- Email: [email protected]
The Natural History of Vertebral Artery Origin Stenosis
The Natural History of Vertebral Artery Origin Stenosis Matthew C. Thompson, BS, Mohammad A. Issa, MD, Marc A. Lazzaro, MD, and Osama O. Zaidat, MD, MS
Background: We sought to determine the long-term survival and natural history of vertebral artery origin stenosis (VAOS) as it relates to stroke. Methods: We retrospectively reviewed clinical data on patients admitted at a single institution for possible stroke between 2004 and 2007 and selected subjects who underwent angiography of the neck. We classified VAOS subjects as having ‘‘moderate’’ to ‘‘severe’’ ($50%) occlusion. Age-, sex-, and race-matched control subjects with no evidence of VAOS on angiography were selected from our study population. Long-term follow-up data were collected and death certificates were searched for comparison among cases and controls. A Kaplan–Meier curve was plotted based on time to event (stroke or death). Results: Fifty-eight of the 358 subjects were found to have VAOS (16.2%). Four subjects were excluded because of stenting; therefore, 54 cases and 54 matched controls were included for long-term follow-up analysis. In our study population, we calculated that the relative risk of having a stroke or dying in patients with VAOS was 6 times that of patients without VAOS (P ,.02). The observed 5-year survival rate for patients with VAOS was 67% (36/54) compared to 89% (48/54) in control subjects (P , .01). Conclusions: Patients with VAOS are at a significantly higher risk of having a stroke or dying. Subsequent prospective, multicenter studies are needed to validate our results. Key Words: Cerebrovascular disease—computed tomographic angiogram—natural history study—vertebral artery origin stenosis. Ó 2014 by National Stroke Association
Stroke is the second most common cause of death worldwide. In addition, it is a major cause of disability, resulting in .$40 billion in health care costs in the United States. With the aging of our population, the burden of stroke is expected to significantly increase during the
From the Departments of Neurology, Neurosurgery, and Radiology, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin. Received November 5, 2012; accepted December 8, 2012. The Biostatistics Consulting Service is supported in part by funds from the Clinical and Translational Science Institutes of Southeastern Wisconsin. Address correspondence to Osama O. Zaidat, MD, MS, Associate Professor of Neurology, Radiology, and Neurosurgery, Director, Neurointerventional Program, Medical College of Wisconsin and Froedtert Hospital, 9200 W Wisconsin Ave, Milwaukee, WI 53226. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2014 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2012.12.004
next 20 years. Despite these statistics, there is a disproportionately low amount of stroke research.1 A large focus of stroke research is focused on the internal carotid artery, which supplies anterior cerebral circulation. However, a quarter of all ischemic strokes occur within the posterior cerebral circulation.2 The majority (approximately 70%) of posterior circulation strokes (PCSs) occurs from artery to artery embolism or extracranial vertebral artery atherosclerosis.3 The vertebral artery origin is particularly prone to atherosclerosis because it is a low flow and high turbulence area.4 Because vertebral artery origin stenosis (VAOS) is therefore highly linked to PCSs and can be easily seen and described, it is of our interest to study. Within the past decade there have been major advances in the diagnosis and management of cerebrovascular disease. The use of noninvasive imaging techniques, such as contrast-enhanced computed tomographic angiography (CTA) and magnetic resonance angiography (MRA), has allowed for more readily available visualization of arterial pathology.5
Journal of Stroke and Cerebrovascular Diseases, Vol. 23, No. 1 (January), 2014: pp e1-e4
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M.C. THOMPSON ET AL.
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Methods After receiving institutional review board approval, we retrospectively reviewed all patients admitted for possible stroke at the Medical College of Wisconsin who underwent either digital subtraction angiography (DSA), MRA, or CTA between January 2004 and December 2006. Only patients who received imaging of the neck were selected. Information on demographics, clinical data, and angiographic data were collected, stored, and analyzed using Microsoft Excel (Microsoft; Redmond, WA). VAOS was defined as ‘‘moderate’’ to ‘‘severe’’ ($50%) narrowing seen on DSA, MRA, or CTA in the origin of the vertebral artery from the subclavian artery.6 Symptoms of vertebrobasilar insufficiency (VBI) were defined as any of the following: visual disturbances, gait and limb ataxia, vertigo, syncope, or dizziness. After discovering 58 patients with VAOS in our study population, we selected age-, sex-, and race-matched controls that did not have VAOS. Follow-up information on the cases and controls were collected using an Excel spreadsheet. These data included information on recurrent strokes and relevant medication regimens, including warfarin, aspirin, and statins. We searched death certificates for patients lost to follow-up. Using a stratified proportional hazards model, we plotted a Kaplan–Meier curve based on time to event (stroke or death).
Table 1. Possible stroke patient characteristics Clinical characteristics
n (%)
No. of patients Age, y (mean 6 SD) Sex Male Female Race White Black Other Presentation Anterior circulation stroke Posterior circulation stroke Mixed stroke Other stroke TIA or no stroke VAOS (n 5 58) Symptomatic Asymptomatic
358 63 6 16
A total of 371 patient records were reviewed. Thirteen patients were excluded because of poor bilateral visualization of the vertebral arteries (VAs). The majority of our patients were white. Most patients (n 5 327; 90%) had a discharge diagnosis of stroke; however, 37 patients (10%) were either diagnosed with a transient ischemic attack or no stroke was found upon work-up. Patient characteristics are described in Table 1. Fifty-eight of 358 cases (16.2%) had VAOS. Table 2 shows the proportion of VAOS broken down into several different groups. No statistical significance was seen between men and women or between races. Patients who suffered from a posterior cerebral circulation stroke had a higher percentage of VAOS (27.6%), which was statistically significant (P , .01). In addition, patients who presented with symptoms of VBI had a significantly (P , .05) higher percentage of VAOS (25.9%). No differences were found in any of the age groups. Fifty-eight patients were found to have VAOS; 4 were excluded because of stenting or other vascular interventions. A total of 54 patients with VAOS and 54 age-, sex-, and race-matched controls were included for additional data collection and analysis. The majority of patients were white males (48%). The most common presentation was a stroke for both cases (93%) and controls (94%).
265 (74) 87 (24) 6 (2) 154 (43) 116 (32) 22 (6) 29 (8) 37 (10) 29 (50) 29 (50)
Abbreviations: SD, standard deviation; TIA, transient ischemic attack; VAOS, vertebral artery origin stenosis.
Table 2. Proportion of vertebral artery origin stenosis within patient groups
Group
Results
185 (52) 173 (48)
Study population (n 5 358) Sex Male (n 5 185) Female (n 5 173) Race White (n 5 265) Black (n 5 87) Other (n 5 6) Presentation Posterior circulation stroke (n 5 116) Anterior circulation stroke (n 5 154) TIA or no stroke (n 5 37) Age (y) 20-49 (n 5 77) 50-59 (n 5 62) 60-69 (n 5 78) 70-79 (n 5 80) 80-99 (n 5 61) Symptoms Symptomatic (n 5 112) Asymptomatic (n 5 227)
With VAOS, n (%)
P value
58 (16)
.1*
34 (18) 24 (14)
— —
42 (16) 15 (17) 1 (17)
— — —
32 (28)
,.01
16 (10)
—
4 (11)
—
7 (9) 13 (21) 11 (14) 16 (20) 11 (18)
— — — — —
29 (26) 29 (13)
,.05 —
Abbreviations: TIA, transient ischemic attack; VAOS, vertebral artery origin stenosis. *Comparison between the proportion of VAOS in our study population to the prevalence of proximal vertebral artery stenosis in 935 patients as calculated by Kim et al.7
NATURAL HISTORY OF VAOS
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However, the cases had a significantly higher proportion of PCSs compared to controls (56% v 24%; P , .01). Similarly, the controls had a significantly higher proportion of anterior circulation strokes compared to cases (59% v 34%; P , .02). Both groups had similar proportions of patients who presented with a transient ischemic attack or no stroke. These characteristics are described in Table 3. Figure 1 is a Kaplan–Meier analysis that compares the overall survival of patients with VAOS (cases) to the overall survival of patients without VAOS (controls). The observed 5-year survival for patients with VAOS was 67% (36/54) compared to 89% (48/54) in control subjects. The relative risk of having an event (stroke or death) for cases compared to controls was calculated to be 6.0 (P 5 .019). Using the stratified proportional hazards model, no medications were found to be significant in the prediction of an event. In addition, when medications were analyzed by separating cases and controls, medications were not significant.
Discussion DSA is currently the criterion standard for detection of VAOS. However, noninvasive imaging techniques, such as MRA and CTA, are routinely used as alternatives for diagnosing arterial pathology. In a systematic review of the different noninvasive imaging modalities used to detect moderate to severe VAOS (50-99%), it was found that contrast-enhanced MRA and CTA have sensitivities of 94% and 100% respectively, and both had specificities of 95%. Ultrasound was found to be only about 70% sensitive for detecting moderate to severe VA stenosis.6 Therefore, we collected data only on patients who underwent imaging using DSA, MRA, or CTA.
Table 3. Case control patient characteristics
Characteristic
VAOS, n (%)
No. of patients 54 Age, y (mean 6 SD) 67 6 14 Sex Male 34 (63) Female 20 (37) Race White 39 (72) Black 15 (28) Presentation Anterior circulation 18 (34) stroke Posterior circulation 30 (56) stroke TIA or no stroke 4 (7)
No VAOS, n (%) P value 54 67 6 13
— —
34 (63) 20 (37)
— —
39 (72) 15 (28)
— —
32 (59)
,.02
13 (24)
,.01
3 (6)
—
Abbreviations: SD, standard deviation; TIA, transient ischemic attack; VAOS, vertebral artery origin stenosis.
Figure 1.
Kaplan–Meier stoke-free survival curve.
A cross-sectional study conducted by Kim et al7 found the prevalence of VAOS to be about 12.7% using contrastenhanced MRA on 935 healthy and stroke patients. Our study population consisted of all possible stroke patients who underwent DSA, CTA, or MRA. The proportion of our study population with VAOS was 16.2%, which was not significantly different (P 5 .1) than the previously calculated prevalence by Kim et al.7 We did not find a statistically significant increase in proportion of VAOS with age. However, we found that patients with symptoms of VBI were 1.6 times as likely (P , .05) to possess VAOS. This is expected because atherosclerotic narrowing of the vertebral arteries may cause ischemia to the brainstem, cerebellum, and occipital cortex, leading to the relative symptoms, such as vertigo, ataxia, syncope, and visual disturbances. Moreover, patients who presented with a PCS were 1.7 times as likely (P , .01) to possess VAOS. This supports the idea that emboli from the vertebral arteries are a significant etiology for PCSs and provides evidence to support that VAOS is a significant risk factor for PCS. The natural history and prognosis of VAOS is not well understood because there are limited data published in the literature. In a 1984 study, Moufarrij et al8 observed a 5-year survival rate of 60% for patients with VAOS and 87% for matched controls. In addition, they found the stroke rate to be 8.5 times the rate of the normal population. We observed similar results in our study population, with a 5-year survival of 67% for patients with VAOS and 89% for our controls. We calculated the relative risk of having a stroke or dying in patients with VAOS to be 6 times that of patients without VAOS (P , .02). This indicates that VAOS is correlated with a high rate of morbidity and mortality. This is likely caused by embolic strokes in the posterior cerebral circulation, as mentioned previously; however, our study
M.C. THOMPSON ET AL.
e4
is limited in assessing the cause of death in the majority of patients because they were lost to follow-up. It is possible that the high rate of mortality associated with VAOS may be confounded by being a representation of systemic vascular disease or other comorbidities. In addition, because death certificates were used to confirm the death of patients lost to follow-up, it is possible that patients who died outside of the United States were assumed to be alive. In conclusion, VAOS is common in the stroke population. Patients with VAOS are at a significantly higher risk of having a stroke or dying. This study reveals the need for subsequent prospective, multicenter studies to determine the validity of our findings and further define the role of VAOS in stroke management and prevention. Acknowledgment: We would like to thank Tarim Sergey and Bernika Melton of the Biostatistics Consulting Service at the Medical College of Wisconsin for their assistance.
References 1. Donnan GA, Fisher M, Macleod M, et al. Stroke. Lancet 2008;371:1612-1623. 2. Bamford J, Sandercock P, Dennis M, et al. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991;337:1521-1526. 3. Caplan LR, Wityk RJ, Glass TA, et al. New England Medical Center Posterior Circulation registry. Ann Neurol 2003;56:389-398. 4. Brody WR, Angeli WW, Kosek JC. Histologic fate of the venous coronary artery bypass in dogs. Am J Pathol 1972; 66:111-130. 5. Cloud GC, Markus HS. Diagnosis and management of vertebral artery stenosis. QJM 2003;96:27-54. 6. Khan S, Cloud GC, Kerry S, et al. Imaging of vertebral artery stenosis. A systematic review. J Neurol Neurosurg Psychiatry 2007;78:1218-1225. 7. Kim SH, Lee JS, Kwon OK, et al. Prevalence study of proximal vertebral artery stenosis using high-resolution contrastenhanced magnetic resonance angiography. Acta Radiologica 2005;4:314-321. 8. Moufarrij NA, Little JR, Furlan AJ, et al. Vertebral artery stenosis: Long-term follow-up. Stroke 1984;15:260-263.
Background: We sought to determine the long-term survival and natural history of vertebral artery origin stenosis (VAOS) as it relates to stroke. Methods: We retrospectively reviewed clinical data on patients admitted at a single institution for possible stroke between 2004 and 2007 and selected subjects who underwent angiography of the neck. We classified VAOS subjects as having ‘‘moderate’’ to ‘‘severe’’ ($50%) occlusion. Age-, sex-, and race-matched control subjects with no evidence of VAOS on angiography were selected from our study population. Long-term follow-up data were collected and death certificates were searched for comparison among cases and controls. A Kaplan–Meier curve was plotted based on time to event (stroke or death). Results: Fifty-eight of the 358 subjects were found to have VAOS (16.2%). Four subjects were excluded because of stenting; therefore, 54 cases and 54 matched controls were included for long-term follow-up analysis. In our study population, we calculated that the relative risk of having a stroke or dying in patients with VAOS was 6 times that of patients without VAOS (P ,.02). The observed 5-year survival rate for patients with VAOS was 67% (36/54) compared to 89% (48/54) in control subjects (P , .01). Conclusions: Patients with VAOS are at a significantly higher risk of having a stroke or dying. Subsequent prospective, multicenter studies are needed to validate our results. Key Words: Cerebrovascular disease—computed tomographic angiogram—natural history study—vertebral artery origin stenosis. Ó 2014 by National Stroke Association
Stroke is the second most common cause of death worldwide. In addition, it is a major cause of disability, resulting in .$40 billion in health care costs in the United States. With the aging of our population, the burden of stroke is expected to significantly increase during the
From the Departments of Neurology, Neurosurgery, and Radiology, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin. Received November 5, 2012; accepted December 8, 2012. The Biostatistics Consulting Service is supported in part by funds from the Clinical and Translational Science Institutes of Southeastern Wisconsin. Address correspondence to Osama O. Zaidat, MD, MS, Associate Professor of Neurology, Radiology, and Neurosurgery, Director, Neurointerventional Program, Medical College of Wisconsin and Froedtert Hospital, 9200 W Wisconsin Ave, Milwaukee, WI 53226. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2014 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2012.12.004
next 20 years. Despite these statistics, there is a disproportionately low amount of stroke research.1 A large focus of stroke research is focused on the internal carotid artery, which supplies anterior cerebral circulation. However, a quarter of all ischemic strokes occur within the posterior cerebral circulation.2 The majority (approximately 70%) of posterior circulation strokes (PCSs) occurs from artery to artery embolism or extracranial vertebral artery atherosclerosis.3 The vertebral artery origin is particularly prone to atherosclerosis because it is a low flow and high turbulence area.4 Because vertebral artery origin stenosis (VAOS) is therefore highly linked to PCSs and can be easily seen and described, it is of our interest to study. Within the past decade there have been major advances in the diagnosis and management of cerebrovascular disease. The use of noninvasive imaging techniques, such as contrast-enhanced computed tomographic angiography (CTA) and magnetic resonance angiography (MRA), has allowed for more readily available visualization of arterial pathology.5
Journal of Stroke and Cerebrovascular Diseases, Vol. 23, No. 1 (January), 2014: pp e1-e4
e1
M.C. THOMPSON ET AL.
e2
Methods After receiving institutional review board approval, we retrospectively reviewed all patients admitted for possible stroke at the Medical College of Wisconsin who underwent either digital subtraction angiography (DSA), MRA, or CTA between January 2004 and December 2006. Only patients who received imaging of the neck were selected. Information on demographics, clinical data, and angiographic data were collected, stored, and analyzed using Microsoft Excel (Microsoft; Redmond, WA). VAOS was defined as ‘‘moderate’’ to ‘‘severe’’ ($50%) narrowing seen on DSA, MRA, or CTA in the origin of the vertebral artery from the subclavian artery.6 Symptoms of vertebrobasilar insufficiency (VBI) were defined as any of the following: visual disturbances, gait and limb ataxia, vertigo, syncope, or dizziness. After discovering 58 patients with VAOS in our study population, we selected age-, sex-, and race-matched controls that did not have VAOS. Follow-up information on the cases and controls were collected using an Excel spreadsheet. These data included information on recurrent strokes and relevant medication regimens, including warfarin, aspirin, and statins. We searched death certificates for patients lost to follow-up. Using a stratified proportional hazards model, we plotted a Kaplan–Meier curve based on time to event (stroke or death).
Table 1. Possible stroke patient characteristics Clinical characteristics
n (%)
No. of patients Age, y (mean 6 SD) Sex Male Female Race White Black Other Presentation Anterior circulation stroke Posterior circulation stroke Mixed stroke Other stroke TIA or no stroke VAOS (n 5 58) Symptomatic Asymptomatic
358 63 6 16
A total of 371 patient records were reviewed. Thirteen patients were excluded because of poor bilateral visualization of the vertebral arteries (VAs). The majority of our patients were white. Most patients (n 5 327; 90%) had a discharge diagnosis of stroke; however, 37 patients (10%) were either diagnosed with a transient ischemic attack or no stroke was found upon work-up. Patient characteristics are described in Table 1. Fifty-eight of 358 cases (16.2%) had VAOS. Table 2 shows the proportion of VAOS broken down into several different groups. No statistical significance was seen between men and women or between races. Patients who suffered from a posterior cerebral circulation stroke had a higher percentage of VAOS (27.6%), which was statistically significant (P , .01). In addition, patients who presented with symptoms of VBI had a significantly (P , .05) higher percentage of VAOS (25.9%). No differences were found in any of the age groups. Fifty-eight patients were found to have VAOS; 4 were excluded because of stenting or other vascular interventions. A total of 54 patients with VAOS and 54 age-, sex-, and race-matched controls were included for additional data collection and analysis. The majority of patients were white males (48%). The most common presentation was a stroke for both cases (93%) and controls (94%).
265 (74) 87 (24) 6 (2) 154 (43) 116 (32) 22 (6) 29 (8) 37 (10) 29 (50) 29 (50)
Abbreviations: SD, standard deviation; TIA, transient ischemic attack; VAOS, vertebral artery origin stenosis.
Table 2. Proportion of vertebral artery origin stenosis within patient groups
Group
Results
185 (52) 173 (48)
Study population (n 5 358) Sex Male (n 5 185) Female (n 5 173) Race White (n 5 265) Black (n 5 87) Other (n 5 6) Presentation Posterior circulation stroke (n 5 116) Anterior circulation stroke (n 5 154) TIA or no stroke (n 5 37) Age (y) 20-49 (n 5 77) 50-59 (n 5 62) 60-69 (n 5 78) 70-79 (n 5 80) 80-99 (n 5 61) Symptoms Symptomatic (n 5 112) Asymptomatic (n 5 227)
With VAOS, n (%)
P value
58 (16)
.1*
34 (18) 24 (14)
— —
42 (16) 15 (17) 1 (17)
— — —
32 (28)
,.01
16 (10)
—
4 (11)
—
7 (9) 13 (21) 11 (14) 16 (20) 11 (18)
— — — — —
29 (26) 29 (13)
,.05 —
Abbreviations: TIA, transient ischemic attack; VAOS, vertebral artery origin stenosis. *Comparison between the proportion of VAOS in our study population to the prevalence of proximal vertebral artery stenosis in 935 patients as calculated by Kim et al.7
NATURAL HISTORY OF VAOS
e3
However, the cases had a significantly higher proportion of PCSs compared to controls (56% v 24%; P , .01). Similarly, the controls had a significantly higher proportion of anterior circulation strokes compared to cases (59% v 34%; P , .02). Both groups had similar proportions of patients who presented with a transient ischemic attack or no stroke. These characteristics are described in Table 3. Figure 1 is a Kaplan–Meier analysis that compares the overall survival of patients with VAOS (cases) to the overall survival of patients without VAOS (controls). The observed 5-year survival for patients with VAOS was 67% (36/54) compared to 89% (48/54) in control subjects. The relative risk of having an event (stroke or death) for cases compared to controls was calculated to be 6.0 (P 5 .019). Using the stratified proportional hazards model, no medications were found to be significant in the prediction of an event. In addition, when medications were analyzed by separating cases and controls, medications were not significant.
Discussion DSA is currently the criterion standard for detection of VAOS. However, noninvasive imaging techniques, such as MRA and CTA, are routinely used as alternatives for diagnosing arterial pathology. In a systematic review of the different noninvasive imaging modalities used to detect moderate to severe VAOS (50-99%), it was found that contrast-enhanced MRA and CTA have sensitivities of 94% and 100% respectively, and both had specificities of 95%. Ultrasound was found to be only about 70% sensitive for detecting moderate to severe VA stenosis.6 Therefore, we collected data only on patients who underwent imaging using DSA, MRA, or CTA.
Table 3. Case control patient characteristics
Characteristic
VAOS, n (%)
No. of patients 54 Age, y (mean 6 SD) 67 6 14 Sex Male 34 (63) Female 20 (37) Race White 39 (72) Black 15 (28) Presentation Anterior circulation 18 (34) stroke Posterior circulation 30 (56) stroke TIA or no stroke 4 (7)
No VAOS, n (%) P value 54 67 6 13
— —
34 (63) 20 (37)
— —
39 (72) 15 (28)
— —
32 (59)
,.02
13 (24)
,.01
3 (6)
—
Abbreviations: SD, standard deviation; TIA, transient ischemic attack; VAOS, vertebral artery origin stenosis.
Figure 1.
Kaplan–Meier stoke-free survival curve.
A cross-sectional study conducted by Kim et al7 found the prevalence of VAOS to be about 12.7% using contrastenhanced MRA on 935 healthy and stroke patients. Our study population consisted of all possible stroke patients who underwent DSA, CTA, or MRA. The proportion of our study population with VAOS was 16.2%, which was not significantly different (P 5 .1) than the previously calculated prevalence by Kim et al.7 We did not find a statistically significant increase in proportion of VAOS with age. However, we found that patients with symptoms of VBI were 1.6 times as likely (P , .05) to possess VAOS. This is expected because atherosclerotic narrowing of the vertebral arteries may cause ischemia to the brainstem, cerebellum, and occipital cortex, leading to the relative symptoms, such as vertigo, ataxia, syncope, and visual disturbances. Moreover, patients who presented with a PCS were 1.7 times as likely (P , .01) to possess VAOS. This supports the idea that emboli from the vertebral arteries are a significant etiology for PCSs and provides evidence to support that VAOS is a significant risk factor for PCS. The natural history and prognosis of VAOS is not well understood because there are limited data published in the literature. In a 1984 study, Moufarrij et al8 observed a 5-year survival rate of 60% for patients with VAOS and 87% for matched controls. In addition, they found the stroke rate to be 8.5 times the rate of the normal population. We observed similar results in our study population, with a 5-year survival of 67% for patients with VAOS and 89% for our controls. We calculated the relative risk of having a stroke or dying in patients with VAOS to be 6 times that of patients without VAOS (P , .02). This indicates that VAOS is correlated with a high rate of morbidity and mortality. This is likely caused by embolic strokes in the posterior cerebral circulation, as mentioned previously; however, our study
M.C. THOMPSON ET AL.
e4
is limited in assessing the cause of death in the majority of patients because they were lost to follow-up. It is possible that the high rate of mortality associated with VAOS may be confounded by being a representation of systemic vascular disease or other comorbidities. In addition, because death certificates were used to confirm the death of patients lost to follow-up, it is possible that patients who died outside of the United States were assumed to be alive. In conclusion, VAOS is common in the stroke population. Patients with VAOS are at a significantly higher risk of having a stroke or dying. This study reveals the need for subsequent prospective, multicenter studies to determine the validity of our findings and further define the role of VAOS in stroke management and prevention. Acknowledgment: We would like to thank Tarim Sergey and Bernika Melton of the Biostatistics Consulting Service at the Medical College of Wisconsin for their assistance.
References 1. Donnan GA, Fisher M, Macleod M, et al. Stroke. Lancet 2008;371:1612-1623. 2. Bamford J, Sandercock P, Dennis M, et al. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 1991;337:1521-1526. 3. Caplan LR, Wityk RJ, Glass TA, et al. New England Medical Center Posterior Circulation registry. Ann Neurol 2003;56:389-398. 4. Brody WR, Angeli WW, Kosek JC. Histologic fate of the venous coronary artery bypass in dogs. Am J Pathol 1972; 66:111-130. 5. Cloud GC, Markus HS. Diagnosis and management of vertebral artery stenosis. QJM 2003;96:27-54. 6. Khan S, Cloud GC, Kerry S, et al. Imaging of vertebral artery stenosis. A systematic review. J Neurol Neurosurg Psychiatry 2007;78:1218-1225. 7. Kim SH, Lee JS, Kwon OK, et al. Prevalence study of proximal vertebral artery stenosis using high-resolution contrastenhanced magnetic resonance angiography. Acta Radiologica 2005;4:314-321. 8. Moufarrij NA, Little JR, Furlan AJ, et al. Vertebral artery stenosis: Long-term follow-up. Stroke 1984;15:260-263.