Donate Help Contact The AHA Sign In Home
American Heart Association
Stroke
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Stroke. 2005;36:268-269
Published online before print January 6, 2005, doi: 10.1161/01.STR.0000153045.33710.bc
This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
36/2/268    most recent
01.STR.0000153045.33710.bcv1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lindsberg, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lindsberg, P. J.
Related Collections
Right arrow Clinical Studies
Right arrow Acute Cerebral Infarction
Right arrow Thrombolysis
Right arrowRelated Article

(Stroke. 2005;36:268.)
© 2005 American Heart Association, Inc.

Original Contributions

Editorial Comment—High Blood Pressure After Acute Cerebrovascular Occlusion

Risk or Risk Marker?

Perttu J. Lindsberg, MD, PhD

Department of Neurology, Helsinki University Central Hospital, Neuroscience Program Biomedicum Helsinki, Helsinki, Finland

Elevated blood pressure (BP) in the typical presentation of stroke belongs to those few physiological variables that a physician truly has the power of controlling. Association of early elevated BP with poor outcome in observational studies1,2 has motivated some to recommend moderate BP reduction to improve outcome. Interventional randomized controlled studies focused on BP reduction have not been conducted, which would be necessary to prove a causal relationship between early BP elevation and unfavorable outcome. The nature of this relationship has been debated over decades,3–5 but surprisingly few randomized controlled studies have since been conducted with agents that reduce BP.

Cerebral blood flow in the human ischemic brain is passively dependent on the mean arterial pressure, because autoregulation is defective.6 Therefore, low BP or abrupt decreases in it are hazardous and risk enlargement of the initial infarction. Elevated BP, on the other hand, effects to maintain cerebral blood perfusion. This leads us to the 2 fundamental pathophysiological dogmas in considering therapeutics of acutely elevated BP. First, poststroke hypertension may be deleterious by facilitating edema and hemorrhage formation in the ischemic tissue where blood-brain barrier is damaged. Secondly, antihypertensive drugs may reduce the pressure-dependent cerebral blood flow in the ischemic penumbra with poor autoregulation.

The central question is, why does BP initially rise in the acute stroke? Hospitalization with paralysis is obviously a tremendous stress and has been viewed to explain BP elevation.7 However, because BP has been found to be elevated already during the first minutes after the onset of stroke symptoms,8 it seems more likely that it is intimately associated with the vascular occlusion. The study reported in this issue of Stroke by Mattle et al9 confirms this by demonstrating that recanalization of the initially occluded vessel is associated with BP reduction. The mechanism of the acute vasopressor response has been debated. The Cushing reflex has been suggested to mediate it to maintain adequate cerebral perfusion. However, it pertains to situations where the intracranial pressure is increased, and this is not the case in the early minutes of focal cerebral ischemia. More likely, it reflects increased activity of the sympathetic nervous system10 to increase cardiac contractility, heart rate, and vessel tone.

Acute BP elevation in stroke seems to be a moderately good marker of prior hypertension, which means that acutely hypertensive patients also experience more end-organ morbidity.11 This may partly explain why patients with highest BP in the acute phase might be destined to poorer prognosis. More importantly, studies show that the initial stroke severity influences the course of BP, not vice versa.7 BP fall within the first 4 hours was associated with mild stroke and a good outcome, whereas a sustained high BP associated with severe stroke and poor outcome. These observational data cohere nicely with the study by Mattle et al,9 which suggested that the BP fall may be indicative of early recanalization, be it spontaneous or induced.

The field is clouded by diverse studies focusing on very different time periods considered to be acute and the fact that intracerebral hemorrhages are included in some studies and others lack neurological scoring on admission.1,2,12 Studies have indicated that in the very acute phase (<12 hours), mild spontaneous decrease in hypertensive BP is associated with mild stroke,7,9 but thereafter (within 1 or 5 days) spontaneous decreases in BP correlate with poor prognosis.12,13 However, contrasting evidence does exist.14

Data are available from interventive trials based on agents that influence BP apart from another nominal effect. Although these results are also conflicting, one study used a neuroprotective compound nimodipine and indicated a clear dose-dependent worsening of outcome when BP was reduced 10 to 20 or >20% from baseline.15 A meta-analysis of BP-reducing agents was reported recently, showing a similar observation.16 Another major reason for withholding antihypertensive treatment is that ultra-acutely elevated BP drops spontaneously in >80% of the patients during the first minutes or hours after the onset.8,17

So where is the evidence that very high BP harms the prognosis? The International Stroke Trial (IST) study demonstrated that systolic hypertension is not linked with cerebral hemorrhages.1 It has been associated with extensive cerebral edema or mortality associated with presumed cerebral edema in some studies.1,2 However, it cannot be ruled out that an initially large infarct, with the vessel nonrecanalized, induced the hypertensive reaction, but there was already a large area of brain to be subjected to blood-brain barrier failure and cumulative edema. Unremitting high BP increases the likelihood of a severe neurological damage already on admission, or persistence of the occlusion, and acute pharmacologic BP reduction will not reverse either one. Surely, especially after the presumed penumbra no longer exists (>24 hours), there is no reason to maintain overtly elevated BP that drives plasma to the intracranial space. Other reasons to decrease very high BP, include myocardial ischemia, imminent cardiac failure, acute renal failure, hypertensive encephalopathy, and aortic arch dissection.20

What is the relationship between BP reduction and stroke prognosis in thrombolytic therapy? Two studies suggest that if the thrombolysed patient is hypertensive and antihypertensives are given, the prognosis is poorer than if BP is not medicated.18,19 In view of the novel pathophysiological data in this study,9 the patient with persistently elevated BP is likely to have still ongoing vessel occlusion. We cannot deviate from the guidelines used to control BP during thrombolysis (<180 to 185/105 to 110 mm Hg),20,21 which are well based on clinical data from existing thrombolysis databases showing baseline hypertension on admission as a risk factor for parenchymal hemorrhage.22–24 What should be studied next in these databases and other stroke thombolysis registries is how the follow-up BP level up to 24 hours, treated or not treated, relates with the risk of hemorrhage or edema formation after thrombolysis. This would help in determining whether high posthrombolytic BP continues to be a risk or only a risk marker and how it should be best managed.


*    References
up arrowTop
 *References
 

  1. Leonardi-Bee J, Bath PM, Phillips SJ, Sandercock PA; IST Collaborative Group. Blood pressure and clinical outcomes in the International Stroke Trial. Stroke. 2002; 33: 1315–1320.[Abstract/Free Full Text]
  2. Vemmos KN, Tsivgoulis G, Spengos K, Zakopoulos N, Synetos A, Manios E, Konstantopoulou P, Mavrikakis M. U-shaped relationship between mortality and admission blood pressure in patients with acute stroke. J Intern Med. 2004; 255: 257–265.[CrossRef][Medline] [Order article via Infotrieve]
  3. Yatsu FM, Zivin J. Hypertens in acute ischemic strokes. Not to treat. Arch Neurol. 1985; 42: 999–1000.[Medline] [Order article via Infotrieve]
  4. Spence JD, Del Maestro RF. Hypertension in acute ischemic strokes. Treat. Arch Neurol. 1985; 42: 1000–1002.[Medline] [Order article via Infotrieve]
  5. Hachinski V. Hypertension in acute ischemic strokes. Arch Neurol. 1985; 42: 1002.[Medline] [Order article via Infotrieve]
  6. Eames PJ, Blake MJ, Dawson SL, Panerai RB, Potter JF. Dynamic cerebral autoregulation and beat to beat blood pressure control are impaired in acute ischaemic stroke. J Neurol Neurosurg Psychiatry. 2002; 72: 467–472.[Abstract/Free Full Text]
  7. Christensen H, Meden P, Overgaard K, Boysen G. The course of blood pressure in acute stroke is related to the severity of the neurological deficits. Acta Neurol Scand. 2002; 106: 142–147.[CrossRef][Medline] [Order article via Infotrieve]
  8. Broderick J, Brott T, Barsan W, Haley EC, Levy D, Marler J, Sheppard G, Blum C. Blood pressure during the first minutes of focal cerebral ischemia. Ann Emerg Med. 1993; 22: 1438–1443.[CrossRef][Medline] [Order article via Infotrieve]
  9. Mattle HP, Kappeler L, Arnold M, Fischer U, Nedeltchev K, Remonda L, Jakob SM, Schroth G. Blood pressure and vessel recanalization in the first hours after ischemic stroke. Stroke. 2005; 36: 267–272.
  10. Korpelainen JT, Sotaniemi KA, Myllyla VV. Autonomic nervous system disorders in stroke. Clin Auton Res. 1999; 9: 325–333.[CrossRef][Medline] [Order article via Infotrieve]
  11. Britton M, Carlsson A. Very high blood pressure in acute stroke. J Intern Med. 1990; 228: 611–615.[Medline] [Order article via Infotrieve]
  12. Boreas AM, Lodder J, Kessels F, de Leeuw PW, Troost J. Prognostic value of blood pressure in acute stroke. J Hum Hypertens. 2002; 16: 111–116.[CrossRef][Medline] [Order article via Infotrieve]
  13. Castillo J, Leira R, Garcia MM, Serena J, Blanco M, Davalos A. Blood pressure decrease during the acute phase of ischemic stroke is associated with brain injury and poor stroke outcome. Stroke. 2004; 35: 520–526.[Abstract/Free Full Text]
  14. Chamorro A, Vila N, Ascaso C, Elices E, Schonewille W, Blanc R. Blood pressure and functional recovery in acute ischemic stroke. Stroke. 1998; 29: 1850–1853.[Abstract/Free Full Text]
  15. Ahmed N, Nasman P, Wahlgren NG. Effect of intravenous nimodipine on blood pressure and outcome after acute stroke. Stroke. 2000; 31: 1250–1255.[Abstract/Free Full Text]
  16. Leonardi-Bee J, Bath-Hextall FJ, Bath PMW. Lowering blood pressure in acute stroke: a systematic review of individual patient data from randomised controlled trials in acute stroke. Cerebrovasc Dis. 2004; 17 (suppl 5): 19.(Abstract).[CrossRef][Medline] [Order article via Infotrieve]
  17. 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]
  18. Brott T, Lu M, Kothari R, Fagan SC, Frankel M, Grotta JC, Broderick J, Kwiatkowski T, Lewandowski C, Haley EC, Marler JR, Tilley BC. Hypertension and its treatment in the NINDS rt-PA Stroke Trial. Stroke. 1998; 29: 1504–1509.[Abstract/Free Full Text]
  19. Lindsberg PJ, Soinne L, Roine RO, Salonen O, Tatlisumak T, Kallela M, Häppölä O, Tiainen M, Haapaniemi E, Kuisma M, Kaste M. Community-based thrombolytic therapy of acute ischemic stroke in Helsinki. Stroke. 2003; 34: 1443–1449.[Abstract/Free Full Text]
  20. Hacke W, Kaste M, Bogousslavsky J, Brainin M, Chamorro A, Lees K, Leys D, Kwiecinski H, Toni P, Langhorne P, Diener C, Hennerici M, Ferro J, Sivenius J, Gunnar N, Bath P, Olsen TS, Gugging M; European Stroke Initiative Executive Committee and the EUSI Writing Committee. European Stroke Initiative recommendations for stroke management-update 2003. Cerebrovasc Dis. 2003; 16: 311–337.[CrossRef][Medline] [Order article via Infotrieve]
  21. Adams HP Jr., Adams RJ, Brott T, del Zoppo GJ, Furlan A, Goldstein LB, Grubb RL, Higashida R, Kidwell C, Kwiatkowski TG, Marler JR, Hademenos GJ; Stroke Council of the Am Stroke Association. Guidelines for the early management of patients with ischemic stroke: a scientific statement from the Stroke Council of the American Stroke Association. Stroke. 2003; 34: 1056–1083.[Free Full Text]
  22. Larrue V, von Kummer RR, Muller A, Bluhmki E. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). Stroke. 2001; 32: 438–441.[Abstract/Free Full Text]
  23. Levy DE, Brott TG, Haley EC Jr., Marler JR, Sheppard GL, Barsan W, Broderick JP. Factors related to intracranial hematoma formation in patients receiving tissue-type plasminogen activator for acute ischemic stroke. Stroke. 1994; 25: 291–297.[Abstract]
  24. Tanne D, Kasner SE, Demchuk AM, Koren-Morag N, Hanson S, Grond M, Levine SR. Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey. Circulation. 2002; 105: 1679–1685.[Abstract/Free Full Text]

Related Article:

Blood Pressure and Vessel Recanalization in the First Hours After Ischemic Stroke
Heinrich P. Mattle, Liliane Kappeler, Marcel Arnold, Urs Fischer, Krassen Nedeltchev, Luca Remonda, Stephan M. Jakob, and Gerhard Schroth
Stroke 2005 36: 264-268. [Abstract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 StrokeHome page
E. S. Prakash, Madanmohan, and P. J. Lindsberg
What Causes the Acute Blood Pressure Elevation After Stroke? * Response:
Stroke, October 1, 2005; 36(10): 2066 - 2066.
[Full Text] [PDF]

This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
36/2/268    most recent
01.STR.0000153045.33710.bcv1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lindsberg, P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lindsberg, P. J.
Related Collections
Right arrow Clinical Studies
Right arrow Acute Cerebral Infarction
Right arrow Thrombolysis
Right arrowRelated Article

Stroke Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2005 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.