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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.

We aimed to investigate the associations among various obesity indices, including visceral (VAT) and subcutaneous adipose tissue (SAT), and cognitive function in community-dwelling Japanese men. This population-based cross-sectional study used data of 853 men who participated in the follow-up examinations of the Shiga Epidemiological Study of Subclinical Atherosclerosis. Among them, we analyzed data of 776 men who completed the Cognitive Abilities Screening Instrument (CASI) and had abdominal VAT and SAT areas measured using computed tomography. The VAT-to-SAT ratio (VSR) was calculated; participants were categorized into VSR quartiles. Using analysis of covariance, we computed crude and adjusted means of the CASI total and domain scores across VSR quartiles, adjusting for potential confounders. No significant differences were observed in total CASI scores among body mass index, VAT, or SAT quartiles. However, in the multivariable-adjusted model, participants in the lowest VSR quartile (Q1) had significantly lower CASI total scores than those in the third quartile (Q3) (Q1: 89.5, Q3: 90.9). Low VSR was independently associated with lower cognitive function in a community-based sample of middle-aged and older Japanese men. In summary, VSR may be associated with cognitive function in Japanese men, highlighting the importance of fat distribution in cognitive health and highlighting VSR as a useful indicator.

Evidence of preclinical interactions between the gut microbiome and brain health is accumulating. Studies of animal models and specific patient populations have suggested a relationship between gut microbiomes and brain volumes, but this association is understudied in apparently healthy humans. We conducted a population-based cross-sectional study of 623 Japanese men from the Shiga Epidemiological Study on Subclinical Atherosclerosis (SESSA). We performed 16S ribosomal RNA gene sequencing of stool samples collected during the follow-up stage (mean [SD] age, 68.0 [8.0] years; range, 46–83 years). All participants underwent brain magnetic resonance imaging and automated voxel-based morphometry. Principal coordinate analysis, linear discriminant, and multivariable linear regression analyses were performed. In multivariable linear regression analysis, after adjusting for age and total intracranial volume, only gray matter volume showed a positive association with alpha diversity (the Shannon index richness, q-value <0.01). However, no association was found after further adjustments for body mass index, physical activity, smoking, drinking, and hypertension. The weighted UniFrac distances (beta diversity) measured using principal coordinate analysis showed that lower and higher white and gray matter volumes formed distinct clusters (q < 0.01). In linear discriminant analysis and multivariable-adjusted linear regression analysis, several genera were significantly associated with gray and white matter volumes (q < 0.01); however, Lachnospiraceae, a butyrate-producing bacterium, was consistently related to a higher white matter volume in different statistical analysis models. Egarthellaceae, Bifidobacteraceae, and Selenomonadaceae showed a positive association with greater gray matter volume. Our findings support an association between gut microbiome diversity and brain volumes in middle-aged to older Japanese men. This study provides insight into the underlying effects of the gut microbiome on human brain volume.

Background: The association of proteinuria and reduced estimated glomerular filtration rate (eGFR) with cognition needs more clarification. We cross-sectionally examined whether proteinuria and reduced eGFR, even in moderate stages, were independently associated with lower cognition in a community-based sample of elderly men. Methods: Our cohort initially comprised 1,094 men aged 40–79 years from a random sample from Shiga, Japan in 2006–2008. Of 853 men who returned for the follow-up examination (2009–2014), we analyzed 561 who were ≥65 years, free of stroke, and completed the Cognitive Abilities Screening Instrument (CASI) at follow-up (higher CASI scores [range 0 to 100] indicate better cognition). Proteinuria was assessed via dipstick. eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration Equation. Participants were divided into three groups either by eGFR (≥60, 59–40, and <40 mL/min/1.73 m2) or by proteinuria (no, trace, and positive), considered normal, moderate, and advanced, respectively. Using linear regression, we computed mean CASI score, with simultaneous adjustment for proteinuria and eGFR in addition to other potential confounders. Results: Significant trends of lower cognition were observed across the groups of worse proteinuria and lower eGFR independently: multivariable-adjusted mean CASI scores were 90.1, 89.3, and 88.4 for proteinuria (Ptrend = 0.029), and 90.0, 88.5, and 88.5 for eGFR (Ptrend = 0.015) in mutual-adjustment model. Conclusions: Proteinuria and reduced eGFR, even in their moderate stages, were independently associated with lower cognition in a community-based sample of elderly men. The results suggest the importance of proteinuria and low eGFR for early detection and prevention of cognitive decline.

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 , respectively) during the early morning and higher (110-140 and 35-43 mmol l , 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.

Equol is an isoflavone (ISF)-derived metabolite by the gut microbiome in certain individuals termed equol-producers (EP). Equol might be the critical anti-atherogenic component of ISFs. In a population-based study of 979 Japanese men aged 40–79 without cardiovascular (CVD) or chronic kidney disease, we measured the urinary levels of equol and ISFs. Aortic calcification (AC) in the entire aorta was assessed by electron-beam or multi-detector-row computed tomography. Subjects with log10 (urinary equol to daidzein concentration) > − 1.5 were classified as EP. EP was further classified as person with low- and high-equol. We analyzed the association between equol-producing status and AC presence, defined as AC score > 0, by the logistic regressions. We found that EP (50% of the sample) had significantly lower odds of AC presence (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.39, 0.98) compared to non-EP. This association was independent of CVD risk factors. For the dose–response association, compared to non-EP, subjects with low and high levels of equol had ORs of 0.51 (95% CI 0.30, 0.84) and 0.67 (95% CI 0.39, 1.14) after adjusting for major CVD risk factors ( p for trend = 0.06). ISFs concentrations were not significantly associated with AC presence (OR: 1.18, 95% CI: 0.82, 1.69). In conclusion, EP had a significantly lower burden of AC than non-EP, while ISFs were not associated with AC presence in Japanese men aged 40–79 years.

Background: Excessive alcohol intake has been shown to be associated with cardiovascular disease via metabolic pathways. However, the relationship between alcohol intake and obesity has not been fully elucidated. We aimed to examine the association of alcohol consumption with fat deposition and anthropometric measures. Methods: From 2006–2008, we conducted a cross-sectional study in a population-based sample of Japanese men aged 40 through 79 years. Areas of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated using computed tomography imaging. Based on a questionnaire, we classified participants into five groups according to weekly alcohol consumption, excluding former drinkers: non-drinkers (0 g/week), 0.1–160.9, 161–321.9, 322–482.9, and ≥483 g/week. Multivariable linear regression was used to estimate adjusted means of obesity indices for each group. Results: We analyzed 998 men (mean age and body mass index [BMI], 63.8 years and 23.6 kg/m2, respectively). Higher weekly alcohol consumption was strongly and significantly associated with higher abdominal VAT area, percentage of VAT, and VAT-to-SAT ratio (all P for trend <0.001), and also with waist circumferences and waist-to-hip ratio (P for trend = 0.042 and 0.007, respectively). These associations remained significant after further adjustment for BMI, whereas alcohol consumption had no significant association with abdominal SAT area. Conclusions: Higher alcohol consumption was associated with higher VAT area, VAT%, and VAT-to-SAT ratio, independent of confounders, including BMI, in general Japanese men. These results suggest that alcohol consumption may have a potential adverse effect on visceral fat deposition.

The Shiga Epidemiological Study of Subclinical Atherosclerosis was conducted in Kusatsu City, Shiga, Japan, from 2006 to 2008. Participants were measured for LDL-p through nuclear magnetic resonance technology. 740 men participated in follow-up and underwent 1.5 T brain magnetic resonance angiography from 2012 to 2015. Participants were categorized as no-ICAS, and ICAS consisted of mild-ICAS (1 to < 50%) and severe-ICAS (≥ 50%) in any of the arteries examined. After exclusion criteria, 711 men left for analysis, we used multiple logistic regression to examine the association between lipid profiles and ICAS prevalence. Among the study participants, 205 individuals (28.8%) had ICAS, while 144 individuals (20.3%) demonstrated discordance between LDL-c and LDL-p levels. The discordance “low LDL-c–high LDL-p” group had the highest ICAS risk with an adjusted OR (95% CI) of 2.78 (1.55–5.00) in the reference of the concordance “low LDL-c–low LDL-p” group. This was followed by the concordance “high LDL-c–high LDL-p” group of 2.56 (1.69–3.85) and the discordance “high LDL-c–low LDL-p” group of 2.40 (1.29–4.46). These findings suggest that evaluating LDL-p levels alongside LDL-c may aid in identifying adults at a higher risk for ICAS.

Conventional office blood pressure (OBP) and home blood pressure (HBP) measurements are often inconsistent. The purpose of this research was (1) to test whether strictly measured OBP values with sufficient rest time before measurement (st-OBP) is comparable to HBP at the population level and (2) to ascertain whether there are particular determinants for the difference between HBP and st-OBP at the individual level. Data from a population-based group of 1056 men aged 40-79 years were analyzed. After a five-min rest, st-OBP was measured twice. HBP was measured after a 2-min rest every morning for seven consecutive days. To determine factors related to ΔSBP (HBP minus st-OBP measurements), multiple linear regression analyses and analyses of covariance were performed. While st-OBP and HBP were comparable (136.5 vs. 137.2 mmHg) at the population level, ΔSBP varied with a standard deviation of 13.5 mmHg. Smoking was associated with a larger ΔSBP regardless of antihypertensive usage, and BMI was associated with a larger ΔSBP in participants using antihypertensive drugs. The adjusted mean ΔSBP in the highest BMI tertile category was 4.6 mmHg in participants taking antihypertensive drugs. st-OBP and HBP measurements were comparable at the population level, although the distribution of ΔSBP was considerably broad. Smokers and obese men taking antihypertensive drugs had higher HBP than st-OBP, indicating that their blood pressure levels are at risk of being underestimated. Therefore, this group would benefit from the addition of HBP measurements.

ObjectiveWe investigated the associations of nocturnal oxygen saturation (SpO2) with prevalence of coronary artery calcification (CAC) and its level of burden, and whether the associations differ by obesity and mediate through diabetes mellitus (DM), dyslipidaemia and hypertension.DesignObservational study.SettingKusatsu, Shiga.ParticipantsWe analysed data from 510 Japanese men (aged 46–76 years) with no history of myocardial infarction.Primary and secondary outcomesMean SpO2, minimum SpO2 and oxygen desaturation index (ODI) were measured using overnight pulse oximetry (primary exposures), while CAC was assessed using CT. Prevalence of CAC (>0) and its burden (CAC 0, >0–100, >100–400 and>400) were evaluated as outcomes. Body mass index≥25.0 kg/m2 defined as obesity.ResultsMean±SD age was 66.7±7.2 years. The prevalence of CAC was 64.7% (CAC scores>0–100, 31.4%; >100–400, 20.0% and>400, 13.3%). In multivariable binary logistic regression, the OR and 95% CI for the prevalence of CAC were 1.25 (1.02 to 1.53) per 1-SD decrement in mean SpO2 and 1.25 (1.01 to 1.55) per 1-SD increment in ODI. The associations lost their significance while further adjusted for DM and dyslipidaemia. Similar trends were observed for the level of CAC burden in multivariable ordinal logistic regression. Obesity did not show significant interaction with SpO2 on CAC. In mediation analysis, the OR (95% CI) for natural indirect effect; percentage mediated through dyslipidaemia in association of 1-SD decrement in mean SpO2 with prevalence of CAC were 1.06 (1.01 to 1.10); 25.4%. These estimates for mediation through DM and dyslipidaemia for 1-SD increment in ODI in the associations were 1.07 (1.01 to 1.12); 29.6% and 1.04 (1.00 to 1.08); 17.5%, respectively.ConclusionsLower mean SpO2 and higher ODI are associated with CAC among Japanese men, independent of age, lifestyle factors and obesity. The associations became non-significant after adjusting for diabetes and dyslipidaemia, but were mediated through these factors.