Professional Documents
Culture Documents
Received July 24, 2014; final revision received February 9, 2015; accepted February 13, 2015.
From the Department of Neurology (H.E., J.F.S., M. Ebinger, A.R., A.M., M. Endres, C.H.N.), Center for Stroke Research (J.F.S., M. Ebinger, U.G.,
A.M., M. Endres, C.H.N.), NeuroCure, Cluster of Excellence (J.F.S., A.M., M. Endres), and Department for Biostatistics and Clinical Epidemiology
(U.G.), CharitUniversittsmedizin Berlin, Berlin, Germany; and Stroke Prevention Research Unit, Nuffield Department of Clinical Neurosciences,
University of Oxford, Oxford, United Kingdom (P.M.R.).
Guest Editor for this article was Natan M. Bornstein, MD.
Presented in part at the European Stroke Conference, Nice, France, May 69, 2014.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.
114.006886/-/DC1.
Correspondence to Hebun Erdur, MD, Department of Neurology, CharitUniversittsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm
30, 12200 Berlin, Germany. E-mail hebun.erdur@charite.de
2015 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.114.006886
Downloaded from http://stroke.ahajournals.org/ 1at Thomas Jefferson Universi on March 11, 2015
2StrokeApril 2015
Methods
Study Population and Data Acquisition
We performed a retrospective analysis of data from all patients treated
between January 2010 and June 2013 for acute (onset of symptoms
3 days) ischemic stroke or TIA in 3 certified stroke units (Campus
Benjamin Franklin, Campus Virchow, and Campus Mitte) of our tertiary
care center (Department of Neurology, Charit, Berlin). Data were derived from the data collection mandated for quality assurance as part of
the Berlin Stroke Register.6 This predefined data set has been described
elsewhere and includes stroke recurrence during hospital stay as complication of an index TIA or stroke (further information on the Berlin
Stroke Register is available in the online-only Data Supplement).7
Diagnosis of the index ischemic stroke was confirmed by the attending neurologist according to the World Health Organization definition and was based on history, clinical presentation, and findings
in neuroimaging (computed tomography [CT] or magnetic resonance
imaging [MRI]).8 TIA was diagnosed using the time-based definition
(symptoms lasting <24 hours regardless of imaging findings).
Documentation of patient characteristics and quality of care measures has been described elsewhere.6,7 We documented history of arterial hypertension, atrial fibrillation, diabetes mellitus, hyperlipidemia,
previous stroke, or TIA. Stroke severity on admission was assessed
with the National Institutes of Health Stroke Scale (NIHSS); clinical
signs (impaired consciousness, aphasia, and paresis or ataxia) were
also documented. We assessed the percentage of patients undergoing CT or MRI, vascular imaging with cerebrovascular ultrasound
(extracranial and transcranial), CT angiography, or magnetic resonance angiography. Etiology of stroke was assigned to severe (70%)
symptomatic stenosis of the internal carotid artery (ICA), to cardioembolic, small-vessel disease, other determined origin, multiple
causes or to unknown etiology according to the Trial of Org 10172 in
Acute Stroke Treatment (TOAST) classification. Stenosis of the ICA
was graded according to the North American Symptomatic Carotid
Endarterectomy Trial (NASCET) criteria.9
Measures of process of care included frequency of treatment with
intravenous recombinant tissue-type plasminogen activator, early (48
hours) treatment with antithrombotics, anticoagulation, blood pressurelowering agents, statins, and antidiabetics during hospitalization.
Development of pneumonia during hospitalization was recorded by
the treating physician based on clinical symptoms and clinical examination and radiological findings and pathogen detection.10 Onset of
pneumonia (based on documented diagnosis and beginning of antimicrobial therapy) was assessed in patients with recurrent stroke or
stroke after TIA by careful review of patients records. Length of stay
was defined as time from admission to day of discharge. Deviating
from this, length of stay was determined as time from admission to
day of recurrence in patients with stroke recurrence because stroke
recurrence was associated with longer hospital stay.
Primary end point was recurrent stroke or stroke after TIA during hospital stay. Stroke recurrence was defined based on previous
recommendations11:
1. a new and persisting (>24 hours) neurological deficit,
2. onset of the new neurological deficit >24 hours after the index
event, and
3. not because of other systemic or neurological causes.
New ischemic events in the same vascular territory as the first event
were considered as recurrent stroke when they were clearly associated
with new neurological symptoms. Progressive or worsening stroke
and neurological deterioration because of other causes such as hemorrhage, brain edema, seizure, pneumonia, sepsis, heart failure, and respiratory failure were not considered to be stroke recurrence. Patients
with recurrent stroke as a complication of endovascular thrombectomy
or carotid endarterectomy (CEA) were not included in the main analysis. Patients who had been recently discharged from our or another
hospital after a first TIA or stroke and presented in our emergency
department because of a new stroke were not included in the analysis.
To ascertain the completeness of recurrent strokes, we additionally used a computer program based on clinical domain ontologies,
Data Analysis
The MannWhitney U test was used to test differences in continuous
variables. The 2 test was used for dichotomized variables in proportions. Using a time to event approach, a Cox proportional hazard
regression analysis was performed to calculate adjusted hazard ratios and corresponding 95% confidence intervals. Variables were included in the multiple model if univariate comparisons suggested an
association with P<0.1 and yielded 1 event. All tests were 2-tailed
and statistical significance was determined at an level of 0.05. To
assess the goodness of fit of our model, Nagelkerke R2 for the Cox
regression model was calculated using Roystons modification of
OQuigley, Xu, and Stares modification of Nagelkerke R2 statistics
for proportional hazard models for censored survival data using command str2ph in STATA/IC.14 A 95% confidence interval for R2 was
calculated using bootstraps. Statistical analyses were performed using SPSS (19.0) and STATA/IC (13.0).
Results
Baseline Characteristics
A total of 5106 patients (median age, 74 years; interquartile
range, 6482; median NIHSS 3; interquartile range, 17;
49.4% women) fulfilled inclusion criteria. Of 85 patients
with recurrent stroke according to our data set and the applied
semantic search system, 40 met our criteria for stroke recurrence. Of the 45 patients not fulfilling our criteria, 10 patients
were not included because of recurrent stroke as complication of endovascular thrombectomy or CEA; 10 patients had a
recurrent stroke during the first 24 hours after the index event;
15 patients did not have a new persisting neurological symptom, but only transient symptoms, deterioration of previous
symptoms, or neurological deterioration because of medical
complications; the remaining 10 patients were mainly not
included because of concomitant brain hemorrhage or clinical
silent stroke on repeated neuroimaging only. Table1 shows
the baseline characteristics of all patients and of patients with
TIA and minor stroke (NIHSS on admission 5). The distribution of specific stroke etiologies in the other determined category of the TOAST classification is presented in Table I in
the online-only Data Supplement.
Characteristic
Recurrent Stroke
(n=40)
P Value*
No Recurrent Stroke
(n=3528)
Recurrent Stroke
(n=24)
P Value
Demographics
Age, median (IQR), y
71 (6382)
0.52
2507 (49.5)
74 (6482)
17 (42.5)
0.24
1227 (24.2)
10 (25.0)
0.52
790 (22.4)
5 (20.8)
0.86
339 (8.1)
9 (22.5)
0.01
281 (9.4)
6 (25.0)
0.01
72 (6279)
1627 (46.1)
71 (6076)
0.49
9 (37.5)
0.40
Comorbidities
1493 (29.5)
12 (30.0)
0.53
747 (21.2)
7 (29.2)
0.34
4174 (82.4)
30 (75.0)
0.16
2815 (79.8)
17 (70.8)
0.28
1361 (26.9)
9 (22.5)
0.34
902 (25.6)
Hyperlipidemia (%)
3010 (59.4)
21 (52.5)
0.23
2180 (61.8)
12 (50)
5 (20.8)
0.24
0.60
3089 (61.0)
26 (65.0)
0.37
1643 (46.6)
10 (41.7)
0.63
Aphasia (%)
1324 (26.1)
6 (15.0)
0.07
567 (16.1)
2 (8.3)
0.30
50 (1.0)
0 (0.0)
0.67
2 (0.1)
0 (0)
0.91
3 (17)
3 (19)
0.32
1 (03)
2 (03)
0.91
142 (2.8)
6 (15.0)
<0.001
92 (2.6)
3 (12.5)
0.003
1636 (32.6)
14 (35.0)
0.43
867 (24.8)
8 (33.3)
0.33
Coma (%)
NIHSS, median (IQR)
Etiology
Severe (70%) symptomatic
carotid disease (%)
Cardioembolic (%)
Small vessel disease (%)
518 (10.3)
0 (0.0)
0.01
463 (13.2)
0 (0)
0.06
155 (3.1)
2 (5.0)
0.35
101 (2.9)
0 (0)
0.40
181 (3.6)
5 (12.5)
0.02
135 (3.9)
4 (16.7)
0.001
2382 (47.5)
13 (32.5)
0.04
1839 (52.6)
9 (37.5)
0.14
Pneumonia (%)
404 (8.0)
7 (17.5)
0.04
64 (1.8)
3 (12.5)
<0.001
157 (3.1)
7 (17.5)
<0.001
19 (0.5)
4 (16.7)
<0.001
Undetermined (%)
Complications and mortality
IQR indicates interquartile range; NIHSS, National Institutes of Health Stroke Scale; and TIA, transient ischemic attack.
*The MannWhitney U test was used to test differences in continuous variables. The 2 test was used for dichotomized variables in proportions.
Information on previous TIA was missing in 888 patients (17.4% of all 5106 patients); none of these patients had a recurrent stroke.
Information on etiology was missing in 52 of all 5106 patients (1.0%); none of these patients had a recurrent stroke.
In patients with stroke recurrence, pneumonia after the first ischemic event but before the recurrent event was considered.
with lung cancer (n=1). None of the patients with initial TIA
or stroke attributable to small vessel disease had a recurrent
stroke. Of 148 patients with stroke attributable to severe ICA
stenosis, 6 had an early recurrent stroke. Of these 6 patients,
3 were not eligible for CEA/CAS because of major stroke,
medical condition, pre-existing disability, or occlusion of the
ICA in the meantime. In the remaining 3 patients stroke recurrence occurred before scheduled CEA/CAS (stroke recurrence
occurred on days 2, 3, and 5, respectively).
In-hospital mortality was significantly higher in patients
with stroke recurrence than in patients without recurrence
(17.5% versus 3.1%; P<0.001).
4StrokeApril 2015
Table 2. Univariate Comparison of Measures of Process of Care
Patients Without Recurrent
Stroke (n=5066)
P
Value*
4091 (80.8)
35 (87.5)
0.42
MRI (%)
3456 (68.2)
32 (80)
0.13
4881 (96.3)
40 (100)
0.40
854 (16.9)
7 (17.5)
0.83
4553 (89.9)
37 (92.5)
0.79
Anticoagulation (%)
1399 (27.6)
9 (22.5)
0.60
4050 (79.9)
29 (72.5)
0.24
Statins (%)
4145 (81.8)
31 (77.5)
0.54
Antidiabetics (%)
1073 (78.8)
6 (66.7)
0.41
32 (78.0)
2 (66.7)
0.65
5 (48)
5 (37)
0.15
CAS indicates carotid angioplasty and stenting; CEA, carotid endarterectomy; CT, computed tomography; IAT, intra-arterial thrombolysis; IQR, interquartile range; IV,
intravenous; and MRI, magnetic resonance imaging.
*The MannWhitney U test was used to test differences in continuous variables. The 2 test was used for dichotomized variables in proportions.
Only in patients with diagnosed diabetes mellitus (1370 patients of whom 9 had a recurrent stroke).
Only in patients eligible for CEA/CAS (44 patients with transient ischemic attack/minor stroke, without occlusion of the internal carotid artery, and without preexisting disability (modified Rankin scale<2) of whom 3 had a recurrent stroke.
In patients with stroke recurrence, length of stay was defined as time from admission to day of recurrence.
Additional Analyses
To assess the robustness of our findings, we performed
sensitivity analyses (multiple Cox proportional hazard
regression models) with subgroups of our total cohort. The
subgroups comprised (a) patients with initial symptom
duration of 24 hours, (b) with initial symptom duration
of 24 hours and additional verification of each initial and
recurrent stroke in neuroimaging, (c) patients with initial
TIA or minor stroke, and (d) all 85 patients with recurrent
stroke (including those who did not fulfill our strict criteria
for stroke recurrence).
History of TIA, severe ICA stenosis, and other determined
etiology were significantly associated with stroke recurrence
in every subgroup. In patients with initial symptom duration of 24 hours (subgroup a), the presence of aphasia on
initial presentation was additionally significantly associated
with freedom from stroke recurrence. In patients with initial
TIA/minor stroke (subgroup c) pneumonia after the inciting
ischemic event was significantly associated with stroke recurrence, whereas aphasia on admission was not. Of note, aphasia had been transient or of minor severity in the majority of
these patients (NIHSS on admission 5). When all patients
with recurrent stroke (including those who did not fulfill our
strict criteria; subgroup d) were included, both aphasia and
pneumonia were additionally associated with stroke recurrence. Unadjusted and adjusted hazard ratios for all subgroups are detailed in Tables III to VI in the online-only Data
Supplement.
Table 3. Cox Proportional-Hazard Analysis: Unadjusted and Adjusted Hazard Ratios for In-Hospital Recurrent Stroke in All Patients
(n=5106)
Unadjusted Hazard Ratio
(95% CI)
P Value
P Value
History of TIA
3.80 (1.808.00)
<0.001
3.23 (1.526.87)
0.002
Aphasia
0.41 (0.170.97)
0.04
0.44 (0.181.05)
0.06
4.66 (1.9511.17)
0.001
4.63 (1.9011.31)
0.001
0.04 (0.004.48)
0.18
3.36 (1.318.62)
0.01
3.91 (1.5010.16)
0.01
Undetermined etiology
0.64 (0.331.24)
0.19
Pneumonia
1.29 (0.553.02)
0.56
Discussion
In-Hospital stroke recurrence was rare (0.8%) in our cohort
of patients with acute ischemic stroke or TIA. History of
TIA, symptomatic stenosis (70%) of the ICA, and other
determined etiology were consistently associated with
higher early stroke recurrence in the total cohort and in all
sensitivity analyses. As a novel finding, pneumonia after
the first ischemic event but before the recurrent stroke was
associated with a higher risk of stroke recurrence in patients
with initial TIA or minor stroke. The rate of in-hospital
mortality was high (17.5%) in patients with stroke recurrence, emphasizing the impact of early recurrence. Of note,
in the group of patients with initial symptom duration of
>24 hours, aphasia was associated with a lower recurrence
rate, suggesting that clinical symptoms at presentation may
conceal new deficits.
In older studies reporting risk of stroke recurrence within 7
days, rates range from 1.0% to 6.2%.1,1522 The comparison of
reported recurrence rates is partly hampered by different definitions of stroke recurrence, patient populations, and time and
frequency of secondary prevention measures.11,23 The low rate
of stroke recurrence in our cohort may be attributable to our
strict definition of stroke recurrence and the high frequency
of early secondary prevention measures in our stroke unit.
These include mainly antithrombotic therapy, anticoagulation, statins, blood pressurelowering agents, and early referral to endarterectomy in patients with symptomatic stenosis of
the ICA, respectively. As has been shown in the Early use of
Existing Preventive Strategies for Stroke (EXPRESS) study,
these measures can result in an 80% reduction of risk of stroke
recurrence.24
Although the frequency of stroke recurrence was low in our
study, we were able to identify several risk factors associated
with stroke recurrence. Our results confirmed the well-known
higher risk of early recurrent stroke in patients with severe
ICA stenosis and history of TIA.2,3,18 Severe ICA stenosis
was associated with early stroke recurrence although a large
proportion of eligible patients (77%) underwent early CEA/
CAS in our cohort. Patients with recurrent stroke attributable
to severe ICA stenosis were either not eligible for CEA/CAS
(because of major stroke, pre-existing disability, or occlusion
of the ICA in the meantime) or recurrence occurred early
before scheduled CEA/CAS.
The higher risk of patients with stroke attributable to other
determined etiology has been described by Ay et al1 and
Arsava et al.15 In our cohort, the other causes in patients with
recurrent stroke were arterial dissection, primary angiitis of
the central nervous system, giant cell arteritis, and nonbacterial thrombotic endocarditis in a patient with lung cancer.
Although rare, these conditions pose an imminent risk of
stroke and stroke recurrence for patients, and early diagnosis may lead to subsequent-specific secondary prevention
measures. Furthermore, our results confirm that patients with
stroke attributable to small vessel disease have a low risk of
early stroke recurrence.18 This finding may indicate that stroke
because of small vessel disease is the result of a more chronic
focal pathophysiology and therefore unlikely to recur at a different site in the short term.
6StrokeApril 2015
by the different definition of stroke recurrence used in our previous study, which did not exclude patients with a temporal
deterioration, whereas our present study required a persisting
(>24 hours) new deficit.
This study has several strengths and limitations. Strengths
of our study include the large cohort of patients with standardized assessment of numerous risk factors, comorbidities,
clinical presentation, and therapeutic interventions. The main
baseline characteristics and therapeutic interventions of our
cohort are representative for an urban area.10 High frequency
of (repeated) neuroimaging with CT and MRI has allowed
confirmation of brain infarction in a high number of patients.
This in turn has allowed additional usage of a more finely
tuned definition of stroke recurrence. We have been able to
exclude clinical deterioration attributable to intracranial hemorrhage, infarct growth, or to other systemic or neurological
causes. Confining our analysis to patients with the imaging
definition of recurrent stroke has not changed our main results.
The main limitation of our study is the retrospective design.
As the length of stay in our cohort was short, our results are
confined to the early phase after the inciting event. The distribution of specific etiologies in the other etiology category may
be different in non-European cohorts, for example, the rate
of stroke attributable to Moyamoya disease is higher in Asian
populations than in European populations.31 Furthermore, the
stroke recurrence risk may be different for specific etiologies
in the other etiology category. The heterogeneity of this group
and the overall low number of recurrent events did not allow
a comparison of specific etiologies. We may have missed
potential confounders. Specifically, we were not able to assess
pattern of infarction in neuroimaging.1,32 The diagnosis of
pneumonia relied on the clinical judgment of the treating physicians and there was no strict application of standardized criteria such as the Centers for Disease Control and Prevention
criteria for the diagnosis of clinically defined pneumonia.
Nevertheless, the rate of pneumonia in our cohort was similar
to reports in previous large studies,22,33 thus making a significant proportion of incorrect diagnoses improbable.10 The low
number of primary end points is a limitation from a statistical
viewpoint. However, our main results were robust findings in
5 different analyses.
Conclusions
In-Hospital stroke recurrence was low. This may be attributed
to specialized stroke unit care with early assessment of etiology of the index event and high frequency of early specific
secondary prevention measures. Patients with previous TIAs,
severe ICA stenosis, other determined etiology, and patients
with TIA/minor stroke and pneumonia are at higher risk. This
should prompt special efforts.
Acknowledgments
We would like to thank Catherine Aubel for language revision and
editing of the article.
Disclosures
Dr Endres receives funding from the Deutsche Forschungsgemeinschaft (DFG, M.E. receives funding from the DFG (Excellence cluster NeuroCure; SFB TR43, KFO 247, KFO 213), Bundesministerium
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ONLINE SUPPLEMENT
In-Hospital Stroke Recurrence and Stroke after Transient Ischemic Attack: Frequency
and Risk Factors
Hebun Erdur, MD, Jan F. Scheitz, MD, Martin Ebinger, MD, Andrea Rocco, MD, Ulrike
Grittner, PhD, Andreas Meisel, MD, Peter M. Rothwell, MD, Matthias Endres, MD, Christian
H. Nolte, MD
Supplemental methods
Supplemental tables
Table I Distribution of specific stroke etiologies in the other determined category
Etiology
Arterial dissection, n, %
Cancer-related, n, %
Disorders of thrombosis and
hemostasis, n, %
Vasculitis, n, %
Other, n, %*
No recurrent stroke
N=181
39 (21.6%)
29 (16.0%)
Recurrent stroke
N=5
2 (40%)
1 (20%)
26 (14.4%)
19 (10.5%)
68 (37.6%)
2 (40%)
0
* This category includes patients with stroke related to Moyamoya disease (n=3), M. Fabry
(n=2), mitochondriopathy (n=1), paroxysmal nocturnal hemoglobinuria (n=2), dilatative
arteriopathy (dolichoectasia) (n=2), aneurysm (n=1), infection (HIV and Treponema
pallidum) (n=4), antiphospholipid antibody syndrome (n=4), migraine (n=8), hypoperfusion
syndromes (n=27), disseminated intravascular coagulation (n=1), illicit drug use (n=1), and
iatrogenic causes (n=12).
Table II Interaction between sex, age, and early application of antithrombotic therapy and
severe symptomatic carotid disease, stroke attributable to other causes, and history of
transient ischemic attack (TIA), respectively, on the risk of stroke recurrence during
hospitalization.
Patients without severe
carotid disease*
(N with/without recurrent
stroke)
Men
19/2449
4/90
Women
15/2432
2/52
Age 72 years
18/2257
5/79
Age 73 years
16/2624
1/63
31/4380
6/132
3/501
0/10
NA
HR (95% CI)
Men
19/2448
4/91
Women
16/2394
1/90
Age 72 years
18/2209
5/127
Age 73 years
Antithrombotic therapy
within 48h
Antithrombotic therapy
>48h
17/2633
0/54
32/4355
5/157
3/487
0/24
NA
HR (95% CI)
Men
17/1939
6/198
Women
14/1905
3/141
Age 72 years
17/1824
6/156
Age 73 years
14/2020
3/183
28/3409
9/306
3/435
0/33
Antithrombotic therapy
within 48h
Antithrombotic therapy
>48h
Antithrombotic therapy
within 48h
Antithrombotic therapy
>48h
HR (95% CI)
4.73(1.60
13.97)
4.78(1.09
21.00)
6.55(2.42
17.71)
1.91(0.25
14.50)
4.84(2.01
11.68)
4.63(1.57
13.66)
1.64(0.22
12.51)
3.96(1.46
10.76)
NA
3.73(1.44
9.64)
3.88(1.52
9.91)
3.66(1.04
2.86)
4.93(1.92
12.66)
2.70(0.78
9.41)
4.14(1.95
8.82)
Pinteraction
0.98
0.28
0.93
P-value
0.36
0.97
0.93
Pinteraction
0.96
0.50
0.92
NA
Table III Cox proportional-hazard analysis: unadjusted and adjusted Hazard Ratios for inhospital recurrent stroke in patients presenting with initial symptom duration 24 hours
(n=3652 of whom 32 had a recurrent stroke)
History of TIA
Aphasia
High-grade
(70%)
symptomatic
carotid disease (%)
Small vessel
disease
Other determined
etiology
Pneumonia
Unadjusted
Hazard Ratio
(95% CI)
3.08(1.188.03)
0.35(0.140.92)
4.81(1.8412.57)
P-value
Adjusted Hazard
Ratio (95% CI)
P-value
0.02
0.03
0.001
2.71(1.037.11)
0.35(0.130.91)
5.33(2.0014.21)
0.04
0.03
0.001
0.04(0.009.22)
0.25
3.82(1.3410.95)
0.01
4.95(1.7014.38)
0.003
1.35(0.563.23)
0.51
Table IV Cox proportional-hazard analysis: unadjusted and adjusted Hazard Ratios for inhospital recurrent stroke in patients presenting with initial symptom duration of 24 hours and
additional verification of each initial and recurrent stroke in repeated neuroimaging (n=3652
of whom 29 had a recurrent stroke)
History of TIA
Aphasia
High-grade
(70%)
symptomatic
carotid disease (%)
Small vessel
disease
Other determined
etiology
Pneumonia
Unadjusted
Hazard Ratio
(95% CI)
3.08(1.267.52)
0.51(0.211.25)
4.68(1.7912.22)
P-value
Adjusted Hazard
Ratio (95% CI)
P-value
0.01
0.14
0.002
2.73(1.116.70)
0.03
4.83(1.8012.93)
0.002
0.04(0.008.21)
0.24
4.35(1.6711.35)
0.003
5.37(2.0314.26)
0.001
1.57(0.653.79)
0.32
Table V. Cox proportional-hazard analysis: unadjusted and adjusted Hazard Ratios for inhospital recurrent stroke in patients presenting with initial transient ischemic attack or minor
stroke (NIHSS 5) (n=3552)
History of TIA
Aphasia
High-grade
(70%)
symptomatic
carotid disease (%)
Small vessel
disease
Other determined
etiology
Pneumonia
Unadjusted
Hazard Ratio
(95% CI)
3.50(1.398.81)
0.45(0.111.90)
4.13(1.2313.90)
P-value
Adjusted Hazard
Ratio (95% CI)
P-value
0.01
0.28
0.02
3.26(1.288.27)
0.01
3.60(1.0312.56)
0.05
0.04(0.006.28)
0.21
4.33(1.4712.73)
0.01
5.64(1.8617.07)
0.002
4.32(1.2614.80)
0.02
4.73(1.3416.70)
0.02
Table VI Cox proportional-hazard analysis: unadjusted and adjusted Hazard Ratios for inhospital recurrent stroke (extended definition)* in all patients (n=5106)
History of TIA
Aphasia
High-grade (70%)
symptomatic
carotid disease (%)
Other determined
etiology
Pneumonia
Unadjusted
Hazard Ratio
(95% CI)
3.41(1.816.43)
0.48(0.260.88)
3.22(1.586.54)
P-value
Adjusted Hazard
Ratio (95% CI)
P-value
<0.001
0.02
0.001
3.26(1.706.24)
0.48(0.260.91)
3.32(1.616.87)
<0.001
0.02
0.001
2.61(1.245.49)
0.01
3.62(1.697.76)
0.001
1.72(0.983.02)
0.06
2.22(1.214.09)
0.01
* This definition includes patients who did not fulfill our strict criteria for stroke recurrence.
Hence, patients with recurrent stroke as complication of endovascular thrombectomy or
carotid endarterectomy, patients with recurrent stroke during the first 24 hours after the index
event; patients with only transient symptoms as the recurrent event or deterioration of
previous symptoms, and patients with concomitant brain hemorrhage or clinical silent stroke
on repeated neuroimaging were included in this definition additionally to those who met our
strict criteria (85 patients of a total of 5106 patients).
Supplemental References
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Development and implementation of evidence-based indicators for measuring quality
of acute stroke care: the Quality Indicator Board of the German Stroke Registers
Study Group (ADSR). Stroke. 2006;37:2573-8.
(2) North American Symptomatic Carotid Endarterectomy Trial. Methods, patient
characteristics, and progress. Stroke. 1991;22:711-20.
(3) Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al.
Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter
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In-Hospital Stroke Recurrence and Stroke After Transient Ischemic Attack: Frequency
and Risk Factors
Hebun Erdur, Jan F. Scheitz, Martin Ebinger, Andrea Rocco, Ulrike Grittner, Andreas Meisel,
Peter M. Rothwell, Matthias Endres and Christian H. Nolte
Stroke. published online March 3, 2015;
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