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Background:Risk factors for atherosclerotic disease including dyslipidemia have been shown to be associated with aortic valve calcification (AVC). Nuclear magnetic resonance (NMR)-measured lipoprotein particles, low-density and high-density lipoprotein particles (LDL-p, HDL-p) in particular, have emerged as novel markers of atherosclerotic disease; however, whether NMR-measured particles are associated with AVC remains to be determined. This study aimed to examine the association between NMR-based lipoprotein particle measurements and standard lipids with AVC. The primary variables of interest were LDL-p (nmol/L), HDL-p (μmol/L), LDL-cholesterol, and HDL-cholesterol (both in mg/dL).Methods and Results:A community-based random sample of Japanese men aged 40-79 years examined in 2006-2008, in Shiga, Japan was studied. Presence of AVC was defined as an Agatston score >0. Lipoprotein particles were measured using NMR spectroscopy. In the main analysis, multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for the prevalence of AVC across the higher quartiles of lipids in reference to the lowest ones were obtained. Of 874 participants analyzed, 153 men had AVC. Multivariable-adjusted ORs of prevalent AVC for the highest vs. the lowest quartile were significantly elevated for LDL-p (OR, 2.20; 95% CI: 1.23-3.93) and LDL-cholesterol (OR, 2.16; 95% CI: 1.23-3.78). In contrast, neither HDL-p nor HDL-cholesterol was associated with AVC., Conclusions:The association of prevalent AVC with NMR-based LDL-p was comparable to that with LDL-cholesterol.

Background: To investigate the association between step counts and brain volumes (BVs)—global and 6a prioriselected cognition-related regions of interest—in Japanese men aged 40–79 years.Methods: The authors analyzed data from 680 cognitively intact participants of the Shiga Epidemiological Study of Subclinical Atherosclerosis—a population-based observational study. Using multivariable linear regression, the authors assessed cross-sectional associations between 7-day step counts at baseline (2006–2008) and BVs at follow-up (2012–2015) for age-stratified groups (Results: In the older adults ≥60 years, step counts at baseline (per 1000 steps) were associated with total BV at follow-up (β = 1.42,P = .022) while adjusted for potential covariates. Regions of interest-based analyses yielded an association of step counts with both prefrontal cortexes (P P = .05). No association was observed with hippocampus, parahippocampal, cingulum, and cerebellum. No association was observed in younger adults (Conclusions: The authors found a positive association between 7-day step counts and BVs, including prefrontal cortexes, and left entorhinal cortex in apparently healthy Japanese men.

Several studies have reported a J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk. However, the mechanisms of this relationship remain unclear. This study aimed to evaluate the relationships of alcohol consumption with established CHD risk factors and with macro-/micro-nutrient intake among Japanese people. Participants were 1,090 Japanese men and women aged 40-59 y enrolled in the INTERLIPID study, excluding former drinkers. Based on two 7-d alcohol records, participants were classified as non-drinkers (0 g/wk), light-drinkers (

Background and purpose:Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association between step counts and CSVD in a healthy Japanese male population., Methods:We analyzed data from 680 men who were free of stroke and participated in this observational study. Seven-day step counts were assessed at baseline (2006-2008) using a pedometer. CSVD was assessed at follow-ups (2012-2015) based on deep and subcortical white matter hyperintensities (WMHs), periventricular hyperintensities, lacunar infarcts, and cerebral microbleeds on magnetic resonance imaging. Using a logistic regression analysis, we computed the adjusted odds ratios, with 95% CIs, of prevalent CSVD according to quartiles of step counts (reference: Q1). We also investigated the association between step counts and WMH volumes using a quantile regression., Results:Steps per day were significantly associated with lower odds ratios, with the lowest at Q3 (8175-10 614 steps/day), of higher (versus low or no burden) deep and subcortical WMHs (odds ratio, 0.52 [95% CI, 0.30-0.89]), periventricular hyperintensities (0.50 [95% CI, 0.29-0.86]), and lacunar infarcts (0.52 [95% CI, 0.30-0.91]) compared with Q1 (≤6060 steps/day) but not cerebral microbleeds. An inverse linear association was observed between step counts and WMH volumes. These associations were independent of age and smoking and drinking status and remained consistent when adjusted for vascular risk factors., Conclusions:We found a J-shaped relationship between step counts and prevalent CSVD in healthy Japanese men, with the lowest risk being observed among participants with ≈8000 to 10 000 steps/day. Higher steps were also associated with lower WMH volumes.

Background and aims Dysfunctional high-density lipoprotein (HDL) is a risk factor for cardiovascular disease (CVD) beyond HDL concentrations. Recently, a novel method has been introduced to measure LOX-1 ligand containing apolipoprotein AI (LAA), which is an indicator of various types of modified HDL with binding capacity to LOX-1 and related to impaired anti-atherogenic functions of HDL. This study aimed to examine the relationship between LAA as a novel marker of dysfunctional HDL and coronary artery calcification (CAC). Methods We selected 910 community-dwelling Japanese men aged 40–79 years without a history of CVD. The odds ratios per 1SD of LAA for the presence of CAC (Agatston score >10) were estimated using logistic regression model adjusted for confounders, including HDL-C or HDL particle (HDL-P) concentration. In addition, we performed further analysis stratified by age ( Results The mean age of the participants was 63.6 years, and the median LAA was 187.0 ng/mL. The prevalent CAC was 46.2%. The multivariable adjusted odds ratio (95% confidence interval) per 1SD of LAA for CAC was 1.14 (0.96–1.36) for all participants. After stratification by age, multivariable adjusted odds ratios per 1SD of LAA were 1.34 (1.02–1.76) and 0.97 (0.77–1.23) in men aged Conclusions The present study showed that LAA was associated with CAC independent of HDL-C or HDL-P in middle-aged Japanese men. This finding suggests that LAA might be an early marker for CVD events. Future longitudinal studies are warranted.

Objective:The prognostic implication of isolated systolic hypertension (ISH), defined as SBP at least 140 mmHg and DBP less than 90 mmHg, among young-to-middle-aged adults remains controversial. We examined the association of ISH with cardiovascular disease (CVD) risk in adults aged 30-49 years., Methods:In a prospective cohort of representative Japanese general populations from the NIPPON DATA80 (1980-2009), we studied 4776 participants (mean age, 39.4 years; 55.4% women) without clinical CVD or antihypertensive medication. Participants were classified as follows: normal blood pressure (BP) (SBP/DBP, Results:ISH was observed in 389 (8.1%) participants. During the 29-year follow-up, 115 participants died of CVD, 28 of coronary heart disease, and 49 of stroke. Cox proportional hazards models adjusted for demographics and CVD risk factors showed that participants with ISH had higher risk of CVD mortality than those with normal BP [hazard ratio (confidence interval), 4.10 (1.87-9.03)]. The magnitude of CVD mortality risk related to ISH was comparable with that related to IDH [3.38 (1.31-8.72)] and not as great as that related to SDH [5.41 (2.63-11.14)]. We found significant associations of ISH with coronary and stroke mortality. The association of ISH with CVD mortality was consistent across men and women and those aged 30-39 and 40-49 years., Conclusion:ISH among young-to-middle-aged Japanese adults was independently associated with higher risk of CVD mortality later in life.

Background and aims: To examine whether smoking habits, including smoking amount and cessation duration at baseline, are associated with atherosclerosis progression., Methods: At baseline (2006-08, Japan), we obtained smoking status, amount of smoking and time since cessation for quitters in a community-based random sample of Japanese men initially aged 40-79 years and free of cardiovascular disease. Coronary artery calcification (CAC) and aortic artery calcification (AAC) as biomarker of atherosclerosis was quantified using Agatston's method at baseline and after 5 years of follow-up. We defined progression of CAC and AAC (yes/no) using modified criteria by Berry., Results: A total of 781 participants was analyzed. Multivariable adjusted odds ratios (ORs) of CAC and AAC progression for current smokers were 1.73 (95% CI, 1.09-2.73) and 2.47 (1.38-4.44), respectively, as compared to never smokers. In dose-response analyses, we observed a graded positive relationship of smoking amount and CAC progression in current smokers (multivariable adjusted ORs: 1.23, 1.72, and 2.42 from the lowest to the highest tertile of pack-years). Among the former smokers, earlier quitters (≥10.7 years) had similar ORs of the progression of CAC and AAC to that of participants who had never smoked., Conclusions: Compared with never smokers, current smokers especially those with greater pack-years at baseline had higher risk of atherosclerosis progression in community-dwelling Japanese men. Importantly, the residual adverse effect appears to be present for at least ten years after smoking cessation. The findings highlight the importance of early avoidance or minimizing smoking exposure for the prevention of atherosclerotic disease.

Aim: Computed tomography (CT) can directly provide information on body compositions and distributions, compared to anthropometric indices. It has been shown that various obesity indices are associated with carotid intima-media thickness (IMT). However, whether CT-based obesity indices are stronger than anthropometric indices in association with atherosclerosis remains to be determined in a general population., Methods: We cross-sectionally assessed carotid IMT using ultrasound in 944 community-dwelling Japanese men free of stroke and myocardial infarction. CT image at the L4–L5 level was obtained to compute areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Anthropometric measures assessed included body mass index (BMI), waist circumference, and waist-to-hip ratio. Using multivariable linear regression, slopes of IMT per 20th to 80th percentile of each index were compared. We also compared the slope of index with simultaneous adjustment for BMI in the same model., Results: Areas of VAT and SAT were positively associated with IMT, but not stronger than those of anthropometric indices in point estimates. Among all obesity indices, BMI was strongest in association with IMT after adjusting for age and lifestyle factors or further adjusting for metabolic factors. In simultaneous adjustment models, BMI, but not CT-based indices, remained significant and showed the strongest association., Conclusions: In community-dwelling Japanese men, anthropometric obesity indices, BMI in particular, were more strongly associated with carotid atherosclerosis than CT-based obesity indices. The association of general obesity with carotid atherosclerosis was strong and adding CT-based obesity measure did not considerably influence in the association.

AIMS The roles of urinary albumin, eGFRcystatin (eGFRcys), and eGFRcreatinine (eGFRcre) in the progression of coronary artery calcification (CAC) remain unclear. Therefore, the present study investigated the relationship between kidney function and CAC progression. METHODS A total of 760 Japanese men aged 40-79 years were enrolled in this population-based study. Kidney function was measured using eGFRcre, eGFRcys, and the urine albumin-to-creatinine ratio. CAC scores were calculated using the Agatston method. CAC progression was defined as an annual increase of ＞10 Agatston units (AU) among men with 0＜CAC＜100 AU at baseline, that of ＞10% among those with CAC ≥ 100 AU, and any progression for those with CAC=0 at baseline. The relative risk (RR) of CAC progression based on kidney function was assessed using a robust Poisson regression model. RESULTS The mean follow-up period was 4.9 years. CAC progression was detected in 45.8% of participants. Positive associations between CAC progression and albuminuria (＞30mg/g) (RR: 1.29; 1.09 to 1.53; p=0.004) and low eGFRcys (＜60ml/min/1.73m2) (RR: 1.27; 1.05 to 1.53; p=0.012) remained significant after adjustments for age, the follow-up time, and computerized tomography type. Following further adjustments for hypertension, diabetes mellitus, dyslipidemia, C-reactive protein, and lifestyle factors, CAC progression was associated with albuminuria (RR: 1.20; 1.01 to 1.43; p=0.04) and low eGFRcys (RR: 1.19; 0.99 to 1.43; p=0.066), but not with eGFRcre. CONCLUSION CAC progression was associated with albuminuria; however, its relationship with eGFRcys was weakened by adjustments for risk factors.

BackgroundElevated resting heart rate (RHR) is associated with an increased risk for cardiovascular disease (CVD) and all-cause mortality. However, the findings of cohort studies differed. Thus, the impact of RHR on CVD mortality might be different according to the background of the population. Therefore, we examined the relationship of RHR and CVD mortality according to serum ALB levels in a Japanese general population.MethodsIn total, 8363 individuals without a history of CVD were followed-up for 24.0 years. The participants were divided into four groups according to the quartiles of RHR (Q1-Q4), and they were further classified into the high and low ALB groups based on a median value of 44 g/L. We estimated the multivariable-adjusted hazard ratios (HRs) of CVD mortality in each RHR group based on ALB levels, and the interaction between RHR and ALB groups on CVD mortality was evaluated.ResultsWe found no significant association between RHR and CVD mortality. However, the Q4 of RHR was significantly associated with an increased risk for CVD mortality (HR: 1.27 [95% confidence interval, CI: 1.02-1.57]) in participants with a low ALB level. Meanwhile, the Q4 of RHR was significantly correlated with a decreased risk for CVD morality in those with a high ALB level (HR: 0.61 [95% CI: 0.47-0.79]) after adjusting for covariates. A significant interaction between RHR and ALB for CVD mortality was shown (p

Background Little is known about the relationships between higher-level functional capacity (HLFC) and mortality, and its gender difference. Methods NIPPON DATA90 is the cohort study of the National Cardiovascular Survey of Japan in 1990. We followed up 1824 Japanese adults over 65 years who were independent in basic activities of daily living in 1995 until 2010. HLFC was measured in 1995 using the total score and 3 subscales (instrumental activities of daily living [IADL], intellectual activity, social role) by the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). The association of HLFC to mortality was evaluated by adjusted hazard ratio (HR) and 95% confidence interval (CI) using the Cox proportional hazard model. Results During average 12.2-year follow-up, 836 participants (45.8%) died. Participants with impaired total TMIG-IC score showed significantly higher risk of mortality (adjusted HR 1.37; 95%CI 1.14-1.66) compared with normal participants, even after adjusting for other variables. The corresponding HR was significant only in women (HR 1.42; 95% CI 1.10-1.83). Among the 3 subscales, only impaired social role showed significantly higher risk of mortality (HR 1.37; 95%CI 1.12-1.67) in men. In contrast, IADL and intellectual activity showed significantly higher risk in women (HR 1.51; 95%CI 1.16-1.96) (HR 1.46; 95%CI 1.19-1.80). Conclusions Impaired HLFC was related to higher risk of long-term mortality in Japanese elderly at baseline. Especially among women, IADL and intellectual activity were important predictors, whereas social role was important in men. Key messages Impaired HLFC was related to long-term mortality in Japanese elderly.

Background Premature atrial contractions (PACs) are known predictor of atrial fibrillation; however very little has been revealed on its factors among Asian general population. We assessed the frequency of higher PAC counts and its association with relevant factors in general Japanese men. Methods We have conducted a population based cross sectional study among 517 healthy men from Kusatsu, Japan, aged between 40 and 79 years. 24 hours Holter electrocardiogram was performed to assess the PAC frequency. We divided participants into quartiles based on number of PACs/hour to compare the characteristics by using Cochran–Mantel–Hanzal test and ANOVA. We defined the highest quartile as event and multivariable logistic regression was performed to assess the significance with relevant factors. Results Median number of PACs was 2.84 PACs/hour. The highest quartile of PAC counts was >7.86PACs/hour. Age, triglycerides, blood pressure, ventricular contractions and heart rates were different among quartiles. In multivariable logistic regression analysis, higher age (OR, 95% CI: 1.35, 1.01-1.67), lower mean heart rates (OR, 95% CI: 0.97, 0.94-0.99), higher heart rate difference in a day (OR, 95% CI: 1.40, 1.12-1.75) and lower triglyceride (OR, 95% CI: 0.53, 0.33-0.82) were independently, significantly associated with highest quartile of PACs. Conclusions Higher PACs evaluated by Holter ECG was associated with higher age, lower heart rate, higher heart rate difference, and lower triglyceride in general Japanese men. Key messages The PAC frequency was high. Age, mean heart rates, difference between maximum and resting heart rates, triglycerides are possible risk factors for frequent PAC counts.

OBJECTIVE: Hypertension and intracranial artery stenosis (ICAS) are closely related; however, few studies have compared the strength of the relationship between strictly measured office and out-of-office blood pressure (BP) measurements. The relationship of day-by-day or short-term variability in BP to asymptomatic ICAS also remains unclear. METHODS: In apparently healthy 677 men (mean age, 70.0 years) from a population-based cohort, we examined the association of strictly measured office BP and 7-day home BP with ICAS on magnetic resonance angiography. We conducted 24-hour ambulatory BP monitoring in 468 of the men. Variability indices included day-by-day, daytime, and nighttime variability, nocturnal decline, and morning pressor surge. Any ICAS was defined as either mild (1%–49%) or severe (≥50%) stenosis. RESULTS: We observed mild and severe ICAS in 153 (22.6%) and 36 (5.3%) participants, respectively. In multivariable-adjusted Poisson regression with robust error variance, higher systolic BP in office, home, or ambulatory BP monitoring was associated with the presence of any or severe ICAS. The associations with ICAS were comparable between office, home, and ambulatory systolic BP (all heterogeneity P-values >0.1). Independent of mean systolic BP, greater nocturnal decline or morning pressor surge, but not day-by-day, daytime, or nighttime variability, in systolic BP was associated with higher burden of any or severe ICAS. CONCLUSIONS: The magnitude of association of strictly measured office BP for asymptomatic ICAS was comparable with that of BP measured at home or in ambulatory BP monitoring. Circadian BP variation based on ambulatory BP monitoring was positively associated with asymptomatic ICAS burden.

In Asian countries, a major source of salt intake is from seasoning or table salt added at home. However, little is known about the adverse effects of salt intake evaluated according to household unit. We investigated the relationship between household salt intake level and mortality from all-cause and cardiovascular diseases (CVDs). Participants included 8702 individuals (56% women) who were living with someone else and who were aged 30-79 years and enrolled in the National Nutritional Survey of Japan in 1980 with a 24-year follow-up. Household nutrient intake was evaluated using a 3-day weighing record method in which all foods and beverages consumed by any of the household members were recorded. The household salt intake level was defined as the amount of salt consumed (g) per 1000 kcal of total energy intake in each household, and its average was 6.25 (2.02) g/1000 kcal. During the follow-up, there were 2360 deaths (787 CVD, 168 coronary heart disease [CHD], and 361 stroke). Cox proportional hazard ratios (HRs) for an increment of 2 g/1000 kcal in household salt intake were calculated and adjusting for sex, age, body mass index, smoking status, alcohol consumption status, self-reported work exertion level, household potassium intake, household saturated fatty acid intake, and household long-chain n-3 polyunsaturated fatty acid intake. The HRs (95% confidence intervals) were 1.07 (1.02, 1.12) for all-cause mortality, 1.11 (1.03, 1.19) for CVD, 1.25 (1.08, 1.44) for CHD, and 1.12 (1.00, 1.25) for stroke. The household salt intake level was significantly associated with long-term risk of all-cause, CVD, CHD, and stroke mortality in a representative Japanese population.

Background:Many studies show that dietary factors such as vegetables, fruit, and salt are associated with cardiovascular disease (CVD) risk. However, a risk assessment chart for CVD mortality according to combinations of dietary factors has not been established., Methods and Results:Participants were 9,115 men and women aged 30–79 years enrolled in the National Nutritional Survey of Japan in 1980 with a 29-year follow-up. Dietary intake was assessed using a 3-day weighed dietary record at baseline. Cox regression models were used to estimate the hazard ratio (HR) of CVD mortality stratified by vegetables, fruit, fish, and salt consumption. HRs of CVD mortality according to combinations of dietary factors were color coded on an assessment chart. Higher intakes of vegetables, fruit, and fish, and lower salt intake were associated with lower CVD mortality risk. HRs calculated from combinations of dietary factors were displayed using 5 colors corresponding to the magnitude of the HR. People with the lowest intake of vegetables, fruit, and fish, and higher salt intake had a HR of 2.87 compared with those with the highest intake of vegetables, fruit, and fish, and lower salt intake., Conclusions:Vegetables, fruit, fish, and salt intake were independently associated with CVD mortality risk. The assessment chart generated could be used in Japan as an educational tool for CVD prevention.

The association between carbohydrate intake and cardiovascular disease (CVD) risk has been investigated, but whether the quality of carbohydrate is more important than its amount is not known. We examined the associations between intake of dietary fibre (DF), carbohydrate, available carbohydrate, and starch with long-term CVD mortality in a Japanese population. We prospectively followed 8925 participants (3916 men and 5009 women) aged 30–79 years without CVD at baseline who participated in the National Nutrition Survey in Japan. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for CVD mortality by quartiles of exposure variables. During 24 years of follow-up, 823 CVD deaths were observed. In men, the multivariable-adjusted HR for CVD mortality was lower in the highest quartile of DF intake (HR: 0.64; 95% CI: 0.47–0.87; Ptrend = 0.007) compared with the lowest quartile. This association was not significant in women. Multivariable-adjusted HR for total stroke mortality was lower in the highest quartile of DF intake (HR: 0.61; 95% CI: 0.38–0.98; Ptrend = 0.046) compared with the lowest quartile in women. Carbohydrate, available carbohydrate, and starch intake were not associated with CVD mortality. Higher intake of DF was associated significantly with a lower risk of CVD mortality in men and lower risk of stroke mortality in women. Intake of carbohydrate, available carbohydrate, and starch were not associated with the risk of CVD mortality in men or women.

Background Oral health is thought to be associated with diet quality, and socioeconomic status (SES) affects both oral health and diet. The aim of this study was to investigate the association between the number of teeth and dietary intake as well as nutritional biomarker, considering the subjects’ SES. Methods We conducted a cross-sectional analysis of data from 2049 individuals aged ≥ 50 years from the National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged 2010. The number of remaining teeth was categorized into age-specific quartiles (Q1 to Q4). We assessed the adjusted means and 95% confidence intervals for dietary variables by the number of teeth using analysis of covariance. Stratified analyses by SES were also conducted. Results The intake of grain products was 31 g higher, and those of vegetables and meat were 30 g and 8 g lower, respectively, in Q1 (fewer teeth) than in Q4 (more teeth). Carbohydrate intake was higher whereas protein, minerals (potassium, magnesium, and zinc), vitamins (vitamins A, E, B1, B6, β-carotene, and folic acid), and dietary fiber intakes were lower among individuals with fewer teeth. Adjusted mean serum albumin levels were low in Q1. The associations between the number of teeth and dietary intake were more evident in individuals with a low SES. Conclusions Having few remaining teeth was associated with a low nutrient intake and low serum albumin levels in middle-aged and older Japanese adults, and these associations were more evident in individuals with low SES. Electronic supplementary material The online version of this article (10.1186/s12199-018-0752-x) contains supplementary material, which is available to authorized users.

AIM: Most patients with dementia frequently encounter various problems in their daily lives. Those troubles embarrass both the patients and their families, and cause problems for society. However, there have been few scientific reports on the difficulties in the daily life of patients with dementia. Therefore, we tried to clarify the frequency and characteristics of troubles experienced by patients with dementia. METHODS: Seven medical centers treating dementia patients in Okayama Prefecture, Japan, participated in this survey. A total of 737 patients were placed in one of the three groups: a dementia group (n = 478), a mild cognitive impairment group (n = 199) and a control group (n = 60). The frequency of 13 difficulties was scored for each patient. RESULTS: Among normal participants, no person caused these problems once a year or more frequently. "Massive, recurrent buying" and "acts that risk causing a fire" were reported once a year or more for >10% of mild cognitive impairment patients. "Troubles with wealth management" and "troubles with money management" were the most frequent problems of dementia patients. CONCLUSIONS: Several problems are already sometimes encountered in patients with mild cognitive impairment. It would be useful to know which social difficulties are often seen in dementia patients in order to protect the safety of the patients. It is always difficult to balance respecting the autonomy of dementia patients and ensuring their safely.

Background: Few studies have compared accurately measured office, self-measured home, and ambulatory blood pressure (BP) for asymptomatic intracranial artery stenosis (ICAS). Relationship of day-by-day or short-term variability in BP to asymptomatic ICAS remains unclear. Objectives: To examine the association of office, home (mean value and day-by-day variability), and ambulatory BP indices (24-hour/daytime/nighttime mean values, short-term variability, nocturnal decline, and morning pressor surge) with asymptomatic ICAS. Methods: Data on office and 7-day home BP and magnetic resonance angiography to assess ICAS were obtained in 677 men (mean age, 70.0 years) from a population-based cohort. Among them, 468 underwent 24-hour ambulatory BP monitoring. Mild- or severe-ICAS was defined as 1-49% or ≥50% stenosis, respectively, and any-ICAS as either mild or severe-ICAS. Results: We observed mild- and severe-ICAS in 153 (22.6%) and 36 (5.3%) participants, respectively. In multivariable Poisson regression with robust error variance, higher systolic BP at office, home, or ambulatory BP monitoring was associated with the presence of any- or severe-ICAS. The associations with ICAS were comparable between office, home, and ambulatory systolic BP (all heterogeneity Ps >0.1). Independent of mean systolic BP, greater nocturnal decline or morning pressor surge in systolic BP was associated with higher burden of any- or severe-ICAS. Conclusion: The magnitude of association of BP accurately measured at office for asymptomatic ICAS was comparable with that of BP at home or ambulatory BP monitoring. Circadian BP variation based on ambulatory BP monitoring may be considered when assessing ICAS in apparently healthy individuals.

BackgroundNon-fasting triglycerides (TG) are considered a better predictor of cardiovascular disease (CVD) than fasting TG. However, the effect of non-fasting TG on fatal CVD events remains unclear. In the present study, we aimed to explore the relationship between non-fasting TG and CVD mortality in a Japanese general population.MethodsA total of 6,831 participants without a history of CVD, in which those who had a blood sampling over 8 hours or more after a meal were excluded, were followed for 18.0 years. We divided participants into seven groups according to non-fasting TG levels: ≤59 mg/dL, 60-89 mg/dL, 90-119 mg/dL, 120-149 mg/dL, 150-179 mg/dL, 180-209 mg/dL, and ≥210 mg/dL, and estimated the multivariable-adjusted hazard ratios (HRs) of each TG group for CVD mortality after adjusting for potential confounders, including high density lipoprotein cholesterol. Additionally, we performed analysis stratified by age

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, Research members：Minoru Horie, Yoshihisa Nakagawa, Takashi Yamamoto, Yasutaka Nakano, Emiko Ogawa, Hiroshi Maegawa, Katsutaro Morino, Itsuko Miyazawa, Yoshiyuki Watanabe, Kazuhiko Nozaki, Ikuo Tooyama, Akihiko Shiino, Akira Andoh, Teruhiko Tsuru, Hisakazu Ogita, Naomi Miyamatsu, Yasuyuki Nakamura, Aya Kadota, Keiko Kondo, Sayuki Torii, Takashi Kadowaki, Sayaka Kadowaki, Sentaro Suzuki, Takahiro Ito, Ayako Kunimura, Hiroyoshi Segawa, Akira Fujiyoshi, Aya Higashiyama, Tomonori Okamura, Koichiro Azuma, Tatsuya Sawamura, Michiya Igase, Yasuharu Tabara, Akira Sekikawa, Emma J M Barinas-Mitchell, Daniel Edmundowicz, Takayoshi Ohkubo, Atsushi Hozawa, Yoshitaka Murakam, Nagako Okuda, Hisatomi Arima, Atsushi Satoh, Yoshikuni Kita, Takashi Hisamatsu, Masahiko Yanagita, Robert D Abbott, Seiko Ohno, Naoyuki Takashima, Naoko Miyagawa, Maryam Zaid, Yoshino Saito

Background & aims:Although accurate assessment of energy intake (EI) is critical in diabetes care, underreporting of EI on dietary records (DR) is often an issue. However, few studies have examined EI with doubly labeled water (DLW) in patients with diabetes mellitus. We aimed to investigate the impact of sex and obesity on the dissociation of DR from total energy expenditure (TEE) evaluated with DLW in patients with type 2 diabetes., Methods:Fifty-two patients with type 2 diabetes aged 60–79 years were enrolled for the Clinical Evaluation of Energy Requirements in Patients with Diabetes Mellitus (CLEVER-DM) study at a single university hospital. TEE was measured over 14 days by the DLW method as standard. EI was calculated by assessment of 3-day DR by registered dietitians., Results:The mean difference between EI and TEE was 238 ± 412 kcal/day (~10% of TEE). Neither EI nor TEE was significantly different between obese (body mass index (BMI) ≥25 kg/m 2) and non-obese (BMI, Conclusions:EI calculated by 3-day DR may underestimate habitual intake, which is assumed to be equal to TEE measured by the DLW method except in non-obese women with diabetes., Clinical trial registration number:UMIN000023051.

Background: Blood pressure (BP) indexes (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], mean arterial pressure [MAP]) shows association with subclinical cerebrovascular diseases (SCVDs). Although various studies reported this association, there are still controversy in the effect size of long period versus short period of these indexes to SCVDs. Aim: Identifying the effect size of four BP indexes measured at two visits on SCVDs assessed by magnetic resonance imaging (MRI) in general Japanese men. Methods: Four office BP indexes were measured at two visits 4.5 years apart in general Japanese men aged 40-79 years. Participants without myocardial infarction or stroke history were analyzed (N=629). MRI obtained at 3 rd visit were investigated for prevalent of five SCVDs diagnosed as follows; lacunar infarction (LI)= any presence, periventricular hyperintensity (PVH)= Fazekas grade ≥2, deep subcortical white matter hyperintensity (DSWMH)= Fazekas grade ≥3, microbleeds= any presence, and intracranial arterial stenosis (ICAS)= ≥1% stenosis. Using multivariable logistic regression, we computed and compared odds ratio OR (95% CI) of each prevalent SCVD for 1 standard deviation higher of each of 4 BP indexes after adjusting for SCVDs’ conventional risk factors. Results: Participants’ mean age at Visit 1 was 63.9 years. Our results show all office BP indexes, except PP, similar association with MRI outcomes at both Visit 1 and Visit 2. SBP, DBP and MAP were associated with LI, PVH, DSWMH, microbleed and ICAS, while PP was associated with LI and ICAS only. Conclusion: In general Japanese men, BP indexes SBP, DBP and MAP measured at two distinct visits show similar association to all future MRI assessed SCVD, while PP shows association to LI and ICAS only.

Background: A lower socioeconomic status (SES) may be related to the intake of unhealthy food; however, this relationship has not been examined in detail. This study was undertaken to examine relationships among food group intakes and SES in a representative Japanese population. Methods: This was a cross-sectional study using the baseline data of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey in Japan. A total of 2,898 participants were included in the baseline survey in 2010. The effects of age (

Background Reducing the urinary sodium-to-potassium ratio is important for reducing both blood pressure and risk of cardiovascular disease. Among free-living Japanese individuals, we carried out a randomized trial to clarify the effect of lifestyle modification for lowering urinary sodium-to-potassium ratio using a self-monitoring device. Methods This was an open, prospective, parallel randomized, controlled trial. Ninety-two individuals were recruited from Japanese volunteers. Participants were randomly allocated into intervention and control groups. A month-long dietary intervention on self-monitoring urinary sodium-to-potassium ratio was carried out using monitors (HEU-001F, OMRON Healthcare Co., Ltd., Kyoto, Japan). All participants had brief dietary education and received a leaflet as usual care. Monitors were handed out to the intervention group, but not to the control group. The intervention group was asked to measure at least one spot urine sodium-to-potassium ratio daily, and advised to lower their sodium-to-potassium ratio toward the target of less than 1. Outcomes included changes in 24-hour urinary sodium-to-potassium ratio, sodium excretion, potassium excretion, blood pressure, and body weight in both groups. Results Mean measurement frequency of monitoring was 2.8 times/day during the intervention. Changes in urinary sodium-to-potassium ratio were -0.55 in the intervention group and -0.06 in the control group (P = 0.088); respective sodium excretion changes were -18.5 mmol/24 hours and -8.7 mmol/24 hours (P = 0.528); and corresponding potassium excretion was 2.6 mmol/24 hours and -1.5 mmol/24 hours (P = 0.300). No significant reductions were observed in either blood pressure or body weight after the intervention. Conclusions Providing the device to self-monitor a sodium-to-potassium ratio did not achieve the targeted reduction of the ratio in "pure self-management" settings, indicating further needs to study an effective method to enhance the synergetic effect of dietary programs and self-monitoring practice to achieve the reduction. However, we cannot deny the possibility of reducing sodium-to-potassium ratio using a self-monitoring device.

Background It is widely supposed that there has been no evidence of increased survival in patients with advanced dementia receiving enteral tube feeding. However, more than a few studies have reported no harmful outcome from tube feeding in dementia patients compared to in patients without dementia. Methods This was a retrospective study. Nine psychiatric hospitals in Okayama Prefecture participated in this survey. All inpatients fulfilling the entry criteria were evaluated. All subjects suffered from difficulty with oral intake. Attending physicians thought that the patients could not live without long-term artificial nutrition. The physicians decided whether to make use of long-term artificial nutrition between January 2012 and December 2014. Results We evaluated 185 patients. Their mean age was 76.6 ± 11.4 years. Of all subjects, patients with probable Alzheimer's disease (n = 78) formed the biggest group, schizophrenia patients (n = 44) the second, and those with vascular dementia (n = 30) the third. The median survival times were 711 days for patients with tube feeding and 61 days for patients without tube feeding. In a comparison different types of tube feeding, median survival times were 611 days for patients with a nasogastric tube and more than 1000 days for those with a percutaneous endoscopic gastrostomy tube. Conclusion Patients with tube feeding survived longer than those without tube feeding, even among dementia patients. This study suggests that enteral nutrition for patients with dementia prolongs survival. Additionally, percutaneous endoscopic gastrostomy tube feeding may be safer than nasogastric tube feeding among patients in psychiatric hospitals.

High sodium-to-potassium ratios are associated with elevated blood pressure levels and an increased risk of cardiovascular diseases. We aimed to determine whether urinary sodium-to-potassium ratios fluctuate diurnally during the day to understand measured values of casual urinary sodium-to-potassium ratios. A total of 13,277 casual urine specimens were collected under free-living conditions from 122 Japanese normotensive and hypertensive individuals. Participants collected all casual urine samples in aliquot tubes, reported urine volumes and the time at each voiding for 10–22 days. Then, specimens were classified into hourly data. Diurnal patterns of urinary sodium-to-potassium ratios and urinary concentrations of sodium and potassium were evaluated. Overall mean values of hourly urinary sodium-to-potassium ratios were highest (4.1–5.0) in the early morning, lower (3.3–3.8) in the daytime and higher (4.0–4.4) toward evening hours. The mean urinary sodium and potassium concentrations were the lowest (90–110 and 24–32 mmol l−1, respectively) during the early morning and higher (110–140 and 35–43 mmol l−1, respectively) after mid-morning. Diurnal variability of potassium concentrations was larger than for sodium concentrations. Diurnal variations in urinary sodium-to-potassium ratios were comparable between normotensive and hypertensive individuals, between hypertensive individuals with and without antihypertensive medications, and among age and gender-specific subgroups. Overall mean hourly urinary sodium-to-potassium ratios fluctuated diurnally under free-living conditions and were higher during the morning and evening and lower during the daytime compared with 24-h urinary sodium-to-potassium ratios. Diurnal variation in urinary sodium-to-potassium ratios should be considered to understand actual daily dietary levels and avoid over- and under-estimation in clinical practice.

Background Many studies have reported the J-shaped relationship between alcohol consumption and coronary heart disease (CHD) risk; therefore, light-drinkers is generally recognized to be associated with the lower risk of CHD. However, the mechanisms of lower risk for CHD in light-drinkers are still unclear. Alcohol drinking status is likely to be associated with not only CHD risk factors but also dietary intake. Nevertheless, few studies report these relationships in detail. Purpose The purpose of this study is to evaluate the relationships of alcohol drinking status with CHD classical risk factors and the intake of macro- and micro- nutrients in Japanese. Methods Study participants were 1,090 Japanese men and women aged 40–59 years from The INTERLIPID study excepted for 55 individuals who had missing data (n=26) and were past-drinkers (n=29). Alcohol consumption was assessed with two 7-day alcohol records, and average ethanol intake (per week) was calculated. Participants were classified into following 4 groups: non-drinkers (0g/week), light-drinkers ( Results Serum HDL cholesterol levels increased and LDL cholesterol levels decreased with increasing alcohol consumption. Systolic and diastolic BP increased with increasing alcohol consumption. J-shaped relationships with alcohol consumption were observed for the proportion of current smoker, number of cigarettes, and the prevalence of hypertension; that is, light-drinkers was lowest among all groups. The prevalence of dyslipidemia was the highest in non-drinkers, and decreased with increasing alcohol consumption. In heavy-drinkers, total energy (kcal/day) was the highest, but energy intake without alcohol (kcal/day) was the lowest. For macronutrients, the intake of carbohydrate (%kcal) decreased, and the intakes of total and animal protein (%kcal) increased with increasing alcohol consumption. The intakes of total cholesterol (mg/1000kcal) and sodium (mg/1000kcal) increased, and total fiber (g/1000kcal) decreased with increasing alcohol consumption. These associations were similar in men and women. Conclusions Alcohol consumption was related with not only CHD classical risk factors but also the intake of macro- and micro-nutrients. Non-drinkers had a higher proportion of some CHD risk factors than light-drinkers. These results might influence on J-shaped relationship between alcohol consumption and CHD risk. Acknowledgement/Funding 1: Ministry of Education, Science, Sports, and Culture of Japan, 2: National Institutes of Health, Bethesda, MD, USA

Introduction Calcific aortic valve disease (CAVD) is one of the most common heart diseases worldwide, and its prevalence has increased in developed countries along with aging populations. Subclinical CAVD is characterized by aortic valve calcification (AVC) that may lead to aortic stenosis. AVC shares the same risk factors with atherosclerotic disease. Recently, nuclear magnetic resonance (NMR)-based lipoprotein particles, low-density and high-density lipoprotein particles (LDL-p, HDL-p) in particular, have emerged as novel markers of atherosclerotic disease. It has been unclear, however, whether NMR-based particles are associated with AVC. Purpose To examine cross-sectional association of NMR-based lipoprotein particles, standard lipids with AVC, and compare their strengths of association. Methods We studied a community-based random sample of Japanese men aged 40–79 years examined in 2006–08 in Japan. We excluded participants with history of myocardial infarction, stroke, aortic valve surgery, serum triglyceride concentration ≥400 mg/dl, estimated glomerular filtration rate (eGFR) 0. Lipoprotein particles were measured using NMR spectroscopy. In our main analysis, we obtained multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) of prevalent AVC in the top quartile (Q4) for each lipid index in reference to the lowest quartile (Q1). Adjusting covariates include age, smoking, drinking, systolic blood pressure, glycated hemoglobin, medications for hypertension and/or for diabetes, eGFR, C-reactive protein. For sensitivity analysis, we repeated similar analyses presenting ORs per 1 standard deviation (SD) higher NMR-lipoproteins particles or standard lipids. Results Of 874 participants we analyzed, 153 (17.5%) men had AVC. The average (SD) age was 63.3 (10.0) years. Those with AVC tended to be older, likely to have clustering of atherosclerotic risk factors. Multivariable-adjusted ORs of prevalent AVC for Q4 versus Q1 were significantly positive for LDL-p [OR, 2.21 (95% CI: 1.24, 3.95] and low-density lipoprotein cholesterol (LDL-c) [2.17 (1.24, 3.80)]. In contrast, neither HDL-p nor high-density lipoprotein cholesterol (HDL-c) was significantly associated with AVC. In sensitivity analyses, however, the corresponding ORs per 1SD higher lipids/lipoprotein particles were smaller in LDL-p [1.33 (1.09, 1.63)] than LDL-c [1.41 (1.15, 1.73)]. The association of HDL-p became significant [1.28 (1.02, 1.61)] (per 1SD decrement) in the sensitivity analysis. Conclusion The overall associations of AVC with NMR-based lipoprotein particles (i.e. LDL-p, HDL-p) are comparable to those of standard lipids. This finding is parallel to the association between atherosclerotic cardiovascular diseases with NMR-based lipoproteins.

Introduction: Evaluation of total energy expenditure (TEE) and physical activity level (PAL) is important for treatment of patients with type 2 diabetes mellitus (T2DM). However, the validity of accelerometers (ACC) and physical activity questionnaires (PAQ) for estimating TEE and PAL remains unknown in elderly populations with T2DM. We evaluated the accuracy of TEE and PAL results estimated by an ACC (TEEACC and PALACC) and a PAQ (TEEPAQ and PALPAQ) in elderly patients with T2DM. Methods: Fifty-one elderly patients with T2DM (aged 61–79 years) participated in this study. TEEACC was calculated with PALACC using a triaxial ACC (Active style Pro HJA-750c) over 2 weeks and predicted basal metabolic rate (BMR) by Ganpule’s equation. TEEPAQ was estimated using predicted BMR and the PALPAQ from the ­Japan Public Health Center Study-Long questionnaire. We compared the results to TEEDLW measured with the doubly labeled water (DLW) method and PALDLW calculated with BMR using indirect calorimetry. Results: TEEDLW was 2,165 ± 365 kcal/day, and TEEACC was 2,014 ± 339 kcal/day; TEEACC was strongly correlated with TEEDLW (r = 0.87, p < 0.01) but significantly underestimated (–150 ± 183 kcal/day, p < 0.05). There was no significant difference in TEEPAQ and TEEDLW (–49 ± 284 kcal/day), while the range of difference seemed to be larger than TEEACC. PALDLW, PALACC, and PALPAQ were calculated to be 1.71 ± 0.17, 1.69 ± 0.16, and 1.78 ± 0.24, respectively. ­PALACC was strongly correlated with PALDLW (r = 0.71, p < 0.01), and there was no significant difference between the 2 values. PALPAQ was moderately correlated with PALDLW (r = 0.43, p < 0.01) but significantly overestimated. Predicted BMR was significantly lower than the BMR ­measured by indirect calorimetry (1,193 ± 186 vs. 1,262 ± 155 kcal/day, p < 0.01). Conclusions: The present ACC and questionnaire showed acceptable correlation of TEE and PAL compared with DLW method in elderly patients with T2DM. Systematic errors in estimating TEE may be improved by the better equation for predicting BMR.

Objective: SGLT2 inhibitors reduce body weight (BW) due to negative energy balance. Although previous reports suggested that SGLT2 inhibitor improved liver dysfunction and steatosis, the efficacy of SGLT2 inhibitor on intrahepatic triglyceride (IHTG) were merely quantified. Methods: The study was an open label randomized controlled trial. Fifty-two overweight patients (BMI > 23) who had inadequate glycemic control with oral antidiabetic agents were randomly assigned to dapagliflozin (Dapa) or standard treatment (Con) and followed for 24 weeks. The Primary endpoint was the change in BW from baseline to week 24 between the two groups. The secondary endpoint was IHTG which was assessed by magnetic resonance spectroscopy (MRS). Results: The change in BW was significantly larger in Dapa group compared to Con. The mean difference in changes between two groups was -1.72 kg (95% CI: -2.85, -0.59, p = 0.004) which was comparable with the previous studies of Caucasians. IHTG measured with MRS was significantly reduced in Dapa group (p = 0.033). Conclusion: Dapagliflozin treatment for 24 weeks resulted in reduction of BW and IHTG. These findings suggest the therapeutic potential of dapagliflozin for patients with NAFLD. Clinical study registration number: UMIN000020239. Disclosure K. Morino: Research Support; Self; Astellas Pharma Inc., AstraZeneca, CMIC Pharma Science, Miki Corp., Ono Pharmaceutical Co., Ltd., Sunstar Inc. K. Kondo: None. S. Tanaka: None. I. Miyazawa: None. K. Fuse: None. S. Ida: None. H. Arima: Consultant; Self; Kyowa Hakko Kirin Co., Ltd. Speaker's Bureau; Self; Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. K. Miura: None. N. Ohashi: None. S. Ugi: None. H. Maegawa: Research Support; Self; Antares Pharma, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. Funding AstraZeneca; Ono Pharmaceutical Co., Ltd.

Objective: Passive smoking was reported to impair endothelial vascular function in an acute phase. However, studies regarding the vascular effect of passive smoking status among general population are still scarce. We investigated the association of passive smoking status to endothelial vascular function among general Japanese women. Methods: Study participants were 243 Japanese women who had never smoked, and aged 69 to 85 years randomly selected from Kusatsu City, Japan. Using self-administered questionnaire, passive smoking status and passive smoking hour per week at recent 1 year and those of 20 years ago were obtained. They were classified into 4 groups (never, past, current; Results: Distribution of passive smoking status was; never 42.4%, past 42.0%, current Conclusion: Passive smoking status was not associated to endothelial vascular function assessed with RHI among general Japanese women. Further investigation is still required.

Glucose-stimulated insulin secretion (GSIS) by pancreatic β cells is biphasic. However, the physiological significance of biphasic GSIS and its relationship to diabetes are not yet fully understood. This study demonstrated that impaired first-phase GSIS follows fasting, leading to increased blood glucose levels and brain glucose distribution in humans. Animal experiments to determine a possible network between the brain and β cells revealed that fasting-dependent hyperactivation of AMP-activated protein kinase in the hypothalamus inhibited first-phase GSIS by stimulating the α-adrenergic pancreatic nerve. Furthermore, abnormal excitability of this brain-β cell neural axis was involved in diabetes-related impairment of first-phase GSIS in diabetic animals. Finally, pancreatic denervation improved first-phase GSIS and glucose tolerance and ameliorated severe diabetes by preventing β cell loss in diabetic animals. These results indicate that impaired first-phase GSIS is critical for brain distribution of dietary glucose after fasting. Furthermore, β cells in individuals with diabetes mistakenly sense that they are under conditions that mimic prolonged fasting. The present study provides additional insight into both β cell physiology and the pathogenesis of β cell dysfunction in type 2 diabetes., Highlights • Fasting-induced hypothalamic AMPK activation inhibited first-phase GSIS by stimulating the α-adrenergic nerve. • The brain-pancreas neural axis was involved in β cell dysfunction and glucose intolerance in diabetes. • Pancreatic denervation improved first-phase GSIS, glucose tolerance and β cell survival in type 2 diabetic animals. Glucose-stimulated insulin secretion (GSIS) from pancreatic β cells is biphasic. Furthermore, first-phase GSIS is inhibited in type 2 diabetes. This study revealed that fasting reduced first-phase GSIS by signaling via the brain-pancreatic β cell neural axis, which is essential for maintaining glucose supply to the brain at re-feeding after fasting. Abnormal excitability of this neural axis was also associated with impaired first-phase GSIS in type 2 diabetes. Surgical pancreatic denervation improved diabetes in an animal study. The present data reveal that diabetic β cells exist under conditions that mimic starvation and provide a therapeutic potency of pancreatic denervation against diabetes., Graphical Abstract Image 2

Aim Artificial nutrition, including tube feeding, continues to be given to dementia patients in numerous geriatric facilities in Japan. However, the clinical characteristics of patients receiving artificial nutrition have not been fully investigated. Therefore, we tried to evaluate the clinical features of those patients in this study. Methods Various clinical characteristics of all inpatients at 18 of 20 psychiatric hospitals in Okayama Prefecture, Japan, with a percutaneous endoscopic gastrostomy tube, nasogastric tube, or total parenteral nutrition were evaluated. Results Two hundred twenty-one patients (5.4% of all inpatients) had been receiving artificial nutrition for more than 1 month, and 187 (130 women, 57 men; 84.6% of 221 patients) were fully investigated. The mean age was 78.3 years old, and the mean duration of artificial nutrition was 29.8 months. Eighty-four patients (44.7% of 187 patients) were receiving artificial nutrition for more than 2 years. Patients with Alzheimer's disease (n = 78) formed the biggest group, schizophrenia (n = 37) the second, and vascular dementia (n = 26) the third. Conclusion About one-fifth of the subjects receiving artificial nutrition were in a vegetative state. More than a few patients with mental disorders, including schizophrenia, also received long-term artificial nutrition. We should pay more attention to chronic dysphasia syndrome in mental disorders.

Background In recent years, individuals with high serum total cholesterol (TC) have been more likely to modify their diet by reducing their intake of dietary lipids. The aim of this study was to investigate time-related changes in the relationships between the Keys score, dietary lipids, and TC between 1980 and 2010 in representative Japanese populations. Methods and Results: We used 3 cross-sectional cohort studies conducted among Japanese representative populations in 1980, 1990, and 2010 (NIPPON DATA80/90/2010) for the analyses. We analyzed data for 10,365, 7,714, and 2,657 participants, respectively, in each dataset. The relationships between TC and the Keys score (calculated by dietary lipids, cholesterol, and energy intake)/dietary lipids were examined. In men, a 1-unit higher Keys score correlated with 0.92 mg/dL and 0.64 mg/dL TC in 1980 and 1990, respectively, but not in 2010. In women, a 1-unit higher Keys score correlated with 0.70 mg/dL and 0.74 mg/dL TC in 1980 and 1990, respectively, but with 0.33 mg/dL in 2010. In men and women, dietary cholesterol, saturated fatty acid (SFA), and trans fatty acid (TFA) levels were positively associated with TC concentrations in 1980 and 1990, but not in 2010. Conclusions In these representative Japanese populations, a higher Keys score as well as dietary cholesterol, SFA, and TFA levels correlated with higher TC concentrations in 1980/1990, but the relationships were weaker or not observed in 2010.

Objective: Weight gain is a common problem in the insulin treatment. SGLT2 inhibitors are expected to reduce body weight (BW) due to negative energy balance. Previous reports suggested that BW reduction is achieved mainly by loss of body fat, and ∼20% of reduction is by lean mass. However, the efficacy of SGLT2 inhibitor on BW and body composition remains unclear. We examined these in the Japanese T2DM treated with insulin. Methods: The study was an open label randomized controlled trial. Primary endpoint was the change in BW from baseline to week 24 between the two groups. Fifty overweight patients (BMI > 23) who had inadequate glycemic control with insulin treatment were randomly assigned to ipragliflozin (Ipra) or standard treatment (Con) and followed for 24 weeks. Body composition was assessed by DEXA and impedance method. Results: The change in BW was significantly larger in Ipra compared to Con. Ipra showed significant larger reduction of HbA1c. Total fat mass was reduced in the Ipra compared to Con mainly due to lower limb fat and trunk fat. Total muscle mass was maintained at lower limbs and trunk but tended to be reduced at arm in Ipra. Conclusion: Ipragliflozin treatment for 24 weeks resulted in reduction of BW mainly due to fat mass at lower limb and trunk. Reduction of the muscle mass at lower limb may be protected by anti-gravity effect. Disclosure K. Morino: Research Support; Self; Astellas Pharma US, Inc., AstraZeneca, Sunstar Inc., CMIC Pharmascience, Kowa Pharmaceutical. H. Inoue: None. K. Fuse: None. S. Tanaka: None. K. Kondo: None. H. Arima: Advisory Panel; Self; Kyowa Kirin. Speaker's Bureau; Self; Takeda Japan, Daiichi Sankyo Company, Limited. K. Miura: None. D. Sato: None. N. Ohashi: None. S. Ida: None. I. Miyazawa: None. O. Sekine: None. S. Ugi: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., MSD K.K. H. Maegawa: Speaker's Bureau; Self; Astellas Pharma US, Inc.. Research Support; Self; Astellas Pharma US, Inc.. Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation. Research Support; Self; Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Nippon Boehringer Ingelheim Co. Ltd.. Research Support; Self; Nippon Boehringer Ingelheim Co. Ltd.. Speaker's Bureau; Self; Daiichi Sankyo Company, Limited. Research Support; Self; Daiichi Sankyo Company, Limited, Takeda Pharmaceutical Company. Speaker's Bureau; Self; Takeda Pharmaceutical Company, Novo Nordisk A/S, Eli Lilly and Company.

Background and Aim: Fatty liver is reported to be associated with type 2 diabetes mellitus. Most of the previous studies are cross-sectional and liver fat was evaluated using ultrasound echography or plasma levels of liver enzyme. We assessed liver fat content in a semi-quantitative method using computed tomographic (CT) images and verified the hypothesis that the L/S ratio for CT attenuation value was associated with the onset of diabetes in longitudinal observational cohort study of Japanese men. Methods: Participants were randomly selected men from Kusatsu City, Japan. We analyzed 622 participants (63.5±9.9 years) without diabetes at baseline. We calculated odds ratio (OR) and 95% confidence interval (CI) of the presence of fatty liver (defined by L/S ratio Results: During 5.1±1.4 years of follow-up period, 36 participants (5.8%) developed diabetes. Although the presence of fatty liver was not significantly associated with the development of diabetes (OR 1.77, 95% CI 0.81-3.85), OR for those of per 1 SD (0.18) decrease in L/S ratio was 1.40 (95% CI 1.02-1.92). We still found the significant results that L/S ratio was associated with the development of diabetes in the stratified analysis. Conclusions: The ratio of liver to spleen for CT attenuation value was associated with the development of diabetes during 5 years regardless of BMI in Japanese community-based study. Disclosure K. Fuse: None. A. Kadota: None. K. Kondo: None. A. Fujiyoshi: None. T. Hisamatsu: None. S. Kadowaki: None. I. Miyazawa: None. K. Morino: Research Support; Self; Astellas Pharma US, Inc., AstraZeneca, Sunstar Inc., CMIC Pharmascience, Kowa Pharmaceutical. O. Sekine: None. S. Ugi: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., MSD K.K. H. Maegawa: Speaker's Bureau; Self; Astellas Pharma US, Inc.. Research Support; Self; Astellas Pharma US, Inc.. Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation. Research Support; Self; Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Nippon Boehringer Ingelheim Co. Ltd.. Research Support; Self; Nippon Boehringer Ingelheim Co. Ltd.. Speaker's Bureau; Self; Daiichi Sankyo Company, Limited. Research Support; Self; Daiichi Sankyo Company, Limited, Takeda Pharmaceutical Company. Speaker's Bureau; Self; Takeda Pharmaceutical Company, Novo Nordisk A/S, Eli Lilly and Company. K. Miura: None. H. Ueshima: None.

Introduction: The Dietary Approaches to Stop Hypertension (DASH) eating pattern is widely used for lowering blood pressure in the United States. Food preference and intake volume are quite different among American and Japanese diet; therefore, it is necessary to develop a modified version of DASH dietary pattern for Japanese people (JDASH). Hypothesis: The JDASH is feasible, safe and effective among Japanese people. Methods: This crossover pilot study recruited Japanese men and women aged 30 years and over. Participants were randomized to a three week JDASH diet followed by a three week control diet, or the reverse sequence. Intervention periods were separated by two weeks’ washout in which participants returned to their usual diet. The JDASH dietary pattern consisted of higher potassium, magnesium, calcium, dietary fiber, and n-3 fatty acid and lower sodium than Japanese typical diet. The nutrient balance of the control diet was average Japanese diet based on the National Health and Nutrition Survey in Japan. Primary outcome of this trial was a change in 24 hour urine sodium-to-potassium (Na/K) ratios and secondary outcomes were changes in home and office blood pressure values, lipoprotein profiles and body mass index. These outcomes were from 24 hour urine and blood specimens taken measured before and on the last day of each experimental period. The impact on these measurements was calculated with generalized estimating equation model in consideration of the sequences of intervention. Results: The JDASH diet was well tolerated and with no dropouts. No participant reported any adverse effect regarding this intervention diet and no adverse effects were also observed in biological measures. There were no differences in biological measurements between two diets before intervention. A significant difference in 24 hour urine Na/K ratio was observed (-4.33 mol/mol, p2 (p=0.002) and -11.0 mg/dl (p=0.038), respectively. Conclusion: Developed modified DASH dietary pattern for Japanese were significantly decrease 24 hour urine Na/K ratio. In conclusion, the results of this pilot study showed the feasibility, safety and efficacy.

Background The relationships among socioeconomic status and lifestyle improvements have not yet been examined in a representative Japanese population. Methods We analyzed data from 2,647 participants (1,087 men and 1,560 women) who participated in NIPPON DATA2010. This survey inquired about lifestyle improvements and socioeconomic status. Education was categorized as low (≤9 years), middle (10-12 years), and high (≥13 years). Marital status was categorized as married, divorced, widowed, and never married/other. A multivariable logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of lifestyle improvements with the intention of preventing cardiovascular diseases for educational attainment and marital status, with adjustments for age and awareness of cardiovascular disease risk factors. Results Overall, 1,507 (56.9%) participants practiced prevention and improvements in hypertension, diabetes, elevated cholesterol, and metabolic syndrome, and the OR of lifestyle improvements was significantly higher with a high education than with a low education in men (OR 2.86; 95% CI, 1.96-4.17) and women (OR 2.36; 95% CI, 1.67-3.33). The number of participants who practiced prevention and improvements in hypertension, diabetes, elevated cholesterol, and metabolic syndrome was significantly lower in divorced than in married men (OR 0.46; 95% CI, 0.22-0.95) and women (OR 0.53; 95% CI, 0.33-0.86). Conclusions Specific differences caused by educational attainment and marital status may exist in lifestyle improvements.

The isomaltulose based liquid formula (MHN-01), suppresses postprandial plasma glucose and insulin levels in healthy persons and patients with impaired glucose tolerance (IGT) or type 2 diabetes. MHN-01 intake as a part of breakfast also suppresses glucose and insulin levels after lunch, suggesting second meal effect. The objective of this study was to investigate the effects of nutritional counseling and long-term (24 weeks) MHN-01 ingestion on biomarkers of metabolic syndrome. Forty-one subjects with criteria of metabolic syndrome participated in this study composed with the control period (0-12 week) followed by nutritional counseling and the experimental period (12-36 week) followed by 200 kcal (837 kJ) of MHN-01 or dextrin-based standard balanced liquid formula (SBF) loading as a part of breakfast. In 16 of 41 subjects became to out of criteria for liquid formula loading study during control period (unqualified group). In the unqualified group, several biomarkers were improved. In experimental period, serum HbA1c levels significantly increased in SBF group (n = 12) but did not change in MHN-01 group (n = 10). Thus, intake of 837 kJ MHN- 01 as a part of breakfast may be effective for suppression of deteriorating glucose metabolism in metabolic syndrome., Journal of Clinical Biochemistry and Nutrition, 57(2), pp.140-144; 2015

Background It is widely supposed that there is no benefit, including extended survival and decreased rate of pneumonia, in patients with severe dementia receiving enteral tube feeding (TF). However, there have been few studies comparing the frequency of pneumonia before and after TF in severe dementia. Methods Nine psychiatric hospitals in Okayama Prefecture participated in this retrospective survey. All inpatients fulfilling the entry criteria were evaluated. All subjects suffered from difficulty in oral intake. Attending physicians thought that the patients could not live without long-term artificial nutrition, and they decided whether or not to make use of long-term artificial nutrition from January 1, 2014 to December 31, 2014. Results We evaluated 58 patients including 46 with TF and 12 without. The mean age of all patients was 79.6 ± 9.0 years old. Patients with probable Alzheimer’s disease (n = 38) formed the biggest group, and those with vascular dementia the second (n = 14). Median survival times were 23 months among patients with TF and two months among patients without TF. The start of TF decreased the frequency of pneumonia and the use of intravenous antibiotics. Conclusions TF decreased pneumonia and antibiotic use, even in patients with severe dementia. The results of this study do not necessarily indicate that we should administer TF to patients with severe dementia. We should consider the quality of life of patients carefully before deciding the use or disuse of TF for patients with severe dementia.

Periodontal disease is related to aging, smoking habits, diabetes mellitus, and systemic inflammation. However, there remains limited evidence about causality from intervention studies. An effective diet for prevention of periodontal disease has not been well established. The current study was an intervention study examining the effects of a high-fiber, low-fat diet on periodontal disease markers in high-risk subjects. Forty-seven volunteers were interviewed for recruitment into the study. Twenty-one volunteers with a body mass index of at least 25.0 kg/m(2) or with impaired glucose tolerance were enrolled in the study. After a 2- to 3-week run-in period, subjects were provided with a test meal consisting of high fiber and low fat (30 kcal/kg of ideal body weight) 3 times a day for 8 weeks and followed by a regular diet for 24 weeks. Four hundred twenty-five teeth from 17 subjects were analyzed. Periodontal disease markers assessed as probing depth (2.28 vs 2.21 vs 2.13 mm; P < .0001), clinical attachment loss (6.11 vs 6.06 vs 5.98 mm; P < .0001), and bleeding on probing (16.2 vs 13.2 vs 14.6 %; P = .005) showed significant reductions after the test-meal period, and these improvements persisted until the follow-up period. Body weight (P < .0001), HbA1c (P < .0001), and high-sensitivity C-reactive protein (P = .038) levels showed improvement after the test-meal period; they returned to baseline levels after the follow-up period. In conclusion, treatment with a high-fiber, low-fat diet for 8 weeks effectively improved periodontal disease markers as well as metabolic profiles, at least in part, by effects other than the reduction of total energy intake.

Dental and dental hygiene students must acquire the skill of measuring periodontal pockets and learn to identify the bottom of a pocket, especially of deep periodontal pockets. A new dental model that would enable students to practice measuring deep periodontal pockets was developed at the Tokyo Medical and Dental University. The purpose of this study was to evaluate the feasibility and effectiveness of this model. Twenty dental hygiene students in their third year at the school and twenty-four instructors or dental hygienists of the University Hospital measured periodontal pockets on the newly designed dental model. Feasibility and effectiveness of the model were evaluated based on periodontal probing by the students and instructors, as well as results of a questionnaire. The results demonstrated an intraexaminer agreement (within ±1 mm) averaging 91 percent. The mean percentages of correct answers of the students and instructors were 82 percent and 80 percent, respectively. More than 90 percent of the instructors and students reported that the new model would be suitable for pocket probing training. In the questionnaire, they responded that this practice using the new model would contribute to students' future and that they wanted to try other dental models with various probing depths. The new dental model designed for periodontal pocket probing training was reported to be feasible and effective for student practice.

Background/Aims: Most patients with dementia suffer from dysphagia in the terminal stage of the disease. In Japan, most elderly patients with dysphagia receive either tube feeding or total parenteral nutrition. Methods: In this study, we investigated the factors determining longer survival with artificial nutrition. Various clinical characteristics of 168 inpatients receiving artificial nutrition without oral intake in psychiatric hospitals in Okayama Prefecture, Japan, were evaluated. Results: Multiple logistic regression analysis showed that the duration of artificial nutrition was associated with a percutaneous endoscopic gastrostomy (PEG) tube, diagnosis of mental disorder, low MMSE score, and absence of decubitus. Conclusion: Patients with mental disorders survived longer than those with dementia diseases on artificial nutrition. A PEG tube and good nutrition seem to be important for long-term survival.

Background & Aims A fiber-rich diet has a cardioprotective effect, but the mechanism for this remains unclear. We hypothesized that a fiber-rich diet with brown rice improves endothelial function in patients with type 2 diabetes mellitus. Methods Twenty-eight patients with type 2 diabetes mellitus at a single general hospital in Japan were randomly assigned to a brown rice (n = 14) or white rice (n = 14) diet and were followed for 8 weeks. The primary outcome was changes in endothelial function determined from flow debt repayment by reactive hyperemia using strain-gauge plethysmography in the fasting state. Secondary outcomes were changes in HbA1c, postprandial glucose excursions, and markers of oxidative stress and inflammation. The area under the curve for glucose after ingesting 250 kcal of assigned rice was compared between baseline (T0) and at the end of the intervention (T1) to estimate glucose excursions in each group. Results Improvement in endothelial function, assessed by fasting flow debt repayment (20.4% vs. −5.8%, p = 0.004), was significantly greater in the brown rice diet group than the white rice diet group, although the between-group difference in change of fiber intake was small (5.6 g/day vs. −1.2 g/day, p

Background:Smoking is an overwhelming, but preventable, risk factor for cardiovascular diseases (CVD), although smoking prevalence remains high in developed and developing countries in East Asia., Methods and results:In a population-based sample of 1019 Japanese men aged 40 to 79 years, without CVD, we examined cross-sectional associations of smoking status, cumulative pack-years, daily consumption, and time since cessation, with subclinical atherosclerosis at 4 anatomically distinct vascular beds, including coronary artery calcification, carotid intima-media thickness (CIMT) and plaque, aortic artery calcification (AoAC), and ankle-brachial index. Current, former, and never smoking were present in 32.3%, 50.0%, and 17.7%, respectively. Compared to never smokers, current smokers had significantly higher risks of subclinical atherosclerosis in all 4 circulations (eg, odds ratios for coronary artery calcification >0, 1.79 [95% CIs, 1.16-2.79]; CIMT >1.0 mm, 1.88 [1.02-3.47]; AoAC >0, 4.29 [2.30-7.97]; and ankle-brachial index 1.0 mm, 1.94 [1.13-3.34]; and AoAC >0, 2.55 [1.45-4.49]). Dose-response relationships of pack-years and daily consumption, particularly with CIMT, carotid plaque, AoAC, and ankle-brachial index, were observed among both current and former smokers, and even a small amount of pack-years or daily consumption among current smokers was associated with coronary artery calcification and AoAC, whereas time since cessation among former smokers was linearly associated with lower burdens of all atherosclerotic indices., Conclusions:Cigarette smoking was strongly associated with subclinical atherosclerosis in multiple vascular beds in Japanese men, and these associations attenuated with time since cessation.

The aim of this study was to develop, implement, and evaluate an inter- and intraprofessional education program with a peer support joint practice in which dental hygiene students teach medical and dental students about oral health care for older people requiring long-term care. In 2015 at Tokyo Medical and Dental University, 22 dental hygiene students in their third year at the School of Oral Health Care Sciences (OH3), 110 students in their third year at the School of Medicine (M3), and 52 students in their third year at the School of Dentistry (D3) participated in this program. The OH3 students practiced with a whole-body-type simulator to learn oral health care for older people and then taught the methods to the M3 and D3 students according to their self-designed teaching plan. All M3 and D3 students experienced being both practitioner and patient. The number of respondents and response rates on the questionnaires after the training were 22 (100%), 102 (92.7%), and 52 (100%) for the OH3, M3, and D3 students, respectively. Self-assessment by the OH3 students indicated that they could supervise other students sufficiently (77-86%), and 91% of them found the preclinical practice with the simulator efficient for the peer support joint practice. Almost all the M3 and D3 students reported that they gained understanding of the methods (99%), significance (100%), and important points of oral health care for older people (97%) in addition to the jobs and roles of dental hygienists (93%) because of this program. The M3 students understood the methods and significance of oral health care more deeply than did the D3 students (p