Published papers

© 2020 Elsevier Inc. The clinical implications of alcohol consumption have been extensively examined; however, its effects on brain structures in apparently healthy community-dwellers remain unclear. Therefore, we investigated the relationship between alcohol consumption and brain gray matter volume (GMV) in community-dwelling Japanese men using voxel-based morphometry (VBM). We recruited cognitively intact Japanese men, aged 40–79 years, from a population-based cohort in Shiga, Japan. Brain magnetic resonance imaging was performed, on average, 2 years after demographic and medical information was obtained in 2010–2014. A multivariable linear regression analysis of 639 men was conducted to elucidate the relationship between the amount of alcohol consumed and GMV. VBM statistics were analyzed by threshold-free cluster enhancement with a family-wise error rate of <0.05. The results obtained demonstrated that the amount of alcohol consumed was associated with lower GMV. The VBM analysis showed lower GMV within the parahippocampal, entorhinal, cingulate, insular, temporal, and frontal cortices and cerebellum in very heavy drinkers (≥42 ethanol g/day) than in non-drinkers. Furthermore, alcohol consumption was associated with a higher white matter lesion volume. These results suggest subclinical structural changes similar to alcohol-related neurological diseases.

Background: Healthy life expectancy (HLE) is a population health indicator that is widely used in developed countries, but little is known about its relationships with combinations of non-communicable disease risk factors. This study was conducted to examine HLE at age 65 years according to combinations of blood pressure levels, body mass index, smoking status, and diabetes mellitus (DM) in a Japanese population. Methods: In a nationwide cohort study (NIPPON DATA90), data on these risk factors were obtained from participants in 1990 through physical examinations, blood tests, interviews, and questionnaires. Subsequently, participants aged ≥65 years underwent surveys on activities of daily living in 1995 and 2000, and multistate life tables were used to calculate combination-specific HLEs and their 95% confidence intervals (CIs). Results: The study population comprised 6,569 participants (men: 2,797; women: 3,772) who were followed until 2010. HLE at age 65 years in men with grade II/III hypertension, obesity, current smoker status, and DM (HLE 12.9; 95% CI, 12.9–13.0 years) was 9.7 years shorter than men without these risk factors (HLE 22.6; 95% CI, 22.4–22.8 years). Similarly, HLE at age 65 years in women with grade II/III hypertension, obesity, current smoker status, and DM (HLE 16.2; 95% CI, 15.9–16.5 years) was 10.1 years shorter than women without these risk factors (HLE 26.3; 95% CI, 26.3–26.3 years). Conclusion: The large discrepancies in HLEs underscore the impact of non-communicable disease risk factors, which should be considered when formulating health interventions to improve HLE in Japanese older adults.

Aims: Long-term exposure to fine particulate matter (PM2.5) is causally associated with mortality and cardiovascular disease. However, in terms of cardiovascular cause-specific outcomes, there are fewer studies about stroke than about coronary heart disease, particularly in Asia. Furthermore, there remains uncertainty regarding the PM2.5-respiratory disease association. We examined whether long-term exposure to PM2.5 is associated with all-cause, cardiovascular and respiratory disease mortality in Japan. Methods: We used data of 46,974 participants (19,707 men; 27,267 women), who were enrolled in 2009 and followed up until 2019, in a community-based prospective cohort study (the second cohort of the Ibaraki Prefectural Health Study). We estimated PM2.5 concentrations using the inverse distance weighing methods based on ambient air monitoring data, and assigned each participant to administrative area level concentrations. A Cox proportional hazard model was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality. Results: During the average follow-up of 10 years, we confirmed 2,789 all-cause deaths. All outcomes including stroke mortality did not significantly increase as the PM2.5 concentration increased. For non-malignant respiratory disease mortality, the multivariable adjusted HR per 1 µg/m3 increase in the PM2.5 concentration was 1.09 (95% CI = 0.97–1.23). Conclusions: In this population exposed to PM2.5 at concentrations of 8.3–13.1 µg/m3, there was no evidence that long-term exposure to PM2.5 had adverse effects on mortality. Weak evidence of positive association observed for non-malignant respiratory disease mortality needs further studies in other populations.

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.

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.

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

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.

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.

Stay-at-home strategies taken during the COVID-19 pandemic changed our lifestyle drastically. Although marital status and household size are important social determinants of health that affect lifestyle, their impacts on lifestyle during the pandemic are still unclear. We aimed to evaluate the association between marital status, household size, and lifestyle changes during the first pandemic in Japan. Questionnaire surveys on lifestyle changes from before to during the first COVID-19 pandemic were conducted on October 2020 in Japan. Classified into age groups, multivariable logistic regression analysis was performed to examine the combined association of marital status and household size on lifestyle, adjusted for potential confounders including socioeconomic factors. In our prospective cohort study, 1928 participants were included. Among older participants, the singles living alone were likely to perceive more unhealthy lifestyle changes (45.8%), compared with the married (33.2%), and significantly associated with at least one unhealthy change [adjusted odds ratio (OR): 1.81, 95% confidence interval (CI): 1, 18-2.78], mainly due to decreased physical activity and increased alcohol consumption. Meanwhile, the younger participants showed no significant association between marital status, household size, and unhealthy changes, while those living alone had 2.87 times higher odds of weight gain (≥ 3 kg) than the married (adjusted OR: 2.87, 95% CI: 0.96-8.54) during the pandemic. Our findings suggest that older singles living alone are potentially vulnerable subgroups to drastic social changes which warrant special attention to prevent adverse health outcomes and additional burden on health systems in the following future.

© 2021, Japan Atherosclerosis Society. All rights reserved. Aim: To examine the association between long-term exposure to suspended particulate matter (SPM) and cardiovascular mortality in Japan after controlling for known major confounding factors among a large middle and elderly cohort study in Ibaraki Prefecture, Japan. Methods: We followed 91,808 residents (men 34%) who undertook a national health check-up at age 40–79 years for 17 years (1993–2010). Two different exposure indices were adopted: baseline SPM concentration (in the year 1990) and average SPM concentration for the first (average of 1990 and 1995) and the second half (average of 2005 to 2009) of the study period. Sex-specific adjusted risk ratios (RRs) for cardiovascular mortality were calculated using general mixed Poisson regression models after adjusting the age, BMI, history of diabetes mellitus and hypertension, creatinine, glutamic pyruvic transaminase, total cholesterol, high-density lipoprotein cholesterol, smoking, alcohol, and temperature. The variation between seven medical administration areas was also taken into account as a random effect. Results: Baseline SPM concentration was associated with an increased risk of mortality from all cardiovascular diseases, coronary artery disease, and stroke. The adjusted RRs (95% confidence interval [CI]) per 10 µg/m3 increase in SPM concentration for all cardiovascular mortality were 1.147 (1.014–1.300) for men and 1.097 (0.985–1.222) for women. The point estimate of RR was highest for non-hemorrhagic stroke in men (1.248 [0.991–1.571]), although CI overlapped the unity. The RRs seemed slightly lower in the second half than in the first half, though the CIs widened in the second half. Conclusion: Our results suggest that long-term exposure to SPM is associated with an increased risk of all cardiovascular mortality for men in Ibaraki, Japan.

Background: Lower socioeconomic status (SES) may be related to inactivity lifestyle; however, the association between SES and physical inactivity has not been sufficiently investigated in Japan. Methods: The study population is the participants of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey 2010 in Japan. They were residents in 300 randomly selected areas across Japan. This study included 2,609 adults. Physical activity was assessed by physical activity index (PAI) calculated from activity intensity and time. The lowest tertile of PAI for each 10-year age class and sex was defined as physical inactivity. Multivariable logistic regression analyses were conducted to examine the association of SES (employment status, educational attainment, living status, and equivalent household expenditure (EHE)) with physical inactivity. Results: In the distribution of PAI by age classes and sex, the highest median PAI was aged 30-39 years among men (median 38.6), aged 40-49 years among women (38.0), and median PAI was decreased with increasing age. Multivariable-adjusted model shows that not working was significantly associated with physical inactivity after adjustment for age in all age groups and sexes. Not living with spouse for adult women and elderly men was significantly associated with physical inactivity compared to those who living with spouse. However, neither educational attainment nor EHE had any significant associations with physical inactivity. Conclusions: The result indicated that physical inactivity was associated with SES in a general Japanese population. SES of individuals need to be considered in order to prevent inactivity lifestyle.

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.

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.

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.

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

In Japan, trends in mortality and lifestyle have not been fully investigated according to subnational socioeconomic factors. Forty-seven prefectures (subnational units) were divided into quartiles by annual per capita prefectural income. Age-standardized mortality from all causes, cancer, heart disease, and stroke was averaged by quartile in 1995, 2000, 2005, 2010, and 2015. Data from the National Health and Nutrition Survey were obtained for periods 1 (1995–1997), 2 (1999–2001), 3 (2003–2005), 4 (2007–2009), 5 (2012), and 6 (2016). Body mass index (BMI), the intake of vegetables and salt, the number of steps, and the prevalence of current smoking and drinking for the 40–69-year age range were standardized by 10-year age groups in the 2010 Japanese population and were averaged by quartile. Differences in mortality and lifestyle by year and period, and quartile were tested using a two-way analysis of variance. Mortality decreased in both sexes and mortality in men from all causes, cancer, and stroke differed by quartile, with mortality highest in the first (lowest) quartile. BMI in men and smoking prevalence in women increased, whereas remaining lifestyle factors except for the prevalence of drinking decreased in women. BMI and the number of steps in both sexes and current smoking prevalence in women differed by quartile, with lower quartiles showing a higher BMI and fewer step counts. In conclusion, favorable trends and significant differences in mortality from all causes, cancer, and stroke in men and BMI in women were observed by per capita prefectural income level.

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.

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.