水野 裕之

BACKGROUND: Less than 50% of non-Hispanic Asian adults taking antihypertensive medication have controlled blood pressure. METHODS: We compared non-persistence and low adherence to antihypertensive medication between non-Hispanic Asian and other race/ethnicity groups among US adults ≥66 years who initiated antihypertensive medication between 2011 and 2018 using a 5% random sample of Medicare beneficiaries (non-Hispanic Asian, n = 2,260; non-Hispanic White, n = 56,000; non-Hispanic Black, n = 5,792; Hispanic, n = 4,212; and Other, n = 1,423). Non-persistence was defined as not having antihypertensive medication available to take in the last 90 of 365 days following treatment initiation. Low adherence was defined as having antihypertensive medication available to take on <80% of the 365 days following initiation. RESULTS: In 2011-2012, 2013-2014, 2015-2016 and 2017-2018, the proportion of non-Hispanic Asian Medicare beneficiaries with non-persistence was 29.1%, 25.6%, 25.4% and 26.7% (p-trend = 0.381), respectively, and the proportion with low adherence was 58.1%, 54.2%, 53.4% and 51.6%, respectively (p-trend = 0.020). In 2017-2018, compared with non-Hispanic Asian beneficiaries, non-persistence was less common among non-Hispanic White beneficiaries (risk ratio 0.74 [95%CI, 0.64-0.85]), non-Hispanic Black beneficiaries (0.80 [95%CI 0.68-0.94]) and those reporting Other race/ethnicity (0.68 [95%CI, 0.54-0.85]) but not among Hispanic beneficiaries (1.04 [95%CI, 0.88-1.23]). Compared to non-Hispanic Asian beneficiaries, non-Hispanic White beneficiaries and beneficiaries reporting Other race/ethnicity were less likely to have low adherence to antihypertensive medication (relative risk 0.78 [95%CI 0.72-0.84] and 0.84 [95%CI 0.74-0.95], respectively); there was no association for non-Hispanic Black or Hispanic beneficiaries. CONCLUSIONS: Non-persistence and low adherence to antihypertensive medication were more common among older non-Hispanic Asian than non-Hispanic White adults.

BACKGROUND: Inconsistencies between office and out-of-office blood pressure (BP) values (described as white-coat hypertension or masked hypertension) may be attributable in part to differences in the BP monitoring devices used. METHODS: We studied consistency in the classification of BP control (well-controlled BP vs. uncontrolled BP) among office, home, and ambulatory BPs by using a validated "all-in-one" BP monitoring device. In the nationwide, general practitioner-based multicenter HI-JAMP study, 2,322 hypertensive patients treated with antihypertensive drugs underwent office BP measurements and 24-h ambulatory BP monitoring (ABPM), consecutively followed by 5-day home BP monitoring (HBPM), for a total of seven BP measurement days. RESULTS: Using the thresholds of the JSH2019 and ESC2018 guidelines, the patients with consistent classification of well-controlled status in office (<140 mmHg) and home systolic BP (SBP) (<135 mmHg) (n=970) also tended to have well-controlled 24-h SBP (<130 mmHg) (n=808, 83.3%). The patients with consistent classification of uncontrolled status in office and home SBP (n=579) also tended to have uncontrolled 24-h SBP (n=444, 80.9%). Among the patients with inconsistent classifications of office and home BP control (n=803), 46.1% had inconsistent ABPM-vs.-HBPM out-of-office BP control status. When the 2017 ACC/AHA thresholds were applied as an alternative, the results were essentially the same. CONCLUSIONS: The combined assessment of office and home BP is useful in clinical practice. Especially for patients whose office BP classification and home BP classification conflict, the complementary clinical use of both HBPM and ABPM might be recommended.

BACKGROUND: Non-dipper and riser patterns of nocturnal blood pressure (BP) are risk factors for cardiovascular disease (CVD), including heart failure (HF). However, the risk associated with a disrupted nocturnal pattern of heart rate is not well known. OBJECTIVES: To investigate whether the nighttime heart rate is a risk factor for HF, alongside nighttime BP phenotype. METHODS: The practitioner-based, nationwide, prospective Japan Ambulatory Blood Pressure Monitoring Prospective (JAMP) study included patients with ≥ 1 CVD risk factor but without symptomatic CVD at baseline. All patients underwent 24-h ambulatory BP monitoring at baseline and were followed annually. Nocturnal heart rate dipping (%) was calculated as 100•[1 - nighttime/daytime heart rate]. RESULTS: During a mean 4.5 years' follow-up in 6,359 patients (mean age 68.6 years), there were 306 CVD events (119 stroke, 99 coronary artery disease, and 88 HF). A 10-beats/min increase in nighttime heart rate was significantly associated with a 36-47% increase in the risk of total CVD, stroke and HF events independently of office SBP and nighttime SBP (all p < 0.005). The CVD and HF risk associated with nocturnal heart rate dipping status was independent of office and 24-h systolic BP and nocturnal BP dipping status (p < 0.001). Performance of the final model for predicting HF including BP parameters was significantly improved by the addition of nocturnal heart rate dipping patterns (p = 0.038; C-statistic 0.852). CONCLUSION: Nighttime non-dipper and riser patterns of heart rate were associated with CVD especially HF, independently and additively of nocturnal BP dipping status, indicating the importance of antihypertensive strategies targeting nighttime hemodynamics. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/ ; Unique identifier: UMIN000020377.

Accurate blood pressure (BP) measurement is necessary for the evaluation and treatment of hypertension to prevent the progression of subclinical vascular disease, including arterial stiffness. We investigated the associations between brachial-ankle pulse wave velocity (baPWV), a measure of arterial stiffness, and each of office brachial systolic BP (SBP) with and without an observer present (attended or unattended office brachial SBP), attended or unattended office central SBP, and home brachial SBPs (specifically, the means of morning, evening, or morning-evening home brachial SBP) in patients being treated for hypertension. Measurements were performed among 70 adults (mean age, 67.0 ± 9.4 years; women, 51.4%) with a mean attended office brachial SBP of 127.6 ± 14.5 mmHg and mean baPWV of 16.3 ± 2.8 m/s. Univariate analysis showed that higher attended office brachial SBP, morning home brachial SBP, and morning-evening home brachial SBP were each statistically significantly associated with higher baPWV (r = 0.25, P = 0.04; r = 0.37, P = 0.002; and r = 0.32, P = 0.006, respectively). Multiple linear regression analysis with adjustments for traditional cardiovascular risk factors showed that only morning home brachial SBP was statistically significantly associated with baPWV [β = 0.06, 95% confidence interval (0.01-0.11), P = 0.02). In conclusion, higher morning home brachial SBP - but none of the office-measured SBP values - was associated with arterial stiffness.

Pulse transit time (PTT), which refers to the travel time between two arterial sites within the same cardiac cycle, has been developed as a novel cuffless form of continuous blood pressure (BP) monitoring. The aim of this study was to investigate differences in BP parameters, including BP variability, between those assessed by beat-to-beat PTT-estimated BP (eBPBTB) and those assessed by intermittent PTT-estimated BP at fixed time intervals (eBPINT) in patients suspected of having sleep disordered breathing (SDB). In 330 patients with SDB (average age, 66.8 ± 11.9 years; 3% oxygen desaturation index [ODI], 21.0 ± 15.0/h) from 8 institutes, PTT-estimated BP was continuously recorded during the nighttime. The average systolic eBPBTB, maximum systolic and diastolic eBPBTB, standard deviation (SD) of systolic and diastolic eBPBTB, and coefficient variation (CV) of systolic and diastolic eBPBTB were higher than the respective values of eBPINT (all P < 0.05). Bland-Altman analysis showed a close agreement between eBPBTB and eBPINT in average systolic BP and SD and CV of systolic BP, while there were disagreements in both minimum and maximum values of eBPBTB and eBPINT in patients with high systolic BP (P < 0.05). Although systolic BP variability incrementally increased according to the tertiles of 3%ODI in both eBPBTB and eBPINT (all P < 0.05), there was no difference in this tendency between eBPBTB and eBPINT. In patients with suspected SDB, the difference between eBPBTB and eBPINT was minimal, and there were disagreements regarding both the minimum and maximum BP. However, there were agreements in regard to the index of BP variability between eBPBTB and eBPINT.

Background The aim of this study was to investigate the association between night-to-night adherence to continuous positive airway pressure (CPAP) therapy and both home blood pressure (BP) level on the following day and seasonal variation in home BP in patients with obstructive sleep apnea. Methods and Results We analyzed 105 participants who had been diagnosed with obstructive sleep apnea (average apnea-hypopnea index, 49.7±18.4 per hour) and who were already receiving CPAP therapy. Home BP (twice every morning and evening) and CPAP adherence data were automatically transmitted to a server for 1 year. A mixed-effects model for repeated measures analysis was used to examine associations of night-to-night good CPAP adherence with day-to-day home BP within the same patient after adjusting for covariates. The average number of days in which patients achieved both CPAP adherence and morning or evening home BP measurement was 206.6±122.7 days (21 487 readings) and 191.2±126.3 days (20 170 readings), respectively. Good CPAP adherence (>4 hours per night of use) was achieved on the evening or morning before home BP measurements (86.8% and 86.9%, respectively). After adjustment for confounders, good CPAP adherence was negatively associated with morning home systolic BP (β, -0.663; P=0.004) and diastolic BP (β, -0.829; P<0.001). Morning home systolic BP in winter in the individuals with good CPAP adherence was significantly lower than that in individuals without such adherence (P<0.05). These associations were not found in evening home BP. Conclusions Good adherence to CPAP therapy was negatively associated with morning home BP on the following day in patients with obstructive sleep apnea. The association was remarkable in the winter season.

Central systolic blood pressure (cSBP) is an independent predictor of future cardiovascular disease. Unattended brachial SBP (bSBP) can eliminate the white-coat effect. However, unattended cSBP and unattended standing cSBP have never been reported. We aimed to compare bSBP and cSBP in attended, unattended, and unattended standing situations. We also aimed to compare the white-coat effect and unattended orthostatic BP change between bSBP and cSBP. Altogether, 104 hypertensive outpatients were included (mean age: 66.0 ± 9.8 years, 41.3% male, mean body mass index: 25.0 ± 4.5). Attended bSBP/cSBP values were 127.3 ± 15.7/119.2 ± 15.0, unattended bSBP/cSBP values were 122.7 ± 15.3/114.4 ± 15.1, and unattended standing bSBP/cSBP values were 123.6 ± 15.7/114.1 ± 14.8 mmHg (correlation coefficients/coefficients of determination between bSBP and cSBP: 0.971/0.943, 0.970/0.941, and 0.964/0.929, respectively; all p < 0.001). No significant difference was observed in the white-coat effect between bSBP and cSBP (4.6 ± 5.8 vs. 4.8 ± 5.7 mmHg). Although there was no significant difference between unattended sitting SBP and unattended standing SBP in terms of both bSBP and cSBP, a numerically small but significant difference was observed in the unattended orthostatic BP change between bSBP and cSBP (0.9 ± 8.0 vs. -0.3 ± 9.0 mmHg, p = 0.002). In conclusion, significant and strong correlations were observed between bSBP and cSBP in attended, unattended, and unattended standing BP measurements. The white-coat effect on bSBP was equivalent to that on cSBP. There was a numerically small but significant difference in the unattended orthostatic BP change between bSBP and cSBP.

BACKGROUND: Ambulatory and home blood pressure (BP) monitoring parameters are better predictors of cardiovascular events than are office BP monitoring parameters, but there is a lack of robust data and little information on heart failure (HF) risk. The JAMP study (Japan Ambulatory Blood Pressure Monitoring Prospective) used the same ambulatory BP monitoring device, measurement schedule, and diary-based approach to data processing across all study centers and determined the association between both nocturnal hypertension and nighttime BP dipping patterns and the occurrence of cardiovascular events, including HF, in patients with hypertension. METHODS: This practitioner-based, nationwide, multicenter, prospective, observational study included patients with at least 1 cardiovascular risk factor, mostly hypertension, and free of symptomatic cardiovascular disease at baseline. All patients underwent 24-hour ambulatory BP monitoring at baseline. Patients were followed annually to determine the occurrence of primary end point cardiovascular events (atherosclerotic cardiovascular disease and HF). RESULTS: A total of 6,359 patients (68.6±11.7 years of age, 48% men) were included in the final analysis. During a mean±SD follow-up of 4.5±2.4 years, there were 306 cardiovascular events (119 stroke, 99 coronary artery disease, 88 HF). Nighttime systolic BP was significantly associated with the risk of atherosclerotic cardiovascular disease and HF (hazard ratio adjusted for demographic and clinical risk factors per 20-mm Hg increase: 1.18 [95% CI, 1.02-1.37], P=0.029; and 1.25 [95% CI, 1.00-1.55], P=0.048, respectively). Disrupted circadian BP rhythm (riser pattern, nighttime BP higher than daytime BP) was significantly associated with higher overall cardiovascular disease risk (1.48 [95% CI, 1.05-2.08]; P=0.024), and especially HF (2.45 [95% CI, 1.34-4.48]; P=0.004) compared with normal circadian rhythm. CONCLUSIONS: Nighttime BP levels and a riser pattern were independently associated with the total cardiovascular event rate, in particular for HF. These findings suggest the importance of antihypertensive strategies targeting nighttime systolic BP. Registration: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000020377.

Objective To prolong the health expectancy, it is important to prevent age-related diseases, such as osteoporosis and cerebrovascular disease, which are major causes of a bedridden state. Early predictable biomarkers for these diseases are urgently required in the clinical setting. Three members of the fibroblast growth factor (FGF) family - FGF19, FGF21, and FGF23 - are designated as endocrine FGFs and play crucial roles in various metabolic processes. We tried to clarify the clinical utility of endocrine FGFs as biomarkers for age-related diseases in elderly patients. Methods We examined the serum endocrine FGF levels and analyzed their association with various clinical parameters in 73 outpatients >60 years old as a single-center cross-sectional study. Results In a multivariable linear regression analysis, FGF19 was associated with ALT, a history of cardiovascular disease, and medication with active vitamin D3. FGF21 was associated with the estimated glomerular filtration rate (eGFR), triglyceride level, and hypertension. FGF23 was associated with the eGFR and the serum levels of 1,25-dihydroxy vitamin D3 and TRACP5b. In addition, a receiver operating characteristics analysis revealed that the measurement of FGF21 and FGF23 was useful for detecting chronic kidney disease (CKD) and its complications, including cardiovascular disease and metabolic bone disorder. Conclusion The measurement of FGF21 and FGF23 may be useful for evaluating CKD and its complications. Using serum endocrine FGFs as biomarkers for age-related conditions may help prevent elderly patients from entering a bedridden state.

Constipation is associated with cardiovascular events. Changes to the intestinal microbiota by constipation can induce atherosclerosis, blood pressure rise, and cardiovascular events. Constipation increases with age and often coexists with cardiovascular risk factors. In addition, strain at stool causes blood pressure rise, which can trigger cardiovascular events such as congestive heart failure, arrhythmia, acute coronary disease, and aortic dissection. However, because cardiovascular medical research often focuses on more dramatic interventions, the risk from constipation can be overlooked. Physicians caring for patients with cardiovascular disease should acknowledge constipation and straining with it as important cardiovascular risk, and prematurely intervene to prevent it. The authors review and discuss the relationship between constipation and cardiovascular disease.

Research suggests that oxygen desaturation and sleep stage during obstructive sleep apnea (OSA) are related to the magnitude of high blood pressure (BP) in a laboratory setting. However, in a clinical setting, these associations have not been well studied. We used a noninvasive oscillometric BP measurement device to investigate the association between oxygen-triggered BP levels at the end of each OSA episode and the characteristics of the preceding OSA episode. In 42 newly diagnosed OSA patients (average age, 63.5±12.5 years; average apnea-hypopnea index, 32.6±18.2 per hour), 258 BP measurements were obtained at the end of OSA episodes. Hypoxia-peak systolic BP (SBP), defined as the maximum oxygen-triggered SBP value, was significantly higher in rapid eye movement sleep (144.9±19.9 mm Hg) than in non-rapid eye movement stage 1 sleep (129.5±15.1 mm Hg; P<0.001) and non-rapid eye movement stage 2 sleep (129.4±14.7 mm Hg; P<0.001). In a multivariate-linear mixed model, the lowest oxygen saturation percentage during each OSA episode was associated with increased hypoxia-peak SBP (-0.501 mm Hg; P<0.001), nocturnal SBP surge (-0.395 mm Hg; P<0.001), defined as the difference between the hypoxia-peak SBP and the mean nocturnal SBP, and maximum value of SBP surge (-0.468 mm Hg; P<0.001), defined as the difference between the hypoxia-peak SBP and the minimum nocturnal SBP independent of sleep stage. These values were not associated with the duration of each OSA episode. The contribution of rapid eye movement sleep and severe oxygen desaturation to OSA-related BP elevation measured with a noninvasive oscillometric method was determined in a clinical setting.

BACKGROUND: Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are prognostic biomarkers. Although these 2 peptides differ with regard to biological characteristics, there are few reports on the differences between BNP and NT-proBNP with regard to cardiovascular events or according to sex.Methods and Results:Between 2005 and 2012, this study analyzed 3,610 of 4,310 Japanese outpatients (mean age, 65 years; men, n=1,664; women, n=1,947) with a history of at least one cardiovascular event who were recruited to the Japan Morning Surge-Home Blood Pressure Study. During an average 4-year follow-up, there were 129 cardiovascular events. Both median BNP (21.1 pg/mL; IQR, 10.9-40.6 pg/mL vs. 16.2 pg/mL, IQR, 7.2-36.2 pg/mL, P<0.001) and median NT-proBNP (54.7 pg/mL; IQR, 30.2-102.6 pg/mL vs. 44.9 pg/mL, IQR, 20.7-92.6 pg/mL, P<0.001) were significantly higher in women than in men. A 1-SD increment in log-transformed BNP (hazard ratio [HR], 2.18; 95% CI: 1.53-3.10) and NT-proBNP (HR, 2.39; 95% CI: 1.73-3.31) was associated with a significant increase in cardiovascular events in women; in men, only NT-proBNP showed this association. There was an interaction between log-transformed BNP (P=0.007) or NT-proBNP (P=0.001) and cardiovascular events according to sex. CONCLUSIONS: Both BNP and NT-proBNP predicted cardiovascular outcomes in a large Japanese clinical population. BNP and NT-proBNP were significantly stronger predictors in women than in men.

We assessed the relationship between day-by-day home blood pressure (BP) variability and incident cardiovascular disease (CVD) in clinical practice. J-HOP study (Japan Morning Surge-Home Blood Pressure) participants underwent home BP monitoring in the morning and evening for a 14-day period, and their BP levels and BP variability independent of the mean (VIM) were assessed. Incident CVD events included coronary heart disease and stroke. Cox models were fitted to assess the home BP variability-CVD risk association. Among 4231 participants (mean±SD age, 64.9±10.9 years; 53.3% women; 79.1% taking antihypertensive medication), mean (SD) home systolic BP (SBP) levels over time and VIMSBP were 134.2 (14.3) and 6.8 (2.5) mm Hg, respectively. During a 4-year follow-up period (16 750.3 person-years), 148 CVD events occurred. VIMSBP was associated with CVD risk (hazard ratio per 1-SD increase, 1.32; 95% confidence interval [CI], 1.15-1.52), independently of mean home SBP levels over time and circulating B-type natriuretic peptide levels or urine albumin-to-creatinine ratio. Adding VIMSBP to the CVD prediction model improved the discrimination (C statistic, 0.785 versus 0.770; C statistic difference, 0.015; 95% CI, 0.003-0.028). Changes in continuous net reclassification improvement (0.259; 95% CI, 0.052-0.537), absolute integrated discrimination improvement (0.010; 95% CI, 0.003-0.016), and relative integrated discrimination improvement (0.104; 95% CI, 0.037-0.166) were also observed with the addition of VIMSBP to the CVD prediction models. In addition to the assessments of mean home SBP levels and cardiovascular end-organ damage, home BP variability measurements may provide a clinically useful distinction between high- and low-risk groups among Japanese outpatients.

BACKGROUND: Data are sparse regarding ambulatory blood pressure (BP) reduction of up-titration from a standard dose to a high dose in both nifedipine controlled-release (CR) and amlodipine. This was a prospective, randomized, multicenter, open-label trial. PATIENTS AND METHODS: Fifty-one uncontrolled hypertensives medicated by two or more antihypertensive drugs including a renin-angiotensin system inhibitor and a calcium antagonist were randomly assigned to either the nifedipine CR (80 mg)/candesartan (8 mg) group or the amlodipine (10 mg)/candesartan (8 mg) group. RESULTS: The changes in 24-hr BP were comparable between the groups. The nifedipine group demonstrated a significant decrease in their urinary albumin creatinine ratio, whereas the amlodipine group demonstrated a significant decrease in their NTproBNP level. However, there was no significant difference in any biomarkers between the two groups. CONCLUSION: Nifedipine showed an almost equal effect on ambulatory blood pressure as amlodipine. Their potentially differential effects on renal protection and NTproBNP should be tested in larger samples.

It has long been thought that there is a close association between hypertension and atrial fibrillation (AF). However, the efficacy of an angiotensin II receptor blocker for the prevention of organ damage in hypertensive individuals with AF is still controversial. The present study was a multicentered, prospective, randomized, open-label clinical trial investigating the differences in the effect of treatment with telmisartan/amlodipine combination tablets on blood pressure (BP) levels and BP variability between morning and bedtime administration in hypertensive patients with paroxysmal AF, using ambulatory BP monitoring (ABPM) and home BP. With this treatment, the patients' 24-hour BP, nighttime BP, preawake BP, and morning BP shown by ABPM were significantly reduced, and the antihypertensive effects were similar regardless of the timing of the drug administration. The standard deviation of day-by-day home systolic BP and the maximum home systolic BP were also significantly reduced, and these effects were similar regardless of the treatment timing. The N-terminal pro-brain natriuretic peptide level was significantly decreased only in the bedtime administration group. A larger study will demonstrate whether the bedtime administration of telmisartan/amlodipine combination tablets maximizes the risk-lowering effect against AF recurrence in paroxysmal AF hypertensive patients.

The aim of this study was to compare an aliskiren/amlodipine combination with high-dose amlodipine monotherapy on ambulatory blood pressure monitoring (ABPM) and organ protection. The study was a prospective, randomized, multicenter, open-label trial in elderly essential hypertensive patients. A total of 105 patients with clinic BP (CBP) ≥140/90 mm Hg with amlodipine 5 mg were randomly allocated to aliskiren (150-300 mg)/amlodipine (5 mg) (ALI/AML group, n=53) or high-dose amlodipine (10 mg) (h-dAML group, n=52) and treated for 16 weeks. Each patient's CBP, ABPM, urine albumin-to-creatinine ratio (UACR), and brachial-ankle pulse wave velocity (baPWV) were measured at baseline and at the end of the study. The ALI/AML and h-dAML groups showed similarly reduced mean 24-hour SBP, daytime SBP, nighttime SBP, and baPWV. However, UACR reduction was significantly greater in the ALI/AML group (P=.02). ALI/AML was significantly less effective in reducing early-morning BP (P=.002) and morning BP surge (P=.001) compared with h-dAML.

A 60-year-old woman with a 6-year history of numbness in her hands was admitted to hospital with dyspnea. Laboratory findings showed the elevation of creatine kinase (creatine kinase MB isoenzyme was less than 4 IU/l). Chest X-ray revealed cardiomegaly and pulmonary edema. Electrocardiogram showed a T wave inversion in V2-5 and a prolonged QT interval. Echocardiography demonstrated reduced left ventricular ejection fraction (LVEF) and massive pericardial effusion. The patient was diagnosed with heart failure. Further testing found hypocalcemia and idiopathic hypoparathyroidism. In addition to diuretics, calcium replacement therapy for hypocalcemia improved the LVEF and reduced pericardial effusion. Hypocalcemia rarely leads to heart failure and pericardial effusion. In our case, heart failure and the massive pericardial effusion were secondary to hypocalcemia due to idiopathic hypoparathyroidism. <Learning objective: Hypocalcemia should be considered in patients with heart failure, reduced ejection fraction, and massive pericardial effusion. Supportive findings for diagnosis of heart failure caused by hypocalcemia are numbness, elevation of creatine kinase, T wave inversion, and prolonged QT interval.>.

BACKGROUND: The aim of this study was to compare the effects of direct renin inhibitor, aliskiren, and amlodipine combination therapy with those of high-dose amlodipine monotherapy on endothelial function in elderly hypertensive patients. METHODS: Participants included 105 patients (mean age 77 years) who had receive 5mg amlodipine for 4 weeks. Patients were allocated to the aliskiren/amlodipine group (AL/AM) or the high-dose amlodipine (AM) group. The AL/AM group received 150mg aliskiren in addition to 5mg amlodipine for 8 weeks; then the dose of aliskiren was doubled to 300mg for another 8 weeks. The AM group received 10mg amlodipine for 16 weeks. Of the 105 patients, 87 who underwent measurements of brachial flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD) before and after the study were included in the analysis. RESULTS: Blood pressure-lowering effects were similar in the 2 groups. Plasma renin activity significantly decreased in the AL/AM group (P < 0.001) but increased in the AM group (P < 0.001). Improvement of FMD was found in the AL/AM group (2.6% to 3.7%, P = 0.001) but not in the AM group, while NMD did not change in either group. The changes in 24-hour systolic blood pressure (r = -0.60, P < 0.001) and diastolic blood pressure (r = -0.46, P = 0.004) were significantly correlated with improvement of FMD in the AL/AM group but not in the AM group. CONCLUSION: Addition of aliskiren improved endothelial function in elderly hypertensive patients treated with amlodipine. CLINICAL TRIAL REGISTRY NUMBER: UMIN000010163.