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From the Department of Cerebrovascular Disease, Institute of
Neuroscience, St Mary's Hospital, Kurume (S.A., Y.S.), and Second
Department of Internal Medicine, Faculty of Medicine, Kyushu University,
Fukuoka (S.I., T.N., M.F.), Japan.
Correspondence to Shuji Arakawa, MD, Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. E-mail arakawa{at}qmed.hosp.go.jp
Methods—We analyzed 74 patients with HBH who were
admitted to our clinic and followed up as outpatients for a mean
of 2.8 years. Blood pressure (BP) and other clinical features were
compared between the groups of patients with and without rebleeding. We
determined the recurrence rate of HBH in relation to BP.
Results—Diastolic BP was significantly higher in the
recurrence group than in the nonrecurrence group
(88±8 versus 82±7 mm Hg; P=0.04).
Systolic BP and other clinical variables were not different
between the groups. The recurrence rate was 10.0% per
patient-year in patients with diastolic BP >90 mm Hg
and <1.5% in those with lower diastolic BP
(P<0.001). No patients with diastolic BP
<70 mm Hg experienced rebleeding.
Conclusions—Higher diastolic BP was related to an
increased rate of rebleeding. Diastolic BP >90 mm Hg
may be regarded as a factor predictive of the recurrence of
HBH.
In this study we evaluated the relationship between recurrence
of HBH and other clinical variables, with special emphasis on
postictal BP levels.
The hypertensive nature of brain hemorrhage was determined by
(1) location of hematoma in the putamen, thalamus, pons, cerebellum, or
subcortical white matter; (2) documentation of hypertension by medical
history or BP readings >160/95 mm Hg (on at least 3 different
days >4 weeks after the onset of hemorrhage) or regular use of
antihypertensive drugs for BP control; and (3) exclusion of known or
suspected causes of hemorrhage such as aneurysm,
arteriovenous malformation, head trauma, brain tumor, anticoagulant
use, and cerebral amyloid angiopathy. The location of
hemorrhage was as follows: 32 patients (43%) in putamen, 27
(36%) in thalamus, 7 (9%) in subcortical white matter, and 8 (11%)
in pons or cerebellum.
Examination of the patients and measurements of BP were made every 4
weeks. At each follow-up examination, data were collected on
neurological status, new cerebrovascular episodes, and BP levels.
Sixty-one patients (82%) received antihypertensive drugs depending on
physicians' judgment.
Mean values of systolic BP (SBP) and diastolic BP
(DBP) during follow-up periods were determined by averaging all values
recorded in the outpatient clinic and were compared between the
groups of patients with and without rebleeding. In patients with
rebleeding, all BP readings before the recurrence were
averaged. We also determined the recurrence rate of HBH in
relation to mean values of BP during follow-up periods.
Other clinical profiles such as age, sex, location of
hemorrhage, history of ischemic stroke, diabetes
mellitus (determined by an oral glucose tolerance test, casual blood
glucose levels >200 mg/dL, or medical history of diabetes),
hyperlipidemia (total cholesterol >220
mg/dL and/or triglycerides >160 mg/dL), liver cirrhosis
(by blood tests and ultrasonography), chronic renal failure (those on
maintenance hemodialysis), ischemic heart disease
(history of angina pectoris or myocardial infarction), and
antihypertensive and antiplatelet therapy after the first
hemorrhage were also analyzed.
Statistical comparisons between the groups were performed with
Student's t test or the Mann-Whitney U test for
the comparison of two groups and Fisher's exact probability test for
the analysis of proportion. Recurrence-free rates were
analyzed with a log-rank test and Cox's proportional hazards
regression model. Values of P<0.05 were considered
significant.
When we analyzed the recurrence rate of HBH in terms of
the level of DBP and SBP, recurrence was more common in
patients with higher DBP during the follow-up. Five of 10 patients
(50%) with DBP >90 mm Hg developed recurrent hemorrhage
(Figure 1
Other clinical variables were not different between the groups of
patients with and without rebleeding. Although patients in the
recurrence group were younger than those in the
nonrecurrence group, the difference did not reach statistical
significance (Table 2
The relationship between BP after the first HBH and rebleeding has been
evaluated in few studies. Some authors reported that patients with
rebleeding did not achieve good BP control after the first
HBH4 5 6 ; however, desirable BP levels have not
been analyzed systematically in these studies. We examined the
relationship between BP control after the first HBH and its
recurrence in terms of SBP and DBP levels. Although elevated
DBP might only be a reflection of advanced hypertensive arteriopathy in
HBH patients, DBP >90 mm Hg may be regarded as one of the
factors predictive of recurrent HBH. It must be determined whether the
control of DBP <90 mm Hg can reduce the recurrence in a
prospective randomized intervention study.
Poststroke SBP, unlike DBP, was not associated with the
recurrence rate of HBH. This may be due to a relatively good
control of SBP in the patients involved in the present
analysis. The range of SBP in our patients was between 113 and
158 mm Hg (mean, 135 mm Hg), and patients with
severe hypertension were not present in this study. The threshold
levels of SBP may be >160 mm Hg in terms of the
recurrence of HBH. Alternatively, DBP plays a more important
role than does SBP in the recurrence of HBH. The predominant
importance of DBP over SBP on the incidence of initial brain
hemorrhage has been reported in some epidemiological
studies.11 12 The incidence of the first brain
hemorrhage was markedly dependent on recent DBP
levels11 and highest in those with
diastolic hypertension in a prospective population
survey.12 Similarly, DBP might also be a critical
factor for recurrent HBH. However, concerning the importance of SBP, we
must be aware that a relatively small number of samples might have
resulted in a type II error in the present study.
We could not find any difference in variables other than BP between
the groups of patients with and without rebleeding. Younger age at the
first HBH10 and the presence of liver
cirrhosis13 were reported to increase the risk of
subsequent brain hemorrhage. However, these were not regarded
as significant risks for recurrence in the present study.
The lack of relationship between the recurrence of HBH and
liver cirrhosis may be due to the small number of patients with liver
cirrhosis in our analysis.
The recurrence rate in this study is higher than that reported
in most previous studies (Hirohata et al,3 1.8%;
Lee et al,4 2.7%; Chen et
al,5 5.3%; Misra and
Kalita,6 4.7%; Passero et
al,9 24%; Maruishi et
al,14 5.9%; and Neau et
al,10 6.4%). This is due, at least in part, to
different follow-up periods. A relatively longer follow-up period in
this study may have resulted in the higher cumulative
recurrence rate. Furthermore, in the present series
patients with a previous HBH were recruited selectively. In the studies
by Passero et al9 and Neau et
al,10 a majority of cases with recurrent brain
hemorrhage exhibited a "lobar-lobar" type
recurrence, which is suggestive of the presence of cerebral
amyloid angiopathy as an etiology of brain hemorrhage.
In conclusion, higher DBP after HBH was related to an increase in
rebleeding, and DBP >90 mm Hg may be a factor predictive of
recurrent HBH. Well-programmed prospective intervention studies are
needed to determine the benefits of DBP control after HBH.
Received April 2, 1998;
revision received June 4, 1998;
accepted June 4, 1998.
2.
Douglas MA, Haerer AF. Long-term prognosis of
hypertensive intracerebral hemorrhage.
Stroke. 1982;13:488–491.
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Takeda T, Murakami Y, Matsui S, Zenke K, Ueda T. Study on
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Cardiovascular Disease in the Elderly. Osaka,
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© 1998 American Heart Association, Inc.
Original Contributions
Blood Pressure Control and Recurrence of Hypertensive Brain Hemorrhage
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—Recent
studies have demonstrated that recurrence of hypertensive brain
hemorrhage (HBH) is not uncommon. However, risk factors for the
recurrence of HBH have not been evaluated
systematically.
Key Words: blood pressure • cerebral hemorrhage • hypertension • stroke prevention
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Although hypertensive
brain hemorrhage (HBH) has been generally considered to be a
one-time event,1 2 recent studies have
demonstrated that recurrence of HBH is more common than
believed. Reported recurrence rates are 1.8% to 5.3% for
various follow-up periods.3 4 5 6 The higher
recurrence rate is due, at least in part, to decreased
mortality from brain hemorrhage7 8 and an
increased number of survivors with high risks for recurrence.
The incidence of recurrent HBH has been a subject of a number of
studies, while risk factors for rebleeding have not been evaluated
systematically. Although uncontrolled hypertension appears to be an
important risk factor for
recurrence,4 5 6 9 10 the level of blood
pressure (BP) that may prevent rebleeding is uncertain.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
From January 1995 to December 1996, 93 patients with HBH visited
our clinic as outpatients. All patients experienced first-ever HBH
between 1982 and 1996 and had been followed up monthly until the time
of inclusion in this study. Nineteen patients with follow-up periods
<3 months were excluded. We analyzed 74 patients (51 men, 23
women; mean age, 59 years) with follow-up periods of 3 to 162 months
(mean, 67 months).
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Eight patients (11%) had recurrent HBH (Table 1
), and the overall
recurrence rate was 2.0% per patient-year. The interval
between the first and recurrent hemorrhage ranged from 1.3 to
12.3 years. All patients but 2 were on antihypertensive medication.
Common antihypertensive agents were calcium antagonists and
angiotensin-converting enzyme inhibitors.
Systolic BP after the first HBH was not different between
groups (recurrence group versus nonrecurrence group:
136±8 versus 135±10 mm Hg [mean±SD]; P=0.7). In
contrast, DBP was significantly higher in the recurrence group
than in the nonrecurrence group (88±8 versus 82±7
mm Hg; P=0.04) (Table 2). In the patients with
recurrence, 2 showed good functional recovery, 1 was moderately
disabled, 2 were severely disabled, 2 were in a vegetative state, and 1
died.
View this table:
[in a new window]
Table 1. Clinical Characteristics of 8 Patients With
Recurrence of HBH
View this table:
[in a new window]
Table 2. Univariate Correlation Between Baseline Variables
and Rebleeding After HBH in 74
Patients ). Patients with DBP >90
mm Hg had a significantly higher recurrence rate than those
with lower DBP (Figures 2 and 3) (P<0.001). The other 3
patients with rebleeding had DBP between 70 and 90 mm Hg (Figure 1). No patients with DBP <70 mm Hg (n=5) had rebleeding. The
recurrence rate of HBH appeared to elevate with increasing SBP,
but the difference was not significant (Figure 2).
View larger version (18K):
[in a new window]
Figure 1. Mean values of poststroke BP and clinical
outcome.
View larger version (12K):
[in a new window]
Figure 2. Poststroke BP and recurrence rate of HBH.
Patients with DBP >90 mm Hg had a significantly higher
recurrence rate than those with lower DBP
(P<0.001, log-rank test).
View larger version (21K):
[in a new window]
Figure 3. Kaplan-Meier curve for probability of
rebleeding-free survival according to stratified poststroke DBP. The
differences between the group of patients with DBP >90 mm Hg and
the other two groups were statistically significant
(P<0.001, log-rank test). 
). Higher DBP was associated with increased
recurrence rate even after correction for age
(P=0.05).
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
In this study we showed that recurrence of HBH was more
frequent in patients with higher poststroke DBP. The recurrence
rate in patients with DBP >90 mm Hg was 10.0% per patient-year,
and this was significantly higher than the rate in those with DBP
<90 mm Hg. None of the patients with DBP <70 mm Hg had
rebleeding. We could not find a consistent relationship between
SBP and recurrence rate.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
1.
Kase CS, Mohr JP. General features of
intracerebral hemorrhage. In: Barnett HJM, Mohr
JP, Stein BM, Yatsu FM, eds. Stroke: Pathophysiology, Diagnosis,
and Management. New York, NY: Churchill Livingstone;
1986:497–523.
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