Behavioral changes of preventive activities of influenza among children in satellite cities of a metropolitan area of Tokyo, Japan, by the COVID-19 pandemic.

OBJECTIVE: In children in a metropolitan area of Tokyo, Japan, behavioral change and influenza infection associated with the frequency of nonpharmaceutical interventions (NPI) was assessed from the 2018-2019 season (Preseason) and the 2020-2021 season (coronavirus disease 2019 [COVID-19] season). METHODS: We conducted an exclusive survey among children attending preschool, elementary school, and junior high school in the Toda and Warabi regions, Japan, during the 2018-2019 (Preseason, distributed via mail) and 2020-2021 seasons (COVID-19 season, conducted online). The proportion of preventive activities (hand washing, face mask-wearing, and vaccination) was compared in the Preseason with that of the COVID-19 season. The multivariate logistic regression model was further applied to calculate the adjusted odds ratio (AOR) with 95% confidence intervals (CIs) for influenza infection associated with NPI frequency (hand washing and face mask wearing) in each Preseason and COVID-19 season. RESULTS: The proportion of vaccinated children who carried out hand washing and face mask wearing was remarkably higher during the COVID-19 season (48.8%) than in the Preseason (18.2%). A significant influenza infection reduction was observed among children who washed hands and wore face masks simultaneously (AOR, 0.87; 95% CI, 0.76-0.99; P = 0.033). CONCLUSIONS: A strong interest and performance in the intensive measures for the prevention of influenza under the COVID-19 pandemic was demonstrated. Positive association was observed from a combination of NPI, hand washing, and face mask-wearing and influenza infection. This study's findings could help in activities or preventive measures against influenza and other communicable diseases in children.

Immunological characteristics of severe acute hepatitis of unknown origin in a child post SARS-CoV-2 infection.

Recent studies have reported that pediatric acute liver failure of unknown origin is immune-mediated, with CD8+ T cells playing a key role. Moreover, investigation of superantigen-mediated T-cell activation by the SARS-CoV-2 spike protein in pediatric severe acute hepatitis is needed in the context of the proposed mechanism of multisystem inflammatory syndrome in children (MIS-C). We investigated the immunological characteristics of a Japanese pediatric patient with severe acute hepatitis post SARS-CoV-2 infection. The patient demonstrated autoimmune hepatitis-like liver histology with CD8+ lymphocyte-predominant infiltration. There was Th1-type immune skewing, including remarkable peripheral CD8+ T-cell activation and a skewed T cell receptor repertoire. We also found elevated plasma levels of the anti-SARS-CoV-2 spike-specific IgG antibody, and the titer peaked after treatment, as seen with MIS-C. These findings support that immunological activation involving SARS-CoV-2 spike protein plays a crucial role in a pediatric patient with acute severe hepatitis post SARS-CoV-2 infection.

Regular dental visits, periodontitis, tooth loss, and atherosclerosis: The Ohasama study.

OBJECTIVE: We aimed to explore the association between regular dental visits and atherosclerosis and between periodontitis, number of remaining teeth, and atherosclerosis among community dwellers in Japan. BACKGROUND: Few studies have examined the association between regular dental visits, periodontitis, tooth loss, and atherosclerosis in community dwellers in Japan. METHODS: The participants of this cross-sectional study included community dwellers aged ≥55 years and residing in Ohasama. Exposure variables were regular dental visits; periodontitis, defined as radiographic alveolar bone loss (BL); the Centers for Disease Control/American Academy of Periodontology (CDC/AAP) classification; and number of remaining teeth. The primary outcome was atherosclerosis, defined as maximum carotid intima-media thickness ≥1.1 mm or confirmation of atheromatous plaque. RESULTS: Of 602 participants, 117 had atherosclerosis. In the multivariate model, compared to those with regular dental visits, the odds ratio (OR) (95% confidence intervals [CIs]) of atherosclerosis among those with the absence of regular dental visits was 2.16 (1.03-4.49). Regarding BL-max, compared with those in the first quartile, ORs (95% CIs) of those in the second, third, and fourth quartiles were 1.15 (0.65-2.30), 0.65 (0.32-1.35), and 1.57 (0.81-3.01), respectively. Regarding CDC/AAP classification, compared to those with no or mild periodontitis, ORs (95% CIs) for those with moderate and severe periodontitis were 2.48 (0.61-10.1) and 4.26 (1.01-17.5), respectively. Regarding the number of remaining teeth, compared to those with ≥20 teeth, ORs (95%CIs) for those with 10-19 and 1-9 teeth were 1.77 (1.004-3.12) and 0.96 (0.52-1.80), respectively. CONCLUSION: The absence of regular dental visits and presence of periodontitis are associated with atherosclerosis among community dwellers in Japan.

Effectiveness of Influenza Vaccination among Children in Satellite Cities of a Metropolitan Area in Tokyo, Japan during the 2014/2015-2018/2019 Season.

Influenza vaccination is recommended for children. In particular, those aged 6 months to 12 years were recommended two vaccinations in Japan, whereas the recommended year range for the twice vaccination is 6 months to 8 years by the World Health Organization (WHO). This study assessed the effectiveness of influenza vaccination and whether the twice vaccinations enhanced preventive effects against influenza infection among children living in two satellite cities of a metropolitan area in Tokyo, Japan. During the influenza season of 2014-2018, parents of all preschool, elementary school, and junior high school children participated in an annual survey. Adjusted odds ratios (AOR) with 95% confidence intervals (CIs) were calculated via multivariate logistic regression analysis to evaluate influenza vaccination effectiveness and trends in the number of vaccinations. Among the 108,362 children who received the research questionnaire, 76,753 (70.8%) responded. After excluding responses without basic information, 64,586 children were included in the analysis. Vaccination was more effective in preschool and lower grade elementary school children given the increase in the number of vaccinations (test for trend: P < 0.001). The AOR of influenza for pre, grade 1 elementary, and grade 2 schoolchildren who received two vaccinations was 0.63 (95% CI, 0.59-0.69), 0.75 (0.67-0.83), and 0.81 (0.71-0.92), respectively, when compared to those without vaccination. However, no trend in vaccinations and their effectiveness was observed in the third and higher-grade school children. Our findings support the recommendation by the WHO, and could help guide influenza vaccination policies for children in Japan.

Oral health-related quality of life is associated with the prevalence and development of depressive symptoms in older Japanese individuals: The Ohasama Study.

OBJECTIVE: This prospective study investigated the cross-sectional association between impaired oral health-related quality of life (OHRQoL) and the prevalence of depressive symptoms, and the longitudinal association between impaired OHRQoL and development of depressive symptoms among older adults. BACKGROUND: Previous studies have shown a relationship between poor oral health and depression among older adults; however, findings are inconsistent. MATERIALS AND METHODS: Participants were 669 community-dwelling older Japanese individuals aged≥55 years (mean: 67.8 ± 7.2 years). Data of 296 participants were used for longitudinal analyses. OHRQoL was evaluated using the Oral Impacts on Daily Performances scale. Impaired OHRQoL was defined as the presence of at least one impact on the scale. Depressive symptoms were assessed using the Japanese version of the Zung self-rating depression scale with a cut-off score of 40. RESULTS: The cross-sectional logistic regression model demonstrated that impaired OHRQoL was significantly associated with depressive symptoms (odds ratio [OR], 5.17; 95% confidence interval [CI], 2.99-8.95) independent of age, sex, body mass index, hypertension, cerebrovascular/cardiovascular disease, smoking, drinking alcohol, education, cognitive function, objective oral health (dentition status) and oral health behaviour (dental visit within 1 year). Similarly, impaired OHRQoL predicted the development of depressive symptoms within 4 years in a fully adjusted longitudinal model (OR, 6.00; 95% CI, 1.38-26.09). CONCLUSION: Impaired OHRQoL was identified as a potential comorbidity of depressive symptoms and a predictor for depressive disorder later in life. OHRQoL may be a useful clinical outcome for elder patients with regard to their mental and oral health.

Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial: rational and protocol.

BACKGROUND: Hypertension and diabetes cause chronic kidney disease (CKD) and diastolic left ventricular dysfunction (DVD) as forerunners of disability and death. Home blood pressure telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling prevention. METHODS: UPRIGHT-HTM (Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform [NCT04299529]) is an investigator-initiated 5-year clinical trial with patient-centred design, which will randomise 1148 patients to be recruited in Europe, sub-Saharan Africa and South America. During the whole study, HTM data will be collected and freely accessible for patients and caregivers. The UPP, measured at enrolment only, will be communicated early during follow-up to 50% of patients and their caregivers (intervention), but only at trial closure in 50% (control). The hypothesis is that early knowledge of the UPP risk profile will lead to more rigorous risk factor management and result in benefit. Eligible patients, aged 55-75 years old, are asymptomatic, but have ≥5 CKD- or DVD-related risk factors, preferably including hypertension, type-2 diabetes, or both. The primary endpoint is a composite of new-onset intermediate and hard cardiovascular and renal outcomes. Demonstrating that combining UPP with HTM is feasible in a multicultural context and defining the molecular signatures of early CKD and DVD are secondary endpoints. EXPECTED OUTCOMES: The expected outcome is that application of UPP on top of HTM will be superior to HTM alone in the prevention of CKD and DVD and associated complications and that UPP allows shifting emphasis from treating to preventing disease, thereby empowering patients.

Comparison of nocturnal blood pressure based on home versus ambulatory blood pressure measurement: The Ohasama Study.

OBJECTIVES: The nocturnal blood pressure (BP) is a strong predictor of hypertensive target organ damage including that in cardiovascular diseases. The use of ambulatory BP (ABP) monitoring has enabled the evaluation of nocturnal BP and detection of non-dippers. This study compared nocturnal BP values, nocturnal decline in BP, and the prevalence of non-dippers based on ABP and home BP (HBP) measurements in a general population. METHODS: Data on HBP measured with HEM 747-IC-N (Omron Healthcare Co., Ltd.) and 24-hour ABP measured with ABPM-630 (Nippon Colin) were obtained from fifty-five participants aged ≥ 20 years (mean age: 65.1 years, 78.2% women). To exclude a systematic difference between the two methods, we conducted a validation study for HBP and ABP in another population that consisted of hypertensive outpatients (mean age: 65.4 years, 53.4% women). RESULTS: After adjusting for the systematic difference in BP between the two methods calculated in the validation study (3.9 mmHg for systolic and 3.0 mmHg for diastolic), morning and daytime (average of morning and evening) HBP were significantly lower than morning (average of 2 h after waking) and daytime (average of being awake) ABP, respectively. No significant difference was found in nocturnal BP between HBP and ABP monitoring regardless of the quality of sleep during nocturnal HBP measurement. Agreement between HBP and ABP in the detection of non-dippers was low mainly due to the difference in daytime BP values. Conclusion: HBP monitoring may be a reliable alternative to ABP for the assessment of nocturnal BP.

Effects of measurement intervals on the values of repeated auscultatory blood pressure measurements.

Objective: For repeated measurements of blood pressure (BP) using the auscultatory method, current guidelines recommend intervals of 1-2 minutes; however, evidence to support this recommendation is insufficient. In the present study, the effects of intervals among repeated BP measurements using the auscultatory method were evaluated.Methods: Systolic and diastolic BPs were measured using the auscultatory method in 37 participants. The measurements were repeated 5 times each at intervals of 15, 30, 60, 90, and 120 seconds. The changes in the BP along with the increasing the number of repetitions were assessed at each measurement interval using a linear mixed model.Results: With an increasing number of measurements, the systolic and diastolic BPs showed significant progressive decrease and increase (p < 0.05), respectively, when the measurement interval was 15 seconds. However, the precision of BP measurements was not affected by performing the measurements at intervals of 30 seconds or longer.Conclusion: Repeated BP measurements using the auscultatory method need to have an interval of at least 30 seconds, which is shorter than the intervals recommended by the current guidelines.

Exercise Habits Are Associated with Improved Long-Term Mortality Risks in the Nationwide General Japanese Population: A 20-Year Follow-Up of the NIPPON DATA90 Study.

Exercise habits are known as a protective factor for a variety of diseases and thus recommended worldwide; however, few studies have examined long-term effects of exercise habits on mortality. We continuously monitored death status in a nationwide population sample of 7,709 eligible persons from the National Integrated Project for Prospective Observation of Noncommunicable Disease and its Trends in the Aged in 1990 (NIPPON DATA90), for which baseline data were obtained in 1990. To investigate the long-term impact of baseline exercise habits, we calculated the relative risk of non-exercisers (participants without regular voluntary exercise habits) in reference to exercisers (those with these habits) for all-cause or cause-specific mortality using a Cox proportional hazard model, in which the following confounding factors were appropriately adjusted: sex, age, body mass index, total energy intake, smoking, drinking, and history of cardiovascular disease. During a median 20 years of follow-up, 1,747 participants died, 99 of heart failure. The risk for all-cause mortality was 12% higher in non-exercisers than in exercisers (95% confidence interval, 1%-24%), which was also observed for mortality from heart failure, as 68% higher in non-exercisers than in exercises (95% confidence interval, 3%-173%). These associations were similarly observed when the participants were divided to subgroups by sex, age, and the light, moderate, or vigorous intensity of physical activity, without any significant heterogeneities (P > 0.1). The present study has revealed significant impact of exercise habits on long-term mortality risks, supporting worldwide recommendations for improvement of exercise habits.

Blood Pressure Phenotypes Defined by Ambulatory Blood Pressure Monitoring and Carotid Artery Changes in Community-Dwelling Older Japanese Adults: The Ohasama Study.

White coat hypertension is defined as elevated blood pressure in the office, but a normal blood pressure out-of-office, whereas masked hypertension is defined as elevated blood pressure in the office, but normal out-of-office blood pressure. The objective was to investigate the associations between these blood pressure phenotypes and carotid artery changes. Conventional blood pressure, ambulatory blood pressure, and carotid ultrasonography were evaluated in 851 Ohasama residents (31.8% men; mean age 66.3 years). The blood pressure phenotypes were defined by the ordinary thresholds (140/90 mmHg for conventional blood pressure, 135/85 mmHg for daytime blood pressure) and then by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) thresholds for hypertension (130/80 mmHg for both conventional and daytime blood pressure), irrespective of antihypertensive medication treatment status. Blood pressure phenotypes were linearly associated with the mean intima-media thickness of the carotid artery in ascending order for sustained normal blood pressure, white coat hypertension, masked hypertension, and sustained hypertension according to the ordinary thresholds and the 2017 ACC/AHA thresholds (both linear trends P < 0.0001) after adjustments for possible confounding factors. The odds ratios for the presence of carotid plaques showed similar linear trends with the blood pressure phenotypes according to the 2017 ACC/AHA thresholds (linear trend P < 0.0191). In conclusion, there was a close relationship between blood pressure phenotypes and carotid artery changes, suggesting that blood pressure phenotypes as defined by ambulatory blood pressure are potentially useful for risk stratification of carotid artery changes in the Japanese general population.

Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes.

Importance: Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. Objective: To evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and Participants: Longitudinal population-based cohort study of 11 135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). Exposures: Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and Measures: Multivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). Results: Among 11 135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P < .001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and Relevance: In this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.

N-Terminal Pro-B-Type Natriuretic Peptide Is Not a Significant Predictor of Stroke Incidence After 5 Years　- The Ohasama Study.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been used for risk stratification in heart failure or acute coronary syndrome, but the beyond 5-year predictive value of NT-proBNP for stroke remains an unsettled issue in Asian patients. The aim of the present study was to clarify this point.Methods and Results:We followed 1,198 participants (33.4% men; mean age, 60.5±11.1 years old) in the Japanese general population for a median of 13.0 years. A first stroke occurred in 93 participants. Referencing previous reports, we stratified participants according to NT-proBNP 30.0, 55.0, and 125.0 pg/mL. Using the NT-proBNP <30.0 pg/mL group as a reference, adjusted HR for stroke (95% CI) in the NT-proBNP 30.0-54.9-pg/mL, 55.0-124.9-pg/mL, and ≥125.0-pg/mL groups were 1.92 (0.94-3.94), 1.77 (0.85-3.66), and 1.99 (0.86-4.61), respectively. With the maximum follow-up period set at 5 years, the hazard ratio of the NT-proBNP≥125.0-pg/mL group compared with the <30.0-pg/mL group increased significantly (HR, 4.51; 95% CI: 1.03-19.85). On extension of the maximum follow-up period, however, the association between NT-proBNP and stroke risk weakened. CONCLUSIONS: NT-proBNP was significantly associated with an elevated stroke risk. Given, however, that the predictive power decreased with the number of years after NT-proBNP measurement, NT-proBNP should be re-evaluated periodically in Asian patients.

The rationale and design of reduction of uncontrolled hypertension by Remote Monitoring and Telemedicine (REMOTE) study.

PURPOSE: Although self-measurement of home blood pressure (HBP) is common in Japan and HBP telemonitoring via the Internet is possible, whether telemonitoring improves HBP control better than conventional practice remains unclear. Furthermore, hypertension care with online communication using telemonitored HBP is feasible, whereas the efficacy and safety of such telemedicine have not been established. We aim to compare traditional care, care with office visits using HBP telemonitoring, and antihypertensive telemedicine based on HBP telemonitoring. METHODS AND DESIGN: In total, 444 patients with uncontrolled hypertension will be recruited and randomly assigned to three groups: (1) control: usual care with office visits and HBP self-report, (2) telemonitoring: weekly assessment of transmitted HBP by physicians and treatment adjustment upon office visits, or (3) telemedicine: online communication instead of office visits to adjust medication using telemonitored HBP. Primary outcome is the time to control of HBP, and secondary outcomes include achieved HBP levels, adherence, treatment intensity, adverse events, patient satisfaction and cost-effectiveness. DISCUSSION: Hypertension care with telemonitoring and telemedicine are expected to require shorter time to achieve HBP control compared to usual care. Combining HBP telemonitoring with telemedicine may lower the hurdles for starting and persisting to hypertension treatment and eventually reduce cardiovascular events.

Evidence-based proposal for the number of ambulatory readings required for assessing blood pressure level in research settings: an analysis of the IDACO database.

BACKGROUND: Guidelines on the required number of ambulatory blood pressure (ABP) readings focus on individual patients. Clinical researchers often face the dilemma of applying recommendations and discarding potentially valuable information or accepting fewer readings. METHODS: Starting from ABP recordings with ≥30/≥10 awake/asleep readings in 4277 participants enrolled in eight population studies in the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes (IDACO), we randomly selected a certain number of readings (from 30 to 1 awake and 10 to 1 asleep readings) at a time over 1000 bootstraps at each step. We evaluated: (i) concordance of the ABP level; (ii) consistency of the cross-classification based on office blood pressure and ABP; and (iii) accuracy in predicting cardiovascular complications. For each criterion, we fitted a regression line joining data points relating outcome to the number of readings covering the ranges of 30-20/10-7 for awake/asleep readings. RESULTS: Reducing readings widened the SD of the systolic/diastolic differences between full (reference) and selected recordings from 1.7/1.2 (30 readings) to 14.3/10.3 mm Hg (single reading) during wakefulness, and from 1.9/1.4 to 10.3/7.7 mm Hg during sleep; lowered the κ statistic from 0.94 to 0.63, and decreased the hazard ratio associated with 10/5 mm Hg increments in systolic/diastolic ABP from 1.21/1.14 to 1.06/1.04 during wakefulness and from 1.26/1.17 to 1.14/1.08 during sleep. The first data points falling off these regression lines during wakefulness/sleep corresponded to 8/3 and 8/4 readings for criteria (i) and (iii) and to 5 awake readings for criterion (ii). CONCLUSIONS: 24-h ambulatory recordings with ≥8/≥4 awake/asleep readings yielded ABP levels similar to recordings including the guideline-recommended ≥20/≥7 readings. These criteria save valuable data in a research setting, but are not applicable to clinical practice.

Effect of amlodipine, efonidipine, and trichlormethiazide on home blood pressure and upper-normal microalbuminuria assessed by casual spot urine test in essential hypertensive patients.

The aim of this study was to assess the effects of irbesartan alone and combined with amlodipine, efonidipine, or trichlormethiazide on blood pressure (BP) and urinary albumin (UA) excretion in hypertensive patients with microalbuminuria (30≤UA/creatinine (Cr) ratio [UACR] <300 mg/g Cr) and upper-normal microalbuminuria (10≤UACR<30 mg/g Cr). This randomized controlled trial enrolled 175 newly diagnosed and untreated hypertensive patients (home systolic blood pressure [SBP]≥135 mmHg; 10≤UACR<300 mg/g Cr of casual spot urine at the first visit to clinic). All patients were treated with irbesartan (week 0). Patients who failed to achieve home SBP ≤125 mmHg on 8-week irbesartan monotherapy (nonresponders, n = 115) were randomized into three additional drug treatment groups: trichlormethiazide (n = 42), efonidipine (n = 39), or amlodipine (n = 34). Irbesartan monotherapy decreased home SBP and first morning urine samples (morning UACR) for 8 weeks (p < 0.0001). At 8 weeks after randomization, all three additional drugs decreased home SBP (p < 0.0002) and trichlormethiazide significantly decreased morning UACR (p = 0.03). Amlodipine decreased morning UACR in patients with microalbuminuria based on casual spot urine samples (p = 0.048). However, multivariate analysis showed that only higher home SBP and UACR at week 8, but not any additional treatments, were significantly associated with UACR reduction between week 8 and week 16. In conclusion, crucial points of the effects of combination therapy on UACR were basal UACR and SBP levels. The effect of trichlormethiazide or amlodipine treatment in combination with irbesartan treatment on microalbuminuria needs to be reexamined based on a larger sample size after considering basal UACR and SBP levels.

Nocturnal blood pressure decline based on different time intervals and long-term cardiovascular risk: the Ohasama Study.

A diminished nocturnal decline in blood pressure (BP) represents a risk factor for cardiovascular disease. To define daytime and nighttime ambulatory BP, clock time-dependent methods are used when information on diary-based sleeping time is unavailable. We aimed to compare fixed-clock intervals with diary records to identify nocturnal BP declines as a predictor of long-term cardiovascular risk among the general population. Data were obtained from 1714 participants with no history of cardiovascular disease in Ohasama, Japan (mean age, 60.6 years; 64.9% women). We defined extreme dippers, dippers, non-dippers, and risers as nocturnal systolic BP decline ≥20%, 10-19%. 0-9%, and <0%, respectively. Over a mean follow-up period of 17.0 years, 206 cardiovascular deaths occurred. Based on diary records, multivariable-adjusted hazard ratios (HRs) for cardiovascular death compared with dippers were 1.24 (95% confidence interval [CI], 0.82-1.87) in extreme dippers, 1.21 (0.87-1.69) in non-dippers, and the highest HR of 2.31 (1.47-3.62) was observed in risers. Using a standard fixed-clock interval (daytime 09:00-21:00; nighttime 01:00-06:00), a nighttime 2 h-early shifted fixed-clock (daytime 09:00-21:00; nighttime 23:00-04:00), or a nighttime 2 h-late shifted fixed-clock (daytime 09:00-21:00; nighttime 03:00-08:00), the HR (95%CI) in risers compared with dippers was 1.57 (1.08-2.27), 2.02 (1.33-3.05), or 1.29 (0.86-1.92), respectively. Although use of diary records remains preferable, the standard and nighttime 2 h-early shifted fixed-clock intervals appear feasible for population-based studies.

Genome-wide association study for white coat effect in Japanese middle-aged to elderly people: The HOMED-BP study.

BACKGROUND: White coat effect (WCE), the blood pressure (BP) difference between clinical and non-clinical settings, can lead to clinical problems such as misdiagnosis of hypertension. Etiology of WCE has been still unclear, especially from genetic aspects. The present article investigated association between genome-wide single nucleotide polymorphisms (SNPs) and WCE in patients with essential hypertension. METHODS: The present cross-sectional analyses were based on 295 Japanese essential hypertensive outpatients aged ≧40 years enrolled in randomized control study, Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study, who were not taking antihypertensive medications before the randomization. Home and clinic BP were measured. WCE was defined by subtracting home BP from clinic BP. Genotyping was conducted with 500K DNA microarray chips. Association between genome-wide SNPs and WCE were analyzed. For replication (p < 10-4), we analyzed participants from Ohasama study who took no antihypertension medications and whose SNPs were collected. RESULTS: Genome-wide SNPs were not significantly associated with WCE of systolic and diastolic BP after corrections of multiple comparisons (p < 2 × 10-7). We found suggestive SNPs associated with WCE of systolic and diastolic BP (p < 10-4). However, the consistent results were not obtained in the replication study. CONCLUSION: The present article showed no significant association between genome-wide SNPs and WCE. Since there were several suggestive SNPs associated with WCE, the present study warrants a further study with bigger sample size for investigating the genetic influence on WCE.

Global Cardiovascular and Renal Outcomes of Reduced GFR.

The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.

Association between tooth loss and cognitive impairment in community-dwelling older Japanese adults: a 4-year prospective cohort study from the Ohasama study.

BACKGROUND: Numerous prospective studies have investigated the association between the number of remaining teeth and dementia or cognitive decline. However, no agreement has emerged on the association between tooth loss and cognitive impairment, possibly due to past studies differing in target groups and methodologies. We aimed to investigate the association between tooth loss, as evaluated through clinical oral examinations, and the development of cognitive impairment in community-dwelling older adults while considering baseline cognitive function. METHODS: This 4-year prospective cohort study followed 140 older adults (69.3% female) without cognitive impairment aged ≥65 years (mean age: 70.9 ± 4.3 years) living in the town of Ohasama, Iwate Prefecture, Japan. Cognitive function was evaluated with the Mini-Mental State Examination (MMSE) in baseline and follow-up surveys. Based on a baseline oral examination, the participants were divided into those with 0-9 teeth and those with ≥10 teeth. To investigate the association between tooth loss and cognitive impairment, we applied a multiple logistic regression analysis adjusted for age, sex, hypertension, diabetes, cerebrovascular/cardiovascular disease, hypercholesterolemia, depressive symptoms, body mass index, smoking status, drinking status, duration of education, and baseline MMSE score. RESULTS: In the 4 years after the baseline survey, 27 participants (19.3%) developed cognitive impairment (i.e., MMSE scores of ≤24). Multiple logistic regression analysis indicated that participants with 0-9 teeth were more likely to develop cognitive impairment than those with ≥10 teeth were (odds ratio: 3.31; 95% confidence interval: 1.07-10.2). Age, male gender, and baseline MMSE scores were also significantly associated with cognitive impairment. CONCLUSIONS: Tooth loss was independently associated with the development of cognitive impairment within 4 years among community-dwelling older adults. This finding corroborates the hypothesis that tooth loss may be a predictor or risk factor for cognitive decline.

Renal function in relation to sodium intake: a quantitative review of the literature.

We undertook a quantitative literature review to search for evidence underpinning current guidelines proposing a reduction of sodium intake to less than 2.4 g/d for the management of chronic kidney disease. We searched PubMed for peer-reviewed articles published from January 1980 through May 2016. Two investigators screened 5072 publications and extracted data from 36, including 11 cross-sectional and 5 longitudinal observational studies and 20 intervention trials. Within-study effect sizes were pooled and standardized to a sodium gradient of 100 mmol/d by using inverse-variance weighted random effects models. Among cross-sectional studies, the pooled odds ratio for albuminuria was 1.23 (95% confidence interval [CI], 0.92-1.64, P = 0.16), and the pooled mean difference in glomerular filtration rate amounted to 8.5 ml/min (CI, -2.3 to 19.2 ml/min; P = 0.12). In the cohort studies, the pooled relative risk of a renal endpoint was 1.08 (CI, 0.92-1.29; P = 0.35). In the intervention trials (median duration, 14 days [range, 4-186 days]), the mean differences in estimated glomerular filtration rate and albuminuria (high vs. low sodium intake) averaged 4.6 ml/min (CI, 3.4-5.8 ml/min; P < 0.0001) and 53% (CI, 21-84; P = 0.001), respectively. Cochran's Q statistic indicated significant heterogeneity among cross-sectional studies for both estimated glomerular filtration rate and albuminuria (P < 0.0001) and among intervention trials for albuminuria (P = 0.04). In conclusion, there is no robust evidence suggesting that long-term reduction of salt intake would prevent chronic kidney disease or delay its progression. However, our current findings, which were mainly obtained in people with slight renal impairment, cannot be extrapolated to patients with moderate or severe chronic kidney disease.