Papers - Okamura, Tomonori

[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

• Access to Document (DOI)

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

　View Summary

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.

• Access to Document (DOI)

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

　View Summary

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.

• Access to Document (DOI)

[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

• Access to Document (DOI)

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

• Access to Document (DOI)

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

　View Summary

Background: Real-world utilization data for evolocumab, the first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to be introduced in Japan in 2016, to date are limited. This study aimed to clarify the current real-world patient user profiles of evolocumab based on large-scale health claims data. Methods and Results: This retrospective database study examined patients from a health administrative database (MDV database) who initiated evolocumab between April 2016 (baseline) and November 2021. Characteristics and clinical profiles of this patient population are described. In all, 4,022 patients were included in the final analysis. Most evolocumab prescriptions occurred in the outpatient setting (3,170; 78.82%), and 940 patients (23.37%) had a recent diagnosis of familial hypercholesterolemia. Common recent atherosclerotic cardiovascular disease events at baseline included myocardial infarction (1,633; 40.60%), unstable angina (561; 13.95%), and ischemic stroke (408; 10.14%). Comorbidity diseases included hypertension (2,504; 62.26%), heart failure (1,750; 43.51%), diabetes (1,199; 29.81%), and chronic kidney disease (297; 7.38%). Among the lipid-lowering regimens concomitant with evolocumab, ezetimibe+statin was used most frequently (1,281; 31.85%), followed by no concomitant lipid-lowering regimen (1,190; 29.59%), statin (950; 23.62%), and ezetimibe (601; 14.94%). The median evolocumab treatment duration for all patients was 260 days (interquartile range 57-575 days). Conclusions: This study provides real-world insights into evolocumab utilization in Japan for optimizing patient care and adherence to guideline-based therapies to better address hypercholesterolemia in Japan.

• Access to Document (DOI)

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

　View Summary

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.

• Access to Document (DOI)

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

　View Summary

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.

• Access to Document (DOI)

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

　View Summary

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.

• Access to Document (DOI)

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

　View Summary

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.

• Access to Document (DOI)

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

　View Summary

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.

• Access to Document (DOI)

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 )  2024.01

ISSN  2218-1989

　View Summary

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.

• Access to Document (DOI)

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

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

Environmental health and preventive medicine 29   22 2024

ISSN  1342-078X

　View Summary

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

• Access to Document (DOI)

Seasonal variation in vascular dehydration risk: insights from the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) study

Nishikawa, T; Miyamatsu, N; Higashiyama, A; Kubota, Y; Nishida, Y; Hirata, T; Hirata, A; Miyazaki, J; Sugiyama, D; Kuwabara, K; Kubo, S; Miyamoto, Y; Okamura, T

ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE 29   62 2024

ISSN  1342-078X

　View Summary

Background: Dehydration, a risk factor for ischemic cerebrovascular diseases, is common in summer; however, the incidence of ischemic diseases is not necessarily higher in summer. Therefore, this study aimed to clarify the relationships between serum osmolarity, hematocrit, daily non-alcohol drink (NAD) intake and factors such as season and age as risk factors for dehydration. Method: Participants (703 women and 306 men) in the follow-up survey, in 2012 and 2013, of the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) Study, consisting of healthy individuals living in Kobe, Japan, were categorized into two groups based on the examination month: the warmer and colder seasons. Multivariate analyses were conducted to examine disparities in serum osmolarity, hematocrit, and NAD intake between these two groups. Results: The colder season was found to be negatively correlated with serum osmolarity and NAD intake, but positively correlated with hematocrit, even after adjusting for relevant factors. Age was independently associated with serum osmolarity, but not with hematocrit and NAD intake. Conclusions: This study suggests that intra-vascular volume depletion is more likely in the colder season despite lower serum osmolarity compared to the warmer season. Age-related increases in serum osmolarity without a corresponding rise in water intake may contribute to this. These findings support the importance of addressing dehydration in the colder season, particularly in older adults.

• Access to Document (DOI)

Association between alcohol intake and death from cardiovascular diseases and its subtypes stratified by dyslipidemia in Japanese men: 20-years follow-up of NIPPON DATA90

Hirata, T; Hirata, A; Torii, S; Takashima, N; Kadota, A; Choudhury, SR; Okayama, A; Miura, K; Okamura, T

ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE 29   61 2024

ISSN  1342-078X

　View Summary

Background: The association between alcohol consumption and atherosclerotic cardiovascular disease (ASCVD) was controversial, and no previous studies have shown the impact of dyslipidemia on the association. We aimed to clarify the association between alcohol consumption and death from cardiovascular disease (CVD) and its subtypes and the impact of dyslipidemia on the association. Methods: We conducted a 20-year cohort study to clarify the association between alcohol intake and death from CVD and its subtypes in 2,909 Japanese men. We estimated the hazard ratio (HR) and 95% confidence intervals (CIs) for current drinkers with non-drinkers as the reference, after adjusting for potential confounders using Cox proportional hazards models. We also investigated the association between alcohol consumption and ASCVD or CVD death stratified by the presence or absence of dyslipidemia. Results: During 50,782 person-years of follow-up period, 223 participants died from total CVD, 110 participants died from ASCVD, and 25 participants died from cerebral hemorrhage. Current drinkers with 1 gou/day were significantly associated with lower risk of ASCVD (HR: 0.60, 95%CI: 0.37–0.98), which is more apparent in those without dyslipidemia, and current drinkers with ²3 gou/day were significantly associated with higher risk of cerebral hemorrhage (HR: 4.13, 95%CI: 1.12–15.19). Conclusions: Small amounts of alcohol drinking were associated with lower risk of ASCVD in Japanese men, especially those without dyslipidemia. Meanwhile, excessive alcohol drinking was associated with higher risk of cerebral hemorrhage. Our findings suggest that it is important for current Japanese drinkers to reduce alcohol consumption for preventing ASCVD or cerebral hemorrhage.

• Access to Document (DOI)

Influence of previous health guidance history: impact and limitations of a single health guidance session.

Hayase A, Onoue T, Nishida K, Nakata Y, Hayashi F, Marutani M, Sakane N, Okamura T, Matsuzaki K, Kawamura T, Tsushita K

Environmental and occupational health practice 6 ( 1 )  2024

　View Summary

Objectives: Metabolic syndrome (MS) is a significant health concern in the working-age population. Since 2008, Japan has mandated health insurers to implement Specific Health Checkups to identify individuals with MS and preliminary groups, making Specific Health Guidance (SHG) compulsory for these groups. People receiving SHG multiple times is increasing as it is conducted as an annual public program. Therefore, we evaluated the influence of a health guidance history on the effectiveness of subsequent guidance. Methods: Using data from 10,191 participants in the 2017 Motivational Health Guidance (a type of SHG involving a single session), this longitudinal study assessed the changes in health checkup findings from 2017 to 2018. Participants were categorized based on their previous year’s (2016) SHG eligibility and participation: Group 1 (n = 3,903) met the 2016 SHG criteria and participated, Group 2 (n = 2,305) met the criteria but did not participate, and Group 3 (n = 3,983) had no MS risk factors and did not need to participate in the 2016 SHG. Results: The entire cohort and Groups 2 and 3 exhibited significant weight loss after 1 year. Group 1 showed a significant negative association, with a 3% (odds ratio [OR] 0.64; 95% confidence interval [CI], 0.55–0.75) and 5% body weight loss (OR 0.66; 95% CI, 0.54–0.81) than Group 3. Men in Group 1 showed a significant association with new-onset MS (OR 2.56; 95% CI, 1.93–3.40). Conclusions: The findings suggest that participants with a history of health guidance in the previous year may have low rates of achieving weight loss and a high incidence of new-onset MS after 1 year.

• Access to Document (DOI)

Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2022.

Okamura T, Tsukamoto K, Arai H, Fujioka Y, Ishigaki Y, Koba S, Ohmura H, Shoji T, Yokote K, Yoshida H, Yoshida M, Deguchi J, Dobashi K, Fujiyoshi A, Hamaguchi H, Hara M, Harada-Shiba M, Hirata T, Iida M, Ikeda Y, Ishibashi S, Kanda H, Kihara S, Kitagawa K, Kodama S, Koseki M, Maezawa Y, Masuda D, Miida T, Miyamoto Y, Nishimura R, Node K, Noguchi M, Ohishi M, Saito I, Sawada S, Sone H, Takemoto M, Wakatsuki A, Yanai H

Journal of atherosclerosis and thrombosis (Journal of atherosclerosis and thrombosis)  31 ( 6 ) 641 - 853 2023.12

ISSN  1340-3478

• Access to Document (DOI)

High blood pressure and colorectal cancer mortality in a 29-year follow-up of the Japanese general population: NIPPON DATA80.

Hisamatsu T, Kadota A, Hayakawa T, Kita Y, Harada A, Okami Y, Kondo K, Ohkubo T, Okamura T, Okayama A, Ueshima H, Miura K, NIPPON DATA80 Research Group

Hypertension research : official journal of the Japanese Society of Hypertension (Hypertension Research)  47 ( 1 ) 206 - 214 2023.11

ISSN  0916-9636

　View Summary

Onco-hypertension has been proposed, although associations of high blood pressure (BP) with cancer risk remain inconsistent. We examined associations of high BP with risk of mortality from stomach, lung, colorectal, liver, and pancreatic cancers independent of possible confounders in an analysis that excluded deaths within the first 5 years of follow-up to consider the reverse causality. In a prospective cohort representative of the general Japanese population (1980–2009), we studied 8088 participants (mean age, 48.2 years; 56.0% women) without clinical cardiovascular disease or antihypertensive medication at baseline. Fine-Gray competing risks regression was used to estimate hazard ratios for 10 mmHg higher BP adjusted for confounders including smoking, alcohol-drinking, obesity, and diabetes mellitus. During 29-year follow-up, 159 (2.0%), 159 (2.0%), 89 (1.1%), 86 (1.1%), and 68 (0.8%) participants died from stomach, lung, colorectal, liver, and pancreatic cancers, respectively. We observed a positive association of high BP with risk of colorectal cancer mortality but not with mortality risks from any other cancers. The association with colorectal cancer mortality for systolic and diastolic BP was evident in those aged 30–49 years (hazard ratios 1.43 [95% confidence interval, 1.22–1.67] and 1.86 [1.32–2.62], respectively) but not in those aged 50–59 years and ≥60 years (P for age interaction <0.01 for systolic and diastolic BP). The associations with colorectal cancer mortality were similar in the analyses stratified by smoking, alcohol-drinking, obesity, and diabetic status. In conclusion, high BP among young to middle-aged adults was independently associated with risk of colorectal cancer mortality later in life. [Figure not available: see fulltext.].

• Access to Document (DOI)

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 34 ( 9 ) 403 - 410 2023.11

ISSN  0917-5040

　View Summary

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.

• Access to Document (DOI)

Association of Pro-Inflammatory Diet with Long-Term Risk of All-Cause and Cardiovascular Disease Mortality: NIPPON DATA80.

Ganbaatar G, Okami Y, Kadota A, Ganbaatar N, Yano Y, Kondo K, Harada A, Okuda N, Yoshita K, Okamura T, Okayama A, Ueshima H, Miura K, NIPPON DATA80 Research Group

Journal of atherosclerosis and thrombosis (Journal of Atherosclerosis and Thrombosis)  31 ( 3 ) 326 - 343 2023.10

ISSN  1340-3478

　View Summary

Aim: A pro-inflammatory diet may increase the risk of cardiovascular disease (CVD) and all-cause mortality. However, this remains inconclusive as there is yet no study using a dietary record method that has been conducted in a large general population. Furthermore, an underestimation of the pro-inflammatory diet may exist due to the unmeasured effect of salt intake. Thus, in this study, we aimed to examine how pro-inflammatory diet is associated with the long-term risk of all-cause and CVD mortality in a representative Japanese population. Methods: A national nutrition survey was conducted throughout Japan in 1980. After considering the exclusion criteria, 9284 individuals (56% women aged 30–92 years) were included in this study. In total, 20 dietary parameters derived from 3-day weighed dietary records were used to calculate the dietary inflammatory index (DII). The causes of death were monitored until 2009. The Cox proportional hazards model was used to determine multivariable-adjusted hazard ratios (HRs). Stratified analysis according to salt intake level was also performed. Results: Compared with the lowest quartile of DII, multivariable-adjusted HRs (95% confidence intervals) in the highest quartile were 1.28 (1.15, 1.41), 1.35 (1.14, 1.60), 1.48 (1.15, 1.92), 1.62 (1.11, 2.38), and 1.34 (1.03, 1.75) for all-cause mortality, CVD mortality, atherosclerotic CVD mortality, coronary heart disease mortality, and stroke mortality, respectively. Stratified analysis revealed stronger associations among individuals with higher salt intake. Conclusions: As per our findings, a pro-inflammatory diet was determined to be positively associated with the long-term risk of all-cause and CVD mortality in a representative Japanese population. Thus, considering both salt intake and pro-inflammatory diet is deemed crucial for a comprehensive assessment of CVD risk.

• Access to Document (DOI)