1. No category

Association of the ankle-brachial index with history of
myocardial infarction and stroke
W. Schuyler Jones, MD, a Manesh R. Patel, MD, a Caron B. Rockman, MD, b Yu Guo, MA, c Mark Adelman, MD, b
Thomas Riles, MD, b and Jeffrey S. Berger, MD b,d Durham, NC; and New York, NY
Background Ankle-brachial index (ABI) testing is a simple, noninvasive method to diagnose peripheral artery disease
(PAD) and is associated with all-cause mortality. The association of ABI levels and myocardial infarction (MI) and stroke is less
certain. We sought to further characterize the association between ABI levels and history of MI and stroke.
Methods
Using data from the Life Line Screening program, 3.6 million self-referred participants from 2003 to 2008
completed a medical questionnaire and had bilateral ABIs performed. Logistic regression was used to estimate the association
between ABI cutoff points (ABI b0.90 and ABI N1.40) and ABI levels with history of MI, stroke, and MI or stroke (MI/stroke).
Models were adjusted for age, sex, race/ethnicity, smoking, diabetes, hypertension, hypercholesterolemia, physical activity,
and family history of cardiovascular disease. Separate sex-specific models were performed.
Results
Conclusions
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Overall, 155,552 (4.5%) had an ABI b0.90, and 42,890 (1.2%) had an ABI N1.40. An ABI b0.90 was
associated with higher odds of MI (adjusted odds ratio [OR] 1.67, 95% CI 1.63-1.71), stroke (OR 1.77, 95% CI 1.72-1.82),
and MI/stroke (OR 1.71, 95% CI 1.67-1.74), all P b .001. An ABI N1.40 was also associated with higher odds of MI (OR
1.19, 95% CI 1.14-1.24), stroke (OR 1.30, 95% CI 1.22-1.38), and MI/stroke (OR 1.22, 95% CI 1.17-1.27), all P b .001.
The ORs for MI/stroke for different ABI levels formed a reverse J-shaped curve in both women and men.
In a large national screening database, there is a strong, consistent relationship between ABI levels and a
history of prevalent MI, stroke, and MI/stroke. (Am Heart J 2014;167:499-505.)
Co
Ankle-brachial index (ABI) testing is a simple, noninvasive screening test to diagnose peripheral artery disease
(PAD), a prevalent condition that affects N8 million adults
in the United States. 1 Patients with ABI b0.90 have been
observed to have more cardiovascular risk factors, more
diffuse atherosclerosis, and higher all-cause mortality
when compared with patients with a normal ABI
(generally considered to be an ABI between 0.91 and
1.40 in epidemiologic studies). 2-9 In these studies, risk for
all-cause mortality is 2-fold to 4-fold higher in patients
with an ABI b0.90. 2,4,9-11 Recent studies have also
From the aDuke Clinical Research Institute, Duke University Medical Center, Durham, NC,
b
Department of Surgery, Division of Vascular Surgery, New York University School of
Medicine, New York, NY, cDepartment of Population Health, Division of Biostatistics, New
York University School of Medicine, New York, NY, and dDepartment of Medicine,
Division of Cardiology, New York University School of Medicine, New York, NY.
Debabrata Mukherjee, MD, served as guest editor for this article.
Funding source: Dr Berger was partially funded by a Doris Duke Clinical Scientist
Development Award (2010055). The funding source had no role in the design and conduct
of the study; collection, management, analysis, and interpretation of the data and
preparation, review, or approval of the manuscript.
Submitted October 17, 2013; accepted December 11, 2013.
Reprint requests: W. Schuyler Jones, MD, Duke University Medical Center, Box 3126,
Durham, NC 27710.
E-mail: [email protected]
0002-8703/$ - see front matter
© 2014, Mosby, Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ahj.2013.12.016
reported a higher incidence of cardiovascular morbidity
and mortality in subjects with high ABI (N1.40), a
concerning finding given the rising prevalence of
diabetes mellitus in the United States. 4,6,12-16 Altohugh
these cutoff points (0.90 and 1.40) have been used
extensively in epidemiologic studies, there is evidence
that even patients with “normal” ABI measurements are
at elevated cardiovascular risk and has prompted
some to consider altering the lower limit ABI cutoff
from 0.90 to 1.00. 17
Although ABI has been reported to improve the
accuracy of cardiovascular risk prediction beyond standard risk scores in patients without known cardiovascular
disease, 17 no large population studies have evaluated the
prevalence of myocardial infarction (MI) or stroke in
patients with low or high ABI. Likewise, the association of
prevalent MI or stroke by ABI level, especially levels
considered to be borderline (ie, ABI value 0.91-1.10), is
unknown. Furthermore, there are limited available data
on the association of ABI values with the prevalence of MI
or stroke stratified by sex.
In the present study, we sought to (1) investigate the
prevalence of abnormal ABI measurements in a large
population; (2) estimate the odds of prior MI, stroke, and
MI/stroke based on patients' clinical characteristics and
ABI values; and (3) evaluate if there were sex-specific
03/04/2014
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April 2014
500 Jones et al
Figure 1
Flow diagram of subjects.
Methods
Study population
Statistical analysis
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differences in the odds of prior MI, stroke, and MI/stroke
based on ABI value.
Co
The current study was based on data provided by Life Line
Screening (LLS, Independence, OH). Study participants were
self-referred and paid for vascular screening tests that were
performed from 2003 to 2008 at N20,000 sites. Ankle and
brachial systolic blood pressures were obtained with the use of
hand-held Doppler machines and oscillometric blood pressure
cuffs. Right and left ABI measurements were calculated by
dividing the highest systolic blood pressure in each leg by the
highest arm pressure. 18 For subjects with ABI values b0.9 in
either leg, the lowest ABI value was assigned to that subject. For
subjects who had an ABI ≥0.9 in both legs, subjects with an ABI
value N1.40 in either or both legs were assigned to the ABI N1.40
group. For those patients with both ABI values between 0.9 and
1.40, the lower ABI value was assigned to that subject.
All subjects completed a health questionnaire that included
information on demographics, comorbid conditions (diabetes
mellitus, hypertension, hyperlipidemia), cardiovascular risk
factors (smoking status, family history of cardiovascular disease),
and the performance of physical activity. Subjects without ABI
values reported in the data set were excluded from the analysis.
Subjects who reported a prior revascularization procedure
for PAD were considered separately in analyses. A history of MI
and stroke was obtained by a medical history survey at the time
of screening.
Age, sex, race, height, and weight were self-reported.
Hypertension, hypercholesterolemia, and diabetes mellitus
were all defined as physician diagnoses or if the subject required
use of medications to control these conditions. Smoking status
was defined as current smoking, former smoking (having
smoked N100 cigarettes during their lifetime), or never. Family history of cardiovascular disease was defined as a firstdegree relative with one of the following: MI, stroke, or
procedure for PAD.
The demographic and clinical characteristics of subject's with
different ABI values are reported using percentages for
categorical variables and mean with SD for continuous variables.
Statistical tests were conducted to evaluate differences in
variables between groups, using χ 2 for categorical variables
and analysis of variance for continuous variables. Logistic
regression was performed to assess the association of ABI with
the prevalence of MI, stroke, and MI/stroke. The ABI was
included as categorical variables, based on the previously
defined PAD cut points (b0.9, 0.9-1.4, N1.4). 19 Adjustment was
made for age, sex, race, smoking status, diabetes, hypertension,
hypercholesterolemia, family history of cardiovascular disease,
body mass index, and performance of physical activity as
potential confounders. In separate models, level of ABI was also
examined (references ABI was 1.11-1.20) with prevalent MI,
stroke, and MI/stroke. Sex-specific models for MI, stroke, and
MI/stroke were also examined.
All statistical analyses were performed with PASW for
Windows (version 18.0; SPSS, Inc, Chicago, IL); SAS software
for Windows, version 9.3; and the R package (R Development
Core Team).
The authors had full access to and take full responsibility for
the integrity of the data. All authors have read and agree to the
manuscript as written.
Results
A total of 3,696,778 subjects underwent screening tests
from 2003 through 2008. Of these, 78,406 subjects
reported a history of prior revascularization for PAD, and
185,518 had incomplete ABI testing information. Figure 1
is a flow diagram of the subjects included in the current
analysis. Table I shows the baseline characteristics and
prevalence of risk factors in patients included in the
study. Compared with subjects with a normal ABI
(defined as ABI between 0.91 and 1.40), those with a
03/04/2014
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Volume 167, Number 4
Jones et al 501
Table I. Patient demographic and clinical characteristics
Age (y), mean (SD)
Female, %
Race
White
Black
Asian
Hispanic
Native American
Other
Body mass index, mean (SD)
Family history
Cardiovascular disease
(MI, stroke, or PAD)
Risk factors
Smoking
Former
Current
Never
Hypertension
Hyperlipidemia
Diabetes mellitus
Family history of
cardiovascular disease
Exercise
63.7(10.6)
64.3%
70.0 (11.0)
71.4%
63.2 (10.4)
64.4%
66.5 (10.7)
28.4%
67.2 (10.7)
65.6%
88.9%
3.1%
2.0%
2.5%
2.8%
0.6%
27.7(5.8)
85.9%
5.6%
1.4%
1.8%
4.6%
0.8%
28.3 (7.1)
89.0%
3.0%
2.1%
2.5%
2.7%
0.6%
27.7 (5.7)
91.1%
1.9%
1.4%
2.1%
3.0%
0.5%
28.2 (5.7)
88.7%
2.9%
1.4%
2.2%
4.0%
0.8%
27.7 (5.7)
23.1%
26.5%
22.4%
21.5%
48.4%
24.1%
25.0%
50.9%
63.7%
53.2%
10.8%
23.1%
28.6%
35.6%
35.8%
83.5%
58.5%
19.8%
26.5%
23.8%
24.4%
51.8%
62.6%
52.8%
10.2%
22.4%
24.1%
21.5%
54.4%
58.5%
53.7%
16.5%
21.5%
28.2%
29.4%
42.4%
69.4%
58.1%
14.7%
48.4%
49.0%
62.9%
64.6%
60.3%
62.3%
Co
Figure 2
Overall population Low ABI b0.90 Normal ABI 0.91-1.40 High ABI N1.40 Prior revascularization
(N = 3,696,778)
(n = 155,552)
(n = 3,221,971)
(n = 42,890)
for PAD (n = 78,406)
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Characteristic
Distribution of abnormal ABI results.
low ABI (b0.90) were older, more frequently female,
current smokers, and have diabetes mellitus and hypertension. Subjects with a high ABI (N1.40) were older,
more frequently male, and more likely to have diabetes
mellitus than those with a normal ABI.
Among 3,432,854 subjects with ABI information
available, 155,552 (4.2%) had an ABI b0.90, and 42,890
(1.1%) had an ABI N1.40 (Figure 1). When using a
traditional ABI cut-off for PAD (b0.90), there was a
significant association with prevalent MI (adjusted odds
ratio [OR] 1.67, 95% CI 1.63-1.71, P b .001), stroke (OR
1.77, 95% CI 1.72-1.82, P b .001), and MI/stroke (OR 1.71,
95% CI 1.67-1.74, P b .001). An ABI b0.90 was
significantly associated with MI, stroke, and MI/stroke
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Figure 3
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Prevalence of cardiovascular events (MI, stroke, MI/stroke) by ABI.
Table II. Cross-sectional association of MI and stroke with PAD and different intervals of ABI results
MI or stroke
OR
Stroke
95% CI
P
OR
95% CI
P
OR
95% CI
P
1.67-1.74
b.0001
1.63-1.71
b.0001
b.0001
b.0001
1.14-1.24
b.0001
1.77
1.0
1.30
1.72-1.82
1.17-1.27
1.67
1.0
1.19
1.22-1.38
b.0001
1.05-1.05
1.98-2.02
b.0001
b.0001
1.06
2.64
1.05-1.06
2.60-2.67
b.0001
b.0001
1.04
1.28
1.04-1.04
1.26-1.30
b.0001
b.0001
1.12-1.19
b.0001
0.99
0.95-1.02
.43
1.38
1.32-1.44
b.0001
1.29-1.32
1.22-1.25
1.42-1.46
1.34-1.38
1.86-1.91
0.92-0.94
3.09-3.15
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
1.37
1.30
1.45
1.31
2.41
0.98
3.30
1.35-1.39
1.28-1.32
1.43-1.47
1.29-1.33
2.38-2.45
0.96-0.99
3.26-3.34
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
1.14
1.11
1.37
1.42
1.27
0.84
3.16
1.12-1.17
1.09-1.13
1.34-1.40
1.39-1.45
1.25-1.29
0.82-0.85
3.11-3.22
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
2.35-2.86
2.16-2.51
2.20-2.47
1.90-2.10
1.84-1.99
1.49-1.58
1.20-1.24
1.05-1.08
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
2.12-2.66
2.01-2.39
2.00-2.29
1.80-2.01
1.79-1.96
1.52-1.63
1.22-1.27
1.07-1.10
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
b.0001
.02
.87
b.0001
0.94-1.00
0.97-1.04
1.20-1.31
.05
.86
b.0001
2.66
2.32
2.38
2.02
1.88
1.44
1.15
1.02
REF
1.00
1.02
1.32
2.33-3.04
2.09-2.57
2.20-2.58
1.89-2.17
1.77-2.00
1.38-1.51
1.12-1.18
1.00-1.04
0.94-1.00
0.97-1.03
1.23-1.33
2.37
2.19
2.14
1.90
1.87
1.57
1.25
1.09
REF
0.97
1.00
1.25
0.95-1.04
0.97-1.07
1.24-1.41
.86
.45
b.0001
Co
Model with low ABI, ABI 0.91-1.40, high ABI
ABI b0.90
1.71
ABI 0.91-1.40 (reference)
1.0
ABI N1.40
1.22
Clinical characteristics
Age (1 y)
1.05
Sex (M vs F)
2.00
Race (white, reference)
Black
1.15
Smoking (never, reference)
Current
1.31
Former
1.24
Diabetes mellitus
1.44
Hypertension
1.36
Hyperlipidemia
1.88
Routine exercise
0.93
Family history of cardiovascular disease
3.12
Interval ABI model
ABI b0.40
2.59
ABI 0.41-0.50
2.32
ABI 0.51-0.60
2.33
ABI 0.61-0.70
2.00
ABI 0.71-0.80
1.91
ABI 0.81-0.90
1.54
ABI 0.91-1.0
1.22
ABI 1.01-1.10
1.06
ABI 1.11-1.2
REF
ABI 1.21-1.3
0.97
ABI 1.31-1.4
1.00
ABI N1.4
1.28
MI
Abbreviations: M, male; F, female.
in both men (OR 1.62, 95% CI 1.57-1.68, P b .001 for MI,
OR 1.93, 95% CI 1.85-2.02, P b .001 for stroke, and OR
1.73, 95% CI 1.68-1.78, P b .001 for MI/stroke) and
women (OR 1.73, 95% CI 1.68-1.79, P b .001 for MI, OR
1.68, 95% CI 1.62-1.74, P b .001 for stroke, and OR 1.71,
95% CI 1.66-1.75, P b .001 for MI/stroke).
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Figure 4
Odds ratios for MI (A), stroke (B), MI/stroke (C) in men and women by ABI.
There was a significant association between ABI N1.40
and prevalent MI (OR 1.19, 95% CI 1.14-1.24, P b .001),
stroke (OR 1.30, 95% CI 1.22-1.38, P b .001), and MI/stroke
(OR 1.22, 95% CI 1.17-1.27, P b .001). An ABI N1.4 was
significantly associated with MI, stroke, and MI/stroke in
both men (OR 1.13, 95% CI 1.08-1.19, P b .001 for MI, OR
1.22, 95% CI 1.13-1.31, P b .001 for stroke, and OR 1.16, 95%
CI 1.11-1.21, P b .001 for MI/stroke) and women (OR 1.37,
95% CI 1.23-1.52, P b .001 for MI, OR 1.55, 95% CI 1.38-1.74,
P b .001 for stroke, and OR 1.42, 95% CI 1.30-1.54, P b .001
for MI/stroke).
Among 198,442 subjects with abnormal ABI (ABI b0.90
and N1.40), 11.0% had ABI b0.60, 23.7% had ABI between
0.60 and 0.80, 43.7% had an ABI between 0.80 and 0.90, and
21.6% had an ABI N1.40 (Figure 2). The prevalence of MI,
stroke, or MI/stroke by ABI value is shown in Figure 3. The
association of ABI level and prevalent MI, stroke, or MI/
stroke after multivariable adjustment is shown in Table II.
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The adjusted ORs for MI/stroke for different levels of
ABI compared with a reference level of 1.11 to 1.20
formed a reverse J-shaped curve for both women and
men (Figure 4). For levels of ABI b1.10, the ORs for MI,
stroke, and MI/stroke increased consistently with decreasing ABI.
Discussion
Limitations
The present study has several limitations. First, subjects
included in this analysis were a self-referred population
who paid for the screening testing. Not only are
symptomatic patients more likely to be evaluated in
clinical practice (rather than in this setting), but also cost
may also deter subjects from lower socioeconomic status
from undergoing screening via the Lifeline testing
process. These factors introduce the possibility of
significant referral bias, and therefore, our findings may
not be applicable to general clinical practice; however,
the prevalence of low ABI (ABI b0.90) in the current
report (4.8%) is very similar to the prevalence of low ABI
from the National Health and Nutrition Examination
Survey in 1999 to 2000 (4.5%). 22 Second, clinical
characteristics, comorbid characteristics, and prior cardiovascular disease were all self-reported variables in this
analysis and subject to recall bias and errors. Third,
symptom status was not assessed in this study. Finally, the
higher prevalence of women and lower representation of
minorities in our cohort are not representative of the US
population, yet the sheer number of women and
minorities adds significantly to the available literature
on the association of ABI and cardiovascular risk.
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Ankle-brachial index testing is a reliable, inexpensive
method to diagnose PAD. In the present study, we report
3 major findings related to ABI testing. First, the overall
proportion of abnormal ABI (b0.90 or N1.40) was 5.4% in
this self-referred cohort, with almost 50% having an ABI
between 0.81 and 0.90. Second, in subjects with an ABI
level b1.10, the odds of prior MI, stroke, or MI/stroke
were inversely proportional to the ABI value, whereas
subjects with an ABI N1.40 had higher odds of MI, stroke,
or MI/stroke. Finally, ABI levels were significantly
associated with prevalent MI, stroke, and MI/stroke in
separate sex-specific models.
In this study, we used the widely accepted ABI value of
b0.90 from clinical and epidemiologic studies as the
cutoff for a low ABI. An ABI b0.90 is associated with a
higher risk of future cardiovascular events and all-cause
mortality. 10,17 The current results confirm prior findings
that have designated low ABI as an accurate indicator of
systemic atherosclerosis and risk factor for cardiovascular
morbidity. 3,12,15,20 The consistency and power of the
graded relationship of a low ABI measurement with
prevalent MI, stroke, MI/stroke in this study of N3 million
subjects strengthen this evidence base, which was
observed after adjustment for known cardiovascular risk
factors such as diabetes mellitus, hypertension, and
hyperlipidemia. Our study also supports conclusions
from prior studies that high ABI (N1.40) is associated with
a higher cardiovascular risk. 4,13,21 In fact, in the current
study, patients with ABI N1.40 and between 0.91 and 1.00
have a similarly high odds of prevalent MI, stroke, and MI/
stroke, suggesting that added consideration is needed for
subjects with ABI measurements that lie outside the
traditional ABI cutoff points.
Our findings are similar to reports from prior smaller
studies. 3,15 In a study of 15,106 patients from the
Atherosclerosis Risk in Communities Study, 15 low ABI
was similarly associated with clinical coronary heart
disease, stroke, and measures of carotid and popliteal
atherosclerosis. Of note, a total of 454 subjects had a low
ABI in this study, and the authors used an ABI N1.3 as the
reference group. In 5,888 patients in the Cardiovascular
Health Study, 3 768 patients had an ABI b0.9, and these
patients were twice as likely to have prevalent cardiovascular disease at baseline when compared with those
with normal ABI. In addition to confirming the findings
from prior studies, the current results highlight the
graded relationship of ABI levels b1.10 with prevalent
cardiovascular disease. Our results also add to an evolving
evidence base on the association of prior PAD revascularization and cardiovascular risk, a fact that has recently
been incorporated into the design of recent clinical trials.
A significant strength of the current study is the
inclusion of N2 million women and 1 million men.
Numerically, more women had low ABI (b0.90), whereas
more men had high ABI (N1.40). The reverse J-shaped
curve demonstrates the adjusted, nonlinear relationship
of ABI with prevalent MI, stroke, and MI/stroke in both
sexes. The magnitude of the association of ABI with
prevalent cardiovascular disease was similar in both men
and women.
Conclusions
We report that low and high ABI measurements are
significantly associated with self-reported history of MI,
stroke, and MI/stroke even after the adjustment for
cardiovascular risk factors. Furthermore, the odds of MI,
stroke, and MI/stroke are increasingly higher with
decreasing ABI levels b1.10, a finding that was consistent
in sex-specific models. These results highlight the clinical
importance of ABI levels in risk of systemic atherosclerosis and cardiovascular disease and the need to develop
strategies to improve cardiovascular morbidity and
mortality in these patients.
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Jones et al 505
Acknowledgements
This work has used computing resources at the High
Performance Computing Facility of the Center for Health
Informatics and Bioinformatics at New York University
Langone Medical Center. We would like to acknowledge
the production of figures by Anthony Doll, Graphics
Manager at the Duke Clinical Research Institute.
Disclosures
There are no potential conflicts of interest. The authors
gratefully acknowledge the participation and generosity of
Life Line Screening (Cleveland, OH), who provided these
data free of charge for the purposes of research and with no
restrictions on its use for research or resultant publications.
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