Reproducibility of ambulatory blood pressure in treated and untreated hypertensive patients.

OBJECTIVE: We tested the reproducibility of ambulatory blood pressure (ABP), BP variability, and BP reduction in hypertensive patients. METHODS: Forty-two hypertensive patients were enrolled, and ABP monitoring (ABPM) was performed four times in each patient: twice before and twice after the treatment. Morning BP was defined as the average of 2 h after waking, and morning BP surge (MBPS) was defined by four ways: sleep-trough, preawake, morning-evening and morning-after-bed surge. The BP variability was evaluated by standard deviation, weighted standard deviation, coefficient of variation and average real variability. The reproducibility was compared using the repeatability coefficient and the Bland-Altman's method. RESULTS: The awake, sleep, 24-h and morning BP were well corresponded in the first and the second ABPM values in each period. The four measures of BP variability also corresponded well between the first and the second ABPM values in each period. MBPS did not correspond well in each period when it was defined by diaries, but the extent of correlation was improved when it was defined by actigraphy. The reproducibility of BP-lowering effect was fair when it was defined by a single parameter, but not very good when it was defined by two parameters (e.g. MBPS). CONCLUSION: The reproducibility of ABP levels and BP variability was fairly good and that of MBPS was moderate when defined by actigraphy. The good reproducibility of BP reduction means that each single ABPM, before and after the treatment, is acceptable for the assessment of drug efficacy.

[Papillary fibroelastoma in the right ventricular outflow tract: a case report].

A 60-year-old female was admitted to our hospital for further examination of heart murmur. Chest radiography revealed cardiomegaly and pulmonary congestion. Two-dimensional echocardiography showed a mobile and pedunculated mass, approximately 20 mm in diameter, attached to the right ventricular outflow tract, and perimembranous ventricular septal defect. Cardiac catheterization and blood sampling were performed, which showed a pulmonary to systemic flow ratio of 3.70. She underwent surgical excision of the tumor, ventricular septal defect patch suture and tricuspid annuloplasty. Histological examination confirmed papillary fibroelastoma. The predominant location of papillary fibroelastoma is the valvular surface. This very rare case of papillary fibroelastoma was located in the right ventricular outflow tract.

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 > 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.

Morning blood pressure hyper-reactivity is an independent predictor for hypertensive cardiac hypertrophy in a community-dwelling population.

BACKGROUND: Morning blood pressure (BP) surge seems to be a risk factor for cardiovascular events. Although physical activity after arising significantly affects morning BP surge, it has remained unclear whether morning BP surge after controlling for physical activity (morning BP reactivity) is associated with target organ damage. METHODS: We performed ambulatory BP monitoring with simultaneous actigraphy and echocardiography in 120 community-dwelling Japanese subjects. We determined the waking time by actigraphy, and defined morning BP surge (MBPS) as the average of systolic BP during the 2 h after awakening minus the average of systolic BPs during the 1 h that included the lowest sleep BP. The ratio of MBPS/(sum of the 2-h physical activity after the arising time)0.5 was calculated as the morning BP reactivity (MBPR). RESULTS: In all the subjects studied (n = 120), MBPR was positively associated with left ventricular (LV) mass index (r = 0.30, P = .001). The MBPR had a positive association with both 24-h BP variability (SD) (r = 0.373, P < .001) and awake BP variability (r = 0.20, P < .05). The MBP hyper-reactive group (the highest quartile [Q4] of MBPR: n = 30) had significantly higher LV mass index than the nonreactive group (the other quartiles [Q1 to 3]: n = 90) (140 v 113 g/m(2), P < .001). Even after controlling for age, body mass index, gender, and 24-h systolic BP, the MBP hyper-reactive status still remained a strong predictor for LV hypertrophy. CONCLUSIONS: Exaggerated MBPS, adjusted for physical activity, is associated with cardiac hypertrophy independent of ambulatory BP level in a community-dwelling population.

Morning blood pressure surge and hypertensive cerebrovascular disease: role of the alpha adrenergic sympathetic nervous system.

BACKGROUND: The morning surge of blood pressure (BP) is associated with alpha-adrenergic activity. We studied the association between the alpha-adrenergic morning surge in BP and silent cerebrovascular disease in elderly patients with hypertension. METHODS: We conducted ambulatory BP monitoring three times (twice at baseline and after nighttime dosing of the alpha1-blocker doxazosin) in 98 elderly hypertensive patients in whom the presence of silent cerebral infarcts (SCI) was assessed by brain magnetic resonance imaging. The morning BP surge (MBPS) was calculated as the mean systolic BP during the 2 h after waking minus the mean systolic BP during 1 h that included the lowest sleep BP. The alpha-adrenergic MBPS was calculated as the reduction of MBPS by doxazosin. RESULTS: The prevalence of multiple SCI was higher in the Surge group (top quartile: MBPS > or = 45 mm Hg, n = 24) than in the Nonsurge group (MBPS < 45 mm Hg, n = 74) (54% v 31%, P = .04), and in the higher alpha-adrenergic surge group (top quartile: alpha-adrenergic MBPS > or = 28 mm Hg, n = 25) than in the lower alpha-adrenergic surge group (< 28 mm Hg, n = 73) (68% v 26%, P < .0001). In the Surge group, subjects with higher alpha-adrenergic surge (n = 17) had a markedly higher frequency of multiple SCI, whereas none in the lower alpha-adrenergic surge group had multiple SCI (n = 7) (77% v 0%, P = .001). The alpha-adrenergic MBPS was closely associated with multiple SCI (10 mm Hg increase: OR = 1.96, P = .006), independently of age, MBPS, 24-h systolic BP, and other confounding factors. CONCLUSION: The morning BP surge, particularly that dependent on alpha-adrenergic activity, is closely associated with advanced silent hypertensive cerebrovascular disease in elderly individuals.

Greater change of orthostatic blood pressure is related to silent cerebral infarct and cardiac overload in hypertensive subjects.

Greater change of postural blood pressure (BP) is often seen in elderly hypertensives and is recognized as a risk factor for cognitive decline and poorer cerebrovascular outcome, but its clinical significance still remains to be clarified. We performed a head-up tilting test, ambulatory BP monitoring, and brain MRI in 59 hypertensives and 27 normotensive subjects. We measured plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels at rest to assess cardiac burden. The 59 hypertensive patients were classified into 3 groups: an orthostatic hypertension (OHT) group with orthostatic increase in systolic BP (SBP) > or = 10 mmHg (n=16); an orthostatic hypotension (OHYPO) group with orthostatic SBP decrease < or = -10 mmHg (n=18); and an orthostatic normotension (ONT) group with neither of these two patterns (n=25). A group of 27 normotensive subjects (NT) was also included as a control. Plasma BNP (72 +/- 92 vs. 29 +/- 24 pg/ml, p < 0.05) and BNP/ANP ratio (4.6 +/- 3.3 vs. 2.4 +/- 1.5, p < 0.05) were significantly higher in the OHYPO than in the NT group. The BNP/ANP ratio was also higher in the OHT than in the NT group (5.1 +/- 3.9 vs. 2.4 +/- 1.5, p < 0.01). The number of silent cerebral infarct (SCI), prevalence of SCI and number of multiple SCIs was the highest in the OHT group, followed in order by the OHYPO, ONT and NT groups. Blood pressure and left ventricular mass index were not significantly different among the 3 hypertensive groups. In conclusion, hypertensive patients with greater change of postural BP (OHT and OHYPO) were shown to have increased risk of advanced silent brain lesions and greater cardiac burden.

Comparison of valsartan and amlodipine on ambulatory and morning blood pressure in hypertensive patients.

BACKGROUND: Cardiovascular events occur most frequently in the morning. We aimed to study the effects of monotherapy with the long-acting angiotensin II receptor blocker valsartan compared with the long-acting calcium antagonist amlodipine on ambulatory and morning blood pressure (BP). METHODS: We performed ambulatory BP monitoring before and after once-daily dose of valsartan (valsartan group, n = 38) and amlodipine (amlodipine group, n = 38) therapy in 76 hypertensive patients. To achieve the target BP of < or =140/90 mm Hg, valsartan was titrated from 40 mg/day to 160 mg/day (mean dose 124 mg/day) and amlodipine was titrated from 2.5 mg/day to 10 mg/day (mean dose 6.4 mg/day). RESULTS: Both drugs significantly reduced clinic and 24-h systolic BP (SBP) and diastolic BP (DBP) (P <.002). However, the antihypertensive effect of amlodipine was superior to that of valsartan in clinical SBP (-26 mm Hg v -13 mm Hg, P =.001) and 24-h SBP (-14 mm Hg v -7 mm Hg, P =.008). In addition, morning SBP was significantly reduced by amlodipine from 156 to 142 mm Hg (P <.001) but not by valsartan. Both agents reduced lowest night SBP to a similar extent (amlodipine 121 to 112 mm Hg, P <.001; valsartan 123 to 114 mm Hg, P <.002). Reduction in morning SBP surge (morning SBP minus lowest night SBP) was significantly greater in patients treated with amlodipine compared with those treated with valsartan (-6.1 mm Hg v +4.5 mm Hg, P <.02). CONCLUSIONS: Amlodipine monotherapy was more effective than valsartan monotherapy in controlling 24-h ambulatory BP and morning BP in hypertensive patients.

Smoking is associated with silent cerebrovascular disease in a high-risk Japanese community-dwelling population.

We aimed to investigate the relationships between smoking and silent cerebrovascular damage. We performed brain MRI to evaluate silent cerebral infarct (SCI) and periventricular hyperintensity (PVH), and carotid-ultrasonography to investigate carotid atherosclerotic plaque in 170 high-risk community-dwelling subjects (mean age: 67.2 years; men: 28.7%) who met more than 3 of the following 9 criteria: 1) high blood pressure (BP); 2) hypercholesterolemia; 3) left ventricular hypertrophy; 4) high hemoglobin A1c; 5) proteinuria; 6) high waist-to-hip ratio; 7) smoking > or =30 cigarettes/day; 8) heavy alcohol intake; 9) family history of stroke. The subjects with SCI (SCI group) were older (70 years vs. 66 years, p=0.004) and had higher systolic BP (SBP) (160 vs. 148 mmHg, p <0.001) and higher carotid plaque score (2.3 vs. 1.5/person, p <0.05) than those without SCI. Among the variables, smoking status (r =0.34, p <0.001), SBP (r =0.28, p <0.001), male gender (r =0.29, p <0.001), left ventricular mass index (r =0.25, p =0.001), and serum creatinine (r =0.20, p =0.006) were significantly correlated with the number of SCIs. Among smokers, the number of SCIs was significantly higher in current smokers than in past smokers (1.9+/-2.2 vs. 0.5+/-0.8, p <0.01). In multiple regression analysis, smoking status (beta =0.183, p =0.045) and SBP (beta =0.196, p =0.011) were independent determinants of the increased number of SCIs. In conclusion, smoking status was an independent determinant of multiple SCIs in a high-risk Japanese community-dwelling population.

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.

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 > 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.

Incomplete benefit of antihypertensive therapy on stroke reduction in older hypertensives with abnormal nocturnal blood pressure dipping (extreme-dippers and reverse-dippers).

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.

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.