Original Contribution

Novel Risk Score to Predict Pneumonia After Acute

Ischemic Stroke
Ruijun Ji, MD, PhD; Haipeng Shen, PhD; Yuesong Pan, PhD; Panglian Wang MD, PhD;
Gaifen Liu, MD, PhD; Yilong Wang, MD, PhD; Hao Li, PhD; Yongjun Wang, MD;
on behalf of China National Stroke Registry Investigators

Background and PurposeTo develop and validate a risk score (acute ischemic stroke-associated pneumonia score [AIS-
APS]) for predicting in-hospital stroke-associated pneumonia (SAP) after AIS.
MethodsThe AIS-APS was developed based on the China National Stroke Registry, in which eligible patients were
randomly classified into derivation (60%) and internal validation cohort (40%). External validation was performed using
the prospective Chinese Intracranial Atherosclerosis Study. Independent predictors of in-hospital SAP after AIS were
obtained using multivariable logistic regression, and -coefficients were used to generate point scoring system of the
AIS-APS. The area under the receiver operating characteristic curve and the HosmerLemeshow goodness-of-fit test
Downloaded from http://stroke.ahajournals.org/ by guest on September 11, 2017

were used to assess model discrimination and calibration, respectively.

ResultsThe overall in-hospital SAP after AIS was 11.4%, 11.3%, and 7.3% in the derivation (n=8820), internal (n=5882)
and external (n=3037) validation cohort, respectively. A 34-point AIS-APS was developed from the set of independent
predictors including age, history of atrial fibrillation, congestive heart failure, chronic obstructive pulmonary disease and
current smoking, prestroke dependence, dysphagia, admission National Institutes of Health Stroke Scale score, Glasgow
Coma Scale score, stroke subtype (Oxfordshire), and blood glucose. The AIS-APS showed good discrimination (area
under the receiver operating characteristic curve) in the internal (0.785; 95% confidence interval, 0.7660.803) and
external (0.792; 95% confidence interval, 0.7610.823) validation cohort. The AIS-APS was well calibrated (Hosmer
Lemeshow test) in the internal (P=0.22) and external (P=0.30) validation cohort. When compared with 3 prior scores, the
AIS-APS showed significantly better discrimination with regard to in-hospital SAP after AIS (all P<0.0001).
ConclusionsThe AIS-APS is a valid risk score for predicting in-hospital SAP after AIS.(Stroke. 2013;44:00-00.)

Key Words: acute ischemic stroke China National Stroke Registry stroke-associated pneumonia

S troke-associated pneumonia (SAP) is a common medical

complication after stroke, with an estimated incidence of
5% to 30%.116 Evidence showed that SAP not only increase the
length of hospital stay and medical cost,4,17,18 but also is an impor-
tant risk factor of mortality and morbidity after stroke.10,15,16,1924
Several risk factors for SAP have been identified, such
as older age,4,8,9,11,21,2527 male sex,4,5,8,26,27 diabetes mellitus,8
hypertension,3 atrial fibrillation,9,26 congestive heart failure,5,9,23
chronic obstructive pulmonary disease,3,5,11 pre-existing
dependency,5,7,11 stroke severity,4,8,1012,2527 stroke subtypes,5,6,8
and dysphagia.3,6,11,12,2528 However, no reliable scoring system
is currently available in routine clinical practice or clinical tri-
als. An effective risk stratification and prognostic model for
SAP would be helpful to identify vulnerable patients, allocate
relevant medical resources, and implement tailored preventive
strategies. In addition, for clinical trial, it could be used in
nonrandomized studies to control for case-mix variation and
in controlled studies as a selection criterion.
The goal of the study is 2-fold as follows: (1) to develop and
validate a risk score (acute ischemic stroke-associated pneu-
monia score [AIS-APS]) for predicting in-hospital SAP after
AIS; and (2) to compare the discrimination of the AIS-APS
and prior scores with regard to in-hospital SAP after AIS.
Methods
Derivation and Internal Validation Cohort
The derivation and internal validation cohort originated from the
largest stroke registry in China, the China National Stroke Registry
(CNSR), which was a nationwide, multicenter, and prospective registry
of consecutive patients with acute cerebrovascular events.29 Briefly,

Received December 24, 2012; accepted January 29, 2013.

From the Tiantan Comprehensive Stroke Center, Tiantan Hospital, Capital Medical University, Beijing, China (R.J., Y.P., P.W., G.L., Y.W., H.L., Y.W.);
and Department of Statistics and Operation Research, University of North Carolina, Chapel Hill, NC (H.S.).
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.
111.000598/-/DC1.
Corresponding to Yongjun Wang, MD, Tiantan Comprehensive Stroke Center, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantanxili,
Dongcheng District, Beijing 100050, China. E-mail yongjunwang1962@gmail.com
2013 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.111.000598

1
 2StrokeMay 2013
hospitals in China are classified into 3 grades: I (community hospitals);
II (hospitals that serve several communities); and III (central hospitals
for a certain district or city). In total, 242 potential sites, including 114
grade III, 71 grade II, and 57 grade I hospitals, from both urban and
rural area, were initially identified by soliciting application. The CNSR
steering committee evaluated the research capability and commitment
to the registry of each hospital with preliminary survey. Finally, a total
of 132 hospitals including 100 grade III and 32 grade II were selected,
which cover 27 provinces and 4 municipalities across China. Trained
research coordinators at each institute reviewed medical records daily
to identify, consent, and enroll consecutively eligible patients. To be
eligible for this study, subjects had to meet the following criteria:
(1) age 18 years; (2) hospitalized with a primary diagnosis of AIS
according to World Health Organization criteria30; (3) stroke confirmed
by head computerized tomography or brain MRI; (4) direct admission
to hospital from a physicians clinic or emergency department. The
eligible patients from the CNSR were randomly classified into
derivation cohort (60%) and internal validation cohort (40%).
External Validation Cohort
The external validation cohort was derived from the cohort of
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Chinese Intracranial Atherosclerosis Study (CICAS). CICAS was a
multicenter and prospective study aiming at investigating prevalence,
risk factors, and impact of intracranial atherosclerosis among patients
with ischemic stroke.31 The CICAS inclusion criteria were as follows:
(1) age between 18 and 80 years; (2) onset of symptom within 7 days;
and (3) hospitalized with a primary diagnosis of AIS or transient
ischemic attack. Exclusion criteria were as follows: (1) preadmission
modified Rankin Scale score >3; and (2) inability to undergo MRI
for cerebral vascular imaging. For this study, patients diagnosed of
transient ischemic attack were excluded.
Data Collection and Definitions
The scientific use of data obtained with informed consent and entered
in the CNSR and CICAS registries was approved by the local ethi-
cal committees. In these registries, a standardized case report form
was used for data collection in the CNSR and CICAS network. The
relevant data were extracted from the medical records by trained re-
search coordinators. Data from each case report form were manually
checked for completeness, correct coding, and proper application of
diagnostic algorithm by a research specialist from an independent
contract research organization. For the present study, the following
candidate variables were analyzed: (1) demographics (age and sex);
(2) stroke risk factors: hypertension (history of hypertension or anti-
hypertensive medication use), diabetes mellitus (history of diabetes
mellitus or antidiabetic medication use), dyslipidemia (history of dys-
lipidemia or lipid-lowering medication use), atrial fibrillation (history
of atrial fibrillation or documentation of atrial fibrillation at admis-
sion), coronary heart disease, history of stroke/transient ischemic at-
tack, current smoking, and excess alcohol consumption (2 standard
alcohol beverages per day); (3) pre-existing comorbidities: congestive
heart failure, valvular heart disease, peripheral artery disease, chronic
obstructive pulmonary disease, hepatic cirrhosis, peptic ulcer, pre-
vious gastrointestinal bleeding, renal failure, arthritis, Alzheimers
disease/dementia, and cancer; (4) prestroke dependence (modified
Rankin Scale 3); (5) admission stroke severity based on National
Institutes of Health Stroke Scale score (NIHSS) and Glasgow Coma
Scale score; (7) symptom of dysphagia; (8) stroke subtype: according
to the Oxfordshire Community Stroke Project criteria,32 AIS was clas-
sified into partial anterior circulation infarct, total anterior circulation
infarct, lacunar infarction, and posterior circulation infarct; (9) admis-
sion blood glucose (mmol/L); and (10) length of hospital stay (days).
In this study, SAP was diagnosed by treating physician accord-
ing to the Centers for Disease Control and Prevention criteria for
hospital-acquired pneumonia,33 on a basis of clinical and laboratory
indices of respiratory tract infection (fever, cough, auscultatory re-
spiratory crackles, new purulent sputum, or positive sputum culture),
and supported by typical chest X-ray findings. Only hospital-acquired
pneumonia was documented and pneumonia before stroke was not
considered. Data on in-hospital SAP was prospectively collected.
Statistical Analysis
Model building was performed exclusively in the derivation cohort.
In univariate analysis, 2 test was used to compare categorical vari-
ables, and MannWhitney test was used to compare continuous vari-
ables. Univariate and multivariable logistic regression was performed
to determine the independent predictors of SAP after AIS in the
derivation cohort. Candidate variables were those with biologically
plausible link to SAP on the basis of prior publication and those as-
sociated with SAP in univariate analysis (P<0.2). On multivariable
analysis, stepwise backward estimation was used to remove nonsig-
nificant variables from the model. To test for collinearity between the
covariates of the final multivariable model, the tolerance and variance
inflation factor of each covariate was calculated. The -coefficients
from the final model were used to generate point scoring system of
the AIS-APS, as in previous studies.34 The resulting AIS-APS was
then validated by assessing model discrimination and calibration,35
in the internal and external validation cohorts. Discrimination was
assessed by calculating the area under the receiver operating charac-
teristic curve (AUROC). Calibration was assessed by performing the
HosmerLemeshow goodness-of-fit test and was graphically depict-
ed in the plot of observed versus predicted SAP risk according to 10
deciles of predicted risk. Furthermore, we compared the discrimina-
tion of the AIS-APS and 3 prior scores,2527 with regard to in-hospital
SAP after AIS. The AUROC and maximum Youden index were used
to assess the discrimination of these scores for in-hospital SAP after
AIS. AUROC was compared using Delong method,36 and sensitivity,
specificity, positive predict value, and negative predictive value were
calculated at each scores maximum Youden index.
All tests were 2-tailed, and statistical significance was determined
at level of 0.05. Statistical analysis was performed using SAS 9.1
(SAS Institute, Cary, NC), SPSS 17.0 (SPSS Inc, Chicago, IL), and
Medcalc software 12.3 (MedCalc, Ostend, Belgium).
Results
Clinical Characteristics
The clinical characteristics of the derivation, internal and
external validation cohort were shown in Table 1. From
September 2007 to August 2008, a total of 14702 patients
with AIS were enrolled in the CNSR network. The median age
was 66 (interquartile range [IQR], 5675), and 61.9% were
men. The median length of hospital stay was 14 days (IQR,
1020), and a total of 1669 (11.4%) patients had SAP dur-
ing hospitalization. The eligible patients from the CNSR were
randomly classified into derivation cohort (60%, n=8820) and
internal validation cohort (40%, n=5882), which were well
matched with respect to patient characteristics and overall rate
of in-hospital SAP (Table 1).
From October 2007 to June 2009, a total of 3580 patients of
AIS were registered in 22 participating hospitals in the CICAS
network. Of these, we excluded 329 patients with transient
ischemic attack (9.1%; median age, IQR: 62, 5471; median
admission NIHSS, IQR: 0, 01) and an additional 214 (6.0%;
median age, IQR: 64, 5573; median admission NIHSS, IQR:
3, 06) who had missing data of 1 covariates in the AIS-
APS. The median length of hospital stay was 14 days (IQR,
1018), and a total of 222 (7.3%) patients had SAP during
hospitalization (Table 1).
Predictors of In-hospital SAP
The univariate analysis for potential predictors of in-hospital
SAP after AIS in the derivation cohort was shown in Table
I in the online-only Data Supplement, and the multivariable
predictors were listed in Table 2. Age, present history of
 Ji et al A Risk Score to Predict SAP After AIS 3

Table 1. Clinical Characteristics

Derivation Internal Validation External Validation
Cohort (n=8820) Cohort (n=5882) P1 Value Cohort (n=3037) P2 Value
Demographics
Age, median (IQR), y 66 (5674) 66 (5775) 0.11 64 (5472) <0.001
Sex (male), n, % 5430 (61.6) 3675 (62.5) 0.26 1997 (65.8) <0.001
Vascular risk factor, n, %
Hypertension 5601 (63.5) 3683 (62.6) 0.27 2016 (66.4) 0.004
Diabetes mellitus 1834 (20.8) 1287 (21.9) 0.11 742 (24.4) <0.001
Dyslipidemia 947 (10.7) 637 (10.8) 0.86 411 (13.5) <0.001
Atrial fibrillation 643 (7.3) 415 (7.1) 0.59 180 (5.9) 0.01
Coronary artery disease 1222 (13.9) 811 (13.8) 0.91 286 (9.4) <0.001
History of stroke/TIA 2795 (31.7) 1822 (31.0) 0.36 777 (25.6) <0.001
Current smoking 3510 (39.8) 2326 (39.5) 0.70 1052 (34.6) <0.001
Excess alcohol consumption 1346 (15.3) 921 (15.7) 0.55 385 (12.7) 0.001
Pre-existing comorbidities, n, %
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Congestive heart failure 169 (1.9) 121 (2.1) 0.55 25 (0.8) <0.001
Valvular heart disease 213 (2.4) 139 (2.4) 0.83 38 (1.3) <0.001
Peripheral artery disease 64 (0.7) 29 (0.5) 0.08 26 (0.9) 0.48
COPD 98 (1.1) 64 (1.1) 0.89 13 (0.4) 0.001
Hepatic cirrhosis 29 (0.3) 21 (0.4) 0.78 7 (0.2) 0.40
Peptic ulcer or previous GIB 283 (3.2) 195 (3.3) 0.72 76 (2.5) 0.05
Renal failure 7 (0.1) 4 (0.1) 0.78 4 (0.1) 0.50
Arthritis 266 (3.0) 176 (3.0) <0.001 46 (1.5) <0.001
Dementia 113 (1.3) 82 (1.4) 0.56 22 (0.7) 0.01
Cancer 150 (1.7) 109 (1.9) 0.50 52 (1.7) 1.00
Prestroke dependence (mRS>3), n, % 809 (9.2) 535 (9.1) 0.87 0 (0.0)
Admission NIHSS score, median (IQR) 5 (29) 5 (29) 0.18 4 (27) <0.001
Admission GCS score, median (IQR) 15 (1415) 15 (1415) 0.36 15 (1515) 0.12
Symptom of dysphagia, n, % 840 (9.5) 529 (9.0) 0.28 236 (7.8) 0.004
OCSP subtype, n, % 0.22 <0.001
Partial anterior circulation infarct 4834 (54.8) 3327 (56.6) 1869 (61.5)
Total anterior circulation infarct 811 (9.2) 519 (8.8) 177 (5.8)
Lacunar infarction 1667 (18.9) 1074 (18.3) 249 (8.2)
Posterior circulation infarct 1508 (17.1) 962 (18.4) 742 (24.4)
Admission blood glucose, median (IQR), 6.2 (5.47.0) 6.2 (5.57.0) 0.28 5.5 (4.96.9) <0.001
mmol/L
Length of hospital stay, median (IQR), d 14 (1020) 14 (1020) 0.96 15 (1220) <0.001
In-hospital SAP, n, % 1007 (11.4) 662 (11.3) 0.76 222 (7.3) <0.001
COPD indicates chronic obstructive pulmonary disease; GCS, Glasgow Coma Scale; GIB, gastrointestinal bleeding; IQR, interquartile range; mRS, modified Rankin
Scale; NIHSS, National Institutes of Health Stroke Scale; OCSP, Oxfordshire Community Stroke Project; SAP, stroke-associated pneumonia; and TIA, transient ischemic
attack.
P 1 denotes significant test between the derivation and internal validation cohort; P2 denotes significant test between the derivation and external validation cohort.

atrial fibrillation, congestive heart failure, chronic obstructive
pulmonary disease, and current smoking, prestroke
dependence (modified Rankin Scale>3), admission NIHSS
score, Glasgow Coma Scale score, symptom of dysphagia,
Oxfordshire Community Stroke Project subtype of total
anterior circulation infarct and posterior circulation infarct,
and blood glucose were significantly predictive of in-hospital
SAP after AIS. The tolerance of covariates in the final
multivariable model ranged between 0.66 and 0.99; the mean
variance inflation factor was 1.16 (range, 1.021.68).
Derivation of the AIS-APS
The -coefficients from the multivariable regression model
were used to generate point scoring system of the AIS-APS.
To derive an integer value for each predictor, the -coefficient
of current smoking was used as reference and the value was
rounded to the closest integer. The point scoring system of the
AIS-APS was shown in Figure 1. The median AIS-APS score
was 8 (range, 032) in the derivation cohort. The risk catego-
ries were assigned in 7-point increments, and the magnitude
of the score had prognostic implication (Figure 2).
 4StrokeMay 2013

Table 2. Multivariable Predictors of In-hospital SAP After AIS in the Derivation Cohort (n=8820)
Variables -Coefficients SE Adjusted OR* 95% CI P Value
Model intercept 6.873
Age (1 yr increase) 0.049 0.003 1.05 1.041.06 <0.001
Atrial fibrillation (yes) 0.199 0.098 1.22 1.031.50 0.03
Congestive heart failure (yes) 0.764 0.162 2.15 1.562.95 <0.001
COPD (yes) 0.510 0.217 1.67 1.092.55 0.02
Current smoking (yes) 0.238 0.063 1.27 1.121.44 <0.001
Prestroke dependence (mRS>3) (yes) 0.313 0.086 1.37 1.161.62 <0.001
Admission NIHSS score (1 increase) 0.077 0.005 1.08 1.071.09 <0.001
Admission GCS score (1 decrease) 0.043 0.015 1.04 1.011.08 0.005
Dysphagia (yes) 0.642 0.083 1.90 1.622.24 <0.001
OCSP subtype
Lacunar infarction) 1.00
Partial anterior circulation infarct 0.001 0.088 1.00 0.831.19 0.99
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Total anterior circulation infarct 0.319 0.115 1.38 1.101.72 0.006

Posterior circulation infarct 0.265 0.106 1.30 1.061.60 0.01
Admission blood glucose (1 mmol increase) 0.057 0.011 1.06 1.041.08 <0.001
AIS indicates acute ischemic stroke; CI, confidence interval; COPD, chronic obstructive pulmonary disease; GCS, Glasgow Coma Scale; mRS, modified Rankin Scale;
NIHSS, National Institutes of Health Stroke Scale; OCSP, Oxfordshire Community Stroke Project; OR, odds ratio; and SAP, stroke-associated pneumonia.
*Multivariable logistic regression adjusted for age, sex, stroke risk factors, comorbidities, prestroke dependence, admission NIHSS score, GCS score, symptom of
dysphagia, OCSP subtypes, blood glucose, and length of hospital stay.

Internal Validation of the AIS-APS
The performance of the AIS-APS (AUROC) in the deriva-
tion (n=8820) and internal validation cohort (n=5882) was
0.797 (95% confidence interval, 0.7820.811) and 0.785
(95% confidence interval, 0.7660.803), respectively. The
HosmerLemeshow test was not significant (P=0.22), and the
predicted and observed risk of in-hospital SAP after AIS were
in close agreement according to 10 deciles of predicted risk in
the internal validation cohort (Figure I in the online-only Data
Supplement).
External Validation of the AIS-APS
In the external validation cohort (n=3037), the AIS-APS
showed good discrimination with an AUROC of 0.792 (95%
confidence interval, 0.7610.823). The HosmerLemeshow
test was not significant (P=0.30). The plot of observed
versus predicted risk of in-hospital SAP after AIS showed
high correlation between observed and predicted risk in the
external validation cohort (Figure I in the online-only Data
Supplement).
Sensitivity Analysis
We completed prespecified subgroup analyses by age, sex,
time delay from onset to hospital arrival, and length of hospital
stay. Similar good discrimination was seen in these subgroups
(AUROC range, 0.7400.837) (Table III in the online-only
Data Supplement).
Comparison of SAP Scores
Table 3 showed the discrimination of the AIS-APS and 3 com-
pared prior scores for in-hospital SAP after AIS. Although
Chumbler and Hoffmann scores consistently showed good
discrimination for in-hospital SAP in the derivation, internal
and external validation cohort, the AIS-APS demonstrated
the highest AUROC. The difference in AUROC between AIS-
APS and 3 compared scores was statistically significant (all
P<0.0001). The AIS-APS had the highest maximum Youden
index and associated sensitivity, specificity, positive predict
value and negative predictive value (Table 3).
Discussion
In the present study, we derived and validated a risk score for
predicting in-hospital SAP after AIS. A 34-point AIS-APS
was developed from the set of independent predictors. The
AIS-APS showed good discrimination and calibration in the
derivation, internal and external validation cohort. When com-
pared with 3 prior scores, the AIS-APS showed significantly
better discrimination with regard to in-hospital SAP after AIS.
To preserve the clinical use of the model for decision-mak-
ing during acute hospitalization, we used only patient char-
acteristics available at presentation. We chose not to include
variables related to in-hospital management and those not
routinely collected, such as quality of care,37 mechanical ven-
tilation, and swallowing test,11,38 despite the fact that these fac-
tors might influence the development of SAP after AIS. This
model therefore predicts the expected risk of in-hospital SAP
at presentation, and as such, the predictions could be used to
guide subsequent in-hospital management.
Several risk factors for SAP have been identified. Consistent
with these studies, we confirmed that in-hospital SAP was sig-
nificantly associated with older age, present history of atrial
fibrillation, congestive heart failure, chronic obstructive pul-
monary disease and smoking, prestroke dependence, admis-
sion NIHSS score, Glasgow Coma Scale score, dysphagia, and
stroke subtypes. In addition, our study showed that admission
blood glucose was significantly associated with in-hospital

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Figure 1. Acute ischemic stroke-associated pneumonia score
(AIS-APS). COPD indicates chronic obstructive pulmonary dis-
ease; GCS, Glasgow Coma Scale; mRS, modified Rankin Scale;
NIHSS, National Institutes of Health Stroke Scale; and OCSP,
Oxfordshire Community Stroke Project.
SAP after AIS. Prior studies have indicated the relationship
between blood glucose and in-hospital acquired infections.39,40
Biological evidence demonstrates that diabetes mellitus can
increase susceptibility of infection by compromising the
Figure 2. The proportion of in-hospital stroke-associated pneumonia (SAP) after acute ischemic stroke (AIS) according to the AISpneu-
monia score (PS) in the derivation, internal and external validation cohort. The potential risk of in-hospital SAP after AIS increased steadily
with higher AIS-PS score. Error bars indicated 95% confidence interval for the proportion of in-hospital SAP after AIS in each category.
Ji et al A Risk Score to Predict SAP After AIS 5
immune system. For example, neutrophils from people with
diabetes mellitus showed reduced chemotaxis and oxidative
killing potential compared with those from nondiabetes con-
trols.41 Leukocyte bactericidal activity is diminished in those
with poor glucose control.42
The present risk stratification and prognostic model for
SAP is unique in that it was derived from a large, multicenter,
and prospective cohort, which included consecutive patients
of AIS, was outside of clinical trial, and was more reflective of
real-world clinical practice; the model included comprehen-
sive information on demographics, medical history, prestroke
functional status, admission stroke-related characteristics, and
laboratory test; in addition, it could be used to predict in-hos-
pital SAP on hospital arrival and could be readily incorporated
into clinical practice by performing a simple score. Several
SAP prediction rules have been developed using similar tech-
niques; however, these models have not been widely used in
clinical practice. It is not our intention to show superiority
of the AIS-APS compared to the earlier scores; however, we
want to point out the major difference. Kwon et al27 developed
a pneumonia score, which included age, sex, NIHSS score,
mechanical ventilation, and dysphagia. However, the study
was limited by small sample size and was not validated exter-
nally. Sellars et al11 presented key predictors for poststroke
pneumonia, including older age, dysarthria or no speech due
to aphasia, modified Rankin Scale score >4, low abbreviated
mental test score, and failed water swallowing test. Although
the model was informative, some predictors were not rou-
tinely collected. Chumbler et al25 presented a 3-level scor-
ing system for predicting pneumonia in acute stroke, which
included medical history of pneumonia, symptom of dyspha-
gia, increasing NIHSS score, being found down at symptom
onset, and age >70 years. Although the model showed accept-
able C-statistics, the study was limited by its retrospective
nature and lacking of validation. Hoffmann et al26 derived
 6StrokeMay 2013

Table 3. Discrimination of AIS-APS and 3 Compared Prior Scores With Regard to In-hospital SAP After AIS
AUROC 95% CI AUROC* P Value Youden Index Cutoff Sensitivity Specificity PPV NPV
In the derivation cohort (n=8850)
Pneumonia score (Kwon et al. 2006)27 0.713 0.7040.723 0.084 <0.0001 0.342 2 0.762 0.580 0.189 0.950
Chumblers score (Chumbler et al. 2010)25 0.752 0.7430.761 0.045 <0.0001 0.401 13 0.605 0.796 0.276 0.940
A2DS2 score (Hoffmann, et al. 2012)26 0.745 0.7360.754 0.052 <0.0001 0.373 5 0.545 0.828 0.291 0.934
AIS-APS score (2012) 0.797 0.7820.811 Ref 0.435 8 0.793 0.769 0.306 0.967
In the internal validation cohort (n=5882)
Pneumonia score (Kwon et al. 2006)27 0.694 0.6820.706 0.091 <0.0001 0.313 2 0.730 0.583 0.182 0.945
Chumblers score (Chumbler et al. 2010)25 0.737 0.7260.749 0.048 <0.0001 0.393 14 0.577 0.816 0.285 0.938
A DS score (Hoffmann et al. 2012)
2 2 26
0.728 0.7160.739 0.057 <0.0001 0.364 5 0.527 0.837 0.290 0.933
AIS-APS (2012) 0.785 0.7660.803 Ref 0.435 8 0.781 0.764 0.300 0.965
In the external validation cohort-A (n=3037)
Pneumonia score (Kwon et al. 2006)27 0.676 0.6590.693 0.116 <0.0001 0.294 2 0.662 0.632 0.124 0.960
Chumblers score (Chumbler et al. 2010) 25
0.752 0.7260.787 0.040 <0.0001 0.418 11 0.658 0.760 0.178 0.966
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A2DS2 score (Hoffmann et al. 2012)26 0.759 0.7440.774 0.033 <0.0001 0.392 5 0.725 0.667 0.146 0.969
AIS-APS score (2012) 0.792 0.7610.823 Ref 0.530 8 0.728 0.802 0.225 0.973
AIS-APS indicates acute ischemic stroke-associated pneumonia score; AUROC, area under the receiver operating characteristic curve; CI, confidence interval; PPV,
positive predictive value; NPV, negative predictive value; and SAP, stroke-associated pneumonia.
*AUROC denotes the difference in AUROC between the AIS-APS and compared scores with regard to in-hospital SAP after AIS.
P value of comparing paired AUROC with Delong method.

a score (A2DS2) to predict pneumonia after AIS in a large
derivation and validation sample. The model showed good
discrimination and calibration properties; however, it was not
externally validated in geographically, culturally, and socio-
economically distinct population.
With several SAP-related risk stratification and prognos-
tic models available, identification of the most accurate and
reliable grading scale(s) would be of great value to patients,
clinicians, and researchers. In this study, we compared the dis-
crimination of the AIS-APS and 3 prior scores with regard to
in-hospital SAP after AIS. When using 2 measures to assess
model discrimination (AUROC and maximum Youden index),
the AIS-APS consistently showed to be superior at predicting
in-hospital SAP after AIS than 3 compared scores in our popu-
lation. In addition, similar results were verified in the deriva-
tion, internal and external validation cohort. It was noteworthy
that all scales had higher negative predictive value than posi-
tive predict value for in-hospital SAP after AIS, which sug-
gested that lower values more consistently predict patients
without in-hospital SAP than higher values predicting those
developing in-hospital SAP after AIS. Development of future
prognostic models might benefit from attempts to make them
more balanced in this regard, with discriminative use distrib-
uted more evenly among higher and lower values.
Prior studies have shown that SAP was an important risk
factor of mortality and morbidity after stroke; however, a sys-
tematic review on efficacy of early antibiotics prophylaxis
after stroke failed to show benefit in patients outcome.43 This
might be attributable to inclusion of patients with low risk of
developing SAP in these studies. The AIS-APS and other SAP
predictive tools could be used to identify patients who are at
high risk of developing SAP after stroke. It is expected that
randomized controlled trials on efficacy of antibiotics pro-
phylaxis on stroke functional outcome with stratification of
patients potential risk of developing SAP.
Our study had some limitations that deserve comment. First,
as all observational studies, we cannot rule out the possibility
that additional baseline variable (unmeasured confounders)
might have some impact on the development of in-hospital
SAP after AIS, such as use of angiotensin-converting enzyme
inhibitors or angiotensin receptor blockers.44 Second, the time
course of SAP after AIS is unclear. Because we only have
information on new-onset SAP during hospitalization without
documentation of the exact date, our data allow no conclu-
sion as to whether patients with a longer length of stay per se
are more likely to develop pneumonia or whether diagnosis of
pneumonia leads to a longer hospitalization. However, by sen-
sitive analysis, the AIS-APS was proven to be valid and signif-
icant, regardless of length of hospital stay. Third, the limited
information on time course of pneumonia also does not allow
for a safe interpretation of causality between mechanical ven-
tilation and pneumonia. We therefore abstained from includ-
ing mechanical ventilation in our predictive score. In addition,
the primary aim of our study was to develop a predictive score
for SAP after AIS at presentation. Fourth, the study included
only hospitalized patients with stroke, and those patients died
in the emergency department, shortly after admission, or
treated in outpatient clinics were not included. Meanwhile,
the results of current analysis apply only to patients of AIS
and cannot be extrapolated to patients of hemorrhagic stroke.
Finally, the AIS-APS need to be further validated in additional
populations.
In summary, the AIS-APS is a valid clinical grading scale for
predicting in-hospital SAP after AIS at presentation. Further
studies on effect of AIS-APS on stroke outcomes are needed.
Sources of Funding
The China National Stroke Registry is funded by the Ministry of
Science and Technology (2006BA101A11) and the Ministry of
Health of the Peoples Republic of China (2009CB521905).

Disclosures
None.
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 Novel Risk Score to Predict Pneumonia After Acute Ischemic Stroke
Ruijun Ji, Haipeng Shen, Yuesong Pan, Panglian Wang, Gaifen Liu, Yilong Wang, Hao Li and
Yongjun Wang
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 SUPPLEMENTARY MATERIAL

Table e-1. Univariable predictor of SAP after AIS in the derivation cohort (n=8820)

Increment/categories OR 95% CI P value

Demographics
Age, year 1 year increase 1.05 1.05-1.07 <0.001
Gender female vs. male 1.18 1.06-1.31 0.002
Vascular risk factor
Hypertension yes vs. no 1.12 1.00-1.25 0.04
Diabetes mellitus yes vs. no 1.09 0.96-1.23 0.19
Dyslipidemia yes vs. no 0.76 0.64-0.91 0.003
Atrial fibrillation yes vs. no 2.91 2.51-3.38 <0.001
Coronary artery disease yes vs. no 1.73 1.53-1.98 <0.001
History of stroke/TIA yes vs. no 1.40 1.26-1.56 <0.001
Current smoking yes vs. no 0.88 0.79-0.98 0.02
Excess alcohol yes vs. no 0.84 0.73-0.98 0.02
Preexisting comorbidities
Congestive heart failure yes vs. no 3.84 2.98-4.95 <0.001
Valvular heart disease yes vs. no 2.29 1.77-2.96 <0.001
Peripheral artery disease yes vs. no 1.27 0.71-2.29 0.42
COPD yes vs. no 3.46 2.46-4.86 <0.001
Hepatic cirrhosis yes vs. no 1.72 0.83-3.54 0.14
Peptic ulcer or previous GIB yes vs. no 1.04 0.78-1.38 0.80
Renal failure yes vs. no 4.47 1.31-15.3 0.02
Arthritis yes vs. no 1.38 1.06-1.81 0.02
Alzheimers disease/dementia yes vs. no 3.14 2.29-4.31 <0.001
Cancer yes vs. no 1.75 1.27-2.41 0.001
Pre-stroke dependence (mRS>3) yes vs. no 2.56 2.22-2.93 <0.001
Admission NIHSS score 1 point increase 1.11 1.10-1.12 <0.001
Admission GCS score 1 point decrease 1.28 1.26-1.31 <0.001
Symptom of dysphagia yes vs. no 2.85 2.46-3.26 <0.001
OCSP subtype, n (%)
Lacunar infarction (LACI) 1.00
Partial anterior circulation infarct (PACI) PACI vs. LACI 1.16 1.00-1.35 0.05
Total anterior circulation infarct (TACI) TACI vs. LACI 3.14 2.61-3.78 <0.001
Posterior circulation infarct (POCI) POCI vs. LACI 1.50 1.26-1.80 <0.001
Admission blood glucose (mmol/L) 1mmol/L increase 1.08 1.06-1.10 <0.001
Length of hospital stay (days) 1 day increase 1.02 1.01-1.03 <0.001
Abbreviation: SAP, Stroke Associated Pneumonia; AIS, Acute Ischemic Stroke; OR, Odds Ratio; CI, Confidence
Interval; TIA, Transient Ischemic Attack; COPD, Chronic Obstructive Pulmonary Disease; GIB, Gastrointestinal
Bleeding; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale score; GCS, Glasgow
Coma Scale; OCSP, Oxfordshire Community Stroke Project
 Table e-2. Subgroup analysis of discrimination of the AIS-PS with regard to in-hospital SAP after AIS
Derivation cohort Internal validation cohort External validation cohort
(n=8820) (n=5882) (n=3037)
AUROC 95% CI AUROC 95% CI AUROC 95% CI
Overall cohort 0.797 0.782-0.811 0.785 0.766-0.803 0.792 0.761-0.823
Subgroups
Age
<59 0.802 0.764-0.840 0.774 0.718-0.830 0.769 0.701-0.840
>60 0.766 0.748-0.783 0.755 0.733-0.777 0.783 0.749-0.818
Gender
Male 0.806 0.789-0.823 0.803 0.779-0.826 0.798 0.759-0.838
Female 0.784 0.760-0.807 0.756 0.725-0.787 0.778 0.78-0.828
Time from onset to arrival (hours)
<6 0.802 0.776-0.829 0.744 0.705-0.784 0.792 0.761-0.823
6-12 0.812 0.771-0.854 0.803 0.751-0.854 0.837 0.749-0.927
12-24 0.803 0.772-0.835 0.780 0.736-0.823 0.740 0.700-0.820
>24 0.781 0.759-0.803 0.792 0.764-0.820 0.744 0.701-0.812
Length of hospital stay (days)
<7 0.830 0.800-0.860 0.809 0.765-0.853 0.782 0.742-0.816
8-13 0.786 0.758-0.815 0.774 0.734-0.813 0.814 0.736-0.893
>14 0.793 0.775-0.812 0.779 0.756-0.802 0.774 0.740-0.809
Abbreviation: SAP, Stroke Associated Pneumonia; AIS, Acute Ischemic Stroke; AUROC, Area Under the Receiver Operating Characteristic Curve; CI, Confidence Interval.

Figure e-1. Plot of observed versus predicted risk of SAP after AIS in the derivation and
validation cohorts
Figure e-1 legend
Plot of observed versus predicted risk of in-hospital SAP after AIS with 95% confidence interval
(C.I.) in the derivation and validation cohorts according to 10 deciles of predicted risk. Overall,
there was a very high correlation between observed and predicted risk in the derivation cohort (A)
(n=8820; r=0.99, P<0.001), internal validation cohort (B) (n=5882; r=0.99, P<0.001), and external
validation cohort (C) (n=3037; r=0.98, P<0.001), which indicated excellent calibration.
Appendix: The CNSR investigators

Yongjun Wang, Beijing Tiantan Hospital; Qi Bi, Beijing Anzhen Hospital; Weiwei Zhang, Beijing Military District
Gengral hospital of Chinese Peoples Liberation Army; Liying Cui, Peking Union Medical College Hospital of
Peking University; Yuheng Sun, Beijing Jishuitan Hospital; Maolin He, Beijing Shijitan Hospital; Dongsheng Fan,
Peking University Third Hospital; Xunming Ji, Beijing Xuanwu Hospital; Jimei Li, Beijing Friendship Hospital
Affiliated to Capital Medical University; Fang Zhang, Beijing Guangwai Hospital; Kai Feng, Beijing Shunyi
District Hospital; Xiaojun Zhang, Beijing Tongren Hospital; Yansheng Li, Shanghai Renji Hospital; Shaoshi Wang,
Shanghai First Municipal Peoples Branch hospital; Wei Fan, Zhongshan Hospital of Fudan University; Zhenguo
Liu, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University; Xiaojiang Sun, The sixth PeoplesHospital
Affiliated to Shanghai JiaoTong University; Wei Li, Shanghai Ninth Peoples Hospital Affiliated to Shanghai
JiaoTong University; Jianrong Liu, ShanghaiRuijin Hospital; Xu Chen, Shanghai 8th Peoples Hospital; Qingke
Bai, Pudong New Area Peoples Hospital; Dexiang Gu, Shanghai Yangpu Area Shidong Hospital; Xin Li, Shanghai
Yangpu Area Center Hospital; Qiang Dong, Huashan Hospital of Fudan University; Yan Cheng, Tianjin Medical
University Gengeal Hospital; Lan Yu, Tianjin Huanhu Hospital; Bin Li, Dagang Oilfield Gengeal Hospital; Tongyu
Wang, Bohai Oilfield Hospital; Kun Zhao, Baodi District Peoples Hospital of Tianjin; Chaodong Zhang, The First
Affiliated Hospital of China Medical University; Dingbo Tao, The First Afflicated Hospital of Dlian Medical
University; Lin Yin, The Second Affiliated Hospital of Dlian Medical University; Fang Qu, Dlian Second Peoples
hospital; Jingbo Zhang, Dlian Third Peoples hospital; Jianfeng Wang, Dalian Central hospital; Ying Lian, Dalian
Economic and Technological Development District Hospital; Fang Qu, Shenying Military District General hospital
of Chinese Peoples Liberation Army; Jun Fan, Shenyang Military District 202 Hospital; Ying Gao, National
Traditional Chinese Medicine (TCM)Thrombus Treatment Center of Liaoning Province; Mingdong Cheng,
Enliang hopital of Taian County; Jiang Wu, The First Clinical College of Jilin University; Huashan Sun, Jilin
Chemical Industrial Group General hopital; Jinying Li, Jilin Oilfield General Hospital; Guozhong Li, The First
Clinical College of Harbin Medical University; Yulan Zhu, The Second Clinical College of Harbin Medical
University; Zichao Yang, The Fourth Clinical College of Harbin Medical University; Fengmin Yang, Daqing
Oilfield General Hospital; Jun Zhou, Mudan Jiang Second hospital of Hailongjiang Province; Minxia Guo,
Shaanxi Provincial Peoples Hospital; Zhengyi Li, The First Afflicated Hospital of Medical College of Xian
Jiaotong University; Qilin Ma, The First Hospital of Xiamen; Renbin Huang, Chenzhou First Peoples Hospital;
Bo Xiao, Xiangya Hospital of Centre-south University; Kangning Chen, Southwest Hospital; Xinyue Qin, The
First Affiliated Hospital of Chongqing Medical University; Changlin Hu, The Second Affiliated Hospital of
Chongqing Medical University; Li Gao, Chengdu Third Municipal Peoples Hospital; Jinsheng Zeng, The First
Affiliated Hospital of Sun Yat-Sen University; Anding Xu, The First Affiliated Hospital of Jinan University; Xiong
Zhang, Guangdong Peoples Hospital; Ming Shao, The First Affiliated Hospital of Guangzhou Medical University;
Feng Qi, LiWan Hospital of GuangZhou Medical College; Weimin Xiao, Dungun Municipal Peoples Hospital;
Suping Zhang, Guangzhou Red Cross Hospital; Xiaoping Pan, Guangzhou First TMUNICIPAL Peoples Hospital;
Suyue Pan, Nan Fang Hospital; Yefeng Cai, Guangdong Provincial Hospital of Traditional Chinese Medicine; Qi
Wan, Jiang Su Peoples Hospital; Yun Xu, Drum Tower Hospital Affiliated to Nanjing Medical University Upper
First-class Hospital; KaiFu Ke, he Affiliated Hospital of Nantong University Upper First class Hospital; Yuenan
Kong,Wuxi Second Peoples Hospital Upper First-class Hospital; Qing Di, Neurology Hospital Affiliated to
Nanjing Medical University Upper First-class Hospital; Fengyang Shao, Jiangsu Province Lianyungang Hospital
of TCM Upper First-class Hospital; Yajun Jiang, Jiangsu Province Hospital of TCM Upper First-class Hospital;
Daming Wang, The First Peoples Hospital of Changzhou Upper First-class Hospital; Li Guo, The Second Hospital
of Hebei Medical University; Wencui Xue, Qinhuangdao C.