苅尾 七臣

Hypertension, a disease whose prevalence increases with age, induces pathological conditions of ischemic vascular disorders such as cerebral infarction and myocardial infarction due to accelerated arteriosclerosis and circulatory insufficiency of small arteries and sometimes causes hemorrhagic conditions such as cerebral hemorrhage and ruptured aortic aneurysm. On the other hand, as it is said that aging starts with the blood vessels, impaired blood flow associated with vascular aging is the basis for the development of many pathological conditions, and ischemic changes in target organs associated with vascular disorders result in tissue dysfunction and degeneration, inducing organ hypofunction and dysfunction. Therefore, we hypothesized that hypertension is associated with all age-related vascular diseases, and attempted to review the relationship between hypertension and diseases for which a relationship has not been previously well reported. Following our review, we hope that a collaborative effort to unravel age-related diseases from the perspective of hypertension will be undertaken together with experts in various specialties regarding the relationship of hypertension to all pathological conditions. (Figure presented.).

Heart failure (HF) is an important health problem worldwide whose stages have traditionally been classified from A to D. In addition, HF can be categorized as that with preserved ejection fraction (HFpEF) and that with reduced ejection fraction (HFrEF). Hypertension and arterial stiffness in stage A HF are major drivers of the progression to left ventricular hypertrophy (LVH), a criterion of stage B HF. Although the pathogenesis of HFpEF is heterogeneous, affected patients tend to be older than HFrEF patients and have a greater prevalence of hypertension, which is closely associated with arterial stiffness and LVH. Thus, to treat HFpEF, the optimal intervention for improving prognosis is an aggressive approach to early-stage, i.e., Stage A and B, HF. This paper reviews the findings on arterial stiffness and LVH using conventional antihypertensive drugs such as angiotensin receptor II blockers (ARBs) and a new drug class for HF, ARB/neprilysin inhibitor (ARNi). Previous studies have suggested that the combination of an ARB with an L–T-type calcium channel blocker might be recommended for the improvement of arterial stiffness and regression of LVH. More recent research has shown that ARNi also improves central BP, which leads to a reduced afterload and a significant reduction in LVH. For optimal treatment of HFpEF, drug therapy should directly address arterial stiffness as well as hypertension.

Unlike other international guidelines but in accord with the earlier Japanese Society of Hypertension (JSH) guidelines, the 2019 JSH guidelines (“JSH 2019”) continue to emphasize the importance of out-of-office blood pressure (BP) measurements obtained with a home BP device. Another unique characteristic of JSH 2019 is that it sets clinical questions about the management of hypertension that are based on systematic reviews of updated evidence. JSH 2019 states that individuals with office BP &lt  140/90 mm Hg do not have normal BP. The final decisions regarding the diagnosis and treatment of hypertension should be performed based on out-of-office BP values together with office BP measurements. For hypertensive adults with comorbidities, the office BP goal is usually &lt 130/80 mm Hg and the home BP goal is &lt 125/75 mm Hg. Recommendations of JSH 2019 would be valuable for not only Japanese hypertensive patients but also Asian hypertensive patients, who share the same features including higher incidence of stroke compared with that of myocardial infarction and a steeper blood pressure-vascular event relationship.

Epidemiologic studies have consistently demonstrated an increased risk of cardiovascular disease during colder temperatures. Hemodynamic changes associated with cold temperature and an increase in thrombogenicity may both account for the increase in cardiovascular risk and mortality. Studies using both in-office and out-of-office BP measurements have consistently shown an elevation in BP during the colder seasons. The large difference in BP between cold and warm months may increase the incidence of hypertension and reduce the hypertension control rate, potentially resulting in increased cardiovascular risk, especially among those at risk of cardiovascular disease. The current trends in global warming and climate change may have a profound impact on the epidemiology of hypertension and cardiovascular disease, as changes in the climate may significantly affect both BP variability and cardiovascular disease, especially in those with high cardiovascular risk and the elderly. Furthermore, climate change could have a significant influence on hypertension in Asia, considering the unique characteristics of hypertensive patients in Asia. As an increase in ambient temperature decreases the mean daytime average and morning surge in BP, but increases the nocturnal BP, it is difficult to predict how environmental changes will affect the epidemiology and prognosis of hypertension in the Asian-Pacific region. However, these seasonal variations in BP could be minimized by adjusting the housing conditions and using anticipation medicine. In this review, we discuss the impact of seasonal variation in the ambient temperature on hypertension and cardiovascular disease and discuss how this may impact the epidemiology of hypertension and cardiovascular disease.

Hypertension professionals from Asia have been meeting together for the last decade to discuss how to improve the management of hypertension. Based on these education and research activities, the Hypertension, brain, cardiovascular and renal Outcome Prevention and Evidence in Asia (HOPE Asia) Network was officially established in June 2018 and includes experts from 12 countries/regions across Asia. Among the numerous research and review papers published by members of the HOPE Asia Network since 2017, publications in three key areas provide important guidance on the management of hypertension in Asia. This article highlights key consensus documents, which relate to the Asian characteristics of hypertension, home blood pressure monitoring (HBPM), and ambulatory blood pressure monitoring (ABPM). Hypertension and hypertension-related diseases are common in Asia, and their characteristics differ from those in other populations. It is essential that these are taken into consideration to provide the best opportunity for achieving “perfect 24-hour blood pressure control”, guided by out-of-office (home and ambulatory) blood pressure monitoring. These region-specific consensus documents should contribute to optimizing individual and population-based hypertension management strategies in Asian country. In addition, the HOPE Asia Network model provides a good example of the local interpretation, modification, and dissemination of international best practice to benefit specific populations.

The Hypertension Cardiovascular Outcome Prevention and Evidence in Asia (HOPE Asia) Network was set up to improve the management of hypertension in Asia with the ultimate goal of achieving “zero” cardiovascular events. Asia is a diverse continent, and the prevalence of hypertension has increased over the last 30 years. There are a number of Asia-specific features of hypertension and hypertension-related cardiovascular complications, which means that a region-specific approach is needed. White-coat hypertension will become more of an issue over time as Asian populations age, and masked hypertension is more prevalent in Asian than in Western countries. Identifying and treating masked hypertension is important to reduce cardiovascular risk. Abnormal patterns of blood pressure (BP) variability common in Asia include exaggerated early morning BP surge and nocturnal hypertension. These are also important cardiovascular risk factors that need to be managed. Home blood pressure monitoring (HBPM) is an important tool for detecting white-coat and masked hypertension, and monitoring BP variability, and practices in Asia are variable. Use of HBPM is important given the Asia-specific features of hypertension, and strategies are needed to improve and standardize HBPM usage. Development of HBPM devices capable of measuring nocturnal BP along with other information and communication technology-based strategies are key developments in the widespread implementation of anticipation medicine strategies to detect and prevent cardiovascular events in patients with hypertension. Region-wide differences in hypertension prevalence, control, and management practices in Asia highlight the importance of information sharing to facilitate best practices.

Ambulatory blood pressure monitoring (ABPM) can measure 24-hour blood pressure (BP), including nocturnal BP and diurnal variations. This feature of ABPM could be of value in Asian populations for preventing cardiovascular events. However, no study has yet investigated regarding the use of ABPM in actual clinical settings in Asian countries/regions. In this study, 11 experts from 11 countries/regions were asked to answer questionnaires regarding the use of ABPM. We found that its use was very limited in primary care settings and almost exclusively available in referral settings. The indications of ABPM in actual clinical settings were largely similar to those of home BP monitoring (HBPM), that is, diagnosis of white-coat or masked hypertension and more accurate BP measurement for borderline clinic BP. Other interesting indications, such as nighttime BP patterns, including non-dipper BP, morning BP surge, and BP variability, were hardly adopted in daily clinical practice. The use of ABPM as treatment guidance for detecting treated but uncontrolled hypertension in the Asian countries/regions didn't seem to be common. The barrier to the use of ABPM was primarily its availability in referral centers, patient reluctance owing to discomfort or sleep disturbance was the most frequent barrier. ABPM use was significantly more economical when it was reimbursed by public insurance. To facilitate ABPM use, more simplified indications and protocols to minimize discomfort should be sought. For the time being, HBPM could be a reasonable alternative.

Hypertension is highly prevalent in Japan, affecting up to 60% of males and 45% of females. Stroke is the main adverse cardiovascular event, occurring at a higher rate than acute myocardial infarction. Reducing blood pressure (BP) therefore has an important role to play in decreasing morbidity and mortality. The high use of home BP monitoring (HBPM) in Japan is a positive, and home BP is a better predictor of cardiovascular event occurrence than office BP. New 2019 Japanese Society of Hypertension Guidelines strongly recommend the use of HBPM to facilitate control of hypertension to new lower target BP levels (office BP &lt  130/80 mm Hg and home BP &lt  125/75 mm Hg). Lifestyle modifications, especially reducing salt intake, are also an important part of hypertension management strategies in Japan. The most commonly used antihypertensive agents are calcium channel blockers followed by angiotensin receptor blockers, and the combination of agents from these two classes is the most popular combination therapy. These agents are appropriate choices in South East Asian countries given that they have been shown to reduce stroke more effectively than other antihypertensives. Morning hypertension, nocturnal hypertension, and BP variability are important targets for antihypertensive therapy based on their association with target organ damage and cardiovascular events. Use of home and ambulatory BP monitoring techniques is needed to monitor these important hypertension phenotypes. Information and communication technology-based monitoring platforms and wearable devices are expected to facilitate better management of hypertension in Japan in the future.

Recent randomized sham-controlled trials have demonstrated significant blood pressure reductions following renal denervation (RDN) in patients with hypertension, both in the presence and absence of antihypertensive therapy. These new data encouraged us to revisit previously published insights into potential clinical trial confounding factors that informed the design and conduct of forthcoming trials. Initially identified confounders related to procedural technique, medication variability, and selected patient subgroups have been addressed in contemporary trial design. Regarding procedural method and technology, blood pressure reductions may be improved by ensuring circumferential lesion creation in the distal renal arteries and branch vessels. Safety of the RDN procedure has been demonstrated in multiple independent meta-analyses including thousands of treated patients with low reported rates of renal vessel complications and maintenance of renal function. However, a newer generation of RDN trials has also introduced insights related to medication adherence, patient selection, and the definition of treatment response. Evolving evidence indicates that RDN therapy may be considered in higher risk populations of uncontrolled hypertension regardless of ethnicity and in patients expressing a strong preference for a nondrug therapy option. Despite advances in procedural technique and clinical trial conduct, inconsistent antihypertensive-drug adherence behavior remains perhaps the most critical clinical trial design issue for device-based hypertension therapies. As the balance in clinical equipoise increasingly favors RDN, justification of sham-controlled trial designs will be revisited, and novel study designs may be required to evaluate the safety and efficacy of novel devices and procedures intended to address the escalating prevalence of poorly controlled hypertension.

In Asian populations, a high prevalence of stroke, high salt intake and high salt sensitivity, the effects of which are partly augmented by epidemic obesity, are associated with hypertension. These factors are closely associated with resistant hypertension, especially with the disrupted circadian rhythm of blood pressure (BP), that is, non-dipper and riser patterns. An ambulatory BP profile-based strategy combined with medication and devices (renal denervation and baroreceptor activation therapy) would help to achieve 'perfect 24-h BP control', consisting of strict reduction of the 24-h BP level, restoring disrupted circadian BP rhythms and reducing excess BP variability. Such BP control would protect high-risk patients with resistant hypertension against systemic hemodynamic atherothrombotic syndrome (which involves systemic atherothrombotic vascular diseases and target-organ damage, advanced by the composite risks of pulsatile hemodynamic stress from central pressure and blood flow and by thrombometabolic risk factors). Information technology-based home sleep BP pressure monitoring may be useful for assessing the risk during sleep in high-risk patients with resistant hypertension and sleep apnea syndrome. © 2013 The Japanese Society of Hypertension.

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. (Hypertension. 2012; 60: 921-928.) center dot Online Data Supplement

Objective: Recently, visit-to-visit blood pressure (BP) variability has been shown to be associated with silent cerebral injury and stroke. However, the relationships between visit-to-visit BP variation and cognitive function are not clear. Methods: The cognitive function was evaluated using a mini-mental state examination (MMSE) and global deterioration scale (GDS) in 201 elderly patients at high risk of cardiovascular disease (CVD) (79.9 +/- 6.4 years old; women 75%). Based on 12 visits (once a month), visit-to-visit BP variability (expressed as the SD and coefficient of variation), maximum BP, minimum BP, and delta (maximum - minimum) BP were measured. Results: The MMSE score had significant negative correlations with coefficient of variation and delta in SBP, and delta DBP. The GDS score had significant positive correlations with coefficient of variation and delta in SBP, and delta DBP. Low MMSE score (<24) had significant positive correlations with coefficient of variation and delta in SBP, and delta DBP. High GDS score (>3) had significant positive correlations with coefficient of variation and delta in SBP, and delta DBP. In a multiple linear regression analysis adjusted for confounders, coefficient of variation (P < 0.001) and delta (P < 0.001) in SBP had significant negative associations with the MMSE score. The delta SBP (P < 0.05) had significant positive association with the GDS score. The coefficient of variation and delta in SBP had significant positive associations with low MMSE score (P < 0.01, P < 0.01, respectively) and high GDS score (P < 0.05, P < 0.001, respectively). Conclusions: In the high-risk elderly, exaggerated visit-to-visit BP fluctuations were significant indicators for cognitive impairment.

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. (Hypertension. 2012;59:11321138.). Online Data Supplement

To determine the role of home blood pressure (BP) monitoring for a reproducible assessment of orthostatic hypertension (OHT) and the effectiveness of hypertension control by doxazosin. In this study, 605 medicated hypertensive outpatients were enrolled. Home BP in the sitting and standing positions was monitored in all patients in the morning and evening for 6 months. According to an open-label multicenter trial design, the patients were randomly allocated to either an intervention group that took doxazosin (1-4 mg) at bedtime or to a control group that did not receive any add-on medication. The patients were divided into deciles of orthostatic BP change as evaluated by home BP monitoring at baseline. Those in the top decile, in the lowest decile and in deciles two through eight were then assigned to the OHT group, the orthostatic hypotension group and the orthostatic normotension group, respectively. Orthostatic BP in the OHYPO group did not change, whereas that of the OHT group was markedly reduced by doxazosin (P<0.01). In the control group, classification into orthostatic BP categories using home BP monitoring was more reproducible (kappa coefficient: 0.42-0.50) than when using clinical BP (kappa coefficient: 0.13-0.24). In all groups, a reduction in the urinary albumin/creatinine ratio was significantly associated with a reduction in orthostatic BP doxazosin (P<0.001). The identification of OHT based on home BP monitoring was highly reproducible. The administration of doxazosin might control OHT and consequently prevent target organ damage. Hypertension Research (2012) 35, 100-106; doi:10.1038/hr.2011.156; published online 15 September 2011

Obstructive sleep apnea (OSA) places an enormous pressure load on the cardiovascular system by inducing a temporary blood pressure (BP) surge (sleep BP surge (SLBPS)), often resulting in target organ damage and cardiovascular events, such as left ventricular hypertrophy, sudden death, myocardial infarction and stroke. Accurate measurement of SLBPS would be valuable for the risk stratification of OSA patients. We developed a new oxygen-triggered BP monitoring system based on a variable SpO(2) threshold (VT algorithm) to selectively detect severe SLBPS, which are associated with morbidity, and evaluated its performance in comparison with a previous technique based on a fixed SpO(2) threshold (FT algorithm). In 23 OSA patients, the correlation between individual minimum SpO(2) values and SLBPS was not significant when the FT algorithm was used alone (r=0.400, P=0.058) but became significant (r=0.725, P<0.0001) when the VT algorithm was additionally used. In another 13 OSA patients, when the FT algorithm was eliminated from the FT+VT algorithm, the number of BP readings was drastically reduced (36 +/- 22.7 vs. 61 +/- 55.0 times, P=0.004) with a similar correlation between minimum SpO(2) and SLBPS. The correlation between the apnea hypopnea index and SLBPS was significant when measured with the present method, but not when assessed with ambulatory BP monitors (ABPM) simulation (r=0.519, P=0.001 vs. r=0.149, P=0.385). In conclusion, oxygen-triggered BP monitoring with a variable threshold is able to detect severe OSA-related BP surges more specifically and reduce the number of BP readings required during sleep compared with detection using a fixed threshold or the conventional ABPM method. Hypertension Research (2011) 34, 922-928; doi:10.1038/hr.2011.52; published online 26 May 2011

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. (Hypertension. 2011;57:1087-1093.). Online Data Supplement

Aims Stroke events occur most frequently in the morning hours. Impaired haemostatic activity and morning blood pressure (BP) surge, defined as the morning BP increase from sleep, have individually been associated with stroke risk in general or hypertensive populations. However, their combined impact on the risk of a stroke remains unknown. Methods and results A total of 514 hypertensive patients aged > 50 years (mean 72.3 years; 37% men) underwent 24 h BP monitoring, measurement of haemostatic risk factors [plasma fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and prothrombin fragment 1+2(F1+2)], and brain MRI at baseline. The incidence of stroke was prospectively ascertained. During an average of 41 months (1751 person-years), there were 43 stroke events (ischaemic, 30; haemorrhagic, 5; undefined, 8). On multivariable analysis adjusted for confounding factors, the hazard ratio [HR (95% confidence interval (CI)] for stroke in the highest vs. lower quartiles of PAI-1 was 2.5 (1.3-4.6), that for F1+2 was 2.6 (1.4-5.0), and that for the morning BP surge was 1.2 (1.1-1.4; all P < 0.01). In particular, the ratio was substantially higher in cases with the highest quartile of both PAI-1 and F1+2 levels compared with those with the lower quartiles of both parameters (HR: 8.2; 95% CI: 3.7-18.2; P < 0.001). Among the patients with the highest quartile of the morning BP surge (n = 128), the multivariable HR (95% CI) for the highest vs. lower quartiles of PAI-1 was 3.4 (1.3-9.1) and that for F1+2 was 3.3 (1.3-8.7) (both P < 0.05). Conclusion High levels of plasma PAI-1 and F1+2, as well as an excessive morning BP surge, are independently and additively associated with an increased risk of stroke in older hypertensive patients.

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, Delta baPWV was significantly associated with Delta UACR, independent of Delta home SBP (beta=0.21, P<0.001). When the patients were divided into a group with Delta baPWV of at least 0 cm/s (positive Delta PWV) and a group with Delta baPWV of less than 0 cm/s (negative Delta PWV), 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. J Hypertens 28: 1752-1760 (c) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.