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Objective: We evaluated the relationship between prenatal folic acid supplementation and autism spectrum disorder (ASD) in 3-year-old offspring., Methods: We used data from the Japan Environment and Children's Study, a nationwide prospective birth cohort study. We analyzed the data to determine the association between folic acid supplement use and the incidence of ASD in offspring, and classified participants into three groups based on the time of initiation of folic acid supplementation, as follows: (1) preconception users of folic acid supplements and (2) post-conception users, and (3) non-users. The dietary folate intake of study participants was also classified into three groups (<200 µg, 200 µg to <400 µg, ≥400 µg)., Results: Overall, 361 offspring of 96,931 participants with single pregnancies were diagnosed with ASD (0.37%). A total of 7,046 participants (7.3%) used folic acid supplements before conception, 29,984 (30.9%) took them after detection of pregnancy, and 59,901 (61.8%) never received them. Multivariate logistic regression analyses demonstrated no association between prenatal folic acid supplementation and ASD in offspring (preconception use: adjusted odds ratio [AOR], 1.189; 95% confidence interval [CI], 0.819-1.727 and post-conception use: AOR, 1.072; 95% CI, 0.840-1.368); additionally, no association was observed with the use of folic acid supplements and/or multivitamin supplements (preconception use: AOR, 1.273; 95% CI, 0.921-1.760 and post-conception use: AOR, 1.132; 95% CI, 0.885-1.449). Moreover, no significant association was observed in participants with combined prenatal supplement use and dietary folate intake., Conclusions: Maternal use of folic acid supplements from the pre- or post-conception period was not significantly associated with ASD in 3-year-old offspring in Japan. Evaluation of the dietary folate intake from preconception also showed no significant association.

Objective: When using administrative data, validation is essential since these data are not collected for research purposes and misclassification can occur. Thus, this study aimed to develop algorithms identifying pregnancy and to evaluate the validity of administrative claims data in Japan., Methods: All females who visited the Tohoku University Hospital Department of Obstetrics in 2018 were included. The diagnosis, medical procedure, medication, and medical service addition fee data were utilized to identify pregnancy, with the electronic medical records set as the gold standard. Combination algorithms were developed using predefined pregnancy-related claims data with a positive predictive value (PPV) ≥80%. Sensitivity (SE), specificity (SP), PPV, and negative predictive value (NPV) with their corresponding 95% confidence intervals (CIs) were calculated for these combination algorithms., Results: This study included 1757 females with a mean age of 32.8 (standard deviation: 5.9) years. In general, the individual claims data were able to identify pregnancy with a PPV ≥80%; however, the number of pregnancies identified using a single claims data was limited. Based on the combination algorithm with all of the categories, including diagnosis, medical procedure, medication, and medical service addition, the calculated SE, SP, PPV, and NPV were 73.4% (95% CI: 71.2%-75.4%), 96.9% (95% CI: 89.3%-99.6%), 99.8%,(95% CI: 99.4%-100.0%), and 12.3% (95% CI: 9.6%-15.4%), respectively., Conclusions: The combination algorithm to identify pregnancy demonstrated a high PPV and moderate SE. The algorithm validated in this study is expected to accelerate future studies that aim to identify pregnancies and evaluate pregnancy outcome.

Objective: In Japan, supplementation with 400 µg of folic acid per day is recommended for women who are planning to get pregnant to decrease the risk of their babies getting neural tube defects (NTD). However, the proportion of women who have taken folic acid supplements before conception is low among Japanese pregnant women. In addition, the dietary intake of folic acid has not yet reached the government recommended dietary intake levels (480 µg per day). This study aimed to clarify the prevalence and determinants of adequate folic acid supplements among Japanese pregnant women with dietary folic acid intake lower than 480 µg per day., Methods: This cross-sectional study was a part of the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. We collected information on folic acid supplements before conception, sociological/lifestyle characteristics, and food consumption. The primary outcome was the use of folic acid supplements (adequate or inadequate, based on the timing of initiation of folic acid supplements). Multiple logistic regression analysis was used to examine the association between sociological/lifestyle characteristics and the adequate intake of folic acid supplements., Results: Among the 11,562 pregnant women who took lower than 480 µg per day of folic acid from food, the prevalence of adequate users was 18.0%. Pregnant women who reported adequate use of folic acid supplements were more likely to be older and educated; and reported higher household income, and history of fertility treatment. Conversely, they were less likely to be ever or current smokers and multipara., Conclusion: This study found that the prevalence of folic acid supplements use for the prevention of NTD among Japanese pregnant women was still low.

Objective: To survey the frequency and risk factors for father-to-infant lack of affection (LA) and anger/rejection (AR) bonding failure at 1 month postpartum. Material and methods: The study participants enrolled in the prospective birth cohort study of an adjunct study of the Japan Environment & Children's Study. Bonding failure, psychological distress during pregnancy and postnatal depression symptoms were evaluated using the Japanese version of the Mother-Infant Bonding Scale (MIBS-J), the Kessler 6-item (K6) psychological distress scale and the Edinburgh Postnatal Depression Scale (EPDS-J). This study extracted relative factors based on approximately 10% occupancy of the total high scores in MIBS-J subscales as a cut-off for bonding failure. The cut-off scores on the paternal EPDS-J were eight, on maternal EPDS-J was 9, and on the K6 psychological distress scale score was 13. Results: A total of 1008 couples who had single delivery were assessed at 1 month postpartum, respectively. The prevalence of paternal MIBS-J&#95;LA scores ≥4 was 8.3%, MIBS-J&#95;AR scores ≥3 was 7.9%, and EPDS-J scores ≥8 was 11.2%, respectively. In the multiple logistics analysis, paternal MIBS-J&#95;LA scores ≥4 were significantly associated with maternal MIBS-J&#95;LA score ≥3 (adjusted odds ratio (AOR) 2.814; 95% confidence interval (CI): 1.377-5.747), mental intimate partner violence (IPV) against the mother during pregnancy (AOR 2.176; 95% CI: 1.185-3.997), maternal K6 psychological distress scale score ≥13 (AOR 2.980; 95% CI: 1.317-6.745), paternal EPDS-J score ≥8 (AOR 3.227; 95% CI: 1.767-5.892), and a history of mental health disorder (AOR 4.125; 95% CI: 1.423-11.963). Paternal MIBS-J&#95;AR scores ≥3 were significantly associated with maternal MIBS-J&#95;AR scores ≥3 (AOR 5.082; 95% CI: 2.453-10.529), a history of physical IPV against the mother during pregnancy (AOR 5.230; 95% CI: 1.016-26.920), paternal K6 psychological distress scale score ≥13 (AOR 4.145; 95% CI: 1.311-13.107), and paternal EPDS-J scores ≥8 (AOR 4.479; 95% CI: 2.503-8.013). In Pearson's product moment correlation coefficient analyses between paternal and maternal MIBS-J score, MIBS-J&#95;LA score was r  = 0.2112, p  < .0001, and MIBS-J&#95;AR score was r  = 0.3281, p  < .0001. Conclusion: Father-to-infant lack of affection bonding failure was associated with mother-to-infant lack of affection bonding failure, mental IPV against mother during pregnancy, maternal psychological distress during pregnancy, paternal postpartum depression symptoms, and history of paternal mental health disorders. Father-to-infant anger/rejection bonding failure was associated with mother-to-infant anger/rejection bonding failure, physical IPV against mother during pregnancy, paternal psychological distress during pregnancy, and paternal postpartum depression symptoms. Since bonding failure is a risk factor for infant maltreatment, further investigations are recommended to fully assess these associations to resolve parent perinatal mental health issues for preventing father-to-infant bonding failure.

Objective: To survey prevalence and risk factors for paternal postpartum depression symptoms at one and 6 months postpartum in Japan. Material and methods: The study participants enrolled in the prospective birth cohort study of an adjunct study of the Japan Environment and Children's Study. Postpartum depression symptoms were evaluated using the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS-J). The cut-off scores on the paternal EPDS-J were eight and on maternal EPDS-J was nine, respectively. The multivariate logistic regression included an adjustment for paternal age, maternal age, the number of children in the family, family structure, paternal employment, paternal academic history, household income, paternal smoking status, paternal history of mental health disorders, the Kessler 6-item psychological distress scale (K6) score during pregnancy, infertility treatment, paternal mental intimate partner violence (IPV) during pregnancy, paternal physical IPV during pregnancy, the sex of the newborn, congenital anomalies of the newborn, infant disease under medical treatment, returning to the maternal parent's house to give birth or take care of infant, the father's history of disease or injury that required medical treatment, paternity leave, and the EPDS-J for mothers. Results: A total of 1023 and 1330 fathers and their spouse who had a single delivery were assessed at one and 6 months postpartum, respectively. The prevalence of paternal EPDS-J scores ≥8 was 11.2 and 12.0% at one and 6 months postpartum, respectively. In the multiple logistics analysis, paternal EPDS-J scores ≥8 at 1 month postpartum was significantly associated with history of mental health disorders (adjusted odds ratio (AOR) 2.825; 95% confidence interval (CI): 1.047-7.623), K6 score ≥13 during pregnancy (AOR 4.116; 95% CI: 1.598-10.599), household income <4000 × 10 3 yen (AOR 1.799; 95% CI: 1.072-3.021), and infant disease under medical treatment (AOR 1.720; 95% CI: 1.015-2.915). Paternal EPDS-J scores ≥8 at 6 months postpartum was significantly associated with K6 scores ≥13 during pregnancy (AOR 4.621; 95% CI: 2.113-10.107), unemployment (AOR 3.751; 95% CI: 1.739-8.091) and maternal EPDS-J scores ≥9 (AOR 2.460; 95% CI: 1.514-3.996). Conclusion: The prevalence of paternal postpartum depression symptoms were 11.2 and 12.0% at one and 6 months postpartum. Paternal postpartum depression symptoms at 1 month postpartum were associated with the history of mental health disorders, psychological distress during pregnancy, low income, and infant disease under medical treatment. Paternal postpartum depression symptoms at 6 months postpartum were associated with psychological distress during pregnancy, unemployment, and maternal postpartum depression. It is important to consider the paternal postpartum depression symptoms, and further enlightenment regarding these issues is recommended in Japan.

Objective: To clarify changes in community pharmacists' knowledge, attitudes, and practice regarding the management of hypertension before and after attending educational interventions based on their self-report on a questionnaire survey. Method: We conducted questionnaire surveys regarding the management of hypertension with a sample of community pharmacists before and after educational interventions. Results: The proportions of pharmacists who knew the 2014 Japanese Society of Hypertension Guidelines, guidelines for home blood pressure measurement, reference values for hypertension based on clinic-measured blood pressure, and reference values for hypertension based on home-measured blood pressure after the educational interventions (59.3%, 41.4%, 75.1%, and 70.8% respectively) were significantly higher relative to those recorded before interventions (31.6%, 13.7%, 47.7%, and 25.4% respectively). Conclusions: These findings suggest that in-house training might increase the knowledge of community pharmacists regarding hypertension management.

Objective: To provide the latest and most promising evidence on the prevalence and determinants for folic acid supplementation in pregnant women in Japan, including differences in prevalence between interview years and determinants across regions. Materials and methods: The study participants were enrolled from 15 regional centers across Japan between January 2011 and March 2014. Information on the use of folic acid supplementation before and during pregnancy and the characteristics of the participants were collected using questionnaires, medical chart reviews, and interviews by research coordinators. Results: Data for 91,538 women who provided sufficient data on folic acid supplementation were analyzed. The prevalence of adequate users was 8.0%, which, although low, tended to improve over the 4-year recruitment period. Various kinds of sociodemographic factors, lifestyle habits, and obstetrical and medication use history were significant and independent determinants for folic acid use. Associations between adequate preconception folic acid use and its major determinants tended to be similar across regions. Conclusions: Although the prevalence of adequate folic acid use was low, it increased from 2011 to 2014. Reproductive-aged women who have determinants for inadequate folic acid use should be informed about the need for preconception folic acid supplementation to help prevent neural tube defects.

Objective: To clarify the present situation of home blood pressure (HBP) measurement among Japanese patients. Methods: A nationwide questionnaire survey regarding HBP measurement was conducted on patients aged 20 years or older who had visited 20 community pharmacies to have their prescriptions filled. Results: In total, 76.7% of 1,103 hypertensives and 40.9% of 1,106 normotensives had their own devices for HBP measurement. Compared with normotensives, a higher proportion of hypertensives recognized the guideline-based reference values for HBP and clinic BP. Compared with hypertensives who did not have a physician's recommendation, those who did more often had their own devices, recognized the guideline-based reference values for HBP, and measured HBP every day (70.4%, 1.5%, and 31.6% vs. 91.1%, 6.9%, and 65.4%, respectively). Among 793 hypertensives who measured HBP, a higher proportion of those with a physician's recommendation measured HBP according to optimal guideline-based procedures compared with those without. Among 560 hypertensives who recorded HBP readings, a higher proportion of those with a physician's recommendation (74.6%) showed all HBP readings to their physicians compared with those without (35.3%). Conclusions: Our findings suggest that physicians should recommend measuring HBP in accordance with the Japanese Society of Hypertension guidelines more aggressively, and provide more detailed explanations to patients regarding how to measure HBP.

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.

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.

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.

Objective: The aim of the study was to clarify the prevalence and determinants of inadequate use of folic acid supplementation in pregnant Japanese women., Methods: This study was part of the Japan Environment and Children's Study, a nationwide and government-funded birth cohort study. We collected information on the use of folic acid supplementation before and during pregnancy and characteristics of participants using self-administered questionnaire., Results: Among 9849 women who completed the data collection for this study, the prevalence of inadequate users was 92.6% of the total population and varied from 84.5% to 96.2% among regions. On the basis of multivariate logistic regression analysis, younger age, not married, lower family income, multipara, natural conception and no history of spontaneous abortion were found to be determinants for inadequate users of folic acid supplementation., Conclusion: Most Japanese pregnant women show inadequate folic acid supplementation use. Japanese women of child-bearing age need to be specifically informed about the need for periconceptional intake of folic acid to prevent neural tube defects.

Background: Information regarding salt intake in pregnant women in Japan is limited. An electronic system for the assessment of salt intake using a 24-h dietary recall method has been developed in Japan. The objectives of the present study were to investigate salt intake in pregnant women and to compare the salt intake estimated by the electronic salt intake assessment system with that measured by 24-h urinary salt excretion (24-hUNaCl)., Methods: Data were collected on 24-hUNaCl and salt intake estimated by the salt intake assessment system for 35 pregnant Japanese women at approximately 20 weeks of gestation. The adjusted 24-hUNaCl (24-hUNaCl/[the number of urinations during the examination day--the number of missing urine collections] × the number of urinations during the examination day, g/day) was used as a standard., Results: The mean adjusted 24-hUNaCl was 7.7 ± 2.5 g/day, and mean systolic/diastolic blood pressure values were 106.1 ± 8.6/62.8 ± 6.5 mmHg. The adjusted 24-hUNaCl was significantly correlated with the salt intake estimated by the salt intake assessment system (r = 0.47, p = 0.004). Bland-Altman analysis showed no significant mean difference (adjusted 24-hUNaCl--salt intake estimated by the assessment system = -0.36 g/day, p = 0.4) and no significant proportional bias (p = 0.1)., Conclusion: These results suggest that pregnant women in Japan restrict their salt intake, at least when they are being examined for salt intake. They also suggest that repeated use of the described system may be useful in estimating salt intake in pregnant women.

Central systolic blood pressure (CSBP) may be a better predictor of cardiovascular risk than clinic brachial (B)SBP. The effects of dose increment from medium dose of angiotensin II receptor blockers (ARBs) to the maximum dose of ARBs (maximum) and changing from medium dose of ARBs to losartan 50 mg/hydrochlorothiazide 12.5 mg combination (combination) were compared in hypertensive patients in whom monotherapy with a medium ARB dose did not achieve goal home SBP (135 mmHg). Four weeks after treatment with a medium ARB dose monotherapy, those whose home SBP level was above 135 mmHg were randomized to receive the maximum ARB dose (n = 101) or the combination (n = 99) once daily for 8 weeks. Both regimens significantly decreased BSBP and CSBP, while a decrease in BSBP and CSBP was greater with combination. The maximum significantly decreased augmentation index (AIx), while the combination did not. The rate of a decrease in reflection to decrease in CSBP was greater in the maximum than in the combination. In the elderly subgroup, the combination more effectively lowered BSBP than the maximum, and only the combination decreased CSBP. However, in the young subgroup, the maximum decreased AIx more than combination, while both regimens lowered CSBP and BSBP to a similar extent. It is explained in part that the maximum may affect pulse wave reflection more predominantly than the combination, especially in young subjects. A weak effect on pulse wave reflection and, thus, on CSBP, of the combination may be overcome by the potent antihypertensive effect of this regimen.

Based on ambulatory blood pressure (BP) monitoring, the aldosterone-to-renin ratio (ARR) has been reported to be associated with a diminished nocturnal decline in BP, generally referred to as a "non-dipping" pattern. The objective of this cross-sectional study was to investigate the association between ARR and the non-dipping pattern based on home BP measurements. This study included 177 participants≥55 years from the general population of Ohasama (mean age: 67.2 years; 74.6% women); no patient was receiving antihypertensive treatment. The median plasma renin activity (PRA), plasma aldosterone concentration (PAC) and ARR were 0.8 ng/mL/h, 8.1 ng/dL and 9.7 ng/dL per ng/mL/h, respectively. Each 1 SD increase in log-transformed (ln) ARR was significantly associated with the prevalence of the non-dipping pattern after adjustments for possible confounding factors including home morning systolic BP (odds ratio, 1.45; p=0.049). However, no significant associations of PRA or PAC with the non-dipping pattern were observed (p≥0.2). When participants were divided into four groups according to median levels of home morning and night-time systolic BPs, the group with a higher home morning systolic BP (≥128.4 mmHg) with a higher home night-time systolic BP (≥114.4 mmHg) had the greatest ARR levels (ANCOVA p=0.01). These results support the hypothesis that relative aldosterone excess may be related to a non-dipping pattern in a general population and suggest that a non-dipping pattern can be accurately observed by home BP measurements.

Background/objective: Eplerenone is a highly selective aldosterone blocker, which has the potential to lower blood pressure (BP) in patients with hypertension. The objective of this study was to assess the hypotensive effects of low-dose eplerenone (25 mg) using home BP measurements. We also assessed the time required to reach 95% of the maximum antihypertensive effect (stabilization time) by analyzing exponential decay functions using home BP measurements., Methods: We reviewed the medical records of 83 hypertensive patients who were taking eplerenone 25 mg (age, 68.6±11.8 years; men, 36.1%) in addition to other antihypertensive agents. Home BPs were averaged in each patient for the last 5 days of each observation period. The morning versus evening effect (M/E ratio) and the evening versus morning effect (E/M ratio) were calculated to assess the duration of action of eplerenone., Results: The mean home systolic/diastolic BPs at baseline were 136.8±8.8/77.2±9.3 mmHg, respectively. After 8 weeks of treatment with eplerenone, home systolic/diastolic BP significantly decreased by -7.1±10.1/-2.6±5.0 mmHg (p<0.0001). The time for stabilization of home systolic and diastolic BPs was 13.7 days (p=0.006) and 16.5 days (p=0.001), respectively. When eplerenone was administered in the morning, the M/E ratio was 1.1±0.3. The corresponding E/M ratio for evening administration was 0.9±0.6. Although no nocturia was observed, there was a slight but significant increase in serum potassium levels (p=0.03)., Conclusions: Our data suggest that the combination of eplerenone with other antihypertensive drugs may be a promising therapeutic strategy for the treatment of essential hypertension.

The factors associated with visit-to-visit variability in blood pressure (BP) measured in the office between the two visits were identified in 1379 treated hypertensive patients (mean age, 66.1 ± 11.0 y; women, 53.8%). Multivariate regression analysis showed that office BP and visit-to-visit heart rate variability were positively associated with visit-to-visit BP variability, whereas body mass index, duration of antihypertensive medication, and taking amlodipine were negatively associated with visit-to-visit BP variability. Further prospective studies are required to clarify the causal relationships between these factors and visit-to-visit BP variability among treated hypertensive patients.

We investigate the change of the management of treated hypertensive patients with or without diabetes in Japan using the data in 2003 and the data in 2005-2006. Physicians treated hypertensive patients more aggressively and evaluated their patients' blood pressure (BP) control more strictly in 2005-2006 than in 2003. However, physicians' assessment of BP control might be still insufficient and the BP control status of patients with diabetes was still poorer than that of non-diabetes patients even in 2005-2006. Further investigation for the change of the management of treated hypertensive patients in Japan is needed.

The aim of this study is to investigate the status of Japanese pharmacists' awareness and attitude toward blood pressure (BP) measurement at home (HBP) and in the pharmacy. Of the 708 community pharmacists and the 117 hospital pharmacists, more than 90% of pharmacists answered that HBP was equally important to or more important than clinic BP, 71.9% (community) and 48.7% (hospital) recommended HBP measurement to the hypertensive patients, and about 15% correctly recognized the reference values of HBP hypertension. Among community pharmacists, 54.0% answered that BP-measuring devices were available in their pharmacy. More aggressive promotion of HBP measurement among pharmacists is warranted.

Although there are some reports that low plasma volume or increased cardiac output is associated with developing preeclampsia, there are few reports of daily serial hemodynamic data during pregnancy. A total of 37,092 home blood pressure (BP) and heart rate (HR) measurements were obtained from 425 normal pregnant women. Heart rate and shock index (SI) gradually increased by gestational week 32 and then decreased, whereas double product (DP) increased linearly during pregnancy. Although systolic BP and DP were consistently and negatively correlated with daily minimum outside temperature, HR and SI were positively correlated with minimum outside temperature in summer.

We identified the factors associated with home blood pressure (BP) variability in 1933 patients treated with hypertensive drugs (mean age, 67 years; women, 55%). Multivariate regression analysis showed that female gender, advanced age, home BP value, and home heart rate variability were positively associated with home BP variability, whereas home heart rate, body mass index, and duration of antihypertensive treatment were negatively associated with home BP variability. Moreover, not being medicated with amlodipine and being medicated with angiotensin II receptor blockers were associated with increased home systolic BP variability only among patients who were treated for less than 12 months.

We investigated morning home blood pressure (BP)- and heart rate (HR)-lowering effects of 2.5/5 mg bisoprolol in 70 patients with essential hypertension. After 4 weeks of treatment, mean home systolic/diastolic BP and HR significantly decreased by 2.6/5.2 mm Hg and by 8.1 bpm, respectively (all P < .05). The time required to reach 95% of the maximum lowering effect of bisoprolol (stabilizing time) was 5.1 days for home systolic BP (P = .2), 5.1 days for home diastolic BP (P = .0007), and 4.3 days for home HR (P < .0001). We demonstrated that the administration of low-dose bisoprolol significantly and rapidly decreased home BP and HR.

The PS-501 device (Parama-Tech, Fukuoka, Japan), an automated device for office blood pressure measurement based on the Korotkoff method and designed for professional use in clinical settings, was validated. Consecutive outpatients with hypertension and ≥30 years old at an outpatient hypertension clinic were recruited. According to the European Society of Hypertension protocol, 33 participants were included in the validation study (phase 1, n = 15; phase 2, n = 18). The cuff deflation rate can be selected manually from 2, 3, and 4 mm Hg/beat. The validation was performed with the device deflating at a rate of 2 mm Hg/beat. All blood pressure readings were measured on the left arm. The tested device passed all criteria for both systolic and diastolic blood pressure measurements. The mean (± standard deviation) differences in systolic and diastolic blood pressure between the tested device and the mean of observer readings were -1.9 ± 4.6 and -2.5 ± 2.9 mm Hg, respectively. The PS-501 device for office blood pressure measurement passed all the validation criteria of the European Society of Hypertension and can therefore be recommended for clinical use in an adult population.

We measured the brachial-ankle pulse wave velocity (baPWV) in 491 normotensives and determined the "PWV index" (measured baPWV-theoretical baPWV) in 491 normotensives and 83 controlled hypertensives. Linear regression analysis revealed that the theoretical baPWV (cm/sec) was 0.21 × age(2) (years(2))-13.73 × age (years) + 0.05 × mean arterial pressure(2) (mmHg(2)) + 3.95 × heart rate (bpm) + 36.49 × gender (1 male; 0 female) + 733 (R(2) = 0.53). The calculated PWV index was significantly higher in 13 smokers than 70 nonsmokers among controlled hypertensives. The calculated PWV index might provide more precise information about inherent arterial stiffness.

Low-dose (25 mg) or very low-dose (12.5 mg) spironolactone were added among 86 uncontrolled hypertensive patients who were undergoing monotherapy with calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin AT1-receptor blockers (ARBs). Morning home systolic/diastolic blood pressure (BP) reduction was similar among the CCB (n = 30, -8.2/-2.6 mmHg), ACEI (n = 22, -13.0/-4.7 mmHg), and ARB (n = 34, -11.5/-5.1 mmHg) groups. An increase in serum potassium correlated positively with the decline in morning systolic BP. Even very low-dose (12.5 mg) spironolactone is clinically effective, although serum potassium should be carefully monitored.

Ambulatory blood pressure monitoring (ABPM) is not widely used in clinical practice, because the measuring procedure is complex and the devices are expensive and need to be fitted by skilled medical technologists. The Microlife WatchBP O3 (Microlife AG, Widnau, Switzerland), which was developed for self blood pressure monitoring at home and adapted for ABPM, is highly affordable for an ABPM device and easy to manipulate. We performed an application test of the WatchBP O3 to confirm reliability of the device. Thirty-seven volunteer participants (age 30.4 ± 13.5 y) underwent blood pressure (BP) measurements every 30 min for 24 h, and were asked to complete a questionnaire about the user-friendliness and acceptability of the device. The participants were asked to attach the device and to detach it the next morning by themselves. The quality of recordings was assessed in terms of percentage of valid readings. The mean number of 24-h BP readings per participant was 46.6 ± 5.3. The percentage of valid readings was 90%, which was similar to that reported for traditional ambulatory devices. Eighty-six percent of participants found it is "easy" or "very easy" to attach the device by themselves. The WatchBP O3, which is easy to manipulate, may be convenient and acceptable for users. The percentage of valid readings is similar to that reported previously. A new era of self-monitoring of ambulatory BP is anticipated in the near future.

We previously demonstrated that heart rate (HR) variability obtained by daytime ambulatory monitoring and that of daily home measurement associated differently with cardiovascular mortality risk; cardiovascular mortality was linked with decreased daytime ambulatory HR variability and increased day-by-day home HR variability. The aim of this study was to identify factors contributing to each variability, clarifying possible reasons for their different predictive values. We obtained daytime ambulatory HR and home HR in 538 individuals of a general Japanese population aged ≥55 years. Daytime ambulatory HR variability and day-by-day home HR variability were estimated as a standard deviation measured every 30 min by daytime ambulatory monitoring and day-by-day home measurements once in the morning for 4 weeks, respectively. There was only weak correlation between daytime ambulatory HR variability and day-by-day home HR variability (r = 0.08∼0.14). In a multiple regression model, daytime ambulatory HR variability was associated with daytime ambulatory HR (P < 0.0001), daytime ambulatory blood pressure (BP) variability (P < 0.0001), and male sex (P = 0.003), while negatively associated with daytime ambulatory systolic blood pressure (SBP) (P < 0.0001) and smoking (P = 0.038). Meanwhile, day-by-day home HR variability was positively associated with home HR (P < 0.0001), day-by-day home BP variability (P < 0.0001), and male sex (P = 0.018). Associated factors of daytime ambulatory HR variability and day-by-day home HR variability were different. Our findings suggest that HR variabilities by different intervals of measurements might be mediated by different mechanisms.

To validate the FM-800 device (Fukuda Denshi Co., Ltd., Tokyo, Japan) for ambulatory blood pressure monitoring (ABPM), this validation study was performed based on the European Society of Hypertension (ESH) protocol and the Association for the Advancement of Medical Instrumentation (AAMI) criteria. Thirty-three participants were included (15 in phase 1 and an additional 18 in phase 2) in the ESH protocol. The device was tested on 85 participants according to the AAMI criteria, which require a mean device-observers discrepancy within 5 ± 8 mmHg. The tested device passed all the criteria for both systolic blood pressure (SBP) and diastolic blood pressure (DBP), and for the Korotkoff and oscillometric methods according to the ESH protocol. The test device also fulfilled the AAMI accuracy criteria for the 85 participants; the mean ± SD of the SBP/DBP differences between the tested device and the mean of the observer readings were -1.1 ± 4.2/-0.8 ± 4.2 mmHg for the Korotkoff method and 2.3 ± 3.9/-2.3 ± 3.9 mmHg for the oscillometric method. The FM-800 device for ABPM passed all the validation criteria of the ESH and AAMI and can, therefore, be recommended for clinical use in an adult population.

The effects and duration of action of bedtime administration of doxazosin 2 mg for 4 weeks on uncontrolled morning home hypertension were investigated. Morning home blood pressure (HBP) was significantly lowered by bedtime administration of doxazosin. Doxazosin significantly lowered evening HBP only in the subgroup of patients with an uncontrolled evening HBP. The evening (E)/morning (M) ratio was greater in patients with an uncontrolled evening HBP than in those with a controlled evening HBP. The results suggest that bedtime administration of doxazosin effectively suppresses morning HBP in uncontrolled morning hypertensives and lowers evening HBP in uncontrolled evening hypertensives.

We investigated the effect of the timing of imidapril administration in patients with morning hypertension (home blood pressure [HBP] in the morning [morning HBP] > or =135/85 mmHg). Eighty-seven patients (mean age, 61 years; 48% women) with morning hypertension each measured HBP in the early morning, before going to bed for the final five days of the observation, and during treatment. Imidapril (2.5 or 5.0 mg) was administered once every morning (n = 57) or at bedtime (n = 30) for four weeks (monotherapy: n = 30, 34%; combined with other antihypertensive drugs: n = 57, 66%). The morning (M) versus evening (E) effect (M/E ratio) and the evening versus morning effect (E/M ratio) were calculated to assess the duration of imidapril action. Morning HBP was significantly reduced (all p < 0.05) except when 2.5 mg of imidapril was administered once at bedtime. The individual M/E ratios expressed as means +/- standard deviation for systolic HBP were 0.9 +/- 0.7 and 0.7 +/- 0.7 for the morning administration of 2.5 and 5.0 mg of imidapril, respectively. The corresponding E/M ratios for bedtime administration were 0.3 +/- 0.5 and 1.0 +/- 0.7, respectively. One daily dose of imidapril taken either in the morning or at bedtime lowered morning HBP, indicating that imidapril is useful for controlling morning hypertension.

To investigate the relationship between morning and evening home blood pressure (BP) measurements to make a diagnosis of masked hypertension, we collected information on the characteristics of 3,303 essential hypertensive outpatients receiving antihypertensive medication in Japan using a physician, self-administered questionnaire. All patients were asked to measure their home BP once every morning and once every evening for two weeks. Morning and evening home BP values of each patient were defined as the average of all morning and all evening home BP values, respectively. The mean BP values of all study subjects were 142.8/80.6 mmHg for office BP, 139.8/81.8 mmHg for morning home BP, 133.7/76.9 mmHg for evening home BP, and 136.8/79.3 mmHg for the average of the morning and evening home BPs. Masked hypertension was defined as an office BP < 140/90 mmHg and a home BP > or = 135/85 mmHg. The prevalence of masked hypertension diagnosed using morning home BP (23.1%) was higher than that diagnosed by evening home BP (14.7%); the prevalence was 19.0% when diagnosed using the average of the morning and evening home BPs. Among the 1,386 patients with a normal office BP, the diagnosis of masked hypertension based on morning and evening home BP values differed in 28.8% of patients for systolic BP and 20.9% for diastolic BP (kappa coefficient = 0.43). The present study showed that the prevalence of masked hypertension was underestimated when the diagnosis of masked hypertension was made on the basis of evening home BP.

The Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) Study is the first large-scale intervention trial in Japan using a PROBE design to determine an optimal target blood pressure (BP) level on the basis of self-measured BP at home and optimal initial antihypertensive medication. The registered patients are randomized to one of two different BP levels and to initial antihypertensive regimens (i.e., calcium antagonist [Ca-A], angiotensin-converting enzyme inhibitor [ACE-I], or angiotensin II receptor antagonist [ARB]). At the end of February 2004, 2729, 1687, and 971 patients were recruited, randomized, and followed-up for 12 months or more. Among the 971 patients, mean systolic/diastolic BP levels at randomization in the Ca-A, ACE-I, and ARB groups were 150/90, 152/89, and 151/89 mmHg, respectively. These values reduced after six months of Ca-A-, ACE-I-, and ARB-based treatment (133/81 mmHg, 135/80 mmHg, and 134/79 mmHg, respectively) and further reduced after 12 months (131/80 mmHg, 134/79 mmHg, and 132/79 mmHg, respectively) without any significant differences among groups. In more intensive and less intensive BP-lowering groups, mean systolic/diastolic BP levels at randomization were 151/90 and 150/89 mmHg, respectively. Although BP levels reduced after 6-month (135/80 mmHg and 133/80 mmHg, respectively) and 12-month treatment (133/79 mmHg and 132/80 mmHg, respectively) in each target group, no significant difference in BP values was observed between groups. These results indicate the necessity of additional interventional strategies to improve the achievement of target BP levels, especially in the more intensive BP-lowering group.