Satoshi Hoshide

Morning Surge in Blood Pressure as a Predictor of Silent and Clinical Cerebrovascular Disease in Elderly Hypertensives: A Prospective Study

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 ≥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.

Silent and clinically overt stroke in older Japanese subjects with white-coat and sustained hypertension

OBJECTIVES We investigated whether white-coat hypertension is a risk factor for stroke in relation to silent cerebral infarct (SCI) in an older Japanese population. BACKGROUND It remains uncertain whether white-coat hypertension in older subjects is a benign condition or is associated with an increased risk of stroke. METHODS We studied the prognosis for stroke 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. In 585 subjects (61%), we also assessed SCI using brain magnetic resonance imaging. RESULTS Silent cerebral infarcts were found in 36% of NT (n = 70), 42% of WCHT (n = 154), and 53% of SHT (n = 361); multiple SCIs (the presence of > or =2 SCIs) 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: three [2.0%]; WCHT: five [2.1%]; SHT: 54 [9.4%]), with 14 fatal cases (NT: one [0.7%]; WCHT: 0 [0%]; SHT: 13 [2.3%]). A Cox regression analysis showed that age (p = 0.0001) and SHT (relative risk, [RR] [95% confidence interval, CI]: 4.3 [1.3-14.2], p = 0.018) were independent stroke predictors, whereas WCHT was not significant. When we added presence/absence of SCI at baseline into this model, the RR (95% CI) for SCI was 4.6 (2.0-10.5) (p = 0.003) and that of SHT was 5.5 (1.8-18.9) versus WCHT (p = 0.004) and 3.8 (0.88-16.7) versus NT (p = 0.07). CONCLUSIONS In older subjects the incidence of stroke in WCHT is similar to that of NT and one-fourth the risk in SHT. Although SCI is a strong predictor of stroke, the difference in stroke prognosis between SHT and WCHT was independent of SCI. It is clinically important to distinguish WCHT from SHT even after assessment of target organ damage in the elderly.

Associations between nondipping of nocturnal blood pressure decrease and cardiovascular target organ damage in strictly selected community-dwelling normotensives

BACKGROUND In hypertensives, nondippers are more likely than dippers to suffer silent, as well as overt, hypertensive target organ damage. In this study, we investigated whether a nondipper status was associated with target organ damage in normotensives. METHODS We performed ambulatory blood pressure (BP) monitoring, echocardiography, and carotid ultrasonography and measured natriuretic peptides and urinary albumin (UAE) in 74 normotensive subjects with the following criteria: 1) clinical BP <140/90 mm Hg; 2) average 24-h ambulatory BP <125/80 mm Hg. RESULTS The left ventricular mass index (LVMI) and the relative wall thickness (RWT) measured by echocardiography were greater in nondippers than dippers (LVMI: 103 +/- 26 v 118 +/- 34 g/m(2), P <.05; RWT: 0.38 +/- 0.07 v 0.43 +/- 0.09, P <.01). Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were higher in nondippers than dippers (ANP: 14 +/- 10 v 36 +/- 63 pg/mL, P <.01; BNP: 16 +/- 12 v 62 +/- 153 pg/mL, P <.05). There were no significant differences in UAE and intima-media thickness measured by carotid ultrasonography. CONCLUSIONS Normotensive nondipping may not reflect renal damage, but may have a predominant effect on cardiac damage. Nondipping of nocturnal BP seems to be a determinant of cardiac hypertrophy and remodeling, and may result in a cardiovascular risk independent of ambulatory BP levels in normotensives.

U-curve relationship between orthostatic blood pressure change and silent cerebrovascular disease in elderly hypertensives: orthostatic hypertension as a new cardiovascular risk factor.

OBJECTIVES The study investigated the clinical significance and mechanism of orthostatic blood pressure (BP) dysregulation in elderly hypertensive patients. BACKGROUND Although orthostatic hypotension (OHYPO), often found in elderly hypertensive patients, has been recognized as a risk factor for syncope and cardiovascular disease, both the clinical significance and the mechanism of orthostatic hypertension (OHT) remain unclear. METHODS We performed a head-up tilting test and brain magnetic resonance imaging (MRI) in 241 elderly subjects with sustained hypertension as indicated by ambulatory BP monitoring. We classified the patients into an OHT group with orthostatic increase of systolic blood pressure (SBP) of >or=20 mm Hg (n = 26), an OHYPO group with orthostatic SBP decrease of >or=20 mm Hg (n = 23), and a normal group with neither of these two patterns (n = 192). RESULTS Silent cerebral infarcts were more common in the OHT (3.4/person, p < 0.0001) and OHYPO groups (2.7/person, p = 0.04) than in the normal group (1.4/person). Morning SBP was higher in the OHT group than in the normal group (159 vs. 149 mm Hg, p = 0.007), while there were no significant differences of these ambulatory BPs between the two groups during other periods. The OHT (21 mm Hg, p < 0.0001) and OHYPO (20 mm Hg, p = 0.01) groups had higher BP variability (standard deviation of awake SBP) than the normal group (17 mm Hg). The associations between orthostatic BP change and silent cerebrovascular disease remained significant after controlling for confounders, including ambulatory BP. The orthostatic BP increase was selectively abolished by alpha-adrenergic blocking, indicating that alpha-adrenergic activity is the predominant pathophysiologic mechanism of OHT. CONCLUSIONS Silent cerebrovascular disease is advanced in elderly hypertensives having OHT. Elderly hypertensives with OHT or OHYPO may have an elevated risk of developing hypertensive cerebrovascular disease.

Ambulatory blood pressure is a better marker than clinic blood pressure in predicting cardiovascular events in patients with/without type 2 diabetes.

BACKGROUND The prognostic significance of ambulatory blood pressure (ABP) has not been established in patients with type 2 diabetes (T2DM). METHODS In order to clarify the impact of ABP on cardiovascular prognosis in patients with or without T2DM, we performed ABP monitoring (ABPM) in 1,268 subjects recruited from nine sites in Japan, who were being evaluated for hypertension. The mean age of the patients was 70.4 +/- 9.9 years, and 301 of them had diabetes. The patients were followed up for 50 +/- 23 months. We investigated the relation between incidence of cardiovascular diseases (CVDs) and different measures of ABP, including three categories of awake systolic blood pressure (SBP <135, 135-150, and >150 mm Hg), sleep SBP (<120, 120-135, and >135 mm Hg), and dipping trends in nocturnal blood pressure (BP) (dippers, nondippers, and risers). Cox regression models were used in order to control for classic risk factors. RESULTS Higher awake and sleep SBPs predicted higher incidence of CVD in patients with and without diabetes. In multivariable analyses, elevated SBPs while awake and asleep predicted increased risk of CVD more accurately than clinic BP did, in both groups of patients. The relationships between ABP level and CVD were similar in both groups. In Kaplan-Meier analyses, the incidence of CVD in nondippers was similar to that in dippers, but risers experienced the highest risk of CVD in both groups (P < 0.01). The riser pattern was associated with a approximately 150% increase in risk of CVD, in both groups. CONCLUSIONS These findings suggest that ABPM is a better predictor of cardiovascular risk than clinic BP, and that this holds true for patients with or without T2DM.

Morning hypertension: the strongest independent risk factor for stroke in elderly hypertensive patients.

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≥135 mmHg and Di-ME-SBP≥20 mmHg) vs. sustained hypertension (Av-ME-SBP≥135 mmHg and Di-ME-SBP<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.

The insular cortex and cardiovascular system: a new insight into the brain-heart axis

The classical literature on neurocardiology has focused mainly on the subcortical regions of the central autonomic nervous system. However, recent studies have supported the notion that the cardiovascular system is regulated by cortical modulation. Modern neuroimaging data, including positron emission tomography and functional magnetic resonance imaging, have revealed that a network consisting of the insular cortex, anterior cingulate gyrus, and amygdala plays a crucial role in the regulation of central autonomic nervous system. Because the insular cortex is located in the region of the middle cerebral arteries, its structure tends to be exposed to a higher risk of cerebrovascular disease. The insular cortex damage has been associated with arrhythmia, diurnal blood pressure variation disruption (eg, a non-dipper or riser pattern), myocardial injury, and sleep disordered breathing, as well as higher plasma levels of brain natriuretic peptide, catecholamine, and glucose. This review article focuses on the role of the insular cortex as a mediator for the cardiovascular system and summarizes current knowledge on the relationships between cerebrovascular disease and cardiovascular system dysregulation. Finally, a hypothesis of the neural network involved in cortical cardiovascular modulation, including modulation of the insular cortex, is provided.

Night time blood pressure variability is a strong predictor for cardiovascular events in patients with type 2 diabetes.

BACKGROUND We aimed this study to test the hypothesis that short-term blood pressure (BP) variability and abnormal patterns of diurnal BP variation, evaluated by ambulatory BP (ABP), predicts risk of incident cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM). METHODS ABP monitoring (ABPM) was performed in 300 patients with uncomplicated T2DM without known CVD and without BP medications, who were followed for 54 +/- 20 months. The relationships of different measures of BP variability, the presence of abnormal patterns of diurnal BP variation (nondipper, riser, or morning BP surge) and the standard deviations of awake and asleep ABP were determined. Cox proportional hazards models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs) before and after controlling for various covariates. RESULTS The mean age was 67.8 +/- 9.6 years, 48% were male, 253 (84%) had a diagnosis of hypertension, and the mean of the standard deviations of awake systolic BP/diastolic BP (SBP/DBP) were 18 +/- 6/11 +/- 4 mm Hg, and those of sleep SBP/DBP were 13 +/- 5/9 +/- 3 mm Hg. During follow-up, there were 29 cardiovascular events. In multivariable analyses, the standard deviations of sleep SBP (HR = 1.08; 95% CI, 1.01-1.16, P < 0.05) and sleep DBP (HR = 1.13; 1.04-1.23, P < 0.01) were independently associated with incident CVD. Neither the nondipper and riser patterns nor the morning BP surge were associated with incident CVD events independently of clinic and 24-h BP levels. CONCLUSIONS Abnormal diurnal BP variation was not a predictor of CVD in patients with T2DM. Night time BP variability was an independent predictor of future incidence of CVD, suggesting that this measure could reflect pathophysiology of T2DM.

Hypertension and Dementia

Although hypertension is well known as a cause of vascular dementia (VaD), recent findings highlight the role of hypertension in the pathogenesis of Alzheimers disease (AD) as well as mild cognitive impairment (MCI). Recent studies have shown that disruption of diurnal blood pressure (BP) variation is closely associated with cognitive impairment via injury of the small cerebral arteries indicating that long-standing hypertension constitutes a risk of brain matter atrophy or white matter lesions (WMLs). In several clinical trials, BP-lowering with antihypertensive agents was suggested to reduce the risk of dementia or cognitive decline. This review paper focuses on the role of hypertension as a risk factor for cognitive impairment, and summarizes current knowledge on the relationships between ambulatory BP monitoring (ABPM) and cognitive impairment. Finally, an overview of the impact of antihypertensive therapy on dementia prevention is provided.

Short Sleep Duration as an Independent Predictor of Cardiovascular Events in Japanese Patients With Hypertension

BACKGROUND It is not known whether short duration of sleep is a predictor of future cardiovascular events in patients with hypertension. METHODS To test the hypothesis that short duration of sleep is independently associated with incident cardiovascular diseases (CVD), we performed ambulatory blood pressure (BP) monitoring in 1255 subjects with hypertension (mean [SD] age, 70.4 [9.9] years) and followed them for a mean period of 50 (23) months. Short sleep duration was defined as less than 7.5 hours (20th percentile). Multivariable Cox hazard models predicting CVD events were used to estimate the adjusted hazard ratio and 95% confidence interval (CI) for short sleep duration. A riser pattern was defined when mean nighttime systolic BP exceeded daytime systolic BP. The end point was a cardiovascular event: stroke, fatal or nonfatal myocardial infarction (MI), and sudden cardiac death. RESULTS In multivariable analyses, short duration of sleep (<7.5 hours) was associated with incident CVD (hazard ratio [HR], 1.68; 95% CI, 1.06-2.66; P = .03). A synergistic interaction was observed between short sleep duration and the riser pattern (P = .09). When subjects were classified according to their sleep time and a riser vs nonriser pattern, the group with shorter sleep duration plus the riser pattern had a substantially and significantly higher incidence of CVD than the group with predominant normal sleep duration plus the nonriser pattern (HR, 4.43; 95% CI, 2.09-9.39; P < .001), independent of covariates. CONCLUSIONS Short duration of sleep is associated with incident CVD risk and the combination of the riser pattern and short duration of sleep that is most strongly predictive of future CVD, independent of ambulatory BP levels. Physicians should inquire about sleep duration in the risk assessment of patients with hypertension.