NEUROL-2094; No.

of Pages 7

revue neurologique xxx (2019) xxx–xxx

Available online at

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Original article

Use of CHADS2 and CHA2DS2-VASc scores to predict

prognosis after stroke

B. Kusznir Vitturi *, R. José Gagliardi

Department of Neurology, Santa Casa de São Paulo School of Medical Sciences, Dr. Cesário Motta Júnior 112 Street,
01221-900, São Paulo, SP, Brazil

info article abstract

Article history: Introduction. – Stroke is one of the most devastating neurological disorders. Currently, we
Received 23 February 2019 don’t have an ideal score that predicts the prognosis of stroke patients. The CHADS2 and
Received in revised form CHA2DS2-VASc scores are well-validated tools for the estimation of stroke risk in patients
23 April 2019 with atrial fibrillation. The purpose of this study was to investigate if these scores can predict
Accepted 20 May 2019 the outcomes of all the patients who suffered an ischemic stroke regardless of atrial
Available online xxx fibrillation.
Methods. – Consecutive patients that were admitted with an acute ischemic stroke were
Keywords: classified into subgroups according to pre-stroke CHADS2 and CHA2DS2-VASc scores and
Stroke after 2 years the functional outcome, stroke recurrence, major cardiovascular events and
CHADS2 mortality were assessed.
CHA2DS2-VASc Results. – Among the 973 patients that were included in analysis, the mean age was 56.7 (SD
Stroke prognosis 15.7) and 46.6% were female. There were 226 (23.2%), 365 (37.5%) and 382 (39.3%) patients
with low, intermediate and high CHADS2 score, respectively. For CHADS2-VASc score there
were 81 (8.3%), 268 (27.6%), and 624 (64.1%) patients with low, intermediate and high,
respectively. Both high-risk scores were associated with middle-term poor functional
outcome, stroke recurrence, major cardiovascular events and all-cause mortality. CHADS2
and CHA2DS2-VASc scores presented a high sensitivity and a high negative predictive value.
CHA2DS2-VASc was more sensitive than CHADS2 score.
Conclusion. – CHADS2 and CHA2DS2-VASc scores were both associated with stroke outcomes
regardless of atrial fibrillation. These scores can be useful tools for the prognosis stratifica-
tion of a patient with an ischemic stroke.
# 2019 Elsevier Masson SAS. All rights reserved.

1. Introduction Several risk factors are associated with stroke and among
them, atrial fibrillation (AF) is one of the most important single
Stroke is one of the most devastating neurological disorder. predictors of ischemic stroke [2,3]. The CHADS2 score is a well-
Worldwide it is a leading cause of death and adult disability [1]. validated tool for the estimation of stroke risk in patients with

* Corresponding author.
E-mail address: z_azul@hotmail.com (B. Kusznir Vitturi).
https://doi.org/10.1016/j.neurol.2019.05.001
0035-3787/# 2019 Elsevier Masson SAS. All rights reserved.

Please cite this article in press as: Kusznir Vitturi B, José Gagliardi R. Use of CHADS2 and CHA2DS2-VASc scores to predict prognosis after stroke.
Revue neurologique (2019), https://doi.org/10.1016/j.neurol.2019.05.001
NEUROL-2094; No. of Pages 7

2 revue neurologique xxx (2019) xxx–xxx

atrial fibrillation [4]. More recently, the CHA2DS2-VASc score patient was already receiving antihypertensives. Diabetes
was developed to improve the accuracy of stroke risk mellitus was defined as patient already receiving antidiabetic
stratification and to complement the CHADS2 score by drugs and/or insulin, or if fasting blood glucose level
incorporating other common stroke risk factors [5,6]. was  126.0 mgl/dl before stroke. Vascular disease was
Most of the individual components of the CHADS2 and understood as coronary artery disease, peripheral artery
CHA2DS2-VASc scores have previously been associated with disease and aortic atherosclerosis. Coronary heart disease
stroke prognosis in both patients with and without AF. Some was defined as typical chest symptoms and cardiologist
studies have shown that the pre-stroke CHADS2 score itself is confirmation. Heart failure were defined based on the
correlated with neurological deterioration and functional European Society of Cardiology Guidelines and patients were
outcomes in short-term in patients with acute ischemic required to have subjective typical symptoms (shortness of
stroke and nonvalvular AF [7,8]. Long-term mortality and breath, fatigue, tiredness, edema) and objective evidence of
cardiovascular events have also been linked to CHADS2 and cardiac abnormalities on the echocardiogram [14]. Stroke was
CHA2DS2-VASc scores in patients with and without AF [9,10]. defined according to World Health Organization and TIA was
In fact, some recent studies suggest that CHADS2 and defined as complete remission of signs and symptoms within
CHA2DS2-VASc might be associated with stroke outcomes 24 h, regardless of infarction being shown on neuroimaging
not only in patients with AF but also in the general stroke [15,16].
population. Both scores seemed to predict neurological Patients were classified into subgroups according to their
outcomes and thromboembolic risk equally in stroke pre-stroke CHADS2 (0–6) and CHA2DS2–VASc (0–9) scores: low
patients with AF and without AF [10–13]. However, the role risk = 0, intermediate risk = 1, high risk  2.
of CHADS2 and CHA2DS2-VASc scores in the prediction of the
middle-term stroke prognosis of all the patients remains
unclear.
Therefore, based on the recent data, we designed the
current study and hypothesized that the pre-stroke CHADS2 Table 1 – Baseline characteristics of the study population.
and CHA2DS2-VASc scores may be independently associated Baseline characteristics Total population (n = 973)
with the 2-year functional outcome, mortality, stroke recur-
Mean age (SD) 56.7 (SD 15.7)
rence and serious cardiovascular events regardless of whether Age  75 years 131 (13.4%)
or not the patient has AF. Age 65–74 years 191 (19.7%)
Age < 65 years 651 (66.9%)
Female 452 (46.6%)
2. Patients and Methods Tobacco use 146 (15.0%)
Heavy drinking 46 (4.7%)
Diabetes 177 (18.2%)
2.1. Study Design and Patient Selection
Cancer 26 (2.6%)
Dementia 35 (3.6%)
This was a prospective cohort study that was developed in a Anticoagulants 198 (20.3%)
stroke outpatient clinic of a university-affiliated, tertiary Antiplatelet therapy 715 (73.5%)
referral hospital. The study enrolled all consecutive patients Antihypertensive agents 634 (65.1%)
(older than 18 years old) admitted to the stroke clinic due to a Lipid-lowering agents 701 (72.0%)
Hipoglycemic agents 165 (16.9%)
confirmed diagnosis of ischemic stroke between January 2006
CHADS2
and December 2018. Patient accrual was based on inpatient
0 226 (23.2%)
admission for stroke. Patients with TIA and patients with a 1 365 (37.5%)
modified Rankin Scale (mRS)  2 before stroke onset were 2 213 (21.9%)
excluded. When a patient was admitted more than twice for a 3 112 (11.5%)
recurrent stroke during the study period, clinical data for the 4 48 (4.9%)
first admission were used for the analysis. Follow-up was 5 9 (1.0%)
CHA2DS2-VASc
routinely performed in the Neurology outpatient clinic. In case
0 81 (8.3%)
of patients with severe handicap, clinical follow-up was 1 268 (27.6%)
assessed by telephone interview. Patients were considered 2 226 (23.2%)
ineligible for the cohort if no clinical evaluation could be 3 163 (16.7%)
performed 2 years after the stroke. The study was approved by 4 136 (14.0%)
the local Ethics Committee. 5 63 (6.5%)
6 30 (3.1%)
7 6 (0.6%)
2.2. Clinical Variables
mRS
Median mRS 2
Clinical characteristics were obtained from electronic medical 0 95 (9.8%)
records of the admission and pre-stroke CHADS2 and 1 309 (31.7%)
CHA2DS2–VASc scores were calculated for each participant 2 569 (58.5%)
using the collected data. Hypertension was defined as systolic Stroke/TIA 186 (19.1%)
Mortality 45 (4.6%)
blood pressure  140 mmHg and/or diastolic blood pressu-
Cardiovascular Events 41 (4.2%)
re  90 mm Hg diagnosed at least twice before stroke and/or if

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NEUROL-2094; No. of Pages 7
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2.3. Clinical Outcomes
The individuals were followed until death or until 2 years after
the stroke onset. If no clinical evaluation could be performed
during this period, first the patient was searched in the
National Registry of Death to detect a possible death before
being excluded of the analysis. The outcome variables include
all-cause mortality, stroke recurrence, myocardial infarction
or new unstable angina and peripheral thromboembolism.
Functional outcome was assessed using the modified
Rankin Scale (mRS). An unfavorable outcome was defined as
a mRS score  3 and a favorable outcome was defined as mRS
score  2. Each patient had the mRS calculated by two
different neurologists, one of whom was blind to the study.
In case of discrepancy, the opinion of the head of the stroke
outpatient clinic was consulted.
2.4. Statistical Analyses
Continuous variables are presented as means and standard
deviations and categorical variables are presented as counts
and percentages. In the univariate analysis of the CHADS2 and
CHA2DS2-VASc subgroups, dichotomous or categorical varia-
bles were compared using the chi-square test. Differences in
continuous variables were assessed using the t test and
bivariate correlation. A logistic regression model was per-
formed to assess the independent association with the risk
scores and the outcomes. Discharge statin use, antithrombotic
medications (antiplatelets or anticoagulants), thrombolysis or
endovascular therapy, baseline NIHSS, smoking and comor-
bidities were the covariates that were adjusted in multi-
variable analysis. The accuracy of the raw pre-stroke CHADS2
Fig. 1 – Pre-Stroke CHADS2 and CHA2DS2-VASc scores (in % of patients) and functional outcome.
Please cite this article in press as: Kusznir Vitturi B, José Gagliardi R. Use of CHADS2 and CHA2DS2-VASc scores to predict prognosis after stroke.
Revue neurologique (2019), https://doi.org/10.1016/j.neurol.2019.05.001
3
and CHA2DS2-VASc scores in predicting the outcomes was
assessed using the area under the receiver operator characte-
ristic curves (AUC). Sensitivity, specificity, positive predictive
value and negative predictive value were calculated as well.
Associations are presented as odds ratios (ORs) with 95%
confidence intervals (CIs). For all the analyses, P < 0.05 for the
two-tailed tests was considered statistically significant. All
statistical analyses were performed using IBM SPSS Statistics
22.0 (IBM Corp. New York, NY, USA).
3. Results
Among 1102 patients admitted with ischemic stroke during
the study period, 88 (8.0%) and 41 (3.7%) were excluded from
the analysis because of lost to follow-up and pre-stroke mRS
score of 2 or more, respectively. The mean age of these
patients was 58.9 (SD 17.8) years and 52.2% were women.
Among the 973 patients that were included in analysis, the
mean age was 56.7 (SD 15.7) and 46.6% were female (Table 1).
Sixty six percent of the patients were less than 65 years old of
age while 13.4% were older than 75 years old. There were no
statistical difference between the clinical characteristics of the
excluded patients and those who were included in the study.
There were 226 (23.2%), 365 (37.5%) and 382 (39.3%) patients
with low, intermediate and high CHADS2 score, respectively.
For CHA2DS2-VASc the corresponding numbers subgroups
were 81 (8.3%), 268 (27.6%), and 624 (64.1%), respectively.
According to TOAST classification, 301 (30.9%) of the patients
suffered from large-artery atherosclerosis, 204 (21.1%) from
cardioembolic disease, 116 (11.9%) from small vessel disease,
245 (25.1%) from a stroke of undetermined cause and 107
NEUROL-2094; No. of Pages 7
4 revue neurologique xxx (2019) xxx–xxx
(11.0%) from other determined etiologies. The median scores
of CHADS2 considering the five soubgroups of TOAST were, 2,
2, 1, 1 and 0 and for CHA2DS2-VASc, 4, 2, 3, 2 and 1, respectively.
Among the patients with cardioembolic stroke, 79.4% had AF.
During the 2-year follow-up, there were 219 composite
vascular events in 215 different patients: 186 recurrent
strokes, 26 coronary artery events (acute myocardial infarc-
tion or unstable angina pectoris) and 7 cases of peripheral
thromboembolism. All-cause mortality was observed in 45
(4.6%) patients. The median mRS score was 2. Four hundred
twenty-six patients had unfavorable outcome (mRS  3) at the
time of follow-up. An univariate analysis revealed that an
unfavorable outcome (mRS score  3) was associated with a
high-risk pre-stroke CHADS2 (P < 0.001) and CHA2DS2-VASc
(P < 0.001) (Fig. 1). Stroke/TIA recurrence and major cardio-
vascular events were positively associated with the scores as
well (P < 0.01 for all comparisons) (Fig. 2). Among the recurrent
strokes, 91% were ischemic. Among the cases of death, 82.2%
and 91.1% of the patients had high-risk CHADS2 and CHA2DS2-
VASc scores, respectively (P < 0.001). Interestingly, there was a
Fig. 2 – Number of major cardiovascular events and stroke
recurrence according to pre-stroke CHADS2 and CHA2DS2-
VASc score risk.
Please cite this article in press as: Kusznir Vitturi B, José Gagliardi R. Use of CHADS2 and CHA2DS2-VASc scores to predict prognosis after stroke.
Revue neurologique (2019), https://doi.org/10.1016/j.neurol.2019.05.001
positive correlation between CHADS2 and CHA2DS2-VASc
scores and NIHSS (r = 0.68; P < 0.05). There was no statistically
significant difference between TOAST subgroups related to the
vascular events prevalence and functional outcomes.
In multivariable analysis, both high-risk scores were
independently associated with a poor functional outcome
(CHADS2: OR 6.0, 2.4–14.8; CHA2DS2-VASc: OR 7.3, 1.8–29.4)
(Tables 2 and 3) and with higher odds for stroke recurrence
(CHADS2: OR 2.1, 1.4–3.0; CHA2DS2-VASc: OR 3.9, 1.9–7.9)
compared to low risk scores. Higher all-cause mortality odds
were associated with both pre-stroke scores as well (CHADS2:
OR 5.1, 1.5–11.9; CHA2DS2-VASc: OR 6.3, 2.1–12.8). In the same
way, increased odds of major cardiovascular events were
only associated with a high risk CHA2DS2-VASc score (OR 7.4,
2.4–24.4). Intermediate risk scores were not independently
associated with any of the outcomes.
The AUC for pre-stroke CHADS2 score was higher than the
pre-stroke CHA2DS2-VASc score for stroke recurrence, all-
cause mortality and functional outcome. However, high-risk
CHA2DS2-VASc score presented a greater sensitivity and
specificity for the four outcomes compared to CHADS2 score
(Table 4). Both CHADS2 and CHA2DS2-VASc scores had high
positive predictive value (PPV) for functional outcome. A high
negative predictive value (NPV) was also found for all the
outcomes in both scores.
4. Discussion
This study showed that the pre-stroke CHADS2 and CHA2DS2-
VASc scores are both independently associated with middle-
term functional outcome, all-cause mortality, stroke recur-
rence and major cardiovascular events regardless of AF. The
CHADS2 and CHA2DS2-VASc scores were created to be used
only in stroke patients with AF. However, approximately 85%
of all strokes occur in people without AF, what at first restricts
the application of the scale [17]. In addition, current prognostic
models for ischemic stroke that have already been published
lack simplicity, which compromises its practical applicability
[18]. Most of the scores are complex, require a lot of time and
involve information about neurological impairment, comor-
bidities and even neuroradiological characteristics [19–21]. In
fact, no single prognostic model has been strongly recom-
mended for clinical use [22]. CHADS2 and CHA2DS2-VASc
scores are both well known to the majority of neurologists and
are very simple to be applied even by physicians of another
specialty, who may often deal with patients with stroke.
Previous studies have suggested that AF would not be a
restriction to the applicability of CHADS2 and CHA2DS2-VASc
scores [23]. More recently, it was shown that anticoagulation
does not influence the predictive power of CHADS2 and
CHA2DS2-VASc scores as well [24]. In line with these studies,
we found that both scores can be useful in estimating not only
the risk of stroke recurrence but the risk of multiple outcomes
independently of AF. Mortality, for example, was strongly
related to high-risk scores, as well as functional outcomes. A
plausible explanation for our findings might be that most of
the clinical components of the CHADS2 and CHA2DS2-VASc
scores were previously shown to be associated with prognosis
in patients with acute stroke. Hypertension, diabetes and
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Table 2 – Multivariate logistic regression showing the independent predictors of a poor functional outcome and stroke/TIA
recurrence.
Poor Functional Outcome P Stroke/TIA P
OR (95% CI) OR (95% CI)
Age
< 65 years 1 1
65–74.9 years 1.4 (0.9–2.1) 0.02 1.2 (0.8–1.7) 0.1
 75 years 1.6 (1.0–2.7) 0.04 1.4 (1.0–2.0) 0.3
Female gender 1.9 (1.3–2.7) 0.01 0.7 (0.5–1.0) 0.09
Congestive heart failure 2.8 (2.1–3.9) 0.03 1.5 (0.4–2.8) 0.1
Hypertension 1.8 (0.9–2.6) 0.07 2.1 (1.3–2.7) 0.02
Diabetes 1.9 (0.9–2.9) 0.1 1.5 (0.7–2.1) 0.2
Vascular disease 1.7 (1.1–2.4) 0.05 1.3 (0.6–2.0) 0.09
Stroke/TIA/thromboembolism history 2.4 (1.9–2.8) 0.08 3.4 (2.8–4.1) 0.01
NIHSS 6.7 (3.4–8.5) < 0.001 1.8 (0.7–2.9) 0.2
CHADS2
0–1 1 1
2 1.6 (0.7–3.7) 0.2 1.50 (0.8–1.1) < 0.001
CHA2DS2-VASc 6.0 (2.4–14.8) < 0.001 2.10 (1.4–3.0) < 0.001
0–1
2 1 1
Age 1.0 (0.2–3.3) 0.9 1.4 (0.8–1.8) 0.03
< 65 years 7.3 (1.8–29.4) < 0.001 3.9 (1.9–7.9) < 0.001

Table 3 – Multivariable logistic regression showing the independent predictors of major cardiovascular events and all-
cause mortality.
Major cardiovascular events P-value Mortality P-value
OR (95% CI) OR (95% CI)
Age
< 65 years 1 1
65–74.9 years 1.3 (0.6–2.8) 0.4 1.5 (1.2–1.8) 0.001
 75 years 2.5 (1.8–3.6) 0.05 1.7 (1.5–2.0) 0.004
Female gender 2.4 (2.0 -2.9) 0.01 1.1 (0.8–1.7) 0.4
Congestive heart failure 1.9 (1.2–2.5) 0.04 1.5 (1.1–1.9) 0.01
Hypertension 1.3 (0.8–1.9) 0.2 1.3 (0.5–2.2) 0.02
Diabetes 1.6 (0.9–2.2) 0.08 1.2 (0.4–2.3) 0.3
Vascular disease 2.6 (2.1–3.3) 0.01 1.8 (0.9–2.6) 0.2
Stroke/TIA/thromboembolism history 4.5 (3.6–5.4) < 0.001 2.6 (2.1–3.7) < 0.01
NIHSS 1.9 (1.1–2.8) 0.01 4.5 (3.4–5.6) < 0.01
CHADS2
0–1 1 1
2 1.6 (1.0–2.2) 0.15 5.1 (1.5–11.9) 0.001
CHA2DS2-VASc
0–1 1 1
2 7.4 (2.2–24.4) < 0.001 6.3 (2.1–12.8) 0.01

Table 4 – AUC, sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for pre-stroke CHADS2 and
CHA2DS2-VASc scores in estimating poor functional outcomes, stroke/TIA recurrence, major cardiovascular events and
all-cause mortality.
AUC (95% CI) P-value Sensitivity Specificity PPV NPV
Poor functional outcomes
CHADS2 0.80 (0.77–0.83) < 0.001 0.68 0.16 0.76 0.83
CHA2DS2-VASc 0.77 (0.74–0.80) < 0.001 0.94 0.40 0.94 0.83
Stroke/TIA
CHADS2 0.71 (0.67–0.75) < 0.001 0.68 0.32 0.33 0.90
CHA2DS2-VASc 0.68 (0.65–0.72) < 0.001 0.94 0.56 0.28 0.96
Major cardiovascular events
CHADS2 0.61 (0.53–0.68) 0.01 0.50 0.38 0.05 0.96
CHA2DS2-VASc 0.65 (0.58–0.72) < 0.001 0.92 0.62 0.05 0.99
Mortality
CHADS2 0.79 (0.74–0.85) < 0.001 0.82 0.37 0.09 0.98
CHA2DS2-VASc 0.68 (0.61–0.75) < 0.001 0.91 0.63 0.06 0.98

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NEUROL-2094; No. of Pages 7
6 revue neurologique xxx (2019) xxx–xxx
heart failure are clearly associated with poor outcomes after a
stroke [25–27]. Age and previous stroke are significant
predictors of stroke outcomes as well [13,25].
Our study results are also in line with past studies reporting
that most of the risk factors of CHADS2 and CHA2DS2-VASc
scores are predictive of severe stroke concerning functional
outcomes. Stroke recurrence and major cardiovascular events
were specially tied to vascular diseases and previous history of
thromboembolic events, which is consistent with other
previous findings as well [27–30]. The determination of risk
factors associated with poor outcome two years after stroke
may provide helpful guidance on identifying those who may
need more intensive medical management or monitoring to
prevent poor prognosis. CHA2DS2-VASc presented higher
sensitivity and specificity for predicting stroke outcomes.
Indeed, gender, vascular disease and age were significant risk
factors for most of the aspects in the present study [28–30]. Our
2-year mortality was lower than previous studies [29],
however, this can be explained by the selection and baseline
characteristics of the patients. We had a high percentage of
patients younger than 65 years old. Explanations are specu-
lative, however, it can be assumed that older patients may
have higher mortality during the acute phase of the event (and
then, they are not followed up in the outpatient clinic) or they
may lose follow-up more easily.
The strengths of the study include the assessment of
several clinical outcome measures in a large sample size with
a prospective design. In addition, differently from previous
studies whose data were obtained from population databases,
we were able to implement a greater rigor in data collection
and patient follow-up. This is the first study that evaluates
CHADS2 and CHA2DS2-VASc scores as potential prognostic
tools to all stroke patients that are being followed up in an
outpatient clinic. The utility of these practical scores to the
entire stroke population in a context of secondary prevention
has never been evaluated and quantified in clinical practice
before. This study has also some limitations that need to be
acknowledged to better interpret the results. We were not able
to evaluate other possible minor comorbidities that may also
influence outcomes (eg. adherence to medications, socio-
educational status), although many other studies [31–33] have
already done this approach and the feasibility of this type of
follow-up is often compromised in prospective cohorts. In
addition, this is a single center and hospital-based study
whose sample, albeit large, may not be representative of the
entire stroke patient population.
5. Conclusions
In summary, CHADS2 and CHA2DS2-VASc scores were
associated with stroke outcomes regardless of atrial fibrilla-
tion. These simple scores can be a very useful way of
stratifying stroke patients according to their prognostic risk.
We propose that these scores can be easily used in the initial
approach of the patient with ischemic stroke and they should
be complemented with a more refined and individualized
analysis performed by a vascular neurologist. Future pros-
pective studies comparing CHADS2 and CHA2DS2-VASc to
other stroke scores are recommended.
Please cite this article in press as: Kusznir Vitturi B, José Gagliardi R. Use of CHADS2 and CHA2DS2-VASc scores to predict prognosis after stroke.
Revue neurologique (2019), https://doi.org/10.1016/j.neurol.2019.05.001
Financial support
None.
Disclosure of interest
The authors declare that they have no competing interest.
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