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Background: This study aimed to propose reference values for day-to-day home blood pressure (BP) variability that align with the established hypertension threshold of home BP for the risk of two different outcomes: cardiovascular mortality and cognitive decline., Methods: This prospective study was conducted in Ohasama town, Japan, with 1212 participants assessed for cardiovascular mortality risk (age: 64.7 years, 33.6% men). Additionally, 678 participants (age: 62.7 years, 31.1% men) were assessed for cognitive decline risk (Mini-Mental Scale Examination score <24). The within-individual coefficient of variation (CV) of home morning SBP (HSBP) was used as the index of day-to-day BP variability (%). Adjusted Cox regression models were used to estimate the HSBP-CV values, which provided the 10-year outcome risk at an HSBP of 135 mmHg., Results: A total of 114 cardiovascular deaths and 85 events of cognitive decline (mean follow-up:13.9 and 9.6 years, respectively) were identified. HSBP and HSBP-CV were associated with increased risks for both outcomes, with adjusted hazard ratios per 1-standard deviation increase of at least 1.25 for cardiovascular mortality and at least 1.30 for cognitive decline, respectively. The adjusted 10-year risks for cardiovascular mortality and cognitive decline were 1.67 and 8.83%, respectively, for an HSBP of 135 mmHg. These risk values were observed when the HSBP-CV was 8.44% and 8.53%, respectively., Conclusion: The HSBP-CV values indicating the 10-year risk of cardiovascular mortality or cognitive decline at an HSBP of 135 mmHg were consistent, at approximately 8.5%. This reference value will be useful for risk stratification in clinical practice., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The Japanese Society of Hypertension updated guidelines for hypertension management (JSH2019), changing the blood pressure (BP) classification. However, evidence is sparse regarding the association of the classification with cardiovascular disease (CVD) events among young to middle-aged workers in Japan. We examined this issue using longitudinal data from Japan Epidemiology Collaboration on Occupational Health Study with a prospective cohort design. Participants were 81,876 workers (aged 20-64 years) without taking antihypertensive medication at baseline. BP in 2011 or 2010 was used as exposure. CVD events that occurred from 2012 to 2021 were retrieved from a within-study registry. Cox regression was used to calculate multivariable-adjusted hazard ratios of CVD events. During 0.5 million person-years of follow-up, 334 cardiovascular events, 75 cardiovascular deaths, and 322 all-cause deaths were documented. Compared with normal BP (systolic BP [SBP] < 120 mmHg and diastolic BP [DBP] < 80 mmHg), multivariable-adjusted hazard ratios (95% confidence intervals) of cardiovascular events were 1.98 (1.49-2.65), 2.10 (1.58-2.77), 3.48 (2.33-5.19), 4.12 (2.22-7.64), and 7.81 (3.99-15.30) for high normal BP (SBP120-129 mmHg and DBP < 80 mmHg), elevated BP (SBP130-139 mmHg and/or DBP80-89 mmHg), stage 1 hypertension (SBP140-159 mmHg and DBP90-99 mmHg), stage 2 hypertension (SBP160-179 mmHg and/or DBP100-109 mmHg), and stage 3 hypertension (SBP ≥ 180 mmHg and/or DBP ≥ 110 mmHg), respectively. The highest population attributable fraction was observed in elevated BP (17.8%), followed by stage 1 hypertension (14.1%). The present data suggest that JSH2019 may help identify Japanese workers at a higher cardiovascular risk., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

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 m 2 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., (© 2024. The Author(s).)

Accurate blood pressure measurement is the key procedure for the diagnosis and treatment of hypertension. In-office and out-of-office blood pressure measurements both have advantages and weak points, and multifaceted blood pressure information in individuals should be appropriately obtained and assessed. Validation of blood pressure measurement devices has long been an important issue, and several consortiums have emerged to try address it. Clinical guidelines should meet the demands of the region in which they are applied, and out-of-office measurements have been widely stated and recommended in the recently published guidelines worldwide. Appropriate assessment of blood pressure should be performed routinely in order to provide timely and accurate evidence regarding hypertension under any situation, including an unexpected pandemic., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

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Aim: Lifetime risk (LTR) indicates the absolute risk of disease during the remainder of an individual's lifetime. We aimed to assess the LTRs for coronary heart disease (CHD) mortality associated with blood pressure (BP) and total cholesterol levels in an Asian population using a meta-analysis of individual participant data because no previous studies have assessed this risk., Methods: We analyzed data from 105,432 Japanese participants in 13 cohorts. Apart from grade 1 and 2-3 hypertension groups, we defined "normal BP" as systolic/diastolic BP ＜130/＜80 mmHg and "high BP" as 130-139/80-89 mmHg. The sex-specific LTR was estimated while considering the competing risk of death., Results: During the mean follow-up period of 15 years (1,553,735 person-years), 889 CHD deaths were recorded. The 10-year risk of CHD mortality at index age 35 years was ≤ 0.11%, but the corresponding LTR was ≥ 1.84%. The LTR of CHD at index age 35 years steeply increased with an increase in BP of participants with high total cholesterol levels [≥ 5.7 mmol/L (220 mg/dL)]. This risk was 7.73%/5.77% (95% confidence interval: 3.53%-10.28%/3.83%-7.25%) in men/women with grade 2-3 hypertension and high total cholesterol levels. In normal and high BP groups, the absolute differences in LTRs between the low and high total cholesterol groups were ≤ 0.25% in men and ≤ 0.40% in women., Conclusions: High total cholesterol levels contributed to an elevated LTR of CHD mortality in hypertensive individuals. These findings could help guide high-risk young individuals toward initiating lifestyle changes or treatments.

Despite the clinical usefulness of self-measured home blood pressure (BP), reports on the characteristics of home BP have not been sufficient and have varied due to the measurement conditions in each study. We constructed a database on self-measured home BP, which included five Japanese general populations as subdivided aggregate data that were clustered and meta-analyzed according to sex, age category, and antihypertensive drug treatment at baseline (treated and untreated). The self-measured home BPs were collected after a few minutes of rest in a sitting position: (1) the morning home BP was measured within 1 h of waking, after urination, before breakfast, and before taking antihypertensive medication (if any); and (2) the evening home BP was measured just before going to bed. The pulse rate was simultaneously measured. Eligible data from 2000 onward were obtained. The morning BP was significantly higher in treated participants than in untreated people of the same age category, and the BP difference was more marked in women. Among untreated residents, home systolic/diastolic BPs measured in the morning were higher than those measured in the evening; the differences were 5.7/5.0 mmHg in women (ranges across the cohorts, 5.3-6.8/4.7-5.4 mmHg) and 7.3/7.7 mmHg in men (ranges, 6.4-8.5/7.0-8.7 mmHg). In contrast, the home pulse rate in women and men was 2.4 (range, 1.5-3.7) and 5.6 (range, 4.6-6.6) beats per minute, respectively, higher in the evening than in the morning. We demonstrated the current status of home BP and home pulse rate in relation to sex, age, and antihypertensive treatment status in the Japanese general population. The approach by which fine-clustered aggregate statistics were collected and integrated could address practical issues raised in epidemiological research settings.

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.

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.

Background The present study assessed the association between blood pressure (BP) and the risk of chronic kidney disease (CKD) according to gender and the use of antihypertensive drugs using data from a large-scale health checkup. Methods and Results We conducted a retrospective cohort study using the JMDC database, which contains annual health checkup data of Japanese employees and their dependents aged <75 years. We included 154 692 participants (men, 69.68%; mean age, 44.74 years) without CKD. CKD was indicated by an estimated glomerular filtration rate <60 mL/min per 1.73 m 2 or the presence of proteinuria. During the mean follow-up period of 4.78 years, new-onset CKD occurred in 14 888 participants. When the normal BP group (systolic/diastolic BP <120/<80 mm Hg) without treatment was used as a reference, the hazard ratios of the high BP (130-139/80-89 mm Hg) and grade 1 (140-159/90-99 mm Hg) and grade 2 or 3 hypertension (≥160/≥100 mm Hg) groups were 1.11 (95% CI, 1.06-1.17), 1.36 (95% CI, 1.28-1.45), and 1.76 (95% CI, 1.56-1.99) for untreated men, respectively. However, in treated men, even normal BP was associated with a 1.5-fold higher risk of CKD. The association between BP and the risk of CKD was weaker in untreated women than in untreated men. The risk of CKD in treated women with normal BP was similar to that of untreated women with normal BP. Conclusions Gender differences were found in the association between BP and CKD risk. Kidney function in treated individuals should be followed carefully, especially in men.

: Blood pressure (BP) exhibits seasonal variation with lower levels at higher environmental temperatures and higher at lower temperatures. This is a global phenomenon affecting both sexes, all age groups, normotensive individuals, and hypertensive patients. In treated hypertensive patients it may result in excessive BP decline in summer, or rise in winter, possibly deserving treatment modification. This Consensus Statement by the European Society of Hypertension Working Group on BP Monitoring and Cardiovascular Variability provides a review of the evidence on the seasonal BP variation regarding its epidemiology, pathophysiology, relevance, magnitude, and the findings using different measurement methods. Consensus recommendations are provided for health professionals on how to evaluate the seasonal BP changes in treated hypertensive patients and when treatment modification might be justified. (i) In treated hypertensive patients symptoms appearing with temperature rise and suggesting overtreatment must be investigated for possible excessive BP drop due to seasonal variation. On the other hand, a BP rise during cold weather, might be due to seasonal variation. (ii) The seasonal BP changes should be confirmed by repeated office measurements; preferably with home or ambulatory BP monitoring. Other reasons for BP change must be excluded. (iii) Similar issues might appear in people traveling from cold to hot places, or the reverse. (iv) BP levels below the recommended treatment goal should be considered for possible down-titration, particularly if there are symptoms suggesting overtreatment. SBP less than 110 mmHg requires consideration for treatment down-titration, even in asymptomatic patients. Further research is needed on the optimal management of the seasonal BP changes.

Objective: Twenty-four-hour ambulatory pulse pressure (PP) is a powerful predictor of outcome. We attempted to apply the recently described PP components, an elastic (elPP), and systolic stiffening (stPP) components from 24-h ambulatory blood pressure (BP) monitoring (AMBP), and examine their influence on outcome in the Ohasama study population., Design and Methods: Included were participants of the Ohasama study without history of cardiovascular disease (CVD), who were followed-up for total and CVD mortality, and for stroke morbidity. The PP components were derived from 24-h SBP and DBP using a model based on the nonlinear pressure--volume relationship in arteries expressing pressure stiffness relationship. Outcome predictive power was estimated by Cox regression models; hazard ratio with 95% confidence interval (CI), applied to elPP, and stPP, adjusted for age, sex, BMI, smoking, alcohol drinking, diabetes mellitus, total cholesterol, antihypertensive treatment, and mean arterial pressure (MAP), whenever appropriate., Results: Of 1745 participants (age 61.4 ± 11.6, 65% women), 580 died, 212 of CVD, and 290 experienced a stroke during 17 follow-up years. PP was strongly correlated with elPP (r = 0.89) and less so with stPP (r = 0.58), and the correlation between the two components was weak (r = 0.15). After the adjustment, hazard ratio of PP per 1 SD increment for total mortality, CVD mortality, and stroke morbidity were 1.095 (95% CI 0.973-1.232), 1.207 (1.000-1.456), and 0.983 (0.829-1.166), respectively. Corresponding hazard ratios and 95% CIs were nonsignificant for elPP, and stPP. However, among participants with median pulse rate 68.5 bpm or less (median, n = 872), total (327 deaths) and CVD (131 deaths) mortality were predicted by elPP (per 1 SD increment), hazard ratio 1.231 (95% CI, 1.082-1.401), and 1.294 (95% CI, 1.069-1.566), respectively. In the subgroup of treated participants with hypertension and pulse rate 68.5 or less bpm (n = 309), total (177 deaths) and CVD (77 deaths) mortality were predicted by elPP, hazard ratio of 1.357 (95% CI, 1.131-1.628), and 1.417 (95% CI, 1.092-1.839), respectively. Stroke morbidity was not predicted by either PP or the PP components., Conclusion: In a rural Japanese population, elPP but not stPP was predictive of total and CVD mortality even when adjusted for MAP and conventional risk factors in the subpopulation with slower pulse rate. This was mostly among the treated hypertensive patients.

This study investigated the association between maternal home blood pressure (HBP) trajectory during pregnancy and infant birth weight. A total of 755 pregnant women were included in this prospective cohort study. A group-based trajectory model identified six trajectory groups for home systolic blood pressure (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). Next, the association of HBP trajectory groups with infant birth weight was evaluated using a general linear model considering potential confounding factors. For home SBP and MAP, the trajectory groups with a low-steep J-curve, moderate J-curve, little high J-curve, and high J-curve were significantly associated with lower infant birth weight than the low-J-curve group. Among the trajectory groups for home DBP, the moderate-steep J-curve, little high J-curve, and high J-curve were significantly associated with lower infant birth weight than the group with low-J-curve. The effect sizes of the trajectory groups varied in infant birth weight from -0.21 standard deviations (SDs) (95% confidence interval (CI): -0.42 to -0.01 SD) to -1.13 SD (95% CI: -1.54 to -0.72 SD). In the analyses of infant birth weight in grams, effect sizes that were significantly associated with infant birth weight varied from -84 g (95% CI: -167 to -1 g) to -567 g (95% CI: -732 to -402 g). Trajectory groups with a moderate-reverse J-curve for home SBP, DBP, and MAP were not significantly associated with infant birth weight. Maternal HBP trajectory during pregnancy was an indicator of infant birth weight. Further studies evaluating the associations between HBP during pregnancy and other perinatal outcomes are needed.

Although high blood pressure (BP) and BP variability have been reported to be associated with cognitive impairment, few studies have investigated the association between home BP (HBP) and cognitive function in the oldest-old. The aim of this study was to evaluate whether the value of and the day-to-day variability in HBP was associated with cognitive function in a Japanese community-dwelling oldest-old population. Among 111 participants aged 85-87 years, cognitive function was assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). HBP was measured two times every morning for a median of 30 days. The value of and variability in HBP were calculated as the average and coefficient of variation (CV) of the measurements, respectively. The associations of HBP variability with MoCA-J were examined using multiple linear regression models. Of 111 participants, 47.7% were men, and 64.0% were taking medications for hypertension. The mean HBP was 141.9 ± 14.8/72.2 ± 8.4 mmHg, and the mean CV of HBP was 6.7 ± 1.9/6.8 ± 2.4. The mean total MoCA-J score was 22.9 ± 3.5. The MoCA-J score was significantly lower with increasing CVs of both systolic BP (b = -0.36, p = 0.034) and diastolic BP (b = -0.26, p = 0.046) after adjustment for possible confounding factors. The value of HBP was not associated with MoCA-J. In the community-dwelling oldest-old population, higher day-to-day HBP variability, but not the value of HBP, was associated with cognitive impairment. When measuring HBP, attention should be paid not only to the values but also to their variations.

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.

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.

Despite the wide use of automated devices for the self-measurement of home blood pressure (BP), no evidence is available regarding the accuracy of such devices in oldest-old populations. The aim of this study was to validate the accuracy of the automated oscillometric upper arm-cuff BP-monitoring device according to an international protocol in oldest-old individuals. In 35 participants aged over 85 years old, BP was measured on the same arm sequentially using a mercury sphygmomanometer (by two observers) and an Omron HEM-7080IC. The difference between the test device and observer measurements and associated factors were evaluated according to the International Organization for Standardization (ISO) 81060-2:2013 protocol. A total of 105 pairs (three pairs per participant) of the test device and observer BP measurements were obtained. The mean (±standard deviation: SD) differences in systolic BP (SBP) and diastolic BP (DBP) between the methods were -0.7 ± 7.1 and -1.1 ± 4.5 mmHg, respectively, and those for each participant were -0.7 ± 5.8 mmHg for SBP and -1.1 ± 4.1 mmHg for DBP; the device therefore fulfilled the requirements of the ISO protocol. In the multivariate analysis with the linear mixed model, the difference was associated with the cuff size for SBP and pulse pressure for DBP. The Omron HEM-7080IC passed the ISO requirements for oldest-old individuals aged 85 years or older. This device can be recommended for clinical and self/home use in oldest-old populations.

Background: Relationships between blood glucose (BG) levels and insulin action, and incidence of hypertension have not been well known epidemiologically. This study aimed to investigate the association between indices of diabetes and the incidence of hypertension and compare the predictive powers of these indices in middle-aged Japanese., Methods: This 5-year cohort study included 2,210 Japanese aged 30-64 years without hypertension. Hazard ratios of high fasting blood glucose (FBG) levels, high post-loaded BG levels, high glycated hemoglobin (HbA1c) levels, insulin resistance (defined by homeostasis model assessment of insulin resistance [HOMA-IR]) and impaired insulin secretion at baseline for the incidence of hypertension were estimated using multivariable-adjusted Cox proportional hazard models. Hypertension was defined as blood pressure ≥ 140/90 mm Hg or receiving antihypertensive treatment., Results: During the follow-up, 456 participants developed hypertension. After adjustment for HbA1c and HOMA-IR, FBG was independently and significantly associated with hypertension. The hazard ratio of participants with FBG ≥ 7.0 mmol/l was 1.79 compared with those with FBG < 5.6 mmol/l. Even among those with HbA1c < 6.5%, HOMA-IR < 2.5, body mass index < 25 kg/m2, age < 55 years old, blood pressure < 130/80 mm Hg or non- and moderate drinking, the results were similar. High 120-minute BG level and impaired insulin secretion did not increase the risk for hypertension., Conclusions: FBG was a predictable index for future incidence of hypertension in middle-aged Japanese men and women. This is the first study comparing predictive powers of indices of diabetes for the incidence of hypertension., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The new American College of Cardiology/American Heart Association guideline reclassified office blood pressure and proposed thresholds for ambulatory blood pressure (ABP). We derived outcome-driven ABP thresholds corresponding with the new office blood pressure categories. We performed 24-hour ABP monitoring in 11 152 participants (48.9% women; mean age, 53.0 years) representative of 13 populations. We determined ABP thresholds resulting in multivariable-adjusted 10-year risks similar to those associated with elevated office blood pressure (120/80 mm Hg) and stages 1 and 2 of office hypertension (130/80 and 140/90 mm Hg). Over 13.9 years (median), 2728 (rate per 1000 person-years, 17.9) people died, 1033 (6.8) from cardiovascular disease; furthermore, 1988 (13.8), 893 (6.0), and 795 (5.4) cardiovascular and coronary events and strokes occurred. Using a composite cardiovascular end point, systolic/diastolic outcome-driven thresholds indicating elevated 24-hour, daytime, and nighttime ABP were 117.9/75.2, 121.4/79.6, and 105.3/66.2 mm Hg. For stages 1 and 2 ambulatory hypertension, thresholds were 123.3/75.2 and 128.7/80.7 mm Hg for 24-hour ABP, 128.5/79.6 and 135.6/87.1 mm Hg for daytime ABP, and 111.7/66.2 and 118.1/72.5 mm Hg for nighttime ABP. ABP thresholds derived from other end points were similar. After rounding, approximate thresholds for elevated 24-hour, daytime, and nighttime ABP were 120/75, 120/80, and 105/65 mm Hg, and for stages 1 and 2, ambulatory hypertension 125/75 and 130/80 mm Hg, 130/80 and 135/85 mm Hg, and 110/65 and 120/70 mm Hg. Outcome-driven ABP thresholds corresponding to elevated blood pressure and stages 1 and 2 of hypertension are similar to those proposed by the current American College of Cardiology/American Heart Association guideline.

Objective: We conducted a cross-sectional study to clarify whether home blood pressure (HBP) is more strongly associated with coronary artery calcification (CAC) than accurately measured office blood pressure (OBP) among the general population of Japanese men., Methods: We analyzed the data of 919 Japanese male participants who were randomly selected from general population (mean age 64.5 years). OBP was measured twice consecutively by a trained nurse using electrical device after 5 min of complete rest alone in a sitting position in a silent room. The participants were asked to measure HBP with an electrical device once in the morning during 7 consecutive days. CAC was assessed using computed tomography. Presence of CAC was defined as Agatston score at least 10. We calculated odds ratios for the presence of CAC per one SD higher OBP and HBP adjusted for age and other cardiovascular risk factors., Results: The mean systolic OBP (SD) and HBP (SD) were 136.8 (19.0) and 137.2 (18.5) mmHg, respectively, without statistical difference between the two (P = 0.595). OBP and HBP were highly correlated (r = 0.74 P < 0.001). CAC was found in 454 (49.4%) participants. Multivariable-adjusted odds ratios [95% confidence interval (CI)] for the presence of CAC were comparable between OBP (1.32, 95% CI: 1.12-1.56) and HBP (1.35, 95% CI: 1.14-1.60) (P heterogeneity = 0.813)., Conclusion: The strength of association of accurately measured OBP with CAC was comparable with that of HBP among randomly selected male general population aged 40-79 years.

Background: The morning period which is recognized as the highest risk for cardiovascular events is associated with a surge in blood pressure (BP). However, it is unclear what aspect of this rise is important., Aim: To determine whether the rate of rise (RoR), the magnitude (day night difference) or the product [BP power (BPPower)] is associated with increased cardiovascular risk., Methods: We developed a logistic equation method to fit individual 24-h patterns of BP to determine RoR, amplitude and BPPower using the ambulatory recordings from the Ohasama study including 564 men and 971 women (16.6 years follow-up)., Results: Men had a higher risk of cardiovascular events than women (24, 16%, P < 0.001). Age and night BP were strong linear risk predictors. In men sorting risk by quintiles of BPPower (adjusted for age, night BP, smoking status) revealed no clear linear or nonlinear pattern. However, in women BPPower had a U-shaped relationship with the lowest risk being the 2-3rd quintile for all cardiovascular events (Pquadratic = 0.01) including cardiovascular death (Pquadratic = 0.03) and nonfatal stroke (Pquadratic = 0.02). A similar but less clear trend was observed with the RoR but only stroke (infarct) reached significance (Pquadratic = 0.03) while sorting by range showed a U shaped pattern for combined cardiovascular events (Pquadratic = 0.04)., Conclusion: These findings suggest that the morning BPPower is an important independent risk factor for predicting cardiovascular events and stroke but only in women with median levels having the lowest risk.

Multiple blood pressure (BP) measurements allow an evaluation of BP variability and BP‑derived arterial stiffness indices. Periodic variations in BP are well known, from beat‑to‑beat BP readings in intra‑arterial measurement to seasonal variations in BP. Diurnal BP variation has been investigated in relation to its prognostic value. People with night‑to‑day BP ratio of 1 or higher, that is, those with a higher nocturnal than daytime BP, were older than those with normal dipping status at baseline and had a greater risk of cardiovascular mortality and morbidity. Short‑term BP variability was evaluated using an intraindividual standard deviation or average real variability without any assumption of a periodic fluctuation. The ambulatory arterial stiffness index (AASI), which is derived from ambulatory BP monitoring, is a surrogate measure of arterial stiffness. An increased short‑term BP variability and the AASI have been linked to target organ damage and poor prognosis, while short‑term BP variability added only 1% or less to the prediction of a cardiovascular event. Although strict BP control at any time of the day is essential, studies are required to clarify how much additional benefit is derived from a treatment considering BP variability or the AASI in patients with hypertension.

: Studies using ambulatory blood pressure (BP) monitoring have shown that BP during night-time sleep is a stronger predictor of cardiovascular outcomes than daytime ambulatory or conventional office BP. However, night-time ambulatory BP recordings may interfere with sleep quality because of the device cuff inflation and frequency of measurements. Hence, there is an unmet need for obtaining high quality BP values during sleep. In the last two decades, technological development of home BP devices enabled automated BP measurements during night-time. Preliminary data suggest that nocturnal home BP measurements yield similar BP values and show good agreement in detecting nondippers when compared with ambulatory BP monitoring. Thus, nocturnal home BP measurements might be a reliable and practical alternative to ambulatory BP monitoring to evaluate BP during sleep. As the use of home BP devices is widespread, well accepted by users and has relatively low cost, it may prove to be more feasible and widely available for routine clinical assessment of nocturnal BP. At present, however, data on the prognostic relevance of nocturnal BP measured by home devices, the optimal measurement schedule, and other methodological issues are lacking and await further investigation. This article offers a systematic review of the current evidence on nocturnal home BP, highlights the remaining research questions, and provides preliminary recommendations for application of this novel approach in BP management.

To develop a risk chart or score that is based on recent data and applicable to the Japanese people, we need a large cohort study representative of the Japanese people without a need for long-term follow-up. The purpose of the present study was to develop a risk scoring system to estimate the 5- and 10-year absolute and cumulative incidence risk of stroke and acute myocardial infarction (AMI), composite outcome of stroke and AMI, and death from all cardiovascular disease (CVD). The cumulative incidence risk ratios were calculated using a multiple Poisson regression model and data from the Japan Arteriosclerosis Longitudinal Study, which included 67,969 men and women aged 40-89 years. An absolute risk scoring system for 5- and 10-year risk was developed. For blood pressure categories, the risk ratios for all outcomes increased from normal blood pressure (systolic blood pressure (SBP) 120-129 mmHg and diastolic blood pressure (DBP) 80-89 mmHg) to grade III hypertension (SBP ≥ 180 and/or DBP ≥ 110) based on the 2014 Guidelines for the Management of Hypertension compared to the reference optimal blood pressure (SBP < 120 and DBP < 80). Grade II (SBP 160-179 and/or DBP 100-109) and III hypertension treated with medication showed a lower risk compared to counterparts without medication. Other risk factors showed reasonable figures. The total of scores for each risk factor indicated the estimated absolute risk for stroke and AMI, the composite outcome of stroke and AMI, and all CVD. This scoring system may contribute to patient education and to the development of strategies for reducing CVD in the population.

Several studies demonstrated that visit-to-visit variability of blood pressure (BP) predicted future events of total death, stroke and cardiovascular disease. Little is known about factors associated with visit-to-visit BP variability in different countries. We recruited participants aged 40-59 years from four countries (Japan, the People's Republic of China [PRC], the United Kingdom [UK] and the United States [US]). At each study visit, BP was measured twice by trained observers using random zero sphygmomanometers after five minutes resting. We defined visit-to-visit BP variability as variation independent of mean (VIM) by using average systolic BP of 1st and 2nd measurement across four study visits. Data on 4680 men and women were analyzed. Mean ± standard deviation of VIM values among participants in Japan, the PRC, the UK and the US were 5.44 ± 2.88, 6.85 ± 3.49, 5.65 ± 2.81 and 5.84 ± 3.01, respectively; VIM value in the PRC participants was significantly higher. Sensitivity analyses among participants without antihypertensive treatment or past history of cardiovascular disease yielded similar results. Higher VIM value was associated with older age, female gender, lower pulse rate and urinary sodium excretion and use of antihypertensive agents such as angiotensin converting enzyme inhibitors, beta blockers and calcium channel blockers. The difference of visit-to-visit BP variability between PRC and other countries remained significant after adjustment for possible confounding factors. In this large international study across four countries, visit-to-visit BP variability in the PRC was higher than in the other three countries. Reproducibility and mechanisms of these findings remain to be elucidated.

The aim was to investigate the risk of developing type 2 diabetes according to blood pressure (BP) levels and presence or absence of hypertensive treatment. This 5-year cohort study comprised 3508 Japanese adults aged 30-74 years without diabetes who had undergone a medical checkup including a 75-g oral glucose tolerance test (OGTT) between April 2008 and March 2009 at Saku Central Hospital. Participants receiving antihypertensive treatment were categorized into controlled hypertension ( < 140/90 mmHg) or uncontrolled hypertension ( ≥ 140/90 mmHg) groups. Participants not receiving antihypertensive treatment were categorized: optimal BP ( < 120/80 mmHg), normal BP (120-129/80-84 mmHg), high-normal BP (130-139/85-89 mmHg), grade I hypertension (140-159/90-99 mmHg), and grade II/III hypertension ( ≥ 160/100 mmHg). Hazard ratios and 95% confidence intervals for the incidence of type 2 diabetes as defined by the 75-g OGTT were estimated using multivariable-adjusted Cox proportional hazard models in reference to optimal BP. During an average of 4.4 years of follow-up, 295 participants developed type 2 diabetes. Those with high-normal BP, grade I hypertension, grade II/III hypertension, and uncontrolled hypertension were at significantly higher risk for developing type 2 diabetes, with hazard ratios (95% confidence intervals) of 1.53 (1.03-2.29), 1.53 (1.02-2.32), 2.19 (1.01-4.77), and 1.81 (1.10-2.99), respectively. In conclusion, compared with those with optimal BP, individuals with BP ≥ 130/85 mmHg not receiving antihypertensive treatment and uncontrolled hypertensives with BP ≥ 140/90 mmHg receiving antihypertensive treatment were at a significantly higher risk for developing type 2 diabetes.

Objective: The conventional nocturnal blood pressure monitoring (NBPM) systems can disturb sleep and lead to false measurements. The present study compared the validity and acceptability of a newly developed wrist-cuff system with that of the conventional upper arm-cuff system for NBPM., Participants and Methods: Home blood pressure (BP) and pulse rate (PR) were measured in hypertensive patients (n=57) every 30 min at night using a wrist-cuff system and at 2 am (fixed time) and 4 h after going to bed (flexible time) using an upper arm-cuff system. The nocturnal BPs with the wrist-cuff system at 2 am and at 4 h after going to bed were selected from the measurements taken every 30 min at night. The same systems were used to measure the morning and evening home BP and PR, after rising and before going to bed. Measurements were taken for two nights separately for each system. BP, PR, sleep quality, and the perception of several stimuli during NBPM were compared between the two systems. Systolic BP/diastolic BP (DBP) in the supine position at 2 am and at 4 h after going to bed were corrected by the mean difference between the wrist-cuff and the arm-cuff systems., Results: Compared with the arm-cuff system, the wrist-cuff system had significantly lower systolic BP (mean±SD: 106.3±13.4 vs. 109.8±10.8 mmHg, P<0.05), DBP (59.4±11.0 vs. 64.5±7.8 mmHg, P<0.005), and PR (53.8±7.1 vs. 60.5±8.1 bpm, P<0.0005) at 2 am and significantly lower DBP (60.2±10.3 vs. 66.0±9.8 mmHg, P<0.005) and PR (53.6±7.4 vs. 60.9±8.5 bpm, P<0.0005) at 4 h after going to bed. Among the participants, sleep disturbance during NBPM was reported in less than 20% with the wrist-cuff system and in 70% with the arm-cuff system. A significantly higher rate of participants who wore the wrist-cuff system reported that they were not bothered by various stimuli, such as noise, during NBPM., Discussion: The newly developed wrist-cuff home NBPM system provided information on BP as a function of time, especially at night, with minimal sleep disturbance and with more frequent BP measurements.

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.

Objective: The mechanism by which higher blood pressure (BP) variability causes cardiovascular events remains unclear. Experimental results indicate that alterations in vessel wall tension related to BP variability may initiate atherosclerosis through oscillatory shear stress. We examined associations of home BP variability with subclinical atherosclerosis at four anatomically distinct vascular beds., Methods: In a cross-sectional population-based study of 1033 Japanese (mean age, 64.0 years; men, 88.7%) without known cardiovascular disease, we defined SBP and DBP variability as variability independent of the mean (VIM) across self-measured home BP values during seven consecutive days and quantified coronary and aortic artery calcification (CAC and AAC) by computed tomography, carotid intima-media thickness (CIMT) by ultrasonography, and ankle-brachial index (ABI)., Results: In multivariable adjusted models including mean SBP, higher VIM of SBP was associated with CIMT greater than1.0 mm [relative risk (95% confidence interval) fourth versus first quartile, 1.71 (1.15-2.54)], AAC score greater than 0 [1.08 (1.02-1.15)], and ABI less than 1.1 [1.49 (1.12-1.97)], and linear trends were also statistically significant. However, there was no significant association between VIM of SBP and CAC score greater than 0. Meanwhile, higher VIM of DBP was associated only with AAC score greater than 0. The associations were similar when modeling subclinical atherosclerosis severity as continuous outcomes and were consistent across subgroups based on demographics, behavioural, and cardiovascular risk factors., Conclusion: Higher variability in home BP, particularly in home SBP, was associated with greater carotid, aortic, and peripheral but not coronary atherosclerosis burdens independent of the mean home BP.

It is not established whether central blood pressure (BP) evaluated by a radial pulse wave analysis is useful to predict cardiovascular prognoses. We tested the hypothesis that central BP predicts future cardiovascular events in treated hypertensive subjects. We conducted a multicenter, observational cohort study of 3566 hypertensives being treated with antihypertensive medications at 27 institutions in Japan. We performed the radial pulse wave analyses using applanation tonometry in all subjects. The primary outcome was the incidence of any of the following: stroke, myocardial infarction (MI), sudden cardiac death, and acute aortic dissection. The mean age of the subjects was 66.0 ± 10.9 years, and 50.6% were male. The mean brachial SBP and central SBP were 138 ± 18 mm Hg and 128 ± 19 mm Hg, respectively. When the central SBP was divided into quintiles, the number of events was least in the 2nd quintile, and we set it as the reference. In the Cox regression analysis adjusting for age, sex, body mass index, creatinine, diabetes, use of β-blocker, and history of MI/stroke, the patients in the 3rd (hazard ratio (HR) 3.55, 95% confidence interval 1.29-9.78, p = 0.014), 4th (HR 4.12, 95% CI 1.53-11.10, p = 0.005), and 5th quintiles (HR 2.87, 95% CI 1.01-8.18, p = 0.048) had a significantly higher incidence of cardiovascular events compared to the 2nd quintile. The results were essentially unchanged when brachial DBP was additionally adjusted. In conclusion, in treated hypertensives, high central SBP was associated with worse cardiovascular outcomes.

We compared the predictive power for a major adverse cardiovascular event (MACE) of four home blood pressure (BP) indices (systolic BP, diastolic BP, mean BP, and pulse pressure (PP)) obtained at baseline before treatment and during the on-treatment follow-up period in 3147 patients with essential hypertension (women: 50.1%, mean age: 59.5 years). Associations between MACE and each index were determined using Cox proportional hazard models and the likelihood ratio (LR) test. During a median follow-up of 5.4 years, 46 patients experienced MACE, which was a composite of cardiovascular death, non-fatal stroke, and non-fatal myocardial infarction. The LR test showed that systolic, diastolic, and mean BP during follow-up was more closely associated with cardiovascular risk than the corresponding indices at baseline (LR χ 2 for baseline versus follow-up: systolic BP, (6.0, P = 0.014) versus (11.3, P = 0.0008); diastolic BP, (0.4, P = 0.53) versus (12.4, P = 0.0004); mean BP, (3.2, P = 0.074) versus (15.0, P = 0.0001)), whereas neither PP at baseline nor that during follow-up was significantly associated with MACE risk. Among home BP indices during follow-up, mean BP further improved prediction models in which systolic or diastolic BP was already included (P ≤ 0.042), but neither systolic nor diastolic BP improved models with mean BP (P = 0.80). In addition to home systolic and diastolic BP, mean BP during follow-up period provides essential information in predicting future cardiovascular diseases, whereas its utilization should be further assessed by an intervention trial targeting mean BP levels.

We conducted individual participant data meta-analysis to examine the validity of interarm blood pressure difference in simultaneous measurement as a marker to identify subjects with ankle-brachial pressure index <0.90 and to predict future cardiovascular events. We collected individual participant data on 13 317 Japanese subjects from 10 cohorts (general population-based cohorts, cohorts of patients with past history of cardiovascular events, and those with cardiovascular risk factors). Binary logistic regression analysis with adjustments identified interarm blood pressure difference >5 mm Hg as being associated with a significant odds ratio for the presence of ankle-brachial pressure index <0.90 (odds ratio, 2.19; 95% confidence interval, 1.60-3.03; P <0.01). Among 11 726 subjects without a past history of cardiovascular disease, 249 developed stroke during the average follow-up period of 7.4 years. Interarm blood pressure difference >15 mm Hg was associated with a significant Cox stratified adjusted hazard ratio for subsequent stroke (hazard ratio, 2.42; 95% confidence interval, 1.27-4.60; P <0.01). Therefore, interarm blood pressure differences, measured simultaneously in both arms, may be associated with vascular damage in the systemic arterial tree. These differences may be useful for identifying subjects with an ankle-brachial pressure index of <0.90 in the overall study population, and also a reliable predictor of future stroke in subjects without a past history of cardiovascular disease. These findings support the recommendation to measure blood pressure in both arms at the first visit., (© 2018 American Heart Association, Inc.)

Background: The clinical significance of long-term seasonal variations in self-measured home blood pressure (BP) has not been elucidated for the cardiovascular disease prevention., Methods and Results: Eligible 2787 patients were classified into 4 groups according to the magnitude of their seasonal variation in home BP, defined as an average of all increases in home BP from summer (July-August) to winter (January-February) combined with all decreases from winter to summer throughout the follow-up period, namely inverse- (systolic/diastolic, <0/<0 mm Hg), small- (0-4.8/0-2.4 mm Hg), middle- (4.8-9.1/2.4-4.5 mm Hg), or large- (≥9.1/≥4.5 mm Hg) variation groups. The overall cardiovascular risks illustrated U-shaped relationships across the groups, and hazard ratios for all cardiovascular outcomes compared with the small-variation group were 3.07 ( P =0.004) and 2.02 ( P =0.041) in the inverse-variation group and large-variation group, respectively, based on systolic BP, and results were confirmatory for major adverse cardiovascular events. Furthermore, when the summer-winter home BP difference was evaluated among patients who experienced titration and tapering of antihypertensive drugs depending on the season, the difference was significantly smaller in the early (September-November) than in the late (December-February) titration group (3.9/1.2 mm Hg versus 7.3/3.1 mm Hg, P <0.001) as well as in the early (March-May) than in the late (June-August) tapering group (4.4/2.1 mm Hg versus 7.1/3.4 mm Hg, P <0.001)., Conclusions: The small-to-middle seasonal variation in home BP (0-9.1/0-4.5 mm Hg), which may be partially attributed to earlier adjustment of antihypertensive medication, were associated with better cardiovascular outcomes., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objectives: Our aim was to assess seasonal variation in home blood pressure (BP) among free-living nationwide participants using home BP values accumulated from a web-based healthcare platform established in Japan., Settings: An observational study. OMRON Healthcare Co., Ltd. has been developing web-based personal healthcare record systems in Japan since November 2010; over two million voluntary participants had joined this platform in September 2015. Nationwide home BP measurements made by oscillometric-type electronic sphygmomanometers from over 110 000 voluntary participants have been transmitted to the system from devices., Participants: Seasonal variation in home BP was evaluated among 64 536 (51 335 men, 13 201 women; mean age 52.9 years) free-living nationwide users for whom data were automatically and simultaneously transmitted to the system from devices., Primary Outcome Measures: Mean monthly and weekly home BP., Results: In multiple regression analysis, the relationship between BP and temperature was a significant inverse association, independent of age, gender and geological locations. Highest and lowest BP was observed in December and July, respectively. Substantial seasonal differences in the mean values of morning and evening home systolic BP between summer and winter were 6.2 mmHg and 5.5 mmHg in men, and 7.3 mmHg and 6.5 mmHg in women. Seasonal variation was a little greater in older (7.3 mmHg in men, 8.7 mmHg in women) than in younger individuals (5.8 mmHg in men, 6.5 mmHg in women). BP from February to July was approximately 1.5 mmHg lower than the value from August to December., Conclusions: A web-based healthcare platform has enabled easier monitoring of population-wide BP. Tighter BP control is necessary in winter than in summer, and especially in a colder climate toward winter than toward summer. New technologies using web-based self-monitoring systems for health-related indexes are expected to initiate a new phase of cardiovascular disease prevention and public health promotion., Competing Interests: Competing interests: TI and TS are employees of OMRON Healthcare Co., Ltd. KO and HN are employees of OMRON Corporation. HU served as a consultant for this project. KM received a research grant from OMRON Healthcare Co., Ltd., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The association between glomerular hyperfiltration and cardiovascular events is not well known. To investigate whether glomerular hyperfiltration is independently associated with risk of adverse outcome we analyzed 8794 participants, average age 52 years enrolled in 8 prospective studies. Of these, 89% had hypertension. Using the 5th and 95th percentiles of the age- and sex-specific quintiles of CKD-EPI-calculated estimated glomerular filtration rate (eGFR), we identified three participant groups with low, high and normal eGFR. The ambulatory pulse pressure interval was wider and nighttime blood pressure fall was smaller in both the low and high than in the normal eGFR participants. During a mean follow-up of 6.2 years, there were 722 cardiovascular events. Crude event rates were significantly higher for both high (1.8 per 100-person-year) and low eGFR groups (2.1 per 100 person-year) as compared with group with normal eGFR (1.2 per 100 person-year). In multivariable Cox models including age, sex, average 24-hour blood pressure, smoking, diabetes, and cholesterol, both high eGFR (hazard ratio 1.5 (95% confidence interval 1.2-2.1) and low eGFR (2.0 [1.5-2.6]) participants had a significantly higher risk of cardiovascular events as compared to those with normal eGFR. Addition of body mass index to the multivariable survival model did not change the magnitude of hazard estimates. Thus, glomerular hyperfiltration is a strong and independent predictor of cardiovascular events in a large multiethnic population of predominantly hypertensive individuals. Our findings support a U-shaped relationship between eGFR and adverse outcome., (Copyright © 2017 International Society of Nephrology. All rights reserved.)

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: Several observational studies have found modifying effects of functional status on the association between conventional office blood pressure (BP) and adverse outcomes. We aimed to examine whether the association between higher BP and stroke was attenuated or inverted among older adults with impaired function using self-measured home BP measurements., Methods: We followed 501 Japanese community-dwelling adults aged at least 60 years (mean age, 68.6 years) with no history of stroke. Multivariate-adjusted hazard ratios for 1-SD increase in home BP and office BP measurements were calculated by the Cox proportional hazards model. Functional status was assessed by self-reported physical function., Results: During a median follow-up of 11.5 years, first strokes were observed in 47 participants. Higher home SBP, but not office SBP, was significantly associated with increased risk of stroke among both 349 participants with normal physical function and 152 participants with impaired physical function [hazard ratio (95% confidence interval) per 14.4-mmHg increase: 1.74 (1.12-2.69) and 1.77 (1.06-2.94), respectively], with no significant interaction for physical function (P = 0.56). Higher home DBP, but not office DBP, was also significantly associated with increased risk of stroke (P ≤ 0.029) irrespective of physical function (all P > 0.05 for interaction). Neither home BP nor office BP was significantly associated with all-cause mortality irrespective of physical function., Conclusion: Higher home BP was associated with increased risk of stroke even among those with impaired physical function. Measurements of home BP would be useful for stroke prevention, even after physical function decline.

Objective: To identify the characteristics of blood pressure (BP), heart rate (HR), and double product in a Japanese population sample., Methods: We pooled individual records from 1999 to 2005 for 111 007 participants in 25 community-based cohorts and seven worksite-based cohorts. The data were analyzed to provide information on BP, HR, and double product according to age-sex groups and use of antihypertensive medication., Results: Average BP was 130/77 mmHg among men and women combined. Among untreated individuals, SBP increased with age, whereas DBP reached a ceiling around the age of 60 years. The average SBP of treated participants was around 140 mmHg, irrespective of age, whereas DBP decreased linearly with age, and 56.4% of treated participants had a BP of 140/90 mmHg or over. HR did not differ across age groups or treatment status. The double product, also called the rate-pressure product, calculated by multiplying the SBP and the HR, increased with age among untreated individuals, whereas it first decreased and then increased with age among treated individuals., Conclusion: Based on these collaborative data, insufficient BP control in Japan, where the average life expectancy is the longest in the world, was seen.

Increased blood pressure (BP) variability predicts cardiovascular disease, but lack of operational thresholds limits its use in clinical practice. Our aim was to define outcome-driven thresholds for increased day-to-day home BP variability. We studied a population-based sample of 6238 individuals (mean age 60.0±12.9, 56.4% women) from Japan, Greece, and Finland. All participants self-measured their home BP on ≥3 days. We defined home BP variability as the coefficient of variation of the first morning BPs on 3 to 7 days. We assessed the association between systolic/diastolic BP variability (as a continuous variable and in deciles of coefficient of variation) and cardiovascular outcomes using Cox regression models adjusted for cohort and classical cardiovascular risk factors, including BP. During a follow-up of 9.3±3.6 years, 304 cardiovascular deaths and 715 cardiovascular events occurred. A 1 SD increase in systolic/diastolic home BP variability was associated with increased risk of cardiovascular mortality (hazard ratio, 1.17/1.22; 95% confidence interval, 1.06-1.30/1.11-1.34; P =0.003/<0.0001) and cardiovascular events (hazard ratio, 1.13/1.14; 95% confidence interval, 1.05-1.21/1.07-1.23; P =0.0007/0.0002). Compared with the average risk in the whole population, risk of cardiovascular deaths (hazard ratio, 1.66/1.84; 95% confidence interval, 1.27-2.17/1.42-2.37; P =0.0002/<0.0001) and events (hazard ratio, 1.46/1.42; 95% confidence interval, 1.21-1.76/1.17-1.71; P <0.0001/0.0004) was increased in the highest decile of systolic/diastolic BP variability (coefficient of variation>11.0/12.8). Increased home BP variability predicts cardiovascular outcomes in the general population. Individuals with a systolic/diastolic coefficient of variation of day-to-day home BP >11.0/12.8 may have an increased risk of cardiovascular disease. These findings could help physicians identify individuals who are at an increased cardiovascular disease risk., (© 2017 American Heart Association, Inc.)

Objective: The relative role of office heart rate (HR) and ambulatory HR for predicting major adverse cardiovascular events (MACEs) and mortality is not well known. Aim of this study was to investigate the association of white-coat tachycardia and masked tachycardia with MACE and mortality in hypertensive patients., Methods: We performed 24-h ambulatory blood pressure and HR monitoring in 7602 hypertensive patients (4165 men) aged 52 ± 16 years enrolled in six prospective studies in Italy, Japan, and Australia. Participants were divided into four groups: normal office and normal night-time HRs (N = 5238), white-coat tachycardia (N = 998), masked tachycardia (N = 796), and sustained tachycardia (N = 570). Median follow-up was 5.0 years., Results: In age-and-sex-adjusted Cox model, using the normal HRs group as a reference, white-coat tachycardia was not a significant predictor of excess MACEs or all-cause death. In contrast, both masked tachycardia [hazard ratio, 95% confidence interval (CI); 1.40, 1.11-1.77] and sustained tachycardia (1.86, 1.44-2.40) were associated with risk of excess MACE. In addition, masked tachycardia (hazard ratio, 95% CI; 1.62, 1.14-2.29) but not sustained tachycardia (1.35, 0.83-2.19) was a significant predictor of excess mortality. These relationships held true in multivariable parsimonious Cox models including major risk factors. In these models, masked tachycardia remained an independent predictor of excess MACE (hazard ratio, 95% CI; 1.34, 1.06-1.71) and all-cause mortality (1.68, 1.18-2.41)., Conclusion: The current study confirms that measurement of HR adds to the risk stratification for MACE and mortality and shows that an elevated night-time HR confers an increased mortality risk to hypertensive patients who have normal office HR.

Seasonal variation of blood pressure (BP) has been reported in small populations or by BP levels captured at only a few points in a year, for example, summer and winter. We aimed to investigate the multiyear seasonal variation in self-measured home BP among hypertensive patients receiving antihypertensive medications. We selected 1649 eligible patients receiving antihypertensive drug treatment, and weekly averaged home BPs were analyzed throughout the follow-up period. Systolic and diastolic home BPs were fitted with the cosine function: 'Variation+Other Effects+Intercept', in which the 'Variation' was expressed by a cosine curve with three parameters representing: (1) maximum-minimum difference of home BP in one cycle of the cosine curve; (2) time required for one cycle of the cosine curve for home BP variation; and (3) time at which home BP reached the maximum point. Maximum-minimum differences in home BP were 6.7/2.9 mm Hg, and the highest home BPs were observed in mid-to-late January. In the multivariable-adjusted model, a large maximum-minimum difference in home BP was associated with lower body mass index and older age, and larger differences were observed in men compared with women. Summer-winter difference in home BP was essentially similar every year, though it was marginally reduced by 0.14/0.04 mm Hg per year, under long-term antihypertensive treatment. Records of daily home BP measurements enable us to capture long-term factors such as seasonal variation. Home BP should therefore be carefully monitored, particularly in patients with increased BP in winter, to mitigate cardiovascular risk.

Background: The role of white-coat hypertension (WCH) and the white-coat-effect (WCE) in development of cardiovascular disease (CVD) risk remains poorly understood., Objectives: Using data from the population-based, 11-cohort IDACO (International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes), this study compared daytime ambulatory blood pressure monitoring with conventional blood pressure measurements in 653 untreated subjects with WCH and 653 normotensive control subjects., Methods: European Society Hypertension guidelines were used as a 5-stage risk score. Low risk was defined as 0 to 2 risk factors, and high risk was defined as ≥3 to 5 risk factors, diabetes, and/or history of prior CVD events. Age- and cohort-matching was done between 653 untreated subjects with WCH and 653 normotensive control subjects., Results: In a stepwise linear regression model, systolic WCE increased by 3.8 mm Hg (95% confidence interval [CI]: 3.1 to 4.6 mm Hg) per 10-year increase in age, and was similar in low- and high-risk subjects with or without prior CVD events. Over a median 10.6-year follow-up, incidence of new CVD events was higher in 159 high-risk subjects with WCH compared with 159 cohort- and age-matched high-risk normotensive subjects (adjusted hazard ratio [HR]: 2.06; 95% CI: 1.10 to 3.84; p = 0.023). The HR was not significant for 494 participants with low-risk WCH and age-matched low-risk normotensive subjects. Subgroup analysis by age showed that an association between WCH and incident CVD events is limited to older (age ≥60 years) high-risk WCH subjects; the adjusted HR was 2.19 (95% CI: 1.09 to 4.37; p = 0.027) in the older high-risk group and 0.88 (95% CI: 0.51 to 1.53; p = 0.66) in the older low-risk group (p for interaction = 0.044)., Conclusions: WCE size is related to aging, not to CVD risk. CVD risk in most persons with WCH is comparable to age- and risk-adjusted normotensive control subjects., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The Ambulatory blood pressure Registry TEleMonitoring of hypertension and cardiovascular rISk project was designed to set up an international registry including clinic blood pressure (CBP) and ambulatory blood pressure (ABP) measurements in patients attending hypertension clinics in all five continents, aiming to assess different daily life hypertension types., Methods: Cross-sectional ABP, CBP and demographic data, medical history and cardiovascular risk profile were provided from existing databases by hypertension clinics. Hypertension types were evaluated considering CBP (≥140/90 mmHg) and 24-h ABP (≥130/80 mmHg)., Results: Overall, 14 143 patients from 27 countries across all five continents were analyzed (Europe 73%, Africa 3%, America 9%, Asia 14% and Australia 2%). Mean age was 57 ± 14 years, men 51%, treated for hypertension 46%, cardiovascular disease 14%, people with diabetes 14%, dyslipidemia 33% and smokers 19%. The prevalence of hypertension was higher by CBP than by ABP monitoring (72 vs. 60%, P < 0.0001). Sustained hypertension (elevated CBP and ABP) was detected in 49% of patients. White-coat hypertension (WCH, elevated CBP with normal ABP) was more common than masked hypertension (elevated ABP with normal CBP) (23 vs. 10%; P < 0.0001). Sustained hypertension was more common in Europe and America and in elderly, men, obese patients with cardiovascular comorbidities. WCH was less common in Australia, America and Africa, and more common in elderly, obese women. Masked hypertension was more common in Asia and in men with diabetes. Smoking was a determinant for sustained hypertension and masked hypertension., Conclusion: Our analysis showed an unbalanced distribution of WCH and masked hypertension patterns among different continents, suggesting an interplay of genetic and environmental factors, and likely also different healthcare administrative and practice patterns.

Office blood pressure measurement has been the basis for hypertension evaluation for almost a century. However, the evaluation of blood pressure out of the office using ambulatory or self-home monitoring is now strongly recommended for the accurate diagnosis in many, if not all, cases with suspected hypertension. Moreover, there is evidence that the variability of blood pressure might offer prognostic information that is independent of the average blood pressure level. Recently, advancement in technology has provided noninvasive evaluation of central (aortic) blood pressure, which might have attributes that are additive to the conventional brachial blood pressure measurement. This position statement, developed by international experts, deals with key research and practical issues in regard to peripheral blood pressure measurement (office, home, and ambulatory), blood pressure variability, and central blood pressure measurement. The objective is to present current achievements, identify gaps in knowledge and issues concerning clinical application, and present relevant research questions and directions to investigators and manufacturers for future research and development (primary goal).

Objective: Currently, normative means and ranges of blood pressure (BP) and pulse rates in Japanese newborns are not available. The objective of the present study was to estimate BP, pulse rate, and their distribution among Japanese newborns., Methods: Using oscillometric devices, arm or calf BP and pulse rate levels were obtained from 3148 infants born between 2007 and 2014, consecutively at Suzuki Memorial Hospital, Iwanuma, Japan. Of those, data from 2628 full-term, singleton newborns with BP measured on day 3 after birth were analyzed., Results: Arm SBP/DBP and pulse rate in the reference group (n = 2628) were 70.5 ± 7.4/44.3 ± 6.7 mmHg and 117.3 ± 16.6 bpm, respectively. The 5-95th percentiles were 58-83 mmHg for SBP, 35-57 mmHg for DBP, and 91-145 bpm for pulse rate. Similar values were obtained from calf measurements. In multiple regression analysis, birth weight and spontaneous cephalic delivery were positively and light/deep sleep was inversely associated with higher arm SBP/DBP (P ≤ 0.04), whereas sex, Apgar score, gestational age, and mother's age did not significantly affect BP levels (P ≥ 0.06). Male sex, gestational age, spontaneous cephalic delivery, and light/deep sleep were inversely associated with higher pulse rate (P ≤ 0.02)., Conclusion: The present study is the first to show the distributions of Asian newborns' BP levels and pulse rate. The assessment of newborns' BP levels and pulse rate should consider birth weight, gestational age after birth, and actual condition at BP measurement.

Home blood pressure (HBP) measurements are known to be lower than conventional office blood pressure (OBP) measurements. However, this difference might not be consistent across the entire age range and has not been adequately investigated. We assessed the relationship between OBP and HBP with increasing age using the International Database of HOme blood pressure in relation to Cardiovascular Outcome (IDHOCO). OBP, HBP and their difference were assessed across different decades of age. A total of 5689 untreated subjects aged 18-97 years, who had at least two OBP and HBP measurements, were included. Systolic OBP and HBP increased across older age categories (from 112 to 142 mm Hg and from 109 to 136 mm Hg, respectively), with OBP being higher than HBP by ∼7 mm Hg in subjects aged >30 years and lesser in younger subjects (P=0.001). Both diastolic OBP and HBP increased until the age of ∼50 years (from 71 to 79 mm Hg and from 66 to 76 mm Hg, respectively), with OBP being consistently higher than HBP and a trend toward a decreased OBP-HBP difference with aging (P<0.001). Determinants of a larger OBP-HBP difference were younger age, sustained hypertension, nonsmoking and negative cardiovascular disease history. These data suggest that in the general adult population, HBP is consistently lower than OBP across all the decades, but their difference might vary between age groups. Further research is needed to confirm these findings in younger and older subjects and in hypertensive individuals.

Background: We aimed to examine the blood pressure (BP)-lowering effect and the time to attain the maximal antihypertensive effect (stabilization time) of several angiotensin II receptor blockers (ARBs) based on home BP measurements., Methods: We surveyed consecutive newly diagnosed, untreated patients with hypertension who started the treatment with a mid-level dose of one of seven ARBs (losartan 50 mg, telmisartan 40 mg, candesartan 8 mg, olmesartan 20 mg, valsartan 80 mg, irbesartan 100 mg, or azilsartan 20 mg). All study participants measured home BP in the morning for at least 1 week during an untreated period and 4 weeks during the treatment period., Results: Age, the proportion of men, and baseline home BP levels did not differ significantly between groups (total n = 232; age, 62.2 years; 50.9% men; home SBP/DBP, 151.6/90.0 mmHg). Significant differences in the BP-lowering effect and the stabilization time between ARBs were observed (P ≤ 0.02). The extent of BP-lowering effects of azilsartan 20 mg was significantly greater than that of valsartan 80 mg or irbesartan 100 mg (15.3 vs. 7.9 or 8.2 mmHg, respectively P ≤ 0.03). The stabilization time of losartan for home SBP was significantly longer than that of valsartan, irbesartan, or azilsartan (22.8 vs. 7.1, 4.7, or 7.1 days, respectively, P ≤ 0.01)., Conclusion: The maximum effect and the stabilization time differed among ARBs used at the mid-level dose in Japan. An ARB should be chosen based on its desired characteristics.