(Stroke. 1995;26:829-833.)
© 1995 American Heart Association, Inc.
Articles |
Diminished Nocturnal Blood Pressure Decline and Lesion Site in Cerebrovascular Disease
From the Department of Neurology, Kyoto Second Red Cross Hospital (Y.Y., K.O.), and the Department of Neurology, Faculty of Medicine, Kyoto University (I.A., H.S., J.K.), Japan.
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Abstract |
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Background and Purpose Many studies have suggested that diminished nocturnal blood pressure decline in hypertensive cardiovascular disease is associated with the extent of hypertensive vascular disease. In our previous observation of cerebrovascular disease, however, we found reduced nocturnal blood pressure decline to be associated not only with the extent of hypertensive vascular disease but also with the specific location of cerebrovascular lesions. The purpose of this study was to elucidate the mechanism of nocturnal blood pressure decline in cerebrovascular disease. Moreover, to clarify whether reduced nocturnal blood pressure decline occurs before cerebrovascular disease, we examined patients with recurring episodes.
Methods Ambulatory blood pressure monitoring was carried out every 30 minutes in 14 control subjects, 15 hypertensive subjects, 90 patients with cerebrovascular disease (16 single lacunar infarctions, 15 multiple lacunar infarctions, 10 putaminal hemorrhages, 14 thalamic hemorrhages, 11 pontine base infarctions, 15 pontine tegmentum infarctions, 8 pontine hemorrhages, 13 wide cortical infarctions), and 7 patients with recurring stroke episodes. The percentage of nocturnal blood pressure decline and the correlations for systolic blood pressure and heart rate were calculated.
Results The percentage of nocturnal blood pressure decline was significantly smaller in the groups with multiple lacunar infarction (systolic, P<.001; diastolic, P<.01), thalamic hemorrhage (P<.01, P<.05), pontine tegmentum infarction (P<.01, P<.05), and pontine hemorrhage (both P<.05). The correlation between systolic blood pressure and heart rate was not significant for almost all the groups with diminished blood pressure decline.
Conclusions Diminished nocturnal blood pressure decline in cerebrovascular disease is thought to be caused by specific injury to the central autonomic nervous system such as the striatum, diencephalon, midbrain, and pontine tegmentum and their connecting fibers.
Key Words: autonomic nervous system • blood pressure • cerebrovascular disorders • hypertension
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Blood pressure is a most powerful risk factor for cerebrovascular disease (CVD). Since noninvasive ambulatory blood pressure monitoring (ABPM) was introduced to evaluate blood pressure more effectively, a considerable number of studies have indicated that target-organ damage from hypertension correlates more closely with the average 24-hour blood pressure than with casual blood pressure values.1 2 3 4 5 However, blood pressure falls at night during sleep and rises in the day.6 7 A commonly accepted explanation for the nocturnal blood pressure decline is a reduction of sympathetic nervous system activity paralleling the change in wakefulness. Many indexes of sympathetic nervous system activity, such as plasma catecholamine level,8 9 cardiac output,10 and peripheral resistance,11 12 are lower at night. Certain conditions in which nocturnal blood pressure decline is diminished due to autonomic dysfunction were reported, such as autonomic failure,13 Shy- Drager syndrome,14 cardiac plantation,15 and diabetic neuropathy.16
On the other hand, many investigators have noticed conditions in which nocturnal blood pressure decline is reduced, such as advanced hypertension,5 hypertension with left ventricular hypertrophy,17 18 19 20 or CVD.21 22 23 These findings suggest that a patient whose blood pressure does not decline is more likely to have more extensive hypertensive vascular disease.
In our preliminary observation, however, we noted that diminished nocturnal blood pressure decline in patients with CVD was associated with the particular cerebral region rather than with extensive target-organ damage. In conducting this study, we therefore hypothesized that diminished nocturnal blood pressure decline in CVD could be caused not only by the extensive vascular disease but also by specific injury of the central autonomic nervous system. The purpose of this study was to elucidate the mechanism of nocturnal blood pressure decline in CVD. Moreover, to clarify whether diminished nocturnal blood pressure decline occurs before CVD, we examined patients with recurring episodes.
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Subjects and Methods |
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The study group comprised 14 control subjects (age, 61.7±7.8 years [mean±SD]; 10 men, 4 women), 15 hypertensive subjects (65.4±8.3, years; 11 men, 4 women), and 90 patients with CVD. In addition, 7 patients with two episodes of cerebral infarction in whom ABPM could be carried out after ictus after both the first and second episodes were enrolled in this study. The patients with recurring cerebral infarction were 4 men and 3 women with a mean age of 75.0±6.5 years and a mean period between the two episodes of 1.5 years.
The 90 patients with CVD were divided into eight groups based on the findings of computed tomography (CT) and magnetic resonance imaging (MRI; 1.5-T Shimazu) as follows: 16 patients with single lacunar infarction (mean age, 63.7±5.2 years; 10 men, 6 women), 15 with multiple lacunar infarction (69.4±6.1 years; 9 men, 6 women), 10 with putaminal hemorrhage (65.9±7.6 years; 7 men, 3 women), 14 with thalamic hemorrhage (66.9±8.6 years; 4 men, 10 women), 11 with infarction in which the lesion was restricted to the pontine base (66.3±9.0 years; 11 men, 1 woman), 15 with infarction in which the lesion involved the pontine tegmentum (72.3±4.7 years; 12 men, 3 women), 8 with pontine hemorrhage (62.2±7.9 years; 7 men, 1 woman), and 13 with wide cortical infarction who were bedridden due to single or double middle cerebral artery occlusion including both thrombosis and embolism (73.4±8.8 years; 6 men, 7 women).
The control subjects comprised 9 patients with tension headache, 3 with cervical spondylosis, and 2 with nonneurological disease who had no risk factors for stroke or autonomic dysfunction. The hypertensive subjects were patients with an office systolic and diastolic pressure persistently above 160 and 90 mm Hg, respectively. Among hypertensive subjects, those manifesting cardiovascular complications or silent stroke detected by MRI were excluded. Those patients entered into the hypertensive group had almost the same risk factors as the CVD patients in terms of age, sex, obesity, glucose tolerance abnormality, and tobacco and alcohol use. Patients with secondary hypertension such as renovascular hypertension and endocrinological hypertension were excluded.
Consecutive patients diagnosed by CT and MRI who met the following criteria were selectively entered into each subgroup. The target number of patients in each group was 15. The patients were enrolled before ABPM was carried out. The patients were requested to record their daily activities and sleep periods and whether they slept soundly. However, patients who had dementia and possibly could not sleep soundly could not be excluded completely, although these patients were very few. Outpatients were prohibited from working or active movement.
Noninvasive ambulatory blood pressure recording was performed with a portable automatic recorder (ABPM-630, Nippon Korin Co) in each subject. Informed consent was obtained from each participant. The accuracy of the equipment had been previously established.24 The oscillometric method was used in this study. CVD patients, including those with recurrence, underwent noninvasive ABPM more than 4 weeks after ictus. All of these subjects were free of medication that could have influenced their blood pressure during ABPM. Antihypertensive drugs at appropriate dosages were prescribed after ABPM recording. Those with cardiovascular complications, sleep apnea syndrome,25 or diabetes mellitus who were receiving insulin or taking antihyperglycemic medication were excluded.
Systolic and diastolic blood pressures and heart rate were recorded at 30-minute intervals over 24 hours (ie, 48 times a day) from 1 PM to 1 PM the next day. Systolic and diastolic blood pressures were averaged over successive 30-minute periods throughout the 24-hour period. The mean values of both daytime (6 AM to 10 PM) and nighttime (10:30 PM to 5:30 AM) systolic and diastolic blood pressures were also calculated. These values were used for each subject as the basis for computing the percentage of nocturnal blood pressure decline ([mean daytime blood pressure - mean nighttime blood pressure/average blood pressure for the entire 24 hours] x100) and the percentage of nocturnal heart rate decline.
In the 7 patients with recurring episodes of CVD, the mean values of systolic blood pressure were calculated after the first and second episodes separately at 30-minute intervals and plotted over 24 hours (48 points). The relationship between the 24-hour systolic blood pressure and the heart rate, which was instantaneously recorded every 30 minutes, was examined in each group. The coefficient of correlation, as well as the linear regression coefficient, for the systolic blood pressure with heart rate was calculated by least-squares linear regression analysis. ANOVA was used to evaluate the differences among groups, and significant difference from control subjects was identified with Dunnett's multiple comparison. Data are expressed as mean±SD.
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Results |
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The mean 24-hour and nighttime average systolic and diastolic blood pressures for each subject group are given in Table 1
, and nocturnal blood pressure reduction is shown in
Table 2. The mean percentages of nocturnal blood
pressure decline in each group for systolic and diastolic blood
pressure are shown graphically in Fig 1. ANOVA revealed
significant differences among the eight CVD groups in the average
systolic and diastolic blood pressures for the entire day and nighttime
(24-hour systolic, P<.01; 24-hour diastolic,
P<.05; nighttime systolic, P<.01; nighttime
diastolic, P<.05).
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ANOVA revealed significant differences among the eight CVD groups in the percentages of nocturnal reduction for both systolic and diastolic blood pressure (both P<.01). Compared with that in normal subjects, the percentage of nocturnal decline in systolic blood pressure was significantly smaller in the patients with multiple lacunar infarction (P<.001), thalamic hemorrhage (P<.01), pontine tegmentum infarction (P<.001), and pontine hemorrhage (P<.05), and that in diastolic blood pressure was significantly smaller in each of these groups (P<.01, P<.05, P<.05, and P<.01, respectively) as well as in those with wide cortical infarction (P<.05). No significant difference from the control value was seen in patients with hypertension, single lacunar infarction, putaminal hemorrhage, or pontine base infarction for either systolic or diastolic nocturnal blood pressure reduction. In patients with wide cortical infarction, no significant difference was seen for systolic blood pressure, but significant difference was seen for diastolic blood pressure (P<.05).
The mean of the average heart rate for the entire day and the
percentages of nocturnal heart rate reduction are shown in Table 3. ANOVA revealed a significant difference among the
eight CVD groups in the percentage of nocturnal reduction for heart
rate (P<.05). Compared with that in normal subjects, the
percentage of nocturnal reduction in heart rate was significantly
smaller in the patients with pontine hemorrhage and wide cortical
infarction (both P<.05).
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In the 7 patients with recurring episodes, the circadian systolic blood
pressure pattern after the second episode differed from that after the
first. Their blood pressures increased after the second episode,
especially from 7 PM to 1 AM, and conversely
decreased from 7:30 AM to 11 AM. Thus, the
nocturnal decline and the morning rise in blood pressure were even
further reduced after the second episode (Fig 2).
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) and
the second episode (
).
A significant positive correlation between systolic blood pressure and
heart rate was found in the group of normal subjects and patients with
hypertension, single lacunar infarction, putaminal hemorrhage, pontine
base infarction, pontine hemorrhage, and wide cortical infarction
(Table 4).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The present results indicate that the percentage of nocturnal blood pressure decline was reduced compared with the control value in certain CVD subgroups, ie, patients with multiple lacunar infarction, thalamic hemorrhage, pontine tegmentum infarction, and pontine hemorrhage. On the basis of these results, it can be inferred that diminished nocturnal blood pressure decline would be more highly associated with the site of the cerebral vascular lesion rather than with the extent of hypertensive vascular disease. Indeed, since these studies were performed after stroke, it is possible that the blood pressure abnormalities existed before stroke. However, the studies of 7 patients with recurring episodes revealed that the relative reduction of nocturnal blood pressure decline after the second episode was even further reduced compared with that after the first. The results of this longitudinal study suggest that diminished nocturnal blood pressure decline is a consequence of CVD rather than a cause. Furthermore, the comparison of the patients with single and multiple lacunae revealed that the percentage of nocturnal blood pressure decline decreased in association with the development of lacunae. It is conceivable that nocturnal blood pressure decline in hypertensive patients would end with the development of multiple lacunae.
Multiple lacunar infarction involves deep and specific cerebral regions including the striatum, diencephalon, frontal operculum, cingulate gyrus, and their connections. This subcortical and cortical gray matter and its connecting fibers are strongly related not only to central levels of the autonomic regulation system but also to ascending central monoaminergic fibers. Furthermore, the midbrain and pontine tegmentum include the major neuron source of the central monoaminergic system, in contrast to the pontine base.26 Therefore, it is conceivable that diminished nocturnal blood pressure decline would be caused by injury to the central autonomic nervous system, which during the night reduces sympathetic activity and increases parasympathetic activity.27 Otsuka and his colleagues28 suggest that the suprachiasmatic nucleus might play a important role in generating circadian rhythm.
Consistent with this hypothesis, most of the subgroups with diminished nocturnal blood pressure decline also showed a weak correlation for systolic blood pressure with heart rate. A strong association between blood pressure and heart rate suggests a close involvement of the autonomic nervous system in the circadian variability of blood pressure.29 Therefore, the weak correlation between blood pressure and heart rate would represent impairment of autonomic nervous system activity. On the other hand, as these lesion sites are also highly related to the sleep-generating and -modulating structures of the brain stem and the diencephalon,26 which also are strongly related to the intracerebral preganglionic autonomic regulation system, there is a possibility that injury to the sleep-associated structures could be the primary lesion responsible for diminished nocturnal blood pressure decline. However, autonomic nervous system disturbances manifested as low correlation between blood pressure and heart rate would play a major role in diminished nocturnal blood pressure decline.
In wide cortical infarction, however, these cerebral structures are spared. Although the patients with wide cortical infarction were bedridden, their nocturnal systolic blood pressure decline was relatively well preserved. This is in contrast to the pattern of diminished blood pressure decline in patients with multiple lacunar infarction, who could walk and continue their routine daily life. These results suggest that nocturnal blood pressure decline in CVD is influenced more strongly by central autonomic nervous system dysfunction rather than by physical activity, although physical activity plays an important role in healthy subjects.
On the other hand, it is reasonable to assume that hypertensive patients whose blood pressure remains high throughout the night will fare more poorly over the long term than those patients whose blood pressure declines. Harshfield and his colleagues30 reported that black boys showed a lack of nocturnal blood pressure decline and hypothesized that they would be susceptible to cardiovascular damage. It is still unclear whether diminished nocturnal blood pressure decline is a compensatory mechanism to maintain organ blood flow or whether autonomic dysfunction under these conditions promotes the impairment of organ blood flow. It is an important problem in managing hypertensive patients whose blood pressure does not decline during the night. A longitudinal study of these sequellae would resolve this issue.
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Footnotes |
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Reprint requests to Dr Yasumasa Yamamoto, Department of Neurology, Kyoto Second Red Cross Hospital, 355-5 Kamanzadori Marutamachi, Kamigyo-ku, Kyoto 602, Japan.
Received June 21, 1994; revision received February 14, 1995; accepted February 14, 1995.
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