, 823 CVD deaths were observed. In men, the multivariable-adjusted HR for CVD mortality was lower in the highest quartile of DF intake (HR: 0.64; 95% CI: 0.47–0.87; Ptrend = 0.007) compared with the lowest quartile. This association was not significant in women. Multivariable-adjusted HR for total stroke mortality was lower in the highest quartile of DF intake (HR: 0.61; 95% CI: 0.38–0.98; Ptrend = 0.046) compared with the lowest quartile in women. Carbohydrate, available carbohydrate, and starch intake were not associated with CVD mortality. Conclusions: Higher intake of DF was associated significantly with a lower risk of CVD mortality in men and lower risk of stroke mortality in women. Intake of carbohydrate, available carbohydrate, and starch were not associated with the risk of CVD mortality in men or women.

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Elevated fasting blood glucose levels are associated with lower cognitive function, with a threshold in non-diabetic individuals: A population-based study

Liu Z., Zaid M., Hisamatsu T., Tanaka S., Fujiyoshi A., Miyagawa N., Ito T., Kadota A., Tooyama I., Miura K., Ueshima H.

Journal of Epidemiology （Journal of Epidemiology） 30 （ 3 ） 121 - 127 2020年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 09175040

Background: Cognitive dysfunction has been recognized as a diabetes-related complication. Whether hyperglycemia or elevated fasting glucose are associated with cognitive decline remains controversial. We aimed to investigate the relationship between fasting glucose levels and cognitive function in diabetic and non-diabetic individuals. Methods: Participants were Japanese diabetic (n = 191) and non-diabetic (n = 616) men, aged 46–81 years, from 2010–2014. Blood samples were taken after a 12 h fast. The Cognitive Ability Screening Instrument (CASI), with a maximum score of 100, was used for cognitive assessment. Cognitive domains of CASI were also investigated. Fractional logit regression with covariate adjustment for potential confounders was used to model cross-sectional relationships between fasting blood glucose and CASI score. Results: For diabetic individuals, CASI score was 0.38 (95% confidence interval: 0.66–0.12) lower per 1 mmol/L higher fasting glucose level. Short-term memory domain also exhibited an inverse association. For non-diabetic individuals, a reverse Ushaped relationship was observed between fasting glucose and cognitive function, identifying a threshold for highest cognitive performance of 91.8 CASI score at 3.97–6.20 mmol/L (71.5–111.6 mg/dL) fasting glucose. Language ability domain displayed a similar relationship with fasting glucose. Conclusions: Elevated fasting glucose levels in diabetic men were associated with lower cognitive function, in which short-term memory was the main associated domain. Interestingly, in non-diabetic men, we identified a threshold for the inverse relationship of elevated fasting glucose with cognitive function. Contrastingly to diabetic men, language ability was the main associated cognitive domain among non-diabetic men.

Exercise habits are associated with improved long-term mortality risks in the nationwide general japanese population: A 20-year follow-up of the Nippon data90 study

Takatsuji Y., Ishiguro A., Asayama K., Ohkubo T., Miura K., Kadota A., Yanagita M., Fujiyoshi A., Arima H., Miyagawa N., Takashima N., Kita Y., Hayakawa T., Kikuya M., Nakamura Y., Okayama A., Okamura T., Ueshima H.

Tohoku Journal of Experimental Medicine （Tohoku Journal of Experimental Medicine） 252 （ 3 ） 253 - 262 2020年

研究論文（学術雑誌）, 共著, ISSN 00408727

Exercise habits are known as a protective factor for a variety of diseases and thus recommended worldwide; however, few studies have examined long-term effects of exercise habits on mortality. We continuously monitored death status in a nationwide population sample of 7,709 eligible persons from the National Integrated Project for Prospective Observation of Noncommunicable Disease and its Trends in the Aged in 1990 (NIPPON DATA90), for which baseline data were obtained in 1990. To investigate the longterm impact of baseline exercise habits, we calculated the relative risk of non-exercisers (participants without regular voluntary exercise habits) in reference to exercisers (those with these habits) for all-cause or cause-specific mortality using a Cox proportional hazard model, in which the following confounding factors were appropriately adjusted: Sex, age, body mass index, total energy intake, smoking, drinking, and history of cardiovascular disease. During a median 20 years of follow-up, 1,747 participants died, 99 of heart failure. The risk for all-cause mortality was 12% higher in non-exercisers than in exercisers (95% confidence interval, 1%-24%), which was also observed for mortality from heart failure, as 68% higher in non-exercisers than in exercises (95% confidence interval, 3%-173%). These associations were similarly observed when the participants were divided to subgroups by sex, age, and the light, moderate, or vigorous intensity of physical activity, without any significant heterogeneities (P > 0.1). The present study has revealed significant impact of exercise habits on long-term mortality risks, supporting worldwide recommendations for improvement of exercise habits.

Proteinuria and reduced estimated glomerular filtration rate are independently associated with lower cognitive abilities in apparently healthy community-dwelling elderly men in Japan: A cross-sectional study

Fujiyoshi A., Miura K., Ohkubo T., Miyagawa N., Saito Y., Miyazawa I., Shiino A., Kadota A., Kadowaki S., Hisamatsu T., Torii S., Takashima N., Tooyama I., Ueshima H.

Journal of Epidemiology （Journal of Epidemiology） 30 （ 6 ） 244 - 252 2020年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 09175040

Background: The association of proteinuria and reduced estimated glomerular filtration rate (eGFR) with cognition needs more clarification. We cross-sectionally examined whether proteinuria and reduced eGFR, even in moderate stages, were independently associated with lower cognition in a community-based sample of elderly men. Methods: Our cohort initially comprised 1,094 men aged 40–79 years from a random sample from Shiga, Japan in 2006–2008. Of 853 men who returned for the follow-up examination (2009–2014), we analyzed 561 who were ≥65 years, free of stroke, and completed the Cognitive Abilities Screening Instrument (CASI) at follow-up (higher CASI scores [range 0 to 100] indicate better cognition). Proteinuria was assessed via dipstick. eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration Equation. Participants were divided into three groups either by eGFR (≥60, 59–40, and <40 mL= min=1.73 m2) or by proteinuria (no, trace, and positive), considered normal, moderate, and advanced, respectively. Using linear regression, we computed mean CASI score, with simultaneous adjustment for proteinuria and eGFR in addition to other potential confounders. Results: Significant trends of lower cognition were observed across the groups of worse proteinuria and lower eGFR independently: multivariable-adjusted mean CASI scores were 90.1, 89.3, and 88.4 for proteinuria (Ptrend = 0.029), and 90.0, 88.5, and 88.5 for eGFR (Ptrend = 0.015) in mutual-adjustment model. Conclusions: Proteinuria and reduced eGFR, even in their moderate stages, were independently associated with lower cognition in a community-based sample of elderly men. The results suggest the importance of proteinuria and low eGFR for early detection and prevention of cognitive decline.

Relationship between Step Counts and Cerebral Small Vessel Disease in Japanese Men

Moniruzzaman M., Kadota A., Segawa H., Kondo K., Torii S., Miyagawa N., Fujiyoshi A., Hisamatsu T., Watanabe Y., Shiino A., Nozaki K., Ueshima H., Miura K.

Stroke （Stroke） 51 （ 12 ） 3584 - 3591 2020年

研究論文（学術雑誌）, 共著, ISSN 00392499

Background and Purpose: Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association between step counts and CSVD in a healthy Japanese male population. Methods: We analyzed data from 680 men who were free of stroke and participated in this observational study. Seven-day step counts were assessed at baseline (2006-2008) using a pedometer. CSVD was assessed at follow-ups (2012-2015) based on deep and subcortical white matter hyperintensities (WMHs), periventricular hyperintensities, lacunar infarcts, and cerebral microbleeds on magnetic resonance imaging. Using a logistic regression analysis, we computed the adjusted odds ratios, with 95% CIs, of prevalent CSVD according to quartiles of step counts (reference: Q1). We also investigated the association between step counts and WMH volumes using a quantile regression. Results: Steps per day were significantly associated with lower odds ratios, with the lowest at Q3 (8175-10 614 steps/day), of higher (versus low or no burden) deep and subcortical WMHs (odds ratio, 0.52 [95% CI, 0.30-0.89]), periventricular hyperintensities (0.50 [95% CI, 0.29-0.86]), and lacunar infarcts (0.52 [95% CI, 0.30-0.91]) compared with Q1 (≤6060 steps/day) but not cerebral microbleeds. An inverse linear association was observed between step counts and WMH volumes. These associations were independent of age and smoking and drinking status and remained consistent when adjusted for vascular risk factors. Conclusions: We found a J-shaped relationship between step counts and prevalent CSVD in healthy Japanese men, with the lowest risk being observed among participants with ≈8000 to 10 000 steps/day. Higher steps were also associated with lower WMH volumes.

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飲酒日におけるエネルギー及び栄養素等摂取量の特徴　NIPPON DATA2010

岩橋明子, 由田克士, 荒井裕介, 尾島俊之, 藤吉朗, 中川秀昭, 奥田奈賀子, 宮川尚子, 門田文, 岡村智教, 大久保孝義, 西信雄, 上島弘嗣, 岡山明, 三浦克之, NIPPON DATA2010研究グループ

日本循環器病予防学会誌（(一社)日本循環器病予防学会） 54 （ 3 ） 178 - 188 2019年12月

研究論文（学術雑誌）, 共著, ISSN 1346-6267

【目的】過度の飲酒はアルコールそのものが与える健康障害や循環器疾患の発症リスクのみならず、食事にも大きく影響する。しかし、国を代表する集団において飲酒量が栄養素等摂取量に与えている影響を詳細に検討した報告は限られている。そこで、飲酒日における栄養素等摂取量の特徴について検討した。【方法】平成22年国民健康・栄養調査にあわせて20歳以上の男女を対象に実施されたNIPPON DATA2010に参加した、生活習慣病の関連疾患での服薬がなく、栄養摂取状況調査の項目に欠損がない男性729名を解析対象とした。調査日1日の飲酒量に基づき、生活習慣病のリスクを高める量(純アルコール40g以上)の飲酒者をO群(111名)、適量飲酒者(同5g以上40g未満)をM群(187名)、非飲酒者(同5g未満)をN群(431名)とし、各群の栄養素及び食品群別の摂取量について比較検討した。【結果】血圧、HDL及びLDLコレステロール、AST、γ-GTPは、飲酒量により有意な差が認められた。総エネルギー摂取量及びアルコールエネルギー比率は、O群、M群、N群の順に有意に高かったのに対し、炭水化物エネルギー比率及び脂肪エネルギー比率は、O群、M群、N群の順に有意に低かった。また、たんぱく質エネルギー比率は、O群がM群及びN群と比較して有意に低かった。アルコール由来のエネルギーを除外して算出した場合、たんぱく質エネルギー比率は、O群及びM群がN群と比較して有意に高かった。脂肪エネルギー比率は、M群がN群と比較して有意に高かった。炭水化物エネルギー比率はO群及びM群がN群と比較して有意に低かった。たんぱく質、脂質、カリウム、マグネシウム、リン、ビタミンB2、ナイアシン、葉酸、パントテン酸、ビタミンB12、飽和脂肪酸及びコレステロールについて、飲酒量により摂取量に有意な差が認められた。穀類、豆類、野菜類、果実類、菓子類及び嗜好飲料類について、飲酒量により摂取量に有意な差が認められた。【結論】多量飲酒日にはアルコールの摂取により総エネルギー摂取量が高値を示したが、それとは逆に主として穀類から由来する炭水化物の摂取量は低値を示した。循環器疾患をはじめとした生活習慣病予防において、過度の飲酒を控えることは、アルコールそのものによる影響だけでなく、食事によるエネルギー産生栄養素バランスを整える上でも重要であることが示唆された。(著者抄録)

The association of home and accurately measured office blood pressure with coronary artery calcification among general Japanese men

Satoh A., Arima H., Hozawa A., Ohkubo T., Hisamatsu T., Kadowaki S., Kadota A., Fujiyoshi A., Miyagawa N., Zaid M., Torii S., Okamura T., Sekikawa A., Miura K., Ueshima H.

Journal of Hypertension （Journal of Hypertension） 37 （ 8 ） 1676 - 1681 2019年08月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 02636352

Objective:We conducted a cross-sectional study to clarify whether home blood pressure (HBP) is more strongly associated with coronary artery calcification (CAC) than accurately measured office blood pressure (OBP) among the general population of Japanese men.Methods:We analyzed the data of 919 Japanese male participants who were randomly selected from general population (mean age 64.5 years). OBP was measured twice consecutively by a trained nurse using electrical device after 5 min of complete rest alone in a sitting position in a silent room. The participants were asked to measure HBP with an electrical device once in the morning during 7 consecutive days. CAC was assessed using computed tomography. Presence of CAC was defined as Agatston score at least 10. We calculated odds ratios for the presence of CAC per one SD higher OBP and HBP adjusted for age and other cardiovascular risk factors.Results:The mean systolic OBP (SD) and HBP (SD) were 136.8 (19.0) and 137.2 (18.5) mmHg, respectively, without statistical difference between the two (P = 0.595). OBP and HBP were highly correlated (r = 0.74 P < 0.001). CAC was found in 454 (49.4%) participants. Multivariable-adjusted odds ratios [95% confidence interval (CI)] for the presence of CAC were comparable between OBP (1.32, 95% CI: 1.12-1.56) and HBP (1.35, 95% CI: 1.14-1.60) (P heterogeneity = 0.813).Conclusion:The strength of association of accurately measured OBP with CAC was comparable with that of HBP among randomly selected male general population aged 40-79 years.

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The impact of sex on risk of cardiovascular disease and all-cause mortality in adults with or without diabetes mellitus: A comparison between the U.S. and Japan

Liu L., Miura K., Kadota A., Fujiyoshi A., Gracely E.J., Xue F., Liu Z., Takashima N., Miyagawa N., Ohkubo T., Arima H., Okayama A., Okamura T., Ueshima H.

Journal of Diabetes and its Complications （Journal of Diabetes and its Complications） 33 （ 6 ） 417 - 423 2019年06月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 10568727

Aims: To test a hypothesis that women with diabetes mellitus (DM)versus those without DM had a significantly higher risk of heart disease (HD), stroke and all-cause mortality than their male counterparts in the U.S. as well as in Japan. Methods: We analyzed two nationally representative datasets, one from the U.S. NHANES III cohort (n = 13,169), and the other from the Japan NIPPON DATA90 cohort (n = 7445). Hazard ratios (HRs)of DM for risk of mortality and sex-DM interaction effect on mortality were analyzed prospectively using Cox's proportional hazards regression models. Results: Patients with DM had significantly higher mortality from HD, stroke and all-cause mortality in the U.S. and in Japan. However, the HRs of DM versus non-DM for HD and all-cause mortality were significantly higher in women compared to men in the U.S. (sex-DM interaction: HR = 1.59, p = 0.01, and 1.24, p = 0.045 for HD and all-cause mortality), but the sex-DM interaction effect was not statistically significant in the Japanese cohort. Discussion: Patients with DM had a significantly higher risk of mortality than those without DM in the U.S. and Japan. However, women with DM versus those without DM had a higher relative risk of HD and all-cause mortality than their counterparts in men in the U.S, but this sex difference by DM status was not observed in the Japanese cohort. Whether the sex-difference effect of DM on HD and all-cause mortality is due to a difference in metabolic disorders between the two populations warrants consideration and further studies.

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Association of alcohol consumption with fat deposition in a community-based sample of Japanese men: The Shiga epidemiological study of subclinical atherosclerosis (SESSA)

Sumi M., Hisamatsu T., Fujiyoshi A., Kadota A., Miyagawa N., Kondo K., Kadowaki S., Suzuki S., Torii S., Zaid M., Sato A., Arima H., Terada T., Miura K., Ueshima H., Horie M., Nakano Y., Yamamoto T., Hayashi H., Ogawa E., Maegawa H., Miyazawa I., Murata K., Mitsunami K., Nozaki K., Tooyama I., Shiino A., Tsuru T., Ogita H., Shimizu A., Miyamatsu N., Kita T., Kimura T., Nishio Y., Nakamura Y., Okamura T., Sekikawa A., Barinas-Mitchell E.J., Edmundowicz D., Ohkubo T., Hozawa A., Miyagi S., Murakami Y., Okuda N., Kita Y., Higashiyama A., Nagasawa S., Azuma K., Yanagita M., Abbott R.D., Ohno S., Takashima N., Kadowaki T., Saito Y., Ito T., Satoh A., Yamazoe M.

Journal of Epidemiology （Journal of Epidemiology） 29 （ 6 ） 205 - 212 2019年06月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 09175040

Background: Excessive alcohol intake has been shown to be associated with cardiovascular disease via metabolic pathways. However, the relationship between alcohol intake and obesity has not been fully elucidated. We aimed to examine the association of alcohol consumption with fat deposition and anthropometric measures. Methods: From 2006–2008, we conducted a cross-sectional study in a population-based sample of Japanese men aged 40 through 79 years. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography imaging. Based on a questionnaire, we classified participants into five groups according to weekly alcohol consumption, excluding former drinkers: Non-drinkers (0 g=week), 0.1–160.9, 161–321.9, 322–482.9, and ≥483 g=week. Multivariable linear regression was used to estimate adjusted means of obesity indices for each group. Results: We analyzed 998 men (mean age and body mass index [BMI], 63.8 years and 23.6 kg=m2, respectively). Higher weekly alcohol consumption was strongly and significantly associated with higher abdominal VAT area, percentage of VAT, and VATto- SAT ratio (all P for trend <0.001), and also with waist circumferences and waist-to-hip ratio (P for trend = 0.042 and 0.007, respectively). These associations remained significant after further adjustment for BMI, whereas alcohol consumption had no significant association with abdominal SAT area. Conclusions: Higher alcohol consumption was associated with higher VAT area, VAT%, and VAT-to-SAT ratio, independent of confounders, including BMI, in general Japanese men. These results suggest that alcohol consumption may have a potential adverse effect on visceral fat deposition.

Socioeconomic and lifestyle factors associated with depressive tendencies in general Japanese men and women: NIPPON DATA2010

Suzuki H., Kadota A., Okuda N., Hayakawa T., Nishi N., Nakamura Y., Arima H., Miyagawa N., Satoh A., Miyamatsu N., Yanagita M., Yatsuya H., Yamagata Z., Ohkubo T., Okamura T., Ueshima H., Okayama A., Miura K.

Environmental Health and Preventive Medicine （Environmental Health and Preventive Medicine） 24 （ 1 ） 37 - 37 2019年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1342078X

Background: The gender-specific characteristics of individuals at an increased risk of developing depression currently remain unclear despite a higher prevalence of depression in women than in men. This study clarified socioeconomic and lifestyle factors associated with an increased risk of subclinical depression in general Japanese men and women. Methods: Study participants were residents not receiving psychiatric treatments in 300 sites throughout Japan in 2010 (1152 men, 1529 women). Multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95%CIs) for socioeconomic factors and lifestyle factors were calculated using a logistic regression analysis. Results: Risk of depressive tendencies was significantly higher in men who were single and living alone (OR, 3.27; 95% CI, 1.56-6.88) than those married. The risk was significantly lower in women who were not working and aged ≥ 60 years (OR, 0.39; 95% CI, 0.22-0.68) and higher in men who were not working and aged < 60 years (OR, 3.57; 95%CI, 1.31-9.72) compared with those who were working. Current smoking was also associated with a significantly increased risk of depressive tendencies in women (OR, 2.96; 95% CI, 1.68-5.22) but not in men. Conclusions: Socioeconomic and lifestyle factors were associated with an increased risk of depressive tendencies in general Japanese. Related factors were different by sex.

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Association of blood levels of marine omega-3 fatty acids with coronary calcification and calcium density in Japanese men

Sekikawa A., Mahajan H., Kadowaki S., Hisamatsu T., Miyagawa N., Fujiyoshi A., Kadota A., Maegawa H., Murata K., Miura K., Edmundowicz D., Ueshima H.

European Journal of Clinical Nutrition （European Journal of Clinical Nutrition） 73 （ 5 ） 783 - 792 2019年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 09543007

Background/objectives:: Clinical trials of eicosapentaenoic acid (EPA) among high-risk groups in Japan in which consumption of mairne-omega-3 fatty acids (OM3) is much higher than other countries showed slower progression of coronary atherosclerosis. We aimed to determine the cross-sectional associations of coronary artery calcification (CAC) and calcium density with OM3, EPA, and docosahexaenoic acid (DHA), two principal OM3, in the general population in Japan. Subjects/methods:: The Shiga Epidemiological Study of Subclinical Atherosclerosis examined a population-based sample of 1074 men aged 40–79 in 2006–08 for computed tomography-measured CAC score (CCS), a well-established biomarker of coronary atherosclerosis, CAC density score (CDS), a potential marker of plaque stabilization, serum levels of OM3, and risk factors. Results:: Prevalence of CCS > 0, ≥ 100, and ≥ 300 was 65.8%, 25.9%, and 12.9%, respectively; the mean (SD) OM3, EPA, and DHA were 10.1% (3.2), 3.2% (1.7), and 5.9% (1.6), respectively. Odds ratios (95% CI, p-value) of CCS 0, 100, and 300 in ordinal logistic regression associated with 1 SD increase of OM3, EPA, and DHA were 0.91 (0.81–1.03, p = 0.12), 0.99 (0.88–1.11, p = 0.87) and 0.84 (0.74–0.94, p = < 0.01), respectively. The inverse association of DHA with CCS remained significant in multivariate-adjusted model: odds ratio of 0.87 (0.77–0.99, p = 0.03). Blood levels of OM3, EPA, or DHA did not have any significant associations with CDS. Conclusions:: DHA but not EPA had a significant inverse association with coronary atherosclerosis in the general population with high levels of OM3. Future trials are warranted comparing the effect of high-dose DHA and EPA on atherosclerosis and cardiovascular outcomes.

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Associations of nutrient patterns with the prevalence of metabolic syndrome: Results from the baseline data of the Japan multi-institutional collaborative cohort study

Iwasaki Y., Arisawa K., Katsuura-Kamano S., Uemura H., Tsukamoto M., Kadomatsu Y., Okada R., Hishida A., Tanaka K., Hara M., Takezaki T., Shimatani K., Ozaki E., Koyama T., Suzuki S., Nakagawa-Senda H., Kuriki K., Miyagawa N., Kadota A., Ikezaki H., Furusyo N., Oze I., Ito H., Mikami H., Nakamura Y., Wakai K.

Nutrients （Nutrients） 11 （ 5 ） 990 - 990 2019年05月

研究論文（学術雑誌）, 共著, 査読有り

The association between nutrient patterns and metabolic syndrome (MetS) has not been examined in a Japanese population. A cross-sectional study was performed on 30,108 participants (aged 35-69 years) in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Dietary intake was assessed using a 46-item food frequency questionnaire. MetS was diagnosed according to the Joint Interim Statement Criteria of 2009, using body mass index instead of waist circumference. Factor analysis was applied to energy-adjusted intake of 21 nutrients, and three nutrient patterns were extracted: Factor 1 (fiber, potassium and vitamins pattern); Factor 2 (fats and fat-soluble vitamins pattern); and Factor 3 (saturated fatty acids, calcium and vitamin B2 pattern). In multiple logistic regression analysis adjusted for sex, age, and other potential confounders, Factor 1 scores were associated with a significantly reduced odds ratio (OR) of MetS and all five components. Factor 2 scores were associated with significantly increased prevalence of MetS, obesity, and high blood pressure. Factor 3 scores were significantly associated with lower OR of MetS, high blood pressure, high serum triglycerides and low HDL cholesterol levels. Analysis of nutrient patterns may be useful to assess the overall quality of diet and its association with MetS.

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Factors associated with intra-individual visit-to-visit variability of blood pressure in four countries: the INTERMAP study

Takashima N., Ohkubo T., Miura K., Okayama A., Okuda N., Nakagawa H., Saito S., Sakata K., Choudhury S.R., Miyagawa N., Chan Q., Zhao L., Elliott P., Ueshima H., Stamler J.

Journal of Human Hypertension （Journal of Human Hypertension） 33 （ 3 ） 229 - 236 2019年03月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 09509240

Several studies demonstrated that visit-to-visit variability of blood pressure (BP) predicted future events of total death, stroke and cardiovascular disease. Little is known about factors associated with visit-to-visit BP variability in different countries. We recruited participants aged 40–59 years from four countries (Japan, the People’s Republic of China [PRC], the United Kingdom [UK] and the United States [US]). At each study visit, BP was measured twice by trained observers using random zero sphygmomanometers after five minutes resting. We defined visit-to-visit BP variability as variation independent of mean (VIM) by using average systolic BP of 1st and 2nd measurement across four study visits. Data on 4680 men and women were analyzed. Mean ± standard deviation of VIM values among participants in Japan, the PRC, the UK and the US were 5.44 ± 2.88, 6.85 ± 3.49, 5.65 ± 2.81 and 5.84 ± 3.01, respectively; VIM value in the PRC participants was significantly higher. Sensitivity analyses among participants without antihypertensive treatment or past history of cardiovascular disease yielded similar results. Higher VIM value was associated with older age, female gender, lower pulse rate and urinary sodium excretion and use of antihypertensive agents such as angiotensin converting enzyme inhibitors, beta blockers and calcium channel blockers. The difference of visit-to-visit BP variability between PRC and other countries remained significant after adjustment for possible confounding factors. In this large international study across four countries, visit-to-visit BP variability in the PRC was higher than in the other three countries. Reproducibility and mechanisms of these findings remain to be elucidated.

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Having few remaining teeth is associated with a low nutrient intake and low serum albumin levels in middle-aged and older Japanese individuals: Findings from the NIPPON DATA2010

Nakamura M., Ojima T., Nagahata T., Kondo I., Ninomiya T., Yoshita K., Arai Y., Ohkubo T., Murakami K., Nishi N., Murakami Y., Takashima N., Okuda N., Kadota A., Miyagawa N., Kondo K., Okamura T., Ueshima H., Okayama A., Miura K.

Environmental Health and Preventive Medicine （Environmental Health and Preventive Medicine） 24 （ 1 ） 1 - 1 2019年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1342078X

Background: Oral health is thought to be associated with diet quality, and socioeconomic status (SES) affects both oral health and diet. The aim of this study was to investigate the association between the number of teeth and dietary intake as well as nutritional biomarker, considering the subjects' SES. Methods: We conducted a cross-sectional analysis of data from 2049 individuals aged ≥ 50 years from the National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged 2010. The number of remaining teeth was categorized into age-specific quartiles (Q1 to Q4). We assessed the adjusted means and 95% confidence intervals for dietary variables by the number of teeth using analysis of covariance. Stratified analyses by SES were also conducted. Results: The intake of grain products was 31 g higher, and those of vegetables and meat were 30 g and 8 g lower, respectively, in Q1 (fewer teeth) than in Q4 (more teeth). Carbohydrate intake was higher whereas protein, minerals (potassium, magnesium, and zinc), vitamins (vitamins A, E, B 1 , B 6 , β-carotene, and folic acid), and dietary fiber intakes were lower among individuals with fewer teeth. Adjusted mean serum albumin levels were low in Q1. The associations between the number of teeth and dietary intake were more evident in individuals with a low SES. Conclusions: Having few remaining teeth was associated with a low nutrient intake and low serum albumin levels in middle-aged and older Japanese adults, and these associations were more evident in individuals with low SES.

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Association of work situation with cardiovascular disease mortality risk among working-age Japanese men: A 20-year follow-up of NIPPON DATA90

Okuda N., Kadota A., Nishi N., Miura K., Ohkubo T., Miyagawa N., Satoh A., Kita Y., Hayakawa T., Takashima N., Fujiyoshi A., Okayama A., Okamura T., Ueshima H.

Circulation Journal （Circulation Journal） 83 （ 7 ） 1506 - 1513 2019年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 13469843

Background: Several cohort studies have demonstrated an association between socioeconomic status (SES) and health outcomes in Japan. As long-term employment is common in Japan, the size of the company may be related to cardiovascular disease (CVD) mortality risk. We examined the association of employment conditions with CVD mortality risk among working-age Japanese men (30–59 years, n=2,091). Methods and Results: We used 20-year follow-up data from NIPPON DATA90, for which baseline data were obtained from the 4th National Survey on Circulatory Disorders in 1990. Participants were classified into 4 groups: 3 strata for indefinite-term employees according to company size (large company/public office, moderate-sized, or small), and the self-employed/administrator group. Multivariable-adjusted hazard ratios (HRs) were adjusted for age, lifestyle, and CVD risk factors. Smokers were more common, habitual exercise was less common, and the average systolic blood pressure was higher among indefinite-term employees of small companies compared with employees at large companies/public offices. There was no significant difference in the total CVD mortality risk between indefinite-term employees and self-employed/administrator participants. The age-adjusted HR (95% confidence interval) for total CVD using indefinite-term employees of large companies/public office as a reference was 2.53 (1.12, 5.69) for employees of small companies. Conclusions: Working as an indefinite-term employee at a small company in Japan was significantly associated with elevated risk of CVD mortality among Japanese men.

Associations of overweight, obesity, and underweight with high serum total cholesterol level over 30 years among the Japanese elderly: NIPPON DATA 80, 90, and 2010

Shibata Y., Ojima T., Nakamura M., Kuwabara K., Miyagawa N., Saito Y., Nakamura Y., Kiyohara Y., Nakagawa H., Fujiyoshi A., Kadota A., Ohkubo T., Okamura T., Ueshima H., Okayama A., Miura K., Saitoh S., Sakata K., Hozawa A., Hayakawa T., Nakamura Y., Nishi N., Okuda N., Murakami Y., Kasagi F., Izumi T., Matsumura Y., Tamakoshi K., Kita Y., Miyamatsu N., Yoshita K., Miyamoto Y., Kodama K.

Journal of Epidemiology （Journal of Epidemiology） 29 （ 4 ） 133 - 138 2019年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 09175040

Background: The trend of association between overweight and high serum total cholesterol (TC) among the elderly is unclear. In addition, there is little evidence of risk of underweight for high TC. Therefore, we examined the trend of association of overweight or underweight with high TC among Japanese elderly people using nationwide population-based data. Methods: Data of the National Survey on Circulatory Disorders and National Health and Nutrition Survey for 1980, 1990, 2000, and 2010 were used in the analysis. High TC was defined as 220mg=dL and above. For participants aged =50 years, sex-specific odds ratios (ORs) of overweight or underweight compared with normal body mass index participants for high TC were calculated using a logistic regression model adjusted for age, smoking, drinking, exercise, food, and treatment of hyperlipidemia. Results: A total of 5,734, 4,673, 5,059, and 2,105 participants enrolled in these surveys in 1980, 1990, 2000, and 2010, respectively. Although overweight was positively and significantly associated with high TC in 1980, the association has gradually weakened since (ORs in 1980 and 2010 were 2.44; 95% confidence interval [CI], 1.83-3.24 and 0.92; 95% CI, 0.66-1.27 among men and 1.43; 95% CI, 1.18-1.72 and 1.08; 95% CI, 0.81-1.44 among women, respectively). While underweight was inversely and significantly associated with high TC in 1980, the association also gradually weakened among women (ORs in 1980 and 2010 were 0.28; 95% CI, 0.12-0.60 and 0.37; 95% CI, 0.10-1.28 among men and 0.39; 95% CI, 0.26-0.57 and 0.96; 95% CI, 0.58-1.57 among women, respectively). Conclusions: These findings provide evidence that high TC prevention efforts must expand the target to not only overweight but also to normal and underweight people.

Cardiovascular risk assessment chart by dietary factors in Japan: NIPPON DATA80

Kondo K., Miura K., Tanaka-Mizuno S., Kadota A., Arima H., Okuda N., Fujiyoshi A., Miyagawa N., Yoshita K., Okamura T., Okayama A., Ueshima H.

Circulation Journal （Circulation Journal） 83 （ 6 ） 1254 - 1260 2019年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 13469843

Background: Many studies show that dietary factors such as vegetables, fruit, and salt are associated with cardiovascular disease (CVD) risk. However, a risk assessment chart for CVD mortality according to combinations of dietary factors has not been established. Methods and Results: Participants were 9,115 men and women aged 30–79 years enrolled in the National Nutritional Survey of Japan in 1980 with a 29-year follow-up. Dietary intake was assessed using a 3-day weighed dietary record at baseline. Cox regression models were used to estimate the hazard ratio (HR) of CVD mortality stratified by vegetables, fruit, fish, and salt consumption. HRs of CVD mortality according to combinations of dietary factors were color coded on an assessment chart. Higher intakes of vegetables, fruit, and fish, and lower salt intake were associated with lower CVD mortality risk. HRs calculated from combinations of dietary factors were displayed using 5 colors corresponding to the magnitude of the HR. People with the lowest intake of vegetables, fruit, and fish, and higher salt intake had a HR of 2.87 compared with those with the highest intake of vegetables, fruit, and fish, and lower salt intake. Conclusions: Vegetables, fruit, fish, and salt intake were independently associated with CVD mortality risk. The assessment chart generated could be used in Japan as an educational tool for CVD prevention.

Vegetable protein intake was inversely associated with cardiovascular mortality in a 15-year follow-up study of the general Japanese population

Kurihara A., Okamura T., Sugiyama D., Higashiyama A., Watanabe M., Okuda N., Kadota A., Miyagawa N., Fujiyoshi A., Yoshita K., Ohkubo T., Okayama A., Miura K., Ueshima H.

Journal of Atherosclerosis and Thrombosis （Journal of Atherosclerosis and Thrombosis） 26 （ 2 ） 198 - 206 2019年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 13403478

Aim: To examine the relationship between the intake of dietary vegetable protein and CVD mortality in a 15-year follow-up study of a representative sample of the Japanese population. Methods: A total of 7,744 participants aged 30 years or older (3,224 males and 4,520 females) who were free of CVD at baseline were included in this analysis. Vegetable protein intake (% energy) was assessed using a threeday semi-weighed dietary record at baseline. Multivariable-adjusted hazard ratios (HRs) were calculated using Cox’s proportional hazards model after adjusting for confounding factors. Results: The total person-years studied were 107,988 with a mean follow-up period of 13.9 years. There were 1,213 deaths during the follow-up period, among which 354 (29.2%) were due to CVD. Vegetable protein intake was associated inversely with CVD and cerebral hemorrhage mortality, with the HRs for a 1% energy increment in vegetable protein intake being 0.86 (95% CI, 0.75-0.99) and 0.58 (95% CI, 0.35-0.95), respectively. In the subgroup analysis of participants with or without hypertension, the inverse association between vegetable protein intake and CVD mortality was more evident in the nonhypertensive group, with the HRs for CVD and stroke being 0.68 (95% CI, 0.50- 0.94) and 0.50 (95% CI, 0.30-0.84), respectively. Conclusions: Vegetable protein intake may prevent future CVD, particularly in nonhypertensive subjects in the Japanese population. However, further studies are necessary to examine the biological mechanisms of this effect.

Relationship of serum irisin levels to prevalence and progression of coronary artery calcification: A prospective, population-based study

Hisamatsu T., Miura K., Arima H., Fujiyoshi A., Kadota A., Kadowaki S., Zaid M., Miyagawa N., Satoh A., Kunimura A., Horie M., Ueshima H.

International Journal of Cardiology （International Journal of Cardiology） 267 177 - 182 2018年09月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 01675273

Background: The mechanisms by which exercise reduces the risk of coronary heart disease remain poorly understood. Irisin, an exercise-induced polypeptide secreted from skeletal muscles, is proposed to potentially mediate beneficial effects of exercise, especially in metabolic regulation and development of atherosclerosis. We examined whether higher serum irisin levels are associated with lower prevalence and progression of coronary atherosclerosis. Methods and results: We performed a prospective, population-based study of Japanese men aged 40–79 years without known coronary heart disease. We measured baseline serum irisin levels using an enzyme-linked immunosorbent assay and quantified coronary artery calcification (CAC) from serial computed tomography scans. Of 1038 participants (mean age, 63.9 years) at baseline, 670 (64.6%) had prevalent CAC. Of 810 participants at follow-up (median, 5.1 years), 407 (50.3%) experienced CAC progression. In Poisson regression with robust error variance adjusted for age and behavioral factors, serum irisin levels were inversely associated with CAC prevalence (relative risk [RR] of 4th versus 1st quartiles [95% confidence interval], 0.88 [0.78–0.99]; trend P = 0.016) and CAC progression (RR, 0.76 [0.63–0.91]; trend P = 0.002). After further adjustment for cardiometabolic risk factors, the inverse association with CAC prevalence disappeared (RR, 0.95 [0.84–1.08]; trend P = 0.319), but that with CAC progression persisted (RR, 0.77 [0.64–0.93]; trend P = 0.003). These associations were consistent when we applied ordinal logistic regression and across subgroups by cardiometabolic risk factor status. Conclusions: Higher serum irisin levels were associated with less burden of coronary atherosclerosis. This association would be mediated through and beyond traditional cardiometabolic pathways.

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Serum magnesium, phosphorus, and calcium levels and subclinical calcific aortic valve disease: A population-based study

Hisamatsu T., Miura K., Fujiyoshi A., Kadota A., Miyagawa N., Satoh A., Zaid M., Yamamoto T., Horie M., Ueshima H.

Atherosclerosis （Atherosclerosis） 273 145 - 152 2018年06月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 00219150

Background and aims: Calcific aortic valve disease (CAVD) is the most common valve disease. Although micronutrients are known to contribute to cardiovascular disease, the relationship with CAVD remains poorly evaluated. We examined the association of serum levels of magnesium, phosphorus, and calcium with prevalence, incidence, and progression of aortic valve calcification (AVC). Methods: We conducted a prospective study in a population-based sample of Japanese men aged 40–79 years without known cardiovascular disease and chronic kidney disease at baseline, and quantified AVC from serial computed tomographic images with the Agatston method. Results: Of 938 participants at baseline (mean age, 63.7 ± 9.9 years), AVC prevalence was observed in 173 (18.4%). Of 596 participants without baseline AVC at follow-up (median duration, 5.1 years), AVC incidence was observed in 138 (23.2%). After adjustment for demographics, behaviors and cardiovascular risk factors, relative risks (95% confidence intervals) in the highest versus lowest categories of serum magnesium, phosphorus, and calcium were 0.62 (0.44–0.86), 1.45 (1.02–2.04), and 1.43 (0.95–2.15), respectively, for AVC prevalence and 0.62 (0.42–0.92), 1.93 (1.28–2.91), and 1.09 (0.77–1.55), respectively, for AVC incidence. Their linear trends of serum magnesium and phosphorus were also all statistically significant. Of 131 participants with baseline AVC, there was no association of any serum micronutrients with AVC progression. Conclusions: Serum magnesium was inversely associated, while serum phosphorus was positively associated with AVC prevalence and incidence, suggesting that these serum micronutrients may be potential candidates for risk prediction or prevention of CAVD, and warranting further studies.

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Overweight or underweight and the risk of decline in activities of daily living in a 22-year cohort study of a Japanese sample

Okamoto S., Okamura T., Sugiyama D., Hayakawa T., Nakamura Y., Miyagawa N., Kurita S., Takashima N., Ohkubo T., Kadota A., Fujiyoshi A., Miura K., Okayama A., Ueshima H.

Geriatrics and Gerontology International （Geriatrics and Gerontology International） 18 （ 5 ） 799 - 805 2018年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 14441586

Aim: The present study aimed to clarify the association between body mass index (BMI) and the activities of daily living (ADL). Although BMI is likely to be concerned regarding the relationship with specific diseases or mortality, few studies have focused on the relationship of BMI and ADL. Methods: A total of 3353 Japanese participants of a 22-year cohort study from 1990 to 2012 aged 45–74 years at baseline were divided into four groups according to their BMI levels: ≤18.5, 18.5–21.9 (reference), 22.0–24.9 and ≥25.0 kg/m 2 . Outcomes were becoming dependent in ADL (including death after ADL decline) and death without observation of ADL decline as a competing risk. Sex-specific multinomial logistic regression analysis was carried out in 2017 to estimate the odds ratios (OR) after adjusting for age, smoking, alcohol drinking, hypertension, hypercholesterolemia, diabetes and serum albumin. Results: After multivariable adjustment, though the relationship between BMI and risk of ADL decline was U-shaped among women, only those with BMI ≥25.0 showed a higher risk for ADL decline (OR 1.39, 95% CI 1.01–1.92) compared with the reference. The OR for death without observation of ADL decline was significantly lower for men with BMI ≥25.0 (OR 0.70, 95% CI 0.50–0.98). Conclusions: This study suggests being overweight is a good predictor of future decline in ADL for women, whereas men with BMI 22.0–24.9 had lower risks of ADL decline. Appropriate management of weight in older women could prevent disabilities. Geriatr Gerontol Int 2018; 18: 799–805.

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Dietary tofu intake and long-term risk of death from stroke in a general population

Nguyen H.N., Miyagawa N., Miura K., Okuda N., Yoshita K., Arai Y., Nakagawa H., Sakata K., Ojima T., Kadota A., Takashima N., Fujiyoshi A., Ohkubo T., Abbott R.D., Okamura T., Okayama A., Ueshima H.

Clinical Nutrition （Clinical Nutrition） 37 （ 1 ） 182 - 188 2018年02月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 02615614

Background & aim: Although dietary soy intake is linked with health benefits, a relation with stroke has not been established. The present study examined the association between the intake of tofu, the richest source of dietary soy, with stroke mortality in a general population cohort of Japanese men and women. Methods: Data comprise 9244 Japanese enrolled in the National Nutrition Survey of Japan in 1980. Participants were free of cardiovascular disease and followed for 24 years. Dietary intake was estimated from 3-day weighed food records. Multivariable Cox regression models were used to estimate hazard ratios across levels of tofu intake. Results: During follow-up, there were 417 deaths due to stroke (88 cerebral hemorrhage [CH], 245 cerebral infarction [CI], and 84 of other subtypes). Among all men, and in women aged 65 years or more, tofu intake was unrelated to each form of stroke. For young women (<65 years of age), a significantly lower risk of CH in the top versus bottom quartile of tofu intake was observed (Multivariable-adjusted HR = 0.26, 95% CI: 0.08–0.85). Conclusions: In this large prospective study with long follow-up of Japanese men and women, consumption of tofu was unrelated to the risk of stroke except for CH in women <65 years of age. Whether the association in younger women is real or due to chance alone warrants further study.

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Associations of high-density lipoprotein particle and high-density lipoprotein cholesterol with alcohol intake, smoking, and body mass index: The INTERLIPID study

Zaid M., Miura K., Okayama A., Nakagawa H., Sakata K., Saitoh S., Okuda N., Yoshita K., Choudhury S.R., Rodriguez B., Masaki K., Willcox B., Miyagawa N., Okamura T., Chan Q., Elliott P., Stamler J., Ueshima H.

Circulation Journal （Circulation Journal） 82 （ 10 ） 2557 - 2565 2018年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 13469843

Background: Recently, high-density lipoprotein particles (HDL-P) have been found to be more strongly inversely associated with coronary artery disease (CAD) risk than their counterpart, HDL cholesterol (HDL-C). Given that lifestyle is among the first targets in CAD prevention, we compared the associations of HDL-P and HDL-C with selected lifestyle factors. Methods and Results: We examined 789 Japanese participants of the INTERLIPID Study: men (n=386) and women (n=403) aged 40–59 years in 1996–1998. Participants treated for dyslipidemias were excluded. Lifestyle factors included alcohol intake, smoking amount, and body mass index (BMI). Multivariable linear regression was used for cross-sectional analyses of these factors with HDL-P, HDL-C, HDL-P size subclasses (small, medium and large) and mean HDL-P size. In men, higher alcohol intake was associated with higher HDL-P and higher HDL-C. The associations of alcohol, however, were strongest with HDL-P. A higher smoking amount tended to be associated with lower HDL-P and HDL-C. In contrast, BMI was not associated with HDL-P, but was strongly inversely associated with HDL-C. While alcohol intake favored larger mean HDL-P size, smoking and BMI favored a lipid profile with smaller HDL-P subclasses and overall smaller mean HDL-P size. Similar, but generally weaker results were observed in women. Conclusions: Although both HDL-P and HDL-C are parameters of HDL, they have different associations with alcohol, smoking and BMI.

Differences in lifestyle improvements with the intention to prevent cardiovascular diseases by socioeconomic status in a representative japanese population: NIPPON DATA2010

Goryoda S., Nishi N., Hozawa A., Yoshita K., Arai Y., Kondo K., Miyagawa N., Hayakawa T., Fujiyoshi A., Kadota A., Ohkubo T., Okamura T., Okuda N., Ueshima H., Okayama A., Miura K.

Journal of Epidemiology （Journal of Epidemiology） 28 （ Supplement_III ） S35 - S39 2018年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 09175040

Background: The relationships among socioeconomic status and lifestyle improvements have not yet been examined in a representative Japanese population. Methods: We analyzed data from 2,647 participants (1,087 men and 1,560 women) who participated in NIPPON DATA2010. This survey inquired about lifestyle improvements and socioeconomic status. Education was categorized as low (≤9 years), middle (10–12 years), and high (≥13 years). Marital status was categorized as married, divorced, widowed, and never married= other. A multivariable logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of lifestyle improvements with the intention of preventing cardiovascular diseases for educational attainment and marital status, with adjustments for age and awareness of cardiovascular disease risk factors. Results: Overall, 1,507 (56.9%) participants practiced prevention and improvements in hypertension, diabetes, elevated cholesterol, and metabolic syndrome, and the OR of lifestyle improvements was significantly higher with a high education than with a low education in men (OR 2.86; 95% CI, 1.96–4.17) and women (OR 2.36; 95% CI, 1.67–3.33). The number of participants who practiced prevention and improvements in hypertension, diabetes, elevated cholesterol, and metabolic syndrome was significantly lower in divorced than in married men (OR 0.46; 95% CI, 0.22–0.95) and women (OR 0.53; 95% CI, 0.33–0.86). Conclusions: Specific differences caused by educational attainment and marital status may exist in lifestyle improvements.

Effectiveness of a Self-monitoring Device for Urinary Sodium-to-Potassium Ratio on Dietary Improvement in Free-Living Adults: a Randomized Controlled Trial

Iwahori T., Ueshima H., Ohgami N., Yamashita H., Miyagawa N., Kondo K., Torii S., Yoshita K., Shiga T., Ohkubo T., Arima H., Miura K.

Journal of Epidemiology （Journal of Epidemiology） 28 （ 1 ） 41 - 47 2018年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 09175040

Background: Reducing the urinary sodium-to-potassium ratio is important for reducing both blood pressure and risk of cardiovascular disease. Among free-living Japanese individuals, we carried out a randomized trial to clarify the effect of lifestyle modification for lowering urinary sodium-to-potassium ratio using a self-monitoring device. Methods: This was an open, prospective, parallel randomized, controlled trial. Ninety-two individuals were recruited from Japanese volunteers. Participants were randomly allocated into intervention and control groups. A month-long dietary intervention on self-monitoring urinary sodium-to-potassium ratio was carried out using monitors (HEU-001F, OMRON Healthcare Co., Ltd., Kyoto, Japan). All participants had brief dietary education and received a leaflet as usual care. Monitors were handed out to the intervention group, but not to the control group. The intervention group was asked to measure at least one spot urine sodium-to-potassium ratio daily, and advised to lower their sodium-to-potassium ratio toward the target of less than 1. Outcomes included changes in 24-hour urinary sodium-to-potassium ratio, sodium excretion, potassium excretion, blood pressure, and body weight in both groups. Results: Mean measurement frequency of monitoring was 2.8 times/day during the intervention. Changes in urinary sodium-to-potassium ratio were –0.55 in the intervention group and –0.06 in the control group (P = 0.088); respective sodium excretion changes were –18.5 mmol/24 hours and –8.7 mmol/24 hours (P = 0.528); and corresponding potassium excretion was 2.6 mmol/24 hours and –1.5 mmol/24 hours (P = 0.300). No significant reductions were observed in either blood pressure or body weight after the intervention. Conclusions: Providing the device to self-monitor a sodium-to-potassium ratio did not achieve the targeted reduction of the ratio in “pure self-management” settings, indicating further needs to study an effective method to enhance the synergetic effect of dietary programs and self-monitoring practice to achieve the reduction. However, we cannot deny the possibility of reducing sodium-to-potassium ratio using a self-monitoring device.

Relationships among food group intakes, household expenditure, and education attainment in a general Japanese population: NIPPON DATA2010

Nagahata T., Nakamura M., Ojima T., Kondo I., Ninomiya T., Yoshita K., Arai Y., Ohkubo T., Murakami K., Nishi N., Murakami Y., Takashima N., Okuda N., Kadota A., Miyagawa N., Kondo K., Okamura T., Ueshima H., Okayama A., Miura K.

Journal of Epidemiology （Journal of Epidemiology） 28 （ Supplement_III ） S23 - S28 2018年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 09175040

Background: A lower socioeconomic status (SES) may be related to the intake of unhealthy food; however, this relationship has not been examined in detail. This study was undertaken to examine relationships among food group intakes and SES in a representative Japanese population. Methods: This was a cross-sectional study using the baseline data of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey in Japan. A total of 2,898 participants were included in the baseline survey in 2010. The effects of age (<65 years and ≥65 years), equivalent household expenditure (EHE), and education attainment on food group intakes (gram per 1,000 kcal) were analyzed using a two-way analysis of variance. Results: When EHE was lower, cereal intake was higher in men and women. Among men, fish, milk, and alcohol intakes were reduced with lower EHE. Among women, vegetable intake was reduced with lower EHE. In men and women, cereal intake was higher with lower education attainment. In contrast, meat intake was reduced with lower education attainment. Conclusions: Lower SES was associated with a higher cereal intake and lower vegetable, fish, meat, and milk intakes in a representative Japanese population. Socioeconomic discrepancies need to be considered in order to promote healthier dietary habits.

Socioeconomic status associated with urinary sodium and potassium excretion in Japan: NIPPON DATA2010

Miyagawa N., Okuda N., Nakagawa H., Takezaki T., Nishi N., Takashima N., Fujiyoshi A., Ohkubo T., Kadota A., Okamura T., Ueshima H., Okayama A., Miura K.

Journal of Epidemiology （Journal of Epidemiology） 28 （ Supplement_III ） S29 - S34 2018年

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り, ISSN 09175040

Background: Although socioeconomic status (SES) may affect food and nutrient intakes, few studies have reported on sodium (Na) and potassium (K) intakes among individuals with various SESs in Japan. We investigated associations of SES with Na and K intake levels using urinary specimens in a representative Japanese population. Methods: This was a cross-sectional study of 2,560 men and women (the NIPPON DATA2010 cohort) who participated in the National Health and Nutrition Survey Japan in 2010. Casual urine was used to calculate estimated excretion in 24-hour urinary Na (E24hr-Na) and K (E24hr-K). The urinary sodium-to-potassium (Na=K) ratio was calculated from casual urinary electrolyte values. An analysis of covariance was performed to investigate associations of aspects of SES, including equivalent household expenditure (EHE), educational attainment, and job category, with E24hr-Na, E24hr-K, and the Na=K ratio for men and women separately. A stratified analysis was performed on educational attainment and the job category for younger (<65 years) and older (≥65 years) participants. Results: In men and women, average E24hr-Na was 176.2 mmol=day and 172.3, average E24hr-K was 42.5 and 41.3, and the average Na=K ratio was 3.61 and 3.68, respectively. Lower EHE was associated with a higher Na=K ratio in women and lower E24hr-K in men and women. A shorter education was associated with a higher Na=K ratio in women and younger men, and lower E24hr-K in older men and women. Conclusion: Lower EHE and a shorter education were associated with a lower K intake and higher Na=K ratio estimated from casual urine specimens in Japanese men and women.

肥満、非肥満別の各種循環器疾患危険因子による循環器疾患死亡の集団寄与危険割合　NIPPON DATA80の29年追跡結果より

宮澤伊都子, 三浦克之, 宮本恵宏, 岡村智教, 東山綾, 辰巳友佳子, 門田文, 高嶋直敬, 宮川尚子, 近藤慶子, 佐藤敦, 有馬久富, 岡山明, 上島弘嗣, NIPPON DATA80研究グループ

日本循環器病予防学会誌（(一社)日本循環器病予防学会） 52 （ 3 ） 269 - 278 2017年12月

研究論文（学術雑誌）, ISSN 1346-6267

【背景】我が国では、2008年より特定健診が開始され、肥満を必須とするメタボリックシンドローム該当者に対する保健指導介入が行われている。残る非肥満に対する有効な介入方法が模索されているが、肥満、非肥満別に循環器疾患危険因子による循環器疾患死亡の集団寄与危険割合を検討した報告は少ない。【目的】循環器疾患危険因子(血圧、血糖、喫煙)による循環器疾患死亡の集団寄与危険割合(Population Attributable Fraction:PAF)を非肥満群、肥満群に分けて検討する。【方法】対象は1980年に実施された循環器疾患基礎調査の受検者を29年間追跡したNIPPON DATA80対象者のうち、40歳〜74歳の男女計6,662人である。肥満の有無と循環器疾患危険因子のカテゴリーを組み合わせて対象者を分類し、"非肥満かつ循環器疾患危険因子正常群"に対する、各群の多変量調整ハザード比とPAFを算出した。PAFはより現在に近い2010年の危険因子の分布でも算出し、1980年との比較を行った。【結果】循環器疾患死亡に対する多変量調整ハザード比(95%信頼区間)は、血圧は正常、正常高値、高血圧1度、高血圧2度以上と上昇するに従い、非肥満群、肥満群ともに上昇を認めた(非肥満かつ高血圧2度以上群:2.10(1.64-2.70)、肥満かつ高血圧2度以上群:2.72(1.95-3.80)。血糖は正常(随時血糖140mg/dl未満)、境界型(140-200mg/dl)、糖尿病域(200mg/dl以上)と上昇するに従い、非肥満群、肥満群ともに上昇を認めた(非肥満かつ糖尿病域群:2.01(1.33-3.03)、肥満かつ糖尿病域群5.08(2.98-8.66)。喫煙は非喫煙、過去喫煙、現在喫煙(≦20本/日、≦21本/日)の順に上昇を認めた(非肥満かつ現在喫煙≦21本/日群:1.94(1.47-2.55)、肥満かつ現在喫煙≧21本/日群:1.98(1.24-3.15)。2010年の危険因子分布を用いた血圧のPAF合計は非肥満群37.2%、肥満群21.7%、血糖のPAF合計は非肥満群14.4%、肥満群16.3%、喫煙のPAF合計は非肥満群7.0%、肥満群0.9%と、いずれにおいても非肥満群のPAFは肥満群と同等もしくは高値を示した。【結論】各種循環器疾患危険因子は非肥満群、肥満群のどちらにおいても循環器疾患死亡リスクと関連していた。PAFは非肥満群の方が肥満群よりも大きい傾向であり、非肥満者に対しても循環器疾患危険因子に対する介入が重要であることが示唆された。(著者抄録)

Comparison of weighed food record procedures for the reference methods in two validation studies of food frequency questionnaires.

Ishii Y, Ishihara J, Takachi R, Shinozawa Y, Imaeda N, Goto C, Wakai K, Takahashi T, Iso H, Nakamura K, Tanaka J, Shimazu T, Yamaji T, Sasazuki S, Sawada N, Iwasaki M, Mikami H, Kuriki K, Naito M, Okamoto N, Kondo F, Hosono S, Miyagawa N, Ozaki E, Katsuura-Kamano S, Ohnaka K, Nanri H, Tsunematsu-Nakahata N, Kayama T, Kurihara A, Kojima S, Tanaka H, Tsugane S

Journal of epidemiology （ELSEVIER SCIENCE INC） 27 （ 7 ） 331 - 337 2017年07月

研究論文（学術雑誌）, 査読有り, ISSN 0917-5040

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Food sources of dietary sodium in the Japanese adult population: the international study of macro-/micronutrients and blood pressure (INTERMAP).

Okuda N, Okayama A, Miura K, Yoshita K, Saito S, Nakagawa H, Sakata K, Miyagawa N, Chan Q, Elliott P, Ueshima H, Stamler J

European journal of nutrition （SPRINGER HEIDELBERG） 56 （ 3 ） 1269 - 1280 2017年04月

研究論文（学術雑誌）, 査読有り, ISSN 1436-6207

Purpose It is often reported that Na intake levels are higher in Japan than in western countries. Detailed analysis of food intake and its association with Na intake are necessary for supporting further decreases in Na consumption in Japan. We investigated the association between Na and food intake by food group using data from the Japanese participants of the INTERMAP Study.
Method Results from the Japanese participants of the INTERMAP Study who did not use antihypertensive medication and/or consume a reduced Na diet were used (531 men and 518 women, aged 40-59 years), obtained from four 24-h dietary recalls and two 24-h urine collections from each participant. We developed a classification system with 46 food group classifications; food consumption and Na intake from these groups were compared across quartiles of participants determined by 24-h urinary Na excretion per unit of body weight (UNa/BW).
Results Average daily Na intake from Japanese high-Na foods was 2552 mg/day. Participants with a higher UNa/BW consumed a significantly greater amount of high-Na Japanese foods, such as salted fish (P= 0.001) and miso soup (P < 0.001). They also had greater amount of rice (P = 0.001). Participants with lower UNa/BW consumed a significantly greater amount of western foods, such as bread (P < 0.001) and milk and dairy products (P < 0.001).
Conclusions Detailed analyses of various Japanese and western food intakes in addition to Na intake were performed. These results can be used to help draw up effective programs for the reduction in Na intake and prevention of prehypertension/hypertension in the Japanese population.

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Significant inverse association of equol-producer status with coronary artery calcification but not dietary isoflavones in healthy Japanese men.

Ahuja V, Miura K, Vishnu A, Fujiyoshi A, Evans R, Zaid M, Miyagawa N, Hisamatsu T, Kadota A, Okamura T, Ueshima H, Sekikawa A

The British journal of nutrition （CAMBRIDGE UNIV PRESS） 117 （ 2 ） 260 - 266 2017年01月

研究論文（学術雑誌）, 査読有り, ISSN 0007-1145

Equol, a metabolite of the dietary isoflavone daidzein, is produced by the action of gut bacteria in some individuals who are termed as equol-producers. It is proposed to have stronger atheroprotective properties than dietary isoflavones. We examined a cross-sectional association of dietary isoflavones and equol-producer status with coronary artery calcification (CAC), a biomarker of coronary atherosclerosis, among men in Japan. A population-based sample of 272 Japanese men aged 40-49 years recruited from 2004 to 2007 was examined for serum isoflavones, serum equol, CAC and other factors. Equol-producers were classified as individuals having a serum level of equol >83 nm. The presence of CAC was defined as a coronary Ca score 10 Agatston units. The associations of dietary isoflavones and equol-producers with CAC were analysed using multiple logistic regression. The median of dietary isoflavones, equol and CAC were 5127 (interquartile range (IQR) 1941, 11700), 91 (IQR 010, 331) and 00 (IQR 00, 10) nm, respectively. Prevalence of CAC and equol-producers was 96 and 160 %, respectively. Dietary isoflavones were not significantly associated with CAC. After multivariable adjustment, the OR for the presence of CAC in equol-producers compared with equol non-producers was 010 (95 % CI 001, 090, P<004). Equol-producers had significantly lower CAC than equol non-producers, but there was no significant association between dietary isoflavones and CAC, suggesting that equol may be a key factor for atheroprotective properties of isoflavones in Japanese men. This finding must be confirmed in larger studies or clinical trials of equol that is now available as a dietary supplement.

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Overall nutrient and total fat intake among Japanese people: The INTERLIPID Study Japan.

Koyama T, Yoshita K, Okuda N, Saitoh S, Sakata K, Okayama A, Nakagawa H, Miyagawa N, Miura K, Chan Q, Elliott P, Stamler J, Ueshima H

Asia Pacific journal of clinical nutrition （H E C PRESS, HEALTHY EATING CLUB PTY LTD） 26 （ 5 ） 837 - 848 2017年

研究論文（学術雑誌）, 査読有り, ISSN 0964-7058

Background and Objectives: Total fat intake is linked to the intake of other nutrients. Little data are available on the extent to which total fat affects diet quality in Japanese people. We investigated the relationship between total fat intake and other nutrient intake using INTERLIPID/INTERMAP data on Japanese people living in Japan. Methods and Study Design: The participants included 371 men and 401 women with a healthy body mass index and between the ages of 40 and 59 from 4 population samples in Japan. Nutrient intake data were based on four in-depth 24-hour dietary recalls per person. Results: Analysis of covariance adjusted for age revealed that total fat intake was positively related to intakes of calcium, thiamine, riboflavin, meat, eggs, and milks and dairy products for both sexes. Total fat intake was inversely associated with carbohydrate and cereals intake for both sexes. On average, men with total fat intake between 25.0 and 27.4% of total energy had saturated fatty acids above 7%, which is the upper limit recommended for preventing lifestyle-related diseases. Men with total fat intake less than 20% of total energy had a higher risk of not meeting the Dietary Reference Intakes for Japanese (2015) for some nutrients. Conclusions: Total fat intake was positively associated with calcium, thiamine, and riboflavin intakes and inversely associated with carbohydrate intake. Our results suggest that in 40-59-year-old men with a healthy body mass index, total fat intake between 20 and 27% of total energy may best support adequate intake of other nutrients.

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Lifetime cigarette smoking is associated with abdominal obesity in a community-based sample of Japanese men: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).

Fujiyoshi A, Miura K, Kadowaki S, Azuma K, Tanaka S, Hisamatsu T, Arima H, Kadota A, Miyagawa N, Takashima N, Ohkubo T, Saitoh Y, Torii S, Miyazawa I, Maegawa H, Murata K, Ueshima H, SESSA Research Group.

Preventive medicine reports 4 225 - 32 2016年12月

研究論文（学術雑誌）, 査読有り, ISSN 2211-3355

Studies from Western countries suggest that smokers tend to display greater abdominal obesity than non-smokers, despite showing lower weight. Whether this holds true in a leaner population requires clarification. Using indices of abdominal obesity including visceral adipose tissue, we examined whether lifetime cigarette smoking is associated with unfavorable fat distribution among Japanese men. From 2006 to 2008, we conducted a cross-sectional investigation of a community-based sample of Japanese men at 40-64 years old, free of cardiovascular diseases and cancer. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography. We divided participants into four groups: never-smokers; and tertiles of pack-years of smoking among ever-smokers. Using multivariable linear regression, we calculated adjusted means of obesity indices (VAT, SAT, VAT-SAT ratio [VSR], and waist-hip ratio [WHR]) for each group, and mean differences between consecutive groups. We analyzed 513 men (median age, 58.2 years; current smokers, 40.1%). Two-thirds showed body mass index (BMI) < 25 kg/m(2) (median, 23.5 kg/m(2)). Overall, greater lifetime smoking group was associated with greater WHR and VSR. On average, one higher smoking group was associated with 0.005 higher WHR (95% CI, 0.001-0.008; P = 0.005) and 0.041 greater VSR (95% CI, 0.009-0.073; P = 0.012) after adjustment for potential confounders, including BMI. In this sample of relatively lean Japanese men, greater lifetime smoking was associated with a metabolically more adverse fat distribution. Although smoking is commonly associated with lower BMI, minimizing the amount of lifetime smoking should be advocated.

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一般国民における循環器疾患危険因子の認知度および危険因子保有と認知度との関連　NIPPON DATA2010

永井雅人, 大久保孝義, 門田文, 宮川尚子, 村上義孝, 高嶋直敬, 奥田奈賀子, 東山綾, 早川岳人, 藤吉朗, 中村好一, 岡村智教, 上島弘嗣, 岡山明, 三浦克之

日本循環器病予防学会誌（(一社)日本循環器病予防学会） 51 （ 3 ） 166 - 175 2016年11月

研究論文（学術雑誌）, ISSN 1346-6267

【目的】循環器疾患危険因子の正しい知識を持つ者ほど、循環器疾患発症に予防的な健康行動をとることが報告されている。そこで本研究では本邦国民における循環器疾患危険因子の認知度を明らかにするとともに、危険因子保有と認知度との関連を検討した。【方法】平成22年国民健康・栄養調査に参加した全国300地区からの20歳以上の男女2,891名に対し、「心筋梗塞または脳卒中の原因として正しいと思うもの」を選択する質問調査を実施した。正答は高血圧、糖尿病、高コレステロール血症、喫煙、不整脈、HDLコレステロール低値である。ロジスティック回帰分析で、各危険因子の保有者をそれぞれの非保有者と比較し、危険因子を認知している年齢調整オッズ比を算出した。【結果】循環器疾患危険因子の認知度はそれぞれ、85.8%(高血圧)、72.6%(高コレステロール血症)、58.5%(喫煙)、49.8%(不整脈)、45.1%(糖尿病)、38.5%(HDLコレステロール低値)であった。男性では、各危険因子の非保有者を基準とした時、高血圧者の高血圧認知度、高コレステロール血症を有する者の高コレステロール血症認知度、過去の喫煙習慣を有する者で喫煙に関する認知度、糖尿病者の糖尿病認知度が有意に高かった(オッズ比1.33〜2.73)。女性では、高コレステロール血症を有する者の高コレステロール血症認知度、過去の喫煙習慣を有する者で喫煙に関する認知度、糖尿病者の糖尿病認知度が有意に高かった(オッズ比1.54〜1.80)。【結論】循環器疾患危険因子の認知度は、高血圧で8割を超える一方、不整脈、糖尿病、HDLコレステロール低値では5割に満たなかった。また、危険因子保有者は保有する危険因子が循環器疾患危険因子であることを認知している傾向が観察されたが、その他の危険因子の認知度は非保有者と同程度、または低い傾向であった。国民に対する循環器疾患危険因子の周知が必要である。(著者抄録)

Relationship between non-high-density lipoprotein cholesterol and the long-term mortality of cardiovascular diseases: NIPPON DATA 90.

Ito T, Arima H, Fujiyoshi A, Miura K, Takashima N, Ohkubo T, Kadota A, Hayakawa T, Kita Y, Miyagawa N, Okayama A, Okamura T, Ueshima H, NIPPON DATA90 Research Group.

International journal of cardiology （ELSEVIER IRELAND LTD） 220 262 - 7 2016年10月

研究論文（学術雑誌）, 査読有り, ISSN 0167-5273

Background: Non-high-density lipoprotein (HDL) cholesterol level, generally less affected by fasting status or serum triglyceride levels, may be useful for predicting future cardiovascular events in daily clinical practice. This study aimed to investigate the role of non-HDL cholesterol in the development of fatal coronary events and stroke in the general Japanese population.
Methods and results: From the NIPPON DATA 90 prospective cohort study, 8383 participants were followed up for 20 years since 1990. After exclusion of 666 cases without lipid or covariates data, 561 cases who were 75 years old or older, 274 cases with history of cardiovascular disease, and 181 cases with lipid-lowering treatment, 6701 participants were included in this analysis. Non-HDL cholesterol was defined as total cholesterol minus HDL cholesterol. Outcomes were death from coronary heart disease and stroke. During the period, 69 participants died from coronary heart disease and 112 from stroke. Compared with participants with non-HDL cholesterol level b3.9 mmol/L, age- and sex-adjusted hazard ratios for mortality by coronary heart disease in those with non-HDL cholesterol levels of 3.9-4.3 mmol/L, 4.4-4.8 mmol/L and >= 4.9 mmol/L were 1.27 (95% confidence interval [CI] 0.65-2.49), 1.81 (95% CI 0.92-3.55) and 2.40 (95% CI 1.30-4.43), respectively (P trend = 0.010). This association remained significant even after adjusting for other cardiovascular risk factors (P trend = 0.010). There was no clear association between non-HDL cholesterol levels and mortality by stroke (P trend= 0.052).
Conclusions: Among the general Japanese population, non-HDL cholesterol levels were clearly associated with future mortality by coronary heart disease, but not by stroke. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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Associations of serum LDL particle concentration with carotid intima-media thickness and coronary artery calcification.

Zaid M, Miura K, Fujiyoshi A, Abbott RD, Hisamatsu T, Kadota A, Arima H, Kadowaki S, Torii S, Miyagawa N, Suzuki S, Takashima N, Ohkubo T, Sekikawa A, Maegawa H, Horie M, Nakamura Y, Okamura T, Ueshima H, SESSA Research Group.

Journal of clinical lipidology （ELSEVIER SCIENCE INC） 10 （ 5 ） 1195 - 1202.e1 2016年09月

研究論文（学術雑誌）, 査読有り, ISSN 1933-2874

BACKGROUND: Low-density lipoprotein particle (LDL-P) has recently been found to be a stronger predictor of cardiovascular disease (CVD) than LDL-cholesterol (LDL-C).
OBJECTIVES: Whether LDL-P is associated with subclinical atherosclerosis, independent of LDLC, as well as other lipid measures has not been fully examined. We aimed to analyze LDL-P associations with measures of subclinical atherosclerosis.
METHODS: We examined 870 Japanese men randomly selected from Kusatsu City, Shiga, Japan, aged 40-79 years from 2006-2008, free of clinical CVD and not using lipid-lowering medication. Cross-sectional associations of lipid measures with carotid intima-media thickness (cIMT) and coronary artery calcification (CAC; >0 Agatston score) were examined.
RESULTS: LDL-P was significantly positively associated with cIMT and maintained this association after adjustments for LDL-C and other lipid measures. Although these lipid measures were positively associated with cIMT, model adjustment for LDL-P removed any significant relationships. Higher LDL-P was associated with a significantly higher odds ratio of CAC and further adjustment for LDL-C did not affect this relationship. In contrast, the LDL-C association with CAC was no longer significant after adjustment for LDL-P. Other lipid measures attenuated associations of LDL-P with CAC. Likewise, associations of these measures with CAC were attenuated when model adjustments for LDL-P were made.
CONCLUSIONS: In a community-based sample of Japanese men, free of clinical CVD, LDL-P was a robust marker for subclinical atherosclerosis, independent of LDL-C and other lipid measures. Associations of LDL-C and other lipid measures with either cIMT or CAC were generally not independent of LDL-P. (C) 2016 National Lipid Association. All rights reserved.

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Smoking, Smoking Cessation, and Measures of Subclinical Atherosclerosis in Multiple Vascular Beds in Japanese Men.

Hisamatsu T, Miura K, Arima H, Kadota A, Kadowaki S, Torii S, Suzuki S, Miyagawa N, Sato A, Yamazoe M, Fujiyoshi A, Ohkubo T, Yamamoto T, Murata K, Abbott RD, Sekikawa A, Horie M, Ueshima H, Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) Research GroupNakanoYasutakaOgawaEmikoMaegawaHiroshiMiyazawaItsukoMitsunamiKenichiNozakiKazuhikoShiinoAkihikoArakiIsaoTsuruTeruhikoToyamaIkuoOgitaHisakazuKuritaSouichiMaedaToshinagaMiyamatsuNaomiKitaToruKimuraTakeshiNishioYoshihikoNakamuraYasuyukiOkamuraTomonoriBarinas‐MitchellEmma J.M.EdmundowiczDanielOhkuboTakayoshiHozawaAtsushiOkudaNagakoHigashiyamaAyaNagasawaShinyaKitaYoshikuniMurakamiYoshitakaTakashimaNaoyukiKadowakiTakash.

Journal of the American Heart Association （WILEY-BLACKWELL） 5 （ 9 ） 2016年08月

研究論文（学術雑誌）, 査読有り, ISSN 2047-9980

Background-Smoking is an overwhelming, but preventable, risk factor for cardiovascular diseases (CVD), although smoking prevalence remains high in developed and developing countries in East Asia.
Methods and Results-In a population-based sample of 1019 Japanese men aged 40 to 79 years, without CVD, we examined cross-sectional associations of smoking status, cumulative pack-years, daily consumption, and time since cessation, with subclinical atherosclerosis at 4 anatomically distinct vascular beds, including coronary artery calcification, carotid intima-media thickness (CIMT) and plaque, aortic artery calcification (AoAC), and ankle-brachial index. Current, former, and never smoking were present in 32.3%, 50.0%, and 17.7%, respectively. Compared to never smokers, current smokers had significantly higher risks of subclinical atherosclerosis in all 4 circulations (eg, odds ratios for coronary artery calcification >0, 1.79 [95% CIs, 1.16-2.79]; CIMT >1.0 mm, 1.88 [1.02-3.47]; AoAC >0, 4.29 [2.30-7.97]; and ankle-brachial index <1.1, 1.78 [1.16-2.74]) and former smokers did in carotid and aortic circulations (CIMT >1.0 mm, 1.94 [1.13-3.34]; and AoAC >0, 2.55 [1.45-4.49]). Dose-response relationships of pack-years and daily consumption, particularly with CIMT, carotid plaque, AoAC, and ankle-brachial index, were observed among both current and former smokers, and even a small amount of pack-years or daily consumption among current smokers was associated with coronary artery calcification and AoAC, whereas time since cessation among former smokers was linearly associated with lower burdens of all atherosclerotic indices.
Conclusions-Cigarette smoking was strongly associated with subclinical atherosclerosis in multiple vascular beds in Japanese men, and these associations attenuated with time since cessation.

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Relationship of three different types of low-carbohydrate diet to cardiometabolic risk factors in a Japanese population: the INTERMAP/INTERLIPID Study.

Nakamura Y, Ueshima H, Okuda N, Miura K, Kita Y, Miyagawa N, Yoshita K, Nakagawa H, Sakata K, Saitoh S, Okamura T, Okayama A, Choudhry SR, Rodriguez B, Masaki KH, Chan Q, Elliott P, Stamler J

European journal of nutrition （SPRINGER HEIDELBERG） 55 （ 4 ） 1515 - 24 2016年06月

研究論文（学術雑誌）, 査読有り, ISSN 1436-6207

Purpose Low-carbohydrate diets (LCD) are a popular dietary strategy for weight reduction. The effects of LCD on long-term outcome vary depending on type of LCD, possibly due to the fact that effects on cardiometabolic risk factors may vary with different types of LCD. Accordingly, we studied these relations.
Methods We assessed serum concentrations of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), high-sensitivity C-reactive protein (CRP), total cholesterol, glycated hemoglobin, and uric acid, and nutrient intakes by standardized methods in men and women ages 40-59 years from four population samples of Japanese in Japan (553 men and 544 women, combined). For people consuming usual, animal-based, and plant-based LCDs, we calculated LCD scores, based on relative level of fat, protein, and carbohydrate, by modifying the methods of Halton et al. Instead of calculating scores based on animal or vegetable fat, we used saturated fatty acids (SFA) or monounsaturated fatty acids (MUFA) + polyunsaturated fatty acids (PUFA).
Results In multivariate regression analyses with adjustment for site, age, sex, BMI, smoking, alcohol intake, physical activity, and years of education, all three LCD scores were significantly positively related to HDLc (all P < 0.001), but not to LDLc. The plant-based LCD score was significantly inversely related to log CRP (coefficient = -0.010, P = 0.018).
Conclusions All three LCD scores were significantly positively related to HDLc. The plant-based LCD score was significantly inversely related to CRP. Carbohydrate intake below 50 % of total energy with higher intakes of vegetable protein and MUFA + PUFA, and lower intakes of SFA may be favorable for reducing cardiometabolic risk factors.

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Lipoprotein-associated phospholipase A2 is related to risk of subclinical atherosclerosis but is not supported by Mendelian randomization analysis in a general Japanese population.

Ueshima H, Kadowaki T, Hisamatsu T, Fujiyoshi A, Miura K, Ohkubo T, Sekikawa A, Kadota A, Kadowaki S, Nakamura Y, Miyagawa N, Okamura T, Kita Y, Takashima N, Kashiwagi A, Maegawa H, Horie M, Yamamoto T, Kimura T, Kita T, ACCESS and SESSA Research Groups.

Atherosclerosis （ELSEVIER IRELAND LTD） 246 141 - 7 2016年03月

研究論文（学術雑誌）, 査読有り, ISSN 0021-9150

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme predominantly bound to low-density lipoprotein (LDL). Lp-PLA2 is recognized as playing a key role in inflammatory processes and the development of atherosclerosis. This study aimed to investigate whether Lp-PLA2 is related to subclinical atherosclerosis, independently from traditional risk factors, in a general Japanese population by analyses of both the observational study and Mendelian randomization using V279F polymorphism.
Methods and results: We cross-sectionally examined community-based sample of 929 Japanese men aged 40-79 years, without statin treatment, who were randomly selected from the resident registration. Multiple regression analyses of Lp-PLA2 activity and concentration were undertaken separately for men aged 40-49 years and 50-79 years, to clarify interactions of age and Lp-PLA2. Lp-PLA2 activity for men aged 50-79 years was significantly and positively related to intima-media thickness (IMT) (P = 0.013) and plaque index (P = 0.008) independent of traditional risk factors including small LDL particles, but not to coronary artery calcification (CAC) score. Associations with Lp-PLA2 concentration were qualitatively similar to those of activity. Corresponding relationships were not observed in men aged 40e49 years. Mendelian randomization analyses based on V279F genotype did not show any significant associations with subclinical atherosclerosis, although the homozygote and heterozygote of V279F showed low LpPLA2 activity and concentration.
Conclusions: Lp-PLA2 activity in Japanese men aged 50-79 years was associated significantly and positively with IMT and plaque in the carotid artery but Mendelian randomization did not support that LpPLA2 is a causative factor for subclinical atherosclerosis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

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Serum level of LOX-1 ligand containing ApoB is associated with increased carotid intima-media thickness in Japanese community-dwelling men, especially those with hypercholesterolemia LOX-1 ligand and IMT in Japanese.

Okamura T, Miura K, Sawamura T, Kadota A, Hisamatsu T, Fujiyoshi A, Miyamatsu N, Takashima N, Miyagawa N, Kadowaki T, Ohkubo T, Murakami Y, Nakamura Y, Ueshima H, SESSA Research Group.

Journal of clinical lipidology （ELSEVIER SCIENCE INC） 10 （ 1 ） 172 - 80.e1 2016年01月

研究論文（学術雑誌）, 査読有り, ISSN 1933-2874

BACKGROUND: The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than usual lipid parameters; however, the relationship between LAB and carotid intima-media thickness (IMT) was not clear even in Asian populations.
METHODS: A total of 992 community-dwelling Japanese men, aged 40 to 79 years, were enrolled in the present study. Serum LAB levels were measured by enzyme-linked immunosorbent assays (ELISAs) with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody.
RESULTS: Serum LAB levels (median [interquartile range], mu g cs/L) were 5341 mu g cs/L (4093-7125). The mean average IMT of the common carotid artery was highest in the fourth LAB quartile (842 mu m) compared with the first quartile (797 mu m) after adjustment for age, high-density lipoprotein cholesterol, triglyceride, body mass index, hypertension, diabetes, high sensitivity C-reactive protein, smoking, and alcohol drinking. However, this statistically significant difference was lost after further adjustment for total cholesterol (TC). After stratification using the combination of median LAB and hypercholesterolemia (serum TC >= 6.21 mmol/L and/or lipid-lowering medication), the adjusted mean average IMT (standard error) in the high LAB/hypercholesterolemia group was 886 mu m (12.7), 856 mu m (16.7) in the low LAB/hypercholesterolemia group, and 833 mu m (8.4) in the low LAB/normal cholesterol group (P = .004). After further adjustment for TC, mean average IMT in the high LAB group was significantly higher than that measured in the low LAB group in hypercholesterolemic participants not taking lipid-lowering medication.
CONCLUSION: Serum LAB was associated with an increased carotid IMT in Japanese men, especially those with hypercholesterolemia. (C) 2016 National Lipid Association. All rights reserved.

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Association of Total Energy Intake with 29-Year Mortality in the Japanese: NIPPON DATA80.

Nagai M, Ohkubo T, Miura K, Fujiyoshi A, Okuda N, Hayakawa T, Yoshita K, Arai Y, Nakagawa H, Nakamura K, Miyagawa N, Takashima N, Kadota A, Murakami Y, Nakamura Y, Abbott RD, Okamura T, Okayama A, Ueshima H, NIPPON DATA80 Research Group.

Journal of atherosclerosis and thrombosis （JAPAN ATHEROSCLEROSIS SOC） 23 （ 3 ） 339 - 54 2016年

研究論文（学術雑誌）, 査読有り, ISSN 1340-3478

Aim: In animals, dietary energy restriction is reported to increase longevity, whereas in humans, all cohort studies from Western countries have not shown an association between the low energy intake and longevity. We examined the association between total energy intake and longevity in Japan where dietary pattern is different from that in the West.
Methods: A total of 7,704 Japanese aged 30-69 years were followed from 1980 to 2009. Participants were divided into the quintiles of total energy (kcal/day) based on data collected from the National Nutrition Survey. Hazard ratios and 95% confidence intervals (CIs) were derived through the use of Cox proportional hazards models to compare the risk of death across and between the quintiles.
Results: There was a significant association between increased energy intake and all-cause mortality risk in only men (P for linear trend 0.008). In cause-specific analysis, compared with the lowest quintile, there was rise in coronary heart disease (CHD) mortality among men (HR; 2.63, 95% CI; 0.95-7.28, P for linear trend 0.016) and women (HR; 2.91, 95% CI; 1.02-8.29, P for linear trend 0.032) and cancer mortality among men (HR; 1.50, 95% CI; 0.999-2.24, P for linear trend 0.038) in the top quintile.
Conclusion: We observed significant associations of high energy intake with all-cause and cancer mortality among men and with CHD mortality among men and women. Further studies are needed to confirm the benefits of caloric restriction.

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Secular trends of the impact of overweight and obesity on hypertension in Japan, 1980-2010.

Nagai M, Ohkubo T, Murakami Y, Takashima N, Kadota A, Miyagawa N, Saito Y, Nishi N, Okuda N, Kiyohara Y, Nakagawa H, Nakamura Y, Fujiyoshi A, Abbott RD, Okamura T, Okayama A, Ueshima H, Miura K, NIPPON DATA80/90/2010 Research Group.

Hypertension research : official journal of the Japanese Society of Hypertension 38 （ 11 ） 790 - 5 2015年11月

研究論文（学術雑誌）, ISSN 0916-9636

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High-density lipoprotein particle concentration and subclinical atherosclerosis of the carotid arteries in Japanese men.

Zaid M, Fujiyoshi A, Miura K, Abbott RD, Okamura T, Takashima N, Torii S, Saito Y, Hisamatsu T, Miyagawa N, Ohkubo T, Kadota A, Sekikawa A, Maegawa H, Nakamura Y, Mitsunami K, Ueshima H, SESSA Research group.

Atherosclerosis （ELSEVIER IRELAND LTD） 239 （ 2 ） 444 - 50 2015年04月

研究論文（学術雑誌）, 査読有り, ISSN 0021-9150

Objective: The association of high-density lipoprotein particle (HDL-P) with atherosclerosis may be stronger than that of HDL-cholesterol (HDL-C) and independent of conventional cardiovascular risk factors. Whether associations persist in populations at low risk of coronary heart disease (CHD) remains unclear. This study examines the associations of HDL-P and HDL-C with carotid intima-media thickness (cIMT) and plaque counts among Japanese men, who characteristically have higher HDL-C levels and a lower CHD burden than those in men of Western populations.
Methods: We cross-sectionally examined a community-based sample of 870 Japanese men aged 40-79 years, free of known clinical cardiovascular disease (CVD) and not on lipid-lowering medication. Participants were randomly selected among Japanese living in Kusatsu City in Shiga, Japan.
Results: Both HDL-P and HDL-C were inversely and independently associated with cIMT in models adjusted for conventional CHD risk factors, including low-density lipoprotein cholesterol (LDL-C) and diabetes. HDL-P maintained an association with cIMT after further adjustment for HDL-C (P < 0.01), whereas the association of HDL-C with cIMT was noticeably absent after inclusion of HDL-P in the model. In plaque counts of the carotid arteries, HDL-P was significantly associated with a reduction in plaque count, whereas HDL-C was not.
Conclusion: HDL-P, in comparison to HDL-C, is more strongly associated with measures of carotid atherosclerosis in a cross-sectional study of Japanese men. Findings demonstrate that, HDL-P is a strong correlate of subclinical atherosclerosis even in a population at low risk for CHD. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

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Fruit and vegetable intake and mortality from cardiovascular disease in Japan: a 24-year follow-up of the NIPPON DATA80 Study.

Okuda N, Miura K, Okayama A, Okamura T, Abbott RD, Nishi N, Fujiyoshi A, Kita Y, Nakamura Y, Miyagawa N, Hayakawa T, Ohkubo T, Kiyohara Y, Ueshima H, NIPPON DATA80 Research Group

European journal of clinical nutrition （NATURE PUBLISHING GROUP） 69 （ 4 ） 482 - 488 2015年04月

査読有り, ISSN 0954-3007

BACKGROUND/OBJECTIVES: There have been few studies on the association of fruit and vegetable (FV) intake with cardiovascular disease (CVD) risk in Asian populations where both dietary habits and disease structure are different from western countries. No study in Asia has found its significant association with stroke. We examined associations of FV intake with mortality risk from total CVD, stroke and coronary heart diseases (CHDs) in a representative Japanese sample.
METHODS: A total of 9112 participants aged from 24-year follow-up data in the NIPPON DATA80, of which baseline data were obtained in the National Nutrition Survey Japan in 1980, were studied. Dietary data were obtained from 3-day weighing dietary records. Participants were divided into sex-specific quartiles of energy adjusted intake of FV. Multivariate-adjusted hazard ratios (HRs) were calculated between strata of the total of FV intake, fruit intake and vegetable intake. The adjustment included age, sex, smoking, drinking habit and energy adjusted intakes of sodium and some other food groups.
RESULTS: Participants with higher FV intake were older, ate more fish, milk and dairy products and soybeans and legumes and ate less meat. Multivariate-adjusted HR (95% confidence interval; P; P for trend) for the highest versus the lowest quartile of the total of FV intake was 0.74 (0.61-0.91; 0.004; 0.003) for total CVD, 0.80 (0.59-1.09; 0.105; 0.036) for stroke and 0.57 (0.37-0.87; 0.010; 0.109) for CHD.
CONCLUSIONS: The results showed that higher total intake of FVs was significantly associated with reduced risk of CVD mortality in Japan.

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Association between Pulse Wave Velocity and Coronary Artery Calcification in Japanese men.

Torii S, Arima H, Ohkubo T, Fujiyoshi A, Kadota A, Takashima N, Kadowaki S, Hisamatsu T, Saito Y, Miyagawa N, Zaid M, Murakami Y, Abbott RD, Horie M, Miura K, Ueshima H, SESSA Research Group.

Journal of atherosclerosis and thrombosis （JAPAN ATHEROSCLEROSIS SOC） 22 （ 12 ） 1266 - 77 2015年

研究論文（学術雑誌）, 査読有り, ISSN 1340-3478

Aim: Pulse wave velocity (PWV) is a simple and valid clinical method for assessing arterial stiffness. Coronary artery calcification (CAC) is an intermediate stage in the process leading to overt cardiovascular disease (CVD) and an established determinant of coronary artery disease. This study aimed to examine the association between PWV and CAC in a population-based sample of Japanese men.
Methods: This is a cross-sectional study of 986 randomly selected men aged 40-79 years from Shiga, Japan. CVD-free participants were examined from 2006 to 2008. Brachial-ankle PWV (baPWV) was measured using an automatic waveform analyzer. CAC was assessed using computed tomography. Agatston scores >= 10 were defined as the presence of CAC.
Results: Prevalence of CAC progressively increased with rising levels of baPWV: 20.6%, 41.7%, 56.3%, and 66.7% across baPWV quartiles < 1378, 1378-1563, 1564-1849, and > 1849 cm/s (P < 0.001 for trend). Associations remained significant after adjusting for age and other factors, including body mass index, systolic blood pressure, pulse rate, total and high-density lipoprotein cholesterol, hemoglobin A1c, drinking, smoking and exercise status, and the use of medication to treat hypertension, dyslipidemia and diabetes (P = 0.042 for trend). The optimal cutoff level of baPWV to detect CAC was 1612 cm/s using receiver operating characteristic curve analysis.
Conclusions: Arterial stiffness as defined by an elevated baPWV is associated with an increased prevalence of CAC in a general population-based setting among Japanese men.

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Lipoprotein particle profiles compared with standard lipids in association with coronary artery calcification in the general Japanese population.

Hisamatsu T, Fujiyoshi A, Miura K, Ohkubo T, Kadota A, Kadowaki S, Kadowaki T, Yamamoto T, Miyagawa N, Zaid M, Torii S, Takashima N, Murakami Y, Okamura T, Horie M, Ueshima H, SESSA Research Group.

Atherosclerosis （ELSEVIER IRELAND LTD） 236 （ 2 ） 237 - 43 2014年10月

研究論文（学術雑誌）, 査読有り, ISSN 0021-9150

Objective: The utility of lipoprotein particle profiles measured by nuclear magnetic resonance (NMR) spectroscopy beyond standard serum lipids remains inconclusive. Furthermore, few studies have compared NMR measurements with standard lipids in association with coronary artery calcification (CAC) in Japanese, where the coronary atherosclerotic burden is low. We examined whether NMR-based lipoprotein particle profiles are associated with CAC, and compared them with standard lipid and lipid ratios in the Japanese general population.
Methods and Results: We conducted a cross-sectional study in 851 men aged 40-79 years without cardiovascular diseases and lipid-lowering therapies. Adjusted odds ratios (ORs) (95% confidence intervals) for the top versus the bottom quartile of NMR-measured particle concentrations were 2.01 (1.24-3.23) for low-density lipoprotein (LDL-P), 1.04 (0.62-1.75) for high-density lipoprotein (HDL-P), 1.82 (1.13-2.95) for very-low-density lipoprotein (VLDL-P), and 1.92 (1.18-3.17) for LDL-P/HDL-P ratio. Similarly adjusted ORs of NMR-measured particle sizes were 0.59 (0.36-0.97) for LDL-P, 0.66 (0.40-1.10) for HDL-P, and 0.67 (0.40-1.12) for VLDL-P. The corresponding ORs were 1.82 (1.14-2.90) for total cholesterol (TC), 2.06 (1.28-3.30) for low-density lipoprotein cholesterol (LDL-C), 0.56 (0.34-0.91) for high-density lipoprotein cholesterol (HDL-C), 2.02 (1.24-3.29) for triglycerides, 2.08 (1.29-3.36) for non-high-density lipoprotein cholesterol (non-HDL-C), 2.27 (1.37-3.78) for TC/HDL-C ratio, and 1.73 (1.06-2.85) for LDL-C/HDL-C ratio. After mutual adjustment for total LDL-P concentration and TC/HDL-C ratio or non-HDL-C, LDL-P was no longer associated, whereas TC/HDL-C ratio remained significantly associated with CAC.
Conclusions: In community-based Japanese men, the overall association of CAC with NMR-measured lipoprotein indices is comparable, but not superior, to that with standard lipids. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

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Low-carbohydrate diets and cardiovascular and total mortality in Japanese: a 29-year follow-up of NIPPON DATA80.

Nakamura Y, Okuda N, Okamura T, Kadota A, Miyagawa N, Hayakawa T, Kita Y, Fujiyoshi A, Nagai M, Takashima N, Ohkubo T, Miura K, Okayama A, Ueshima H, NIPPON DATA Research Group.

The British journal of nutrition （CAMBRIDGE UNIV PRESS） 112 （ 6 ） 916 - 24 2014年09月

研究論文（学術雑誌）, ISSN 0007-1145

Long-term safety of consuming low-carbohydrate diets (LCD) in Asian populations, whose carbohydrate intake is relatively high, is not known. In the present study, the association of LCD with CVD and total mortality was assessed using data obtained in the NIPPON DATA80 (National Integrated Project for Prospective Observation of Non-communicable Disease and Its Trends in the Aged 1980) during 29 years of follow-up. At baseline in 1980, data were collected from study participants aged >= 30 years from randomly selected areas in Japan. LCD scores were calculated based on the percentage of energy as carbohydrate, fat and protein, estimated by 3 d weighed food records. A total of 9200 participants (56% women, mean age 51 years) were followed up. During the follow-up, 1171 CVD deaths (52% in women) and 3443 total deaths (48% in women) occurred. The multivariable-adjusted hazard ratio (HR) for CVD mortality using the Cox model comparing the highest v. lowest deciles of LCD score was 0 60 (95% CI 0 38, 0 94; P-trend = 0 021) for women and 0 78 (95% CI 0 58, 1 05; P-trend = 0 079) for women and men combined; the HR for total mortality was 0 74 (95% CI 0 57, 0 95; P-trend = 0 029) for women and 0 87 (95% CI 0 74, 1 02; P-trend = 0 090) for women and men combined. None of the associations was statistically significant in men. No differential effects of animal-based and plant-fish-based LCD were observed. In conclusions, moderate diets lower in carbohydrate and higher in protein and fat are significantly inversely associated with CVD and total mortality in women.

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High long-chain n-3 fatty acid intake attenuates the effect of high resting heart rate on cardiovascular mortality risk: a 24-year follow-up of Japanese general population.

Hisamatsu T, Miura K, Ohkubo T, Yamamoto T, Fujiyoshi A, Miyagawa N, Kadota A, Takashima N, Okuda N, Yoshita K, Kita Y, Murakami Y, Nakamura Y, Okamura T, Horie M, Okayama A, Ueshima H, NIPPON DATA80 Research Group.

Journal of cardiology （ELSEVIER SCIENCE BV） 64 （ 3 ） 218 - 24 2014年09月

研究論文（学術雑誌）, 査読有り, ISSN 0914-5087

Background: Increased resting heart rate (RHR) independently predicts cardiovascular mortality. Meanwhile, long-chain n-3 fatty acids (LCn3FAs) have a cardioprotective effect. Our aim was to evaluate whether higher LCn3FAs intake attenuates the elevated risk of cardiovascular mortality associated with increased RHR.
Methods: We conducted a population-based 24-year prospective cohort study of Japanese, whose LCn3FAs intake is relatively high. Study participants included 8807 individuals aged 30-95 years from randomly selected areas across Japan without cardiovascular diseases and anti-hypertensive drugs at baseline. The primary endpoint was cardiovascular mortality, and the secondary endpoints were cardiac and stroke mortality during 24 years of follow-up. Individual dietary LCn3FAs intake was estimated from household-based 3-day weighed food records. RHR was obtained from 3 consecutive R-wave intervals on 12-lead electrocardiography. Cox models were used to estimate the multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) adjusting for possible confounders.
Results: During the follow-up period, 617 cardiovascular deaths were observed. The median daily intake of LCn3FAs was 0.37% kcal (0.86 g/day). The interaction between dietary LCn3FAs intake and RHR in the risk of cardiovascular mortality was statistically significant (p = 0.033). The risk of cardiovascular mortality was significantly higher in the low-intake group (<0.37% kcal) with an RHR >85 beats/min (bpm) [hazard ratio (HR), 1.67; 95% confidence interval (CI), 1.15-2.43], but not in the high-intake group (>= 0.37% kcal) with an RHR >85 bpm (HR, 0.92; 95% CI, 0.61-1.38), compared with those in the high-intake group with an RHR <70 bpm. Similar results were observed with stroke mortality, but not with cardiac mortality.
Conclusions: The risk of cardiovascular mortality associated with increased RHR is elevated in participants with low dietary LCn3FAs intake, but not in participants with high dietary LCn3FAs intake in a representative Japanese general population. These results suggest that high dietary LCn3FAs intake may prevent cardiovascular mortality associated with increased RHR. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

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Six random specimens of daytime casual urine on different days are sufficient to estimate daily sodium/potassium ratio in comparison to 7-day 24-h urine collections.

Iwahori T, Ueshima H, Miyagawa N, Ohgami N, Yamashita H, Ohkubo T, Murakami Y, Shiga T, Miura K

Hypertension research : official journal of the Japanese Society of Hypertension （NATURE PUBLISHING GROUP） 37 （ 8 ） 765 - 71 2014年08月

研究論文（学術雑誌）, 査読有り, ISSN 0916-9636

The objective of this study was to determine the optimal number and type of casual (spot) urine specimens required to estimate an individual's urinary sodium/potassium (Na/K) ratio. A total of 48 participants, 25 men and 23 women, aged between 25 and 59 years, was recruited from healthy volunteers. The Na/K ratio in each casual urine and 7-day 24-h urine sample was measured. Correlation analysis and the quality of agreement by the Bland and Altman method between casual urine and 24-h urine were analyzed. The mean Na/K ratio of 7-day 24-h urine was 4.3. The mean Na/K ratio of six random specimens of daytime (collected between 09 and 17 hours) casual urine correlated most strongly with the Na/K ratio of 7-day 24-h urine (r=0.87). The bias for the mean Na/K ratio between 7-day 24-h urine and daytime casual urine was almost negligible (0.03), and the quality of agreement for the mean of the six random, daytime casual urine specimens on different days was similar to that of the 2-day 24-h urine samples for estimating 7-day 24-h values. Our findings show that the mean Na/K ratio of six random daytime casual urine specimens on different days was a good substitute for the 2-day 24-h urine Na/K ratio.

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レセプト情報・特定健診等情報データベースを利用した滋賀県における循環器疾患危険因子の有病率、治療率、コントロール率

宮川尚子, 村上義孝, 岡山明, 角野文彦, 三浦克之

日本公衆衛生雑誌（日本公衆衛生学会） 61 （ 7 ） 333 - 341 2014年07月

研究論文（学術雑誌）, 筆頭著者, 査読有り, ISSN 0546-1766

目的生活習慣病の予防戦略立案において、循環器疾患危険因子の有病率、治療率およびそのコントロール率を性・年齢別に詳細に実態把握することは公衆衛生上重要である。高齢者の医療の確保に関する法律に基づく「レセプト情報・特定健診等情報データベース」の研究利用が可能になったことに伴い、滋賀県の特定健診全受診者における高血圧、糖尿病および高LDLコレステロール血症の有病率、治療率およびコントロール率を明らかにする。方法滋賀県在住の平成20年度特定健診受診者全員を対象者とし、本データベースにおける特定健診に関する提供データを用い、性・年齢別(5歳階級)に高血圧、糖尿病、高LDLコレステロール血症の有病率、治療率、コントロール率およびその95%信頼区間を算定した。コントロール率は、高血圧、糖尿病、高LDLコレステロール血症治療者のうち、検査値が基準値未満の者の割合とした。結果滋賀県在住の平成20年度特定健診受診者は211,976人であった。高血圧では男女ともに有病率(男性16〜60%、女性6〜58%)と治療率(男性23〜71%、女性24〜71%)は年齢上昇に伴い増加したが、コントロール率は約55%で年齢による違いがなかった。糖尿病では、男女の有病率(男性3〜15%、女性1〜10%)と男性の治療率(44〜62%)は年齢上昇に伴い増加し、コントロール率も男性で43〜51%、女性で32〜50%と緩やかに増加した。高LDLコレステロール血症では女性の有病率(16〜57%)と男女の治療率(男性6〜44%、女性6〜51%)、コントロール率が年齢上昇に伴い増加し、コントロール率は男性で63〜80%、女性で64〜77%と高い値を示した。結論レセプト情報・特定健診等情報データベースの特定健診データの活用により循環器疾患危険因子の有病率、治療率の詳細把握が可能になるとともに、これまで報告がなかったコントロール率が明らかとなり、本データベースは生活習慣病の実態把握に有効に利用できることが示された。(著者抄録)

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滋賀県野洲市における特定健診未受診理由を踏まえた特定健診受診勧奨手法の開発と受診率向上への効果

宮川尚子, 門田文, 清水めぐみ, 山澤幸子, 宇野裕子, 大黒清夏, 今堀初美, 山下亜希代, 櫻井真汐, 駒井文昭, 吉田和司, 門脇崇, 上島弘嗣, 三浦克之, 岡村智教

厚生の指標（(一財)厚生労働統計協会） 61 （ 4 ） 28 - 34 2014年04月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り, ISSN 0452-6104

目的平成20年度より開始された特定健診の平均受診率は市町村国保で31%前後であり,参酌標準の65%と大きく乖離している。健診受診率に影響を及ぼす要因について,受診勧奨施策の受診率への効果を検討した報告は少ない。本研究では,滋賀県野洲市において特定健診未受診者の未受診理由を明らかにし,得られた未受診理由を踏まえた健診受診勧奨手法を開発して,その効果について検討した。方法滋賀県野洲市の国保加入者を対象として,平成21年度に,前年度(平成20年度)の特定健診未受診者4,122人のうち無作為抽出した1,579人に郵送にて特定健診未受診の理由を尋ねる質問紙調査を実施し,760人(48.1%)から回答を得た。特定健診未受診理由に基づき,未受診理由を踏まえた受診勧奨手法を開発し,平成22年度に受診率向上のための対策を実施した。勧奨手法の効果は,健診実施期間が平成22年度と同じであった平成20年度の健診受診率との比較により評価した。結果健診未受診理由調査の結果,年齢層に関わらず「病院などにかかっている」「事業所健診等を受けている」「たまたま受け忘れた」「健康だから」が多く,中壮年層では加えて「受ける時間がない」も多かった。これらの未受診理由を踏まえて,個人と集団,それぞれへのアプローチを組み合わせた受診勧奨手法を開発した。個人へのアプローチとしては健診開始時に受診券と一緒に受診勧奨チラシを対象者全員に個別送付し,また健診期間の中間時点に,その時点の未受診者全員に再度,受診勧奨チラシと健診実施機関一覧表を個別送付した。集団に対するアプローチとしては同じく健診期間の中間時点で,「健康で自覚症状のない時の受診の重要性」をテーマにした記事の広報掲載とポスターの掲示を行った。この受診勧奨手法を用いた平成22年度の特定健診受診率は,用いていない平成20年度に比べて7.2%有意に上昇し,これは年齢層に分けても同様の結果であった。受診のきっかけを調査したところ,今回の受診勧奨手法をあげた者の割合は,ほぼ受診率の増加分に相当する660人(受診率8%相当)であった。結語特定健診未受診理由を踏まえた受診勧奨手法を開発し,その効果を評価した。タイミングを見計らった個別通知や,健診受診の意義を伝える勧奨を,集団および個人を対象に実施したことにより,高年層,中壮年層ともに健診受診率は大きく上昇し,本受診勧奨手法の有用性が示された。(著者抄録)

Long-chain n-3 polyunsaturated fatty acids intake and cardiovascular disease mortality risk in Japanese: a 24-year follow-up of NIPPON DATA80.

Miyagawa N, Miura K, Okuda N, Kadowaki T, Takashima N, Nagasawa SY, Nakamura Y, Matsumura Y, Hozawa A, Fujiyoshi A, Hisamatsu T, Yoshita K, Sekikawa A, Ohkubo T, Abbott RD, Okamura T, Okayama A, Ueshima H, NIPPON DATA80 Research Group.

Atherosclerosis （ELSEVIER IRELAND LTD） 232 （ 2 ） 384 - 9 2014年02月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り, ISSN 0021-9150

Background: Dietary intake of long-chain n-3 PUFA (LCn3FA) among Japanese is generally higher than that in Western populations. However, little is known whether an inverse association of LCn3FA with cardiovascular disease (CVD) risk exists in a population with higher LCn3FA intake.
Objective: To investigate the association between LCn3FA intake and the long-term risk of CVDs in a Japanese general population.
Methods: We followed-up a total of 9190 individuals (56.2% women, mean age 50.0 years) randomly selected from 300 areas across Japan and free from CVDs at baseline. Dietary LCn3FA intake was estimated using household weighed food records. Cox models were used to calculate multivariate-adjusted hazard ratios (HR) and confidence intervals (CI) according to sex specific quartiles of LCn3FA intake.
Results: During 24-year follow-up (192,897 person-years), 879 cardiovascular deaths were observed. The median daily intake of LCn3FA was 0.37% kcal (0.86 g/day). Adjusted HR for CVD mortality was lower in the highest quartile of LCn3FA intake (HR 0.80; 95% CI 0.66-0.96) compared with the lowest quartile, and the trend was statistically significant (P = 0.038). The similar but statistically non-significant trends were observed for coronary heart disease death and stroke death. In analyses by age groups, the inverse associations of LCn3FA intake with the risk of total CVD death and stroke death were significant in younger individuals (30-59 years at baseline).
Conclusion: LCn3FA intake was inversely and independently associated the long-term risk of total CVD mortality in a representative sample of Japanese with high LCn3FA intake. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

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Impact of metabolic syndrome on the risk of cardiovascular disease mortality in the United States and in Japan.

Liu L, Miura K, Fujiyoshi A, Kadota A, Miyagawa N, Nakamura Y, Ohkubo T, Okayama A, Okamura T, Ueshima H

The American journal of cardiology （EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC） 113 （ 1 ） 84 - 9 2014年01月

研究論文（学術雑誌）, 査読有り, ISSN 0002-9149

The United States has a higher prevalence of metabolic syndrome (MS) and cardiovascular disease (CVD) mortality than Japan, but it is unknown how much of the difference in MS accounts for the mortality difference. The aim of this study was to examine the impact of MS on the excess CVD mortality in the United States compared with that in Japan. Data from the United States Third National Health and Nutrition Examination Survey (NHANES 111; n = 12,561) and the Japanese National Integrated Project for Prospective Observation of Noncommunicable Disease and Its Trends in Aged (NIPPON DATA; n = 7,453) were analyzed. MS was defined as of 5 risk factors (obesity, high blood pressure, decreased high-density lipoprotein cholesterol, elevated glycosylated hemoglobin, and elevated triglycerides). The results show that after a median of 13.8 years of follow-up in the United States, 1,683 patients died from CVD (11.75 per 1,000 person-years), and after a median of 15 years of follow-up in Japan, 369 patients died from CVD (3.56 per 1,000 person-years). The age-adjusted prevalence of MS was 26.7% in the United States and 19.3% in Japan. Of 5 MS factors, obesity, high blood pressure, elevated triglycerides, and glycosylated hemoglobin in the United States, and high blood pressure and elevated glycosylated hemoglobin in Japan were significant risk factors for CVD mortality. Estimates of 13.3% and 44% of the excess CVD mortality for the United States could be explained by the higher prevalence of MS and MS plus baseline CVD history than in Japan. In conclusion, the present study is the first to quantitatively demonstrate that MS and MS plus baseline CVD history may significantly contribute to the explanation of excess CVD mortality in the United States compared with Japan. (C) 2014 Elsevier Inc. All rights reserved.

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Interaction between dietary marine-derived n-3 fatty acids intake and J-point elevation on the risk of cardiac death: a 24-year follow-up of Japanese men.

Hisamatsu T, Miura K, Ohkubo T, Yamamoto T, Fujiyoshi A, Miyagawa N, Kadota A, Takashima N, Okuda N, Matsumura Y, Yoshita K, Kita Y, Murakami Y, Nakamura Y, Okamura T, Horie M, Okayama A, Ueshima H, NIPPON DATA80 Research Group.

Heart (British Cardiac Society) （BMJ PUBLISHING GROUP） 99 （ 14 ） 1024 - 9 2013年07月

研究論文（学術雑誌）, ISSN 1355-6037

Objective Higher marine-derived n-3 fatty acids (MDn3FAs) intake reduces the risk of sudden cardiac death via antiarrhythmic effects. The article evaluates whether MDn3FAs intake attenuates the increased risk of cardiac death associated with J-point elevation (JPE), characterised by an elevation of QRS-ST junction (J-point) >= 0.1 mV on electrocardiography.
Design A prospective population-based cohort study.
Setting The National Survey on Circulatory Disorders and the National Nutrition Survey of Japan.
Participants A total of 4348 community-dwelling men (mean age 49.3 years), without cardiovascular diseases at baseline, from randomly selected areas across Japan.
Main outcome measures Cardiac death (200 men) during the 24-year follow-up.
Results Dietary MDn3FAs intake was assessed using a dietary method to estimate individual intake of household-based weighed food records for 3 days. Cox models were used to calculate HRs and 95% CIs adjusted for possible confounding factors. JPE was present in 340 participants (7.8%). The median daily intake of MDn3FAs was 0.35% kcal (0.92 g/day). The risk of cardiac death was significantly higher in participants with JPE than in those without JPE in the low intake group (<0.35% kcal; adjusted HR 3.51; 95% CI 1.84 to 6.73; p<0.001), but not in the high intake group (>= 0.35% kcal; adjusted HR 1.09; 95% CI 0.56 to 2.16; p=0.795). The interaction between dietary MDn3FAs intake and JPE on the risk of cardiac death was statistically significant (p=0.006).
Conclusions The increased risk of cardiac death associated with JPE may be attenuated by higher dietary MDn3FAs intake.

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Association between J-point elevation and death from coronary artery disease--15-year follow up of the NIPPON DATA90.

Hisamatsu T, Ohkubo T, Miura K, Yamamoto T, Fujiyoshi A, Miyagawa N, Kadota A, Takashima N, Nagasawa SY, Kita Y, Murakami Y, Okayama A, Horie M, Okamura T, Ueshima H, NIPPON DATA90 Research Group.

Circulation journal : official journal of the Japanese Circulation Society 77 （ 5 ） 1260 - 6 2013年

研究論文（学術雑誌）, 査読有り, ISSN 1346-9843

Background: An early repolarization pattern, characterized by an elevation of the QRS-ST junction (J-point) on 12-lead electrocardiography (ECG) is associated with cardiac and sudden death. However, little is known about the prognostic significance of J-point elevation for various disease-specific cardiovascular outcomes, including coronary artery disease (CAD). Methods and Results: To investigate the association between the presence of J-point elevation ≥0.1 mV and various disease-specific cardiovascular outcomes, we conducted a 15-year prospective study in a representative general Japanese population of 7,630 individuals (41% men, mean age 52.4 years) who participated in the National Survey of Circulatory Disorders. Cox models were used to estimate the hazard ratios (HRs) adjusted for possible confounding factors. J-point elevation was present in 264 individuals (3.5%) and was associated with an increased risk of cardiac death (adjusted HR, 2.54
95% confidence interval [CI] 1.40-4.58
P=0.002) and death from CAD (adjusted HR, 4.66
95% CI 2.30-9.46
P&lt
0.001). In a subgroup analysis by age, the association between J-point elevation and cardiovascular outcomes was more remarkable in middle-aged (&lt
60 years) than in older individuals (≥60 years) (all P for interaction &lt
0.05). Conclusions: J-point elevation on standard 12-lead ECG was an independent predictor of cardiac death and death from CAD in a representative sample of the general Japanese population, particularly among the middle-aged.

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Fatty acid intakes and coronary heart disease mortality in Japan: NIPPON DATA90, 1990-2005

Yasuyuki Nakamura, Yutaka Kiyohara, Nagako Okuda, Tomonori Okamura, Aya Higashiyama, Makoto Watanabe, Aya Kadota, Shin-ya Nagasawa, Naoko Miyagawa, Takayoshi Ohkubo, Yoshikuni Kita, Katsuyuki Miura, Akira Okayama, Hirotsugu Ueshima

Current Nutrition and Food Science 9 （ 1 ） 26 - 32 2013年

ISSN 1573-4013

Associations between dietary fatty acid intakes and risk of coronary heart disease (CHD) are not entirely consistent in prospective studies in the U.S. and Europe. Such studies in Japan are rare. The objective of this study was to examine the association between dietary total, saturated (SFA), and polyunsaturated (PUFA) fatty acids, cholesterol intake and CHD mortality using the dataset of NIPPON DATA90. At the baseline in 1990, we performed blood biochemical measurements and a nutritional survey on participants from 300 randomly selected districts. After exclusion of participants with a history of CHD and/or stroke at the baseline, we followed 7,819 community residents (3,254 men and 4,565 women, age ≥ 30) for 15 years. We estimated individual nutrient intakes among family members by weighed food records in three consecutive representative days. During the follow-up, there were 42 CHD deaths in men and 30 in women. Mean daily SFA and PUFA % calorie intakes were 5.90±1.36%, and 5.59±1.30%, respectively in men, and 6.48±1.53%, and 6.08±1.14% in women. A Cox analysis adjusted for age, vegetable and fruit intakes, and other confounders in women found that SFA intake was significantly associated with CHD mortality (hazards ratio per one quintile increment=1.34, 95% confidence intervals: 1.02-1.74, P=0.03), while no such association was noted in men. No associations were found between other fat intakes and CHD mortality in men or women. In conclusion, SFA intake was positively associated with CHD mortality independent of confounders in women, but not in men. © 2013 Bentham Science Publishers.

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Long-term risk of BP values above normal for cardiovascular mortality: a 24-year observation of Japanese aged 30 to 92 years.

Takashima N, Ohkubo T, Miura K, Okamura T, Murakami Y, Fujiyoshi A, Nagasawa SY, Kadota A, Kita Y, Miyagawa N, Hisamatsu T, Hayakawa T, Okayama A, Ueshima H, NIPPON DATA80 Research Group.

Journal of hypertension （LIPPINCOTT WILLIAMS & WILKINS） 30 （ 12 ） 2299 - 306 2012年12月

研究論文（学術雑誌）, 査読有り, ISSN 0263-6352

Objective: In Western populations, blood pressure (BP) measured at baseline has been reported to predict long-term (over 20 years) risk of mortality from cardiovascular diseases (CVDs). However, corresponding evidence is scarce in Asia where stroke is dominant. We investigated the association between baseline BP and 24-year mortality risk due to CVD, in a representative Japanese general population.
Methods: We followed up a nationwide sample of 8592 Japanese, aged 30 years or above without a history of CVD and antihypertensive medication at baseline, for 24 years. Hazard ratios for CVD mortality in BP categories defined according to JCN7 criteria were estimated using Cox model adjusted for potential confounding factors with normal BP treated as the reference category.
Results: We observed 689 CVD deaths. Hazard ratios for CVD mortality were progressively and significantly increased from the category of prehypertension. Population-attributable fraction (PAF) demonstrated that 43 and 48% of CVD and stroke deaths were explained by non-normal BP at baseline. Hazard ratios and PAF were remarkably higher in younger participants (aged 30-59 years) than those in the elderly (aged 60 years or above). Particularly, in younger men, 81% of CVD deaths were explained by non-normal BP. In sensitivity analysis, participants with antihypertensive medication showed the highest hazard ratio for CVD morality compared with the other categories.
Conclusions: BP levels above normal at baseline retained significant relative and absolute risks of CVD and stroke mortality during 24 years. Long-lasting burden of non-normal BP particularly in younger individuals suggests the importance of primary prevention of high BP from younger generation.

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