論文 - 岡村　智教

Casual serum triglyceride as a predictor of premature type 2 diabetes mellitus: an 8-year cohort study of middle-aged Japanese workers.

Nishikawa T, Okamura T, Shima A, Kawatsu Y, Sugiyama D, Kadota A, Morimoto A, Tatsumi Y, Godai K, Miyamatsu N

Diabetology international 7 （ 3 ） 252 - 258 2016年09月

ISSN  2190-1678

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<p>Background: The utility of casual serum triglyceride (TG) as a predictor of type 2 diabetes mellitus (DM) is unclear, especially during the most productive years. Methods: Participants were 3271 workers (913 men and 2358 women, age 20–57) without DM at baseline. They underwent consecutive annual medical check-ups for 8 years. The association between newly diagnosed DM and casual serum TG level was determined by classifying the participants into 4 groups according to casual serum TG level at baseline: below 50 mg/dL (group A), 50–100 mg/dL (group B), 100–150 mg/dL (group C), and ≥150 mg/dL (group D). The effects of casual serum TG level in combination with sex, obesity, or serum glucose level on newly diagnosed DM were also evaluated. Results: A total of 222 newly diagnosed type 2 DM cases with a mean age of 50 years old were observed during the follow-up period, i.e., 10/406 in group A, 66/1534 in group B, 58/712 in group C, and 88/619 in group D. Compared with group A, the odds ratio (ORs) for newly diagnosed DM (after adjusting for DM-associated factors) was found to increase with casual serum TG level: 1.38 (group B), 1.79 (group C), and 2.36 (group D). Moreover, the OR for newly diagnosed DM was higher in participants with high casual serum TG levels who were also male (OR 2.46), obese (OR 4.18), or had a high serum glucose level (OR 6.96) than in the reference group. Conclusions: Serum TG level ≥150 mg/dL when fasting or nonfasting is a significant predictor of type 2 diabetes in middle-aged Japanese workers.</p>

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Validation of the european SCORE risk chart in the healthy middle-aged Japanese.

Sawano M, Kohsaka S, Okamura T, Inohara T, Sugiyama D, Watanabe M, Nakamura Y, Higashiyama A, Kadota A, Okud N, Murakami Y, Ohkubo T, Fujiyoshi A, Miura K, Okayama A, Ueshima H, National Integrated Project for Prospective Observation of Non-Communicable Disease and its Trends in the Aged (NIPPON DATA 80) Research Group.

Atherosclerosis 252   116 - 121 2016年09月

研究論文（学術雑誌）,  ISSN  0021-9150

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<p>Background and aims The European Society of Cardiology developed prediction models (SCORE) for low- and high-risk populations in the European countries. However, whether or not these models are valid in different ethnicities is unknown. We aimed to evaluate the performance of the low-risk SCORE model in the general Japanese population. Methods Healthy middle-aged Japanese participating in the NIPPON DATA80 cohort had been observed. The predicted 10-year cardiovascular death risk was calculated using the low-risk SCORE model for the overall population as well as for each gender individually. The model performance of the low-risk SCORE model was evaluated with the Harrel's c-statistics for discrimination and the Grønnesby and Borgan goodness-of-fit test for calibration. Results A total of 4842 participants aged 40–64 years old and 47,606 person-years were evaluated in our study. 203 (4.19%) died within the ten-years of follow-up and 44 (0.91%) CV deaths were observed. The low-risk SCORE model in the overall population had reasonable discrimination (c statistics 0.72, 95% CI 0.71–0.73) but poor calibration (R², 0.67, Chi-square value 6.15, p = 0.01). Discrimination was reasonable in both men (c statistics 0.71, 95% CI 0.69–0.73) and women (c statistics 0.71, 95% CI 0.70–0.73). However, calibration was poor in men (R², 0.22, Chi-square value 0.749, p = 0.38) compared to women (R², 0.96, Chi-square value 1.39, p = 0.24). Conclusions Although the low-risk SCORE model performs reasonably well in women, the SCORE models generally overestimated the risk of cardiovascular death risk in the Japanese general population.</p>

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Does the flushing response modify the relationship between alcohol intake and hypertension in the Japanese population? NIPPON DATA2010.

Kogure M, Tsuchiya N, Hozawa A, Nakaya N, Nakamura T, Miyamatsu N, Tanaka H, Wakabayashi I, Higashiyama A, Okuda N, Takashima N, Fujiyoshi A, Kadota A, Ohkubo T, Okamura T, Ueshima H, Okayama A, Miura K

Hypertension research : official journal of the Japanese Society of Hypertension 39 （ 9 ） 670 - 679 2016年09月

研究論文（学術雑誌）,  ISSN  0916-9636

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<p>The influence of alcohol intake on hypertension may vary depending on the flushing response, but this relationship has not been confirmed. The relationship between alcohol intake and hypertension was examined according to the flushing response in a representative sample of the Japanese population. Participants in the National Health and Nutrition Survey in 2010 were asked to participate in the baseline survey of NIPPON DATA2010. Here, we investigated the relationship between alcohol intake and hypertension according to the flushing response. Statistical analyses were performed in a cross-sectional manner using multiple logistic regression models after adjusting for age, body mass index, smoking status, present illness of diabetes mellitus and present illness of dyslipidemia. Of the 1139 men and 1263 women, 659 and 463, respectively, had hypertension. Among the men, alcohol intake was positively associated with hypertension, regardless of the flushing response (P for linear trend both &lt;0.05). This positive relationship was observed for both users and non-users of antihypertensive drugs. No interaction with the flushing response was observed (P for interaction=0.360). In women, although the direction differed between flushers and non-flushers, the association between alcohol intake and hypertension was not significant, regardless of flushing response. In conclusion, In Japanese men, alcohol intake was positively associated with hypertension in a manner that was not influenced by the flushing response.</p>

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Dietary sodium-to-potassium ratio as a risk factor for stroke, cardiovascular disease and all-cause mortality in Japan

Okayama Akira, Okuda Nagako, Miura Katsuyuki, Okamura Tomonori, Hayakawa Takehito, Akasaka Hiroshi, Ohnishi Hirofumi, Saitoh Shigeyuki, Arai Yusuke, Kiyohara Yutaka, Takashima Naoyuki, Yoshita Katsushi, Fujiyoshi Akira, Zaid Maryam, Ohkubo Takayoshi, Ueshima Hirotsugu

BMJ Open 6 （ 7 ） e011632 2016年07月

ISSN  2044-6055

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<p>OBJECTIVES: To evaluate the impact of dietary sodium and potassium (Na-K) ratio on mortality from total and subtypes of stroke, cardiovascular disease (CVD) and all causes, using 24-year follow-up data of a representative sample of the Japanese population.</p><p>SETTING: Prospective cohort study.</p><p>PARTICIPANTS: In the 1980 National Cardiovascular Survey, participants were followed for 24 years (NIPPON DATA80, National Integrated Project for Prospective Observation of Non-communicable Disease And its Trends in the Aged). Men and women aged 30-79 years without hypertensive treatment, history of stroke or acute myocardial infarction (n=8283) were divided into quintiles according to dietary Na-K ratio assessed by a 3-day weighing dietary record at baseline. Age-adjusted and multivariable-adjusted HRs were calculated using the Mantel-Haenszel method and Cox proportional hazards model.</p><p>PRIMARY OUTCOME MEASURES: Mortality from total and subtypes of stroke, CVD and all causes.</p><p>RESULTS: A total of 1938 deaths from all causes were observed over 176 926 person-years. Na-K ratio was significantly and non-linearly related to mortality from all stroke (p=0.002), CVD (p=0.005) and total mortality (p=0.001). For stroke subtypes, mortality from haemorrhagic stroke was positively related to Na-K ratio (p=0.024). Similar relationships were observed for men and women. The observed relationships remained significant after adjustment for other risk factors. Quadratic non-linear multivariable-adjusted HRs (95% CI) in the highest quintile versus the lowest quintile of Na-K ratio were 1.42 (1.07 to 1.90) for ischaemic stroke, 1.57 (1.05 to 2.34) for haemorrhagic stroke, 1.43 (1.17 to 1.76) for all stroke, 1.39 (1.20 to 1.61) for CVD and 1.16 (1.06 to 1.27) for all-cause mortality.</p><p>CONCLUSIONS: Dietary Na-K ratio assessed by a 3-day weighing dietary record was a significant risk factor for mortality from haemorrhagic stroke, all stroke, CVD and all causes among a Japanese population.</p>

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Dietary sodium-to-potassium ratio as a risk factor for stroke, cardiovascular disease and all-cause mortality in Japan: the NIPPON DATA80 cohort study.

Okayama A, Okuda N, Miura K, Okamura T, Hayakawa T, Akasaka H, Ohnishi H, Saitoh S, Arai Y, Kiyohara Y, Takashima N, Yoshita K, Fujiyoshi A, Zaid M, Ohkubo T, Ueshima H, NIPPON DATA80 Research Group.

BMJ open 6 （ 7 ） e011632 2016年07月

研究論文（学術雑誌）

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Dietary sodium-to-potassium ratio as a risk factor for stroke, cardiovascular disease and all-cause mortality in Japan: the NIPPON DATA80 cohort study.

Okayama A, Okuda N, Miura K, Okamura T, Hayakawa T, Akasaka H, Ohnishi H, Saitoh S, Arai Y, Kiyohara Y, Takashima N, Yoshita K, Fujiyoshi A, Zaid M, Ohkubo T, Ueshima H, NIPPON DATA80 Research Group.

BMJ open 6 （ 7 ） e011632 2016年07月

研究論文（学術雑誌）

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Prognostic significance of endogenous erythropoietin in long-term outcome of patients with acute decompensated heart failure.

Nagai T, Nishimura K, Honma T, Higashiyama A, Sugano Y, Nakai M, Honda S, Iwakami N, Okada A, Kawakami S, Kanaya T, Asaumi Y, Aiba T, Nishida Y, Kubota Y, Sugiyama D, Okamura T, Noguchi T, Kusano K, Ogawa H, Yasuda S, Anzai T, NaDEF investigators.

European journal of heart failure 18 （ 7 ） 803 - 813 2016年07月

研究論文（学術雑誌）,  ISSN  1388-9842

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<p>Aims: Although previous reports suggest that an elevated endogenous erythropoietin (EPO) level is associated with worse clinical outcomes in chronic heart failure (HF) patients, the prognostic implication of EPO in patients with acute decompensated HF (ADHF) and underlying mechanisms of the high EPO level in severe HF patients who have a poor prognosis remain unclear. Methods and results: We examined 539 consecutive ADHF patients with EPO measurement on admission from our registry. During a median follow-up period of 329 days, a higher EPO level on admission was independently associated with worse clinical outcomes [hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.06–1.48, P = 0.008], and haemoglobin level was the strongest determinant of EPO level (P &lt;0.001), whereas estimated glomerular filtration rate (eGFR) was not significant in multivariate regression analysis. In the anaemic subgroup of 318 patients, a higher EPO level than expected on the basis of their haemoglobin level was related to increased adverse events (HR 1.63, 95% CI 1.05–2.49, P = 0.028). Moreover, estimated plasma volume excess rate was positively associated with EPO level (P = 0.003), and anaemic patients with a higher than expected EPO level tended to have a higher estimated plasma volume excess rate and plasma lactate level, and lower systemic oxygen saturation level with the preservation of the reticulocyte production index than those with a lower than expected EPO level. Conclusion: A high EPO level predicts long-term worse clinical outcomes in ADHF patients, independent of anaemia and impaired renal function. Anaemia and hypoxia due to severe congestion may synergistically contribute to a high EPO level in high-risk HF patients.</p>

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Impact of hypertension on the lifetime risk of coronary heart disease.

Turin TC, Okamura T, Afzal AR, Rumana N, Watanabe M, Higashiyama A, Nakao YM, Nakai M, Takegami M, Nishimura K, Kokubo Y, Okayama A, Miyamoto Y

Hypertension research : official journal of the Japanese Society of Hypertension 39 （ 7 ） 548 - 551 2016年07月

研究論文（学術雑誌）,  ISSN  0916-9636

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<p>The lifetime risk estimate conveys the probability of disease in the remaining lifetime for an index age. These estimates may be useful for general audience-targeted knowledge translation activities against hypertension. There are only a few reports on the impact of hypertension on the lifetime risk of cardiovascular events. The Suita Study, a cohort study of urban residents, was established in 1989. We included all participants who were coronary heart disease (CHD) free at baseline. Age (in years) was used as the timescale. Age-specific incidence rates were calculated with the person-year method within 5-year bands. We estimated the sex- and index-age-specific lifetime risk of first-ever CHD, taking the competing risk of death into account. We followed 5834 participants from 1989 to 2007 for a total of 75 387.5 person-years. At age 45 years, the competing risk of death-adjusted lifetime risk for all CHD for men was 14.12% for normotensive men and 26.95% for hypertensive men. The competing risk of death-adjusted lifetime risk for all CHD at 45 years of age for women was 6.21% for normotensive women and 14.85% for hypertensive women. This increased lifetime risk of CHD for hypertensive patients was observed among both men and women across all index ages. Although the overall lifetime risk of CHD was lower than in the Western population, hypertension showed a significant effect on the residual lifetime risk of CHD among Japanese middle-aged men and women. This easy-to-understand knowledge may be used as an important index to assist public health education and planning.</p>

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Erratum to: Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men.

Harada S, Takebayashi T, Kurihara A, Akiyama M, Suzuki A, Hatakeyama Y, Sugiyama D, Kuwabara K, Takeuchi A, Okamura T, Nishiwaki Y, Tanaka T, Hirayama A, Sugimoto M, Soga T, Tomita M

Environmental health and preventive medicine 21 （ 4 ） 283 - 284 2016年07月

研究論文（学術雑誌）,  ISSN  1342-078X

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Erratum to: Metabolomic profiling reveals novel biomarkers of alcohol intake and alcohol-induced liver injury in community-dwelling men.

Harada S, Takebayashi T, Kurihara A, Akiyama M, Suzuki A, Hatakeyama Y, Sugiyama D, Kuwabara K, Takeuchi A, Okamura T, Nishiwaki Y, Tanaka T, Hirayama A, Sugimoto M, Soga T, Tomita M

Environmental health and preventive medicine 21 （ 4 ） 283 - 284 2016年07月

研究論文（学術雑誌）,  ISSN  1342-078X

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NIPPON DATA (National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged)

Okamura Tomonori

Nihon rinsho. Japanese journal of clinical medicine 74 Pt 1   685 - 690 2016年06月

ISSN  0047-1852

[NIPPON DATA (National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged)].

Okamura T

Nihon rinsho. Japanese journal of clinical medicine 74 Suppl 4 Pt 1   685 - 90 2016年06月

研究論文（学術雑誌）,  ISSN  0047-1852

[NIPPON DATA (National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged)].

Okamura T

Nihon rinsho. Japanese journal of clinical medicine 74 Suppl 4 Pt 1   685 - 90 2016年06月

研究論文（学術雑誌）,  ISSN  0047-1852

Independent Prognostic Value of Single and Multiple Non-Specific 12-Lead Electrocardiographic Findings for Long-Term Cardiovascular Outcomes: A Prospective Cohort Study.

Sawano M, Kohsaka S, Okamura T, Inohara T, Sugiyama D, Shiraishi Y, Watanabe M, Nakamura Y, Higashiyama A, Kadota A, Okuda N, Murakami Y, Ohkubo T, Fujiyoshi A, Miura K, Okayama A, Ueshima H, NIPPON DATA 80/90 Research Group.

PloS one 11 （ 6 ） e0157563 2016年06月

研究論文（学術雑誌）,  ISSN  1932-6203

　概要を見る

<p>Aims The long-term prognostic effect of non-specific 12-lead electrocardiogram findings is unknown. We aimed to evaluate the cumulative prognostic impact of axial, structural, and repolarization categorical abnormalities on cardiovascular death, independent from traditional risk scoring systems such as the Framingham risk score and the NIPPON DATA80 risk chart. Methods and Results A total of 16,816 healthy men and women from two prospective, longitudinal cohort studies were evaluated. 3,794 (22.6%) individuals died during a median follow-up of 15 years (range, 2.0-24 years). Hazard ratios for cardiovascular death, all-cause death, coronary death and stroke death were calculated for the cumulative and independent axial, structural, and repolarization categorical abnormalities adjusted for the Framingham risk score and the NIPPON DATA80 risk chart. Individuals with two or more abnormal categories had a higher risk of cardiovascular death after adjustment for Framingham risk score (men: HR 4.27, 95%CI 3.35-5.45; women: HR 4.83, 95%CI 3.76-6.22) and NIPPON DATA80 risk chart (men: HR 2.39, 95%CI 1.87-3.07; women: HR 2.04, 95%CI 1.58-2.64). Conclusion Cumulative findings of axial, structural, and repolarization abnormalities are significant predictors of long-term cardiovascular death in asymptomatic, healthy individuals independent of traditional risk stratification systems.</p>

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Cross-sectional association between exposure to particulate matter and inflammatory markers in the Japanese general population: NIPPON DATA2010.

Michikawa T, Okamura T, Nitta H, Nishiwaki Y, Takebayashi T, Ueda K, Kadota A, Fujiyoshi A, Ohkubo T, Ueshima H, Okayama A, Miura K, NIPPON DATA2010 Research Group.

Environmental pollution (Barking, Essex : 1987) 213   460 - 467 2016年06月

研究論文（学術雑誌）,  ISSN  0269-7491

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<p>A suggestive mechanism behind the association between particulate matter and cardiovascular disease is inflammatory response. Earlier population-based studies investigating the association between particulate matter and inflammatory biological markers, in particular C-reactive protein (CRP), showed inconsistent results. In addition, evidence from the Asian population, in which CRP levels are typically lower than those observed in Western populations, was sparse. We examined the cross-sectional association between short- and long-term exposure to particulate matter and inflammatory markers, including high-sensitivity CRP (hs-CRP) and white blood cell (WBC) count, in a representative population of Japanese community dwellers (NIPPON DATA2010). We analysed data from 2360 participants (1002 men and 1358 women), aged 20 years or older, who resided in 300 randomly selected districts (222 public health centre areas) throughout Japan. We used background concentrations of suspended particulate matter (SPM, defined as particles with a 100% cut-off level at 10 μm aerodynamic diameter) and co-pollutants within the public health centre area. A logistic regression model was applied to estimate odds ratios (ORs) of elevated hs-CRP (&gt; 0.3 mg/dl) or WBC (&gt; 9000/μl). Since smoking is an important confounding factor, we firstly included this in the models, and additionally conducted the analyses after excluding current smokers. The one-month average concentration of SPM was positively associated with hs-CRP (OR per 10 μg/m³ increase in SPM = 1.42, 95% confidence interval = 1.00-2.04), and high exposure to SPM on the day of blood draw was associated with increased WBC count, after excluding current smokers (OR = 1.13, 1.01-1.28). Similar association patterns were observed for ozone. In conclusion, exposure to particulate matter was associated with inflammatory markers in the general Japanese population. Systemic inflammation may play a role in the link between particulate matter and cardiovascular disease.</p>

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

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

Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 51 （ 3 ） 173 - 183 2016年06月

研究論文（学術雑誌）,  ISSN  1341-8963

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

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

Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 51 （ 3 ） 173 - 183 2016年06月

研究論文（学術雑誌）,  ISSN  1341-8963

Relationship between outpatient visit frequency and hypertension control: a 9-year occupational cohort study.

Shima A, Tatsumi Y, Ishizaki T, Godai K, Kawatsu Y, Okamura T, Nishikawa T, Morimoto A, Morino A, Miyamatsu N

Hypertension research : official journal of the Japanese Society of Hypertension 39 （ 5 ） 376 - 381 2016年05月

研究論文（学術雑誌）,  ISSN  0916-9636

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<p>The purpose of this study was to investigate the relationship between the frequency of outpatient visits and hypertension control as determined from health insurance records. This 9-year cohort study in Japan was based on 518 participants with hypertension who underwent health checkups in 2004. Participants were aged 35-56 years and none had a history of cardiovascular or cerebrovascular disease. All were covered by the same employee health insurer. Mean annual outpatient visit days at a hospital/clinic during the 9-year period were classified within four quartiles (Q1, Q2, Q3, Q4). Uncontrolled hypertension was defined as a systolic blood pressure (BP) ≥140 mm Hg and a diastolic BP ≥90 mm Hg. Logistic regression analysis was used to estimate the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the prevalence of uncontrolled hypertension in groups Q1, Q2 and Q3 vs. Q4. The median (25th-75th percentile) annual outpatient visit days was 9.4 (4.0-15.5). Uncontrolled hypertension was observed in 62.4% of the participants in 2013. The multivariable-adjusted ORs and 95% CIs for uncontrolled hypertension in Q1, Q2 and Q3 vs. Q4 were 4.03 (2.28-7.12), 1.67 (0.99-2.81) and 1.44 (0.86-2.41), respectively. Uncontrolled hypertension increased significantly as the number of outpatient visits decreased (P for trend </p>

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

Nguyen H., 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., Okamura T., Okayama A., Ueshima H.

Clinical Nutrition （Clinical Nutrition）  37 （ 1 ） 182 - 188 2016年04月

研究論文（学術雑誌）,  ISSN  0261-5614

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© 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism 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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Profiling of plasma metabolites in postmenopausal women with metabolic syndrome.

Iida M, Harada S, Kurihara A, Fukai K, Kuwabara K, Sugiyama D, Takeuchi A, Okamura T, Akiyama M, Nishiwaki Y, Suzuki A, Hirayama A, Sugimoto M, Soga T, Tomita M, Banno K, Aoki D, Takebayashi T

Menopause (New York, N.Y.) 23 （ 7 ） 749 - 58 2016年04月

研究論文（学術雑誌）,  ISSN  1072-3714

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<p>OBJECTIVE:: The aim of the study was to investigate the associations of amino acids and other polar metabolites with metabolic syndrome (MetS) in postmenopausal women in a lean Asian population. METHODS:: The participants were 1,422 female residents enrolled in a cohort study from April to August 2012. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III modified for Japanese women. Associations were examined between MetS and 78 metabolites assayed in fasting plasma samples using capillary electrophoresis-mass spectrometry. Replication analysis was performed to confirm the robustness of the results in a separate population created by random allocation. RESULTS:: Analysis was performed for 877 naturally postmenopausal women, including 594 in the original population and 283 in the replication population. The average age, body mass index, and levels of high- and low-density lipoprotein cholesterol of the entire population were 64.6 years, 23.0?kg/m, 72.1?mg/dL, and 126.1?mg/dL, respectively. There was no significant difference in low-density lipoprotein cholesterol levels between women with and without MetS. Thirteen metabolites were significantly related to MetS: multiple plasma amino acids were elevated in women with MetS, including branched-chain amino acids, alanine, glutamate, and proline; and alpha-aminoadipate, which is generated by lysine degradation, was also significantly increased. CONCLUSIONS:: Our large-scale metabolomic profiling indicates that Japanese postmenopausal women with MetS have abnormal polar metabolites, suggesting altered catabolic pathways. These results may help to understand metabolic disturbance, including in persons with normal body mass index and relatively high levels of high-density lipoprotein cholesterol, and may have clinical utility based on further studies.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0</p>

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