The prevalence of unruptured cerebral aneurysms (UCAs) in ischemic stroke patients is not clearly defined. This study aimed to measure the prevalence and characteristics of UCAs in patients with acute ischemic stroke (AIS) and to compare our findings with those of the general population. In addition, we investigated the factors associated with cerebral aneurysms in AIS patients.
We retrospectively reviewed the brain magnetic resonance angiography images of 955 patients with AIS and 2,118 controls who had received a brain magnetic resonance angiography as part of a health check-up. We investigated the prevalence, size, location, and risk factors of the subjects in the context of UCAs.
UCAs were found in 74 patients with AIS (7.7%) and in 79 who received a health check-up (3.7%). The prevalence of UCAs was significantly higher in the AIS group than in the health check-up group (odds ratio 2.17, 95% confidence interval 1.56-3.01). The mean aneurysm diameter was larger in the AIS group than in the health check-up group (3.75 mm vs. 3.02 mm,
This study identified a higher prevalence and larger size of UCAs in AIS patients than in the general population. Hypertension was an independent risk factor of UCA in AIS.
Cerebral aneurysms are abnormal focal pouch-like dilatations of the cerebral artery. The most dreaded complication of an unruptured cerebral aneurysm (UCA) is subarachnoid hemorrhage, which is associated with high morbidity and mortality [
The reported prevalence of UCAs ranges from 0.2 to 9% [
While UCA and ischemic stroke share many risk factors, the prevalence of UCAs has not been investigated in patients with acute ischemic stroke (AIS). Thus, the purpose of this study was to evaluate the prevalence and characteristics of UCAs in AIS patients in comparison to a control population for the evaluation of comorbid factors related to the prevalence of UCAs in AIS patients.
This retrospective, cross-sectional study was conducted in a tertiary university hospital setting. Patients were classified into two groups for the study. The AIS group included patients with acute ischemic stroke who were admitted to the hospital and underwent brain magnetic resonance angiography (MRA) between January 2011 and December 2014. The health check-up (HC) group, which was used as the control group, consisted of individuals who underwent a brain MRA between January 2011 and December 2012 as part of a routine health examination.
Patient data including age, sex, past medical history (hypertension, diabetes, hyperlipidemia, previous stroke history, and smoking), family history of cerebrovascular disease (intracerebral hemorrhage, subarachnoid hemorrhage, or cerebral infarction), and follow-up results were obtained from medical records. In the AIS group, stroke subtypes were categorized by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria [
The retrospective study design and protocol were approved by our institutional review board. The requirement for written informed consent from the patients was waived due to the retrospective nature of the design.
All 3-dimensional time-of-flight MRA examinations were performed using one of two 3.0T magnetic resonance imaging systems at our institution (Discovery MR750, GE Medical Systems, Milwaukee, WI, USA; Achieva, Philips Medical Systems, Best, The Netherlands). Three-dimensional time-of-flight MRA was performed with the following parameters for the Discovery MR750 instrument: repetition time/echo time, 23/2.5 ms; flip angle, 20 degrees; field of view, 210×185 mm; 4 slabs (176 slices); slice thickness, 1.4 mm; matrix, 416×224; and acquisition time, 5 minutes and 9 seconds; and for the Achieva instrument: repetition time/echo time, 25/3.5 ms; flip angle, 20 degrees; field of view, 250×198 mm; 1 slab (170 slices); slice thickness, 1.4 mm; matrix, 832×414; and acquisition time, 6 minutes and 52 seconds.
UCAs were defined as abnormal focal outpouchings of the cerebral arteries [
Aneurysm size was measured by the largest diagonal measurement. Aneurysm locations were classified as internal carotid artery (ICA), anterior cerebral artery, anterior communicating artery, middle cerebral artery (MCA), posterior communicating artery, and vertebrobasilar artery (including vertebral artery, basilar artery, posterior cerebral artery, and anterior and posterior cerebellar arteries). In addition, multiple aneurysms and the presence of daughter sacs were analyzed.
Differences between the two groups were evaluated using Student’s
A total of 1,163 patients with suspected ischemic stroke were admitted to our hospital during the study period. Patients with transient ischemic attack (n=203), and no MRA due to pacemaker implantation (n=2), bionic ear (n=1), and poor general condition (n=2) were excluded from our analysis. Eventually, a total of 955 patients with AIS and 2,118 individuals who had undergone a brain MRA as part of a health check-up were enrolled in the study (
The baseline characteristics of the patients in each group are shown in
UCAs were found in 74 patients in the AIS group (7.7%; 38 men and 36 women; age 43 to 91 years, mean 67.2±11.2 years) and 79 people in the control (3.7%; 35 men and 44 women; age 37 to 76 years, mean 57.2±8.8 years). Eight patients in the AIS group and 4 patients in the HC group had been diagnosed and treated for their UCA before this study. The prevalence of UCAs was significantly higher in the AIS group than in the HC group (OR 2.17, 95% CI 1.56-3.01,
In an age-matched comparison, the prevalence of UCAs was higher in the AIS group compared to the HC group based on the Cochran-Mantel-Haenszel test (OR 1.79, 95% CI 1.24-2.60,
A total of 187 aneurysms were detected in 153 patients. Multiple aneurysms were noted in 13 patients (17.6%) in the AIS group and 11 patients (13.9%) in the HC group. The mean diameter of the UCAs was larger in the AIS group than in the HC group (3.75 mm vs. 3.02 mm;
Age, female sex, hypertension, diabetes, hyperlipidemia, previous stroke history, smoking, and family history of stroke were analyzed using logistic regression analysis (
The mean follow-up duration was 18.3 months (median 13.0, range 1-48 months) in the AIS group and 17.6 months (median 15.0, range 1-48 months) in the HC group. Eight of the 66 patients (12%) in the AIS group were treated by clipping (n=5) or coiling (n=3), and 21 of the 75 (28%) patients in HC group were treated by clipping (n=12) or coiling (n=9). Among the patients who did not undergo treatment, aneurysm rupture occurred in 3 patients in the AIS group and none in the HC group.
The overall prevalence of UCAs in the HC group in the present study was similar to that estimated in a recent systemic review published in 2011, which estimated the overall UCA prevalence to be 3.2% in a population without comorbidity (mean age, 50 years; 50% men) [
We found that the prevalence of UCAs was higher in the AIS group than in the HC group. We hypothesized that this difference was due to the high proportion of risk factors related to cerebral aneurysm in the AIS group. This difference was especially significant in the 7th decade. There is some controversy with respect to the age-related increase in the prevalence of UCAs. Specifically, some studies reported that the prevalence of UCAs steadily increased with age in both genders [
Besides the higher prevalence and larger aneurysm size observed in the AIS group, some important determinants of eventual cerebral aneurysm rupture were also more common in this group, such as hypertension, smoking, and alcohol consumption [
There are several limitations of this study. First, the diagnosis of UCAs was based on 3-dimensional time-of-flight MRA, not conventional angiography, which may have made it more difficult to diagnose small UCAs and to differentiate small aneurysms from junctional dilatations. However, recent studies [
In summary, UCAs were more common in AIS patients than in the control group. The mean size of aneurysms in the AIS group was larger than that in the HC group, and aneurysm size increased significantly with age in the AIS group only. Among the various risk factors evaluated, only hypertension was associated with the increased prevalence of aneurysms in the AIS group. Ultimately, a follow-up study of UCAs in ischemic stroke patients is required to evaluate the precise risk of aneurysmal rupture in order to assist in refining treatment plans.
The authors have no financial conflicts of interest.
Characteristics of the patients with unruptured cerebral aneurysm
Size of aneurysm by location
Flow diagram of participants. TIA, transient ischemic attack; MRA, magnetic resonance angiography; UCA, unruptured cerebral aneurysm.
Relationship between the size of unruptured cerebral aneurysms and age in the acute ischemic stroke group (A) and the health check-up group (B). The regression lines are y=0.052x+0.233 (A) and y=0.022x+1.768 (B) where y is aneurysm size (mm) and x is age (years).
Baseline characteristics of subjects
Characteristics | AIS (n=955) | HC (n=2,118) | |
---|---|---|---|
Age (mean ± SD), (year) | 64.9 ± 14.1 | 53.9 ± 9.6 | < 0.001 |
Male | 586 (61.4) | 1,188 (56.1) | 0.06 |
Hypertension | 600 (62.8) | 622 (29.4) | < 0.001 |
Diabetes | 289 (30.3) | 241 (11.4) | < 0.001 |
Hyperlipidemia | 134 (14.0) | 189 (8.9) | < 0.001 |
Previous stroke | 170 (17.8) | 20 (0.9) | < 0.001 |
Smokers | 417 (43.7) | 710 (33.5) | < 0.001 |
Family history of stroke | 94 (9.8) | 44 (2.1) | < 0.001 |
Values are number of patients (%) unless otherwise specified.
AIS, acute ischemic stroke; HC, health check-up.
Age- and sex-specific prevalence of unruptured cerebral aneurysms
Age (year) | Acute ischemic stroke group |
Health check-up group |
|||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Men |
Women |
Total |
Men |
Women |
Total |
||||||||
Pop | UCA | Pop | UCA | Pop | UCA | Pop | UCA | Pop | UCA | Pop | UCA | ||
< 50 | 99 | 3 (3.0) | 38 | 3 (7.9) | 137 | 6 (4.4) | 371 | 8 (2.2) | 282 | 8 (2.8) | 653 | 16 (2.5) | 0.212 |
50-59 | 146 | 8 (5.5) | 42 | 3 (7.1) | 188 | 11 (5.9) | 522 | 16 (3.1) | 390 | 20 (5.1) | 912 | 36 (3.9) | 0.240 |
60-69 | 162 | 14 (8.6) | 75 | 11 (14.7) | 237 | 25 (10.5) | 224 | 8 (3.6) | 209 | 11 (5.3) | 433 | 19 (4.4) | 0.002 |
≥ 70 | 179 | 13 (7.3) | 214 | 19 (8.9) | 393 | 32 (8.1) | 71 | 3 (4.2) | 49 | 5 (10.2) | 120 | 8 (6.7) | 0.598 |
Total | 586 | 38 (6.5) | 369 | 36 (9.8) | 955 | 74 (7.7) | 1,188 | 35 (3.0) | 930 | 44 (4.7) | 2,118 | 79 (3.7) | < 0.001 |
0.138 | 0.932 | 0.118 | 0.325 | 0.038 | 0.024 |
Values are number of patients (%) unless otherwise specified.
Pop, population; UCA, unruptured cerebral aneurysm.
Distribution of unruptured cerebral aneurysm
Location | AIS | HC | OR (95% CI) | |
---|---|---|---|---|
ICA | 48 (52.2) | 65 (68.4) | Reference | |
MCA | 22 (23.9) | 8 (8.4) | 3.72 (1.53-9.08) | 0.004 |
A-com | 9 (9.8) | 7 (7.4) | 1.74 (0.61-5.00) | 0.303 |
P-com | 6 (6.5) | 9 (9.5) | 0.90 (0.30-2.71) | 0.855 |
VB | 7 (7.6) | 2 (2.1) | 4.74 (0.94-21.83) | 0.059 |
ACA | 0 (0) | 4 (4.2) | - | 0.999 |
Values are number of patients (%) unless otherwise specified.
AIS, acute ischemic stroke; HC, health check-up; OR, odds ratio; CI, confidence interval; ICA, internal carotid artery; MCA, middle cerebral artery; A-com, anterior communicating artery; P-com, posterior communicating artery; VB, vertebrobasilar artery; ACA, anterior cerebral artery.
Independent predictors of unruptured cerebral aneurysms in acute ischemic stroke patients
Predictors | Univariate |
Multivariate |
||
---|---|---|---|---|
OR (95% CI) | OR (95% CI) | |||
Age, per 1-year increase | 1.01 (0.99-1.03) | 0.142 | 1.01 (0.99-1.03) | 0.571 |
Female sex | 1.56 (0.97-2.51) | 0.067 | 1.82 (0.95-3.49) | 0.072 |
Hypertension | 2.09 (1.19-3.65) | 0.010 | 1.95 (1.07-3.53) | 0.029 |
Diabetes | 0.84 (0.50-1.44) | 0.529 | 0.70 (0.40-1.20) | 0.189 |
Hyperlipidemia | 1.48 (0.80-2.73) | 0.210 | 1.43 (0.75-2.71) | 0.273 |
Previous stroke | 1.30 (0.73-2.33) | 0.372 | 1.15 (0.63-2.10) | 0.642 |
Smoking | 0.93 (0.57-1.50) | 0.749 | 1.46 (0.76-2.81) | 0.256 |
Family history of stroke | 0.95 (0.42-2.14) | 0.908 | 1.11 (0.49-2.55) | 0.806 |
TOAST | 0.235 | 0.276 | ||
Large-artery atherosclerosis | Reference | Reference | ||
Cardioembolism | 2.12 (0.99-4.49) | 0.051 | 1.98 (0.92-4.22) | 0.079 |
Small-vessel disease | 1.89 (0.89-3.99) | 0.098 | 2.01 (0.97-4.49) | 0.060 |
Other determined etiology | 1.53 (0.19-12.73) | 0.693 | 1.84 (0.21-16.12) | 0.581 |
Undetermined etiology | 2.39 (1.12-5.13) | 0.024 | 2.31 (1.07-4.98) | 0.033 |