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(Stroke. 1997;28:1185-1188.)
© 1997 American Heart Association, Inc.

Articles

Prognostic Value of Admission Blood Pressure in Patients With Intracerebral Hemorrhage

Keio Cooperative Stroke Study

Yasuo Terayama, MD; Norio Tanahashi, MD; Yasuo Fukuuchi, MD; Fumio Gotoh, MD

From the Division of Neurology, Shimizu Municipal Hospital (Y.T.), and the Department of Neurology, School of Medicine, Keio University, Tokyo (N.T., Y.F., F.G.), Japan.

Correspondence to Dr Yasuo Terayama, CBF Laboratory, VA Medical Center, 151-A, 2002 Holcombe Blvd, Houston, TX 77030.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose Patients with acute stroke on admission to the hospital are often found to have high blood pressure. The purpose of the present study was to investigate the prognostic value of admission blood pressure in patients with acute intracerebral hemorrhage, including putaminal, thalamic, subcortical, cerebellar, and pontine hemorrhage.

Methods A total of 1701 patients with intracerebral hemorrhage of the putamen (n=776; mean±SD age, 58±14 years), thalamus (n=538; 63±12 years), subcortex (n=153; 61±16 years), cerebellum (n=110; 64±11 years), and pons (n=124; 59±13 years) were examined. The mean blood pressure on admission in patients with a fatal outcome was compared with that in patients who survived.

Results The mean age in each patient group (putaminal, thalamic, subcortical, cerebellar, and pontine hemorrhage) with fatal outcome was older than that with nonfatal outcome, while ANCOVA indicated no correlation between age and blood pressure on admission or age and volume of hematoma. The mean arterial blood pressure on hospital admission was 126.9±25.8 mm Hg (±SD) in cases of putaminal, 127.4±22.6 mm Hg in thalamic, 116.4±20.6 mm Hg in subcortical, 123.5±23.9 mm Hg in cerebellar, and 133.0±26.0 mm Hg in pontine hemorrhage. The mean blood pressure on admission in patients with a fatal outcome among those with putaminal (136.0±36.3 mm Hg) and thalamic (133.2±22.1 mm Hg) hemorrhage was significantly higher than that in those with a nonfatal outcome (123.8±20.6 mm Hg for putaminal, 101.6±22.5 mm Hg for thalamic) (P<.01). No correlation between mean blood pressure and outcome was observed in the patients with subcortical (116.5±22.2 mm Hg for nonfatal, 114.9±22.0 mm Hg for fatal outcome), cerebellar (125.2±22.2 mm Hg, 116.9±28.8 mm Hg), and pontine (129.9±23.8 mm Hg, 136.0±27.7 mm Hg) hemorrhage. The volume of hematoma on admission in patients with fatal outcome with putaminal (58.2±24.4 mL), thalamic (27.0±13.1 mL), subcortical (32.9±14.4 mL), and cerebellar (31.4±28.6 mL) hemorrhage was greater than that in those with nonfatal outcome (20.8±11.4 mL, 7.1±4.8 mL, 18.3±10.6 mL, and 8.1±4.2 mL, respectively; P<.01), while no correlation between volume of hematoma and outcome was observed in patients with pontine hemorrhage.

Conclusions The above data suggest that an increased mean blood pressure and volume of hematoma on admission in putaminal and thalamic hemorrhage were related to increased mortality, while in patients with subcortical, cerebellar, and pontine hemorrhage, the mean blood pressure was not related to the clinical outcome.

Key Words: blood pressure • intracerebral hemorrhage • hematoma • outcome

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Patients with acute stroke on admission to the hospital are often found to have high blood pressure.^{1 2 3 4} Previous studies have shown variable results regarding the prognostic value of high blood pressure in acute stroke.^{5 6 7 8 9 10 11 12 13} The purpose of the present study was to determine whether initial blood pressure level in acute stroke patients, especially in patients with acute intracerebral hemorrhage (ICH), is of prognostic value in relation to mortality.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The present study included 1701 patients with ICH, including putaminal (n=776 patients; mean age, 57.9±14.4 years), thalamic (n=538; 63.4±11.8 years), subcortical (n=153; 60.7±15.5 years), cerebellar (n=110; 64.3±10.7 years), and pontine hemorrhage (n=124; 58.7±12.9 years) (Table 1). The subjects were consecutive patients admitted to the Department of Neurology, Keio University Hospital and its 10 affiliated neurological institutes and hospitals in the 5-year period from 1984 to 1988. Of these patients, 1698 were indigenous Japanese (99.8%) and 3 were American, Korean, and Chinese; 84% had a history of hypertension, and 69% of them had been treated. Blood pressure was measured in each patient in the supine position on arrival at the hospital. Every patient was diagnosed by brain CT scan within 24 hours after onset. Blood pressure on admission was reviewed, and volume of hematoma was measured with the use of the CT scan retrospectively in each subject. Patients in whom the cause of death was directly related to the hemorrhage were classified as patients with fatal outcome. The mean interval from admission to fatal outcome of these patients was 7.6±6.8 days. Volume of hematoma was calculated as 1/2xLong DiameterxShort DiameterxThick-ness of the high-density area on CT scan.¹⁴

View this table: [in this window] [in a new window]   Table 1. Age, Sex, and Mean Arterial Blood Pressure in 1701 Patients With Intracerebral Hemorrhage

Values are expressed as mean±SD unless otherwise stated. Differences between groups were compared with Student's t test. A level of P<.05 was accepted as statistically significant. During this period, 4320 ischemic stroke patients were seen in these hospitals.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Table 1 shows mean blood pressure on hospital admission in patients with ICH. As shown, mean blood pressure in patients with pontine hemorrhage was significantly higher than that in the other groups of ICH. Fig 1 illustrates systolic, diastolic, and mean blood pressure in patients with ICH. As shown, patients with pontine hemorrhage showed significantly higher systolic and mean blood pressure values than the other groups.

View larger version (23K): [in this window] [in a new window]   Figure 1. Comparison of systolic, diastolic, and mean arterial blood pressure on hospital admission among patients with intracerebral hemorrhage. *P<.05, **P<.01 compared with pontine hemorrhage.

Mean Age in Patients With Fatal and Nonfatal Outcome
All patients were divided into two groups according to their outcome (fatal or nonfatal). Table 2 compares mean age between patients with acute ICH with fatal and nonfatal outcome. As shown, the mean age in each patient group (putaminal, thalamic, subcortical, cerebellar, and pontine hemorrhage) with fatal outcome was older than that with nonfatal outcome, while ANCOVA indicated no correlation between age and blood pressure on admission or volume of hematoma. Mean age of the fatal group was 62.5±13.9 years, which was significantly (P<.01) older than that of the nonfatal group (59.2±14.2 years).

View this table: [in this window] [in a new window]   Table 2. Mean Age in Patients With Fatal and Nonfatal Outcome

Mean Blood Pressure in Patients With Fatal and Nonfatal Outcome
Table 3 compares mean blood pressure in patients with fatal and nonfatal outcome in acute ICH including putaminal, thalamic, subcortical, cerebellar, and pontine hemorrhage. As shown, mean blood pressure in patients with fatal outcome in putaminal and thalamic hemorrhage was significantly (P<.01) higher than that in patients with nonfatal outcome.

View this table: [in this window] [in a new window]   Table 3. Mean Arterial Blood Pressure in Patients With Fatal and Nonfatal Outcome

Correlation Between Mean Blood Pressure and Volume of Hematoma Among Patients With Intracerebral Hemorrhage
Figs 2 and 3 illustrate the correlation between mean blood pressure and volume of hematoma in patients with fatal and nonfatal outcome in acute ICH groups. As shown in Fig 2, in putaminal and thalamic hemorrhage, volume of hematoma in patients with fatal outcome (putaminal, 58.2±24.4 mL; thalamic, 27.0±13.1 mL) was significantly greater than that in patients with nonfatal outcome (putaminal, 20.8±11.4 mL; thalamic, 7.1±4.8 mL; P<.01) as well as the correlation of mean blood pressure between the two groups. This suggests that mean blood pressure and volume of hematoma correlate well with patient outcome in putaminal and thalamic hemorrhage.

View larger version (12K): [in this window] [in a new window]   Figure 2. Correlation between mean arterial blood pressure (MABP) and volume of hematoma in patients with putaminal and thalamic hemorrhage. Open symbols indicate patients with nonfatal outcome; closed symbols indicate patients with fatal outcome. **P<.01 compared with patients with nonfatal outcome.

View larger version (13K): [in this window] [in a new window]   Figure 3. Correlation between mean arterial blood pressure (MABP) and volume of hematoma in patients with subcortical, cerebellar, and pontine hemorrhage. Open symbols indicate patients with nonfatal outcome; closed symbols indicate patients with fatal outcome. **P<.01 compared with patients with nonfatal outcome.

In subcortical and cerebellar hemorrhage, volume of hematoma in patients with fatal outcome (subcortical, 32.9±14.4 mL; cerebellar, 31.4±28.6 mL) was significantly greater than in those with nonfatal outcome (subcortical, 18.3±10.6 mL; cerebellar, 8.1±4.2 mL; P<.01), while mean blood pressure in the two groups showed no difference. In pontine hemorrhage, volume of hematoma on hospital admission in patients with fatal prognosis (7.0±2.8 mL) showed no difference compared with that in those with nonfatal outcome (3.8±3.5 mL) as well as no correlation of mean blood pressure between the two groups (Fig 3). ANCOVA indicated no correlation between blood pressure on admission and volume of hematoma in all types of hemorrhage in this study.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
We have previously reported the superiority of conservative treatment over surgical therapy for hypertensive putaminal hemorrhage and thalamic hemorrhage in terms of functional outcome and suggested that quality of life should be assessed to determine the patient's prognosis.^{15 16} If we are able to assess the patient's prognosis from various factors on admission, this may lead to a prompt approach to stroke patients on admission and conclusively improve the patients' quality of life at discharge. From this point of view, we investigated the prognostic value of admission blood pressure in patients with acute ICH.

The mechanisms of high blood pressure on admission for stroke patients are unclear but may be related to stroke-induced changes in sympathoadrenal activity,^{17 18} stress reaction to hospital admission or blood pressure measurement, central mechanisms,¹⁹ or the Cushing reflex.²⁰

This increase of blood pressure after hemorrhage may be advantageous as well as disadvantageous. The Cushing reflex in patients with increased intracranial pressure increases blood pressure. Sympathetic activation secondary to the brain lesion may be a beneficial homeostatic response to increased blood flow in the ischemic penumbra.²¹ Blood pressure reduction of 20% or more is reported to cause a reduction of cerebral blood flow.²² In patients with ICH, however, rebleeding in the acute stage is more common in patients with high blood pressure on admission.^{23 24}

The present study, which does not provide a basis for recommending antihypertensive therapy for these patients, also suggests that hypertension and volume of hematoma in putaminal and thalamic hemorrhage provide an important prognostic indicator in relation to patient mortality.

Few investigators have studied the correlation between admission blood pressure and outcome in patients with ICH.^{4 13} The prognostic value of initial elevated blood pressure levels after acute stroke has been unclear. Britton and Carlsson⁷ reported that patients with a very high pressure on admission had greater mortality, whereas Allen¹⁰ reported that higher systolic blood pressure on admission but not at 24 hours after admission indicated a good prognosis.

Although the value of treating an elevated blood pressure at this stage after stroke remains unclear, most general practitioners continue antihypertensive treatment during the initial phase of stroke.²⁵ There is a theoretical advantage in delaying antihypertensive therapy after stroke in that it allows recovery of the damaged cerebral vessels, restoration of local autoregulation, and improvement in the collateral supply,^{26 27 28} but at this time the prevalence and duration of these changes are unknown in humans.

The present study suggests that mean and systolic blood pressure on admission strongly correlate with mortality in patients with putaminal and thalamic hemorrhage. Among patients with putaminal or thalamic hemorrhage, mean pressure on admission above 136 mm Hg and/or systolic blood pressure on admission above 178 mm Hg indicates poor outcome. Among patients with subcortical, cerebellar, and pontine hemorrhage, no significant correlation was observed between blood pressure on admission and clinical outcome.

Some reports show a correlation between the size of hematoma and functional outcome of patients based on the location of hematoma.^{14 29} The present study revealed a significant correlation between size of hematoma and outcome among patients with putaminal and thalamic hemorrhage. In these patients, size of hematoma may indirectly influence the vasopressor center in the brain stem, causing hypertension on admission. On the other hand, more severe degrees of hypertension might cause an expanded volume of hematoma, although this did not seem to occur in subcortical, cerebellar, and pontine hemorrhage. In patients with subcortical, cerebellar, and pontine hemorrhage, no significant correlation was observed between volume of hematoma and outcome. In patients with pontine hemorrhage, the immediate effect of the hematoma on the vasopressor center in the brain stem, irrespective of the size of the hematoma, may contribute to the poor prognosis and the elevated blood pressure on admission.

Conclusion
In conclusion, in patients with putaminal and thalamic hemorrhage, mean blood pressure on admission in those with a fatal outcome was significantly higher than in those with nonfatal outcome. No correlation between mean blood pressure and outcome was observed in patients with subcortical, cerebellar, and pontine hemorrhage. Elevated mean blood pressure on admission and increased volume of hematoma in putaminal and thalamic hemorrhage were related to increased mortality, while in patients with subcortical, cerebellar, and pontine hemorrhage, mean blood pressure was not correlated with the clinical outcome. Although these results do not provide a basis for recommending antihypertensive therapy for such patients, hypertension and volume of hematoma in putaminal and thalamic hemorrhage are of important prognostic significance in relation to patient mortality.

Received December 4, 1996; revision received March 7, 1997; accepted March 7, 1997.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Wallace JD, Levy LL. Blood pressure after stroke. JAMA. 1981;246:2177-2180.[Abstract]
2. Britton M, Carlsson A, de Faire U. Blood pressure course in patients with acute stroke and matched controls. Stroke. 1986;17:861-864.[Abstract/Free Full Text]
3. Schulte BPM, Leyten ACM, Herman B. Pre-stroke and immediate post-stroke hypertension: neuroepidemiological data. In: Meyer JS, Lechner H, Reivich M, Ott E, eds. Cerebral Vascular Disease (12th Salzburg Conference). Amsterdam, Netherlands: Excerpta Medica; 1985;286:31-33.
4. Harper G, Castleden CM, Potter JF. Factors affecting changes in blood pressure after acute stroke. Stroke. 1994;25:1726-1729.[Abstract]
5. Harmsen P, Tibblin G. A stroke register in Goteborg, Sweden. Acta Med Scand. 1972;191:463-470.[Medline] [Order article via Infotrieve]
6. Hatano S. Experience from a multicentre stroke register: a preliminary report. Bull World Health Organ. 1976;54:541-552.[Medline] [Order article via Infotrieve]
7. Britton M, Carlsson A. Very high blood pressure in acute stroke. J Intern Med. 1990;228:611-615.[Medline] [Order article via Infotrieve]
8. Tuhrim S, Dambrosia JM, Price TR, Mohr JP, Wolf PA, Heyman A, Kase CS. Prediction of intracerebral hemorrhage survival. Ann Neurol. 1988;24:258-263.[Medline] [Order article via Infotrieve]
9. Dunne JW, Chakera T, Kermode S. Cerebellar hemorrhage—diagnosis and treatment: a study of 75 consecutive cases. Q J Med. 1987;245:739-754.
10. Allen CMC. Predicting the outcome of acute stroke: a prognostic score. J Neurol Neurosurg Psychiatry. 1984;47:475-480.[Abstract]
11. Nath FP, Nicholls D, Fraser RJA. Prognosis in intracerebral hemorrhage. Acta Neurochir (Wien). 1983;67:29-35.[Medline] [Order article via Infotrieve]
12. Dollberg S, Rosin AJ, Fisher D. A new look at the natural history and clinical features of intracerebral hemorrhage: a clinical CT scan correlation. Gerontology. 1986;32:211-216.[Medline] [Order article via Infotrieve]
13. Carlberg B, Asplund K, Hagg E. The prognostic value of admission blood pressure in patients with acute stroke. Stroke. 1993;24:1372-1375.[Abstract/Free Full Text]
14. Kwak R, Kadoya S, Suzuki T. Factors affecting the prognosis in thalamic hemorrhage. Stroke. 1983;14:493-500.[Abstract/Free Full Text]
15. Gotoh F. Comparison of conservative treatment and surgical treatment for hypertensive putaminal hemorrhage in 819 cases: Keio Cooperative Stroke Study. Jpn J Stroke. 1990;12:493-500.
16. Gotoh F, Fukuuchi Y. Comparison of conservative treatment and surgical treatment for thalamic hemorrhage: Keio Cooperative Stroke Study. Jpn J Stroke. 1992;14:72-78.
17. Myers MG, Norris JW, Hachinski VC, Sole MJ. Plasma norepinephrine in stroke. Stroke. 1981;12:200-204.[Abstract/Free Full Text]
18. Jansen PAF, Thein TH, Gribnau FWJ, Schulte BP, Willemsen JJ, Lamers KJ, Poels EF. Blood pressure and both venous and urinary catecholamines after cerebral infarction. Clin Neurol Neurosurg. 1988;90:41-45.[Medline] [Order article via Infotrieve]
19. Olsson T, Marklund N, Gustafson Y, Nasman B. Abnormalities at different levels of the hypothalamic-pituitary-adrenocortical axis early after stroke. Stroke. 1992;23:1573-1576.[Abstract/Free Full Text]
20. Cushing HW. Concerning a definite regulatory system mechanism of the vasomotor center which controls blood pressure during cerebral compression. Johns Hopkins Hosp Bull. 1901;12:290-292.
21. Brott T, MacCarthy P. Antihypertensive therapy in stroke. In: Fisher M, ed. Medical Therapy of Acute Stroke. New York, NY: Marcel Dekker, Inc; 1989:117-141.
22. Kaneko T, Sawada T, Niimi T, Naritomi H, Kuriyama Y, Kinugawa H. Lower limit of blood pressure treatment in acute hypertensive intracranial hemorrhage (AHCH). J Cereb Blood Flow Metab. 1983;3(suppl 1):S51-S52.
23. Chen ST, Chen SD, Hsu CT, Hogan EL. Progression of hypertensive intracerebral hemorrhage. Neurology. 1989;39:1509-1514.[Abstract/Free Full Text]
24. Broderick JP, Brott TG, Tomsick T, Barsan W, Spilker J. Ultra-early evaluation of intracerebral hemorrhage. J Neurosurg. 1990;72:195-199.[Medline] [Order article via Infotrieve]
25. Fotherby MD, Harper GD, Potter JF. General practitioners' management of hypertension in elderly patients. BMJ. 1992;305:750-752.
26. Meyer JS, Shimazu K, Fukuuchi Y, Ohuchi T, Okamoto S, Koto A, Ericsson AD. Impaired neurogenic cerebrovascular control and dysautoregulation after stroke. Stroke. 1973;4:169-186.[Abstract/Free Full Text]
27. Barnett GH, Bose B, Little JR, Jones SC, Friel HT. Effects of nimodipine on acute focal cerebral ischemia. Stroke. 1986;17:884-890.[Abstract/Free Full Text]
28. Britton M, de Faire U, Helmers C. Hazards of therapy for excessive hypertension in acute stroke. Acta Med Scand. 1980;207:253-257.[Medline] [Order article via Infotrieve]
29. Kanno T, Sano H, Shinomiya Y, Katada K, Nagata J, Hoshino M, Mitsuyama F. Role of surgery in hypertensive intracerebral hematoma: a comparative study of 305 nonsurgical and 154 surgical cases. J Neurosurg. 1984;61:1091-1099.[Medline] [Order article via Infotrieve]

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Terayama, Y. Articles by Gotoh, F. Search for Related Content PubMed PubMed Citation Articles by Terayama, Y. Articles by Gotoh, F.