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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.)

Objective: This study aimed to identify the factors influencing home blood pressure measurement (HBPM) continuation in community-dwelling older adults., Methods: A longitudinal analysis used the NOSE study intervention group datasets. The participants were encouraged HBPM with self-monitoring devices provided to them twice in the morning and twice in the evening. Every 7-day interval from the HBPM start date was defined as 1 week, and the number of HBPMs per week was counted. The first week in which the number of HBPMs was zero was defined as the week in which HBPM was discontinued. Participants who did not experienced discontinuation until the end of the observation period were considered complete survivors in the survival time analysis., Results: Data from 437 participants were included in the analysis. Of these, 120 (27.5%) discontinued HBPM. In univariate analysis, factors significantly associated with HBPM discontinuation included exercise habits [hazard ratio per one unit 0.47; 95% confidence interval (CI) 0.31-0.69], social participation (hazard ratio 0.65; 95% CI 0.42-0.99), MoCA-J score (hazard ratio 0.94; 95% CI 0.90-0.98), and frailty (hazard ratio 5.20; 95% CI 2.87-9.43). In multivariate analysis, factors significantly associated with HBPM discontinuation included sex (hazard ratio 0.55; 95% CI 0.32-0.95; ref. = female individuals), smoking history (hazard ratio 1.69; 95% CI 1.02-2.80), exercise habits (hazard ratio 0.51; 95% CI 0.30-0.85), MoCA-J score (hazard ratio 0.93; 95% CI 0.88-0.98), and frailty (hazard ratio 3.31; 95% CI 1.50-7.29)., Conclusion: Among community-dwelling older adults, female sex, smoking history, lack of exercise, cognitive decline, and frailty were identified as factors influencing HBPM discontinuation., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: There is intense effort to develop cuffless blood pressure (BP) measuring devices, and several are already on the market claiming that they provide accurate measurements. These devices are heterogeneous in measurement principle, intended use, functions, and calibration, and have special accuracy issues requiring different validation than classic cuff BP monitors. To date, there are no generally accepted protocols for their validation to ensure adequate accuracy for clinical use., Objective: This statement by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability recommends procedures for validating intermittent cuffless BP devices (providing measurements every >30 sec and usually 30-60 min, or upon user initiation), which are most common., Validation Procedures: Six validation tests are defined for evaluating different aspects of intermittent cuffless devices: static test (absolute BP accuracy); device position test (hydrostatic pressure effect robustness); treatment test (BP decrease accuracy); awake/asleep test (BP change accuracy); exercise test (BP increase accuracy); and recalibration test (cuff calibration stability over time). Not all these tests are required for a given device. The necessary tests depend on whether the device requires individual user calibration, measures automatically or manually, and takes measurements in more than one position., Conclusion: The validation of cuffless BP devices is complex and needs to be tailored according to their functions and calibration. These ESH recommendations present specific, clinically meaningful, and pragmatic validation procedures for different types of intermittent cuffless devices to ensure that only accurate devices will be used in the evaluation and management of hypertension., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To develop scientific consensus recommendations for the optimal design and functions of different types of blood pressure (BP) measuring devices used in clinical practice for the detection, management, and long-term follow-up of hypertension., Methods: A scientific consensus meeting was performed by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability and STRIDE BP (Science and Technology for Regional Innovation and Development in Europe) during the 2022 Scientific Meeting of the ESH in Athens, Greece. Manufacturers were also invited to provide their feedback on BP device design and development. Thirty-one international experts in clinical hypertension and BP monitoring contributed to the development of consensus recommendations on the optimal design of BP devices., Statement: International consensus was reached on the requirements for the design and features of five types of BP monitors, including office (or clinic) BP monitors, ambulatory BP monitors, home BP monitors, home BP telemonitors, and kiosk BP monitors for public spaces. For each device type "essential" requirements (must have), and "optional" ones (may have) are presented, as well as additional comments on the optimal device design and features., Conclusions: These consensus recommendations aim at providing manufacturers of BP devices with the requirements that are considered mandatory, or optional, by clinical experts involved in the detection and management of hypertension. They are also directed to administrative healthcare personnel involved in the provision and purchase of BP devices so that they can recommend the most appropriate ones., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The role of pulse pressure (PP) 'widening' at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of two components: 'elastic PP' (elPP) and 'stiffening PP' (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP ('PP variables') with mortality and composite cardiovascular events in different age classes., Method: Longitudinal population-based cohort study of adults with baseline observations that included 24-h ambulatory BP. Age classes were age 40 or less, 40-50, 50-60, 60-70, and over 70 years. Co-primary endpoints were total mortality and composite cardiovascular events. The relative risk expressed by hazard ratio per 1SD increase for each of the PP variables was calculated from multivariable-adjusted Cox regression models., Results: The 11 848 participants from 13 cohorts (age 53 ± 16 years, 50% men) were followed for up for 13.7 ± 6.7 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or nonfatal cardiovascular event (12.9 per 1000 person-years). Mean PP, elPP, and stPP were, respectively, 49.7, 43.5, and 6.2 mmHg, and elPP and stPP were uncorrelated ( r  = -0.07). At age 50-60 years, all PP variables displayed association with risk for almost all outcomes. From age over 60 years to age over 70 years, hazard ratios of of PP and elPP were similar and decreased gradually but differently for pulse rate lower than or higher than 70 bpm, whereas stPP lacked predictive power in most cases. For age 40 years or less, elPP showed protective power for coronary events, whereas stPP and PP predicted stroke events. Adjusted and unadjusted hazard ratio variations were similar over the entire age range., Conclusion: This study provides a new basis for associating PP components with outcome and arterial properties in different age groups and at different pulse rates for both old and young age. The similarity between adjusted and unadjusted hazard ratios supports the clinical usefulness of PP components but further studies are needed to assess the prognostic significance of the PP components, especially at the young age., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Many cuffless blood pressure (BP) measuring devices are currently on the market claiming that they provide accurate BP measurements. These technologies have considerable potential to improve the awareness, treatment, and management of hypertension. However, recent guidelines by the European Society of Hypertension do not recommend cuffless devices for the diagnosis and management of hypertension., Objective: This statement by the European Society of Hypertension Working Group on BP Monitoring and Cardiovascular Variability presents the types of cuffless BP technologies, issues in their validation, and recommendations for clinical practice., Statements: Cuffless BP monitors constitute a wide and heterogeneous group of novel technologies and devices with different intended uses. Cuffless BP devices have specific accuracy issues, which render the established validation protocols for cuff BP devices inadequate for their validation. In 2014, the Institute of Electrical and Electronics Engineers published a standard for the validation of cuffless BP devices, and the International Organization for Standardization is currently developing another standard. The validation of cuffless devices should address issues related to the need of individual cuff calibration, the stability of measurements post calibration, the ability to track BP changes, and the implementation of machine learning technology. Clinical field investigations may also be considered and issues regarding the clinical implementation of cuffless BP readings should be investigated., Conclusion: Cuffless BP devices have considerable potential for changing the diagnosis and management of hypertension. However, fundamental questions regarding their accuracy, performance, and implementation need to be carefully addressed before they can be recommended for clinical use., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This observational retrospective cohort study investigates the effect of antihypertensive therapy with angiotensin II receptor blockers (ARBs) or dihydropyridine calcium channel blockers (dCCBs) monotherapy on renal function using longitudinal real-world health data of a drug-naive, hypertensive population without kidney disease., Methods: Using propensity score matching, we selected untreated hypertensive participants ( n  = 10 151) and dCCB ( n  = 5078) or ARB ( n  = 5073) new-users based on annual health check-ups and claims between 2008 and 2020. Participants were divided by the first prescribed drug., Results: The mean age was 51 years, 79% were men and the mean estimated glomerular filtration rate (eGFR) was 78 ml/min per 1.73 m 2 . Blood pressure rapidly decreased by approximately 10% in both treatment groups. At the 1-year visit, eGFR levels decreased in the ARB group by nearly 2% but increased in the dCCB group by less than 1%. However, no significant difference was apparent in the annual eGFR change after the 1-year visit. The risk for composite kidney outcome (new-onset proteinuria or eGFR decline ≥30%) was lowest in the ARB group owing to their robust effect on preventing proteinuria: hazard ratio (95% confidence interval) for proteinuria was 0.91 (0.78-1.05) for the dCCB group and 0.54 (0.44-0.65) for the ARB group, compared with that for the untreated group after ending follow-up at the last visit before changing antihypertensive treatment., Conclusion: From the present findings based on the real-world data, ARBs can be recommended for kidney protection even in a primary care setting. Meanwhile, dCCB treatment initially increases eGFR with no adverse effects on proteinuria., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study was performed to investigate the association of hypertension subtypes with glucose metabolism among the Japanese general population., Methods: The study involved 646 residents (mean age: 62.4 years) without treatment for hypertension or a history of diabetes from Ohasama, a rural Japanese community, who underwent an oral glucose tolerance test. Hypertension subtypes [normotension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic and diastolic hypertension (SDH)] were defined on the basis of home and office SBP and DBP (HBP and OBP, respectively). The estimated means of blood glucose related indices among the groups were compared by analysis of covariance adjusted for possible confounding factors., Results: Blood glucose related indices were not different among the morning HBP-defined hypertension subtypes. Participants with evening HBP-defined ISH had a significantly higher estimated mean BG at 120 min, higher homeostasis model assessment-insulin resistance (HOMA-IR) and lower Matsuda-DeFronzo index than participants with NT (all P < 0.021). Participants with OBP-defined SDH had a significantly higher estimated mean fasting blood glucose; blood glucose at 30, 60 and 120 min; and HOMA-IR and a lower Matsuda-DeFronzo index than participants with NT (all P < 0.0025)., Conclusion: The blood glucose related indices were different among hypertension subtypes. Participants with evening HBP-defined ISH and OBP-defined SDH had higher blood glucose levels and insulin resistance than participants with correspondingly defined normotension, while those with morning HBP did not. These findings suggest the importance of measuring evening HBP and office blood pressure for early detection of coexisting hypertension and diabetes., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: No studies have demonstrated the association between urinary sodium-to-potassium (Na/K) ratio and all out-of-office blood pressure (BP) [home morning and evening BP (self-measured at home), and 24-h, daytime, and night-time ambulatory BP] in the same cohort. We aimed to assess, which type of out-of-office BP is more strongly associated with urinary Na/K ratio in the general population., Methods: This cross-sectional study was conducted in the general population of Ohasama, Japan. Home and ambulatory BP levels were measured, and 24-h urine samples were obtained from 875 participants (men, 25.5%; mean age, 60.1 years). The urinary Na/K ratio in the 24-h urine samples was calculated., Results: The median (interquartile range) urinary Na/K ratio was 4.19 (3.36-5.26). Significant positive trends of home morning, home evening, 24-h, and daytime SBP were observed across quartiles of urinary Na/K ratio (trend P  < 0.041; adjusted mean values between Q1 and Q4 of urinary Na/K ratio: 121.0-125.5 mmHg for home morning, 120.1-123.8mmhg for home evening, 121.6-123.4mmHg for 24-h, 127.5-129.5 mmHg for daytime). Urinary Na/K ratio was not significantly associated with office or night-time SBP and nocturnal BP fall (trend P > 0.13). In the model with both home morning or evening SBP and daytime SBP, only home SBP was significantly associated with urinary Na/K ratio (P < 0.048 for home SBP)., Conclusion: These findings suggest that urinary Na/K ratio might be more strongly associated with home BP than with 24-h and daytime BP but was not associated with night-time BP., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim was to compare short-term and long-term reproducibilities of in-office unattended blood pressure (BP), namely automated office blood pressure (AOBP), conventionally measured attended office BP, and self-measured home BP., Methods: A multicentre, clinical study was conducted in Japan, and 287 Japanese outpatients on antihypertensive drug medication were followed-up for 1 year., Results: The intensity of drug treatment was sustained consistently throughout the study period (defined daily doses, 1.62-1.68; P = 0.12). The mean SBP differences between baseline and 1 month later, as well as baseline and 1 year later, were less than 1.5 mmHg, whereas the standard deviations of the differences for home, AOBP, and attended office measurements for the 1-year interval were 7.7, 14.5, and 15.3 mmHg, respectively. The coefficients of variation were significantly smaller for home BP than for AOBP among all patients at both 1-month and 1-year intervals (P < 0.0001). In the 1-month interval, partial correlation coefficients of home BP (r, 0.73/0.88 for systolic/diastolic measures) were significantly higher than of conventional BP (r, 0.47/0.69). However, the correlations converged to the modest level regardless of BP information (r, 0.49-0.54/0.63-0.73) when the 1-year interval was assessed. Results were confirmatory when patients on the same drug regimen (n = 167) were analysed., Conclusion: A higher reproducibility of home BP was demonstrated compared with in-office BP, including AOBP. However, the modest correlations for the 1-year interval support the importance of regular assessment of BP, regardless of in-office or home measurements for treatment of hypertension., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Hypertension and intracranial artery stenosis (ICAS) are closely related; however, few studies have compared the strength of the relationship between strictly measured office and out-of-office blood pressure (BP) measurements. The relationship of day-by-day or short-term variability in BP to asymptomatic ICAS also remains unclear., Methods: In apparently healthy 677 men (mean age, 70 years) from a population-based cohort, we examined the association of strictly measured office BP and 7-day home BP with ICAS on magnetic resonance angiography. We conducted 24-h ambulatory BP monitoring in 468 of the men. Variability indices included day-by-day, daytime, and night-time variability, nocturnal decline, and morning pressor surge. Any ICAS was defined as either mild (1-49%) or severe (≥50%) stenosis., Results: We observed mild and severe ICAS in 153 (22.6%) and 36 (5.3%) participants, respectively. In multivariable-adjusted Poisson regression with robust error variance, higher SBP in office, home, or ambulatory BP monitoring was associated with the presence of any or severe ICAS. The associations with ICAS were comparable between office, home, and ambulatory SBP (all heterogeneity P values >0.1). Independent of mean SBP, greater nocturnal decline or morning pressor surge, but not day-by-day, daytime, or night-time variability, in SBP was associated with higher burden of any or severe ICAS., Conclusion: The magnitude of association of strictly measured office BP for asymptomatic ICAS was comparable with that of BP measured at home or in ambulatory BP monitoring. Circadian BP variation based on ambulatory BP monitoring was positively associated with asymptomatic ICAS burden., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The prognostic implication of isolated systolic hypertension (ISH), defined as SBP at least 140 mmHg and DBP less than 90 mmHg, among young-to-middle-aged adults remains controversial. We examined the association of ISH with cardiovascular disease (CVD) risk in adults aged 30-49 years., Methods: In a prospective cohort of representative Japanese general populations from the NIPPON DATA80 (1980-2009), we studied 4776 participants (mean age, 39.4 years; 55.4% women) without clinical CVD or antihypertensive medication. Participants were classified as follows: normal blood pressure (BP) (SBP/DBP, <120/<80 mmHg), high-normal BP (120-129/<80 mmHg), elevated BP (130-139/80-89 mmHg), ISH, isolated diastolic hypertension (IDH) (<140/≥90 mmHg), and systolic--diastolic hypertension (SDH) (≥140/≥90 mmHg)., Results: ISH was observed in 389 (8.1%) participants. During the 29-year follow-up, 115 participants died of CVD, 28 of coronary heart disease, and 49 of stroke. Cox proportional hazards models adjusted for demographics and CVD risk factors showed that participants with ISH had higher risk of CVD mortality than those with normal BP [hazard ratio (confidence interval), 4.10 (1.87-9.03)]. The magnitude of CVD mortality risk related to ISH was comparable with that related to IDH [3.38 (1.31-8.72)] and not as great as that related to SDH [5.41 (2.63-11.14)]. We found significant associations of ISH with coronary and stroke mortality. The association of ISH with CVD mortality was consistent across men and women and those aged 30-39 and 40-49 years., Conclusion: ISH among young-to-middle-aged Japanese adults was independently associated with higher risk of CVD mortality later in life.

: 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.

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.

: 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.

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.

Objective: There is little evidence to support an increased risk of blood pressure (BP) elevation among elderly individuals receiving antihypertensive drug treatment., Methods: To clarify the impact on BP level and residual cardiovascular risk in treated elderly individuals, we analysed individual participant data of 26 133 residents aged 60-89 years from seven Japanese general populations and cross-classified participants by age category, 60-74 (young-old) versus 75-89 years (old-old), and by usage of antihypertensive medication at baseline survey (1980-1995)., Results: During a median follow-up period of 12.7 years, 2451 cardiovascular deaths were observed. Multivariable-adjusted hazard ratios of cardiovascular mortality in treated participants compared with untreated participants were 1.30 [95% confidence intervals, 1.16-1.46) and 1.35 (95% confidence interval, 1.16-1.56) in young-old and old-old participants, respectively. Irrespective of antihypertensive medication, the risk increase of total cardiovascular and stroke mortality with elevation of BP was significant among young-old (P ≤ 0.0013), but not significant among old-old participants (P ≥ 0.061)., Conclusion: Although impact on BP was more evident among young-old than old-old individuals, clinicians who prescribe antihypertensive medication to elderly patients should consider that such patients require further monitoring.

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.

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.

Objective: To investigate associations between socioeconomic status (SES) and prevalence, awareness, treatment, and control of hypertension in Japan's general population., Methods: In 2010, we established a cohort of participants in the National Health and Nutrition Survey of Japan. The cohort included 2623 adults from 300 randomly selected areas across Japan. Using baseline data, four cross-sectional analyses were performed: association of SES with prevalent hypertension in 2623 participants; association of SES with unawareness of hypertension and with no treatment in 1282 hypertensive patients; and association of SES with uncontrolled hypertension in 720 treated hypertensive patients. SES was classified according to employment status, length of education, marital and living status, and household expenditure., Results: The overall prevalence of hypertension was 48.9%. Among hypertensive participants, the proportions of unawareness and no treatment were 33.1 and 43.8%, respectively. Target blood pressure levels were not achieved among 61.2% of treated hypertensive patients. Hypertension was more prevalent in the unmarried and living alone group than in the married group (odds ratio 1.76; 95% confidence interval 1.26-2.44), after adjustment for age, sex, BMI, smoking, alcohol consumption, habitual exercise, history of cardiovascular diseases, diabetes mellitus, hypercholesterolemia, dietary sodium, and potassium intake. SES was not clearly associated with unawareness, no treatment, nor poor control of hypertension., Conclusion: Being unmarried and living alone was associated with increased prevalence of hypertension. There was no clear association of SES with unaware, untreated, and uncontrolled hypertension.

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.

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.

Background: In addition to day-to-day variability in blood pressure (BP) or heart rate (HR), N-terminal pro B-type natriuretic peptide (NT-proBNP) has been reported to be a predictor of cardiovascular disease. Here, we tested the hypothesis that day-to-day BP or HR variability calculated as the intraindividual standard deviation (SD) of home BP or HR is associated with elevated NT-proBNP in a cross-sectional study., Methods: Among 664 participants (mean age, 61.9 years; female, 70.5%) from a general Japanese population without a history of heart disease, 86 (13.0%) had NT-proBNP at least 125 pg/ml., Results: Each 1 SD increase in the SD of home systolic BP (SBP) [odds ratio (OR), 1.82; P < .0001) and in the SD of home HR (OR, 1.44; P = 0.008) were significantly associated with the prevalence of NT-proBNP at least 125 pg/ml after adjustment for possible confounding factors including home SBP and HR. Among the four groups defined by the median SD of home SBP and of home HR, the group with higher SDs in home SBP (≥8.0 mmHg) and HR (≥5.0 bpm) had the greatest OR for the prevalence of NT-proBNP at least 125 pg/ml (OR, 4.80; P = 0007 vs. a reference group with lower SDs of home SBP and HR)., Conclusion: These results suggest that day-to-day variability in BP and HR may be associated with target-organ damage or complications, which can lead to an elevated NT-proBNP level. An elevated NT-proBNP level may be involved in the prognostic significance of day-to-day variability in BP or HR.

Given the increasing use of ambulatory blood pressure monitoring (ABPM) in both clinical practice and hypertension research, a group of scientists, participating in the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability, in year 2013 published a comprehensive position paper dealing with all aspects of the technique, based on the available scientific evidence for ABPM. The present work represents an updated schematic summary of the most important aspects related to the use of ABPM in daily practice, and is aimed at providing recommendations for proper use of this technique in a clinical setting by both specialists and practicing physicians. The present article details the requirements and the methodological issues to be addressed for using ABPM in clinical practice, The clinical indications for ABPM suggested by the available studies, among which white-coat phenomena, masked hypertension, and nocturnal hypertension, are outlined in detail, and the place of home measurement of blood pressure in relation to ABPM is discussed. The role of ABPM in pharmacological, epidemiological, and clinical research is also briefly mentioned. Finally, the implementation of ABPM in practice is considered in relation to the situation of different countries with regard to the reimbursement and the availability of ABPM in primary care practices, hospital clinics, and pharmacies.

Objective: Ambulatory blood pressure (BP) is reportedly associated with target organ damage. However, whether ambulatory BP carries prognostic significance for the development of chronic kidney disease (CKD) has not been confirmed., Method: We measured ambulatory BP in 843 participants without CKD at baseline from a general Japanese population and examined the incidence of CKD defined as positive proteinuria or an estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m at health checks. The association between baseline ambulatory BP and CKD incidence was examined using the Cox proportional hazard regression model adjusted for sex, age, BMI, habitual smoking, habitual alcohol consumption, diabetes mellitus, hypercholesterolemia, a history of cardiovascular disease, antihypertensive medication, eGFR at baseline, the number of follow-up examinations, and the year of the baseline examination., Results: The mean age of the participants averaged 62.9 ± 8.1 years, 71.3% were women and 23.7% were under antihypertensive medication. During a median follow-up of 8.3 years, 220 participants developed CKD events. The adjusted hazard ratios for CKD in a 1-standard deviation increase in daytime and night-time SBP were 1.13 [95% confidence interval (CI) 0.97-1.30] and 1.21 (95% CI 1.04-1.39), respectively. When night-time and daytime BP was mutually adjusted into the same model, only night-time BP persisted as an independent predictor of CKD., Conclusion: Night-time BP is a better predictor of CKD development than daytime BP in the general population. Ambulatory BP measurement is considered useful for evaluating the risk of progression to CKD.

Ambulatory blood pressure monitoring (ABPM) is being used increasingly in both clinical practice and hypertension research. Although there are many guidelines that emphasize the indications for ABPM, there is no comprehensive guideline dealing with all aspects of the technique. It was agreed at a consensus meeting on ABPM in Milan in 2011 that the 34 attendees should prepare a comprehensive position paper on the scientific evidence for ABPM.This position paper considers the historical background, the advantages and limitations of ABPM, the threshold levels for practice, and the cost-effectiveness of the technique. It examines the need for selecting an appropriate device, the accuracy of devices, the additional information and indices that ABPM devices may provide, and the software requirements.At a practical level, the paper details the requirements for using ABPM in clinical practice, editing considerations, the number of measurements required, and the circumstances, such as obesity and arrhythmias, when particular care needs to be taken when using ABPM.The clinical indications for ABPM, among which white-coat phenomena, masked hypertension, and nocturnal hypertension appear to be prominent, are outlined in detail along with special considerations that apply in certain clinical circumstances, such as childhood, the elderly and pregnancy, and in cardiovascular illness, examples being stroke and chronic renal disease, and the place of home measurement of blood pressure in relation to ABPM is appraised.The role of ABPM in research circumstances, such as pharmacological trials and in the prediction of outcome in epidemiological studies is examined and finally the implementation of ABPM in practice is considered in relation to the issue of reimbursement in different countries, the provision of the technique by primary care practices, hospital clinics and pharmacies, and the growing role of registries of ABPM in many countries.

Objectives: We evaluated the predictive power of home blood pressure and clinic blood pressure based on the long-term cardiovascular outcome in hypertensive patients with and without impaired glucose metabolism (IGM)., Method: The multicentre Hypertension Objective Treatment Based on Measurement by Electrical Devices Blood Pressure trial (HOMED-BP) involved 3080 patients (50.5% women; mean age 59.7 years) with a baseline, untreated home/clinic blood pressure as well as follow-up, on-treatment blood pressure. Of those, 979 had IGM and 475 of these patients had diabetes. We applied Cox regression pooling all participants in a cohort analysis in which IGM and normal glucose metabolism (NGM) were separated., Results: During median 5.45 years follow-up, cardiovascular events occurred in 48 patients with IGM and 53 patients with NGM. Baseline home SBP significantly predicted cardiovascular outcome among IGM group [hazard ratio 1.68, 95% CI 1.26-2.26, P = 0.0005]. On-treatment home blood pressure was a significant predictor for cardiovascular risk even after the further adjustment of baseline blood pressure level (P ≤ 0.027), whereas on-treatment clinic blood pressure was not in NGM group (P ≥ 0.37). The event rate in IGM was approximately two times higher than that in NGM (9.95 vs. 4.88 per 1000 patient-years), resulted to the low 5-year number needed to treat in IGM patients [83 vs. 121 for 1-SD (13.1 mmHg) home SBP reduction, and 62 vs. 104 for 1-SD (9.5 mmHg) home DBP reduction)., Conclusion: The present findings suggest that long-term cardiovascular risk in IGM patients should be assessed based on home blood pressure, not on clinic blood pressure.

Objective: In Western populations, blood pressure (BP) measured at baseline has been reported to predict long-term (over 20 years) risk of mortality from cardiovascular diseases (CVDs). However, corresponding evidence is scarce in Asia where stroke is dominant. We investigated the association between baseline BP and 24-year mortality risk due to CVD, in a representative Japanese general population., Methods: We followed up a nationwide sample of 8592 Japanese, aged 30 years or above without a history of CVD and antihypertensive medication at baseline, for 24 years. Hazard ratios for CVD mortality in BP categories defined according to JCN7 criteria were estimated using Cox model adjusted for potential confounding factors with normal BP treated as the reference category., Results: We observed 689 CVD deaths. Hazard ratios for CVD mortality were progressively and significantly increased from the category of prehypertension. Population-attributable fraction (PAF) demonstrated that 43 and 48% of CVD and stroke deaths were explained by non-normal BP at baseline. Hazard ratios and PAF were remarkably higher in younger participants (aged 30-59 years) than those in the elderly (aged 60 years or above). Particularly, in younger men, 81% of CVD deaths were explained by non-normal BP. In sensitivity analysis, participants with antihypertensive medication showed the highest hazard ratio for CVD morality compared with the other categories., Conclusions: BP levels above normal at baseline retained significant relative and absolute risks of CVD and stroke mortality during 24 years. Long-lasting burden of non-normal BP particularly in younger individuals suggests the importance of primary prevention of high BP from younger generation.

Background: The aldosterone-to-renin ratio (ARR) is used to screen for primary aldosteronism and could be an index for salt sensitivity. The association between ARR and the development of chronic kidney disease (CKD) is completely unknown., Method: A longitudinal observational study involving 689 participants from a general Japanese population (mean age 58.2 years; 68.5% women) who did not have CKD and were not receiving antihypertensive medication at baseline was conducted. The estimated glomerular filtration rate (eGFR) was calculated from serum creatinine levels, and CKD was defined as eGFR less than 60 ml/min per 1.73 m(2) and/or dipstick-positive proteinuria. The associations of baseline plasma renin activity (PRA), plasma aldosterone concentration, and ARR with the development of CKD were examined using Cox proportional hazard regression analysis adjusted for sex, age, BMI, smoking, drinking, history of hypercholesterolemia, diabetes mellitus, and cardiovascular disease, SBP, and baseline eGFR., Results: During a mean 9.1-year follow-up, 118 participants developed CKD. A 1 standard deviation increment in the natural log-transformed (ln) ARR was positively associated with the incidence of CKD (hazard ratio 1.29, P = 0.012). LnPRA showed an inverse association (hazard ratio 0.76, P = 0.007). Meanwhile, plasma aldosterone concentration was not associated with CKD. Individuals who developed CKD had significantly lower baseline PRA (0.97 vs. 1.14 ng/ml per h; P = 0.03) and higher baseline ARR levels [66.6 vs. 56.8 (pg/ml)/(ng/ml per h); P = 0.02] than those who did not., Conclusions: Lower PRA and higher ARR were associated with the development of CKD in a general population, suggesting that they are independent predictors of CKD.

Objective: The hypotensive effect and the time to attain the maximum antihypertensive effect (stabilization time) of losartan/hydrochlorothiazide (HCTZ) combination therapy and therapy with a maximal dose of angiotensin II receptor blockers (ARBs) in patients who failed to achieve adequate blood pressure (BP) control on a medium-dose of ARBs were compared by analyzing exponential decay functions using daily serial morning home BP measurements., Methods: Essential hypertensive patients treated with a medium dose of ARB, in whom a target home SBP (135 mmHg) was not achieved, were randomized into two groups: a combination group (n = 110) and a maximal-dose ARB group (n = 111)., Results: The combination therapy provided additional reduction of 5.2 mmHg [95% confidence interval (CI) 1.8 to 8.5 mmHg, P = 0.003] in home SBP over the maximal-dose ARB therapy in 8 weeks after randomization. A greater reduction in the home SBP values was seen in the combination group than in the maximal-dose ARB group from the second day after randomization on the basis of a linear mixed model. The maximum antihypertensive effect and stabilization time for home SBP were 10.9 ± 5.0 mmHg and 7.3 ± 29.7 days, respectively, in the combination group, whereas the corresponding values in the maximal-dose ARB group were 7.9 ± 2.6  mmHg and 122.3 ± 42.7 days, respectively, on the basis of a nonlinear mixed model., Conclusions: Changing from a medium dose of ARB monotherapy to combination therapy was more effective in the reduction of home SBP and achieved goal BP more rapidly than increasing the ARB dose. Home BP measurement is a useful tool for characterizing the antihypertensive effects of drugs.

Objectives: Essential hypertension is a complex condition whose cause involves the interaction of multiple genetic and environmental factors such as salt intake. Salt-inducible kinase 1 (SIK1) is a sucrose-nonfermenting-like kinase isoform that belongs to the AMPK (5' adenosine monophosphate-activated protein kinase) family. SIK1 activity is increased by high salt intake and plays an essential role in regulating the plasma membrane Na(+),K(+)-ATPase. The objective of this study was to examine whether SIK1 is present in vascular smooth muscle cells (VSMCs) and endothelial cells, whether it affects VSMC Na(+),K(+)-ATPase activity and whether human SIK1 (hSIK1) represents a potential candidate for blood pressure regulation., Methods: Localization of SIK1 was performed using immunohistochemistry, mRNA and western blot. Functional assays (Na(+),K(+)-ATPase activity) were performed in VSMCs derived from rat aorta. Genotype-phenotype association studies were performed in three Swedish and one Japanese population-based cohorts., Results: SIK1 was localized in human VSMCs and endothelial cells, as well as a cell line derived from rat aorta. A nonsynonymous single nucleotide polymorphism in the hSIK1 gene exon 3 (C→T, rs3746951) results in the amino acid change (15)Gly→Ser in the SIK1 protein. SIK1-(15)Ser was found to increase plasma membrane Na(+),K(+)-ATPase activity in cultured VSMC line from rat aorta. Genotype-phenotype association studies in three Swedish and one Japanese population-based cohorts suggested that T allele (coding for (15)Ser) was associated with lower blood pressure (P = 0.005 for SBP and P = 0.002 for DBP) and with a decrease in left ventricular mass (P = 0.048)., Conclusion: The hSIK1 appears to be of potential relevance within VSMC function and blood pressure regulation.

Background: Aldosterone-to-renin ratio (ARR) is an index for inappropriate aldosterone activity and salt sensitivity. We previously reported that elevated ARR might be associated with salt-sensitive hypertension. Because salt-sensitive hypertensive patients are reported to show a diminished nocturnal decline in blood pressure, we hypothesized that high ARR may be associated with diminished nocturnal decline in blood pressure (generally referred to as a 'nondipping' pattern), especially in individuals with high sodium intake., Methods: This study tested this hypothesis in 184 participants aged at least 55 years not receiving antihypertensive treatment in a general Japanese population (age: 67.6 ± 6.9 years; 71.7% women)., Results: Ambulatory blood pressure monitoring identified 63 (34.2%) participants with a nondipping pattern (nocturnal decline of SBP <10%). The median plasma renin activity (PRA), plasma aldosterone concentration (PAC), and ARR were 0.8 ng/ml per h, 8.3 ng/dl, and 8.7 ng/dl per (ng/ml per h), respectively. After adjustment for possible confounding factors, each 1 SD increase in logARR was associated with the prevalence of nondipping pattern (odds ratio, 1.95; P = 0.002). This association was observed in individuals in the highest tertile of 24-h urinary sodium excretion estimated from spot urine data (e24-hUNa; ≥179.6 mEq/day; P = 0.01) but disappeared in those in the lowest tertile of e24-hUNa (<147.9 mEq/day; P = 0.6). In those in the highest tertile of e24-hUNa, PRA was significantly lower in nondippers than in dippers (0.49 vs. 0.85 ng/ml per h) despite no differences in PAC., Conclusion: These results suggest that relative aldosterone excess might be related to a nondipping pattern of blood pressure, especially in individuals with high sodium intake.

Background: We and other investigators previously reported that isolated nocturnal hypertension on ambulatory measurement (INH) clustered with cardiovascular risk factors and was associated with intermediate target organ damage. We investigated whether INH might also predict hard cardiovascular endpoints., Methods and Results: We monitored blood pressure (BP) throughout the day and followed health outcomes in 8711 individuals randomly recruited from 10 populations (mean age 54.8 years, 47.0% women). Of these, 577 untreated individuals had INH (daytime BP <135/85 mmHg and night-time BP ≥120/70 mmHg) and 994 untreated individuals had isolated daytime hypertension on ambulatory measurement (IDH; daytime BP ≥135/85 mmHg and night-time BP <120/70 mmHg). During follow-up (median 10.7 years), 1284 deaths (501 cardiovascular) occurred and 1109 participants experienced a fatal or nonfatal cardiovascular event. In multivariable-adjusted analyses, compared with normotension (n = 3837), INH was associated with a higher risk of total mortality (hazard ratio 1.29, P = 0.045) and all cardiovascular events (hazard ratio 1.38, P = 0.037). IDH was associated with increases in all cardiovascular events (hazard ratio 1.46, P = 0.0019) and cardiac endpoints (hazard ratio 1.53, P = 0.0061). Of 577 patients with INH, 457 were normotensive (<140/90 mmHg) on office BP measurement. Hazard ratios associated with INH with additional adjustment for office BP were 1.31 (P = 0.039) and 1.38 (P = 0.044) for total mortality and all cardiovascular events, respectively. After exclusion of patients with office hypertension, these hazard ratios were 1.17 (P = 0.31) and 1.48 (P = 0.034)., Conclusion: INH predicts cardiovascular outcome in patients who are normotensive on office or on ambulatory daytime BP measurement.

Objective: Only a few of numerous epidemiological studies have demonstrated a positive association between environmental tobacco smoke (ETS) exposure and blood pressure (BP), despite experimental studies showing such a positive association. The association between home blood pressure (HBP) and ETS exposure was investigated in the general population., Methods: Five hundred and seventy-nine nonsmoking Japanese women were enrolled. The participants were classified into four categories according to their responses to a self-administered questionnaire: unexposed women (non-ETS), women exposed at home [ETS(home)], at the workplace/other places [ETS(work/other)] and at home and at the workplace/other places [ETS(both)]. Variables were compared using analysis of covariance adjusted for age, marital status, body mass index, diabetes mellitus, stroke, heart disease, hyperlipidemia, alcohol intake, salt intake and activity levels., Results: In participants without antihypertensive medication, systolic morning HBP in ETS(both) was 4 mmHg higher than that in non-ETS (116.8 +/- 1.01 vs. 113.1 +/- 1.08 mmHg, P = 0.02) and systolic morning HBP in ETS(home) and systolic evening HBP in ETS(both) were 3 mmHg higher than those in non-ETS (116.2 +/- 1.07 vs. 113.1 +/- 1.08 mmHg, P = 0.04; and 115.3 +/- 1.02 vs. 111.9 +/- 1.09 mmHg, P = 0.03, respectively). In participants with antihypertensive medication, ETS exposure status was not significantly associated with increased HBP levels., Conclusions: A positive association between HBP levels and ETS exposure was confirmed. HBP measurement is recommended in population-based studies investigating the effects of ETS exposure. ETS exposure may increase BP, thereby synergistically contributing to unfavorable cardiovascular outcomes along with other deleterious effects of ETS.

Objective: Longevity is clustered in particular families. Some studies using conventional blood pressure (BP) reported an association between parental longevity and offspring's BP. No study has used self-measurement of BP at home (home BP). We examined the association between parental longevity and home BP values of adult Japanese offspring., Method: Home and conventional BPs were measured in 1961 residents aged 40 years and over in the general population of Ohasama, Japan. Information about the ages of offspring's parents (age at death or current age) was obtained from a standardized questionnaire., Results: The mean +/- SD values of systolic/diastolic home BP in offspring whose mothers died at less than 69 years of age, at 69-84 years of age, and in offspring whose mothers were alive at age 84 years were 127.4 +/- 13.2/76.2 +/- 9.1, 124.8 +/- 15.0/74.4 +/- 10.0, and 123.4 +/- 15.2/74.4 +/- 10.3 mmHg (P = 0.0002/0.009), respectively. Corresponding values in offspring whose fathers died at less than 66 years of age, at 66-80 years of age, and in offspring whose fathers were alive at age 80 years were 125.7 +/- 15.2/75.6 +/- 10.6, 124.7 +/- 14.1/75.0 +/- 9.2 and 122.4 +/- 14.6/73.6 +/- 9.5 mmHg (P = 0.001/0.003), respectively. Multivariate analysis demonstrated associations that were only weakly observed for conventional BP values (conventional BP: P = 0.3/0.4 for maternal and P = 0.3/0.3 for paternal longevity; home BP: P = 0.05/0.2 for maternal and P = 0.0004/0.007 for paternal longevity)., Conclusion: Parental premature death was significantly associated with higher home BP levels in adult offspring, suggesting that parental longevity might be a useful additional marker for screening adult offspring at higher risk of hypertension.

Objective To investigate the risk of silent cerebrovascular lesions in individuals with masked hypertension (MHT) and white-coat hypertension. Methods Self-measured home blood pressure (HBP) and casual blood pressure (CBP) measurements were recorded in 1060 individuals at least 55 years of age (mean age, 66.3 years) in a general population of Ohasama, Japan. The relationships between silent cerebrovascular lesions (white matter hyperintensity and lacunar infarct) detected on MRI and four blood pressure groups [sustained normal blood pressure (SNBP), HBP <135/85 mmHg, CBP <140/ 90 mmHg; white-coat hypertension, HBP <135/85 mmHg, CBP > or =140/90 mmHg; MHT, HBP > or =135/85 mmHg, CBP <140/90 mmHg; sustained hypertension, HBP > or =135/85 mmHg, CBP > or =140/90 mmHg] were examined using multivariate analysis adjusted for possible confounding factors. Results The odds ratios of sustained hypertension (1.74, 95% confidence interval 1.18-2.57) and MHT (2.31, 95% confidence interval 1.32-4.04) for the presence of silent cerebrovascular lesions were significantly higher than the odds ratio of SNBP, whereas there was no significant difference between white-coat hypertension and SNBP (1.03, 95% confidence interval 0.75-1.41). The odds ratios for the presence of either lacunar infarct or white matter hyperintensity in the four groups were similar to those for silent cerebrovascular lesions. Conclusion The present study is the first to demonstrate that the risk of silent cerebrovascular lesions is higher with MHT than with SNBP and similar to that of sustained hypertension.

Objective: To evaluate the association between stroke risk and blood pressure (BP) levels with regard to the usage of antihypertensive medications., Methods: From the Japan arteriosclerosis longitudinal study, 11,371 participants from the four population-based cohort studies (aged 40-89) were followed up for a mean of 9.5 years. A Poisson regression model, adjusting for possible confounding factors, was used to investigate the risk of first stroke among six BP-based categories (BP defined according to recent guidelines), in relation to the use of antihypertensive medications., Results: There were 324 incident cases of first stroke. Among untreated groups, the relative hazard increased linearly with the elevation of BP grade (trend P = 0.0001). The untreated group with normal BP had a significantly higher stroke risk [relative hazard 2.09, 95% confidence interval 1.09-4.01] than the untreated group with optimal BP. There was no stepwise increase in stroke risk observed among treated groups (trend P = 0.1). The stroke risk among treated groups, even among those with optimal BP (relative hazard 4.10, 95% confidence interval 1.17-14.4), was significantly higher than that in the untreated groups with the same BP level., Conclusion: Treated individuals with optimal BP had a higher stroke risk than untreated ones with optimal BP. Healthcare providers need to be vigilant for residual cardiovascular risks in treated hypertensive patients.

Objective: Blood pressure (BP) increases both in winter and in the last trimester of pregnancy. Some interaction seems to exist between season and gestational age. The present study observed home BP values during pregnancy with adjustment for seasonal variation and gestational age., Methods: We observed 10353 home BP measurements from 101 normal pregnant women attending a maternity hospital in Japan. Home BP values were examined by mixed linear model adjusting for meteorological data and gestational age., Results: The lowest home BP values were observed in the second trimester [mean (+/-standard deviation) systolic/diastolic BP, 101.8 +/- 7.9/59.8 +/- 5.8 mmHg at gestational week 20]. In the last trimester, home BP values gradually increased and the values after gestational week 26 were significantly higher than those at gestational week 20 (110.1 +/- 9.7/66.8 +/- 7.7 mmHg at gestational week 40). A 10 degrees C increase in daily minimum outdoor temperature was associated with a mean reduction of 2.5/2.5 mmHg (Delta systolic BP/Delta diastolic BP: 95% confidence interval, 2.3/2.4 to 2.6/2.7 mmHg) in home BP with adjustment for gestational age. The largest and smallest estimated home BP changes during pregnancy were 12.8/12.5 and 3.1/3.0 mmHg in pregnant woman who delivered in January and July, respectively., Conclusion: Interactions among BP, season and gestational age should be considered when evaluating BP in pregnant women. Risks associated with high BP might be underestimated in pregnant woman in summer who will deliver in winter.

Background: Resting heart rate can predict cardiovascular disease mortality or all-cause mortality. Because of the effect of the alert reaction, heart rates measured out-of-office should have better predictive power than those obtained at clinics. However, only a few studies have described the relationship between heart rate measured by ambulatory blood pressure monitoring devices and cardiovascular disease prediction., Methods: We studied 1444 individuals from the Japanese general population who did not have a history of cardiovascular diseases including arrhythmia. We used multiple adjusted Cox proportional hazards to calculate the mortality risk of daytime heart rate, night-time heart rate, and the day-night heart rate dip ratio [day-night heart rate dip ratio = (daytime heart rate--night-time heart rate)/daytime heart rate x 100]., Results: After 12 years of follow-up, 101, 195, and 296 participants died due to cardiovascular diseases, noncardiovascular diseases, and all causes, respectively. As shown by others, neither daytime nor night-time heart rate predicted cardiovascular disease mortality, whereas both predicted noncardiovascular disease mortality. The day-night heart rate dip ratio was significantly related to all-cause mortality. When night-time heart rate and day-night heart rate dip ratio were simultaneously included into the same Cox model, only night-time heart rate significantly and independently predicted all-cause mortality (relative hazard per 10 bpm increase = 1.29, 95% confidence interval, 1.07-1.54)., Conclusion: Night-time heart rate value seems to have the most important predictor of all-cause mortality among ambulatory heart rate parameters in this population.

This document summarizes the available evidence and provides recommendations on the use of home blood pressure monitoring in clinical practice and in research. It updates the previous recommendations on the same topic issued in year 2000. The main topics addressed include the methodology of home blood pressure monitoring, its diagnostic and therapeutic thresholds, its clinical applications in hypertension, with specific reference to special populations, and its applications in research. The final section deals with the problems related to the implementation of these recommendations in clinical practice.