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This study aimed to evaluate the relationship between pulse pressure (PP) and sarcopenia, frailty, and cognitive function in elderly patients with hypertension. We evaluated 435 elderly patients with a history of hypertension who visited the frail outpatient clinic between July 2015 and October 2021. Data at the 1-, 2-, and 3-year follow-ups were available for 222, 177, and 164 patients, respectively. Sarcopenia, frailty, and cognitive function, including Mini-Mental State Examination (MMSE) scores, were evaluated. The patients' mean age was 79.2 ± 6.3 years (male, 34.9%). PP and mean blood pressure (BP) were 60.1 ± 13.6 mmHg and 94.1 ± 13.0 mmHg, respectively. At baseline, lower PP was associated with probable dementia (MMSE score ≤23 points) (OR = 0.960 per 1 mmHg increase; 95% CI, 0.933-0.989; P = 0.006) in the model adjusted for conventional confounding factors and comorbidities, whereas higher PP was associated with low handgrip strength (OR = 1.018 per 1 mmHg increase; 95% CI, 1.001-1.036; P = 0.041). In multivariate-adjusted logistic regression analysis of patients with preserved handgrip strength at baseline, reductions in PP (OR = 0.844; 95% CI, 0.731-0.974; P = 0.020) and mean BP (OR = 0.861; 95% CI, 0.758-0.979; P = 0.022) were significantly associated with the incidence of low handgrip strength at 3 years. In conclusion, a higher PP induced by increased arterial stiffness was associated with lower handgrip strength, whereas a lower PP was associated with probable dementia. Reduced PP was associated with decreased handgrip strength after three years., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Objectives: Automated office blood pressure (AOBP) measurement often requires assistance. Accompanied by an instructional video, AOBP measurement could be performed independently by patients., Design and Methods: Seventy-five patients with hypertension were enrolled. AOBP was measured three times at 1-min intervals after 5 min of rest by an automated BP measurement device with the assistance of an animated instructional video. The video was designed originally to instruct patients on the way to measure BP appropriately. Perceived stress was evaluated using a questionnaire after the AOBP measurement. Office BP was measured three times using the same device. Home BP measurement was performed on 5 consecutive days., Results: The mean age of the patients was 74.5 ± 10.6 years, and 96% were taking antihypertensive drugs. Mean AOBP, office BP and home BP measurements were 135.2 ± 17.2/81.3 ± 11.1, 139.3 ± 16.3/78.6 ± 10.9 and 129.2 ± 16.7/72.7 ± 8.9 mmHg, respectively. Regarding SBP, the mean AOBP was significantly lower than office BP ( P  = 0.005) and higher than home BP ( P  = 0.004). The differences in SBP and DBP between AOBP and home BP measurements were significantly related to patients' perceived stress when performing AOBP measurements ( r  = 0.289; P  = 0.013 and r  = 0.328; P  = 0.004). In a multivariate analysis, patients' perceived stress was a significant predictor of the difference between AOBP and home BP ( P  = 0.013), even after adjusting for age, sex, BMI and mean of AOBP and home BP., Conclusion: AOBP values measured with the assistance of an instructional video were between conventional office and home BP measurements. Perceived stress during AOBP measurement was related to the difference in AOBP from home BP., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: The aim of this study was to clarify the relationship between high or low blood pressure (BP) and cognitive function in elderly outpatients with cardiometabolic diseases., Methods: We evaluated the association between BP and the Dementia Assessment Sheet for Community-based Integrated Care System-21 items (DASC-21), Mini Mental State Examination (MMSE), and Montreal Cognitive Assessment Tool (MoCA) (N = 677)., Results: The patients' mean age was 79.2 ± 6.3 years (male 35.3%), and BP was 132.1 ± 18.1/73.5 ± 12.2 mmHg. Systolic BP (SBP) was linearly related to the DASC-21 score (r = -0.122, P = 0.004), but not to the MMSE score (P = 0.101) or MoCA score (P = 0.802). Multiple linear regression analysis showed that lower SBP was significantly related to the DASC-21 score, even after controlling for confounding factors (B = -0.411 per 10 mmHg; 95% confidence interval [CI], -0.673 to -0.149; P = 0.002). Moreover, logistic regression analysis showed that lower SBP was associated with DASC-21 ≥ 31 (odds ratio = 0.838 per 10 mmHg, P = 0.048). An MMSE score ≤23 was significantly associated with higher SBP in patients without a history of hypertension but with lower SBP in those with hypertension, those on hypertensive medication, and those with dyslipidemia., Conclusion: Higher BP was associated with a higher prevalence of probable dementia in those without a history of hypertension, even in late life. In those with hypertension and those taking antihypertensives with comorbidities of stroke or heart failure, lower BP was associated with probable dementia, which was largely dependent on reduced activities of daily living, as measured by the DASC-21 score. Geriatr Gerontol Int 2024; 24: 110-117., (© 2023 Japan Geriatrics Society.)

Aim: We aimed to examine the relationship between changes in clinic blood pressure (BP) and frailty and sarcopenia in elderly outpatients with cardiometabolic disease., Methods: In 691 elderly outpatients with cardiometabolic diseases, the associations of frailty according to the modified Japanese Cardiovascular Health Study score (J-CHS) and Kihon Checklist (KCL) criteria with clinic BP were evaluated at baseline and followed up for 3 years., Results: Among the patients (79.2 ± 6.3 years, male 35.6%), 30.4% had frailty by the J-CHS criteria and 38.0% by the KCL criteria. A J-curve relationship was observed between BP and frailty; the prevalence of frailty was the lowest in patients with systolic BP (SBP) 119.5-130.5 mmHg and in those with diastolic BP (DBP) 72.0-80.5 mmHg. Frailty by the J-CHS criteria correlated with lower DBP (OR = 0.892 per 5 mmHg increase, 95% confidence interval [CI] 0.819-0.972, P = 0.009), whereas that by the KCL criteria correlated with lower SBP (OR = 0.872 per 10 mmHg increase, 95% CI 0.785-0.969, P = 0.011) in multivariate-adjusted models. In patients with frailty by the J-CHS criteria at baseline, changes in DBP (OR = 0.921 per 1 mmHg change, 95% CI 0.851-0.996, P = 0.038) were associated with sustained frailty 1 year later. Changes in DBP were associated with progression to a slow walking speed 1 year later (OR = 0.939, 95% CI 0.883-0.999, P = 0.047). Changes in SBP (OR = 0.928, 95% CI 0.878-0.981, P = 0.008) and DBP (OR = 0.926, 95% CI 0.859-0.997, P = 0.042) were associated with progression to a weak hand grip strength 3 years later., Conclusion: A J-curve relationship was observed between frailty and BP, and a decline in BP was associated with progression to a slow walking speed and weak hand grip strength in elderly outpatients with cardiometabolic diseases. Geriatr Gerontol Int 2023; 23: 506-516., (© 2023 Japan Geriatrics Society.)

Frailty is a state of increased vulnerability to stress resulting from physiological decline associated with aging. Topics of hypertension management and its association with frailty and cognitive function, recent studies of coronavirus disease 2019 infection (COVID-19) in elderly is discussed in this narrative review. While various guidelines for hypertension recommend that frailty is taken into account in treatment decisions, specific assessment tools and clinical decision criteria have not been explicitly established. Hypertension is prevalent in frail individuals, although a direct association has not been reported. Therefore, optimal blood pressure (BP) control is critical for managing cardiovascular risk reduction and preserving quality of life in frail hypertensive patients. BP typically decreases in later life or situations in which patients are dependent on nursing care. Mortality is reported to be high among frail patients with lower BP, raising questions about appropriate BP targets for frail patients. Cognitive decline is one of the domains of frailty, and is associated with a loss of autonomy, lack of self-management, and compromised quality of life. It remains to be clarified whether antihypertensive treatment is beneficial for cognitive function especially in older individuals. Increased severity and mortality of COVID-19 infection has been reported in older people. Clinical manifestations and biomarkers particular to older patients, and lifestyle changes including social isolation during the COVID-19 pandemic is reported. From the knowledge from recent literatures, future perspectives for holistic approach and management of frail older people is addressed., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Transcatheter aortic valve replacement (TAVR) is a standard treatment for elderly and high-risk patients with aortic valve stenosis (AS); however, its short-term effects on blood pressure (BP) and cardiac function are not clear. Therefore, we aimed to determine the short-term effects of TAVR in elderly patients (>75 years), who reflect the clinical situation in Japan., Method and Results: Twenty-eight consecutive elderly patients with severe AS and hypertension who underwent TAVR under general anesthesia were retrospectively investigated. All patients had hypertension that was well controlled with antihypertensive drugs. Serum brain natriuretic peptide level and peak velocity in the aortic valve were significantly reduced. TAVR induces an increase in BP that requires additional antihypertensive agents. There was no correlation between the change rate of SBP and stroke volume index (SVI), but there was a positive correlation between the rate of change in pulse pressure (PP) and SVI. This tendency was particularly observed in patients with low brachial-ankle pulse wave velocity (baPWV)., Conclusion: We observed post-TAVR hypertension and required additional antihypertensive drugs. The increases in SVI and PP after TAVR resulted in post-TAVR hypertension. Moreover, post-TAVR hypertension is less likely to occur in elderly patients with a high baPWV, which indicates advanced arteriosclerosis., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Frailty and depression may play important roles in the management of older patients with cardiometabolic diseases. We explored the determinants of depressive symptoms and their association with frailty among patients with cardiometabolic diseases (hypertension, diabetes, and atrial fibrillation) in a cross-sectional study., Methods: A total of 633 outpatients aged 65 years or older with cardiometabolic disease and suspected symptoms of frailty participated in this study. Depressive symptoms, physical activity, and social network were assessed using the Geriatric Depression Scale (GDS)-15, International Physical Activity Questionnaire, and Lubben Social Network Scale-6 (LSNS-6), respectively. Frailty was evaluated using the Kihon Checklist (KCL) based on the Comprehensive Geriatric Assessment (CGA), the modified Cardiovascular Health Study (mCHS), and the Clinical Frailty Scale (CFS). Binomial logistic regression analysis was used to examine the determinants of depressive symptoms and their association with frailty., Results: Depressive symptoms with GDS-15 scores ≥ 5 were present in 43.6% of the patients. In logistic regression, after adjusting for covariates, the determinants of depressive symptoms in all patients were lack of social network, low years of education, and frailty. In contrast, in logistic regression with frailty as the dependent variable, depressive symptoms were independently associated KCL-defined frailty (OR = 6.28, 95% CI: 4.13-9.55) and mCHS-defined frailty (OR = 2.66, 95% CI: 1.70-4.17), but not with CFS. Similarly, significant associations between depression and frailty were observed in patients with hypertension, diabetes, or atrial fibrillation., Conclusions: Lack of social networks, low education, and frailty based on the KCL and mCHS were important determinants of depressive symptoms in all patients. The relatively strong associations between depressive symptoms and frailty based on CGA in patients with hypertension, diabetes, or atrial fibrillation suggest that the assessment of depressive symptoms is of great importance in clinical practice in those patients at high risk of frailty., Competing Interests: AA has received a speaker honoraria from Merck Sharp & Dohme, Sumitomo Parma Co. Ltd., Ono Pharmaceutical Co.Ltd., Takeda Pharmaceutical Co. Ltd., and Novo Nordisk Pharma Ltd. The other authors declare no conflict of interest., (Copyright: © 2023 Yorikawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: An increased blood pressure variability (BPV) has been reported to be associated with older age and cognitive dysfunction; however, associations between increased BPV and rapid eye movement sleep behaviour disorder (RBD) has not been thoroughly investigated in patients without clinical Lewy body diseases., Materials and Methods: In frailty outpatient clinic, we evaluated ambulatory BP, RBD screening questionnaire (RBDSQ), and beat-to-beat heart rate variability during positional change from sitting to standing in 112 elderly hypertensive patients., Results: The mean age was 81.2 ± 6.3 years (68% male). There were 15 patients who had probable RBD (RBDSQ scores ≥ 5). Patients with RBD had a greater body mass index, coefficient of variation (CV) in 24-h diastolic BP (23.5 ± 6.1 versus 18.7 ± 5.8, p  = 0.005), awake diastolic BP (23.0 ± 7.7 versus 18.6 ± 6.2, p  = 0.017), and nocturnal systolic BP (14.9 ± 5.5 versus 12.0 ± 4.4, p  = 0.025) compared with those without RBD, while systolic BP, diastolic BP, and cognitive function did not differ significantly between patients with and without RBD. Patients with RBD exhibited larger orthostatic BP fall compared with patients without RBD (-4.9 ± 11.0 versus 7.5 ± 11.8, p  = 0.009) and lower CV of R-R intervals while standing (1.3 ± 0.6 versus 2.4 ± 1.5, p  = 0.039). Multiple regression analysis revealed that patients with RBD had significantly greater CV of nocturnal systolic BP independent of age, sex, BMI, history of diabetes and dyslipidaemia, and use of antihypertensive drugs ( p  = 0.008)., Conclusion: An increased BPV in ambulatory BP, associated with autonomic dysfunction, can be observed in patients with probable RBD even in elderly patients without clinical presentation of Lewy body diseases.

Minor ST-T changes on electrocardiograms are observed in patients with hypertensive heart disease with a preserved left ventricular ejection fraction (LVEF); however, the relationship between minor ST-T changes and global myocardial work on echocardiograms remains unclear. We evaluated the global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) in 186 hypertensive patients with preserved LVEF (>50%) using an offline analysis system (View Pal, GE). Minor ST-T changes as well as major ST-T changes (depression in ST in lead V5 > 1 mV) were also evaluated by electrocardiography. The mean age was 79.4 ± 8.2 years (men 37.6%). Patients with minor and major ST-changes had a smaller absolute GLS (-20.3 ± 3.1, -18.2 ± 3.7, and -15.2 ± 5.0%, P < 0.001) and a smaller constructive workload [GWI (2148 ± 486, 1938 ± 462, and 1685 ± 701 mmHg%, P = 0.002) and GCW (2419 ± 510, 2185 ± 466, and 1865 ± 702 mmHg%, P < 0.001)] than those with no ST-T changes. Additionally, patients with minor and major ST-T changes had increased wasted myocardial work [GWW (87 ± 61, 105 ± 56, and 127 ± 75 mmHg%, P = 0.045)], which resulted in reductions in the myocardial work efficiency [GWE (95 ± 4, 94 ± 3, and 89 ± 12%, P < 0.001)]. Even after adjustments for confounding factors, including EF, diastolic function parameters, LV hypertrophy, history of heart failure and atrial fibrillation, patients with minor ST-T changes had significantly smaller LV global constructive work in comparison to those without [GWI (2260 ± 33 vs. 2025 ± 76 mmHg%, P = 0.007) and GCW (2501 ± 45 vs. 2210 ± 105 mmHg%, P = 0.003)]. In conclusion, in hypertensive patients with preserved LVEF, minor ST-T changes on electrocardiograms were associated with reduced constructive work in the LV., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Objective: Unattended automated office blood pressure (AOBP) may be a better estimate of true blood pressure (BP) than conventional office BP by physicians or nurses. However, measurement of AOBP is cumbersome in general clinical practice. We compared unattended AOBP by the patients themselves using the rigid cuff in the waiting room with attended AOBP and home BP (HBP) (N = 72)., Methods: Unattended AOBP by patients was measured in the waiting room using a rigid cuff with the fully automated device (Omron, HEM-907, triple BP readings taken at 1-min intervals after 5 min of rest). Attended AOBP was measured using a soft cuff by a physician in an examination room without specific resting time. HBP was measured for 5 consecutive days., Results: The mean age was 76.5 ± 8.6 years. The mean systolic unattended AOBP by patients, attended AOBP and HBP were 139.3 ± 16.6, 144.8 ± 17.1 and 139.1 ± 14.4 mmHg, respectively. Unattended AOBP by patients was significantly related to attended AOBP (r = 0.798; P < 0.01) and to HBP (r = 0.404; P < 0.001). It was significantly lower than attended AOBP (difference 5.5 ± 10.7 mmHg; P < 0.001) and comparable with HBP (difference 0.26 ± 17.0 mmHg; P = 0.90) in Bland-Altman plots. However, 22% of patients had a difference of over 20 mmHg between unattended AOBP by patients and HBP. Multivariate regression demonstrated older age (B = -0.73; P = 0.002) to be related to the difference between unattended AOBP by patients and HBP., Conclusion: The mean unattended AOBP by patients was lower than attended AOBP and comparable with HBP, but older age affected the difference between unattended AOBP by patients and HBP., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The change of left ventricular function deteriorated with age because of gradual increases of blood pressure may result in increased energy loss (EL) in left ventricle (LV). The present study investigated EL in LV among hypertensive elderly patients and examined factors contributing to EL., Methods: A single-center retrospective study was performed on elderly hypertensive outpatients (≥65 years) who underwent echocardiography (N = 105). EL in the LV was measured using a vector flow mapping system, and factors affecting peak EL during the early-diastolic phase (ED-EL), late-diastolic phase (LD-EL), and systolic phase (Sys-EL) were evaluated., Result: Mean age was 79.9 ± 6.4 years (male 43%). Mean ED-EL, LD-EL, and Sys-EL were 42.1 ± 46.7, 75.6 ± 60.2, and 40.4 ± 40.2 mJ/N/s. In a stepwise regression analysis, the E/e'(lateral) (unstandardized B = 0.005, 95%CI -0.03 to 0.007, standardized β = 0.434, P < .001) was identified as factors affecting ED-EL. The factors affecting LD-EL were E/A ratio (B = -0.122, 95%CI -0.176 to -0.068, β = -0.470, P < .001) and time velocity integral (TVI) in LVOT (unstandardized B = 0.002, 95%CI 0.000 to 0.004, β = 0.247, P = .021). The factors influencing Sys-EL were TVI in LVOT (B = 0.002, 95%CI 0.001 to 0.004, β = 0.390, P < .001), E/A ratio (B = -0.054, 95%CI -0.093 to -0.015, β = -0.258, P = .008), left ventricular outflow tract (LVOT) diameter (B = -0.006, 95%CI -0.010 to -0.002, β = -0.307, P = .006), and left ventricular mass index (B = 0.000, 95%CI 0.000 to 0.001, β = 0.208, P = .039)., Conclusion: Peak EL in the LV was higher during diastolic phase than systolic phase among elderly hypertensive patients. Peak EL both during late-diastolic phase and systolic phase was affected by systolic blood flow in LVOT and LV transmitral flow pattern., (© 2020 Wiley Periodicals LLC.)

Aim: Orthostatic blood pressure (BP) can fall with reduced stroke volume and arterial elasticity. However, as the reason for orthostatic BP rise is unclear, we investigated the relationship of orthostatic BP rise with frailty in older patients., Methods: In 169 consecutive outpatients who visited the frailty clinic, we evaluated orthostatic BP and heart rate changes (i.e. in the sitting position, just after standing up, 1 min after standing and after sitting down). Frailty was evaluated using the Kihon Checklist (KCL) established by the Ministry of Health, Labor and Welfare., Results: The mean age was 77.4 ± 6.9 years, and 29% of patients had frailty with a KCL score ≥8. The systolic BP declined in both groups, but patients with frailty experienced a smaller decrease just after standing (-0.2 ± 10.3 vs -6.2 ± 11.5, P = 0.001). During standing for 1 min, elevation of systolic BP was greater in patients with frailty than in those without (8.4 ± 11.6 mmHg vs 3.2 ± 11.2 mmHg, P = 0.009). The difference in elevation of systolic BP remained significant, even after adjusting for confounding factors including systolic BP before standing (P = 0.013). In particular, the KCL score for motor function was significantly correlated with an elevation of orthostatic systolic BP after standing for 1 min, even after controlling for systolic BP before standing and confounding factors (P = 0.020)., Conclusions: The elevation of systolic BP after standing for 1 min was greater in patients with frailty as diagnosed by the KCL score, especially in relation to reduced motor function. Geriatr Gerontol Int 2019; 19: 525-529., (© 2019 Japan Geriatrics Society.)

Electrocardiographic left ventricular hypertrophy (LVH) diagnosed by Cornell product and the Sokolow-Lyon voltage are associated with anatomical LVH; therefore, we investigated whether Cornell product and the Sokolow-Lyon voltage were associated with echocardiographic regional wall motion (measured by 2D-strain imaging). We reviewed data on 288 consecutive hypertensive patients who underwent both echocardiography and electrocardiography. Electrocardiographic LVH was calculated as follows: Cornell voltage, S in lead V3 + R in lead aVL; Cornell product, Cornell voltage (+0.6 mV for females) × QRS duration; and Sokolow-Lyon voltage, S in lead V1 + R in lead V5. The mean age of the subjects was 64.3 ± 13.2 years; 47.9% were men, and 65.2% were taking antihypertensive medications. Both Cornell product (r = 0.392, P < 0.001) and the Sokolow-Lyon voltage (r = 0.315, P < 0.001) were significantly related to left ventricular mass index (LVMI), and the relationship between Cornell product and LVMI (beta = 0.24, P = 0.001) was independent of the Sokolow-Lyon voltage (beta = 0.25, P < 0.001). In multivariate linear regression analysis in which the two ECG-LVH were included together, Cornell product was related to global longitudinal strain (beta = 0.24, P = 0.002), even after adjusting for the Sokolow-Lyon voltage (P = 0.835). Additionally, the Cornell voltage was related to the inner/outer ratio of circumferential strain (beta = 0.17, P = 0.033) after adjusting for the Sokolow-Lyon voltage (P = 0.318). By contrast, the Sokolow-Lyon voltage was related to the relative wall thickness and E/e' on tissue Doppler imaging, even after adjusting for Cornell product. In conclusion, Cornell product and voltage were associated with longitudinal regional wall motion and with the transmurality of regional wall motion in the short axis direction.

In the Japanese population, the electrocardiographic (ECG) Cornell voltage and product predict cardiovascular events at lower values (Cornell voltage of 2.04 mV in males and 1.71 mV in females, and Cornell product of 158.7 mV× msec) than in the guidelines (2.8 mV, 2.0 mV, and 244 mV× msec, respectively). We evaluated the ECG criteria for left ventricular hypertrophy (LVH) corresponding to echocardiographic LVH (Echo-LVH) in Japanese patients.We reviewed data on 345 consecutive hypertensive patients who underwent echocardiography, and evaluated the Cornell voltage (S in leads V3 + R in leads aVL), Cornell product [ (Cornell voltage + 0.6 mV for females) × QRS duration], and left ventricular mass index (LVMI) (Echo-LVH: LVMI ≥ 116 g/m 2 in males and ≥ 96 g/m 2 in females).The mean age was 63.8 ± 12.5 years (174 males/172 females). Echo-LVH was found in 22.7% of males and 37.2% of females. The equations for estimating LVMI from the Cornell voltage were (1) LVMI = 14.5 × Cornell voltage + 78.9 for males and (2) LVMI = 21.5 × Cornell voltage + 61.5 for females. The Cornell voltage corresponding to Echo-LVH was 2.6 mV in males and 1.6 mV in females, which were below the guideline levels and close to the values indicating cardiovascular risk. The equation for estimating LVMI from the Cornell product was LVMI = 0.15 × Cornell product + 68.8. The Cornell product corresponding to Echo-LVH was 170 mV× msec (sensitivity: 0.730, specificity: 0.601), which was also close to the cardiovascular risk level.Cornell voltage and product values indicating Echo-LVH are lower than those in the current guidelines and closer to the cardiovascular risk levels.

Backgrounds: Orthostatic hypotension (OH) is associated with cardiovascular diseases, heart failure, and increased mortality. We evaluated whether OH was affected by cardiac structure and function or autonomic function in elderly hypertensive outpatients., Patients and Methods: In 64 hypertension patients (mean age 74.2±1.7 years old), we evaluated changes in blood pressure (BP) and heart rate variability before and after standing up using the MemCalc system. In addition, we retrospectively reviewed their medical records and echocardiographic data., Results: Of the total patients, 28% had OH [decrease of systolic blood pressure (SBP) ≥20 mmHg and/or diastolic BP ≥10 mmHg]. Multivariate linear regression analysis showed that stroke volume (SV)/pulse pressure (PP) was associated independently with orthostatic change in SBP (P=0.007). The patients with OH tended to have a lower SV (57.3±13.1 vs. 68.1±16.3 ml, P=0.009) and lower SV/PP (1.02±0.26 vs. 1.33±0.45, P=0.001) than those without OH. The significance in difference in SV/PP remained even after adjustment for age, sex, BMI, estimated glomerular filtration rate, number of antihypertesive drugs, history of diabetes, and SBP at rest (P=0.036). However, there were no significant differences in change in the low frequency/high frequency ratio after standing up (P=0.899) between patients with and without OH., Conclusion: Elderly hypertensive patients with OH may have a reduced arterial compliance, measured as SV/PP, and may not have differences in sympathetic nerve activities, measured as the low frequency/high frequency ratio.

Background: Subjects with prehypertension (pre-HT; 120/80 to 139/89 mm Hg) have an increased risk of cardiovascular disease (CVD); however, whether the risk of pre-HT can be seen at the pre-HT status or only after progression to a hypertensive (HT; ≥140/90 mm Hg) state during the follow-up period is unknown., Methods: The Jichi Medical Cohort study enrolled 12,490 subjects recruited from a Japanese general population. Of those, 2227 subjects whose BP data at baseline and at the middle of follow-up and tracking of CVD events were available (median follow-up period: 11.8 years). We evaluated the risk of HT in those with normal BP or pre-HT at baseline whose BP progressed to HT at the middle of follow-up compared with those whose BP remained at normal or pre-HT levels., Results: Among the 707 normotensive patients at baseline, 34.1% and 6.6% of subjects progressed to pre-HT and HT, respectively, by the middle of follow-up. Among 702 subjects with pre-HT at baseline, 26.1% progressed to HT. During the follow-up period, there were 11 CVD events in normotensive patients and 16 CVD events in pre-HT patients at baseline. The subjects who progressed from pre-HT to HT had 2.95 times higher risk of CVD than those who remained at normal BP or pre-HT in a multivariable-adjusted Cox hazard model., Conclusion: This relatively long-term prospective cohort study indicated that the CVD risk with pre-HT might increase after progression to HT; however, the number of CVD events was small. Therefore, the results need to be confirmed in a larger cohort., (Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Unlabelled: Our aim is to determine the optimal time schedule for home blood pressure (BP) monitoring that best predicts stroke and coronary artery disease in general practice. The Japan Morning Surge-Home Blood Pressure (J-HOP) study is a nationwide practice-based study that included 4310 Japanese with a history of or risk factors for cardiovascular disease, or both (mean age, 65 years; 79% used antihypertensive medication). Home BP measures were taken twice daily (morning and evening) over 14 days at baseline. During a mean follow-up of 4 years (16 929 person-years), 74 stroke and 77 coronary artery disease events occurred. Morning systolic BP (SBP) improved the discrimination of incident stroke (C statistics, 0.802; 95% confidence interval, 0.692-0.911) beyond traditional risk factors including office SBP (0.756; 0.646-0.866), whereas the changes were smaller with evening SBP (0.764; 0.653-0.874). The addition of evening SBP to the model (including traditional risk factors plus morning SBP) significantly reduced the discrimination of incident stroke (C statistics difference, -0.008; 95% confidence interval: -0.015 to -0.008; P=0.03). The category-free net reclassification improvement (0.3606; 95% confidence interval, 0.1317-0.5896), absolute integrated discrimination improvement (0.015; SE, 0.005), and relative integrated discrimination improvement (58.3%; all P<0.01) with the addition of morning SBP to the model (including traditional risk factors) were greater than those with evening SBP and with combined morning and evening SBP. Neither morning nor evening SBP improved coronary artery disease risk prediction. Morning home SBP itself should be evaluated to ensure best stroke prediction in clinical practice, at least in Japan. This should be confirmed in the different ethnic groups., Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/. Unique identifier: UMIN000000894., (© 2016 American Heart Association, Inc.)

Background: We evaluated the reduction in central blood pressure (BP) that occurs after bathing in hot water., Methods: We subjected 28 Japanese hypertensive patients receiving treatment to 24 h ambulatory central BP monitoring. Japanese often bathe in hot water, and BP measurements were obtained on both bathing and nonbathing days. The patients removed the BP monitors by themselves before bathing and reattached them afterwards., Results: The patients' mean age was 65.5±9.7 years (men: 46.4%) and their mean office BP was 131.2±12.6/73.0±7.5 mmHg. The mean temperature of the bathing water was 40.6±1.5°C. The postbathing reduction in central systolic BP (N=20; 140.7±26.7 to 127.7±18.4 mmHg, reduction: 13.0±22.6 mmHg; P=0.019) was greater than the equivalent reductions in brachial systolic and diastolic BP (N=28; systolic/diastolic 139.1±21.0/80.3±14.4 to 131.1±16.2/72.0±10.7 mmHg, reduction: 8.0±17.5/8.3±9.6 mmHg; P=0.023 and P<0.001, respectively). The patients' mean brachial BP decreased significantly after bathing (8.5±12.1 mmHg, P=0.001), but their brachial pulse pressure did not (-1.0±9.7 mmHg, P=0.60). Multivariate analysis showed that the postbathing reduction in central BP was affected by the reduction in the augmentation index, even after adjusting for the associated decrease in the mean brachial BP. However, the patients' night-time brachial and central BP levels did not differ significantly between bathing and nonbathing days., Conclusion: The postbathing decrease in central BP was 5 mmHg greater than that in brachial BP and was influenced by the reduction in wave reflection. However, night-time brachial and central BP did not differ between bathing days and nonbathing days.

Background: The pathophysiological mechanism causing awakening blood pressure (BP) rise is not clear., Case Report: We report the case of a 66-year-old man with a history of spinal cord injury, and who had remarkable awakening BP rise in ambulatory BP monitoring. The patient also had orthostatic hypotension and post-prandial hypotension associated with an increased insulin level. This case suggests that awakening BP rise can occur without increased physical activity or positional changes, in those with autonomic nerve dysreflexia associated with a spinal cord injury. The reduction of elevated awakening BP level can be affected by eating breakfast in association with an increased insulin level. However, in ambulatory BP monitoring, the awakening BP rise was reproducible, but this patient also exhibited evening BP rise in home BP monitoring when he took a nap., Conclusions: Exaggerated awakening BP rise can occur in patients with spinal cord injury without positional change, and the recovery of BP may be modified by post-prandial and orthostatic BP drop.

Background: Although obtaining multiple home blood pressure (HBP) measurements on a single occasion was recommended in European and Japanese hypertension guidelines, the clinical implications of the differences in BP measurements on a single occasion have been uncertain., Methods: Here, 4,149 patients with cardiovascular risk factors were enrolled. We asked the patients to measure their HBP 3 times on a single occasion each day over a 2-week period. We evaluated the target organ damage (TOD) indicators left ventricular mass index (LVMI), urinary albumin creatinine ratio, B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-pro BNP), high-sensitive cardiac troponin, brachial-ankle pulse wave velocity (ba PWV), intima-media thickness, and estimated glomerular filtration rate (eGFR). The associations between TOD and the difference between the first home systolic BP (SBP) value and the average of the second and third home SBP values were assessed by multiple regression analyses with adjustment for covariates., Results: Compared to the quintile median, the TOD of the first-quintile patients (i.e., those with elevated the second and third home SBP values compared to the first value) were significantly higher BNP, higher NT-pro BNP, higher ba PWV, and lower eGFR. In a univariate analysis of variance, compared to the median quintile, the first-quintile patients had independently and significantly higher BNP, higher NT-pro BNP, and lower eGFR., Conclusion: The patients with elevated the second and third home SBP values compared to the first value taken on a single occasion were likely to have deteriorated BNP, NT-pro BNP, and eGFR., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Some previous studies have shown that central blood pressure (BP) is more closely related to cardiovascular risks than brachial BP. This study compared the correlations between asymptomatic organ damages and each of central BP, brachial clinic BP, and home BP during antihypertensive treatment., Methods: In the Japan Morning Surge-Target Organ Protection (J-TOP) study, which compared bedtime or awakening dosing of candesartan (+diuretics as needed) among subjects with home systolic BP (SBP) higher than 135 mm Hg, we evaluated 180 hypertensive patients who successfully underwent pulse wave analysis by HEM-9000AI and measured their urinary albumin/creatinine ratio (UACR) and left ventricular mass index (LVMI) (n = 144) at baseline and after 6 months of treatment., Results: During antihypertensive treatment, significant reductions were found in central SBP, UACR, and LVMI (all P < 0.001). Multiple regression analyses showed that the decrease in central SBP was associated with those of log-transformed UACR (β = 0.24, P < 0.01) and LVMI (β = 0.23, P = 0.04), independently of the decrease in both clinic and home SBP. The goodness-of-fit of the association between the reduction in SBP and the UACR (P < 0.01) or LVMI (P = 0.04) was improved by adding central SBP to the SBP measurement., Conclusion: These findings suggest that the change in central BP could be an important therapeutic target during antihypertensive treatment, in addition to peripheral clinic and home BP., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

To study whether sleep blood pressure (BP) self-measured at home is associated with organ damage, the authors analyzed the data of 2562 participants in the J-HOP study who self-measured sleep BP using a home BP monitoring (HBPM) device, three times during sleep (2 am, 3 am, 4 am), as well as the home morning and evening BPs. The mean sleep home systolic BPs (SBPs) were all correlated with urinary albumin/creatinine ratio (UACR), left ventricular mass index (LVMI), brachial-ankle pulse wave velocity (baPWV), maximum carotid intima-media thickness, and plasma N-terminal pro-hormone pro-brain-type natriuretic peptide (NTproBNP) (all P<.001). After controlling for clinic SBP and home morning and evening SBPs, associations of home sleep SBP with UACR, LVMI, and baPWV remained significant (all P<.008). Even in patients with home morning BP <135/85 mm Hg, 27% exhibited masked nocturnal hypertension with home sleep SBP ≥120 mm Hg and had higher UACR and NTproBNP. Masked nocturnal hypertension, which is associated with advanced organ damage, remains unrecognized by conventional HBPM., (©2015 Wiley Periodicals, Inc.)

To control blood pressure for throughout a day, one of antihypertensive drugs will be administered at bedtime. Calcium channel blocker or angiotensin II receptor blocker will be the first line drug for bedtime administration. Alpha-blocker or beta-blocker will be the last choice.

Background: Several guidelines recommend that home blood pressure (HBP) be measured both in the morning and in the evening. However, there have been fewer reports about the clinical significance of morning HBP than about the clinical significance of evening HBP., Methods: Our study included 4,310 patients recruited for the Japan Morning Surge Home Blood Pressure Study who had one or more cardiovascular risk factors. We measured morning and evening HBP, urinary albumin-creatinine ratio (UACR), left ventricular mass index (LVMI), brachial-ankle pulse wave velocity (baPWV), maximum carotid intima media thickness (IMT), N-terminal pro-brain-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T (Hs-cTnT)., Results: The correlation coefficients for the associations between morning systolic BP (SBP) and log-transformed baPWV, NT-proBNP, or Hs-cTnT were significantly greater than the corresponding relationships for evening SBP (all P < 0.01). The goodness-of-fit of the associations between morning home SBP and UACR (P < 0.05) or baPWV (P < 0.01) was improved by adding evening home SBP to the SBP measurement. In contrast, the goodness-of-fit values of the associations between evening SBP and UACR (P < 0.001), LVMI (P < 0.05), baPWV (P < 0.001), NT-proBNP (P < 0.001), and Hs-cTnT (P < 0.001) were improved by adding morning home SBP to the SBP measurement., Conclusions: Morning BP and evening BP provide equally useful information for subclinical target organ damage, yet multivariate modeling highlighted the stand-alone predictive ability of morning BP., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Night-time blood pressure (BP) is strongly associated with hypertensive target organ damage; however, no previous studies have compared home BP monitor measurements of the reduction in night-time BP induced by antihypertensive medications with those obtained with ambulatory BP monitors., Methods: As part of the Japan Morning Surge-Target Organ Protection study, in which candesartan (thiazide diuretics were added, if needed) was administered to hypertensive patients in the morning or at bedtime, 50 hypertensive patients had their night-time home and ambulatory BP successfully measured at the baseline and 6 months. In addition, three night-time home BP readings were taken during sleeping hours (at 2, 3, and 4 o'clock) for 6 months., Results: The mean reduction in night-time BP did not differ significantly between home and ambulatory BP monitoring (10.4 ± 17.9/6.0 ± 12.0 vs. 13.3 ± 14.6/7.6 ± 8.9 mmHg, P = 0.219/0.344), but the differences varied among individual patients. The reduction in night-time BP according to home BP monitoring was significantly correlated with the value obtained with ambulatory BP monitoring (r = 0.51/0.38, P < 0.001/=0.006). The reduction in night-time SBP according to home BP monitoring was significantly correlated with the reductions in left ventricular mass index (r = 0.385, P = 0.013, N = 41) and Sokolow-Lyon voltage (r = 0.335, P = 0.035, N = 40)., Conclusion: Home BP monitoring produces estimates of mean night-time BP reductions comparable to those from ambulatory monitoring, while the differences varied among individual patients. The reduction in night-time home BP according to home BP monitoring is significantly correlated with the reduction in left ventricular hypertrophy.

Backgrounds: Although the European Society of Hypertension International Protocol for the validation of blood pressure (BP) measuring devices has simplified the validation protocol, it is still not feasible for use in routine clinical practice., Objectives: We sought to devise a method for validating individual home blood pressure (HBP) monitors that is simple enough for use in routine clinical practice., Methods: We consecutively enrolled 92 hypertensive patients (mean age: 63.2 ± 14.6 years) from the hypertension clinic at the Columbia University Medical Center. Five sequential same-arm BP readings were recorded by a physician: first (D1), second (D2), and fourth (D3) using an HBP device; the third (M1) and fifth (M2) readings were taken manually using a mercury sphygmomanometer. Analyses focused on the absolute values of the differences in the BP values. In step 1, differences D2-M1, M1-D3, and D3-M2 were calculated and if two of three BP differences were within 5 mmHg (or 10 mmHg), the monitor 'passed'. When a monitor failed step 1, if either the difference between M1 and the average of D2 and D3, or the difference between D3 and the average of M1 and M2 was within 5 mmHg (or 10 mmHg), it was judged to have 'passed'., Results: We used only systolic blood pressure to simplify the protocol. In step 1, the number of monitors in which two of three BP differences were within 5 mmHg was 43 (46.7%) and those within 10 mmHg was 73 (79.4%) of 92 total monitors. Of those that failed the 5 mmHg criterion of step 1 (N = 49), 20 passed step 2. Therefore, a total of 63 monitors (68.5%) fulfilled the 5 mmHg criteria. Of 19 monitors that failed step 1 using the 10 mmHg criterion, 12 fulfilled the 10 mmHg criterion for step 2, resulting in 85 of the 92 (92.4%) monitors passing the test., Conclusion: This simplified validation protocol may be of value for the routine evaluation of HBP monitors in clinical practice.

In ambulatory blood pressure (BP) monitoring, nighttime BP has a superior ability to predict hypertensive target organ damage than awake BP. We evaluated whether nighttime BP, assessed by a home BP monitor, was associated with hypertensive target organ damage. We measured clinic BP, out-of-clinic BP including nighttime home BP, and the urinary albumin:creatinine ratio (UACR) in 854 patients who had cardiovascular risk factors. Nighttime home BP was measured at 2:00, 3:00, and 4:00 am, in addition to clinic, awake ambulatory, nighttime ambulatory, and awake home BP. Nighttime home systolic BP (SBP) was slightly higher than nighttime ambulatory SBP (difference, 2.6 mm Hg; P<0.001). Clinic (r=0.186), awake ambulatory (r=0.173), nighttime ambulatory (r=0.194), awake home (r=0.298), and nighttime home (r=0.311) SBPs were all associated with log-transformed UACR (all P<0.001). The correlation coefficient for the relationship between nighttime home SBP and log-transformed UACR was significantly greater than that for the relationship between nighttime ambulatory SBP and log-transformed UACR (P<0.001). The goodness of fit of the association between SBP and UACR was improved by adding nighttime home SBP to the other SBPs (P<0.001). Nighttime home diastolic BP also improved the goodness-of-fit of the association between diastolic BP and UACR (P=0.001). Similar findings were observed for the left ventricular mass index in the subgroup (N=594). In conclusion, nighttime home BP is slightly different from (but comparable to) nighttime ambulatory BP. The addition of nighttime home BP to other BP measures improves the association of BP with hypertensive target organ damage.

Background: We aimed to investigate the association of the change in the ambulatory arterial stiffness index (AASI) with that in carotid-femoral pulse wave velocity (cfPWV) during treatment with antihypertensive medication., Methods: We enrolled 207 hypertensive patients treated with olmesartan monotherapy for 12 weeks. Patients were randomly assigned to treatment with hydrochlorothiazide (HCTZ; n = 104) or azelnidipine (n = 103) for 24 weeks. The cfPWV and 24-h ambulatory blood pressure monitoring (ABPM) results were assessed at baseline and 24 weeks later. The AASI was defined as 1 minus the regression slope of diastolic blood pressure (DBP) on systolic BP (SBP), and was calculated by standard and symmetric regression., Results: The changes in the AASI and symmetrical AASI were similar between the two groups, while cfPWV in the azelnidipine group decreased more than in the HCTZ group (P < 0.001). The change in AASI was not significantly correlated with change in cfPWV (r = 0.08, P = 0.26), whereas the change in symmetrical AASI was significantly but weakly correlated with change in cfPWV (r = 0.22, P < 0.001). The multivariable linear regression analysis revealed that the association of the change in symmetrical AASI with change in cfPWV remained significant even after adjustments for covariates derived from ABPM (regression coefficient (95% confidence interval): 1.33 (0.35-2.30), P = 0.01)., Conclusions: The present study demonstrated that neither AASI nor symmetrical AASI may be an unequivocal marker of arterial stiffness during antihypertensive treatment.

It is unknown whether home blood pressure (BP) variability reduction is associated with target organ damage (TOD) protection independently of home mean BP reduction. We enrolled 310 hypertensive patients whose systolic BP (SBP) at home was over 135 mm Hg. The subjects measured their BP in the morning and evening for 7 days. In addition, we measured urinary albumin excretion (UAE) as a marker of TOD before and after 6 months of candesartan treatment (+thiazidediuretics). At baseline, UAE was associated with average home SBP (r=0.24, P<0.001), the s.d. of home SBP (r=0.15, P=0.011), and the maximum home SBP (r=0.27, P<0.001). During the intervention, significant reductions were found in average home SBP (146±13 vs. 132±12 mm Hg, P<0.001), s.d. of home SBP (12.9±4.8 vs. 11.8±4.4 mm Hg, P<0.001), and maximum home SBP (172.5±18.0 vs. 155.9±17.5 mm Hg, P<0.001). UAE levels were significantly reduced after 6 months of therapy compared with baseline (18.9 vs. 12.1 mg g(-1) Cre, P<0.001). In multiple regression analysis, the treatment-induced reduction in UAE was significantly associated with that of average home BP (P=0.003) but was not associated with that of s.d. of home SBP or that of maximum home SBP. Home BP variability is not itself an interventional target beyond lowering mean home BP during anti-hypertensive treatment.

Day-by-day home blood pressure (BP) variability (BPV) was reported to be associated with increased cardiovascular risk. We aimed to test the hypothesis that the angiotensin II receptor blocker/calcium-channel blocker combination decreases day-by-day BPV more than the angiotensin II receptor blocker/diuretic combination does and investigated the mechanism underlying the former reduction. We enrolled 207 hypertensive subjects treated with olmesartan monotherapy for 12 weeks. The subjects were randomly assigned to treatment with hydrochlorothiazide (n = 104) or azelnidipine (n = 103) for 24 weeks. Home BP was taken in triplicate with a memory-equipped device in the morning and evening, respectively, for 5 consecutive days before each visit. Visits occurred at 4-week intervals. Home BPV was defined as within-individual SD of the 5-day home BP. Arterial stiffness was assessed by aortic pulse wave velocity at baseline and 24 weeks later. The reductions in home systolic BP were similar between the 2 groups, whereas the SD of home systolic BP decreased more in the azelnidipine group than in the hydrochlorothiazide group during the follow-up period (follow-up mean: 6.3 versus 7.1 mm Hg; P = 0.007). In the azelnidipine group, the change in aortic pulse wave velocity was independently associated with the change in SD of home systolic BP (regression coefficient ± SE = 0.79 ± 0.37; P = 0.036). This study demonstrated that the angiotensin II receptor blocker/calcium-channel blocker combination improved home BPV in addition to home BP reduction and that the reduction in home BPV was partly attributable to the arterial stiffness reduction by this combination.

Background: We evaluated the agreement between office blood pressure (OBP) measured by a mercury sphygmomanometer (Sphyg) and an automatic (Auto) device without any observers, and compared Auto and Sphyg OBP with ambulatory blood pressure (ABP) and home blood pressure (HBP)., Methods: OBP was measured in 75 hypertensive patients at two sites using an automatic monitor without a doctor or a nurse present and by Sphyg during three clinic visits. Between visits, monitoring of ABP and HBP was also performed., Results: The mean Auto OBP was similar to that of Sphyg OBP and the values were closely correlated (intraclass correlation coefficient=0.84 for systolic OBP and 0.91 for diastolic OBP); however, the difference between Auto and Sphyg systolic OBP (1.6 ± 8.2 mmHg) varied by the first office visit, sex, and the site. Auto systolic OBP was lower than both systolic awake ABP (137.1 ± 14.7 mmHg) and HBP (139.2 ± 15.6 mmHg). Auto systolic OBP and Sphyg OBP were similarly correlated with systolic awake ABP (both r=0.59, P<0.001). The mean Auto diastolic OBP was similar to that of Sphyg OBP (81.1 ± 11.3 vs. 80.3 ± 13.3 mmHg, P=0.20, intraclass correlation coefficient=0.91), and diastolic awake ABP and HBP. Auto diastolic OBP and Sphyg OBP were related to diastolic awake ABP (both r>0.68, P<0.001). In multivariable analyses, neither OBP measure was a significantly stronger predictor of out-of-office blood pressure than the other., Conclusion: Auto systolic OBP measured without a doctor or a nurse present was lower than systolic awake ABP and HBP. Auto and rigorously assessed Sphyg OBP had similar means and were similarly related to awake ABP. Auto OBP might be an advantageous alternative to Sphyg measurements in the usual clinic setting.

Background: Asleep blood pressure (BP) has been shown to better reflect cardiovascular risk than awake BP in hypertensive patients. This study investigated the correlation of brain natriuretic peptide (BNP) to asleep BP during antihypertensive treatment., Methods: In the Japan Morning Surge-Target Organ Protection (J-TOP) study, which was an open-label multicenter trial to compare bedtime or awakening dosing of candesartan (+ diuretics as needed) among individuals with home SBP higher than 135  mmHg, we evaluated 254 hypertensive patients who underwent ambulatory BP monitoring, and measured their BNP at baseline and after 6th month of treatment., Results: At follow-up, the decrease in log-transformed BNP was significantly related to the decrease in asleep SBP (r = 0.27, P < 0.001); the relationship remained significant (β = 0.20, P = 0.002) even after adjusting for the decrease in the awake SBP (β = 0.001, P = 0.991). When we divided participants by their time of candesartan administration, the relationship between the decrease in log-transformed BNP and asleep SBP was still significant in both the awakening-dosing group (β = 0.21, P = 0.028) and the bedtime-dosing group (β = 0.21, P = 0.029). Furthermore, this relationship was strong in the participants who were receiving diuretics., Conclusion: The decrease in BNP is associated with asleep BP reduction by candesartan (+ diuretics as needed) over and above the awake BP reduction, regardless of the time of administration.

Background: Our aim was to assess whether home blood pressure (HBP) and ambulatory BP monitoring measurement (ABPM), in addition to office BP (OBP) predict changes of cardiovascular biomarkers during antihypertensive treatment., Methods: Two hundred and fifty-two hypertensive patients (mean age, 68 years; men: 41%) underwent measurements of OBP, HBP, ABPM, and cardiovascular biomarkers (urinary albumin excretion (UAE) and brain natriuretic peptide (BNP)) before and after 6 months of treatment with candesartan (± thiazide-diuretics)., Results: During the intervention, the OBP, HBP, daytime and night-time BP, and UAE levels were all significantly reduced (all P < 0.01). BNP was reduced only in the patients using diuretics (P = 0.003). For predicting the treatment-induced change in UAE, each of home systolic BP (SBP) and night-time SBP changes, but not daytime SBP change, had independent and significant value beyond OBP measurement (both P < 0.05). In contrast, for predicting the treatment-induced change in BNP, night-time SBP changes, but not home or daytime SBP changes, had significant value beyond OBP measurement (both P < 0.05). Patients who achieved a reduction in all three SBP parameters (office, home, and night-time SBP; n = 122) showed a more significant reduction of UAE compared with those who did not (-52.6 vs. -32.5%; P = 0.001), and patients who achieved a reduction in both office and night-time SBP (n = 134) showed a more significant reductions of BNP than those who did not (-12.9 vs. +12.8%; P < 0.05)., Conclusions: HBP and ABPM measurements, particularly night-time SBP values provide additional information for predicting treatment-induced changes of cardiovascular biomarkers when used in conjunction with office SBP measurement during antihypertensive treatment., (© 2012 American Journal of Hypertension, Ltd.)

Objectives: To clarify the implications of the home arterial stiffness index (HASI), we compared HASI with other arterial stiffness measures and investigated the association between HASI and hypertensive target organ damage (TOD)., Methods: We assessed brachial-ankle pulse wave velocity (baPWV) and the carotid augmentation index (cAIx) as measures of arterial stiffness and wave reflection, and the left ventricular mass index (LVMI), carotid intima-media thickness (IMT) using ultrasonography, and the urinary albumin/creatinine ratio (UACR) as measures of TOD in 356 never-treated hypertensive subjects. Home blood pressure (BP) was taken in triplicate in the morning and evening, respectively, for 14 consecutive days with a memory-equipped device. HASI was defined as 1 minus the respective regression slope of diastolic on systolic BP., Results: HASI was significantly correlated with age (r = 0.32, P < 0.001), home pulse pressure (r = 0.36, P < 0.001), morning-evening difference in home systolic BP (r = -0.29, P < 0.001), baPWV (r = 0.18, P < 0.001), cAIx (r = 0.16, P = 0.002), carotid IMT (r = 0.26, P < 0.001), and UACR (r = 0.24, P < 0.001), but not with LVMI (r = 0.05, P = 0.38). After adjustment for age and sex, the significant correlation between HASI and baPWV/cAIx was lost. In multivariate regression analyses, HASI and baPWV were significantly associated with carotid IMT (standardized β = 0.21, P<0.001; β = 0.14, P = 0.014) and UACR (β = 0.13, P = 0.018; β = 0.21, P < 0.001), independently of age, sex, and home mean arterial pressure. On the other hand, cAIx was independently associated only with LVMI (β = 0.24, P < 0.001)., Conclusion: These findings indicate that HASI adds nothing to the existing measures of arterial stiffness, but might be a BP component that can aid in the detection of carotid atherosclerosis and renal damage, similar to PWV., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Morning blood pressure surge (MBPS) has been shown to be a risk factor for cardiovascular disease and is associated with vascular remodeling. This study investigated whether the cerebrovascular risk of MBPS is modified by low-grade inflammation., Methods: We evaluated ambulatory BP, high sensitivity C-reactive protein (hsCRP), and brain MRI at baseline in 514 Japanese hypertensive patients, and followed them for the incidence of stroke for an average of 41 months (range: 1-68 months, 1751 person-years)., Results: MBPS was significantly correlated with the hsCRP level in patients with the highest quartile of MBPS, but not in the other quartiles. The odds ratio for silent cerebral infarcts (SCIs) was significantly higher only in patients in the highest quartile of MBPS with higher (above median) hsCRP [odds ratio 2.74, 95% confidence interval (CI) 1.42-5.30] in comparison with those in other quartiles of MBPS and with lower (below median) hsCRP. Conversely, being in the highest quartile of MBPS and having a higher hsCRP were independently and additively associated with an increased risk for clinical stroke events (both the highest quartile of MBPS and the higher hsCRP; hazard ratio [HR] 5.77, 95%CI 2.11-15.81, only the highest quartile of MBPS; HR 3.03, 95%CI 0.89-10.33, only the higher hsCRP; HR 2.89, 95%CI 1.12-7.47), even after adjusting for confounding factors., Conclusion: Exaggerated MBPS and increased low-grade inflammation independently increase the risk of stroke, while the relationship between exaggerated MBPS and the presence of SCIs is slightly affected by low-grade inflammation., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Ambulatory blood pressure (BP) (ABP) is a better predictor of adverse cardiovascular events than office BP (OBP). Owing to the extensive literature on the 'white coat effect', it is widely believed that ABP tends to be lower than OBP, with statements to this effect in Joint National Committee VII. However, recent evidence suggests that the difference varies systematically with age., Methods: We searched PubMed to identify population studies, published before April 2009, which assessed OBP and either ABP or home BP (HBP). On account of significant heterogeneity in the outcomes, random effect models were used for the meta-analyses., Results: OBP increased with age more steeply than awake ABP. OBP became higher than awake systolic/diastolic ABP at the age of 51.3/42.7 years in men (13 studies, N=3562) and 51.9/42.3 years in women (11 studies, N=2585). In the data in which OBP and HBP were measured (eight studies, N=4916), OBP was higher than HBP at all ages. In the data in which OBP, awake ABP, and HBP were all measured (two studies, N=895), awake ABP was higher than HBP at younger ages, becoming similar at the older age., Conclusion: OBP tends to be higher than awake ABP only after the age of 50 years for systolic and after the age of 45 years for diastolic BP, but is lower than ABP at younger ages; in contrast OBP tends to exceed HBP at all ages.

The maximum office systolic blood pressure (SBP) has been shown to be a strong predictor of cardiovascular events, independently of the mean SBP level. However, the clinical implications of maximum home SBP have never been reported. We investigated the association between the maximum home SBP and target organ damage (TOD). We assessed the left ventricular mass index (LVMI) and carotid intima-media thickness (IMT) using ultrasonography and the urinary albumin/creatinine ratio (UACR) as measures of TOD in 356 never-treated hypertensive subjects. Home BP was taken in triplicate in the morning and evening, respectively, for 14 consecutive days with a memory-equipped device. The maximum home SBP was defined as the maximum mean triplicate BP reading in the 14-day period for each individual and was significantly correlated with LVMI (r=0.51, P<0.001), carotid IMT (r=0.40, P<0.001), and UACR (r=0.29, P<0.001). The correlation coefficients with LVMI and carotid IMT were significantly larger for the maximum home SBP than the mean home SBP. In multivariate regression analyses, the maximum home SBP was independently associated with LVMI and carotid IMT, regardless of the mean home BP level. In the prediction of left ventricular hypertrophy and carotid atherosclerosis, the goodness-of-fit of the model was significantly improved when the maximum home SBP was added to the sum of the mean office and home BPs (P=0.002 and P<0.001, respectively). These findings indicate that assessment of the maximum home SBP, in addition to the mean home SBP, might increase the predictive value of hypertensive TOD in the heart and artery.

Objectives: It is not well known how clinic, home, and ambulatory measures of blood pressure (BP) correlate with each other. We performed this study to clarify the level of agreement among these different BP measures., Materials and Methods: We enrolled 56 hypertensive patients (mean age: 60 ± 14 years; 54% were females). The study consisted of three clinic visits, self-monitoring of home BP between visits, and ambulatory blood pressure (ABP) monitoring at the second visit. Patients were given a home BP monitor programmed to automatically take three consecutive readings at fixed intervals of 1 min. The associations between clinic BP (mercury sphygmomanometer and HEM-5001), home BP (the average of morning and evening, second and third BP readings), and average awake ABP were compared using the intraclass correlation for agreement and Bland-Altman plots., Results: The averages of clinic sphygmomanometer, clinic HEM-5001, awake ABP, and home BP were 129 of 77, 131 of 76, 131 of 79, and 133 of 77 mmHg, respectively. Clinic BP by HEM-5001 was strongly correlated with that of mercury sphygmomanometer. Home systolic blood pressure was moderately correlated with awake ABP, but mercury diastolic blood pressure (DBP) was more closely correlated with awake DBP than home DBP., Conclusion: Clinic BP measured with the automated monitor could be used as an alternative for the evaluation of BP in the office. Under rigorously standardized conditions, clinic and home BP could be used as an alternative to awake ABP.

This study was performed to test whether morning hypertension defined by the morning-evening difference in home blood pressure (BP) (MEdif) and the average of morning and evening BP (MEave) is a determinant of concentric left ventricular hypertrophy (LVH). The authors enrolled patients with untreated hypertension and performed echocardiography and home BP monitoring for 14 consecutive days. All patients were classified into 4 groups by the MEave and MEdif and morning hypertension was defined by MEave ≥135 mm Hg and MEdif ≥15 mm Hg. Left ventricular (LV) geometry was classified as normal, concentric remodeling, eccentric LVH, or concentric LVH. The morning hypertensive patients had a higher LV mass index and relative wall thickness than the other groups. According to multivariable logistic regression analysis, morning hypertensive patients had a significantly increased risk of the concentric LVH (odds ratio, 6.5; 95% confidence interval, 2.5-17.2; P<.001) compared with home normotensive patients with MEdif <15 mm Hg, after adjusting for confounders. Moreover, even among the home normotensives (white-coat hypertensives), patients with MEdif ≥15 mm Hg had a higher percentage of concentric remodeling than those with MEdif <15 mm Hg (32.5% vs 14.7%, P=.017). Morning hypertension defined by the MEdif and MEave is a strong determinant of concentric LVH, suggesting that this definition could be used to determine the cardiovascular risk of morning hypertension., (© 2010 Wiley Periodicals, Inc.)

The authors evaluated the relationship of hypertensive target organ damage to masked hypertension assessed by ambulatory blood pressure (BP) and home blood pressure (HBP) monitoring in 129 participants without taking antihypertensive medication. Masked hypertension was defined as office BP < or =140/90 mm Hg and 24-hour ambulatory BP > or =130/80 mm Hg. The masked hypertensive participants defined by 24-hour ambulatory BP (n=13) had a higher serum glucose level (126 vs 96 mg/dL, P=.001) and urinary albumin-creatinine ratio (38.0 vs 7.5 mg/gCr, P<.001) than the normotensive participants (n=74); however, these relationships were not observed when the authors defined groups using HBP (> or =135/85 mm Hg). Masked hypertension by both 24-hour ambulatory BP and HBP had a higher urinary albumin-creatinine ratio than normotension by both 24-hour ambulatory BP and HBP (62.1 vs 7.4 mg/gCr, P=.001), and than masked hypertension by HBP alone (9.3 mg/gCr, P=.009). Masked hypertension defined by 24-hour ambulatory BP is associated with an increased serum glucose level and urinary albumin-creatinine ratio, but these relationships are not observed in masked hypertension defined by HBP.

Objectives: There has been no report investigating the impact of the arterial stiffness reduction induced by antihypertensive medications on the improvement of target organ damage in hypertension. The aim of this study was to assess the association of the change in pulse wave velocity (PWV) with that in urinary albumin excretion as a measure of renal damage., Methods: We studied 404 treated hypertensive patients (mean age, 70.5 +/- 9.5 years), who were allocated to either an active treatment group (doxazosin and atenolol when needed) or a control group. Blood pressure, urinary albumin-to-creatinine ratio (UACR), and brachial-ankle PWV (baPWV) were measured at baseline and after 6 months of treatment., Results: In the total population, home/office SBP, UACR, and baPWV decreased significantly from the baseline. In multivariate regression analyses, DeltabaPWV was significantly associated with DeltaUACR, independent of Deltahome SBP (beta = 0.21, P < 0.001). When the patients were divided into a group with DeltabaPWV of at least 0 cm/s (positive DeltaPWV) and a group with DeltabaPWV of less than 0 cm/s (negative DeltaPWV), the reduction of UACR was greater in the latter group, even after adjustment for the covariates including the change in home SBP. These results were essentially the same when office SBP was entered in place of home SBP, and similar both in the active treatment group and the control group., Conclusion: These findings suggest that the arterial stiffness reduction induced by antihypertensive medications is associated with the improvement of renal damage, independent of home/office SBP reduction.

Background: Prehypertension is associated with an increased risk of the development of hypertension and subsequent cardiovascular disease. However, it is unclear whether the increased risk of cardiovascular disease associated with prehypertension varies by duration of follow-up (i.e., the first 5 years vs. second 5 years) or varies between nonelderly and elderly individuals., Methods: We enrolled 11,000 community dwelling persons (6739 women and 4261 men, aged 18-90 years) from the Japanese general population, followed them for an average of 10.7 +/- 2.4 years (117,517 person-years) and evaluated the incidence of cardiovascular events (including both stroke and myocardial infarction)., Results: In the full cohort, prehypertension was associated with a 45% higher risk of cardiovascular events than normal blood pressure after adjusting for traditional cardiovascular risk factors (hazard ratio = 1.45, P = 0.03). The risk of cardiovascular events with prehypertension during the second 5-year period was elevated in the nonelderly subgroup (<65 years) (hazard ratio = 2.13, P = 0.01), but not in the elderly subgroup (>or=65 years) (hazard ratio = 0.93, P = 0.82) (P = 0.054 for the difference in hazard ratio). The elevated risk with prehypertension during the first 5-year period was not significant in either the nonelderly (hazard ratio = 1.60, P = 0.36) or elderly (hazard ratio = 1.19, P = 0.63) group. However, the risks with prehypertension were not statistically different between the first and second 5-year period., Conclusion: Prehypertension is associated with an increased 10-year risk of cardiovascular disease; the provocative finding that this risk may be especially elevated during the second 5-year period in the nonelderly requires confirmation in a larger cohort.

Background: There have been few reports on the relationship between variation in the diurnal pulse rate (PR) in relation to a nondipper blood pressure (BP) pattern and cardiovascular events in elderly hypertensives., Methods: Ambulatory BP monitoring (ABPM) was conducted at baseline in 811 older Japanese hypertensives (clinical BP >140/90 mm Hg; age >50 years old) enrolled in the Jichi Medical School ABPM study, wave 1. They were followed up for an average of 41 months, and the incidence of subsequent cardiovascular event and death was evaluated. PR nondipping status was defined as (awake PR - sleep PR)/awake PR <0.1., Results: The mean age of patients was 72.3 +/- 9.8 years (311 men and 500 women). The nondipper patients had a higher risk of cardiovascular events (11.5% vs. 6.1%, P = 0.006) and stroke (9.9% vs. 5.7%, P = 0.039) than the dippers. Patients were classified into four subgroups: BP dipping plus PR dipping status (n = 471), BP dipping plus PR nondipping (n = 37), BP nondipping plus PR dipping (n = 250), and BP nondipping plus PR nondipping (n = 53). The combination of BP and PR nondipping constituted a higher risk of cardiovascular events and stroke than the other three combinations combined (cardiovascular events: 17.0% vs. 7.5%, P = 0.015; stroke: 17.0% vs. 6.6%, P = 0.005). On Cox proportional hazards modeling, BP nondipping with PR nondipping led to a significant synergistic increase in the risk of stroke (hazard ratio: 8.92; 95% confidence interval: 1.03-77.5, P = 0.048)., Conclusions: A blunted PR dip might predict a stroke in elderly hypertensives with a nondipping BP status.

Objectives: To study the impact of the dosing time of an angiotensin II receptor blocker (ARB) titrated by self-measured home blood pressure (HBP) on cardiorenal damage in hypertensives., Methods: We conducted an open-label multicenter trial, the J-TOP study, that enrolled 450 hypertensives with self-measured systolic HBP more than 135 mmHg. The study patients were stratified into three groups according to the difference between their morning and evening SBPs difference: a morning hypertension group (morning and evening difference at least 15 mmHg; n = 170), a morning and evening hypertension group (0 mmHg < or = morning and evening difference <15 mmHg; n = 198), and an evening hypertension group (morning and evening difference <0 mmHg; n = 82). Individuals were then randomly allocated to receive bedtime dosing or awakening dosing of candesartan (+/- diuretic as needed) titrated to achieve a target systolic HBP less than 135 mmHg. The 6-month change in the urinary albumin/creatinine ratio (UACR) was assessed., Results: In total patients, the UACR was more markedly reduced in the bedtime-dosing group than in the awakening-dosing group (-45.7 vs. -34.5%, P = 0.02), whereas there were no differences in the reduction of any of the HBPs including the sleep blood pressures (BPs) between the two groups. Among the three subgroups stratified by the morning and evening difference, the difference in the UACR reduction between the bedtime-dosing and awakening-dosing groups was only significant in the morning hypertension group (-50.6 vs. -31.3%, P = 0.02)., Conclusion: In HBP-guided antihypertensive treatment in hypertensives, bedtime dosing of an ARB may be superior to awakening dosing for reducing microalbuminuria.

We aimed this study to test the hypotheses that heart rate (HR) variability, evaluated by ambulatory blood pressure monitoring (ABPM), predicts risk of incident cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM). ABPM was performed in 200 normotensive or hypertensive subjects with T2DM and 257 hypertensive subjects without diabetes (the mean age: 66.9+/-9.2 years; 38% were male). All subjects were untreated at the time of ABPM, and were followed for 67+/-27 months. Various measures of HR variability-standard deviation (s.d.) of HR, the root-mean-square of successive differences (RMSSD) of HR, systolic blood pressure (SBP)-HR relationships evaluated by slope and coefficients of correlation between SBP and HR-were used for the analyses. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals, after controlling for age, sex, body mass index, serum creatinine and 24-h SBP. During follow-up, there were 34 cardiovascular events. Awake HR variability in diabetics was smaller than non-diabetics, but sleep HR variability was similar between the groups. In multivariable analyses, increased sleep HR variability evaluated by s.d. and RMSSD of sleep HR, and slope and correlation coefficient of SBP-HR each was independently associated with the increased risk of CVD in T2DM. For non-diabetics, decreased slope of 24 h SBP-HR, and decreased correlation of 24 h SBP-HR were associated with increased risk of CVD. In conclusion, increased HR variability during sleep was a predictor for incident CVD in T2DM, but not in non-diabetics. Increased HR variability at night would reflect pathophysiological mechanism of T2DM.

Background: Excess visceral adipose tissue (VAT) is considered to be a component in metabolic syndrome, an accumulation of cardiovascular risk factors that includes increased blood pressure; however, there are no previous data showing an association between increases in the VAT-subcutaneous adipose tissue (SAT) ratio and difficult-to-treat hypertension., Methods: In 572 patients who had cardiovascular risk factors and who were under stable antihypertensive treatment, we evaluated whether the VAT-SAT ratio, as assessed by abdominal computed tomography, predicted difficult-to-treat hypertension, which we defined as an elevation of clinic blood pressure (i.e., clinic blood pressure >or=140/90 mmHg) during treatment with at least three antihypertensive drugs., Results: In men, an elevated VAT-SAT ratio [odds ratio (OR) 1.44 per 1 SD (0.52), 95% confidence interval (CI) 1.08-1.92] and alcohol drinking habit (OR 2.16, 95% CI 1.07-4.36) were significant predictors of difficult-to-treat hypertension, independently of the presence of metabolic syndrome or the insulin level. However, when we included diuretic use in the diagnosis of difficult-to-treat hypertension (i.e., resistant hypertension), the significance of the VAT-SAT ratio disappeared (P = 0.06), and a decreased estimated glomerular filtration rate (OR 0.74 per 10 ml/min per 1.73 m, 95% CI 0.58-0.94) and alcohol drinking habit (OR 4.31, 95% CI 1.74-10.68) were the significant predictors. In contrast, in women, the VAT-SAT ratio did not predict difficult-to-treat hypertension (P = 0.18)., Conclusion: An increased VAT-SAT ratio was associated with difficult-to-treat hypertension in men, but not with resistant hypertension, suggesting that diuretic use may partly affect the relationship between the VAT-SAT ratio and difficult-to-treat hypertension.

There has been no report comparing the changes in home blood pressure (HBP) and target organ damage between depressive and nondepressive hypertensives receiving antihypertensive therapy based on HBP monitoring. This study was a multicenter prospective study conducted by 7 doctors at 2 institutions. The authors prospectively studied 42 hypertensive patients with home systolic blood pressure >135 mm Hg. Participants were divided into a depression group (Beck Depression Inventory score >10; n=21) and a nondepression group (Beck Depression Inventory score <9, matched for HBP level; n=21). The authors performed antihypertensive therapy to reduce home systolic blood pressure to below 135 mm Hg and, 6 months later, evaluated the urinary albumin/creatinine ratio (UACR). Although patients in the depression group tended to require the addition of a greater number of medications than those in the nondepression group (2.3+/-1.0 vs 1.7+/-1.0 drugs, P<.05), HBP was reduced similarly in both groups at 6 months (depression group: 150+/-17/78+/-11 mm Hg to 139+/-11/73+/-8 mm Hg, P<.001; nondepression group: 150+/-11/76+/-9 mm Hg to 135+/-9/70+/-8 mm Hg, P<.01). The reduction of UACR was smaller in the depression group than in the nondepression group (2.4 vs 10.1 mg/gCr, P<.05). Depressive hypertensive patients required a larger number of antihypertensive drugs to control HBP, and showed a smaller reduction in UACR than nondepressive hypertensives.

Background: The significance of home blood pressure (BP) measurement in type 2 diabetes (T2DM) has not been well investigated. We aimed to test the hypotheses that home BP is more closely associated with target-organ damage than clinic BP, and that the presence of prediabetes/T2DM enhances the impact of home BP measurement., Methods: We studied 551 hypertensives (99 diabetics and 452 nondiabetics) whose self-measured systolic BP (SBP) was >135 mm Hg while on medication. The subjects were followed for 6 months after allocation to either a control group or an active treatment group. The changes in clinic BP and home BP were analyzed in relation to the changes in the spot urine albumin-creatinine ratio (UAR)., Results: The extent of clinic and home BP reduction was similar between the diabetic and nondiabetic groups. The change in UAR in nondiabetics was significantly associated with the extent of SBP reduction in the clinic (r = 0.19), morning (r = 0.33), and evening (r = 0.22, all P < 0.01). In contrast, in the diabetic group, the change in UAR was significantly associated with the changes in morning SBP (r = 0.23, P = 0.02) and evening SBP (r = 0.39, P < 0.001), but not with clinic BP. The correlation with evening SBP in the diabetic group tended to be stronger than the nondiabetic group., Conclusions: In hypertensives with prediabetes/T2DM, changes in home BP were better than changes in clinic BP to predict changes in UAR. In particular, this suggests the hypothesis that aggressive control of evening home BP might be equally or more important to morning BP in hypertensives with prediabetes/T2DM.

Objective: It has not been established whether nocturnal nondipping of heart rate (HR) predicts future cardiovascular disease (CVD). We performed this study to test the hypothesis that nocturnal nondipping of HR predicts the risk of incident CVD independent of nocturnal blood pressure dipping pattern., Methods: Ambulatory blood pressure monitoring was performed in 457 uncomplicated patients, who were being treated or evaluated for hypertension. They were followed for an average of 72 +/- 26 months. Nondipping HR was defined as a night/day HR ratio greater than 0.90. We chose two outcomes for this analysis: CVD events (defined as stroke, myocardial infarction, or sudden cardiac death) and all-cause mortality. Cox regression analyses (stepwise method) were used to estimate hazard ratios and their 95% confidence interval after adjusting for covariates., Results: In univariate analysis, increased sleep HR and nondipping of HR were associated with increased risk of CVD and all-cause mortality, but awake HR was not. In multivariable analyses, HR nondipping status significantly predicted an increased risk of CVD events (hazard ratio, 2.37; 95% confidence interval, 1.22-4.62; P = 0.01), but not for all-cause mortality. Increased 24-h HR was significantly associated with increased risk of all-cause mortality (hazard ratio, 1.67; 95% confidence interval, 1.11-2.51; P = 0.01)., Conclusion: The risk of future CVD was shown to be 2.4 times higher in those whose HR does not exhibit the typical nocturnal decline. The relationship was independent of nondipping of SBP and was not dependent on diabetes status or blood pressure level.

The aim of this study was to compare the effects between calcium channel blockers and diuretics when used in combination with angiotensin II receptor blocker on aortic systolic blood pressure (BP) and brachial ambulatory systolic BP. We conducted a prospective, randomized, open-label, blinded end point study in 207 hypertensive patients (mean age: 68.4 years). Patients received olmesartan monotherapy for 12 weeks, followed by additional use of azelnidipine (n=103) or hydrochlorothiazide (n=104) for 24 weeks after randomization. The central BP by radial artery tonometry, aortic pulse wave velocity, and ambulatory BP were assessed at baseline and 24 weeks later. After adjustment for baseline covariates, the extent of the reduction in central systolic BP in the olmesartan/azelnidipine group was significantly greater than that in the olmesartan/hydrochlorothiazide group (the between-group difference was 5.2 mm Hg; 95% CI: 0.3 to 10.2 mm Hg; P=0.039), whereas the difference in the reduction in brachial systolic BP between the groups was not significant (2.6 mm Hg; 95% CI: -2.2 to 7.5 mm Hg; P=0.29). The aortic pulse wave velocity showed a significantly greater reduction for the olmesartan/azelnidipine combination than for the olmesartan/hydrochlorothiazide combination (0.8 m/s; 95% CI: 0.5 to 1.1 m/s; P<0.001) after adjustment for covariates. The extent of the reduction in brachial ambulatory systolic BP was similar between the groups. These data showed that the combination of olmesartan (20.0 mg) and azelnidipine (16.0 mg) had a more beneficial effect on central systolic BP and arterial stiffness than the combination of olmesartan (20.0 mg) and hydrochlorothiazide (12.5 mg), despite the lack of a significant difference in brachial systolic BP reduction between the 2 treatments.