Low ankle brachial index predicts new va (1)
See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/256447543
Low ankle-brachial index predicts new vascular
events and functional outcome after 1 year in
patients with...
Article in European Journal of Neurology · September 2013
DOI: 10.1111/ene.12253 · Source: PubMed
CITATIONS
READS
5
24
5 authors, including:
José Alvarez-Sabín
Olga Maisterra
University Hospital Vall d'Hebron
University Hospital Vall d'Hebron
488 PUBLICATIONS 11,234 CITATIONS
30 PUBLICATIONS 523 CITATIONS
SEE PROFILE
SEE PROFILE
Antonio Gil Núñez
Hospital General Universitario Gregorio Mara…
110 PUBLICATIONS 851 CITATIONS
SEE PROFILE
All content following this page was uploaded by José Alvarez-Sabín on 16 September 2014.
The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document
and are linked to publications on ResearchGate, letting you access and read them immediately.
European Journal of Neurology 2014, 21: 100–106
doi:10.1111/ene.12253
Low ankle brachial index predicts new vascular events
and functional outcome after 1 year in patients with
non-cardioembolic stroke: our experience and review
~ezb
n
J. Alvarez-Sabına, M. Quintanaa, E. Santamarinaa, O. Maisterraa and A. Gil-Nu
a
Neurovascular Unit, Department of Neurology, Universitat Aut
onoma de Barcelona, Hospital Vall d’Hebron, Barcelona; and bStroke
Unit, Department of Neurology, Hospital Universitario Gregorio Mara~
non, Universidad Complutense, Madrid, Spain
Keywords:
ankle brachial index,
atherothrombotic stroke,
outcome, recurrence,
stroke
Received 7 June 2013
Accepted 26 July 2013
Background and purpose: The ankle brachial index (ABI) has been defined as an
important factor associated with vascular events. Our objective was to analyze the
prognostic value of the ABI as a predictive factor of new vascular events and functional status at 1 year in patients with non-cardioembolic ischaemic stroke.
Methods: A prospective, longitudinal, observational and multicenter study was performed, including consecutive patients ≥50 years old who had suffered from a noncardioembolic ischaemic stroke. Pathological ABI (PI) was defined when the value
was ≤0.9. The logistic regression model, survival analysis and the Cox proportional
hazard regression model were used to identify factors independently associated with
functional outcome and occurrence of new vascular events, including recurrent
stroke.
Results: In all, 977 patients were evaluated. The mean age was 69.1 9.5 years.
40.5% patients had PI. Stroke recurrence and new vascular events global rates were
9% and 20% respectively at 1 year. PI was independently associated with new vascular events [hazard ratio 1.764 (1.274–2.444), P = 0.001]. A cut-off point of
ABI ≤ 0.8 (14% vs. 7%, P = 0.002) independently predicted stroke recurrence in an
adjusted regression model [hazard ratio 1.807 (1.102–2.963), P = 0.019]. PI was also
associated with functional dependence [odds ratio 1.490 (1.011–2.196), P = 0.044].
Conclusions: In non-cardioembolic ischaemic stroke patients, PI was an independent predictive factor of new vascular events and functional outcome after 1 year of
follow-up.
Introduction
Stroke is the largest single cause of long-term disability in adults and one of the main causes of mortality
[1]. Recurrence after an ischaemic stroke or transient
ischaemic attack (TIA) frequently leads to additional
mortality or disability [2]. Although the average
annual rate of recurrent stroke has declined substantially over the last few decades due to the cumulative
advances in secondary prevention [3], about a quarter
of strokes are still recurrent [4].
The functional prognosis after a year of follow-up
in stroke patients has been assessed in some studies
[5–9], giving values of functional independence from
63% to 70% at 1 year. With regard to possible facCorrespondence: J. Alvarez-Sabın, Department of Neurology, Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron 119-129, 08035
Barcelona, Spain (tel.: (+34)934894257; fax: (+34)934894257;
e-mail: [email protected]).
100
tors associated with functional prognosis in stroke
patients at 1 year, in most studies stroke severity was
found to be a constant variable [6–8,10]. However,
other factors have been defined: age [6,7,10], presence
of previous stroke [8,10], blood glucose levels [11] and
baseline C-reactive protein [11].
In the general population, low ankle brachial index
(ABI) ( 2] at 3 months of
follow-up.
The main objective of our study was to evaluate
ABI as a predictive factor of functional outcome and
new vascular events, including recurrent stroke, in
patients who had recently suffered from a non-cardioembolic ischaemic stroke.
Methods
A prospective, longitudinal, observational and multicenter study was performed, including basal data of
patients referred to 121 different hospitals from rural
or urban areas in Spain. Each investigator included a
maximum of 10 consecutive ≥50-year-old patients suffering from a non-cardioembolic TIA or ischaemic
stroke and admitted to a neurology department.
Patients were included in the study at discharge. The
average time between stroke and inclusion in the
study was 7.2 days. All participants signed an
informed consent form. The study was approved by
the local ethics committee, Vall d’ Hebron Hospital
Institutional Review Board.
Transient ischaemic attack and ischaemic stroke etiology were classified according to the TOAST criteria
[21]. The risk factors considered in the study were the
same as defined in previous reports [22]. Basal neurological status on admission was evaluated using the
NIH Stroke Scale (NIHSS) [23]. Follow-up assessment
at 1 year was performed via telephone interviews with
the patients or their next of kin. The mRS [24,25] was
evaluated to assess the functional status of the patient.
mRS ≤ 2 indicated no functional dependence. New
vascular events were defined as a composite of coronary heart disease (coronary death, myocardial infarction, stable or unstable angina and coronary
revascularization), cerebrovascular events (ischaemic
stroke, hemorrhagic stroke and TIA), peripheral
artery disease (intermittent claudication and lower
extremity arterial revascularization) and vascular
death.
In the present study demographic data, cerebrovascular risk factors, previous vascular disease, previous
pharmacological treatment, blood pressure (BP) measurement, weight and height and also blood test
results were collected.
To calculate the ABI, systolic BP (SBP) was measured using a Doppler probe in both the humeral and
posterior tibial arteries. Right ABI was calculated
© 2013 The Author(s)
European Journal of Neurology © 2013 EFNS
101
from the SBP of the right leg divided by the maximum SBP of the arms and in the same way left ABI
(SBP left leg/maximum SBP of the arms), taking the
smallest value of them as the valid ABI. A pathological ABI (PI) was defined as a value ≤0.9 [26]. A lower
cut-off point of ABI (≤0.8) [27] was also explored in
order to better predict the evolution of these patients.
Statistical analysis
The analyses were performed with the use of SPSS
15.0 software for Windows.
In the descriptive analysis, categorical data are
shown as frequencies (%)and quantitative data as
mean standard deviation or median (interquartile
range), the latter in the case of numerical variables
that were not close to a normal distribution.
Statistical significance for intergroup differences was
assessed by Pearson’s chi-squared for categorical variables and the Student’s t test or Mann Whitney
U test for continuous variables. Multivariate analysis
using a logistic regression model was done to determine factors independently associated with PI.
Survival curves and tables were used to analyze the
rate of vascular events, stroke recurrence and mortality during follow-up. Survival analysis was performed
with the Kaplan Meier method, using the log-rank
test to determine variables associated with a higher
risk of new vascular events and mortality.
Finally, multivariate analysis using forward stepwise
Cox regression [presented as hazard ratio (HR) with
95% confidence interval (CI)] was used to identify factors independently associated with risk of new vascular events, stroke recurrence or mortality; a forward
stepwise logistic regression analysis was also performed to find independently associated factors of
functional dependence or death (mRS > 2) at 1 year
[presented as odds ratio (OR) with 95% CI]. All factors associated in univariate analysis were included in
the multivariate models. HR and OR for continuous
variables are per 1 unit increase.
P values < 0.05 were considered statistically significant for all tests.
Results
Initial visit
In all, 977 patients were included; 66.7% were male.
The median age was 69.1 9.5 years. Main baseline
characteristics including risk factors and previous vascular events are shown in Table 1. 18.5% of patients
had suffered a TIA. With regard to etiology, atherothrombotic etiology was the most prevalent (57.2%)
102
J. Alvarez-Sabın et al.
Table 1 Demographic and risk factor profile
1.0
Variable
Frequency, n (%)
Age, mean SD
Gender, male
Waist circumference (cm), mean SD
SBP (mmHg), mean SD
Risk factors
Hypertension
Diabetes mellitus
Tobacco
Alcohol
Dyslipidemia
Vascular antecedents
Ischaemic heart disease
Heart failure
Atrial fibrillation
Other arrythmias
Dilated cardiomyopathy
Previous TIA or cerebral infarction
Intracerebral hemorrhage
Known carotid stenosis ≥50%
Carotid surgery/angioplasty
Aneurysm and/or aortic dissection
Previous arteriopathy
69.1 9.5
678 (66.3)
100.1 13.9
142.9 19.4
715
385
293
112
457
(73.8)
(40.1)
(30.3)
(11.7)
(47.8)
141 (14.5)
27 (2.8)
25 (2.6)
18 (1.9)
26 (2.7)
195 (20.2)
20 (2.1)
35 (3.6)
13 (1.4)
9 (0.9)
96 (9.9)
ABI ≤0.9
0.8
0.6
0.4
0.2
n = 836
A total of 836 patients were evaluated 1 year after the
index stroke. Of these, 166 (19.8%) patients suffered
from some type of vascular event during follow-up: 72
of them had stroke, 53 had an ischaemic heart disease
event and 41 showed episodes of intermittent claudication. Recurrence rates of vascular events in these
patients were 7.7% (5.9–9.5%), 12.7% (10.5–14.9%)
and 19.7% (17–22.4%) at 3, 6 and 12 months respectively. In Fig. 1 it can be seen that individuals with PI
had more vascular events during follow-up. Thus, in
patients with PI, the rate of vascular events within the
first year was 27% compared with 14% in the normal
ABI group (log-rank, P < 0.001). Table 2 shows the
variables significantly associated with occurrence of
new vascular events. The results of the Cox regression
showed, as independent predictors of new vascular
n = 667
n = 570
Table 2 Variables significantly associated with new vascular events
during follow-up
New vascular events
Variables
Follow-up
n = 721
Figure 1 Kaplan Meier curves comparing PI with new vascular
events.
SBP, systolic blood pressure; TIA, transient ischaemic attack.
followed by lacunar stroke (29.7%), undetermined
(12.5%) and 0.5% of unusual cause.
Mean ABI was 0.92 0.21; 40.5% of patients had
PI. After performing a logistic regression analysis, factors independently associated with PI were established
stroke, atherothrombotic etiology, previous arteriopathy (defined as previous physician diagnosis of peripheral arterial disease), SBP, waist perimeter, age,
tobacco, coronary revascularization, previous stroke
and intermittent claudication.
n = 769
0.0
No
Age
68.9 9.4
Hypertension
72.4%
Diabetes mellitus
39.6%
Previous ischaemic
11.7%
heart disease
Previous antiplatelet
34.2%
treatment
Previous lipid-lowering
27.6%
therapy
Previous antidiabetic
28.4%
treatment
Peripheral vasodilators
4.5%
treatment
Systolic blood pressure
142.1 19.8
HDL (mg/dl)
46.0 13.4
Triglycerides
148.7 82.2
ABI
0.94 0.20
Etiologic classification (TOAST)
Atherothrombotic
53.1%
Lacunar
32.2%
Undetermined
14.7%
Yes
P
70.6 9.4
81.7%
51.5%
24.8%
0.030
0.023
0.007
Low ankle-brachial index predicts new vascular
events and functional outcome after 1 year in
patients with...
Article in European Journal of Neurology · September 2013
DOI: 10.1111/ene.12253 · Source: PubMed
CITATIONS
READS
5
24
5 authors, including:
José Alvarez-Sabín
Olga Maisterra
University Hospital Vall d'Hebron
University Hospital Vall d'Hebron
488 PUBLICATIONS 11,234 CITATIONS
30 PUBLICATIONS 523 CITATIONS
SEE PROFILE
SEE PROFILE
Antonio Gil Núñez
Hospital General Universitario Gregorio Mara…
110 PUBLICATIONS 851 CITATIONS
SEE PROFILE
All content following this page was uploaded by José Alvarez-Sabín on 16 September 2014.
The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document
and are linked to publications on ResearchGate, letting you access and read them immediately.
European Journal of Neurology 2014, 21: 100–106
doi:10.1111/ene.12253
Low ankle brachial index predicts new vascular events
and functional outcome after 1 year in patients with
non-cardioembolic stroke: our experience and review
~ezb
n
J. Alvarez-Sabına, M. Quintanaa, E. Santamarinaa, O. Maisterraa and A. Gil-Nu
a
Neurovascular Unit, Department of Neurology, Universitat Aut
onoma de Barcelona, Hospital Vall d’Hebron, Barcelona; and bStroke
Unit, Department of Neurology, Hospital Universitario Gregorio Mara~
non, Universidad Complutense, Madrid, Spain
Keywords:
ankle brachial index,
atherothrombotic stroke,
outcome, recurrence,
stroke
Received 7 June 2013
Accepted 26 July 2013
Background and purpose: The ankle brachial index (ABI) has been defined as an
important factor associated with vascular events. Our objective was to analyze the
prognostic value of the ABI as a predictive factor of new vascular events and functional status at 1 year in patients with non-cardioembolic ischaemic stroke.
Methods: A prospective, longitudinal, observational and multicenter study was performed, including consecutive patients ≥50 years old who had suffered from a noncardioembolic ischaemic stroke. Pathological ABI (PI) was defined when the value
was ≤0.9. The logistic regression model, survival analysis and the Cox proportional
hazard regression model were used to identify factors independently associated with
functional outcome and occurrence of new vascular events, including recurrent
stroke.
Results: In all, 977 patients were evaluated. The mean age was 69.1 9.5 years.
40.5% patients had PI. Stroke recurrence and new vascular events global rates were
9% and 20% respectively at 1 year. PI was independently associated with new vascular events [hazard ratio 1.764 (1.274–2.444), P = 0.001]. A cut-off point of
ABI ≤ 0.8 (14% vs. 7%, P = 0.002) independently predicted stroke recurrence in an
adjusted regression model [hazard ratio 1.807 (1.102–2.963), P = 0.019]. PI was also
associated with functional dependence [odds ratio 1.490 (1.011–2.196), P = 0.044].
Conclusions: In non-cardioembolic ischaemic stroke patients, PI was an independent predictive factor of new vascular events and functional outcome after 1 year of
follow-up.
Introduction
Stroke is the largest single cause of long-term disability in adults and one of the main causes of mortality
[1]. Recurrence after an ischaemic stroke or transient
ischaemic attack (TIA) frequently leads to additional
mortality or disability [2]. Although the average
annual rate of recurrent stroke has declined substantially over the last few decades due to the cumulative
advances in secondary prevention [3], about a quarter
of strokes are still recurrent [4].
The functional prognosis after a year of follow-up
in stroke patients has been assessed in some studies
[5–9], giving values of functional independence from
63% to 70% at 1 year. With regard to possible facCorrespondence: J. Alvarez-Sabın, Department of Neurology, Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron 119-129, 08035
Barcelona, Spain (tel.: (+34)934894257; fax: (+34)934894257;
e-mail: [email protected]).
100
tors associated with functional prognosis in stroke
patients at 1 year, in most studies stroke severity was
found to be a constant variable [6–8,10]. However,
other factors have been defined: age [6,7,10], presence
of previous stroke [8,10], blood glucose levels [11] and
baseline C-reactive protein [11].
In the general population, low ankle brachial index
(ABI) ( 2] at 3 months of
follow-up.
The main objective of our study was to evaluate
ABI as a predictive factor of functional outcome and
new vascular events, including recurrent stroke, in
patients who had recently suffered from a non-cardioembolic ischaemic stroke.
Methods
A prospective, longitudinal, observational and multicenter study was performed, including basal data of
patients referred to 121 different hospitals from rural
or urban areas in Spain. Each investigator included a
maximum of 10 consecutive ≥50-year-old patients suffering from a non-cardioembolic TIA or ischaemic
stroke and admitted to a neurology department.
Patients were included in the study at discharge. The
average time between stroke and inclusion in the
study was 7.2 days. All participants signed an
informed consent form. The study was approved by
the local ethics committee, Vall d’ Hebron Hospital
Institutional Review Board.
Transient ischaemic attack and ischaemic stroke etiology were classified according to the TOAST criteria
[21]. The risk factors considered in the study were the
same as defined in previous reports [22]. Basal neurological status on admission was evaluated using the
NIH Stroke Scale (NIHSS) [23]. Follow-up assessment
at 1 year was performed via telephone interviews with
the patients or their next of kin. The mRS [24,25] was
evaluated to assess the functional status of the patient.
mRS ≤ 2 indicated no functional dependence. New
vascular events were defined as a composite of coronary heart disease (coronary death, myocardial infarction, stable or unstable angina and coronary
revascularization), cerebrovascular events (ischaemic
stroke, hemorrhagic stroke and TIA), peripheral
artery disease (intermittent claudication and lower
extremity arterial revascularization) and vascular
death.
In the present study demographic data, cerebrovascular risk factors, previous vascular disease, previous
pharmacological treatment, blood pressure (BP) measurement, weight and height and also blood test
results were collected.
To calculate the ABI, systolic BP (SBP) was measured using a Doppler probe in both the humeral and
posterior tibial arteries. Right ABI was calculated
© 2013 The Author(s)
European Journal of Neurology © 2013 EFNS
101
from the SBP of the right leg divided by the maximum SBP of the arms and in the same way left ABI
(SBP left leg/maximum SBP of the arms), taking the
smallest value of them as the valid ABI. A pathological ABI (PI) was defined as a value ≤0.9 [26]. A lower
cut-off point of ABI (≤0.8) [27] was also explored in
order to better predict the evolution of these patients.
Statistical analysis
The analyses were performed with the use of SPSS
15.0 software for Windows.
In the descriptive analysis, categorical data are
shown as frequencies (%)and quantitative data as
mean standard deviation or median (interquartile
range), the latter in the case of numerical variables
that were not close to a normal distribution.
Statistical significance for intergroup differences was
assessed by Pearson’s chi-squared for categorical variables and the Student’s t test or Mann Whitney
U test for continuous variables. Multivariate analysis
using a logistic regression model was done to determine factors independently associated with PI.
Survival curves and tables were used to analyze the
rate of vascular events, stroke recurrence and mortality during follow-up. Survival analysis was performed
with the Kaplan Meier method, using the log-rank
test to determine variables associated with a higher
risk of new vascular events and mortality.
Finally, multivariate analysis using forward stepwise
Cox regression [presented as hazard ratio (HR) with
95% confidence interval (CI)] was used to identify factors independently associated with risk of new vascular events, stroke recurrence or mortality; a forward
stepwise logistic regression analysis was also performed to find independently associated factors of
functional dependence or death (mRS > 2) at 1 year
[presented as odds ratio (OR) with 95% CI]. All factors associated in univariate analysis were included in
the multivariate models. HR and OR for continuous
variables are per 1 unit increase.
P values < 0.05 were considered statistically significant for all tests.
Results
Initial visit
In all, 977 patients were included; 66.7% were male.
The median age was 69.1 9.5 years. Main baseline
characteristics including risk factors and previous vascular events are shown in Table 1. 18.5% of patients
had suffered a TIA. With regard to etiology, atherothrombotic etiology was the most prevalent (57.2%)
102
J. Alvarez-Sabın et al.
Table 1 Demographic and risk factor profile
1.0
Variable
Frequency, n (%)
Age, mean SD
Gender, male
Waist circumference (cm), mean SD
SBP (mmHg), mean SD
Risk factors
Hypertension
Diabetes mellitus
Tobacco
Alcohol
Dyslipidemia
Vascular antecedents
Ischaemic heart disease
Heart failure
Atrial fibrillation
Other arrythmias
Dilated cardiomyopathy
Previous TIA or cerebral infarction
Intracerebral hemorrhage
Known carotid stenosis ≥50%
Carotid surgery/angioplasty
Aneurysm and/or aortic dissection
Previous arteriopathy
69.1 9.5
678 (66.3)
100.1 13.9
142.9 19.4
715
385
293
112
457
(73.8)
(40.1)
(30.3)
(11.7)
(47.8)
141 (14.5)
27 (2.8)
25 (2.6)
18 (1.9)
26 (2.7)
195 (20.2)
20 (2.1)
35 (3.6)
13 (1.4)
9 (0.9)
96 (9.9)
ABI ≤0.9
0.8
0.6
0.4
0.2
n = 836
A total of 836 patients were evaluated 1 year after the
index stroke. Of these, 166 (19.8%) patients suffered
from some type of vascular event during follow-up: 72
of them had stroke, 53 had an ischaemic heart disease
event and 41 showed episodes of intermittent claudication. Recurrence rates of vascular events in these
patients were 7.7% (5.9–9.5%), 12.7% (10.5–14.9%)
and 19.7% (17–22.4%) at 3, 6 and 12 months respectively. In Fig. 1 it can be seen that individuals with PI
had more vascular events during follow-up. Thus, in
patients with PI, the rate of vascular events within the
first year was 27% compared with 14% in the normal
ABI group (log-rank, P < 0.001). Table 2 shows the
variables significantly associated with occurrence of
new vascular events. The results of the Cox regression
showed, as independent predictors of new vascular
n = 667
n = 570
Table 2 Variables significantly associated with new vascular events
during follow-up
New vascular events
Variables
Follow-up
n = 721
Figure 1 Kaplan Meier curves comparing PI with new vascular
events.
SBP, systolic blood pressure; TIA, transient ischaemic attack.
followed by lacunar stroke (29.7%), undetermined
(12.5%) and 0.5% of unusual cause.
Mean ABI was 0.92 0.21; 40.5% of patients had
PI. After performing a logistic regression analysis, factors independently associated with PI were established
stroke, atherothrombotic etiology, previous arteriopathy (defined as previous physician diagnosis of peripheral arterial disease), SBP, waist perimeter, age,
tobacco, coronary revascularization, previous stroke
and intermittent claudication.
n = 769
0.0
No
Age
68.9 9.4
Hypertension
72.4%
Diabetes mellitus
39.6%
Previous ischaemic
11.7%
heart disease
Previous antiplatelet
34.2%
treatment
Previous lipid-lowering
27.6%
therapy
Previous antidiabetic
28.4%
treatment
Peripheral vasodilators
4.5%
treatment
Systolic blood pressure
142.1 19.8
HDL (mg/dl)
46.0 13.4
Triglycerides
148.7 82.2
ABI
0.94 0.20
Etiologic classification (TOAST)
Atherothrombotic
53.1%
Lacunar
32.2%
Undetermined
14.7%
Yes
P
70.6 9.4
81.7%
51.5%
24.8%
0.030
0.023
0.007