Etiology and Risk Factors of Posterior Circulation Infarction Compared with Anterior Circulation Infarction Quantao Zeng, MD, Wendan Tao, MD, Chunyan Lei, MD, Wei Dong, MD, and Ming Liu, MD, PhD
Background: Many clinicians regard posterior circulation infarction (PCI) as different from anterior circulation infarction (ACI), leading them to apply different treatments. Few studies have validated this practice by directly comparing the etiology and risk factors of PCI and ACI. Methods: We compared the etiology and risk factors of 2245 consecutive patients with a diagnosis of PCI or ACI confirmed by magnetic resonance imaging in the Chengdu Stroke Registry. Stroke etiology in each patient was classified according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results: Our sample included 482 patients (21.5%) with PCI and 1763 (78.5%) with ACI. The most frequent etiology for both infarction types was small-artery occlusion, occurring in 37.6% of patients with PCI and 37.1% of those with ACI. Cardioembolism caused infarction in a significantly smaller proportion of patients with PCI (5.4%) than in patients with ACI (13.3%; odds ratio [OR] 5 .373; 95% confidence interval [CI], .245-.566). Frequencies of other stroke etiologies were similar between the 2 patient groups. Analysis of risk factor frequencies in the 2 groups showed hypertension to be the most common, occurring in 47.9% of patients in either group. Multivariable analysis identified 2 factors as conferring greater risk of PCI than ACI: male gender (OR 5 1.392; 95% CI, 1.085-1.786) and diabetes mellitus (OR 5 1.667; 95% CI, 1.275-2.180). The same analysis identified 2 factors as conferring greater risk of ACI: atrial fibrillation (OR 5 .530; 95% CI, .295-.951) and heart valve disease (OR 5 .433; 95% CI, .203-.922). Frequencies of other possible risk factors were similar between the 2 groups. Conclusions: These findings suggest that PCI and ACI are more similar than different in their etiology and risk factors and that the 2 types of infarction should be treated based more on etiology and risk factors than on their posterior or anterior localization. Key Words: Posterior circulation infarction—anterior circulation infarction—etiology—risk factors. Ó 2015 by National Stroke Association
From the Department of Neurology, West China Hospital, Sichuan University, Chengdu, China. Received November 6, 2014; revision received January 24, 2015; accepted March 18, 2015. The authors declare no conflicts of interest. This work was supported by a research grant from the Science and Technology Pillar Program of Sichuan Province (2011SZ0202). The agency that supported this research did not have any conflict of interests with the study. Address correspondence to Ming Liu, MD, PhD, Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, China. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.03.033
Approximately 80% of strokes are ischemic, with posterior circulation infarction (PCI) accounting for 20% of these cases.1 Many clinicians regard PCI as different from anterior circulation infarction (ACI) in terms of risk factors, etiology, clinical manifestations, and prognosis.2-7 As a result, they often treat the 2 conditions using different approaches, sometimes without careful consideration of specific stroke etiology and risk factors. Analysis of patient data from 3 stroke registries suggested that cardioembolism occurs less frequently among patients with PCI than among those with ACI,8-10 but other studies have failed to replicate this finding.6,11 In addition, several studies have failed to
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identify significant differences in clinical manifestation and prognosis between the 2 stroke localizations.6,10,12,13 Given the specific anatomical localization of PCI, its diagnosis is more dependent on magnetic resonance imaging (MRI).14,15 However, previous studies have varied in their use of MRI examination. This situation highlights the need for rigorous, direct comparisons of etiology and risk factors between PCI and ACI under identical conditions of MRI-based diagnosis. Here, we retrospectively analyzed data for Chinese patients with MRI-confirmed PCI or ACI treated at a single large medical center to compare etiology and risk factors in the 2 patient groups.
Patients and Methods Study Design Between March 2002 and May 2014, data were collected prospectively on 6505 patients with acute ischemic stroke admitted to the Department of Neurology, West China Hospital, Chengdu, China. This is a large tertiary hospital serving a greater metropolitan area of 14 million and numerous patients from surrounding cities. Patient data were entered into the Chengdu Stroke Registry, which was approved by the Scientific Research Department of West China Hospital, as conforming to local ethics criteria for human research. All patients received a clinical diagnosis of ischemic stroke according to World Health Organization criteria, based on the presence of an acute focal neurologic deficit with symptoms lasting longer than 24 hours and corresponding neuroimaging findings.16 We excluded patients admitted to our hospital 1 week after stroke onset (n 5 1415), patients without an MRI-verified ischemic lesion (n 5 1143), patients with previous stroke (n 5 862), and patients with multiple infarcts involving both anterior and posterior circulation (n 5 840). We analyzed the remaining 2245 patients and classified them as having infarction involving only posterior circulation or only anterior circulation. Patients were assigned to the PCI group if the infarcts involved the posterior cerebral artery territory, brainstem, cerebellum, or thalamus; they were assigned to the ACI group if the infarcts occurred in the region of the anterior cerebral artery, middle cerebral artery, or anterior choroidal artery.17,18
Data Collection Data were collected at the time of patient assessment using a standardized form19,20; these data included patient demographics (age and sex), time of stroke onset, stroke severity assessed by the National Institute of Health Stroke Scale (NIHSS) and the Glasgow Coma Scale (GCS), and risk factors (hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, myocardial infarction, heart valve disease, coronary artery disease,
current smoking, and alcohol consumption). All patients underwent a standard etiological workup, comprising the following: hematological examination, involving at least routine blood analysis, blood biochemistry, and coagulation function; 12-lead electrocardiography; transthoracic echocardiography; and carotid duplex sonography. Most patients were analyzed by computed tomography (CT) within 4 hours of admission or computed tomography angiography (CTA) within 24 hours of admission. All patients were analyzed by either conventional MRI or diffusion-weighted MRI (DWI), usually within 2 days of admission. After 2008, ischemic stroke patients admitted to our hospital were routinely analyzed using DWI and three-dimensional time-of-flight MR angiography (MRA). All MRIs were performed using 3-T devices from 2003 onward. All diagnoses were based on at least 1 cerebrovascular assessment by MRA or CTA. Digital subtraction angiography was performed if necessary. For patients who had negative findings on vascular examination and transthoracic echocardiography, transesophageal echocardiography or dynamic electrocardiography was used to determine cardiac and aortic arch sources of cardiac embolization. Stroke subtype was classified according to the TOAST categories21 and was obtained from clinicians based on the results of clinical findings, radiological findings, and other diagnostic tests.
Statistical Analysis Frequencies of etiologies and of other categorical variables were compared between the PCI and ACI groups using the Pearson chi-squared test. Means of continuous variables were compared using Student t test. When appropriate, odds ratios (ORs) were calculated together with associated 95% confidence intervals (95% CIs). A binary logistic regression model was generated to explore potential association of the above-mentioned demographic and risk factors with risk of PCI. All variables were entered and retained in the regression model. Significance was assessed using 2-tailed P values, with the threshold defined as P less than .05. All statistical analyses were performed using SPSS 16.0 for Windows (IBM, Chicago, IL).
Results Baseline Characteristics of PCI and ACI Patients A total of 2245 patients (1357 men, 60.4%) with a mean age of 62.50 6 13.94 years experiencing first-ever ischemic stroke were enrolled in this study, including 482 (21.5%) with PCI and 1763 (78.5%) with ACI. Most patients (77.3%) arrived at our hospital or were transferred there within 3 days of stroke onset. The mean NIHSS score on admission was 6.14 6 6.00, and mean GCS score was 13.91 6 2.04.
ETIOLOGY AND RISK FACTORS OF PCI VERSUS ACI
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Table 1. Demographics, stroke severity, and risk factors between PCI and ACI Characteristics
Total (n 5 2245)
PCI (n 5 482)
ACI (n 5 1763)
P value
Age(y), mean (SD) Male, n (%) Admission delay, n (%) &3 d 3-7 d Stroke severity NIHSS, mean (SD) GCS, mean (SD) Risk factors, n (%) Hypertension Current smoking Alcohol consumption Diabetes mellitus Hyperlipidemia Atrial fibrillation Coronary artery disease Heart valve disease Myocardial infarction
62.50 (13.94) 1357 (60.4)
61.77 (14.15) 325 (67.4)
62.71 (13.86) 1032 (58.5)
.190 ,.001 .004
1735 (77.3) 510 (22.7)
349 (72.4) 133 (27.6)
1386 (78.6) 377 (21.4)
6.14 (6.00) 13.91 (2.04)
5.18 (6.77) 14.29 (1.87)
6.40 (5.74) 13.80 (2.08)
,.001 ,.001
1076 (47.9) 757 (33.7) 503 (22.4) 344 (15.3) 145 (6.5) 147 (6.5) 117 (5.2) 97 (4.3) 25 (1.1)
231 (47.9) 182 (37.8) 111 (23.0) 101 (21.0) 31 (6.4) 14 (2.9) 15 (3.1) 8 (1.7) 3 (.6)
845 (47.9) 575 (32.6) 392 (22.2) 243 (13.8) 114 (6.5) 133 (7.5) 102 (5.8) 89 (5.0) 22 (1.2)
.999 .034 .711 ,.001 .978 ,.001 .019 .001 .246
Abbreviations: ACI, anterior circulation infarction; GCS, Glasgow Coma Scale; NIHSS, National Institutes of Health Stroke Scale; PCI, posterior circulation infarction; SD, standard deviation.
Comparison of the PCI and ACI groups showed that PCI patients were more likely to be men (67.4% versus 58.5%, P , .001), and they had a lower mean NIHSS score on admission (5.18 versus 5.74, P , .001) and a higher mean GCS score (14.29 versus 13.80, P , .001). The proportion of PCI patients admitted at least 3 days after stroke was larger than the corresponding proportion of ACI patients (27.6% versus 21.4%, P 5 .004; Table 1).
Stroke Etiology in PCI and ACI Patients The etiology of ischemic stroke in all included patients is shown in Table 2. Across both PCI and ACI groups, the most frequent etiology was small-artery occlusion (37.2%), followed by large-artery atherosclerosis (27.3%), stroke of undetermined etiology (21.4%), cardioembolism (11.6%), and stroke of other determined etiology (2.5%). The overall distribution of etiologies differed significantly between PCI and ACI patients (P , .001), and this difference was because of the significantly lower frequency of
cardioembolism among PCI patients than among ACI patients (5.4% versus 12.7%; OR 5 .373, 95% CI, .245.566). The frequencies of other etiologies did not differ significantly between the 2 patient groups (Table 2, Fig 1).
Risk Factors in PCI and ACI Patients Both patient groups showed a similar distribution of risk factors, with relative frequencies following the sequence: hypertension . current smoking . alcohol consumption . diabetes mellitus . hyperlipidemia z atrial fibrillation . coronary artery disease . heart valve disease . myocardial infarction (Table 1). Nevertheless, some risk factors were present at significantly different frequencies in the 2 groups, with PCI patients showing a significantly higher proportion of diabetes mellitus (21.0% versus 13.8%, P , .001) and current smoking (37.8% versus 32.6%, P 5 .034), and a significantly lower proportion of atrial fibrillation (2.9% versus 7.5%, P , .001), heart valve disease (1.7% versus 5.0%,
Table 2. Etiology of PCI and ACI in Chinese patients Etiology LAA SAO CE SOE SUE
Total (n 5 2245)
PCI (n 5 482)
ACI (n 5 1763)
612 (27.3) 835 (37.2) 260 (11.6) 57 (2.5) 481 (21.4)
140 (29.0) 181 (37.6) 26 (5.4) 17 (3.5) 118 (24.5)
472 (26.8) 654 (37.1) 234 (13.3) 40 (2.3) 363 (20.6)
P value .321 .854 .007 .120 .856
Total ,.001
Abbreviations: ACI, anterior circulation infarction; CE, cardioembolism; LAA, large-artery atherosclerosis; PCI, posterior circulation infarction; SAO, small-artery occlusion; SOE, stroke of other determined etiology; SUE, stroke of undetermined etiology. Data are n (%).
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Fig 2).Other risk factors showed similar strengths of association with both PCI and ACI.
Discussion
Figure 1. Etiology of PCI compared with ACI. *P , .05, error bars: 95% CI. Abbreviations: ACI, anterior circulation infarction; CE, cardioembolism; CI, confidence interval; LAA, large-artery atherosclerosis; PCI, posterior circulation infarction; SAO, small-artery occlusion; SOE, stroke of other determined etiology; SUE, stroke of undetermined etiology.
P 5 .001), and coronary artery disease (3.1% versus 5.8%, P 5 .019; Tables 1 and 3). Multivariate analysis was used to identify risk factors associated more with PCI than ACI or vice versa. ORs were calculated relative to risk of ACI, so ORs greater than 1 indicate that the risk factor in question is associated more with risk of PCI than with risk of ACI. Two factors were found to be associated with PCI over ACI: male gender (OR 5 1.392; 95% CI, 1.085-1.786) and diabetes mellitus (OR 5 1.667; 95% CI, 1.275-2.180). Conversely, 2 factors were found to be associated with ACI over PCI: atrial fibrillation (OR 5 .530; 95% CI, .295-.951) and heart valve disease (OR 5 .433; 95 % CI, .203-.922) (Table 3,
The present study describes what we believe to be one of the most rigorous studies to date directly comparing etiology and risk factors in patients with PCI and ACI. In addition, all patients were diagnosed using MRI to ensure accurate detection of PCI. Our results suggest that PCI and ACI, although commonly regarded as distinct diseases, are actually more similar than dissimilar in terms of etiology and risk factors. Nevertheless, we did identify some significant differences: cardioembolism occurred less often among PCI patients than ACI patients, and PCI patients were less likely to present cardiogenic risk factors and more likely to have diabetes mellitus. Relying solely on clinical neurologic deficits can lead to inaccurate determination of infarct localization and thus to mistakes in diagnosis of PCI and ACI.12 To ensure more accurate diagnosis of PCI, all our patients were examined by MRI, which has been shown to be more accurate than CT for diagnosing posterior fossa infarction.14,15 In addition, all our patients were diagnosed in the same way at a single medical center, reducing heterogeneity within the PCI and ACI groups. This may help make our results more reliable. We found that the distribution of etiologies was similar between PCI and ACI patients, except that the frequency of cardioembolism was significantly lower among PCI patients. A recent study in Korean patients similarly revealed lower incidence of cardioembolism in PCI (13.8% versus 23.2%),22 as have studies in Caucasian patients.8-10 This may reflect the fact that thrombus in the heart is more likely to enter the anterior circulation, which accounts for nearly 80% of cerebrovascular blood flow. On the other hand, some studies in Caucasian
Table 3. Logistic regression to identify risk factors for PCI relative to ACI in Chinese patients Univariable
Multivariable
Vascular risk factors
OR
95% CI
b-Coefficient
OR
95% CI
b-Coefficient
Age(y), mean (SD) Male, n (%) Hypertension Diabetes mellitus Hyperlipidemia Atrial fibrillation Myocardial infarction Heart valve disease Coronary artery disease Current smoking Alcohol consumption
.995 1.466 .999 1.658 .994 .367 .496 .317 .523 1.253 1.046
.988-1.002 1.185-1.814 .817-1.223 1.281-2.146 .660-1.499 .209-.642 .148-1.663 .153-.659 .301-.908 1.017-1.545 .823-1.330
2.005 .383 .000 .506 2.006 21.003 2.702 21.147 2.648 .226 .045
.996 1.392 .950 1.667 .896 .530 .620 .433 .637 1.108 .820
.989-1.004 1.085-1.786 .767-1.178 1.275-2.180 .586-1.370 .295-.951 .182-2.112 .203-.922 .361-1.125 .847-1.449 .615-1.093
2.004 .331 2.051 .511 2.110 2.635 2.479 2.838 2.450 .103 2.198
Abbreviations: ACI, anterior circulation infarction; CI, confidence interval; OR, odds ratio; PCI, posterior circulation infarction; SD, standard deviation.
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5 22
Figure 2. Association between vascular risk factors and location of ischemic stroke. *P , .05.
patients have suggested identical distributions of etiologies, including cardioembolism, between PCI and ACI.6,11,23 Further research may be needed to resolve whether etiology differs significantly between the 2 types of stroke. Part of the challenge in resolving this question lies in the fact that ischemic stroke etiology has been shown to depend on ethnicity.24,25 A meta-analysis has suggested that the most frequent etiologies of ischemic stroke in Caucasians are cardioembolism, followed by small-artery occlusion, and then large-artery atherosclerosis.26 In contrast, our study identified the 3 most frequent causes in Chinese patients to be smallartery occlusion, followed by large-artery atherosclerosis, and then cardioembolism. Similar results were obtained in other stroke database studies in other Asian countries, including the Takashima stroke registry in Japan,27 the Aga Khan University stroke databank in Pakistan,28 and the Korean stroke registry.29 Our results are also consistent with previous work showing that small-artery occlusion causes ischemic stroke more frequently in Asia than in the West.30 The frequency of cardioembolism in our study for all patients was 11.6%, lower than the frequency reported in several studies with Caucasian patients. This is consistent with evidence suggesting that cardioembolism is the most common cause of ischemic stroke in Caucasian populations.31,32 The frequency of cardioembolism in our sample of Chinese patients is lower than 22.9% reported in a Japanese study27 and 20.6% in a Korean
study. The following 2 observations may help explain this. First, ischemic stroke patients with a metal heart valve, coronary stent, or cardiac pacemaker are not typically analyzed by MRI at our medical center, although evidence suggests that MRI examination is safe for at least some of these patients,33,34 and these patients were excluded from our study. It is possible that at least some of these excluded patients had cardioembolic stroke. Second, few stroke patients in China undergo transesophageal echocardiography, which may lead to underestimates of how many stroke patients have heartrelated diseases, including cardioembolism. PCI and ACI patients in our study presented similar risk factors, with the relative frequency following the trend: hypertension . current smoking . alcohol consumption . diabetes mellitus . hyperlipidemia . atrial fibrillation. Multivariate analysis showed male gender and diabetes mellitus to be associated with greater likelihood of PCI than ACI. Conversely, atrial fibrillation and heart valve disease were associated with greater likelihood of ACI than PCI. Other factors that we examined were not preferentially related to PCI or ACI, including age, hypertension, hyperlipidemia, myocardial infarction, coronary artery disease, current smoking, or alcohol consumption. Our observation of an association between diabetes mellitus and PCI is consistent with 2 small observational studies35,36 and a large study in Canada.4 Why diabetes mellitus is preferentially associated with PCI is unclear and should be investigated in future. PCI patients were at lower risk of cardioembolism than ACI patients, and this may be linked with our observation that risk factors for cardioembolism (atrial fibrillation and heart valve disease) were preferentially associated with ACI over PCI. This is consistent with previous studies.3,4 The proportion of women was significantly higher among ACI patients than among PCI patients, and ACI patients had higher NIHSS and lower GCS scores. This suggests that women tend to have more severe strokes than men, which may help explain the association between female gender and poor clinical outcomes after stroke.37,38 The relatively mild stroke in PCI patients may help explain why a greater proportion of these patients were admitted more than 3 days after stroke onset than ACI patients. We found that most risk factors showed similar strength of association with PCI and ACI and that even factors showing a preferential association with one stroke localization or the other gave ORs near 1. These results, together with the similar clinical manifestations and prognosis for PCI and ACI,6,10,12,13 suggest that the clinical practice of treating PCI and ACI differently is not supported by the available evidence. For example, some clinicians believe that the thrombolytic time window can be longer in PCI than in ACI and that PCI patients were an appropriate subgroup for acute anticoagulant therapy.7 However, our finding that PCI patients had
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relatively low NIHSS score on admission does not support extending the thrombolytic time window, and our finding that they were less likely to present cardiogenic risk factors argues against using positive anticoagulant therapy. Our data suggest that in most respects, PCI patients and ACI patients should be treated in the same way for the same etiology and risk factors. For example, substantial proportions of PCI and ACI patients have diabetes mellitus and/or hypertension, and these comorbidities should be managed in the same way regardless of stroke lesion location. Thus, clinicians should treat PCI and ACI patients more according to specific etiology and risk factors than according to infarct localization per se. Our relatively small study had several limitations. First, we excluded patients who were not examined by MRI, and patients with multiple lesions involving both posterior and anterior circulation. This may have introduced selection bias in our results. Second, we did not analyze the specific arteries affected or infarct localization in our patients, preventing us from correlating etiology or risk factors with specific pathogenesis. On the other hand, our study population was diagnosed according to the same rigorous standards, improving the reliability of our findings.
Conclusion PCI and ACI showed similar etiology in our Chinese patients, with the exception that cardioembolic stroke affected anterior circulation more often than posterior circulation. Risk factors were also similar for PCI and ACI, with the exceptions that diabetes mellitus occurred more often in PCI, whereas atrial fibrillation and heart valve disease occurred more often in ACI. The extensive similarities between PCI and ACI do not justify the different risk factor stratifications or treatments often applied in the clinic for the 2 types of ischemic stroke. These findings suggest that during stroke patient workup, less attention should be paid to whether the infarct affects posterior or anterior circulation, and more attention should be paid to specific etiology and risk factors to guide treatment during the acute phase and to prevent secondary stroke.
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Background: Many clinicians regard posterior circulation infarction (PCI) as different from anterior circulation infarction (ACI), leading them to apply different treatments. Few studies have validated this practice by directly comparing the etiology and risk factors of PCI and ACI. Methods: We compared the etiology and risk factors of 2245 consecutive patients with a diagnosis of PCI or ACI confirmed by magnetic resonance imaging in the Chengdu Stroke Registry. Stroke etiology in each patient was classified according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results: Our sample included 482 patients (21.5%) with PCI and 1763 (78.5%) with ACI. The most frequent etiology for both infarction types was small-artery occlusion, occurring in 37.6% of patients with PCI and 37.1% of those with ACI. Cardioembolism caused infarction in a significantly smaller proportion of patients with PCI (5.4%) than in patients with ACI (13.3%; odds ratio [OR] 5 .373; 95% confidence interval [CI], .245-.566). Frequencies of other stroke etiologies were similar between the 2 patient groups. Analysis of risk factor frequencies in the 2 groups showed hypertension to be the most common, occurring in 47.9% of patients in either group. Multivariable analysis identified 2 factors as conferring greater risk of PCI than ACI: male gender (OR 5 1.392; 95% CI, 1.085-1.786) and diabetes mellitus (OR 5 1.667; 95% CI, 1.275-2.180). The same analysis identified 2 factors as conferring greater risk of ACI: atrial fibrillation (OR 5 .530; 95% CI, .295-.951) and heart valve disease (OR 5 .433; 95% CI, .203-.922). Frequencies of other possible risk factors were similar between the 2 groups. Conclusions: These findings suggest that PCI and ACI are more similar than different in their etiology and risk factors and that the 2 types of infarction should be treated based more on etiology and risk factors than on their posterior or anterior localization. Key Words: Posterior circulation infarction—anterior circulation infarction—etiology—risk factors. Ó 2015 by National Stroke Association
From the Department of Neurology, West China Hospital, Sichuan University, Chengdu, China. Received November 6, 2014; revision received January 24, 2015; accepted March 18, 2015. The authors declare no conflicts of interest. This work was supported by a research grant from the Science and Technology Pillar Program of Sichuan Province (2011SZ0202). The agency that supported this research did not have any conflict of interests with the study. Address correspondence to Ming Liu, MD, PhD, Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, China. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2015 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.03.033
Approximately 80% of strokes are ischemic, with posterior circulation infarction (PCI) accounting for 20% of these cases.1 Many clinicians regard PCI as different from anterior circulation infarction (ACI) in terms of risk factors, etiology, clinical manifestations, and prognosis.2-7 As a result, they often treat the 2 conditions using different approaches, sometimes without careful consideration of specific stroke etiology and risk factors. Analysis of patient data from 3 stroke registries suggested that cardioembolism occurs less frequently among patients with PCI than among those with ACI,8-10 but other studies have failed to replicate this finding.6,11 In addition, several studies have failed to
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identify significant differences in clinical manifestation and prognosis between the 2 stroke localizations.6,10,12,13 Given the specific anatomical localization of PCI, its diagnosis is more dependent on magnetic resonance imaging (MRI).14,15 However, previous studies have varied in their use of MRI examination. This situation highlights the need for rigorous, direct comparisons of etiology and risk factors between PCI and ACI under identical conditions of MRI-based diagnosis. Here, we retrospectively analyzed data for Chinese patients with MRI-confirmed PCI or ACI treated at a single large medical center to compare etiology and risk factors in the 2 patient groups.
Patients and Methods Study Design Between March 2002 and May 2014, data were collected prospectively on 6505 patients with acute ischemic stroke admitted to the Department of Neurology, West China Hospital, Chengdu, China. This is a large tertiary hospital serving a greater metropolitan area of 14 million and numerous patients from surrounding cities. Patient data were entered into the Chengdu Stroke Registry, which was approved by the Scientific Research Department of West China Hospital, as conforming to local ethics criteria for human research. All patients received a clinical diagnosis of ischemic stroke according to World Health Organization criteria, based on the presence of an acute focal neurologic deficit with symptoms lasting longer than 24 hours and corresponding neuroimaging findings.16 We excluded patients admitted to our hospital 1 week after stroke onset (n 5 1415), patients without an MRI-verified ischemic lesion (n 5 1143), patients with previous stroke (n 5 862), and patients with multiple infarcts involving both anterior and posterior circulation (n 5 840). We analyzed the remaining 2245 patients and classified them as having infarction involving only posterior circulation or only anterior circulation. Patients were assigned to the PCI group if the infarcts involved the posterior cerebral artery territory, brainstem, cerebellum, or thalamus; they were assigned to the ACI group if the infarcts occurred in the region of the anterior cerebral artery, middle cerebral artery, or anterior choroidal artery.17,18
Data Collection Data were collected at the time of patient assessment using a standardized form19,20; these data included patient demographics (age and sex), time of stroke onset, stroke severity assessed by the National Institute of Health Stroke Scale (NIHSS) and the Glasgow Coma Scale (GCS), and risk factors (hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, myocardial infarction, heart valve disease, coronary artery disease,
current smoking, and alcohol consumption). All patients underwent a standard etiological workup, comprising the following: hematological examination, involving at least routine blood analysis, blood biochemistry, and coagulation function; 12-lead electrocardiography; transthoracic echocardiography; and carotid duplex sonography. Most patients were analyzed by computed tomography (CT) within 4 hours of admission or computed tomography angiography (CTA) within 24 hours of admission. All patients were analyzed by either conventional MRI or diffusion-weighted MRI (DWI), usually within 2 days of admission. After 2008, ischemic stroke patients admitted to our hospital were routinely analyzed using DWI and three-dimensional time-of-flight MR angiography (MRA). All MRIs were performed using 3-T devices from 2003 onward. All diagnoses were based on at least 1 cerebrovascular assessment by MRA or CTA. Digital subtraction angiography was performed if necessary. For patients who had negative findings on vascular examination and transthoracic echocardiography, transesophageal echocardiography or dynamic electrocardiography was used to determine cardiac and aortic arch sources of cardiac embolization. Stroke subtype was classified according to the TOAST categories21 and was obtained from clinicians based on the results of clinical findings, radiological findings, and other diagnostic tests.
Statistical Analysis Frequencies of etiologies and of other categorical variables were compared between the PCI and ACI groups using the Pearson chi-squared test. Means of continuous variables were compared using Student t test. When appropriate, odds ratios (ORs) were calculated together with associated 95% confidence intervals (95% CIs). A binary logistic regression model was generated to explore potential association of the above-mentioned demographic and risk factors with risk of PCI. All variables were entered and retained in the regression model. Significance was assessed using 2-tailed P values, with the threshold defined as P less than .05. All statistical analyses were performed using SPSS 16.0 for Windows (IBM, Chicago, IL).
Results Baseline Characteristics of PCI and ACI Patients A total of 2245 patients (1357 men, 60.4%) with a mean age of 62.50 6 13.94 years experiencing first-ever ischemic stroke were enrolled in this study, including 482 (21.5%) with PCI and 1763 (78.5%) with ACI. Most patients (77.3%) arrived at our hospital or were transferred there within 3 days of stroke onset. The mean NIHSS score on admission was 6.14 6 6.00, and mean GCS score was 13.91 6 2.04.
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Table 1. Demographics, stroke severity, and risk factors between PCI and ACI Characteristics
Total (n 5 2245)
PCI (n 5 482)
ACI (n 5 1763)
P value
Age(y), mean (SD) Male, n (%) Admission delay, n (%) &3 d 3-7 d Stroke severity NIHSS, mean (SD) GCS, mean (SD) Risk factors, n (%) Hypertension Current smoking Alcohol consumption Diabetes mellitus Hyperlipidemia Atrial fibrillation Coronary artery disease Heart valve disease Myocardial infarction
62.50 (13.94) 1357 (60.4)
61.77 (14.15) 325 (67.4)
62.71 (13.86) 1032 (58.5)
.190 ,.001 .004
1735 (77.3) 510 (22.7)
349 (72.4) 133 (27.6)
1386 (78.6) 377 (21.4)
6.14 (6.00) 13.91 (2.04)
5.18 (6.77) 14.29 (1.87)
6.40 (5.74) 13.80 (2.08)
,.001 ,.001
1076 (47.9) 757 (33.7) 503 (22.4) 344 (15.3) 145 (6.5) 147 (6.5) 117 (5.2) 97 (4.3) 25 (1.1)
231 (47.9) 182 (37.8) 111 (23.0) 101 (21.0) 31 (6.4) 14 (2.9) 15 (3.1) 8 (1.7) 3 (.6)
845 (47.9) 575 (32.6) 392 (22.2) 243 (13.8) 114 (6.5) 133 (7.5) 102 (5.8) 89 (5.0) 22 (1.2)
.999 .034 .711 ,.001 .978 ,.001 .019 .001 .246
Abbreviations: ACI, anterior circulation infarction; GCS, Glasgow Coma Scale; NIHSS, National Institutes of Health Stroke Scale; PCI, posterior circulation infarction; SD, standard deviation.
Comparison of the PCI and ACI groups showed that PCI patients were more likely to be men (67.4% versus 58.5%, P , .001), and they had a lower mean NIHSS score on admission (5.18 versus 5.74, P , .001) and a higher mean GCS score (14.29 versus 13.80, P , .001). The proportion of PCI patients admitted at least 3 days after stroke was larger than the corresponding proportion of ACI patients (27.6% versus 21.4%, P 5 .004; Table 1).
Stroke Etiology in PCI and ACI Patients The etiology of ischemic stroke in all included patients is shown in Table 2. Across both PCI and ACI groups, the most frequent etiology was small-artery occlusion (37.2%), followed by large-artery atherosclerosis (27.3%), stroke of undetermined etiology (21.4%), cardioembolism (11.6%), and stroke of other determined etiology (2.5%). The overall distribution of etiologies differed significantly between PCI and ACI patients (P , .001), and this difference was because of the significantly lower frequency of
cardioembolism among PCI patients than among ACI patients (5.4% versus 12.7%; OR 5 .373, 95% CI, .245.566). The frequencies of other etiologies did not differ significantly between the 2 patient groups (Table 2, Fig 1).
Risk Factors in PCI and ACI Patients Both patient groups showed a similar distribution of risk factors, with relative frequencies following the sequence: hypertension . current smoking . alcohol consumption . diabetes mellitus . hyperlipidemia z atrial fibrillation . coronary artery disease . heart valve disease . myocardial infarction (Table 1). Nevertheless, some risk factors were present at significantly different frequencies in the 2 groups, with PCI patients showing a significantly higher proportion of diabetes mellitus (21.0% versus 13.8%, P , .001) and current smoking (37.8% versus 32.6%, P 5 .034), and a significantly lower proportion of atrial fibrillation (2.9% versus 7.5%, P , .001), heart valve disease (1.7% versus 5.0%,
Table 2. Etiology of PCI and ACI in Chinese patients Etiology LAA SAO CE SOE SUE
Total (n 5 2245)
PCI (n 5 482)
ACI (n 5 1763)
612 (27.3) 835 (37.2) 260 (11.6) 57 (2.5) 481 (21.4)
140 (29.0) 181 (37.6) 26 (5.4) 17 (3.5) 118 (24.5)
472 (26.8) 654 (37.1) 234 (13.3) 40 (2.3) 363 (20.6)
P value .321 .854 .007 .120 .856
Total ,.001
Abbreviations: ACI, anterior circulation infarction; CE, cardioembolism; LAA, large-artery atherosclerosis; PCI, posterior circulation infarction; SAO, small-artery occlusion; SOE, stroke of other determined etiology; SUE, stroke of undetermined etiology. Data are n (%).
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Fig 2).Other risk factors showed similar strengths of association with both PCI and ACI.
Discussion
Figure 1. Etiology of PCI compared with ACI. *P , .05, error bars: 95% CI. Abbreviations: ACI, anterior circulation infarction; CE, cardioembolism; CI, confidence interval; LAA, large-artery atherosclerosis; PCI, posterior circulation infarction; SAO, small-artery occlusion; SOE, stroke of other determined etiology; SUE, stroke of undetermined etiology.
P 5 .001), and coronary artery disease (3.1% versus 5.8%, P 5 .019; Tables 1 and 3). Multivariate analysis was used to identify risk factors associated more with PCI than ACI or vice versa. ORs were calculated relative to risk of ACI, so ORs greater than 1 indicate that the risk factor in question is associated more with risk of PCI than with risk of ACI. Two factors were found to be associated with PCI over ACI: male gender (OR 5 1.392; 95% CI, 1.085-1.786) and diabetes mellitus (OR 5 1.667; 95% CI, 1.275-2.180). Conversely, 2 factors were found to be associated with ACI over PCI: atrial fibrillation (OR 5 .530; 95% CI, .295-.951) and heart valve disease (OR 5 .433; 95 % CI, .203-.922) (Table 3,
The present study describes what we believe to be one of the most rigorous studies to date directly comparing etiology and risk factors in patients with PCI and ACI. In addition, all patients were diagnosed using MRI to ensure accurate detection of PCI. Our results suggest that PCI and ACI, although commonly regarded as distinct diseases, are actually more similar than dissimilar in terms of etiology and risk factors. Nevertheless, we did identify some significant differences: cardioembolism occurred less often among PCI patients than ACI patients, and PCI patients were less likely to present cardiogenic risk factors and more likely to have diabetes mellitus. Relying solely on clinical neurologic deficits can lead to inaccurate determination of infarct localization and thus to mistakes in diagnosis of PCI and ACI.12 To ensure more accurate diagnosis of PCI, all our patients were examined by MRI, which has been shown to be more accurate than CT for diagnosing posterior fossa infarction.14,15 In addition, all our patients were diagnosed in the same way at a single medical center, reducing heterogeneity within the PCI and ACI groups. This may help make our results more reliable. We found that the distribution of etiologies was similar between PCI and ACI patients, except that the frequency of cardioembolism was significantly lower among PCI patients. A recent study in Korean patients similarly revealed lower incidence of cardioembolism in PCI (13.8% versus 23.2%),22 as have studies in Caucasian patients.8-10 This may reflect the fact that thrombus in the heart is more likely to enter the anterior circulation, which accounts for nearly 80% of cerebrovascular blood flow. On the other hand, some studies in Caucasian
Table 3. Logistic regression to identify risk factors for PCI relative to ACI in Chinese patients Univariable
Multivariable
Vascular risk factors
OR
95% CI
b-Coefficient
OR
95% CI
b-Coefficient
Age(y), mean (SD) Male, n (%) Hypertension Diabetes mellitus Hyperlipidemia Atrial fibrillation Myocardial infarction Heart valve disease Coronary artery disease Current smoking Alcohol consumption
.995 1.466 .999 1.658 .994 .367 .496 .317 .523 1.253 1.046
.988-1.002 1.185-1.814 .817-1.223 1.281-2.146 .660-1.499 .209-.642 .148-1.663 .153-.659 .301-.908 1.017-1.545 .823-1.330
2.005 .383 .000 .506 2.006 21.003 2.702 21.147 2.648 .226 .045
.996 1.392 .950 1.667 .896 .530 .620 .433 .637 1.108 .820
.989-1.004 1.085-1.786 .767-1.178 1.275-2.180 .586-1.370 .295-.951 .182-2.112 .203-.922 .361-1.125 .847-1.449 .615-1.093
2.004 .331 2.051 .511 2.110 2.635 2.479 2.838 2.450 .103 2.198
Abbreviations: ACI, anterior circulation infarction; CI, confidence interval; OR, odds ratio; PCI, posterior circulation infarction; SD, standard deviation.
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Figure 2. Association between vascular risk factors and location of ischemic stroke. *P , .05.
patients have suggested identical distributions of etiologies, including cardioembolism, between PCI and ACI.6,11,23 Further research may be needed to resolve whether etiology differs significantly between the 2 types of stroke. Part of the challenge in resolving this question lies in the fact that ischemic stroke etiology has been shown to depend on ethnicity.24,25 A meta-analysis has suggested that the most frequent etiologies of ischemic stroke in Caucasians are cardioembolism, followed by small-artery occlusion, and then large-artery atherosclerosis.26 In contrast, our study identified the 3 most frequent causes in Chinese patients to be smallartery occlusion, followed by large-artery atherosclerosis, and then cardioembolism. Similar results were obtained in other stroke database studies in other Asian countries, including the Takashima stroke registry in Japan,27 the Aga Khan University stroke databank in Pakistan,28 and the Korean stroke registry.29 Our results are also consistent with previous work showing that small-artery occlusion causes ischemic stroke more frequently in Asia than in the West.30 The frequency of cardioembolism in our study for all patients was 11.6%, lower than the frequency reported in several studies with Caucasian patients. This is consistent with evidence suggesting that cardioembolism is the most common cause of ischemic stroke in Caucasian populations.31,32 The frequency of cardioembolism in our sample of Chinese patients is lower than 22.9% reported in a Japanese study27 and 20.6% in a Korean
study. The following 2 observations may help explain this. First, ischemic stroke patients with a metal heart valve, coronary stent, or cardiac pacemaker are not typically analyzed by MRI at our medical center, although evidence suggests that MRI examination is safe for at least some of these patients,33,34 and these patients were excluded from our study. It is possible that at least some of these excluded patients had cardioembolic stroke. Second, few stroke patients in China undergo transesophageal echocardiography, which may lead to underestimates of how many stroke patients have heartrelated diseases, including cardioembolism. PCI and ACI patients in our study presented similar risk factors, with the relative frequency following the trend: hypertension . current smoking . alcohol consumption . diabetes mellitus . hyperlipidemia . atrial fibrillation. Multivariate analysis showed male gender and diabetes mellitus to be associated with greater likelihood of PCI than ACI. Conversely, atrial fibrillation and heart valve disease were associated with greater likelihood of ACI than PCI. Other factors that we examined were not preferentially related to PCI or ACI, including age, hypertension, hyperlipidemia, myocardial infarction, coronary artery disease, current smoking, or alcohol consumption. Our observation of an association between diabetes mellitus and PCI is consistent with 2 small observational studies35,36 and a large study in Canada.4 Why diabetes mellitus is preferentially associated with PCI is unclear and should be investigated in future. PCI patients were at lower risk of cardioembolism than ACI patients, and this may be linked with our observation that risk factors for cardioembolism (atrial fibrillation and heart valve disease) were preferentially associated with ACI over PCI. This is consistent with previous studies.3,4 The proportion of women was significantly higher among ACI patients than among PCI patients, and ACI patients had higher NIHSS and lower GCS scores. This suggests that women tend to have more severe strokes than men, which may help explain the association between female gender and poor clinical outcomes after stroke.37,38 The relatively mild stroke in PCI patients may help explain why a greater proportion of these patients were admitted more than 3 days after stroke onset than ACI patients. We found that most risk factors showed similar strength of association with PCI and ACI and that even factors showing a preferential association with one stroke localization or the other gave ORs near 1. These results, together with the similar clinical manifestations and prognosis for PCI and ACI,6,10,12,13 suggest that the clinical practice of treating PCI and ACI differently is not supported by the available evidence. For example, some clinicians believe that the thrombolytic time window can be longer in PCI than in ACI and that PCI patients were an appropriate subgroup for acute anticoagulant therapy.7 However, our finding that PCI patients had
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relatively low NIHSS score on admission does not support extending the thrombolytic time window, and our finding that they were less likely to present cardiogenic risk factors argues against using positive anticoagulant therapy. Our data suggest that in most respects, PCI patients and ACI patients should be treated in the same way for the same etiology and risk factors. For example, substantial proportions of PCI and ACI patients have diabetes mellitus and/or hypertension, and these comorbidities should be managed in the same way regardless of stroke lesion location. Thus, clinicians should treat PCI and ACI patients more according to specific etiology and risk factors than according to infarct localization per se. Our relatively small study had several limitations. First, we excluded patients who were not examined by MRI, and patients with multiple lesions involving both posterior and anterior circulation. This may have introduced selection bias in our results. Second, we did not analyze the specific arteries affected or infarct localization in our patients, preventing us from correlating etiology or risk factors with specific pathogenesis. On the other hand, our study population was diagnosed according to the same rigorous standards, improving the reliability of our findings.
Conclusion PCI and ACI showed similar etiology in our Chinese patients, with the exception that cardioembolic stroke affected anterior circulation more often than posterior circulation. Risk factors were also similar for PCI and ACI, with the exceptions that diabetes mellitus occurred more often in PCI, whereas atrial fibrillation and heart valve disease occurred more often in ACI. The extensive similarities between PCI and ACI do not justify the different risk factor stratifications or treatments often applied in the clinic for the 2 types of ischemic stroke. These findings suggest that during stroke patient workup, less attention should be paid to whether the infarct affects posterior or anterior circulation, and more attention should be paid to specific etiology and risk factors to guide treatment during the acute phase and to prevent secondary stroke.
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