Combined effects of blood pressure and glucose status on the risk of chronic kidney disease.

This study aimed to assess the combined effects of blood pressure (BP) and glucose status on chronic kidney disease (CKD) incidence in young and middle-aged adults. We examined data from 1,297,341 Japanese individuals aged <60 years (60.1% men; mean age 41.4 ± 9.3 years) with no history of CKD at baseline. The interval-censored Cox proportional hazards model with covariates was used. During a median follow-up period of 2.1 years, new onset CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2 and/or proteinuria) occurred in 80,187 participants. In participants without antihypertensive treatment (AHT), the adjusted hazard ratios (95% confidence interval) per 1-standard deviation, that is, 15 mmHg increase in systolic BP for CKD incidence, were 1.08 (1.07-1.09), 1.12 (1.10-1.13), and 1.15 (1.12-1.18) in normoglycemia, borderline glycemia, and diabetes groups, respectively. These ratios were significantly higher in the borderline glycemia and diabetes groups compared with those in the normoglycemia group (interaction p < 0.0001). The interaction between BP and borderline glycemia was evident when the outcome definition was restricted to proteinuria. In participants under AHT, systolic BP was most strongly associated with CKD risk in the diabetes group, although no significant interaction was observed. High BP and high glucose status may synergistically increase the incidence of CKD. Strict BP management may play an important role in the early prevention of CKD in individuals with worse glucose status within the young and middle-aged population. This large-scale longitudinal cohort study showed high BP and diabetes synergistically increased the risk of CKD in individuals without AHT. Strict BP management may play an important role in the early prevention of CKD in individuals with worse glucose status within the young and middle-aged population.

Progress report of the Tohoku Medical Megabank Community-Based Cohort Study: Study profile of the repeated center-based survey during second period in Miyagi Prefecture.

BACKGROUND: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period (2nd period survey) of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants' characteristics based on their participation type in the baseline survey. METHODS: The 2nd period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the 2nd period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The 2nd period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC). RESULTS: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the 2nd period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the 2nd period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits. CONCLUSIONS: The 2nd period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.

Association between Maternal Birth Weight and Prevalence of Congenital Malformations in Offspring: The Japanese Environment and Children's Study.

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that an MBW of <2500 g (low MBW) was associated with an increased risk of congenital heart disease (adjusted odds ratio: 1.388, [95% confidence interval: 1.075-1.792]), angioma (1.491 [1.079-2.059]), and inguinal hernia (1.746, [1.189-2.565]), while those with an MBW of ≥4000 g (high MBW) were associated with congenital anomalies of the urinary tract (2.194, [1.261-3.819]) and arrhythmia (1.775, [1.157-2.725]) compared with those with an MBW of 3000-3499 g. Low MBW was associated with cleft lip and/or palate (1.473, [1.052-2.064]), congenital heart disease (1.615, [1.119-2.332]), genital organs (1.648, [1.130-2.405]), hypospadias (1.804, [1.130-2.881]), and inguinal hernia (1.484, [1.189-1.851]) in male infants and CAKUT (1.619, [1.154-2.273]) in female infants, whereas high MBW was associated with congenital heart disease (1.745, [1.058-2.877]) and CAKUT (2.470, [1.350-4.517]) in male infants. The present study is the first to demonstrate a link between MBW and congenital malformations in Japanese children. While these results must be interpreted with caution, MBW should be considered a major predictor of congenital malformation risk.

Maternal birth weight as an indicator of early and late gestational diabetes mellitus: The Japan Environment and Children's Study.

AIMS: This study aimed to investigate the association of maternal birth weight (MBW) with early and late gestational diabetes mellitus (GDM). METHODS: A total of 69318 pregnant Japanese women were included in this birth cohort study. The associations between maternal birth weight and early gestational diabetes mellitus (diagnosed at <24 gestational weeks) and late GDM (diagnosed at ≥24 gestational weeks) were investigated using a multinomial logistic regression model, with an maternal birth weight of 3000-3499 g as the reference category. RESULTS: Lower maternal birth weight was associated with higher odds of developing early and late gestational diabetes mellitus (P < 0.0001 and P < 0.0001, respectively). The adjusted odds ratios (aORs) for early gestational diabetes mellitus in participants with a MBW of <2500 g and 2500-2999 g were 1.345 (95% confidence interval [CI]: 0.912-1.984) and 1.338 (95% CI: 1.098-1.629), respectively. The aORs for late gestational diabetes mellitus in participants with a MBW of <2500 g and 2500-2999 g were, 1.657 (95% CI: 1.298-2.115) and 1.218 (95% CI: 1.058-1.402), respectively. CONCLUSIONS: Regardless of the gestational age when gestational diabetes mellitus was diagnosed, a lower maternal birth weight was associated with an increased risk of gestational diabetes mellitus. Furthermore, the association of a MBW <2500 g with late gestational diabetes mellitus tended to be stronger than that with early gestational diabetes mellitus.

Association of parity with the prevalence of hypertension in Japan: The Tohoku Medical Megabank Community-based cohort study.

This study investigated the association of parity with hypertension prevalence in Japanese women while considering a clinical history of hypertensive disorders of pregnancy (HDP) and menopausal status. This cross-sectional study included 30,530 Japanese women (6700 premenopausal; 23 830 postmenopausal). The association between parity and the prevalence of hypertension was evaluated using a multiple logistic regression model with possible confounders. In premenopausal women, no statistically significant association between parity and hypertension prevalence was found. When not adjusted for current body mass index (BMI), a linear graded association was observed between parity and the prevalence of hypertension in postmenopausal women. However, the association between parity and hypertension prevalence in postmenopausal women was attenuated after adjustment for current BMI. Both current BMI and a clinical history of HDP were significantly associated with a high risk of hypertension in both premenopausal and postmenopausal women. Our results also suggest that continuous surveillance and preventive measures for hypertension should be provided for women with HDP and high parity.

The association between blood pressure control in women during pregnancy and adverse perinatal outcomes: the TMM BirThree Cohort Study.

Blood pressure (BP) control in pregnancy is essential to prevent adverse outcomes. However, BP levels for hypertension treatment are inconsistent among various guidelines. This study investigated the association between BP control and adverse perinatal outcomes. A total of 18,155 mother-offspring pairs were classified into four groups according to BP after 20 gestational weeks: normal BP (<140/90 mmHg without antihypertensive drugs), high BP (≥140/90 mmHg without antihypertensive drugs), controlled BP (<140/90 mmHg with antihypertensive drugs), and uncontrolled BP (≥140/90 mmHg with antihypertensive drugs). The prevalence of small for gestational age was 1,087/17,476 offspring in normal BP, 78/604 in high BP, 5/42 in controlled BP, and 7/33 in uncontrolled BP. Compared to normal BP, adjusted odds ratios (ORs) (95% confidence intervals (CIs)) were 1.76 (1.32-2.35) for high BP, 2.08 (0.79-5.50) for controlled BP, and 2.34 (0.94-5.85) for uncontrolled BP (multiple logistic regression analysis). Similarly, the adjusted ORs (95% CIs) were 1.80 (1.35-2.41), 3.42 (1.35-8.63), and 5.10 (1.93-13.45) for high, controlled, and uncontrolled BPs for low birth weight, respectively; 1.99 (1.48-2.68), 2.70 (1.12-6.50), and 6.53 (3.09-13.82) for high, controlled, and uncontrolled BPs for preterm birth, respectively; 1.64 (1.19-2.24), 2.17 (0.88-5.38), and 2.12 (0.80-5.65) for high, controlled, and uncontrolled BPs for admission to the Neonatal Intensive Care Unit or Growing Care Unit, respectively; and 1.17 (0.70-1.95), 2.23 (0.65-7.68), and 0.91 (0.20-4.16) for high, controlled, and uncontrolled BPs for 1-min Apgar score < 7, respectively. BP ≥ 140/90 mmHg might be taken care for preventing various adverse perinatal outcomes.

The Population-Attributable Fractions of Small-for-Gestational-Age Births: Results from the Japan Birth Cohort Consortium.

A fetal growth restriction is related to adverse child outcomes. We investigated risk ratios and population-attributable fractions (PAF) of small-for-gestational-age (SGA) infants in the Japanese population. Among 28,838 infants from five ongoing prospective birth cohort studies under the Japan Birth Cohort Consortium, two-stage individual-participant data meta-analyses were conducted to calculate risk ratios and PAFs for SGA in advanced maternal age, pre-pregnancy underweight, and smoking and alcohol consumption during pregnancy. Risk ratio was calculated using modified Poisson analyses with robust variance and PAF was calculated in each cohort, following common analyses protocols. Then, results from each cohort study were combined by meta-analyses using random-effects models to obtain the overall estimate for the Japanese population. In this meta-analysis, an increased risk (risk ratio, [95% confidence interval of SGA]) was significantly associated with pre-pregnancy underweight (1.72 [1.42-2.09]), gestational weight gain (1.95 [1.61-2.38]), and continued smoking during pregnancy (1.59 [1.01-2.50]). PAF of underweight, inadequate gestational weight gain, and continued smoking during pregnancy was 10.0% [4.6-15.1%], 31.4% [22.1-39.6%], and 3.2% [-4.8-10.5%], respectively. In conclusion, maternal weight status was a major contributor to SGA births in Japan. Improving maternal weight status should be prioritized to prevent fetal growth restriction.

Maternal social isolation and behavioral problems in preschool children: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

It is essential to clarify factors associated with mental health and behavioral problems in early childhood, because children are critical stages of life for mental health. We aimed to prospectively examine the associations between maternal social isolation and behavioral problems in preschool children. We analyzed data from 5842 mother-child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. The Lubben Social Network Scale-abbreviated version was used to assess social isolation (defined as scores < 12) one year after delivery. The Child Behavior Checklist 1½-5 was used to assess behavioral problems, and its subscales were used to assess internalizing and externalizing problems in children at 4 years of age. Multiple logistic regression analyses were conducted to examine the associations between social isolation and behavioral problems, after adjustment for age, education, income, work status, marital status, extraversion, neuroticism, depressive symptoms, child sex, and number of siblings. Multiple logistic regression analyses were also conducted for internalizing problems and externalizing problems. The prevalence of maternal social isolation was 25.4%. Maternal social isolation was associated with an increased risk of behavioral problems in children: the odds ratio (OR) was 1.37 (95% confidence interval [CI] 1.14-1.64). Maternal social isolation was also associated with increased risks of internalizing problems and externalizing problems in children: the ORs were 1.33 (95% CI, 1.12-1.59) and 1.40 (95% CI, 1.18-1.66), respectively. In conclusion, maternal social isolation one year after delivery was associated with behavioral problems in children at 4 years of age.

The association between depressive symptoms and masked hypertension in participants with normotension measured at research center.

Masked hypertension is a risk factor for cardiovascular diseases. However, masked hypertension is sometimes overlooked owing to the requirement for home blood pressure measurements for diagnosing. Mental status influences blood pressure. To reduce undiagnosed masked hypertension, this study assessed the association between depressive symptoms and masked hypertension. This cross-sectional study used data from the Tohoku Medical Megabank Project Community-Based Cohort Study (conducted in Miyagi Prefecture, Japan, from 2013) and included participants with normotension measured at the research center (systolic blood pressure<140 mmHg and diastolic blood pressure <90 mmHg). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (Japanese version). Masked hypertension was defined as normotension measured at the research center and home hypertension (home systolic blood pressure ≥135 mmHg or home diastolic blood pressure ≥85 mmHg). The study comprised 6705 participants (mean age: 55.7 ± 13.7 years). Of these participants, 1106 (22.1%) without depressive symptoms and 393 (23.2%) with depressive symptoms were categorized to have masked hypertension. Sex-specific and age-adjusted least mean squares for home blood pressure, not for research blood pressure were significantly higher in the group with depressive symptoms in both sex categories. The multivariate odds ratio for masked hypertension in the patients with depressive symptoms was 1.72 (95% confidence interval: 1.26-2.34) in male participants and 1.30 (95% confidence interval: 1.06-1.59) in female ones. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at the research center. Depressive symptoms may be one of the risk factors for masked hypertension. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at research center.

Association between an Antioxidant-Rich Japanese Diet and Chronic Kidney Disease: The Ohasama Study.

AIMS: Although physiological effects of hydrophilic- (H-) and lipophilic- (L-) antioxidant capacities (AOCs) are suggested to differ, the association of an antioxidant-rich diet and chronic kidney disease (CKD) incidence has not been examined. We therefore explored the association between the H- or L-AOC of a whole Japanese diet and CKD risk in a general population. METHODS: A total of 922 individuals without CKD (69.2% women; mean age, 59.5 years old) from Ohasama Town, Japan, were examined. CKD incidence was defined as the presence of proteinuria and/or an estimated glomerular filtration rate (eGFR) of ＜60 ml/min/1.73 m2. Consumption of H-/L-AOC was determined based on the oxygen radical absorbance capacity in a specially developed Japanese food AOC database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for new-onset CKD using a Cox proportional hazards model. RESULTS: During the median follow-up of 9.7 years, 137 CKD incidents were recorded. After adjusting for potential confounding variables, the highest quartile of L-AOC was significantly associated with a 51% reduced CKD risk among only women. An increased L-AOC intake was more effective in preventing eGFR reduction than in preventing proteinuria in women. These associations were not seen for H-AOC intake in both sexes and L-AOC intake in men. CONCLUSIONS: A high intake of lipophilic antioxidants may be associated with a reduced CKD risk. The balance between dietary antioxidant intake and pro-oxidants induced by unhealthy lifestyles may be crucial for preventing future kidney deterioration.

The impact of clinical inertia on uncontrolled blood pressure in treated hypertension: real-world, longitudinal data from Japan.

We aimed to quantify the impact of inadequate pharmacological therapy on uncontrolled blood pressure (BP) using Japanese real-world data. This retrospective cohort study used databases provided by DeSC Healthcare, Inc (Tokyo, Japan). We identified 27,652 patients with hypertension (age, 60.7 ± 9.1 years; men, 56.4%) who were not receiving antihypertensive treatment at the initial visit (pre-treatment) and were under treatment at the next visit (post-treatment). Patients were classified into the following groups by the number of antihypertensive drug classes and defined daily dose (DDD): one antihypertensive drug class with a low dose (DDD < 1.0), one antihypertensive drug class with a moderate-to-high dose (DDD ≥ 1.0), two antihypertensive drug classes with a low dose (DDD < 2.0), two antihypertensive drug classes with a moderate-to-high dose (DDD ≥ 2.0), and ≥three antihypertensive drug classes. The pre-treatment systolic/diastolic BP was 157.7 ± 15.4/94.2 ± 11.5 mmHg. Overall, 43.0% of patients had uncontrolled BP (post-treatment BP ≥ 140/ ≥ 90 mmHg). High pre-treatment BP was a strong factor for uncontrolled BP. After adjustments for covariates, including the pre-treatment mean BP, the proportion of patients with uncontrolled BP was 2.08 times higher in the one antihypertensive drug class with a low dose group than in the ≥three antihypertensive drug classes group. The preventable fraction due to

Maternal birth weight as an indicator of early-onset and late-onset hypertensive disorders of pregnancy: The Japan Environment and Children's study.

OBJECTIVES: This study aimed to investigate the association between maternal birth weight (MBW) and hypertensive disorders of pregnancy (HDP) according to the gestational age when HDP develops. STUDY DESIGN: A total of 77,345 subjects were included in this prospective birth cohort study. The association between MBW and HDP was investigated by a multinomial logistic regression model. MAIN OUTCOME MEASURES: Early-onset HDP (EO-HDP), preterm late-onset HDP (preterm LO-HDP), and term late-onset HDP (term LO-HDP). RESULTS: Lower MBW was associated with higher odds of preterm and term LO-HDP (p-values for trend < 0.0001 and = 0.0005, respectively). A linear association between MBW and EO-HDP was observed (p-values for trend = 0.0496). The shape of the association between MBW and preterm LO-HDP was a combination of the associations between MBW with EO-HDP or LO-HDP. The effect size of the association between MBW < 2,500 g and EO-HDP was lower than that of MBW < 2,500 g with preterm or term LO-HDP. The adjusted odds ratios for EO-HDP, preterm LO-HDP, and term LO-HDP in subjects with MBW < 2,500 g were 1.052 (95 % confidence interval [CI]: 0.665-1.664), 1.745 (95 % CI: 1.220-2.496), and 1.496 (95 % CI: 1.154-1.939), respectively. CONCLUSIONS: MBW was associated with HDP, regardless of gestational age when HDP developed. Furthermore, the association of MBW < 2,500 g with preterm or term LO-HDP was stronger than that with EO-HDP.

Functional hearing loss and developmental imbalances.

OBJECTIVE: Functional hearing loss (FHL) is a disorder in which there are abnormal values on a hearing test, despite the absence of organic abnormalities in the peripheral and central auditory pathways. Here, we examined the developmental characteristics of FHL and the importance of intervention by analyzing the clinical characteristics of children with this disorder. METHODS: We retrospectively examined 16 patients assessed under a diagnosis of FHL. After interventions such as psychological counseling by our pediatrics and psychiatry departments, we compared the clinical profiles of patients in which hearing was "improved/normalized" and "unimproved". RESULTS: Fourteen patients visited a pediatrician and two chose not to do so. A discrepancy between the maximum and minimum values of the four index scores was observed in all patients in which WISC-IV (the fourth version of the Wechsler Intelligence Scale for Children) was performed (n = 12). The discrepancy between the verbal comprehension index (VCI) and perceptual reasoning index (PRI) was significantly greater in "unimproved" patients than in "improved/normalized" patients. Hearing improved, or was normalized, after intervention in six of 16 patients. CONCLUSIONS: Developmental imbalances were suspected in all 12 children who visited a pediatrician and completed the WISC-IV. Cooperation with pediatricians, psychiatrists, and other health professionals is desirable in supporting patients diagnosed with FHL.

Associations of Dental Health With the Progression of Hippocampal Atrophy in Community-Dwelling Individuals: The Ohasama Study.

BACKGROUND AND OBJECTIVES: Although tooth loss and periodontitis have been considered risk factors of Alzheimer disease, recent longitudinal researches have not found a significant association with hippocampal atrophy. Therefore, this study aimed to clarify a longitudinal association between the number of teeth present (NTP) and hippocampal atrophy dependent on the severity of periodontitis in a late middle-aged and older adult population. METHODS: This study included community-dwelling individuals aged 55 years or older who had no cognitive decline and had undergone brain MRI and oral and systemic data collection twice at 4-year intervals. Hippocampal volumes were obtained from MRIs by automated region-of-interest analysis. The mean periodontal probing depth (PD) was used as a measure of periodontitis. Multiple regression analysis was performed with the annual symmetric percentage change (SPC) of the hippocampal volume as the dependent variable and including an interaction term between NTP and mean PD as the independent variable. The interaction details were examined using the Johnson-Neyman technique and simple slope analysis. The 3-way interaction of NTP, mean PD, and time on hippocampal volume was analyzed using a linear mixed-effects model, and the interaction of NTP and time was examined in subgroups divided by the median mean PD. In all models, dropout bias was adjusted by inverse probability weighting. RESULTS: Data of 172 participants were analyzed. The qualitative interaction between NTP and the mean PD was significant for the annual SPC in the left hippocampus. The regression coefficient of the NTP on the annual SPC in the left hippocampus was positive (B = 0.038, p = 0.026) at the low-level mean PD (mean -1 SD) and negative (B = -0.054, p = 0.001) at the high-level mean PD (mean +1 SD). Similar results were obtained in the linear mixed-effects model; the interaction of NTP and time was significant in the higher mean PD group. DISCUSSION: In a late middle-aged and older cohort, fewer teeth were associated with a faster rate of left hippocampal atrophy in patients with mild periodontitis, whereas having more teeth was associated with a faster rate of atrophy in those with severe periodontitis. The importance of keeping teeth healthy is suggested.

Association of Central Blood Pressure and Carotid Intima Media Thickness with New-Onset Hypertension in People with High Normal Blood Pressure.

AIM: People with high normal blood pressure (BP) have a higher risk of cardiovascular events than those with normal BP; therefore, progression to hypertension (HT) should be prevented. We aimed to assess the HT risk using central BP and carotid intima media thickness (CIMT) in people with high normal BP. METHODS: This prospective cohort study used the Tohoku Medical Megabank Community-Based Project Cohort Study (conducted from 2013 in Miyagi Prefecture in Japan). The participants had a high normal BP, defined as a systolic BP of 120-139 mmHg and diastolic BP ＜90 mmHg using brachial BP measurement during the baseline survey. The outcome was new-onset HT during the secondary survey, conducted four years after the baseline survey. RESULTS: Overall, 4,021 participants with high normal BP during the baseline survey, with an average age of 58.7 years, were included; 1,030 (26%) were diagnosed with new-onset HT during the secondary survey, 3.5±0.7 years after the baseline survey. The multivariable odds ratio (95% confidence interval) for HT in the highest versus lowest quartile of central BP was 1.7 (1.2-2.4, p=0.0030), and that of CIMT was 1.8 (1.4-2.4, p＜0.001). Subgroup analysis according to age (＜60 and ≥ 60 years) and sex revealed that the central BP was influential in groups with younger age and female individuals; CIMT was influential in all groups. CONCLUSIONS: Higher central BP and thicker CIMT at the baseline were correlated with new-onset HT in individuals with high normal BP, independent of brachial systolic BP and other cardiovascular risk factors.