Papers - Okamura, Tomonori

A Randomized Clinical Trial of ICT-based Interventions for Sodium and Potassium Regulation in Healthy Adults.

Yano Y, Kitaoka K, Ohkubo T, Okamura T, Kanegae H, Yoshita K, Tsukinoki R, Okami Y, Node K, Rakugi H, Itoh H, Miura K

American journal of hypertension  2025.04

ISSN  0895-7061

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Atherosclerotic Cardiovascular Disease Risk Prediction Models in China, Japan, and Korea: Implications for East Asians?

Nguyen P.K., Zhao D., Okamura T., Chang Kim H., Wong N.D., Yang E.

JACC: Asia 5 ( 3 ) 333 - 349 2025.03

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The management of atherosclerotic cardiovascular disease (ASCVD) in the United States is currently based upon large epidemiological studies in primarily non-Hispanic White subjects. Although this strategy provides a uniform approach that is simpler to implement, it may result in inappropriately targeting certain Asian populations for treatment based on inaccurate ASCVD risk estimation. In this state-of-the-art review, we detail the similarities and differences in the prevalence of ASCVD and its risk factors among Chinese, Japanese, and Korean people living in the United States and in their native countries. We highlight the limitations of current risk calculators when applied to East Asian immigrants and summarize risk stratification approaches in China, Japan, and Korea. Our review underscores the need to disaggregate registry, cohort, and clinical trial data by East Asian subgroups, to actively engage these populations in research, and to initiate studies to better define ASCVD risk in East Asian people living in the United States.

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All-Cause and Cause-Specific Mortality Associated with Long-Term Exposure to Fine Particulate Matter in Japan: The Ibaraki Prefectural Health Study

Michikawa, T; Nishiwaki, Y; Asakura, K; Okamura, T; Takebayashi, T; Hasegawa, S; Milojevic, A; Minami, M; Taguri, M; Takeuchi, A; Ueda, K; Sairenchi, T; Yamagishi, K; Iso, H; Irie, F; Nitta, H

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS  2025.01

ISSN  1340-3478

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Comprehensive assessment of the impact of blood pressure, body mass index, smoking, and diabetes on healthy life expectancy in Japan: NIPPON DATA90.

Tsukinoki R, Murakami Y, Hayakawa T, Kadota A, Harada A, Kita Y, Okayama A, Miura K, Okamura T, Ueshima H

Journal of epidemiology  2025.01

ISSN  0917-5040

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Long-term risk of cardiovascular mortality according to age group and blood pressure categories of the latest guideline

Satoh M., Ohkubo T., Miura K., Harada A., Tsutsui A., Hozawa A., Shimizu Y., Ishikawa S., Kokubo Y., Okamura T., Murakami Y.

Hypertension Research 48 ( 4 ) 1428 - 1433 2025

ISSN  09169636

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This study examined the association between the latest blood pressure (BP) classification and cardiovascular disease (CVD) mortality risk, using data from 70,570 individuals across 10 Japanese cohorts. Participants were stratified by age (40–64 and 65–89 years) and antihypertensive treatment use. BP was classified according to the 2019 Japanese Society of Hypertension Guidelines. During a follow-up period of approximately 10 years, 2304 CVD deaths occurred. Cox models demonstrated that CVD mortality risk increased stepwise with the BP category, with this association being especially pronounced in patients aged 40–64 years, where the Grade I hypertension group showed the highest population-attributable fraction (PAF). When the treated participants were included in the hypertension group, the overall PAF for CVD mortality was 41.1%. Similar patterns were observed for CVD subtype mortality risk, with hypertension showing particularly high PAFs for intracerebral hemorrhage. These findings highlight the importance of early-stage prevention and management of hypertension. (Figure presented.)

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[Effect of the combination of "weight gain of more than 10 kg since age 20" and obesity on the new onset of diabetes mellitus].

Naruse H, Kuwabara K, Hirata A, Imai Y, Sugiyama D, Funamoto M, Okamura T

[Nihon koshu eisei zasshi] Japanese journal of public health 72 ( 3 ) 199 - 207 2024.12

ISSN  0546-1766

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Progression of aortic calcification among Japanese in Japan and white and Japanese Americans: a prospective cohort study

Li, MY; Fujiyoshi, A; Willcox, BJ; Li, JT; Kadota, A; Kadowaki, S; Seto, T; Kadowaki, T; Chang, YF; Evans, R; Miura, K; Edmundowicz, D; Okamura, T; Masaki, KH; Ueshima, H; Sekikawa, A

EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING 26 ( 2 ) 273 - 279 2024.11

ISSN  2047-2404

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Aims Continued low mortality from coronary heart disease in Japan, despite deleterious changes in traditional risk factors, remains unexplained. Since aortic calcification (AC) was an early predictor of cardiovascular mortality, we compared the progression and incidence of AC between Japanese in Japan, white Americans, and third-generation Japanese Americans in the ERA JUMP cohort. We examined whether higher blood levels of marine-derived n-3 fatty acids (FAs) in Japanese than in Americans accounted for the difference. Methods Men (n = 700) aged 40–49 years (252 Japanese in Japan, 238 white, and 210 Japanese Americans) were examined at baseline and results and 4–7 years later. AC was evaluated from the aortic arch to the iliac bifurcation with computed tomography and quantified by the Agatston method. Robust linear regression and linear mixed models were used to compare the progression of AC. Multivariable logistic regression models were fitted to compare the incidence of AC (AC ≥ 50 at follow-up) among those with baseline AC < 50. Japanese in Japan had a significantly slower progression of AC than white and Japanese Americans after adjusting for age, baseline AC, follow-up time, and traditional risk factors. White Americans had a significantly higher incidence of AC than Japanese in Japan [OR = 4.61 (95% CI, 1.27–16.82)]. Additional adjustment for blood levels of n-3 FAs accounted for the difference in AC incidence but not progression. Conclusion Japanese in Japan had a significantly slower progression and lower incidence of AC than white Americans. High levels of marine-derived n-3 FAs in Japanese in Japan partly accounted for the difference in incidence.

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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 2024.08

ISSN  1053-8569

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

Kubo K, Hirata A, Kadota A, Harada A, Nakamura Y, Hayakawa T, Takashima N, Fujiyoshi A, Okami Y, Kita Y, Okayama A, Miura K, Ueshima H, Okamura T, NIPPON DATA90 Research Group

Circulation journal : official journal of the Japanese Circulation Society 88 ( 9 ) 1478 - 1487 2024.07

ISSN  1346-9843

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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 71 ( 8 ) 430 - 437 2024.06

ISSN  0546-1766

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A Novel Risk Score for Major Bleeding in Japanese Patients with Non-Valvular Atrial Fibrillation: The J-RISK AF Study.

Akao M, Tomita H, Nakai M, Kodani E, Suzuki S, Hayashi K, Sawano M, Goya M, Yamashita T, Fukuda K, Tsuda T, Isobe M, Toyoda K, Miyamoto Y, Okamura T, Sasahara Y, Okumura K, J-RISK AF Research Group

Journal of atherosclerosis and thrombosis 31 ( 11 ) 1591 - 1606 2024.05

ISSN  1340-3478

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Aim: Oral anticoagulants (OACs) reduce the risk of ischemic stroke but may increase the risk of major bleeding in patients with non-valvular atrial fibrillation (NVAF). Various risk scores, such as HAS-BLED, ATRIA, ORBIT, and DOAC, have been proposed to assess the risk of major bleeding in patients with NVAF receiving OACs. However, limited data are available regarding bleeding risk stratification in Japanese patients with NVAF. Methods: Of the 16,098 NVAF patients from the J-RISK AF study, the combined data of the five major AF registries in Japan (J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry), we analyzed 11,539 patients receiving OACs (median age, 71 years old; women, 29.6%; median CHA2DS2-VASc score, 3). Results: During the 2-year follow-up period, major bleeding occurred in 274 patients (1.3% per patient-year). In a multivariate Cox proportional hazards analysis, an advanced age, hypertension (systolic blood pressure ≥ 150 mmHg), bleeding history, anemia, thrombocytopenia, and concomitant antiplatelet agents were significantly associated with a higher incidence of major bleeding. We developed a novel risk stratification system, HED-[EPA]2-B3 score, which had a better predictive performance for major bleeding (C-statistics 0.67, [95% confidence interval, 0.63-0.70]) than the HAS-BLED (0.64, [0.60-0.67], P for difference 0.02) and ATRIA (0.63, [0.60-0.66], P for difference ＜0.01) scores. Furthermore, it was non-significantly higher than the ORBIT (0.65, [0.62-0.68], P for difference 0.07) and DOAC (0.65, [0.62-0.68], P for difference 0.17) scores. Conclusion: Our novel risk stratification system, the HED-[EPA]2-B3 score, may be useful for identifying Japanese patients receiving OACs at a risk of major bleeding.

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Low-density lipoprotein particle profiles compared with standard lipids measurements in the association with asymptomatic intracranial artery stenosis.

Vu T, Yano Y, Pham HKT, Mondal R, Ohashi M, Kitaoka K, Moniruzzaman M, Torii S, Shiino A, Tsuji A, Hisamatsu T, Okamura T, Kondo K, Kadota A, Watanabe Y, Nozaki K, Ueshima H, Miura K

Scientific reports (Scientific Reports)  14 ( 1 ) 10765 2024.05

ISSN  2045-2322

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The Shiga Epidemiological Study of Subclinical Atherosclerosis was conducted in Kusatsu City, Shiga, Japan, from 2006 to 2008. Participants were measured for LDL-p through nuclear magnetic resonance technology. 740 men participated in follow-up and underwent 1.5 T brain magnetic resonance angiography from 2012 to 2015. Participants were categorized as no-ICAS, and ICAS consisted of mild-ICAS (1 to < 50%) and severe-ICAS (≥ 50%) in any of the arteries examined. After exclusion criteria, 711 men left for analysis, we used multiple logistic regression to examine the association between lipid profiles and ICAS prevalence. Among the study participants, 205 individuals (28.8%) had ICAS, while 144 individuals (20.3%) demonstrated discordance between LDL-c and LDL-p levels. The discordance “low LDL-c–high LDL-p” group had the highest ICAS risk with an adjusted OR (95% CI) of 2.78 (1.55–5.00) in the reference of the concordance “low LDL-c–low LDL-p” group. This was followed by the concordance “high LDL-c–high LDL-p” group of 2.56 (1.69–3.85) and the discordance “high LDL-c–low LDL-p” group of 2.40 (1.29–4.46). These findings suggest that evaluating LDL-p levels alongside LDL-c may aid in identifying adults at a higher risk for ICAS.

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[Development of a new method for assessing the availability of low-sodium foods in Japan].

Hayabuchi H, Takemi Y, Ohta M, Sakata I, Sakaguchi K, Kubo A, Yoshita K, Kitaoka K, Okami Y, Ohkubo T, Okamura T, Node K, Miura K

[Nihon koshu eisei zasshi] Japanese journal of public health 71 ( 7 ) 366 - 375 2024.03

ISSN  0546-1766

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Correction: Universal health coverage in the context of population ageing: catastrophic health expenditure and unmet need for healthcare.

Okamoto S, Sata M, Rosenberg M, Nakagoshi N, Kamimura K, Komamura K, Kobayashi E, Sano J, Hirazawa Y, Okamura T, Iso H

Health economics review 14 ( 1 ) 20 2024.03

ISSN  2191-1991

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Real-World Clinical Profile of Patients Prescribed Evolocumab in Japan.

Sheng F, Wang AY, Miyawaki K, Tsuchiya T, Osada N, Miller R, Fu Z, Okamura T

Circulation journal : official journal of the Japanese Circulation Society 88 ( 10 ) 1629 - 1636 2024.03

ISSN  1346-9843

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Mortality from major causes and lifestyles by proportions of public assistance recipients among 47 prefectures in Japan: Ecological panel data analysis from 1999 to 2016.

Nishi N, Kitaoka K, Tran Ngoc Hoang P, Okami Y, Kondo K, Sata M, Kadota A, Nakamura M, Yoshita K, Okamura T, Ojima T, Miura K

Preventive medicine reports (Preventive Medicine Reports)  39   102635 2024.03

ISSN  2211-3355

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Objective: Comprehensive investigations of correlations between subnational socioeconomic factors and trends in mortality and lifestyle are important for addressing public health problems. Methods: Forty-seven prefectures in Japan were divided into quartiles based on the proportion of public assistance recipients (PPAR). Age-standardized mortality from all causes, cancer, heart disease, and stroke in each prefecture were averaged for these quartiles in 2000, 2005, 2010, and 2015. Data from the National Health and Nutrition Survey were obtained for the following periods: 1999–2001, 2003–2005, 2007–2009, 2012, and 2016. Body mass index (BMI), intake of total energy, vegetable and salt, step count, and prevalence of current smoking and drinking for individuals aged 40–69 years age range were standardized for each prefecture and averaged by quartile. A two-way analysis of variance was used to assess differences in mortality and lifestyle across different years or periods, and quartiles. Results: Mortality rates decreased, with the first (lowest) quartile showing the lowest rates, across all causes, cancer and heart diseases in both sexes. BMI exhibited an increase in men, whereas, BMI in women and other lifestyle factors in both sexes, excluding smoking and drinking in women, exhibited a decrease. BMI, vegetable and salt intake, total energy intake in men, and smoking in women varied across quartiles. Lower quartiles exhibited lower BMI and smoking prevalence but higher energy, vegetables, and salt intake. Conclusions: PPAR exhibited favorable trends and significant differences in mortality related to all causes, cancer and heart disease across both sexes, along with BMI among women.

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Relationship Between Hemoglobin Concentration and Cardiovascular Disease Mortality in a 25-Year Follow-up Study of a Japanese General Population　- NIPPON DATA90.

Kawashima M, Hisamatsu T, Harada A, Kadota A, Kondo K, Okami Y, Hayakawa T, Kita Y, Okayama A, Ueshima H, Okamura T, Miura K, NIPPON DATA90 Research Group

Circulation journal : official journal of the Japanese Circulation Society (Circulation journal : official journal of the Japanese Circulation Society)  88 ( 5 ) 742 - 750 2024.02

ISSN  1346-9843

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BACKGROUND: Deviations of hemoglobin from normal levels may be a factor in cardiovascular disease (CVD) risk; however, conclusive evidence is lacking. In addition, preclinical conditions may influence hemoglobin concentrations, but studies focusing on reverse causation are limited. Thus, we examined the relationship between hemoglobin concentrations and CVD mortality risk, considering reverse causation.Methods and Results: In a prospective cohort representative of the general Japanese population (1990-2015), we studied 7,217 individuals (mean age 52.3 years; 4,219 women) without clinical CVD at baseline. Participants were categorized into sex-specific hemoglobin quintiles (Q1-Q5) and data were analyzed using the Cox proportional hazards model adjusted for possible confounders. During a 25-year follow-up, 272 men and 334 women died from CVD. Adjusted hazard ratios for CVD mortality across sex-specific quintiles, using Q3 as the reference, were significantly higher for Q1 (1.40; 95% confidence interval [CI] 1.08-1.82) and Q5 (1.49; 95% CI 1.14-1.96), and remained significant after excluding deaths within the first 5 years of follow-up to consider reverse causation (1.35 [95% CI 1.02-1.79] and 1.45 [95% CI 1.09-1.94], respectively). A similar U-shaped association was seen between transferrin saturation levels and CVD mortality, but after excluding deaths within the first 5 years the association was significant only for Q1. CONCLUSIONS: Low and high hemoglobin concentrations were associated with an increased risk of CVD mortality.

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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 (Journal of atherosclerosis and thrombosis)  31 ( 7 ) 1031 - 1047 2024.02

ISSN  1340-3478

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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.

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Universal health coverage in the context of population ageing: catastrophic health expenditure and unmet need for healthcare.

Okamoto S, Sata M, Rosenberg M, Nakagoshi N, Kamimura K, Komamura K, Kobayashi E, Sano J, Hirazawa Y, Okamura T, Iso H

Health economics review (Health Economics Review)  14 ( 1 ) 8 2024.01

ISSN  2191-1991

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Background: Universal health coverage means that all people can access essential health services without incurring financial hardship. Even in countries with good service coverage and financial protection, the progress towards universal health coverage may decelerate or be limited with respect to the growing older population. This study investigates the incidence/prevalence, determinants, and consequences of catastrophic health expenditure (CHE) and unmet need for healthcare and assesses the potential heterogeneity between younger (≤ 64 years) and older people (65 years≤). Methods: Utilising an annual nationally representative survey of Japanese aged 20 years and over, we estimated the incidence of CHE and unmet need for healthcare using disaggregated estimates by household members’ age (i.e. ≤64 years vs. 65 years≤) between 2004 and 2020. Using a fixed-effects model, we assessed the determinants of CHE and unmet need along with the consequences of CHE. We also assessed the heterogeneity by age. Results: Households with older members were more likely to have their healthcare needs met but experienced CHE more so than households without older members. The financial consequences of CHE were heterogeneous by age, suggesting that households with older members responded to CHE by reducing food and social expenditures more so than households without older members reducing expenditure on education. Households without older members experienced an income decline in the year following the occurrence of CHE, while this was not found among households with older members. A U-shaped relationship was observed between age and the probability of experiencing unmet healthcare need. Conclusions: Households with older members are more likely to experience CHE with different financial consequences compared to those with younger members. Unmet need for healthcare is more common among younger and older members than among their middle-aged counterparts. Different types and levels of health and financial support need to be incorporated into national health systems and social protection policies to meet the unique needs of individuals and households.

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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 34 ( 8 ) 393 - 401 2024.01

ISSN  0917-5040

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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.

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