Kazuo Eguchi

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.

Differential Effects Between a Calcium Channel Blocker and a Diuretic When Used in Combination With Angiotensin II Receptor Blocker on Central Aortic Pressure in Hypertensive Patients

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

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.

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.

Relationship Between Extreme Dippers and Orthostatic Hypertension in Elderly Hypertensive Patients

Among elderly hypertensive subjects, extreme dippers with marked nocturnal fall in blood pressure (BP) as well as nondippers with absent nocturnal fall in BP are more prone to cerebrovascular disease when compared with those with appropriate nocturnal BP fall. However, the relationship between these abnormal diurnal BP variation patterns and postural BP variation has not been investigated. We investigated the diurnal BP variation by ambulatory BP monitoring and postural BP variation during 70 degrees head-up tilt in 110 asymptomatic hypertensive elderly subjects, who consisted of 29 subjects with white-coat hypertension and 81 with sustained hypertension with various patterns of nocturnal fall in BP (14 extreme dippers, with asleep systolic BP decrease by > or =20% of awake systolic BP; 56 dippers, with decrease by > or =0% to <20%; 11 nondippers, with decrease by <0%). During tilt, the mean (SD) systolic BP increased 10 (19) mm Hg in the extreme dippers (P<.02), and it decreased by 7.5 (13) mm Hg in the nondippers (P<.05), whereas it did not change in the dippers and white-coat hypertensive subjects. The heart rate increased in all four groups to similar degrees during tilt. Orthostatic hypertension defined as systolic BP rise of 10 mm Hg or more during tilt was found in 10 (72%) of the 14 extreme dippers, 6 (11%) of the 56 dippers, and 1 (9%) of the 11 nondippers, while orthostatic hypotension defined as systolic BP decrease of 20 mm Hg or more was found in 3 (27%), 5 (9%), and 1 (7%) of the nondippers, dippers, and extreme dippers, respectively (chi2=29.3, P<.0001). In conclusion, the abnormal diurnal BP variation is closely related to the abnormal postural BP variation in elderly hypertensive patients, with extreme dippers showing orthostatic hypertension and nondippers showing orthostatic hypotension. The upright position during the daytime, which increases the BP in the extreme dippers and decreases it in the nondippers, may in part produce abnormal diurnal BP variation.

Greater Impact of Coexistence of Hypertension and Diabetes on Silent Cerebral Infarcts

Background and Purpose— Silent cerebral infarcts (SCIs), often found in the elderly and hypertensives, have been proposed as an indicator of poorer cerebrovascular prognosis. The aim of this study was to evaluate the prevalence and determinants of SCI in hypertensives with or without diabetes mellitus (DM). Methods— We studied 360 asymptomatic hypertensive subjects with or without DM (mean age, 67.4 years; range, 41 to 88 years). We performed 24-hour ambulatory blood pressure (BP) monitoring and brain MRI. The subjects were classified into a diabetic hypertension group with DM (DHT, n=159) or a non-DM hypertension group (non-DHT, n=201). Results— SCIs (presence of ≥1) were found in 82% of the DHT and 58% of the non-DHT (P <0.001) group; multiple SCIs (the presence of ≥3) were found in 62% of the DHT and 35% of the non-DHT group (P <0.001); and 24-hour ambulatory BP levels were comparable between groups. DM was a powerful determinant of both SCIs (odds ratio [OR], 2.95; P <0.01) and multiple SCIs (OR, 3.05; P <0.001) independently of age and 24-hour systolic BP, whereas only multiple SCIs were associated with 24-hour systolic BP. When patients were subclassified by ambulatory BP and the presence of DM (sustained hypertension [SHT]+DM, white-coat hypertension [WCHT]+DM, SHT, and WCHT groups), the prevalence of SCI and multiple SCIs was higher in the SHT+DM than in the SHT group, and only multiple SCIs were higher in the WCHT+DM than the WCHT group. Conclusions— Diabetes was the major determinant of SCIs in both SHT and WCHT.

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.

Association Between Diabetes Mellitus and Left Ventricular Hypertrophy in a Multiethnic Population

It is still controversial whether type 2 diabetes mellitus (T2DM) is associated with increased left ventricular (LV) mass independent of body size. We tested the hypothesis that T2DM is independently associated with LV mass in a multiethnic cohort. In the Northern Manhattan Study (NOMAS) cohort sample, a total of 1,932 subjects (67.9+/-9.6 years, 769 men and 1,163 women, 443 with DM and 1,489 without DM) were studied by transthoracic echocardiography, and LV mass was calculated. LV hypertrophy was defined as the upper quartile of LV mass. Multivariable models were used to assess the association of T2DM with LV mass after adjusting for age, gender, race, body mass index (BMI), systolic blood pressure, education, history of coronary artery disease, physical activity, and alcohol consumption. LV mass (189+/-60 vs 174+/-59 g, p<0.0001), BMI, and systolic blood pressure were higher in the DM group than in the non-DM group, whereas age and gender distributions were similar between groups. In multivariable analysis, T2DM was independently associated with increased LV mass (p=0.03). Presence of T2DM was associated with increased risk of LV hypertrophy (adjusted odds ratio 1.46, 95% confidence interval 1.13 to 1.88, p=0.004). Although no interactions were observed between T2DM and BMI on LV hypertrophy (p=0.6), there was a significant interaction between T2DM and waist circumference on LV hypertrophy (p=0.01). In conclusion, T2DM was independently associated with increased LV hypertrophy independent of various covariates in this multiethnic sample. Presence of T2DM increased the risk of LV hypertrophy by about 1.5-fold, and it possibly interacted with central obesity.

Visit-to-visit and ambulatory blood pressure variability as predictors of incident cardiovascular events in patients with hypertension.

BACKGROUND Visit-to-visit blood pressure variability (BPV) has been shown to be a prognostic indicator in hypertensive patients. We designed this study to clarify the impacts of clinic and ambulatory BPV in predicting cardiovascular disease (CVD). METHODS We performed ambulatory BP monitoring (ABPM) in 457 hypertensive patients. Visit-to-visit BPV and ambulatory BPV were calculated as the SDs of clinic BP, awake BP, and sleep BP. The mean age of the subjects was 67.0 ± 9.2 years, and they were followed for 67 ± 26 months. Stroke, myocardial infarction, and sudden cardiac death were defined as Hard CVD events, and these plus angina, heart failure, and other CVDs were defined as All CVD events. Multivariable Cox hazard regression models predicting CVD events were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI) for different measures of BPV with adjustment for significant covariates. RESULTS In multivariable analyses, the BPV of clinic systolic BP (SBP) was an independent predictor for All CVD events (HR, 2.20; 95% CI, 1.25-3.88; P < 0.01), but not for Hard CVD events (P = 0.20). On the other hand, the BPV of sleep SBP was an independent predictor for Hard CVD events (HR, 2.21; 95% CI, 1.08-4.53; P = 0.03), but not for All CVD events (P = 0.88). Diastolic BPV exhibited the same pattern. CONCLUSIONS These findings suggest that visit-to-visit BPV and ambulatory BPV are separately useful in predicting cardiovascular outcomes.

Maximum Value of Home Blood Pressure: A Novel Indicator of Target Organ Damage in Hypertension

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.