Association between trunk-to-peripheral fat ratio and renal function in elderly Japanese men: baseline data from the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study.

BACKGROUND: Central obesity as measured by waist-to-hip circumference ratio (WHR) has been reported to be associated with renal hemodynamics and function. However, the adipose component of WHR, which is a composite measure of fat mass and fat-free mass, is small, particularly in nonobese subjects. Trunk-to-peripheral fat ratio as measured using dual-energy absorptiometry (DXA) is a more precise method for evaluating central fat distribution than WHR. The present study investigated the cross-sectional association between DXA-measured trunk-to-peripheral fat ratio and estimated glomerular filtration rate (eGFR) in community-dwelling elderly Japanese men. METHODS: Participants were 575 men aged ≥65 years at the time of the baseline survey of the second Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study. Trunk-to-appendicular fat ratio (TAR) was calculated as trunk fat divided by appendicular fat (sum of arm and leg fat), and trunk-to-leg fat ratio (TLR) as trunk fat divided by leg fat. RESULTS: eGFR values significantly decreased from the lowest to the highest quintile of TAR/TLR. After adjusting for potential confounding factors including whole-body fat, the highest quintile of both TAR and TLR showed statistically significant odds ratios for the risk of eGFR <60 ml/min/1.73 m2, relative to the lowest quintile. In addition, a significant decreasing trend was observed for eGFR values from the lowest to the highest quintile of TAR/TLR after adjusting for confounding factors including whole-body fat. CONCLUSION: Elderly men with a large trunk-to-peripheral fat ratio tended to have a lower eGFR. This association occurred independently of that between whole-body fat and eGFR.

Association between household solid fuel use and tuberculosis: cross-sectional data from the Mongolian National Tuberculosis Prevalence Survey.

BACKGROUND: Tuberculosis (TB) and indoor air pollution (IAP) are equally critical public health issues in the developing world. Mongolia is experiencing the double burden of TB and IAP due to solid fuel combustion. However, no study has assessed the relationship between household solid fuel use and TB in Mongolia. The present study aimed to assess the association between household solid fuel use and TB based on data from the Mongolian National Tuberculosis Prevalence Survey (MNTP Survey). METHOD: The MNTP Survey was a nationally representative population-based cross-sectional survey targeting households in Mongolia from 2014 to 2015, with the aim of evaluating the prevalence of TB. The survey adopted a multistage cluster sampling design in accordance with the World Health Organization prevalence survey guidelines. Clusters with at least 500 residents were selected by random sampling. A sample size of 98 clusters with 54,100 participants was estimated to be required for the survey, and 41,450 participants were included in the final analysis of the present study. A structured questionnaire was used to collect information on environmental and individual factors related to TB. Physical examination, chest X-ray, and sputum examinations were also performed to diagnose TB. RESULTS: The use of solid fuels for heating (adjusted odds ratio (aOR): 1.5; 95% confidence interval (CI): 1.1-2.1), male gender (aOR: 2.2; 95% CI: 1.6-3.2), divorced or widowed (aOR: 2.6; 95% CI: 1.7-3.8), daily smoker (aOR: 1.8; 95% CI: 1.3-2.5), contact with an active TB case (aOR: 1.7; 95% CI: 1.2-2.3), being underweight (aOR: 3.7; 95% CI: 2.4-5.7), and previous history of TB (aOR: 4.3; 95% CI: 3.0-6.1) were significantly associated with bacteriologically confirmed TB after adjusting for confounding variables. CONCLUSION: The use of solid fuels for heating was significantly associated with active TB in Mongolian adults. Increased public awareness is needed on the use of household solid fuels, a source of IAP.

Oxidized LDL (oxLDL) activates the angiotensin II type 1 receptor by binding to the lectin-like oxLDL receptor.

The angiotensin II type 1 receptor (AT1) is a 7-transmembrane domain GPCR that when activated by its ligand angiotensin II, generates signaling events promoting vascular dysfunction and the development of cardiovascular disease. Here, we show that the single-transmembrane oxidized LDL (oxLDL) receptor (LOX-1) resides in proximity to AT1 on cell-surface membranes and that binding of oxLDL to LOX-1 can allosterically activate AT1-dependent signaling events. oxLDL-induced signaling events in human vascular endothelial cells were abolished by knockdown of AT1 and inhibited by AT1 blockade (ARB). oxLDL increased cytosolic G protein by 350% in Chinese hamster ovary (CHO) cells with genetically induced expression of AT1 and LOX-1, whereas little increase was observed in CHO cells expressing only LOX-1. Immunoprecipitation and in situ proximity ligation assay (PLA) assays in CHO cells revealed the presence of cell-surface complexes involving LOX-1 and AT1. Chimeric analysis showed that oxLDL-induced AT1 signaling events are mediated via interactions between the intracellular domain of LOX-1 and AT1 that activate AT1. oxLDL-induced impairment of endothelium-dependent vascular relaxation of vascular ring from mouse thoracic aorta was abolished by ARB or genetic deletion of AT1. These findings reveal a novel pathway for AT1 activation and suggest a new mechanism whereby oxLDL may be promoting risk for cardiovascular disease.

Body weight at 1.5- and 3-year health checks and body fat at 14 years of age: a population-based retrospective cohort study using dual-energy X-ray absorptiometry.

BACKGROUND: In Japan, height and weight measurements, taken for all children at birth and 1.5- and 3-year health checks, are recorded in the Mother and Child Health (MCH) Handbook, as required by the law. The present population-based retrospective cohort study aimed to evaluate the diagnostic performance of height and weight records in the Handbook for predicting excessive adiposity in adolescents. METHODS: The source population consisted of 8th grade students (800 students aged 14 years) registered at two public junior high schools. Of these, we excluded students who were born at a gestational age < 37 weeks or > 42 weeks. The present analyses included 435 participants who provided complete information. Body mass index (BMI) was calculated using height and weight records. Body fat mass at 14 years of age was measured by dual-energy X-ray absorptiometry (DXA). Diagnostic performance of BMI calculated from the MCH Handbook records to discriminate between the presence and absence of excessive adiposity at 14 years of age was evaluated using receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC) was used to quantify the diagnostic accuracy of BMI. RESULTS: With regard to the prediction of excessive fat at 14 years of age, AUCs and 95% confidence intervals for BMI at 1.5 and 3 years of age were greater than 0.5. Meanwhile, the AUC of BMI at birth was not significantly greater than 0.5. CONCLUSION: The present study findings indicate that BMI values calculated using MCH Handbook data have potential ability to distinguish between the presence and absence of excessive fat at 14 years of age.

Use of heated tobacco products by people with chronic diseases: The 2019 JASTIS study.

Heated tobacco products (HTPs) have become popular recently. People with chronic disease, such as diabetes, cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD) and cancer, should quit smoking for treatment and recurrence of tobacco-related diseases. However, they have difficulty in quitting smoking, and they may start HTPs use to quit smoking. The purpose of this study is to examine the use of HTPs in people with chronic disease. We used data from an internet study, the Japan Society and New Tobacco Internet Survey (JASTIS). We analyzed 9,008 respondents aged 15-73 years in 2019 using logistic regression. Current use of tobacco products was defined as use within the previous 30 days. Prevalence of current HTP use including dual use and dual use with cigarettes was 9.0% and 6.1% respectively in total. By disease: hypertension 10.2% and 7.4%, diabetes 15.9% and 12.3%, CVD 19.2% and 15.7%, COPD 40.5% and 33.3%, and cancer 17.5% and 11.9%. Diabetes, CVD, COPD, and cancer were positively associated with current use of HTPs (odds ratios (ORs) and 95% confidence intervals (CIs): 1.48 (1.06, 2.07), 2.29 (1.38, 3.80), 3.97(1.73, 9.11), and 3.58(1.99, 6.44), respectively) and dual use of cigarettes and HTPs (ORs and 95% CIs: 2.23 (1.61, 3.09), 3.58 (2.29, 5.60), 7.46 (3.76, 14.80), and 2.57 (1.46, 4.55), respectively) after adjusting for confounders. People with chronic disease were more likely to use HTPs and HTPs together with cigarettes. Further research on the smoking situation of HTPs in patients with chronic diseases is necessary.

Assessing the risk of COVID-19 from multiple pathways of exposure to SARS-CoV-2: Modeling in health-care settings and effectiveness of nonpharmaceutical interventions.

We assessed the risk of COVID-19 infection in a healthcare worker (HCW) from multiple pathways of exposure to SARS-CoV-2 in a health-care setting of short distance of 0.6 m between the HCW and a patient while caring, and evaluated the effectiveness of a face mask and a face shield using a model that combined previous infection-risk models. The multiple pathways of exposure included hand contact via contaminated surfaces and an HCW's fingers with droplets, droplet spray, and inhalation of inspirable and respirable particles. We assumed a scenario of medium contact time (MCT) and long contact time (LCT) over 1 day of care by an HCW. SARS-CoV-2 in the particles emitted by coughing, breathing, and vocalization (only in the LCT scenario) by the patient were considered. The contribution of the risk of infection of an HCW by SARS-CoV-2 from each pathway to the sum of the risks from all pathways depended on virus concentration in the saliva of the patient. At a virus concentration in the saliva of 101-105 PFU mL-1 concentration in the MCT scenario and 101-104 PFU mL-1 concentration in the LCT scenario, droplet spraying was the major pathway (60%-86%) of infection, followed by hand contact via contaminated surfaces (9%-32%). At a high virus concentration in the saliva (106-108 PFU mL-1 in the MCT scenario and 105-108 PFU mL-1 in the LCT scenario), hand contact via contaminated surfaces was the main contributor (41%-83%) to infection. The contribution of inhalation of inspirable particles was 4%-10% in all assumed cases. The contribution of inhalation of respirable particles increased as the virus concentration in the saliva increased, and reached 5%-27% at the high saliva concentration (107 and 108 PFU mL-1) in the assumed scenarios using higher dose-response function parameter (0.246) and comparable to other pathways, although these were worst and rare cases. Regarding the effectiveness of nonpharmaceutical interventions, the relative risk (RR) of an overall risk for an HCW with an intervention vs. an HCW without intervention was 0.36-0.37, 0.02-0.03, and <4.0 × 10-4 for a face mask, a face shield, and a face mask plus shield, respectively, in the likely median virus concentration in the saliva (102-104 PFU mL-1), suggesting that personal protective equipment decreased the infection risk by 63%->99.9%. In addition, the RR for a face mask worn by the patient, and a face mask worn by the patient plus increase of air change rate from 2 h-1 to 6 h-1 was <1.0 × 10-4 and <5.0 × 10-5, respectively in the same virus concentration in the saliva. Therefore, by modeling multiple pathways of exposure, the contribution of the infection risk from each pathway and the effectiveness of nonpharmaceutical interventions for COVID-19 were indicated quantitatively, and the importance of the use of a face mask and shield was confirmed.

Infant weight gain and DXA-measured adolescent adiposity: data from the Japan Kids Body-composition Study.

BACKGROUND: Rapid weight gain in early life is associated with adiposity later in life. However, there is limited information on the association between weight gain and body fat mass measured using precise methods. This study aimed to investigate whether weight gain is associated with body fat mass measured by dual-energy X-ray absorptiometry (DXA) in adolescents. METHODS: Participants of this retrospective cohort study were 423 adolescents born at full-term who were enrolled in the Japan Kids Body-composition Study. Anthropometric measurements related to pregnancy, delivery, and child health were obtained from the Japanese Maternal and Child Health Handbook. Fat mass in adolescents was measured with a DXA scanner. Weight gain was defined as the change in body weight from birth to age 1.5 years. Associations between birthweight and fat mass, and between weight gain and fat mass, were evaluated using multiple regression analysis. RESULTS: There was a significant positive association between weight gain from birth to age 1.5 years and fat mass in adolescents (boys: standardized regression coefficient (ß) = 0.253, p < 0.01; girls: ß = 0.246, p < 0.01), but not between birthweight standardized for gestational age and fat mass. CONCLUSION: Children with a greater change in weight from birth to age 1.5 years tended to have increased fat mass in adolescence. Weight gain in early life has a greater impact on fat mass in adolescents than birthweight.

Cross-sectional association of bone mineral density with coronary artery calcification in an international multi-ethnic population-based cohort of men aged 40-49: ERA JUMP study.

INTRODUCTION: Inverse associations of cardiovascular disease (CVD) and atherosclerosis with osteoporosis and bone mineral density (BMD) have been reported in post-menopausal women and elderly men. We aimed to investigate an association between vetebral bone density (VBD) and coronary artery cacification (CAC) in an international multi-ethnic cohort of middle-aged men in the EBCT and Risk Factor Assessment among Japanese and US Men in the Post-World-War-II birth cohort (ERA JUMP). METHODS: ERA JUMP examined 1134 men aged 40-49 (267 white, 84 black, and 242 Japanese Americans, 308 Japanese in Japan, and 233 Koreans in South Korea) free from CVD for CAC, and VBD, biomarkers of coronary atherosclerosis and BMD, respectively, with electron-beam computed tomography, and other risk factors. CAC was quantified with the Agatston method and VBD by computing the mean Hounsfield Unit (HU) value of the T12 to L3 vertebrae. To examine multivariable-adjusted associations of CAC with VBD, we used robust linear and logistic regressions. RESULTS: The mean VBD and median CAC were 175.4 HU (standard deviation: 36.3) and 0 (interquartile range: (0, 4.5)), respectively. The frequency of CAC was 19.0%. There was no significant interaction by race. VBD had a significant inverse association with CAC score (ß = -0.207, p-value = 0.005), while a 10-unit increase in VBD was significantly associated with the frequency of CAC (odds ratio (95% confidence interval) = 0.929 (0.890-0.969)). Both associations remained significant after adjusting for covariates. CONCLUSIONS: VBD had a significant inverse association with CAC in this international multi-ethnic cohort of men aged 40-49.

Relationship between atherosclerosis and occlusal support of natural teeth with mediating effect of atheroprotective nutrients: From the SONIC study.

Whereas most of studies investigating relationship between oral health and atherosclerosis have focused on periodontitis, very few of them were examined about occlusal status of natural teeth which possibly influence dietary habit. The primary aim of this cross-sectional study was to investigate the association between the occlusal support of posterior teeth and the prevalence of atherosclerosis in community-dwelling septuagenarians. Also, the second aim was to test the hypothesis that the intake of key nutrients for atherosclerosis prevention would have a mediating effect on the relationship between the occlusal status and atherosclerosis. The study population included 468 community-dwelling dentate persons aged 69-71 years recruited from the local residential registration in Japan. Participants were divided into three groups, according to the number of occlusal support zones (OSZ) in the posterior area: Complete (four OSZ), Moderate (three or two OSZ), and Collapsed (one or no OSZ). Dietary intakes were assessed using a brief-type self-administered diet history questionnaire. Atherosclerosis was defined as carotid intima-media thickness ≧1.10 mm by using carotid ultrasonography test. The logistic or linear regression model was used in multivariate analysis to assess relationship between occlusal status and atherosclerosis, and the mediating effect of key nutrients within the relationship. Multivariable analysis showed a significant association between occlusal status and atherosclerosis (odds ratio for Collapsed group to Complete group: 1.87; 95% CI: 1.45-2.41), independent of periodontal status (odds ratio: 2.01, 95%CI: 1.46-2.78). Fish and shellfish, vitamin B6 and n-3PUFAs were significantly related to both of occlusal status and atherosclerosis, and also was indicated a mediating effect on the association between occlusal status and atherosclerosis. This study implied that, within the limitation of the cross-sectional study design, the reduced posterior occlusion was related to the increased prevalence of atherosclerosis via the decline of key dietary intakes among Japanese community-dwelling dentate individuals.

Longitudinal association of hypertension and diabetes mellitus with cognitive functioning in a general 70-year-old population: the SONIC study.

Both hypertension and diabetes in middle-aged individuals have been suggested to be predictive indicators of cognitive decline. However, the association of hypertension, diabetes and their combination with cognitive functioning is still controversial in older people. The purpose of this study was to investigate the association between cognitive decline and hypertension, diabetes, and their combination in 70-year-old people based on a 3-year longitudinal analysis. Four hundred and fifty-four people aged 70 (±1) years who participated in the Japanese longitudinal cohort study of Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians (SONIC) were recruited randomly from a general population and were monitored for 3 years. The data, including most of the demographics, cognitive functioning measured by the Montreal Cognitive Assessment Japanese version (MoCA-J), blood pressure, blood chemistry and other medical histories, were collected at baseline and during the follow-up. The prevalence of hypertension noted in the follow-up survey was significantly higher than than noted at baseline. The mean MoCA-J score at follow-up was not significantly different from the score obtained at baseline. However, the participants with diabetes, especially combined with hypertension at baseline, had significantly lower MoCA-J scores than those without lifestyle-related diseases. The combination of hypertension and diabetes was still a significant risk factor for cognitive decline, considering the MoCA-J scores obtained during the follow-up after adjustments at baseline, relative to sex, body mass index, dyslipidemia, smoking, excessive alcohol intake, antihypertensive treatment and education level (ß=-0.14; P<0.01). Our findings indicate that diabetes and the combination of hypertension and diabetes are clear risk factors for future cognitive decline in elderly individuals who are 70 years of age.

Association Analysis of FOXO3 Longevity Variants With Blood Pressure and Essential Hypertension.

BACKGROUND: The minor alleles of 3 FOXO3 single nucleotide polymorphisms (SNPs)- rs2802292 , rs2253310 , and rs2802288 -are associated with human longevity. The aim of the present study was to test these SNPs for association with blood pressure (BP) and essential hypertension (EHT). METHODS: In a primary study involving Americans of Japanese ancestry drawn from the Family Blood Pressure Program II we genotyped 411 female and 432 male subjects aged 40-79 years and tested for statistical association by contingency table analysis and generalized linear models that included logistic regression adjusting for sibling correlation in the data set. Replication of rs2802292 with EHT was attempted in Japanese SONIC study subjects and of each SNP in a meta-analysis of genome-wide association studies of BP in individuals of European ancestry. RESULTS: In Americans of Japanese ancestry, women homozygous for the longevity-associated (minor) allele of each FOXO3 SNP had 6mm Hg lower systolic BP and 3mm Hg lower diastolic BP compared with major allele homozygotes (Bonferroni corrected P < 0.05 and >0.05, respectively). Frequencies of minor allele homozygotes were 3.3-3.9% in women with EHT compared with 9.5-9.6% in normotensive women ( P = 0.03-0.04; haplotype analysis P = 0.0002). No association with BP or EHT was evident in males. An association with EHT was seen for the minor allele of rs2802292 in the Japanese SONIC cohort ( P = 0.03), while in European subjects the minor allele of each SNP was associated with higher systolic and diastolic BP. CONCLUSION: Longevity-associated FOXO3 variants may be associated with lower BP and EHT in Japanese women.

Differences in the association between high blood pressure and cognitive functioning among the general Japanese population aged 70 and 80 years: The SONIC study.

High blood pressure in middle age (up to 64 years) has been proposed as a predictive indicator of dementia. However, the association between hypertension and the cognitive functioning is controversial in older age groups. The aim of this study was to investigate this association in 70-80-year-old participants in the Japanese study of Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians (SONIC). Participants aged 70 (±1) and 80 (±1) years (n=1000 and 973, respectively) were randomly recruited from the general population in Japan. Cognitive functioning was measured by the Montreal Cognitive Assessment. Blood pressure and other medical and social variables were analyzed by multiple regression analyses. High systolic blood pressure (SBP) was significantly correlated with a reduced cognitive functioning only in participants aged 70 years. Additionally, this correlation became more marked in participants with uncontrolled blood pressure at age 70 years. In contrast, SBP was not significantly correlated with the cognitive functioning at age 80 years. Nutritional status indicators such as serum albumin and frequency of going outdoors were significantly associated with cognitive functioning at age 80 years. Our findings indicate that high SBP has a significant role in cognitive functioning at age 70 years; however, blood pressure is less important as a risk factor for cognitive decline at age 80 years.

Disease-associated polymorphisms in 9p21 are not associated with extreme longevity.

AIM: The 9p21 region has been pointed out by the genome-wide association studies as a hot spot for disease-associated variants. Most of the diseases linked with the locus are aging-related conditions, such us cardiovascular disease, diabetes and cancer. Centenarians are known to present a reduced risk and delayed onset for these conditions. Here, we aimed to assess if the 9p21 variants contribute to this protection by possibly altering basic aging mechanisms. METHODS: We genotyped 15 tag single-nucleotide polymorphisms (SNP) along the CDKN2A/B/ANRIL locus in 1505 individuals. The participants were divided in three groups: centenarians, septuagenarians and young controls. Centenarians were 593 participants (age range 100-116 years, mean 105.9 years), septuagenarians were 434 volunteers aged between 69 and 71 years (mean 70.1 ± 0.9 years) and the 478 young controls were under the age of 50 years (range 14-50 years, mean 41.8 years). We genotyped the SNP rs1333049 in an additional sample of 231 coronary artery disease patients to confirm the 9p21 association. RESULTS: The leading coronary artery disease-associated SNP rs1333049 was associated with coronary artery disease; however, none of the 9p21 SNP evaluated in the present study were associated with extreme longevity. CONCLUSIONS: Our findings suggest that the 9p21 disease-associated polymorphisms do not contribute to the life-long protection from cardiovascular and other age-related diseases observed in centenarians. It is likely that this protection is mediated by mechanisms different from the ones underlying the 9p21 association.

The influence of aging on the diagnosis of primary aldosteronism.

Primary aldosteronism (PA) is common in young or middle-aged hypertensive patients, but PA among the elderly has recently become more common. As salt sensitivity increases with age, plasma renin activity (PRA) tends to decrease, whereas the aldosterone-to-renin ratio (ARR) tends to increase in the elderly. The aim of this study was to clarify the influence of aging on the diagnosis of PA. We retrospectively evaluated 155 consecutively admitted patients who were not taking antihypertensive medications or calcium channel blockers and α blockers that underwent PRA and plasma aldosterone concentration (PAC) measurements. The study subjects included 13 PA and 69 essential hypertensive (EHT) patients aged over 65 years, and 32 PA and 41 EHT patients under aged 65 years. Our study clarified the influence of aging through screening and confirmatory tests for the diagnosis of PA. Our results showed the ARR cutoff value for a screening test to be 556 (area under the curve: AUC=0.906), its sensitivity and specificity to be 84.6% and 89.9%, respectively, and the likelihood ratio to be 8.34 in the elderly, whereas the ARR cutoff value was 272 in the non-elderly. In the saline infusion test, the mean PAC was 86.6 ± 41.8 pg ml(-1) in the elderly and 158.1 ± 116.5 pg ml(-1) in the non-elderly (P = 0.04). There was no influence from age in both the captopril challenge test and the furosemide upright test. Aging may influence PA screening and saline infusion tests; thus, we should consider the influence of aging in the diagnosis of elderly subjects with PA.

Differences between daytime and nighttime blood pressure variability regarding systemic atherosclerotic change and renal function.

Recently, new parameters related to hypertension, such as variability in blood pressure and ambulatory arterial stiffness index (AASI), were demonstrated to correlate with arteriosclerotic change. In this study, we investigated the correlation between circadian variability in blood pressure/AASI and renal function. We also investigated differences in the clinical impact of 24 h, daytime and nighttime blood pressure variability on renal and systemic atherosclerotic changes. We analyzed data from 120 patients who underwent renal Doppler ultrasonography (RDU) and ambulatory blood pressure monitoring (ABPM) at our hospital ward, and investigated the correlation between circadian variability in blood pressure/AASI and renal function, including resistive index (RI) evaluated with RDU, which is thought to be a good indicator of renal vascular resistance. Subjects with higher circadian variability in systolic blood pressure (SBP) had significantly higher RI. Daytime variability in SBP correlated more strongly with RI than nighttime variability. Meanwhile, only nighttime variability, but not daytime variability, in SBP was related to carotid atherosclerosis. Similarly, AASI was significantly correlated with RI. Circadian variability in SBP and AASI were both significantly correlated with renal function. Daytime SBP s.d. was especially more strongly correlated with renal vascular resistance, and nighttime SBP s.d. was significantly correlated with intima-media thickness (IMT) and plaque score. These results indicate that evaluating both daytime and nighttime blood pressure variability enables an assessment of pathological conditions in hypertensive patients to prevent cardiovascular diseases.