| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2007;38:3225.)
© 2007 American Heart Association, Inc.
Original Contributions |
From the Stroke Unit (F.P.), Department of Neurology, Universitat de Lleida, Hospital Universitari Arnau de Vilanova de Lleida, Spain; and the Neurovascular Unit (J.M., C.A.M., P.D., M.R., J.A.-S.), Department of Neurology, Universitat Autònoma de Barcelona, Hospital Universitari de la Vall dHebron, Barcelona, Spain.
Correspondence to Francisco Purroy, MD, PhD, Stroke Unit, Department of Neurology, Universitat de Lleida, Hospital Universitari Arnau de Vilanova de Lleida, Avda Rovira Roure 80, Lleida 25198, Spain. E-mail 34271fpg{at}comb.es
| Abstract |
|---|
|
|
|---|
Methods— We prospectively studied 388 TIA patients. The cause of TIA was classified according to the Trial of ORG 10172 criteria: large-artery atherosclerosis (LAA, n=90), cardioembolism (n=87), small-vessel disease (n=68), undetermined (n=127), and other determined cause (n=16). Patients were followed up at 3 months. Risk factors and clinical symptoms for each subtype were recorded.
Results— The duration of symptoms and clinical symptoms varied significantly among the different subtypes. LAA was associated with recurrent short episodes of weakness, whereas speech impairment and cortical symptoms were associated with cardioembolism (P<0.05). The association of vascular risk factors was highest in LAA (P<0.05). New strokes were recorded in 35 (9%) patients. Recurrent stroke risk varied among subtypes (P<0.001): LAA, 20.0%; cardioembolism, 11.5%; undetermined, 4.7%; small-vessel disease, 1.5%; and other cause, 0%. Cox proportional-hazards multivariate analyses did not identify any independent predictor of further cerebral ischemic events for LAA, cardioembolism, undetermined, or small-vessel disease.
Conclusions— The risk of early recurrent stroke is highest in patients with LAA. This supports the need for urgent carotid and transcranial imaging for identifying those patients at highest risk. Some risk factors and clinical symptoms are related to some etiologic subtypes, but stronger predictors of stroke recurrence are needed to identify those patients with highest risk for each TIA subtype.
Key Words: etiology outcome risk factors stroke classification transient ischemic attack
| Introduction |
|---|
|
|
|---|
In this study, we aimed to determine the early risk of stroke in different etiologic subtypes of TIA according to the Trial of ORG 10172 (TOAST) criteria12 and to evaluate risk factors associated with individual subtypes and stroke recurrence.
| Subjects and Methods |
|---|
|
|
|---|
Determination of the ABCD2 risk score6 was performed retrospectively (
60 years=1 point; systolic blood pressure
140 mm Hg or diastolic blood pressure
90 mm Hg=1 point; unilateral weakness=2 points; speech disturbance without weakness=1 point; other symptoms=0 points; duration of symptoms
60 minutes=2 points, 10 to 59 minutes=1 point, and <10 minutes=0 points; and diabetes=1 point), although the components of the score were prospectively collected. Examinations during admission included medical history; physical examination; routine blood biochemistry; ECG; chest x-ray; transthoracic echocardiography and Holter ECG when indicated; cervical carotid ultrasound and transcranial Doppler ultrasonography; and computed tomography (CT) scan. Transcranial Doppler recordings were performed on admission, within the first 24 hours after symptoms onset, with the use of a Multi-Dop-X transcranial Doppler device (DWL Elektronische Systeme GmbH). Intracranial stenoses were diagnosed when the mean blood flow velocity at a circumscribed insonation depth was >80 cm/s, with side-to-side differences >30 cm/s and signs of disturbed flow. Baseline cervical ICA atherosclerosis was categorized by echo Doppler as follows: absent; mild, if 1 or both ICAs had <50% stenoses; moderate, when any of the ICAs presented with 50% to 70% stenoses; and severe, if any ICA had >70% stenoses. Cranial CT was performed on a Multislice MX8000 Philips spiral CT scanner with 4 rows of detectors.
Baseline Vascular Risk Factors
Hypertension was defined as a systolic blood pressure
140 mm Hg, a diastolic blood pressure
90 mm Hg, or current use of antihypertensive medications. Cigarette smoking was defined as present if the patient reported smoking cigarettes during the past 5 years. Hypercholesterolemia was defined as a total cholesterol concentration
220 mg/dL or current use of lipid-lowering agents. Diabetes mellitus was defined by a history of fasting glucose
126 mg/dL or current use of hypoglycemic drugs. History of diagnosed coronary artery disease, intermittent claudication, atrial fibrillation, and valvular heart disease was also recorded.
Classification of Stroke Subtypes and Clinical End Point
TIAs were classified etiologically according to TOAST criteria12 as due to large-artery occlusive disease (LAA), small-vessel disease (SV), cardioembolism (CE), other cause (OC), or undetermined cause (UND). Patients were followed up by face-to-face interview at 90 days. Endpoint events included further stroke. Stroke was defined as rapidly developed clinical symptoms of focal disturbance of cerebral function lasting >24 hours with an apparent vascular cause.13 We also recorded death and any major vascular event other than stroke. A recurrent TIA was considered when it occurred after the first week of the index event.
Statistical Analysis
Analyses were performed with the SPSS statistical package, version 12.0. Statistical significance for intergroup differences was assessed by the
2 test for categorical variables and the Student t and Mann-Whitney U tests for continuous variables. Univariate analysis was performed to detect variables associated with the occurrence of a cerebral ischemic event. Cox proportional-hazards multivariate analyses were used to identify predictors of further cerebral ischemic events in which age, sex, vascular risk factors, and variables showing P<0.1 on univariate testing were included. Finally, cumulative event-free rates for the time to an ischemic event were estimated by the Kaplan-Meier product-limit method. A probability value <0.05 was considered significant. A Bonferroni correction (a multiple-comparison correction) was applied to all significant associations to reduce the risk of finding false-positive associations. The study was approved by our local ethics committee. Because it was an observational longitudinal study, written, informed consent from all study participants was not needed.
| Results |
|---|
|
|
|---|
|
Follow-Up End Points
Recurrent strokes occurred in 35 patients (9%) within the first 90 days after the index TIA, 26 (6.7%) at 7 days and 9 (2.3%) at 2 days. New TIAs were recorded in 21 patients at the 90-day follow-up. Six patients (1.5%) had an acute myocardial infarction and 1 patient (0.3%) had an intracranial hemorrhage. Finally, peripheral arterial disease was identified in 2 patients. Six patients (1.5%) died, 5 after cerebral ischemic stroke and 1 after an intracranial hemorrhage.
There was heterogeneity among the different subtypes for the 3-month risk of recurrent stroke (log-rank P<0.001; the Figure). Patients with LAA had the highest risk of further cerebral ischemic events at 3 months (20.0%, 95% CI=11.7 to 28.3 vs 5.7%, 95% CI=4.4 to 7.0 in the rest; P<0.001). Moreover, recurrent stroke risk varied among the degrees of carotid stenosis: absent 5%, mild 25%, moderate 11.1%, and severe 35% (P<0.001). The presence of intracranial stenoses (11.9%) was also associated with stroke risk within the first 7 days after the index TIA (25%, 95 CI=20.7 to 29.3 vs 6.1%, 95% CI=3.7 to 8.5; P=0.026). No recurrence was observed beyond the 7-day follow-up.
|
Independent Predictors of New Cerebral Ischemic Events
In univariate analyses, after Bonferroni adjustment, only LAA was associated with stroke recurrence at 7 and 90 days after the onset of symptoms. In Cox proportional-hazards multivariate analyses, LAA remained an independent predictor of stroke recurrence at the 7-day follow-up (hazard ratio=4.07, 95% CI=1.88 to 8.80, P<0.001) and after 90 days of follow-up (hazard ratio=3.78, 95% CI=1.95 to 7.33, P<0.001).
With regard to subtypes of TIA (Table 2), no clinical variables were associated with stroke recurrence. Oral anticoagulants were better than antiaggregants for secondary prevention after CE transient cerebral ischemic events (30.0%, 95% CI=20.3 to 39.6 vs 77.9%, 95% CI=69.2 to 86.6; P=0.056). Moreover, early carotid endarterectomy was associated with a low risk of stroke in patients with TIA due to LAA (5.6%, 95% CI=0.8 to 10.3 vs 25.0%, 95% CI=16.1 to 33.9; P=0.114) without statistical significance. No discharge treatment was more effective than any other after TIA due to UND or SV.
|
| Discussion |
|---|
|
|
|---|
These findings are consistent with previous studies. Diagnosis of TIA is a difficult clinical problem because many of the symptoms may have resolved before patients arrive at the hospital,5,14 and there are many different conditions that mimic cerebral ischemic events.15,16 Therefore, TIA patients are mainly classified as the UND subtype compared with ischemic stroke patients.17 On the other hand, it is known that patients who have a hemispheric TIA or stroke related to ICA disease have a high risk of stroke in the first few days after the index event.2,18 Moreover, according to our previous findings, not only TIA patients with moderate to severe extracranial stenoses but also patients with intracranial stenosis have a higher risk of stroke recurrence. These findings have important implications for targeting stroke prevention. The routine use of combined carotid/transcranial ultrasound testing within the first 24 hours after an index TIA will be useful for identifying those patients at high risk and who might most benefit from aggressive prevention therapies.19,20 Additionally, clinical data are insufficient to distinguish those patients at higher risk.20
Nevertheless, strong predictors within the different subtypes are lacking. Further studies are needed to identify new predictors within the different subgroups. Biomarkers of systemic inflammation that should be higher in patients with an exaggerated inflammatory response and that might accelerate atheroma progression and facilitate plaque instability could be useful.21 Moreover, performing magnetic resonance diffusion-weighted imaging (DWI) in TIA patients could also be useful. Recently, an association between DWI abnormalities in TIA patients and poor outcome has been proposed.22–24 New infarction on the CT scan performed within 48 hours of a clinical event could also be predictive of recurrent stroke.25 During the follow-up, only recurrent ischemic events, and not recurrent TIAs, were considered because this outcome is much more relevant to clinicians and patients.
This study has several limitations. Namely, a larger cohort would be necessary to better explore TIA subgroups. A complete diagnostic procedure with transesophageal echocardiography could improve the etiologic classification. It provides a better estimate of left ventricular function and is more sensitive for detecting other potential sources of CE. Transesophageal echocardiography is superior for the detection of atheromatous disease of the thoracic aorta. On the other hand, if DWI magnetic resonance imaging were performed in all patients, some cases would be classified in other ways. In those patients with DWI lesions, the different magnetic resonance imaging patterns of acute ischemic brain lesions can suggest the most likely causative mechanism of infarction.26–28 In addition, the TOAST criteria were meant to be applied to stroke and not to TIA. Patients presenting without cortical symptoms or signs are difficult to classify. Also, patients with DWI abnormalities could be classified in a different way.
In conclusion, our study confirms that early recurrence rates for stroke due to LAA are higher than those for other subtypes. This supports the need for urgent carotid and transcranial imaging for identifying those patients at highest risk. Some risk factors and clinical symptoms are related to some etiologic subtypes, but stronger predictors of stroke recurrence are needed to identify those patients at highest risk in each TIA subtype.
| Acknowledgments |
|---|
None.
| Footnotes |
|---|
Received March 20, 2007; revision received May 9, 2007; accepted May 11, 2007.
| References |
|---|
|
|
|---|
2. Eliasziw M, Kennedy J, Hill MD, Buchan AM, Barnett HJ. Early risk of stroke after a transient ischemic attack in patients with internal carotid artery disease. Can Med Assoc J. 2004; 170: 1105–1109.
3. Coull AJ, Lovett JK, Rothwell PM. Population based study of early risk of stroke after transient ischaemic attack or minor stroke: implications for public education and organisation of services. BMJ. 2004; 328: 326.
4. Kleindorfer D, Panagos P, Pancioli A, Khoury J, Kissela B, Woo D, Schneider A, Alwell K, Jauch E, Miller R, Moomaw C, Shukla R, Broderick JP. Incidence and short-term prognosis of transient ischemic attack in a population-based study. Stroke. 2005; 36: 720–723.
5. Johnston SC, Gress DR, Browner WS, Sidney S. Short-term prognosis after emergency department diagnosis of TIA. JAMA. 2000; 284: 2901–2906.
6. Johnston SC, Rothwell PM, Nguyen-Huynh MN, Giles MF, Elkins JS, Bernstein AL, Sidney S. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007; 369: 283–292.[CrossRef][Medline] [Order article via Infotrieve]
7. Johnston SC, Sidney S, Bernstein AL, Gress DR. A comparison of risk factors for recurrent TIA and stroke in patients diagnosed with TIA. Neurology. 2003; 60: 280–285.
8. Rothwell PM, Giles MF, Flossmann E, Lovelock CE, Redgrave JN, Warlow CP, Mehta Z. A simple score (ABCD) to identify individuals at high early risk of stroke after transient ischaemic attack. Lancet. 2005; 366: 29–36.[CrossRef][Medline] [Order article via Infotrieve]
9. Tsivgoulis G, Spengos K, Manta P, Karandreas N, Zambelis T, Zakopoulos N, Vassilopoulos D. Validation of the ABCD score in identifying individuals at high early risk of stroke after a transient ischemic attack: a hospital-based case series study. Stroke. 2006; 37: 2892–2897.
10. Donnan GA, Davis SM, Hill MD, Gladstone DJ. Patients with transient ischemic attack or minor stroke should be admitted to hospital. Stroke. 2006; 37: 1137–1138.
11. Gladstone DJ, Kapral MK, Fang J, Laupacis A, Tu JV. Management and outcomes of transient ischemic attacks in Ontario. Can Med Assoc J. 2004; 170: 1099–1104.
12. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. TOAST: Trial of Org 10172 in acute stroke treatment. Stroke. 1993; 24: 35–41.
13. The World Health Organization MONICA project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. WHO MONICA project principal investigators. J Clin Epidemiol. 1988; 41: 105–114.[CrossRef][Medline] [Order article via Infotrieve]
14. Albers GW, Caplan LR, Easton JD, Fayad PB, Mohr JP, Saver JL, Sherman DG. Transient ischemic attack: proposal for a new definition. N Engl J Med. 2002; 347: 1713–1716.
15. Garcia-Monco JC, Marrodan A, Foncea Beti N, Gomez Beldarrain M. Stroke and transient ischemic attack-mimicking conditions: a prospective analysis of risk factors and clinical profiles at a general hospital. Neurologia. 2002; 17: 355–360.[Medline] [Order article via Infotrieve]
16. Kidwell CS, Warach S. Acute ischemic cerebrovascular syndrome: diagnostic criteria. Stroke. 2003; 34: 2995–2998.
17. Daffertshofer M, Mielke O, Pullwitt A, Felsenstein M, Hennerici M. Transient ischemic attacks are more than ministrokes. Stroke. 2004; 35: 2453–2458.
18. Lovett JK, Coull AJ, Rothwell PM. Early risk of recurrence by subtype of ischemic stroke in population-based incidence studies. Neurology. 2004; 62: 569–573.
19. Purroy F, Montaner J, Delgado P, Arenillas JF, Molina CA, Santamarina E, Quintana M, Alvarez-Sabin J. Usefulness of urgent combined carotid/transcranial ultrasound testing in early prognosis of TIA patients. Med Clin (Barc). 2006; 126: 647–650.[CrossRef][Medline] [Order article via Infotrieve]
20. Purroy F, Molina CA, Montaner J, Alvarez Sabin J. Absence of usefulness of ABCD score in the early risk of stroke of transient ischemic attack patients. Stroke. 2007; 38: 855–856.
21. Purroy F, Montaner J, Molina CA, Delgado P, Arenillas JF, Chacon P, Quintana M, Alvarez-Sabin J. C-reactive protein predicts further ischemic events in transient ischemic attack patients. Acta Neurol Scand. 2007; 115: 60–66.[CrossRef][Medline] [Order article via Infotrieve]
22. Purroy F, Montaner J, Rovira A, Delgado P, Quintana M, Alvarez-Sabin J. Higher risk of further vascular events among transient ischemic attack patients with diffusion-weighted imaging acute ischemic lesions. Stroke. 2004; 35: 2313–2319.
23. Ay H, Koroshetz WJ, Benner T, Vangel MG, Wu O, Schwamm LH, Sorensen AG. Transient ischemic attack with infarction: a unique syndrome? Ann Neurol. 2005; 57: 679–686.[CrossRef][Medline] [Order article via Infotrieve]
24. Coutts SB, Simon JE, Eliasziw M, Sohn CH, Hill MD, Barber PA, Palumbo V, Kennedy J, Roy J, Gagnon A, Scott JN, Buchan AM, Demchuk AM. Triaging transient ischemic attack and minor stroke patients using acute magnetic resonance imaging. Ann Neurol. 2005; 57: 848–854.[CrossRef][Medline] [Order article via Infotrieve]
25. Douglas VC, Johnston CM, Elkins J, Sidney S, Gress DR, Johnston SC. Head computed tomography findings predict short-term stroke risk after transient ischemic attack. Stroke. 2003; 34: 2894–2899.
26. Rovira A, Grive E, Alvarez-Sabin J. Distribution territories and causative mechanisms of ischemic stroke. Eur Radiol. 2005; 15: 416–426.[CrossRef][Medline] [Order article via Infotrieve]
27. Kang DW, Chalela JA, Ezzeddine MA, Warach S. Association of ischemic lesion patterns on early diffusion-weighted imaging with TOAST stroke subtypes. Arch Neurol. 2003; 60: 1730–1734.
28. Wessels T, Wessels C, Ellsiepen A, Reuter I, Trittmacher S, Stolz E, Jauss M. Contribution of diffusion-weighted imaging in determination of stroke etiology. AJNR Am J Neuroradiol. 2006; 27: 35–39.
This article has been cited by other articles:
![]() |
J. W. Schrock, A. Victor, and T. Losey Can the ABCD2 Risk Score Predict Positive Diagnostic Testing for Emergency Department Patients Admitted for Transient Ischemic Attack? Stroke, October 1, 2009; 40(10): 3202 - 3205. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Amarenco, J. Labreuche, P. C. Lavallee, E. Meseguer, L. Cabrejo, T. Slaoui, C. Guidoux, J.-M. Olivot, H. Abboud, B. Lapergue, et al. Does ABCD2 Score Below 4 Allow More Time to Evaluate Patients With a Transient Ischemic Attack? Stroke, September 1, 2009; 40(9): 3091 - 3095. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Ois, E. Cuadrado-Godia, A. Rodriguez-Campello, J. Jimenez-Conde, and J. Roquer High Risk of Early Neurological Recurrence in Symptomatic Carotid Stenosis Stroke, August 1, 2009; 40(8): 2727 - 2731. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. H. Lichtman, S. B. Jones, E. Watanabe, N. B. Allen, Y. Wang, V. J. Howard, and L. B. Goldstein Elderly Women Have Lower Rates of Stroke, Cardiovascular Events, and Mortality After Hospitalization for Transient Ischemic Attack Stroke, June 1, 2009; 40(6): 2116 - 2122. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Ay, E. M. Arsava, S. C. Johnston, M. Vangel, L. H. Schwamm, K. L. Furie, W. J. Koroshetz, and A. G. Sorensen Clinical- and Imaging-Based Prediction of Stroke Risk After Transient Ischemic Attack: The CIP Model Stroke, January 1, 2009; 40(1): 181 - 186. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Calvet, E. Touze, C. Oppenheim, G. Turc, J.-F. Meder, and J.-L. Mas DWI Lesions and TIA Etiology Improve the Prediction of Stroke After TIA Stroke, January 1, 2009; 40(1): 187 - 192. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Talelli and R. J. Greenwood Review: Recurrent stroke: where do we stand with the secondary prevention of noncardioembolic ischaemic strokes? Therapeutic Advances in Cardiovascular Disease, October 1, 2008; 2(5): 387 - 405. [Abstract] [PDF] |
||||
![]() |
A. Y. Poppe, S. B. Coutts, and A. M. Demchuk Transient Ischemic Attack Etiologic Subtype and Early Risk of Stroke Stroke, July 1, 2008; 39(7): e108 - e108. [Full Text] [PDF] |
||||
![]() |
F. Purroy, J. Montaner, C. A. Molina, P. Delgado, M. Ribo, and J. Alvarez-Sabin Response to Letter by Poppe et al Stroke, July 1, 2008; 39(7): e109 - e110. [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Stroke Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 2007 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |