(Stroke. 1996;27:2188-2190.)
© 1996 American Heart Association, Inc.
Articles |
Is Impaired Cerebral Vasomotor Reactivity a Predictive Factor of Stroke in Asymptomatic Patients?
the Department of Neurology, Tel Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel Aviv University, Israel.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose Identification of the subgroup of asymptomatic patients with severe internal carotid artery stenosis and high risk of stroke has important clinical implications. Cerebral vasomotor reactivity provides information regarding intracranial hemodynamic features and might have a prognostic value in predicting cerebrovascular ischemic events, especially in patients with carotid stenosis. The aim of our study was to assess the cerebral vasomotor reactivity in asymptomatic patients with carotid stenosis and evaluate its role in stroke occurrence.
Methods Cerebral vasomotor reactivity was assessed using transcranial Doppler ultrasonology and the Diamox test (intravenous administration of 1.0 g acetazolamide) in 44 asymptomatic patients with severe (>70%) internal carotid artery stenosis. Patients were followed up prospectively (mean, 2 years).
Results Cerebral vasomotor reactivity was estimated as good (>40% increase of blood flow velocity in the middle cerebral artery ipsilateral to the carotid stenosis after undergoing the Diamox test) in 23 patients; it was impaired in the other 21. During the follow-up period, the overall annual rate for ipsilateral stokes was 2.3%; it was 7.9% for all ischemic cerebral events. No strokes or transient ischemic attacks occurred in the former group, but there were 7 cerebral ischemic events (2 strokes [1 fatal] and 5 transient ischemic attacks) in the latter group. There was a statistically significant correlation between cerebral ischemic events and impaired cerebral vasomotor reactivity (P=.009).
Conclusions The data of this preliminary study suggest an important role of impaired cerebral vasomotor reactivity in predicting ischemic cerebral events. Preventive vascular surgery might be considered in this high-risk subgroup of asymptomatic patients with severe carotid stenosis.
Key Words: acetazolamide • carotid stenosis • ultrasonics • vasomotor reactivity
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The results of two major clinical trials, the ACAS and the Veterans Affairs Trial, showed that vascular surgery benefits asymptomatic patients with severe carotid stenosis (ACAS).1 2 Two other trials, CASANOVA and Mayo Asymptomatic Carotid Endarterectomy, reported no such benefit.3 4 Furthermore, all of these investigations were criticized as to their design, statistical interpretations, and conclusions.5 6 Therefore, the question of whether ACAS patients should undergo surgery remains undecided, and probably only when the results of a large study, such as the Asymptomatic Carotid Surgery Trial, are available will a more decisive verdict be at hand.7 Also unanswered is the question of which ACAS patients bear a greater likelihood to develop stroke and who could benefit from preventive surgery, that is, the identification of those ACAS patients who belong to a high-risk subgroup and are thereby candidates for surgical intervention.6 8
The intracerebral hemodynamic status of patients with carotid stenosis was shown to play a significant role in stroke incidence.9 10 11 The assessment of CVR provides information regarding collateral circulation and cerebral autoregulation and is used to determine various intracerebral hemodynamic features.12 13 14 TCD combined with a potent vasodilatory stimulus (eg, CO2 or acetazolamide) has recently become the technique of choice for measuring CVR.15 16 17
The aim of this preliminary study was to assess CVR in ACAS patients by using TCD and the Diamox (acetazolamide) test and prospectively follow up the subjects to determine the role of CVR in predicting cerebrovascular events.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Forty-four consecutive patients (21 men, 23 women; mean±SD age, 69±6.5 years) with asymptomatic severe (70% to 99%) ICA stenosis were included in the study and followed up prospectively.
Carotid artery disease was assessed and defined by B-mode Doppler ultrasound (CME-1060) in all patients according to validated criteria.18 Additional conventional angiography was performed in 25 patients (57%). The intracranial blood flow velocities were assessed with TCD (Rimed Trans-link 9900 TCD). The TCD examinations were performed while the patients were in a supine position and included the transtemporal insonation of the MCAs at a depth of 50 to 55 mm. The most powerful signal during a 10-second period was used for the measurement of blood flow velocity.
CVR was evaluated by recording the differences in peak flow velocities in each MCA (Vmca) at rest and after the Diamox test. Thus, injection of 1.0 g acetazolamide IV (given over 5 minutes) was followed 20 minutes later by the measurement of blood flow velocity, with the ultrasound sample volume at the same depth. The highest peak Vmca recording over a period of 10 seconds was used for the analysis. Blood pressure and heart rate were monitored simultaneously during the Diamox test, and an increase of >20% in either of them excluded the data from analysis. On the basis of previous studies on healthy subjects,19 20 we considered increases of blood flow velocity of 40% and more after administration of acetazolamide as being indicative of good CVR19 20 and classified our study patients as having good or impaired CVR accordingly.
All patients were followed up at 6-month intervals for a mean period of 24 months. They were either interviewed by telephone or examined in our outpatient clinic. End points were defined as the occurrence of stroke or a TIA on the side ipsilateral to the most severe ICA stenosis.
Statistical analysis to correlate the occurrence of cerebrovascular events of ACAS patients with good or impaired CVR was performed using the 
2 test, and a value of P<.05 was considered significant.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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On the basis of the TCD and Diamox test results from 44 ACAS patients, 23 patients were determined to have good CVR (10 men, 13 women; mean±SD age, 70±7.4 years), whereas 21 patients had impaired CVR (12 men, 9 women; mean age, 68±5.6 years). The frequencies of the major vascular risk factors were similar in both groups: ischemic heart disease (in the group with good CVR, 14 patients; with impaired CVR, 13 patients), diabetes mellitus (good CVR, 9; impaired CVR, 9), arterial hypertension (good CVR, 15; impaired CVR, 14), hyperlipidemia (good CVR, 5; impaired CVR, 5), and smoking (good CVR, 6; impaired CVR, 5); P<.2 for each factor. All patients in both groups were receiving antiaggregant therapy throughout the study period.
The follow-up period was 24±8 (mean±SD) months, during which 1 patient died due to a cerebrovascular event, but no other patient was lost to follow-up. No stroke or TIA event occurred in the group with good CVR during this period. However, there were 7 cerebrovascular ischemic events (2 strokes [1 fatal] and 5 TIAs) in the group of ACAS patients with impaired CVR. All of these events were ipsilateral to the side of the most severe stenosis of the ICA and impaired CVR.
The overall annual rate for ipsilateral strokes was 2.3%, and for all events it was 7.9%. There was a statistically significant correlation between ipsilateral ischemic events and impaired CVR (2=6.8 [1], P=.009).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Our results in a group of ACAS patients for whom there was an overall annual rate of 2.3% for ipsilateral strokes are comparable with the results of other studies on ACAS patients.21 22 23 However, we found a significant increase (7.9%) in the rate of ischemic cerebral events when all the cerebrovascular events, including TIAs, were taken into account. A significant relationship was shown to exist between ipsilateral ischemic cerebral events and impaired CVR. At least two previous successful attempts to evaluate the predictive role of impaired CVR and stroke occurrence appear in the literature.9 10 However, in the study of Yonas et al,10 the compromised CVR increased the risk of stroke only in symptomatic patients, whereas asymptomatic patients were not studied. There is an important difference between asymptomatic and symptomatic patients in terms of their natural history; therefore, the only conclusion that can be drawn from the study of Yonas et al is about CVR as a predictor for stroke recurrence but not about the likelihood of stroke occurrence in asymptomatic patients. Kleiser and Widder9 performed their cerebral hemodynamic investigations in a combined group of symptomatic and asymptomatic patients. Although they also found a positive relationship between stroke incidence and diminished or exhausted cerebrovascular reserve capacity, these results are not necessarily applicable when asymptomatic patients are considered as an independent group. Moreover, all their patients had either unilateral or bilateral occlusion of the ICA and therefore would not be considered as potential candidates for carotid endarterectomy.
Nicolaides suggested that a high-risk subgroup of ACAS patients could be arbitrarily defined as a group that has an annual rate of at least 4% of ipsilateral ischemic cerebrovascular events.8 Identification of a high-risk group will be the main goal of the Asymptomatic Carotid Stenosis and Risk of Stroke Study (ACSRS), in which special attention will be given to parameters such as plaque morphology, vascular risk factors, silent brain infarcts, progression of stenosis, and blood flow characteristics.24 Frey6 wrote that the prospect of predicting stroke on the basis of blood flow data is especially intriguing.
Our present results support the important role of impaired CVR in predicting the occurrence of cerebrovascular events in ACAS patients. While further studies are needed to confirm our findings among a large number of patients, our results presented here may be useful in identifying patients belonging to a high-risk subgroup of ACAS patients for whom surgery is justified to prevent ischemic cerebrovascular events.
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Selected Abbreviations and Acronyms |
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Footnotes |
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Reprint requests to N.M. Bornstein, MD, Stroke Unit, Department of Neurology, Tel Aviv Sourasky Medical Center, 6 Weizman St, Tel Aviv 64239, Israel.
Received June 19, 1996; revision received August 21, 1996; accepted August 28, 1996.
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References |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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1. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid stenosis. JAMA. 1995;273:1421-1428.
2.
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CASANOVA Study Group. Carotid surgery versus medical therapy in asymptomatic carotid stenosis. Stroke. 1991;22:1229-1235.
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Barnett HJM, Meldrum HE, Eliasziw M. The dilemma of surgical treatment for patients with asymptomatic carotid disease. Ann Intern Med. 1995;123:723-725.
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Kleiser B, Widder B. Course of carotid artery occlusions with impaired cerebrovascular reactivity. Stroke. 1992;23:171-174.
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