Details of a Researcher - Okamura, Tomonori

Papers - Okamura, Tomonori

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[Determinants of salt taste threshold among urban residents: the KOBE study].

Wakako M, Sata M, Kubota Y, Nishida Y, Kubo S, Higashiyama A, Hirata T, Kadota A, Hirata A, Miyazaki J, Kawahara M, Kuwabara K, Sugiyama D, Miyamatsu N, Miyamoto Y, Okamura T

[Nihon koshu eisei zasshi] Japanese journal of public health 70 ( 5 ) 300 - 310 2023.02

ISSN 0546-1766

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Association between proprotein convertase subtilisin/kexin type 9 (PCSK9) and subclinical cerebrovascular disease in the community.

Kunimura A, Yano Y, Hisamatsu T, Torii S, Kondo K, Kadota A, Fujiyoshi A, Okamura T, Watanabe Y, Shiino A, Nozaki K, Ueshima H, Miura K, SESSA research group

European journal of neurology (European Journal of Neurology) 30 ( 5 ) 1327 - 1334 2023.02

ISSN 1351-5101

Background and purpose: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new target for reducing low-density lipoprotein cholesterol and incident cardiovascular disease, including stroke. However, the clinical relevance of circulating PCSK9 levels has been poorly elucidated in the general population, particularly in association with subclinical cerebrovascular disease including cerebral small vessel disease (CSVD) and intracranial artery stenosis (ICAS). Methods: In community-dwelling Japanese men (n = 526) aged 46–82 years without a history of cardiovascular disease, the associations of serum PCSK9 levels with the prevalence of CSVD and ICAS were assessed using magnetic resonance imaging. CSVD included lacunar infarction, deep and subcortical white matter hyperintensity, periventricular hyperintensity and cerebral microbleeds. Results: The median (interquartile range) age at baseline and serum PCSK9 levels were 69 (63–74) years and 240 (205–291) ng/ml, respectively. After adjusting for traditional cardiovascular risk factors including low-density lipoprotein cholesterol, multivariable Poisson regression with robust error variance revealed a significant association between PCSK9 levels (per 1 SD) and ICAS (relative risks 1.18, 95% confidence interval 1.02–1.37). Multivariable ordinal logistic regression for ICAS, with stenosis graded as mild (<50%) or moderate–severe (≥50%), revealed a similar association (common odds ratio 1.31, 95% confidence interval 1.04–1.64). However, no significant association was observed between serum PCSK9 levels and CSVD. Conclusions: Higher circulating PCSK9 levels were independently associated with an ICAS prevalence but not with CSVD prevalence. The quantification of circulating PCSK9 levels may help to identify individuals at high risk for cerebrovascular disease in the general population.

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The association between sleep parameters and sarcopenia in Japanese community-dwelling older adults.

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

Archives of gerontology and geriatrics (Archives of Gerontology and Geriatrics) 109 104948 2023.01

ISSN 0167-4943

Purpose: This study aimed to examine the association between sleep duration and quality and sarcopenia, assessed by factors such as low muscle mass (LMM), low muscle strength (LMS), and low physical performance (LPP) among older community-dwellers in Japan. Methods: In this cross-sectional study, a total of 2,069 (men, 902; women, 1,167) participants aged 65 to 80 years were included. Sarcopenia and each low physical function were defined using the definitions of the Asian Working Groups of Sarcopenia 2019. Sleep duration was stratified into three categories: short sleep (<6 h), normal sleep (6-8 h), and long sleep (>8 h). Sleep quality was classified into two groups based on 8-item Athens Insomnia Scale score: insomnia (≥6), and non-insomnia (<6). We analyzed the association between sleep parameters and sarcopenia, including low physical functions, by logistic regression analysis. Results: Compared to normal sleepers, long sleepers had a positive association with sarcopenia (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.25-3.58). In particular, long sleep was strongly associated with LMS (OR 1.77, 95%CI 1.07-2.94) and LPP (OR 1.90, 95%CI 1.25-2.88). On the other hand, poor sleep quality was not associated with sarcopenia in long sleepers, but in normal sleepers. Conclusions: Long sleep was associated with sarcopenia, including LMS and LPP. However, in long sleepers, insomnia was not associated with sarcopenia or any of its components.

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Fatty liver index predicts the development of hypertension in a Japanese general population with and without dysglycemia.

Wu D, 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 ( 4 ) 879 - 886 2023.01

ISSN 0916-9636

Fatty liver has been suggested to be associated with the development of hypertension. However, whether this association is related to glycemia has not been elucidated. Therefore, we investigated whether the fatty liver index (FLI) predicts the development of hypertension among individuals with and without dysglycemia in a general Japanese population. A total of 3114 participants (1036 males and 2078 females) without hypertension who underwent a Specific Health Checkup in the fiscal year 2013 were followed up until 2018. The participants were divided into six groups based on FLI tertiles (low, moderate, or high) and whether they had dysglycemia. We estimated the hazard ratios (HRs) of each group by sex using the Cox proportional hazard model. Models were adjusted for age, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, smoking, and alcohol consumption and further adjusted for systolic blood pressure (SBP). During the mean follow-up period of 2.8 years, 160 of the 3114 participants developed hypertension. Using the low FLI group with normoglycemia as a reference, the HR for incident hypertension was increased in the high FLI group with and without dysglycemia in both sexes after adjusting for confounders, except SBP (HR [95% confidence interval]: male: 1.52 (1.06–2.17) in normoglycemia and 2.05 (1.43–2.92) in dysglycemia, and female: 1.86 (1.43–2.42) in normoglycemia and 2.98 (2.19–4.07) in dysglycemia). Furthermore, in females, this association was observed after adjusting for SBP. We concluded that FLI was independently associated with an increased risk of incident hypertension in individuals with and without dysglycemia. [Figure not available: see fulltext.].

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Offering on-site mammography in workplaces improved screening rates: Cluster randomized controlled trial.

Shima A, Tanaka H, Okamura T, Nishikawa T, Morino A, Godai K, Tatsumi Y, Kawahara M, Kiyohara M, Kawatsu Y, Kimura T, Miyamatsu N

Journal of occupational health (Journal of occupational health) 65 ( 1 ) e12389 2023.01

ISSN 1341-9145

OBJECTIVES: Despite evidence of breast cancer screening efficacy, the screening rate has remained less than 50% in Japan. This study aimed to evaluate the effect of an environmental approach offering on-site mammography in workplaces. METHODS: Supermarket stores were randomly assigned into two groups, the intervention group (leaflet and mammography) and the control group (leaflet). From May to July 2018, participants in the intervention group were given a leaflet informing them of the subsidies for breast cancer screening and offered the opportunity to have mammography in their workplaces. Participants in the control group were given the same leaflet, but had to arrange their own screening outside the workplace. The primary outcome was the breast cancer screening rate in 2018. The odds ratio (OR) and 95% confidence interval (CI) for having screening in the intervention group compared with the control group were estimated using multilevel logistic regression. RESULTS: We analyzed data from 1624 participants (mean age 53 years) from 25 supermarket stores (intervention: 8 stores, control: 17 stores). Among participants who had not attended screening in the previous year, the screening rate was 7% in the control group and 53% in the intervention group, with an adjusted OR (95% CI) of 14.22 (8.97-22.54). The effect was greater in those who had never attended screening before. CONCLUSION: In a worksite-based cluster randomized controlled trial in Japanese supermarket stores, an environmental approach offering mammography in workplaces substantially increased the breast cancer screening rate within 1 year (UMIN000030465).

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Determinants of double product: a cross-sectional study of urban residents in Japan.

Nakagoshi N, Kubo S, Nishida Y, Kuwabara K, Hirata A, Sata M, Higashiyama A, Kubota Y, Hirata T, Tatsumi Y, Kawamura K, Miyazaki J, Miyamatsu N, Sugiyama D, Miyamoto Y, Okamura T

Environmental health and preventive medicine (Environmental Health and Preventive Medicine) 28 ( 1 ) 37 2023

ISSN 1342-078X

Background: The current study aimed to investigate the determinants of high double product (DP) by evaluating the association between resting DP, which is calculated as systolic blood pressure (SBP) multiplied by heart rate (HR), and blood test results and lifestyle factors. Methods: This research included 973 participants in the baseline survey of the KOBE study, which included a cohort of urban residents. The possible DP determinants were identified by examining the association between lifestyle factors and laboratory findings and DP by analyzing covariance adjusted for sex and age. Logistic regression analysis was performed with high DP (SBP © HR ² 9145 mmHg beats/min or quintile according to sex) as outcome and DP determinants as independent variables. Results: Age, hematocrit, and gamma-glutamyl transferase (log) level were positively associated with a high DP in both men and women. In addition, a high DP was positively associated with Homeostatic Model Assessment for Insulin Resistance score in women alone. Meanwhile, the amount of exercise was negatively associated with a high DP in men alone. Conclusions: High DP values at rest were associated with insulin resistance, gamma-glutamyl transferase, and the amount of exercise in participants without underlying disease.

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Correction to: Determinants of double product: a cross-sectional study of urban residents in Japan.

Nakagoshi N, Kubo S, Nishida Y, Kuwabara K, Hirata A, Sata M, Higashiyama A, Kubota Y, Hirata T, Tatsumi Y, Kawamura K, Miyazaki J, Miyamatsu N, Sugiyama D, Miyamoto Y, Okamura T

Environmental health and preventive medicine 28 74 2023

ISSN 1342-078X

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Predicting habitual water intake from lifestyle questions

Tanaka H., Mizuma K., Nakamura Y., Hirata A., Miyazaki J., Suzuki K., Seta H., Watanabe H., Suzuki T., Watanabe R., Murayama N., Okamura T., Nakamura S.

European Review for Medical and Pharmacological Sciences (European Review for Medical and Pharmacological Sciences) 27 ( 18 ) 8829 - 8841 2023

ISSN 11283602

– OBJECTIVE: Previous studies have used selective recall and descriptive dietary record methods, requiring considerable effort for assessing food and water intake. This study created a simplified lifestyle questionnaire to predict habitual water intake (SQW), accurately and quickly assessing the habitual water intake. We also evaluated the validity using descriptive dietary records as a cross-sectional study. SUBJECTS AND METHODS: First, we used crowdsourcing and machine learning to collect data, predict water intake records, and create questionnaires. We collected 305 lifestyle-related questions as predictor variables and selective recall methods for assessing water intake as an outcome variable. Random forests were used for the machine learning models because of their interpretability and accurate estimation. Random forest and single regression correlation analysis were augmented by the synthetic minority oversampling that trained the model. We separated the data by sex and evaluated our model using unseen hold-out testing data, predicting the individual and overall habitual water intake from various sources, including non-alcoholic beverages, alcohol, and food. RESULTS: We found a 0.60 Spearman’s correlation coefficient for total water intake between the predicted and the selective recall method values, reflecting the target value to be achieved. This question set was then used for feasibility tests. The descriptive dietary record method helped to obtain a ground-truth value. We categorized the data by gender, season, and source: non-alcoholic beverages, alcohol, food, and total water intake, and the correlation was confirmed. Consequently, our results showed a Pearson’s correlation coefficient of 0.50 for total water intake between the predicted and the selective recall method values. CONCLUSIONS: We hypothesize that dissemination of SQW can lead to better health management by easily determining the habitual water intake.

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Dietary Factors, Dietary Patterns, and Cardiovascular Disease Risk in Representative Japanese Cohorts: NIPPON DATA80/90.

Kondo K, Miura K, Okamura T, Okayama A, Ueshima H, NIPPON DATA80/90 Research Group

Journal of atherosclerosis and thrombosis (Journal of atherosclerosis and thrombosis) 30 ( 3 ) 207 - 219 2022.11

ISSN 1340-3478

Diet is one of the most important factors affecting healthy life expectancy through the onset of cardiovascular disease (CVD) risk as well as various chronic diseases. Because dietary habits and disease structure differ depending on the country, region, and/or race, evidence from each population is required. NIPPON DATA80/90 is a long-term cohort study of a representative Japanese population that participated in national nutrition surveys. Among the many findings of this cohort study, a dietary pattern with higher intake of fruits, vegetables, fish (n-3 polyunsaturated fatty acids), and dietary fiber and lower intake of salt as well as sodium-to-potassium ratio was found to be associated with a lower risk of CVD mortality. The results from our cohort study would be useful for effectively preventing CVD. This article reviews the published studies from the NIPPON DATA80/90 to highlight the significant findings that may be used to develop risk prevention strategies for CVD.

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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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