Details of a Researcher - Okamura, Tomonori

Papers - Okamura, Tomonori

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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 (Journal of atherosclerosis and thrombosis) 30 ( 8 ) 884 - 906 2022.11

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's 1H-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.

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Impact of baseline blood pressure on adverse outcomes in Japanese patients with non-valvular atrial fibrillation: the J-RISK AF.

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

European heart journal open (European Heart Journal Open) 2 ( 6 ) oeac081 2022.11

Aims This study aimed to investigate the impact of baseline blood pressure (BP) on adverse outcomes in patients with atrial fibrillation (AF), using a pooled analysis performed on data from J-RISK AF, a large-scale cohort of Japanese patients with AF. ..................... Methods and results Of the 16 918 patients from five major AF registries including the J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry, 15 019 non-valvular AF (NVAF) patients with baseline BP values (age, 70.0 ± 11.0 years; men, 69.1%) were analysed. Incidence rates of adverse events were evaluated between patients divided into baseline systolic BP quartiles or at 150 mmHg. During the follow-up period of 730 days, ischaemic stroke, major bleeding, all-cause death, and cardiovascular death occurred in 277, 319, 718, and 275 patients, respectively. Hazard ratios (HRs) for ischaemic stroke and major bleeding were comparable among the quartiles, whereas HRs for all-cause and cardiovascular deaths in the lowest quartile with systolic BP <114 mmHg were significantly higher [HR 1.43, 95% confidence interval (CI) 1.13–1.81; and HR 1.47, 95% CI 1.01–2.12, respectively] than in the third quartile, even after adjusting for known confounding factors. In patients with a systolic BP of ≥150 mmHg, adjusted HR for major bleeding was significantly higher than that of <150 mmHg (HR 1.64, 95% CI 1.12–2.40). Conclusion In Japanese patients with NVAF, a baseline systolic BP <114 mmHg was significantly associated with higher all-cause and cardiovascular mortality. In contrast, a systolic BP ≥150 mmHg was an independent risk factor for major bleeding.

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

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

Endocrine journal (Endocrine journal) 70 ( 1 ) 97 - 106 2022.10

ISSN 0918-8959

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

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

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

Hypertension research : official journal of the Japanese Society of Hypertension (Hypertension Research) 46 ( 2 ) 311 - 320 2022.09

ISSN 0916-9636

Hypertension (HT) and diabetes mellitus (DM) are both major risk factors for chronic kidney disease (CKD); however, few studies have examined the impacts of the combination of HT and DM on CKD development in general populations. We aimed to explore whether HT or DM contributes more to CKD development in a Japanese community. A total of 5823 individuals without a history of CKD who underwent specific health checkups in fiscal year 2013 were monitored until the end of March 2018. Participants were categorized as having neither HT nor DM (none group), either HT or DM, and both (HT + DM). We calculated the hazard ratios (HRs) for developing CKD in each category using Cox proportional hazards models after adjusting for age, dyslipidemia, smoking, and alcohol drinking and with the none group as the reference. We also estimated the population attributable fraction (PAF) for CKD development in populations with either HT or DM or both. During a mean follow-up of 3.0 years, 759 individuals developed CKD, with HRs of 1.56 with a 95% confidence interval (CI) [1.33, 1.83], 1.22 with a 95% CI [0.86, 1.75], and 2.83 with a 95% CI [2.22, 3.63] for the HT only, DM only and HT + DM categories, respectively. Sex-specific analysis showed similar findings. The PAFs for CKD (14.1% and 17.2% for men and women, respectively) were the highest among participants with HT only. We concluded that in this Japanese community, HT contributed more than DM to CKD development; hence, managing hypertension is important to prevent CKD as well as diabetes.

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Relationship between Serum Proprotein Convertase Subtilisin/Kexin Type 9 Concentration and Prevalence of Coronary Artery Calcium in a Community-Based Sample of Japanese Men.

Kunimura A, Miura K, Segawa H, Torii S, Kondo K, Hisamatsu T, Kadota A, Fujiyoshi A, Yano Y, Nakagawa Y, Okamura T, Ueshima H, SESSA research group.

Journal of atherosclerosis and thrombosis (Journal of atherosclerosis and thrombosis) 30 ( 7 ) 767 - 777 2022.09

ISSN 1340-3478

AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for reducing low-density lipoprotein cholesterol (LDL-C) and cardiovascular events in high-risk patients. However, the influence of circulating PCSK9 concentration on atherosclerotic plaque formation in the general population remains unknown. We assessed the relationship between serum PCSK9 concentration and coronary artery calcium (CAC) prevalence in the general population. METHODS: Community-dwelling Japanese men (n=622) aged 46-82 years without a history of cardiovascular disease and lipid-lowering medications were included. Serum PCSK9 concentration and CAC score were measured using the Agatston method, and the multivariable analysis was used to assess their association. CAC was defined as an Agatston score of ＞10. We conducted further analysis stratified by age (＜60, 60-69, and ≥ 70 years). RESULTS: The average age, LDL-C, and median serum PCSK9 concentration were 68 years, 122 mg/dL, and 240 ng/mL, respectively. After multivariable adjustment for traditional cardiovascular risk factors, no significant association was observed between serum PCSK9 concentration and CAC prevalence (adjusted relative risk [aRR] 1.05, 95% confidence interval [CI] 0.97-1.13). With age stratification, serum PCSK9 concentration was significantly associated with CAC prevalence in men aged ＜60 years (aRR 1.38, 95% CI 1.01-1.88) but not in men aged 60-69 years (aRR 0.96, 95% CI 0.85-1.10) or ≥ 70 years (aRR 1.08, 95% CI 0.99-1.19). CONCLUSIONS: A higher serum PCSK9 concentration was associated with a higher CAC prevalence in men aged ＜60 years, which was independent of traditional cardiovascular risk factors.

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Reliable Information from Health Professionals Encourages Urban Japanese Mothers' Continued Participation in Health Checkups.

Tsukinoki R, Murakami Y, Imamura H, Okamura T

Healthcare (Basel, Switzerland) (Healthcare (Switzerland)) 10 ( 8 ) 2022.08

ISSN 2227-9032

We examined mothers’ health information sources and their relationships with continued participation in health checkups among urban Japanese mothers. Participants were 152 mothers below 40 years old with one or more children under 12 years old. We collected data at a children’s festival in Tokyo in 2019. A self-administered questionnaire was used to collect information regarding health checkups, trusted sources of information regarding mother’s health, and anthropological variables. Continued participation in health checkups was defined as participating in health checkups almost every year during the past five years. Logistic regression analysis was used to adjust for health insurance, mothers’ age, number of children, and current medical history. the sources of mothers’ health information trusted by over 20% of mothers in the two groups were “family”, “friends”, “Web/SNS”, and “healthcare professionals.” However, continued participation in health checkups was significantly associated with only the source of health information from “healthcare professionals” (odds ratio: 2.8 [95% confidence interval: 1.26–6.31], p = 0.01). These findings suggest that reliable information from health professionals encourages urban Japanese mothers’ continued participation in health checkups among Japanese mothers under 40 years old who have children under 12 years of age.

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Alcohol consumption and subclinical and clinical coronary heart disease: A Mendelian randomization analysis.

Hisamatsu T, Miura K, Tabara Y, Sawayama Y, Kadowaki T, Kadota A, Torii S, Kondo K, Yano Y, Fujiyoshi A, Yamamoto T, Nakagawa Y, Horie M, Kimura T, Okamura T, Ueshima H, SESSA and ACCESS Research Groups.

European journal of preventive cardiology (European Journal of Preventive Cardiology) 29 ( 15 ) 2006 - 2014 2022.07

ISSN 2047-4873

Aims: The potential effect of alcohol consumption on coronary heart disease (CHD) remains unclear. We used the variant rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) as an instrument to investigate the causal role of alcohol intake in subclinical and clinical CHD. Methods: We conducted two Mendelian randomization studies: a cross-sectional study of coronary artery calcification (CAC) on computed tomography of 1029 healthy men (mean age, 63.8 years) and a case-control study of 421 men with CHD [acute coronary syndrome (ACS) or stable angina pectoris] who underwent coronary revascularization and 842 age-matched male controls. Results: In the CAC study, medians (25%tiles, 75%tiles) of alcohol consumption by ALDH2-rs671 ∗2 homozygotes [n = 86 (8.4%)], ∗1∗2 heterozygotes [n = 397 (38.5%)], and ∗1 homozygotes [n = 546 (53.1%)] were 0.0 (0.0, 0.0), 28.0 (0.0, 129.0), and 224.0 (84.0, 350.0) g/week, respectively. In age-adjusted Poisson regression with robust error variance, compared with ∗2 homozygotes, relative risks for prevalent CAC score >0, ≥100, and ≥300 in ∗1 homozygotes were 1.29 (95% confidence interval, 1.06-1.57), 1.76 (1.05-2.96), and 1.81 (0.80-4.09), respectively. In age-adjusted ordinal logistic regression for CAC distributions, we observed higher odds among ∗1 homozygotes [odds ratio, 2.19 (1.39-3.46)] and even among ∗1∗2 heterozygotes [1.77 (1.11-2.82)] compared with ∗2 homozygotes. In the case-control study, conditional logistic regression revealed lower prevalence of ∗1 homozygotes among men with CHD [odds ratio, 0.54 (0.35-0.82)], especially ACS [0.46 (0.27-0.77)], than controls. Conclusion: Our findings indicate a positive association of alcohol consumption with CAC burden but an inverse association with clinical CHD, especially ACS.

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An Accelerated Failure Time Cure Model with Shifted Gamma Frailty and Its Application to Epidemiological Research.

Aida H, Hayashi K, Takeuchi A, Sugiyama D, Okamura T

Healthcare (Basel, Switzerland) (Healthcare (Switzerland)) 10 ( 8 ) 2022.07

ISSN 2227-9032

Survival analysis is a set of methods for statistical inference concerning the time until the occurrence of an event. One of the main objectives of survival analysis is to evaluate the effects of different covariates on event time. Although the proportional hazards model is widely used in survival analysis, it assumes that the ratio of the hazard functions is constant over time. This assumption is likely to be violated in practice, leading to erroneous inferences and inappropriate conclusions. The accelerated failure time model is an alternative to the proportional hazards model that does not require such a strong assumption. Moreover, it is sometimes plausible to consider the existence of cured patients or long-term survivors. The survival regression models in such contexts are referred to as cure models. In this study, we consider the accelerated failure time cure model with frailty for uncured patients. Frailty is a latent random variable representing patients’ characteristics that cannot be described by observed covariates. This enables us to flexibly account for individual heterogeneities. Our proposed model assumes a shifted gamma distribution for frailty to represent uncured patients’ heterogeneities. We construct an estimation algorithm for the proposed model, and evaluate its performance via numerical simulations. Furthermore, as an application of the proposed model, we use a real dataset, Specific Health Checkups, concerning the onset of hypertension. Results from a model comparison suggest that the proposed model is superior to existing alternatives.

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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 2022.06

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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Ono T, Kato S, Kokubo Y, Hasegawa Y, Kosaka T, Maeda Y, Okamura T, Miyamoto Y, Ikebe K

International journal of environmental research and public health (International Journal of Environmental Research and Public Health) 19 ( 11 ) 2022.05

ISSN 1661-7827

We examined whether the number of teeth could be a surrogate marker for metabolic syndrome (MetS) risk in cross-section. A total of 3771 individuals from the general urban Japanese population (1690 men, 2081 women; mean age 67.1 ± 11.0 years) participated in this study. Participants were diagnosed with MetS with three or more components hypertension, hyperglycemia, lipid metabolism abnormality, and abnormal abdominal girth. Questionnaires were administered to determine the number of teeth, smoking status, drinking status, and past illnesses. To clarify the relationships between the number of teeth and the presence of MetS components, we divided subjects into two groups: those with less than 20 residual teeth and those with 20 or more, then statistical analyses (Mantel-Haenszel tests and logistic regression analysis) were performed. MetS were higher for those with ≤19 teeth than those with ≥20 teeth when examining all participants and women-only groups. Hyperglycemia, low HDL cholesterol, high triglycerides, and diagnosis with MetS were all significantly higher in the ≤19 teeth group for both sexes combined and for women. These results suggest that less than 20 teeth may be a surrogate marker for MetS risk, but further studies on gender differences and pathological background are needed.

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

Kato S, Harada S, Iida M, Kuwabara K, Sugiyama D, Takeuchi A, Sata M, Matsumoto M, Kurihara A, Hirata A, Okamura T, Takebayashi T

BMJ open (BMJ Open) 12 ( 4 ) e052787 2022.04

ISSN 2044-6055

Objectives To date, the association between accumulated unhealthy behaviours and insomnia in individuals stratified according to the presence or absence of major cardiovascular risk factors is unclear. This study aimed to examine the effect of accumulated unhealthy behaviours on insomnia in Japanese dwellers. Design Cross-sectional study. Setting Baseline data between April 2012 and March 2015. Participants Our study used cross-sectional data among Japanese aged 35-74 years in a rural community (N=9565), the attendees of annual municipal or work site health check-up programmes. Main outcome measures Insomnia was assessed by Athens Insomnia Scale, which was set at 6 points and greater; other scales were given. Participants were categorised into three groups by their number of unhealthy behaviours (no exercise habit, smoking, alcohol drinking, skipping breakfast and obesity): 0-1, 2-3, 4 or more. The association between accumulated unhealthy behaviours and insomnia was estimated by logistic regression analysis. Further analysis was done after stratification of cardiovascular risk factors assessed by anthropometrics and clinical biochemistry measurements. Results The overall prevalence of insomnia was 13.3% for men and 19.3% for women. Men with unhealthy behaviour factors were more likely to have insomnia after adjusting for potential confounders, compared with the least unhealthy group (trend p=0.013). Women with four or more unhealthy behaviour factors were more likely to have insomnia, compared with the lowest groups (OR 1.175, 95% CI 1.077 to 1.282). Insomnia has an association with the unhealthy behaviours among men without cardiovascular risk factors (lowest groups: OR 1.133, 95% CI 1.037 to 1.238, trend p=0.026). Women without hypertension were more likely to have suspected insomnia, compared with the lowest group (OR 1.215, 95% CI 1.101 to 1.341). Conclusion The results showed accumulated unhealthy behaviours were associated with increased risk of insomnia in Japanese dwellers. For healthy population without cardiovascular risk factors, unhealthy behaviours should be considered as background conditions for insomnia.

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Trends in Prevalence, Treatment, and Control of Hypertension According to 40-Year-Old Life Expectancy at Prefectures in Japan from the National Health and Nutrition Surveys

Sata M., Okamura T., Nishi N., Kadota A., Nakamura M., Kondo K., Okami Y., Kitaoka K., Ojima T., Yoshita K., Miura K.

Nutrients (Nutrients) 14 ( 6 ) 2022.03

The prevalence of hypertension has been decreasing in Japan due to improved medical treatment and a decrease in dietary salt intake. However, disparities in the prevalence, treatment, and control of hypertension are expected to occur in different regions. This study aimed to investigate the trends in the prevalence, treatment, and control of hypertension at the prefectural level of life expectancy among Japanese population. We used data from the National Health and Nutrition Survey and analysed the individual survey information of individuals aged 40–69 years by dividing it into six terms, i.e., 1995–1997, 1999–2001, 2003–2005, 2007–2009, 2012, and 2016. Prefectures were classified into four groups according to their 40-year-old life expectancy in 2000. Outcome values were standardised to the population by 10-year age groups in 2010, and they were tested by two-way analysis of variance according to six terms and life expectancies. The prevalence of hypertension tended to decrease, especially among women, whereas the treatment and control tended to improve from the first to the sixth period in both men and women. The prevalence and treatment of hypertension in men with longer life expectancy tended to be lower than that in other groups, and there was no obvious difference in the control. In women, there were no obvious differences in the prevalence, treatment, or control. Reducing the prevalence of hypertension by improving lifestyle factors, such as high salt intake in each prefecture with a relatively short life expectancy, may be important to resolve the disparity in life expectancy among prefectures.

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Metabolic profiling of charged metabolites in association with menopausal status in Japanese community-dwelling midlife women: Tsuruoka Metabolomic Cohort Study.

Watanabe K, Iida M, Harada S, Kato S, Kuwabara K, Kurihara A, Takeuchi A, Sugiyama D, Okamura T, Suzuki A, Amano K, Hirayama A, Sugimoto M, Soga T, Tomita M, Kobayashi Y, Banno K, Aoki D, Takebayashi T

Maturitas (Maturitas) 155 54 - 62 2022.01

Research paper (scientific journal), ISSN 0378-5122

Background: Emerging evidence has shown that charged metabolites, such as amino acids, may play an important role in the pathogenesis of various metabolic disorders, many of which women in the postmenopausal period are at high risk of developing. This study examined the metabolic profile of middle-aged Japanese women to investigate alterations in charged metabolites induced by menopausal transition. Methods: The participants were 1193 female residents aged 40–60 at the baseline survey of the Tsuruoka Metabolomics Cohort Study. We investigated the cross-sectional association of menopausal status with 94 metabolomic biomarkers assayed in fasting plasma samples via capillary electrophoresis time-of-flight mass spectrometry using linear regression analysis. Results: Among the participants, 529 were premenopausal, 132 were in menopausal transition (MT), and 532 were postmenopausal. Significant differences were found in age, blood pressure, glucose and lipid levels, and smoking and drinking habits among the three groups. The concentrations of 5 metabolites in the MT group and 15 metabolites in the postmenopausal group were significantly higher than those in the premenopausal group after adjusting for confounding factors. When classified into pathways, these metabolites were related to the tricarboxylic cycle, urea cycle, and homocysteine metabolism, some of which are linked to arteriosclerosis. Conclusion: Multiple charged metabolites were associated with women's menopausal status, showing a gradual increase as women shifted from pre-, to peri-, to postmenopause. These findings might reflect the early changes behind the increased risk of dyslipidemia, diabetes, cardiovascular disease, and osteoporosis in later life.

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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, NIPPON DATA90 Research Group.

PloS one (PLoS ONE) 17 ( 2 ) e0261716 2022

Research paper (scientific journal), 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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A Strategy for Further Wellness for All: A Population Approach to Prevent Cardiovascular Diseases in Japan.

Okamura T

Journal of nutritional science and vitaminology (Journal of Nutritional Science and Vitaminology) 68 ( Supplement ) S104 - S106 2022

ISSN 0301-4800

A population approach may be effective in reducing cardiovascular disease (CVD) in the entire population. In Japan, the first public population approach is Health Japan 21 from 2000 to 2012. In 2013, it was revised as Health Japan 21 (the second term), which was promoting the health of all citizens until 2022. In the final assessment, although a significant decrease in age-adjusted CVD mortality was observed, it is unclear why these findings occurred. An assessment system for a population approach for CVD needs to be developed in Japan.

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

Kubo K., Okamura T., Sugiyama D., Hisamatsu T., Hirata A., Kadota A., Kondo K., Hirata T., Higashiyama A., Hayakawa T., Miyamoto Y., Okayama A., Miura K., Ueshima H.

American Journal of Cardiology (American Journal of Cardiology) 184 1 - 6 2022

ISSN 00029149

The relation between chronic kidney disease (CKD) and cardiovascular disease (CVD) in the general population is well elucidated. In patients with CKD, anemia is associated with adverse outcomes. However, the effects of CKD and anemia on CVD in the general population remains poorly explored, especially in Asian populations. This study aimed to investigate the effect of CKD and/or anemia on CVD mortality in a long-term cohort study involving Japanese community dwellers. We assessed 7,339 participants (aged ≥30 years) with no CVD history. These participants were divided into 4 categories according to their CKD (estimated glomerular filtration rate <60 or urine protein >1+ by dipstick qualitative test) and/or anemia (hemoglobin: <13 g/100 ml [men], <12 g/100 ml [women]) statuses. For each category, we calculated the hazard ratios (HRs) of CVD mortality by using the Cox proportional hazards model after adjusting for age, body mass index, hypertension, diabetes, dyslipidemia, smoking, and alcohol drinking. Within 25 years of follow-up, 637 participants died because of CVD. The HRs of CVD in patients with CKD only, anemia only, and both were 1.27, 1.59, and 2.60 (95% confidence intervals [CI] 1.06 to 1.53, 1.34 to 1.90, and 1.80 to 3.76) in men and 1.42, 1.08, and 2.00 (95% CI 1.19 to 1.69, 0.99 to 1.18, and 1.54 to 2.60) in women, respectively. In conclusion, CKD with anemia is associated with an increased risk for CVD mortality in a general population in Japan.

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Lifestyle behaviors associated with the initiation of renal replacement therapy in Japanese patients with chronic kidney disease: a retrospective cohort study using a claims database linked with specific health checkup results

Hara A., Hirata T., Okamura T., Kimura S., Urushihara H.

Environmental Health and Preventive Medicine (Environmental Health and Preventive Medicine) 26 ( 1 ) 102 2021.12

Research paper (scientific journal), ISSN 1342078X

Background: Chronic kidney disease (CKD) is an independent risk factor for progression to an end-stage renal disease requiring dialysis or kidney transplantation. We investigated the association of lifestyle behaviors with the initiation of renal replacement therapy (RRT) among CKD patients using an employment-based health insurance claims database linked with specific health checkup (SHC) data. Methods: This retrospective cohort study included 149,620 CKD patients aged 40–74 years who underwent a SHC between April 2008 and March 2016. CKD patients were identified using ICD-10 diagnostic codes and SHC results. We investigated lifestyle behaviors recorded at SHC. Initiation of RRT was defined by medical procedure claims. Lifestyle behaviors related to the initiation of RRT were identified using a Cox proportional hazards regression model with recency-weighted cumulative exposure as a time-dependent covariate. Results: During 384,042 patient-years of follow-up by the end of March 2016, 295 dialysis and no kidney transplantation cases were identified. Current smoking (hazard ratio: 1.87, 95% confidence interval, 1.04─3.36), skipping breakfast (4.80, 1.98─11.62), and taking sufficient rest along with sleep (2.09, 1.14─3.85) were associated with the initiation of RRT. Conclusions: Among CKD patients, the lifestyle behaviors of smoking, skipping breakfast, and sufficient rest along with sleep were independently associated with the initiation of RRT. Our study strengthens the importance of monitoring lifestyle behaviors to delay the progression of mild CKD to RRT in the Japanese working generation. A substantial portion of subjects had missing data for eGFR and drinking frequency, warranting verification of these results in prospective studies.

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

Imai Y, Mizuno Tanaka S, Satoh M, Hirata T, Murakami Y, Miura K, Waki T, Hirata A, Sairenchi T, Irie F, Sata M, Ninomiya T, Ohkubo T, Ishikawa S, Miyamoto Y, Ohnishi H, Saitoh S, Tamakoshi A, Yamada M, Kiyama M, Iso H, Sakata K, Nakagawa H, Okayama A, Ueshima H, Okamura T, Evidence for Cardiovascular Prevention From Observational Cohorts in Japan (EPOCH‐Japan) Research Group *.

Journal of the American Heart Association (Journal of the American Heart Association) 10 ( 23 ) e021753 2021.11

Research paper (scientific journal)

BACKGROUND: Lifetime risk is an informative estimate for driving lifestyle and behavioral changes especially for young adults. The impact of composite risk factors for cardiovascular disease on lifetime risk stratified by sex has not been investigated in the Japanese population, which has a much lower mortality of coronary heart disease compared with the Western population. We aimed to estimate lifetime risk of death from cardiovascular disease attributable to traditional risk factors. METHODS AND RESULTS: We analyzed pooled individual data from the Evidence for Cardiovascular Prevention from Observational Cohorts in a Japanese cohort study. A modified Kaplan– Meier approach was used to estimate the remaining lifetime risk of cardiovascular death. In total, 41 002 Japanese men and women with 537 126 person-years of follow-up were included. The lifetime risk at the index-age of 45 years for those with optimal risk factors (total cholesterol <4.65 mmol/L, systolic blood pressure <120 mm Hg, diastolic blood pressure <80 mm Hg, absence of diabetes, and absence of smoking habit) was lower compared with the highest risk profile of ≥2 risk factors (6.8% [95% CI, 0%–11.9%] versus 19.4% [16.7%– 21.4%] for men and 6.9% [1.2%–11.5%] versus 15.4% [12.6%–18.1%] for women). CONCLUSIONS: The magnitude and the number of risk factors were progressively associated with increased lifetime risk even in individuals in early adulthood who tend to have low short-term risk. The degree of established cardiovascular risk factors can be converted into lifetime risk. Our findings may be useful for risk communication in the early detection of future cardiovascular disease risk.

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Risk Classification for Metabolic Syndrome and the Incidence of Cardiovascular Disease in Japan With Low Prevalence of Obesity: A Pooled Analysis of 10 Prospective Cohort Studies.

Iso H, Cui R, Takamoto I, Kiyama M, Saito I, Okamura T, Miyamoto Y, Higashiyama A, Kiyohara Y, Ninomiya T, Yamada M, Nakagawa H, Sakurai M, Shimabukuro M, Higa M, Shimamoto K, Saito S, Daimon M, Kayama T, Noda M, Ito S, Yokote K, Ito C, Nakao K, Yamauchi T, Kadowaki T

Journal of the American Heart Association (Journal of the American Heart Association) 10 ( 23 ) e020760 2021.11

Research paper (scientific journal)

BACKGROUND: It is uncertain whether risk classification under the nationwide program on screening and lifestyle modification for metabolic syndrome captures well high-risk individuals who could benefit from lifestyle interventions. We examined the validity of risk classification by linking the incidence of cardiovascular disease (CVD). CONCLUSIONS: Similar CVD excess and attributable risks among individuals with metabolic syndrome components in the absence and presence of obesity/overweight imply the need for lifestyle modification in both high-risk groups. METHODS AND RESULTS: Individual-level data of 29 288 Japanese individuals aged 40 to 74 years without a history of CVD from 10 prospective cohort studies were used. Metabolic syndrome was defined as the presence of high abdominal obesity and/ or overweight plus risk factors such as high blood pressure, high triglyceride or low high-density lipoprotein cholesterol levels, and high blood glucose levels. The risk categories for lifestyle intervention were information supply only, motivation-support intervention, and intensive support intervention. Sex-and age-specific hazard ratios and population attributable fractions of CVD, which were also further adjusted to consider non– high density lipoprotein cholesterol levels, were estimated with reference to nonobese/overweight individuals, using Cox proportional hazard regression. Since the reference category included those with risk factors, we set a supernormal group (nonobese/overweight with no risk factor) as another reference. We documented 1023 incident CVD cases (565 men and 458 women). The adjusted CVD risk was 60% to 70% higher in men and women aged 40 to 64 years receiving an intensive support intervention, and 30% higher in women aged 65 to 74 years receiving a motivation-support intervention, compared with nonobese/overweight individuals. The population attributable fractions in men and women aged 40 to 64 years receiving an intensive support intervention were 17.7% and 6.6%, respectively, while that in women aged 65 to 74 years receiving a motivation-support intervention was 9.4%. Compared with the supernormal group, nonobese/overweight individuals with risk factors had similar hazard ratios and population attributable fractions as individuals with metabolic syndrome.

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Changes in smoking habits and behaviors following the introduction and spread of heated tobacco products in Japan and its effect on FEV<sub>1</sub> decline: a longitudinal cohort study.

Harada S, Sata M, Matsumoto M, Iida M, Takeuchi A, Kato S, Hirata A, Kuwabara K, Shibuki T, Ishibashi Y, Sugiyama D, Okamura T, Takebayashi T

Journal of epidemiology (Journal of epidemiology) 32 ( 4 ) 180 - 187 2021.10

Research paper (scientific journal), ISSN 0917-5040

BACKGROUND: Heated tobacco product (HTP) use in Japan has rapidly increased. Despite this rapid spread, little is known about the health effects of HTP use. We conducted a longitudinal cohort study to investigate the change in smoking habits following the spread of HTP use and its effect on forced expiratory volume in 1 second (FEV1) decline. METHODS: Participants consisted of a resident population (n = 2,612; mean age, 67.7 years) with FEV1 measurement in 2012-2014 and 2018-2019, and a worksite population (n = 722; mean age 49.3 years) without FEV1 data. Participants were categorized as combustible cigarette-only smokers, HTP-only users, dual users, past smokers, and never smokers. The association between smoking group and the change in smoking consumption over a mean 5.6 years was examined. Differences in annual FEV1 change between smoking groups were examined in the resident population. RESULTS: Prevalence of HTP-only and dual users in 2018-2019 was 0.8% and 0.6% in the resident population, and 5.0% and 1.9% in the worksite population, respectively. The overall number of tobacco products smoked/used increased in dual users compared to baseline, but not in others. Annual FEV1 decline in dual users tended to be greater than that in cigarette-only smokers (16; 95% confidence interval, -34 to 2 mL/year after full adjustment). Participants switching to HTP-only use 1.7 years before had a similar FEV1 decline as cigarette-only smokers. CONCLUSIONS: HTP use, including dual use, is prevalent even in a rural region of Japan. Dual users appear to smoke/use tobacco products more and have a greater FEV1 decline. Tobacco policy should consider dual use as high-risk.

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