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Background: The long-term benefit of achieving the Japanese Society of Hypertension home systolic blood pressure (SBP) target of <125 mm Hg has not been fully evaluated. This study investigated the long-term risk of cardiovascular disease events in individuals with home SBP <125 versus 125 to <135 or ≥135 mm Hg who participated in the J-HOP study (Japan Morning Surge-Home Blood Pressure)., Methods: The J-HOP study enrolled outpatients with ≥1 cardiovascular risk factor between 2005 and 2012, with follow-up until March 2015 and extended follow-up from December 2017 to May 2018. Cardiovascular disease events (stroke, coronary artery disease, congestive heart failure, and aortic dissection) were compared between home SBP subgroups., Results: During mean 5.9 years of follow-up in 4231 participants (mean age, 65 years), cardiovascular events included stroke (n=89), coronary artery disease (n=116), congestive heart failure (n=37), and aortic dissection (n=8). The adjusted 10-year risk of total cardiovascular disease was slightly higher, and stroke risk was significantly higher when baseline home SBP was ≥135 versus <125 mm Hg (adjusted hazard ratio, 1.39 [95% CI, 0.97-2.00] for overall cardiovascular disease and 2.68 [95% CI, 1.34-5.38] for stroke; this was largely due to between-group differences in the first 5 years of follow-up, which were maintained over the subsequent 5 years). Findings were similar in the subgroup of high-risk patients (those with diabetes or stroke history)., Conclusions: These data highlight the potential long-term benefit of strict home SBP control and validate this as an appropriate Japanese Society of Hypertension guideline target although confirmation in larger populations is needed., Registration: URL: https://www.umin.ac.jp/ctr/; University Hospital Medical Information Network Clinical Trials Registry; Unique identifier: UMIN000000894 (Japan Morning Surge-Home Blood Pressure study)., Competing Interests: Disclosures K. Kario received research funding from Omron Healthcare Co, Fukuda Denshi, and A&D Co. The other authors report no conflicts.

Time in therapeutic range (TTR) for office systolic blood pressure (SBP) is an independent predictor of major cardiovascular events. However, the clinical implications of TTR for home SBP have not yet been investigated. This study determined the association between TTR of home SBP and cardiovascular events in individuals with ≥1 cardiovascular risk factor who were enrolled in The Japan Morning Surge-Home Blood Pressure (J-HOP) study. The therapeutic range for home SBP was defined as home SBP of 100-135 mmHg during the 13-day baseline period of the J-HOP study. Participants were divided into subgroups based on quartiles of TTR for home SBP, and the risk of cardiovascular events was determined in each quartile. During a mean 6.3 years of follow-up in 4070 participants (mean age 65 years), cardiovascular events included stroke in 92, coronary artery disease in 119, heart failure in 41 and aortic dissection in 8. The adjusted hazard ratio (95% confidence interval) for the risk of total cardiovascular events in participants with home SBP TTR in the lowest (100%) versus highest quartile (<15.3%) was 1.74 (1.16-2.61); the corresponding hazard ratio for stroke events was 2.11 (1.06-4.21). A 10% decrease in home SBP TTR was associated with a 4% increase in the risk of total cardiovascular events (p = 0.033) and a 9% increase in the risk of stroke (p = 0.004). The significant association seen between home SBP TTR and the occurrence of cardio- and cerebrovascular events highlights the importance of achieving stable reductions in home SBP and minimizing day-by-day home BP variability.Clinical Trial Registration: University Hospital Medical Information Network Clinical Trials Registry, UMIN000000894 (J-HOP study)., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

While home blood pressure (BP) measurement is recommended for hypertension management, the clinical implications of peak home BP values have not been well studied. This study investigated the association between pathological threshold or frequency of peak home BP and cardiovascular events in patients with ≥1 cardiovascular risk factor. The Japan Morning Surge-Home Blood Pressure (J-HOP) study enrolled participants from 2005-2012 with extended follow-up from December 2017 to May 2018, which generated the dataset for this analysis. Average peak home systolic BP (SBP) was defined as average of the highest three BP values on 14-day measurement period. Patients were divided into quintiles of peak home BP, and the risk of stroke, coronary artery disease (CAD) and atherosclerotic cardiovascular disease (ASCVD; stroke+CAD) was determined. In 4231 patients (mean 65 years) followed for 6.2 years there were 94 strokes and 124 CAD events. The adjusted hazard ratio (HR) (95% CI) for the risk of stroke and ASCVD in patients with average peak home SBP in the highest versus lowest quintile was 4.39 (1.85-10.43) and 2.04 (1.24-3.36), respectively. Risk was greatest for stroke in the first 5 years: HR 22.66 (2.98-172.1). The pathological threshold of average peak home SBP for 5-year stroke risk was 176 mmHg. There was a linear association between the number of times peak home SBP > 175 mmHg and stroke risk. Peak home BP was a strong risk factor for stroke, especially within the first 5 years. We propose exaggerated peak home SBP > 175 mmHg as an early and strong novel risk factor for stroke., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The aim of this study was to determine whether a high daytime maximum blood pressure (BP) assessed by ambulatory BP monitoring (ABPM) constitutes a risk for atherosclerotic cardiovascular disease (ASCVD) events, especially in those with increased arterial stiffness, because BP variability is linked to arterial stiffness. A total of 6294 participants (mean age, 68.6 ± 11.7 years; 78% treated hypertensive patients), who had at least 1 cardiovascular risk factor, were followed for 4.5 years. Daytime maximum BP was calculated as the highest 1-hour moving average of 2 consecutive systolic BP (SBP) readings during the daytime. The ambulatory arterial stiffness index (AASI) was calculated as 1 minus the slope of the linear regression line between SBP and diastolic BP during 24-hour BP. During the follow-up, there were 217 ASCVD events (119 stroke and 98 coronary artery disease [CAD]). In the higher-AASI group (≥0.5783), subjects in the top quartile of daytime maximum SBP (≥179.4 mmHg) had a greater risk of stroke events compared to those in other quartiles (adjusted hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.13-3.15). In the higher-AASI group, participants with 24-hour SBP of 130 mmHg or more and in the top quartile of daytime maximum SBP had an adjusted HR (95%CI) of 2.55 (1.32-4.95) compared to those without. The analysis did not suggest that daytime maximum SBP posed a risk for CAD events and in the lower-AASI group. Daytime maximum SBP did pose a risk of stroke events, especially for those with higher arterial stiffness represented as AASI., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Introduction: Stroke is the second-leading cause of death worldwide and the second-leading cause of disability-adjusted life-years. It is well known that hypertension is a significant risk factor for cardiovascular events, including stroke., Areas Covered: Recent interventional trials have demonstrated the superiority of intensive blood pressure (BP) control for prevention of cardiovascular events compared to standard BP control. Notably, in the Strategy of Blood Pressure Intervention in Elderly Hypertensive Patients (STEP) trial, intensive BP control showed superiority in the prevention of stroke events in elderly hypertensive patients. Novel medications such as angiotensin receptor-neprilysin inhibitors and sodium glucose cotransporter 2 inhibitors have the potential to suppress various CVD events including stroke. Non-pharmacological antihypertensive therapies such as renal denervation have demonstrated BP-lowering effects and may be useful for stroke prevention. Additionally, new methods and systems of BP monitoring including various kinds of nighttime BP measurement devices, wearable devices, and methods using information and communication technology can be used to assess the pathophysiology of BP variability as a risk factor and an event trigger of stroke incidence., Expert Opinion: Novel therapies and new technologies for BP evaluation strongly support the development of individualized anticipatory medicine, which should be useful for the prevention of stroke.

Cardiovascular disease (CVD) is becoming the most important burden to health care systems in most part of the world, especially in Asia. Aiming at identifying high risk individuals and tailoring preventive treatment, many cardiovascular risk assessment tools have been established and most of them were developed in Western countries. However, these cardiovascular risk assessment tools cannot be used interchangeably without recalibration because of the different risk factor profiles (ie, greater absolute burden of hypertension and lower level of total-cholesterol in Asians and higher prevalence of metabolic disorders in South Asians) and different CVD profiles (higher ratio of stroke/coronary heart disease in Asians) between Western and Asian populations. Original risk models such as Prediction for ASCVD Risk in China (China-PAR) and Japan Arteriosclerosis Longitudinal Study (JALS) score have been developed and well validated for specific countries, while most of countries/regions in Asia are using established models. Due to higher incidence of stroke in Asians, risk factors like hypertension should weigh more in cardiovascular risk assessment comparing with Western populations, but their actual proportions should be based on CVD profiles in specific countries/regions. The authors encourage the development of new cardiovascular risk assessment tools for Asians, if possible. Still, modifying established models with native epidemiological data of risk factor as well as CVD is acceptable in regions where health care resources are insufficient., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: The relationship between notched P-wave characteristics on digital electrocardiogram (ECG) and long-term cardiovascular events remains unclear., Methods: We enrolled 810 subjects from the Japan Morning Surge Home Blood Pressure study who had one or more cardiovascular risk factors. Twelve-lead electrocardiography was conducted, and the peak-to-peak distance in the M shape was calculated automatically using a 12-lead ECG analysis system. We compared two definitions: P-waves were defined as "notched" if the peak-to-peak distance in the M shape was ≥20 ms or ≥40 ms in lead II. We assessed the left atrial diameter and left ventricular mass index (LVMI) by echocardiography. The primary endpoint was defined as a composite endpoint that combines fatal events (stroke, heart failure, coronary artery disease, and sudden death) and nonfatal events (acute myocardial infarction, angina, congestive heart failure, stroke, and aortic dissection)., Results: The mean follow-up period was 101 ± 34 months, during which 85 cardiovascular events occurred. When we defined a notched P-wave as ≥20 ms in the M shape (n = 92), a notched P-wave was a significant predictor of cardiovascular events after adjustment for age, gender, and comorbidity (hazard ratio: 1.83; 95% confidence interval: 1.01-3.31, p = 0.045). When we defined a notched P-wave as ≥40 ms in the M shape (n = 25), the hazard ratio of cardiovascular events in the notched P-wave group was not significant after adjustment for covariates (hazard ratio: 1.52; 95% confidence interval: 0.51-4.53, p = 0.455). The left atrial diameter and LVMI in the patients in the notched P-wave group (peak-to-peak distance of ≥20 ms in the M shape) were significantly higher than those in the control group (left atrial diameter: 38.8 ± 5.9 vs. 36.8 ± 5.0 mm, p = 0.001; LVMI: 103.9 ± 27.7 vs. 96.3 ± 25.7 g/m2, p = 0.010)., Conclusions: The notched P-wave by digital ECG analysis was associated with cardiovascular events and left atrial enlargement., (© 2022 S. Karger AG, Basel.)

In diagnosis of treatment-resistant hypertension (TRH), guidelines recommend out-of-office blood pressure (BP) measurements, ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM). Although evidence of an association between ABPM-evaluated TRH and cardiovascular disease (CVD) prognosis has accumulated, data are sparse regarding HBPM-evaluated TRH. We investigated this issue using data from the nationwide practice-based J-HOP (Japan Morning-Surge Home BP) study, which recruited 4,261 outpatients (mean age 64.9 years; 46.8% men; 91.5% hypertensives) who underwent morning and evening HBPM for 14 days. During 6.2 ± 3.8 years (26,418 person-years) follow-up, 270 total CVDs (stroke, coronary artery disease, aortic dissection, and heart failure) occurred. The adjusted hazard ratio (HR) (95% CIs) of uncontrolled TRH, i.e., uncontrolled BP using 3 classes of medications including diuretics or ≥4 classes of medications, for total CVD risk compared to controlled BP using <3 classes were 2.02 (1.38-2.94) and 1.81 (1.23-2.65) in home BP of 135/85 mmHg and 130/80 mmHg, respectively. Additionally, patients with TRH defined by guidelines, i.e., uncontrolled BP using 3 classes of medications including diuretics or controlled/uncontrolled BP using ≥4 classes of medications, also had higher total CVD risk compared to non-TRH under all home BP criteria. Moreover, in patients with uncontrolled apparent-TRH, i.e., TRH defined by office BP, uncontrolled home BP (≥135/85 mmHg) was still associated with atherosclerotic CVD (CVDs except heart failure) risk (adjusted HR [95% CI], 2.38 [1.09-5.19]). This is the first study to demonstrate an independent association between TRH evaluated by HBPM and CVD outcomes., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background Growth differentiation factor-15 (GDF-15) has emerged as a novel biomarker to predict all-cause death in community-dwelling individuals and patients with cardiovascular disease. We evaluated the prognostic value of GDF-15 in outpatients with cardiovascular risk factors. Methods and Results GDF-15 levels were measured in 3562 outpatients with cardiovascular risk factors in the J-HOP (Japan Morning Surge-Home Blood Pressure) study, a nationwide prospective study. Participants were stratified according to tertiles of GDF-15 and followed up for all-cause death and cardiovascular disease. During a mean follow-up period of 6.6 years, there were 155 all-cause deaths, 81 stroke events including cerebral infarction and intracranial hemorrhage, and 141 cardiac events including cardiac artery disease and heart failure. Patients with higher GDF-15 levels were associated with risks of all-cause death and stroke events (except for cardiac events) after adjustment for traditional risk factors and other prognostic biomarkers (NT-proBNP [N-terminal pro-B-type natriuretic peptide], high-sensitivity troponin T; all-cause death, hazard ratio, 2.38; 95% CI, 1.26-4.48; P =0.007; stroke events, hazard ratio, 2.93; 95% CI, 1.31-6.56, P =0.009; compared with the lowest tertile). Furthermore, incorporating GDF-15 to the predictive models for all-cause death improved discrimination and reclassification significantly. For stroke events, GDF-15 showed similar diagnostic accuracy to NT-proBNP and high-sensitivity troponin T. Conclusions In Japanese outpatients with cardiovascular risk factors, GDF-15 improves risk stratification for all-cause death when compared with NT-proBNP and high-sensitivity troponin T. GDF-15 was associated with increased risks of stroke events beyond conventional risk factors and other prognostic markers; however, the predictive ability for stroke events was equivalent to NT-proBNP and high-sensitivity troponin T. Registration URL: http://www.umin.ac.jp/ctr.; Unique identifier: UMIN000000894.

Stroke is the primary cause of disability and vascular death worldwide, including Asia. Asian characteristics that differ from the West lead to higher stroke incidence. Stroke epidemiology studies in Asia have shown varying levels of mortality, incidence, prevalence, and burden of disease. Hypertension is the most prevalent risk factor found in Asia. Besides ethnicity that is associated with stroke incidence, both systolic blood pressure, diastolic blood pressure, and blood pressure variability are positively correlated with stroke incidence. Post-stroke cognitive impairment is one of the sequelae that affect one-third of stroke survivors and has become a significant public health concern that is often neglected despite its increasing prevalence. Therefore, it is very important to prevent recurrence by treating stroke optimally and effectively. Increasing awareness and treatment adherence to hypertension, the leading risk factor for stroke, became the main goal in several countries in Asia., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Approximately 365 million people in Asia were classified as elderly in 2017. This number is rising and expected to reach approximately 520 million by 2030. The risk of hypertension and cognitive impairment/dementia increases with age. Recent data also show that the prevalence of hypertension and age-related dementia are rising in Asian countries. Moreover, not many people in Asian countries are aware of the relationship between hypertension and cognitive impairment/dementia. Furthermore, hypertension control is poorer in Asia than in developed countries. Hypertension is known to be a major risk factor for damage to target organs, including the brain. Decreased cognitive function can indicate the presence of target organ damage in the brain. Twenty-four-hour blood pressure profiles and blood pressure variability have been associated with cognitive impairment and/or silent cerebral diseases, such as silent cerebral infarction or white matter lesions, which are predisposing conditions for cognitive impairment and dementia. Hypertension that occurs in midlife also affects the incidence of cognitive impairments in later life. Managing and controlling blood pressure could preserve cognitive functions, such as by reducing the risk of vascular dementia and by reducing the global burden of stroke, which also affects cognitive function., (©2019 Wiley Periodicals, Inc.)

Background: Home blood pressure (BP) measurement has been well accepted for use in the diagnosis and treatment of hypertension. However, data regarding the association between home BP levels and cardiovascular events in a general practice population aged ≥80 years are sparse., Methods: We analyzed the cases of 349 patients ≥80 years old from the Japan Morning Surge-Home Blood Pressure (J-HOP) Study, a nationwide practice-based study of 4,310 Japanese with a history of and/or risk factors for cardiovascular disease. Home BP measurements were performed twice daily (morning and evening) over 14 consecutive days at baseline., Results: During a median follow-up of 3.0 years, 32 composite cardiovascular events (13 strokes and 19 nonstroke events) occurred. Higher morning systolic BP (SBP) was a significant risk factor for composite cardiovascular events (hazard ratio (HR) per 10mm Hg, 1.23; 95% confidence interval (CI): 1.01-1.50) and stroke events (HR per 10mm Hg, 1.47; 95% CI: 1.08-2.00) after adjustment by the 4-year cardiovascular risk scores and clinic SBP. In the adjusted model, morning diastolic BP also tended to be a significant risk factor of stroke events (HR per 5 mm Hg, 1.43; 95% CI: 1.00-2.05). However, these associations were not found for evening BP or clinic BP., Conclusions: Morning home BP showed a positive linear association with cardiovascular events, especially with stroke. This association was not observed for clinic BP or evening home BP. Based on these results, in very elderly Asian populations, measuring morning home BP might be important in clinical practice regardless of the individual's office BP level.

Importance: The clinical outcomes associated with masked hypertension defined by home blood pressure monitoring (HBPM) in clinical settings remain uncertain., Objective: To assess the association between masked hypertension and cardiovascular disease events in clinical settings., Design, Setting, and Participants: This observational cohort study used data from 4261 outpatients treated at 71 primary practices or university hospitals throughout Japan who were enrolled in the Japan Morning Surge-Home Blood Pressure study between January 1, 2005, and December 31, 2012. Participants had a history of or risk factors for cardiovascular disease and were followed up through March 31, 2015. Participants underwent clinic blood pressure (BP) measurements on 2 occasions as well as HBPM measurements in the morning and evening for a 14-day period. Urine albumin to creatinine ratio and circulating brain (or B-type) natriuretic peptide levels were quantified at baseline as a marker of cardiovascular end-organ damage. Data were analyzed from July 1, 2017, to October 31, 2017., Exposures: Participants were categorized into 4 BP groups: (1) masked hypertension-hypertensive home BP levels (systolic, ≥135 mm Hg; diastolic, ≥85 mm Hg) and nonhypertensive clinic BP levels (systolic, <140 mm Hg; diastolic, <90 mm Hg); (2) white-coat hypertension-nonhypertensive home BP levels (systolic, <135 mm Hg; diastolic, <85 mm Hg) and hypertensive clinic BP levels (systolic, ≥140 mm Hg; diastolic, ≥90 mm Hg); (3) sustained hypertension-hypertensive home and clinic BP levels; and (4) controlled BP-nonhypertensive home and clinic BP levels., Main Outcomes and Measures: Incident stroke and coronary heart disease., Results: Of the 4261 participants, 2266 (53.2%) were women, 3374 (79.2%) were taking antihypertensive medication, and the mean (SD) age was 64.9 (10.9) years. During a median (interquartile range) follow-up of 3.9 (2.4-4.6) years, 74 stroke (4.4 per 1000 person-years) and 77 coronary heart disease (4.6 per 1000 person-years) events occurred. The masked hypertension group had a greater risk for stroke compared with the controlled BP group (hazard ratio, 2.77; 95% CI, 1.20-6.37), independent of traditional cardiovascular risk factors, urine albumin to creatinine ratio, and circulating B-type natriuretic peptide levels. Conversely, masked hypertension yielded no association with coronary heart disease risk., Conclusions and Relevance: In the Japanese general practice population, masked hypertension defined by HBPM may be associated with an increased risk for stroke events. Use of HBPM may improve the assessment of BP-related risks and identify new therapeutic interventions aimed at preventing cardiovascular disease events.

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 VIM SBP 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. VIM SBP 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 VIM SBP 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 VIM SBP 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., (© 2017 American Heart Association, Inc.)

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.)

Obstructive sleep apnea syndrome (OSAS) causes resistant hypertension and a hypopnea-related nocturnal blood pressure (BP) surge. This could lead to an increase of not only the nocturnal BP level but also nocturnal BP variability, both of which increase an individual's cardiovascular risk. We recently developed a trigger sleep BP monitoring method that initiates BP measurement when an individual's oxygen desaturation falls below a variable threshold, and we demonstrated that it can detect a BP surge during apnea episodes. We here report the case of a 36-year-old man with severe OSAS who experienced the recurrence of stroke due to nocturnal hypoxia and a nocturnal BP surge measured by this trigger sleep BP monitoring device. A nocturnal BP surge during sleep in OSAS patients could be a strong trigger of cardiovascular events., (Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: Whether ambulatory blood pressure (BP) among hypertensive patients better predicts cardiovascular events (CVEs) in women relative to men is unclear., Methods: We searched PUBMED and OVID databases. Cohorts were required to have hypertension, 1+ years of follow-up, with stroke and coronary artery disease as outcomes. Lead investigators for these cohorts provided ad hoc analyses. Random-effect meta-analyses gave hazard ratios for CVEs from a 1 standard deviation (SD) mmHg increase and a 10 mmHg increase in SBP. Subgroup and meta-regression analyses quantified the relative increase in risk in women versus men., Results: Patients were from Europe, Brazil, and Japan (10 cohorts, n = 17 312, CVEs = 1892). One cohort lacked sex-specific hazard ratios from 24 h and clinic SBP. Compared with men, women tended to have greater SDs and coefficients of variation of SBP. Subgroup analyses showed higher hazard ratios in women than in men from increases in ambulatory but not clinic SBPs. For women relative to men, a 1 SD increase in night-time, daytime, 24 h, and clinic SBP gave hazard ratios (95% confidence limits) of 1.17 (1.06-1.30), 1.24 (1.10-1.39), 1.21 (1.08-1.36), and 0.94 (0.84-1.05), respectively, whereas a 10 mmHg increase in SBP, gave hazard ratios of 1.06 (0.99-1.14), 1.13 (1.03-1.23), 1.10 (1.01-1.21), and 0.96 (0.89-1.03), respectively., Conclusion: In patients with hypertension, increases in ambulatory, but not clinic, SBP predict higher risks for CVEs in women than in men. Although women tended to have greater variability in SBP, this did not entirely explain the sex-ambulatory BP interactions.

To examine the effects of antihypertensive treatment on cardiovascular disease (CVD) in Asian populations, we systematically evaluated prospective randomized studies carried out in Asia (1991-2013). We identified 18 trials with 23,215 and 21,986 hypertensive patients in the intervention (ie, strict blood pressure [BP] lowering or add-on treatment) and reference groups, respectively (mean age, 65 years; follow-up duration, 3.2 years). Analysis was performed through 1) first subgroup: eight trials that compared active antihypertensive treatment with placebo or intensive with less intensive BP control and 2) second subgroup: 10 trials that compared different antihypertensive treatments. In the first subgroup analysis, BP was reduced from 160.3/87.3 mm Hg to 140.2/78.4 mm Hg in the intervention group with a -6.7/-2.2 mm Hg (P < .001) greater BP reduction than the reference group. Compared with the reference group, the intervention group had a lower risk of composite CVD events (odd ratio [OR], 0.73; 95% confidence interval [CI], 0.66-0.81), myocardial infarction (OR, 0.79; 95% CI, 0.63-1.0), stroke (OR, 0.71; 95% CI, 0.63-0.80), and CVD mortality (OR, 0.81; 95% CI, 0.68-0.97; all P ≤ .05). In the second subgroup analysis, no difference was found for any outcome between renin-angiotensin blockers and calcium-channel blockers or diuretics. The meta-regression line among the 18 trials indicated that a 10 mm Hg reduction in systolic BP was associated with a reduced risk for composite CVD events (-39.5%) and stroke (-30.0%). Our meta-analysis shows a benefit when a BP target of less than 140/80 mm Hg is achieved in Asian hypertensives. BP reduction itself, regardless of BP lowering agents, is important for achieving CVD risk reduction., (Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: Among elderly hypertensive patients, we aimed to assess the association of nocturnal blood pressure (BP) pattern on stroke; interaction of dipping pattern with kidney disease was explored., Methods: We retrospectively analyzed the records of 1,276 elderly (≥60 years) hypertensive Japanese patients (mean 74 years; 40% were men) who had measurements of estimated glomerular filtration rate and ambulatory BP., Results: Stroke events occurred in 73 people over an average of 3.2 years (4,026 person-years). Chronic kidney disease (CKD) at baseline (n = 634, 50%) was more prevalent in people with strokes (71%) than those without strokes (48%; p < 0.01). Both CKD and nocturnal systolic BP (SBP) increase (10 mm Hg) were independently associated with increased risk for stroke [hazard ratio (HR), 1.9; 95% confidence interval (CI), 1.1-3.1 for CKD and HR 1.2; 1.1-1.4 for SBP]. After adjustment for office SBP, a 10-mm Hg increase in nocturnal SBP was similarly associated with strokes in patients with CKD (HR 1.2; 95% CI 1.0-1.3) and those without CKD (HR 1.2; 95% CI 0.97-1.5). Although reverse dipping (nocturnal SBP ≥ daytime SBP) was associated with stroke only in patients with CKD (HR 2.1; 95% CI 1.1-4.1) and not those without CKD (HR 1.1; 95% CI 0.3-3.8), the interaction effect was not significant (p = 0.30)., Conclusion: In elderly hypertensive patients, both high nocturnal SBP and CKD are independent risk factors for stroke., (Copyright © 2013 S. Karger AG, Basel.)

Apart from the well-known role of hypertension in cerebrovascular disease, chronic kidney disease is emerging as an independent risk factor for stroke. Although the mechanism underlying the relationship between blood pressure variability, diurnal blood pressure variation disruption (e.g. nondipping) and kidney dysfunction is not fully understood, these factors are closely associated with each other. This review article summarizes the recent literature on these topics. Cerebral small vessel disease is considered to serve as a common pathophysiology in the relationship of hypertension and chronic kidney disease with cognitive impairment and stroke. Strict 24-hour blood pressure control is necessary to prevent the progression of kidney dysfunction, dementia and stroke., (Copyright © 2013 S. Karger AG, Basel.)

Objective: Evidence is now available about the association between chronic kidney disease (CKD) and stroke. However, less is known about the underlying mechanisms, and there is currently no reliable marker for identifying stroke-prone high-risk patients among CKD patients., Methods: A total of 514 hypertensive patients aged >50 years (mean, 72.3 years; 37% men) underwent 24-h BP monitoring and measurement of circulatory high-sensitivity C-reactive protein (hs-CRP) and norepinephrine at baseline. CKD was defined as eGFR<60 ml/min/1.73 m(2) using the Cockcroft-Gault equation., Results and Conclusion: During an average of 41 months (1751 person-years), there were 43 stroke events. Compared with hypertensive patients without CKD, those with CKD (n=225) had higher levels of sleep systolic BP (SBP) (125 mmHg vs. 129 mmHg), circulatory hs-CRP (0.12 mg/L vs. 0.20 mg/L) and norepinephrine (332.2 pg/ml vs. 372.8 pg/ml; all P<0.05). On multivariable analysis, the hazard ratio (HR) (95% CI) for stroke in CKD vs. non-CKD was 2.7 (1.2-6.9) (P<0.05). CKD, as well as the baseline presence of silent cerebral infarction, sleep SBP increase, and high hs-CRP level (highest quartile: ≥0.42 mg/L) were independently and additively associated with stroke events; above all, there was a synergistic effect of CKD and high norepinephrine level (highest quartile: ≥538 pg/ml) on stroke risk (all P<0.05). Among hypertensive patients with CKD, those within the highest quartiles of norepinephrine had a greater stroke risk compared to those who were in the lower quartiles of norepinephrine (HR (95% CI): 2.2 (1.0-4.5); P=0.045). In conclusion, CKD is an independent predictor of stroke in Japanese hypertensive patients; in particular, hypertensive patients with CKD and a high norepinephrine level have a synergistically augmented stroke risk., (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.)

Recently, visit-to-visit variability in systolic blood pressure (SBP) has been shown to be a predictor of stroke. In this study, we investigated the relationship of visit-to-visit blood pressure (BP) variations (based on 12 visits once a month) with intima-media thickness (IMT) and stiffness in common carotid artery among the 201 high-risk elderly (female 75%) at cardiovascular disease. Max-IMT was significantly positively correlated with age, smoking, renin-angiotensin system inhibitor use, coefficient of variation (CV), and delta (maximum-minimum) in SBP, and CV in diastolic BP (DBP) but was significantly negatively correlated with female, high-density lipoprotein (HDL), and minimum in SBP. Stiffness parameter β was significantly positively correlated with age, standard deviation (SD), CV, maximum, and delta in SBP, and SD, CV, and delta in DBP but was significantly negatively correlated with smoking, HDL, average, and minimum in DBP. In a multiple regression analysis, delta SBP (P < .001) was associated with max-IMT independently of average SBP. CV (P < .05) and delta (P < .05) in SBP, and CV (P < .001) and delta (P < .01) in DBP were associated with stiffness parameter β independently of average BP. In the high-risk elderly, exaggerated visit-to-visit BP fluctuations were significant indicators for carotid artery atherosclerosis and stiffness independently of average BP., (Copyright © 2011 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

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.

Data relating habitual sleep duration to the risk of silent or overt stroke are sparse. We tested the hypothesis that short duration of sleep is associated with increased risk of silent cerebral infarct (SCI) and stroke events in hypertensive patients. We performed ambulatory BP monitoring in 1268 hypertensives (mean age: 70.4 years) and followed them for 50 months. Brain MRI was performed in 932 of these subjects for the assessment of SCI, and these subjects were analyzed in this study. Cox proportional hazard models were used to calculate the hazard ratios (HR) of sleep-duration-associated risk for cardiovascular events while controlling for significant covariates. In multivariable Cox regression analysis, a sleep duration <7.5 h was independently associated with the risk of stroke (HR = 2.21; P = 0.003). The presence of SCI was also associated with stroke events (HR = 2.60; P = 0.005). When the subjects were divided into an SCI(+) group and SCI(-) group, the short sleep duration was a significant predictor for incident stroke only in the SCI(+) group (HR = 2.52; P = 0.001). Shorter sleep duration was an independent risk for future incidence of stroke events in hypertensive patients, especially those with SCIs., (Copyright © 2010 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

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.

Stroke is sometimes seen in patients with congestive heart failure (CHF). The factors that best predict incident stroke in hospitalized CHF patients are not well known. We performed this pilot study to explore the clinical markers of incident stroke in CHF patients. We studied 111 hospitalized patients with CHF (mean age, 67+/-11 years). Ambulatory blood pressure (BP) monitoring, blood tests, and echocardiography were performed in these patients just before they left the hospital, and all cardiovascular events during the study period were followed for an average of 18+/-9 months. Cox regression analysis was performed to explore the predictors of incident stroke using age, sex, body mass index (BMI), casual and ambulatory systolic BP (SBP), and brain-type natriuretic peptide (BNP). There were 10 stroke events (9%) during the follow-up period. The stroke group had higher nocturnal SBP and plasma BNP levels than the non-stroke group. With Cox regression analysis, both nocturnal SBP and BNP were significant predictors of incident stroke independent of other covariates. When nocturnal BP of 120 mmHg and BNP of 600 pg/mL (75th percentile) were used as cutoffs, nocturnal SBP > or =120 mmHg was associated with a 7-fold increase in the risk of incident stroke, while BNP > or =600 pg/mL was associated with a 46.6-fold increase. However, abnormal circadian BP patterns were not associated with incident stroke. In this pilot study, elevated nocturnal BP and high plasma BNP just before patients left the hospital were significant predictors of stroke events in CHF patients. Further study is needed to confirm this hypothesis.

Background and Purpose: High-sensitivity C-reactive protein (hsCRP), a marker of inflammation, is associated with atherosclerosis, hypertensive target organ damage, and cardiovascular events. In the general Japanese population, the level of hsCRP is reported to be lower than that in Western countries, and the relationships among hsCRP, silent cerebral infarcts (SCIs), and clinical stroke events in older Japanese hypertensives remain unclear., Methods: We conducted brain MRI and measured hsCRP at baseline in 514 older Japanese hypertensives (clinic blood pressure > or =140/90 mm Hg, age > or =50 years old) who were enrolled in the Jichi Medical School ABPM Study, wave 1. They were followed up for an average of 41 months (range: 1 to 68 months, 1751 person-years) and the incidence of subsequent clinical stroke events was evaluated., Results: The subjects with SCIs at baseline (n=257) had a higher hsCRP level than those without SCIs (geometric mean hsCRP [SD range]; 0.19 [0.18 to 0.21] versus 0.14 [0.13 to 0.16] mg/L, P=0.007) after adjustment for confounding factors, and the OR for the presence of SCIs was increased with the quartile of hsCRP levels. In Cox regression analysis, the patients with above median hsCRP level (> or =0.21 mg/L) (hazard ratio [HR]: 2.50, 95% CI: 1.24 to 5.00, P=0.01) and those with SCIs (HR: 4.60, 95% CI: 1.91 to 11.03, P=0.001) at baseline had independently higher risks for clinical stroke events after adjustment for age, smoking status, antihypertensive medication use, and 24-hour systolic blood pressure level. Compared with the patients with below median hsCRP level without SCIs, those with above median hsCRP level and SCIs at baseline had a higher risk for clinical stroke events (HR: 7.32, 95% CI: 2.17 to 24.76, P=0.001), although those with below median hsCRP level and SCIs (HR: 2.46, 95% CI: 0.64 to 9.47, P=0.19) and those with above median hsCRP level without SCIs (HR: 1.11, 95% CI: 0.22 to 5.55, P=0.90) did not have significant risks., Conclusions: High-sensitivity C-reactive protein is a risk factor for clinical stroke events in addition to silent cerebral infarcts in Japanese older hypertensives, indicating that the risk for clinical stroke events increases with preexisting hypertensive target organ damage in the brain and additionally with ongoing low-grade inflammation.

Stroke occurs most frequently in the morning hours, but the impact of the morning blood pressure (BP) level on stroke risk has not been fully investigated in hypertensives. We studied stroke prognosis in 519 older hypertensives in whom ambulatory BP monitoring was performed, and who were followed prospectively. During an average duration of 41 months (range: 1-68 months), 44 stroke events occurred. The morning systolic BP (SBP) was the strongest independent predictor for stroke events among clinic, 24-h, awake, sleep, evening, and pre-awake BPs, with a 10 mmHg increase in morning SBP corresponding to a relative risk (RR) of 1.44 (p<0.0001). The average of the morning and evening SBP (Av-ME-SBP; 10 mmHg increase: RR=1.41, p=0.0001), and the difference between the morning and evening SBP (Di-ME-SBP; 10 mmHg increase: RR=1.24, p=0.0025) were associated with stroke risks independently of each other. The RR of morning hypertension (Av-ME-SBP > or = 135 mmHg and Di-ME-SBP > or = 20 mmHg) vs. sustained hypertension (Av-ME-SBP > = 135 mmHg and Di-ME-SBP < or = 20 mmHg) for stoke events was 3.1 after controlling for other risk factors (p=0.01). In conclusion, morning hypertension is the strongest independent predictor for future clinical stroke events in elderly hypertensive patients, and morning and evening BPs should be monitored in the home as a first step in the treatment of hypertensive patients.

Background: It remains uncertain which is the stronger predictor for stroke in older hypertensives, ambulatory pulse pressure (PP) or mean blood pressure (MBP)., Methods: We studied the prognosis for stroke in 811 older hypertensives in whom ambulatory BP monitoring was performed. We also assessed silent cerebral infarct (SCI) by brain magnetic resonance imaging., Results: Silent cerebral infarcts were found in 50% of 515 subjects (64% of the total population) in whom we assessed SCI using brain magnetic resonance imaging. During a mean of a 42-month follow-up period, stroke events occurred in 59 subjects. After adjustment for covariates, for each 10 mm Hg increase in sleep PP, there was an independent 43% (95% confidence interval [CI]:16%-75%, P =.001) increase in the stroke risk, and sleep MBP was not a significant factor after controlling for sleep PP. On the other hand, for each 10 mm Hg increase in awake MBP, there was an independent 48% (95% CI: 21%-81%, P =.0002) increase in the stroke risk, and awake PP was not a significant factor after controlling for awake MBP. After adjusting for SCI (a strong predictor, P <.0001) at baseline, the effects of awake MBP (38% risk increase for each 10 mm Hg, P =.007) and sleep PP (32% risk increase for each 10 mm Hg, P =.016) remained significant., Conclusions: In older hypertensives, the impacts of PP and MBP on stroke risk are different during sleep and awake periods. Sleep PP and awake MBP are both predictors of stroke events independently of SCI.

Background: Cardiovascular events occur most frequently in the morning hours. We prospectively studied the association between the morning blood pressure (BP) surge and stroke in elderly hypertensives., Methods and Results: We studied stroke prognosis in 519 older hypertensives in whom ambulatory BP monitoring was performed and silent cerebral infarct was assessed by brain MRI and who were followed up prospectively. The morning BP surge (MS) was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP. During an average duration of 41 months (range 1 to 68 months), 44 stroke events occurred. When the patients were divided into 2 groups according to MS, those in the top decile (MS group; MS > or =55 mm Hg, n=53) had a higher baseline prevalence of multiple infarcts (57% versus 33%, P=0.001) and a higher stroke incidence (19% versus 7.3%, P=0.004) during the follow-up period than the others (non-MS group; MS <55 mm Hg, n=466). After they were matched for age and 24-hour BP, the relative risk of the MS group versus the non-MS group remained significant (relative risk=2.7, P=0.04). The MS was associated with stroke events independently of 24-hour BP, nocturnal BP dipping status, and baseline prevalence of silent infarct (P=0.008)., Conclusions: In older hypertensives, a higher morning BP surge is associated with stroke risk independently of ambulatory BP, nocturnal BP falls, and silent infarct. Reduction of the MS could thus be a new therapeutic target for preventing target organ damage and subsequent cardiovascular events in hypertensive patients.

To determine whether the benefits of antihypertensive treatment vary according to dipper status, 811 asymptomatic elderly Japanese hypertensives underwent 24-h ambulatory blood pressure monitoring. During a mean follow-up period of 41 months, 32 stroke events were observed in patients who remained nonmedicated (n = 385), and in 27 patients in the medicated group (n = 426), indicating a 24% lower rate of stroke as a result of antihypertensive therapy. Patients were divided into a white-coat hypertensive (WCHT) group (ambulatory blood pressure <130/80 mm Hg; n = 236) and a sustained hypertensive (SHT) group (n = 575). Sixty-one percent of SHT and 32% of WCHT patients were being medicated. In the SHT group, the stroke rates were 12.4% in nonmedicated and 7.4% in medicated group (P =.04), whereas in the WCHT group the stroke rates were 2.5% in nonmedicated and 1.3% in medicated group (P = not significant). The SHT were further classified according to their nocturnal systolic blood pressure (BP) decrease, as follows: 97 extreme-dippers with >20% nocturnal systolic BP decrease; 230 dippers with >10% but <20% decrease; 185 nondippers with >0% but <10% decrease; 63 reverse-dippers with <0% decrease. In the dipping groups of SHT, the stroke rates were similar according to medication versus no-medication in extreme-dippers (12% v 13%), and reverse-dippers (23% v 22%), but in nondippers there was a significantly lower rate (by 65%, P =.038) in the medicated (4.4%) than the nonmedicated (13%) groups. In dippers, the stroke rate was also lower in the medicated than the nonmedicated patients (4.7% v 8.8%), a decrease of 47% (P =.217), although the difference was not significant. In conclusion, in older SHT subjects, antihypertensive therapy using clinic BP may be less effective for the groups with extremely abnormal diurnal BP patterns (extreme-dippers and reverse-dippers) than those with relatively normal patterns (dippers and nondippers). Patients with WCHT also showed no benefit.

Background: Whether white-coat hypertension in older subjects is a benign condition or is associated with an increased risk for stroke remains uncertain. White-coat hypertension as a risk factor for stroke was investigated in relation to silent cerebral infarct in the older Japanese population., Methods: The prognosis for stroke was studied in 958 older Japanese subjects [147 normotensives (NT), 236 white-coat hypertensives (WCHT), and 575 sustained hypertensives (SHT)] in whom ambulatory blood pressure monitoring was performed in the absence of antihypertensive treatment. Silent cerebral infarct was also assessed using brain magnetic resonance imaging in 585 subjects (61%)., Results: Silent cerebral infarcts were found in 36% of NT (n = 70), 42% of WCHT (n = 154), and 53% of SHT (n = 361), and multiple silent cerebral infarcts(presence of > or = 2 silent cerebral infarcts) were found in 24% of NT, 25% of WCHT, and 39% of SHT. During a mean 42-month-follow-up period, clinically overt strokes occurred in 62 subjects [NT 3(2.0%), WCHT 5(2.1%), SHT 54(9.4%)], with 14 fatal cases [NT 1(0.7%), WCHT 0(0%), SHT 13 (2.3%)]. Cox regression analysis showed that age (p = 0.0001) and SHT [RR(95% confidence interval): 4.3 (1.3-14.2), p = 0.018] were independent stroke predictors, whereas WCHT was not significant. Adding presence/absence of silent cerebral infarct at baseline into this model, the RR (95% confidence interval) for silent cerebral infarct was 4.6 (2.0-10.5) (p = 0.003), and that of SHT was 5.5 (1.8-18.9) vs WCHT (p = 0.004) and 3.8 (0.88-16.7) vs NT (p = 0.07)., Conclusions: The incidence of stroke in WCHT is similar to that of NT, and one fourth the risk in SHT in older subjects. Although silent cerebral infarct is a strong predictor of stroke, the difference in stroke prognosis between SHT and WCHT was independent of silent cerebral infarct. It is clinically important to distinguish WCHT from SHT even after assessment of target organ damage in the elderly.

It remains uncertain whether abnormal dipping patterns of nocturnal blood pressure influence the prognosis for stroke. We studied stroke events in 575 older Japanese patients with sustained hypertension determined by ambulatory blood pressure monitoring (without medication). They were subclassified by their nocturnal systolic blood pressure fall (97 extreme-dippers, with >/=20% nocturnal systolic blood pressure fall; 230 dippers, with >/=10% but <20% fall; 185 nondippers, with >/=0% but <10% fall; and 63 reverse-dippers, with <0% fall) and were followed prospectively for an average duration of 41 months. Baseline brain magnetic resonance imaging (MRI) disclosed that the percentages with multiple silent cerebral infarct were 53% in extreme-dippers, 29% in dippers, 41% in nondippers, and 49% in reverse-dippers. There was a J-shaped relationship between dipping status and stroke incidence (extreme-dippers, 12%; dippers, 6.1%; nondippers, 7.6%; and reverse-dippers, 22%), and this remained significant in a Cox regression analysis after controlling for age, gender, body mass index, 24-hour systolic blood pressure, and antihypertensive medication. Intracranial hemorrhage was more common in reverse-dippers (29% of strokes) than in other subgroups (7.7% of strokes, P=0.04). In the extreme-dipper group, 27% of strokes were ischemic strokes that occurred during sleep (versus 8.6% of strokes in the other 3 subgroups, P=0.11). In conclusion, in older Japanese hypertensive patients, extreme dipping of nocturnal blood pressure may be related to silent and clinical cerebral ischemia through hypoperfusion during sleep or an exaggerated morning rise of blood pressure, whereas reverse dipping may pose a risk for intracranial hemorrhage.