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Circulation. 2005 November 29; 112(22): 3501–3508. doi:10.1161/CIRCULATIONAHA.105.548099.

Exertional Leg Pain in Patients With and Without Peripheral

Arterial Disease
Jimmy C. Wang, MD, Michael H. Criqui, MD, MPH, Julie O. Denenberg, MA, Mary M.
McDermott, MD, Beatrice A. Golomb, MD, PhD, and Arnost Fronek, MD, PhD
University of California, San Diego, School of Medicine (J.C.W.) and Departments of Family and
Preventive Medicine (M.H.C., J.O.D.), Medicine (M.H.C., B.A.G.), and Surgery and
Bioengineering (A.F.), La Jolla, Calif; and the Feinberg School of Medicine, Northwestern
University, Departments of Medicine and Preventive Medicine, Chicago, Ill (M.M.M.)

Abstract
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Background—Although exertional leg pain is a hallmark of peripheral arterial disease (PAD)

and can occur in persons without PAD, symptom variation has received inadequate attention.

Methods and Results—Three cohort studies were combined for cross-sectional analysis. The
San Diego Claudication Questionnaire assessed exertional leg pain. PAD was defined as ankle
brachial index (ABI) ≤0.90 or history of lower-extremity revascularization. Of 3658 subjects,
3629 were analyzed after exclusions. Of these, 24.1% had PAD in 1 or both legs. There was a
stepwise decrease in average ABI, from no pain to pain on exertion and rest, noncalf pain, atypical
calf pain, and classic claudication (P=0.002). When stratified by PAD, this trend was no longer
significant. Legs with ABIs >0.90 and revascularization had pain distributions intermediate
between that of normal legs (ABI, 1.00 to 1.39) and legs with ABIs ≤0.90. Compared with normal
legs, legs with low-normal (0.91 to 0.99) and high-normal (≥1.40) ABIs had higher pain rates,
suggesting borderline disease and vascular stiffness, respectively. Multivariable logistic regression
models showed that ABI was a strong correlate of pain category throughout the ABI range.
Independently of ABI, age, male sex, diabetes, smoking history, high body mass index,
myocardial infarction, and previous revascularization were all significant correlates of exertional
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leg pain.

Conclusions—No category of exertional leg pain was sufficiently sensitive or specific for
routine PAD diagnosis. Legs with low-normal and high-normal ABIs appeared to have ischemic
leg pain; thus, a “normal ABI” is likely to range from 1.00 to 1.39. In addition to ABI, several risk
variables were independent correlates of exertional leg pain.

Keywords
claudication; epidemiology; exercise; peripheral vascular disease

© 2005 American Heart Association, Inc.

Correspondence to: Michael H. Criqui, MD, MPH, Professor, Department of Family and Preventive Medicine, 9500 Gilman Dr, La
Jolla, CA 92093-0607. mcriqui@ucsd.edu.
 Wang et al. Page 2

Peripheral arterial disease (PAD) is a highly prevalent condition in middle-aged and older
persons that frequently goes undiagnosed.1 PAD is often undertreated when diagnosed
relative to other manifestations of cardiovascular disease.1–5 PAD affects ≈8 million people
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in the United States and portends an increased risk of myocardial infarction (MI) and stroke,
critical leg ischemia and amputation, and overall mortality, as well as a compromised quality
of life.2–6

PAD classically presents as intermittent claudication.7 Reduced perfusion of leg muscles

(mainly calf, occasionally thigh or buttock) secondary to atherosclerotic narrowing of
peripheral arteries, aggravated by exercise, leads to pain that typically subsides within 10
minutes of rest. However, up to 90% of persons with PAD in the general population do not
have classic symptoms of intermittent claudication.1 For example, in the multicenter
PARTNERS study, 29% of the 6417 patients had PAD, but only 11% of PAD patients had
classic claudication.1 Fully one third of PAD patients reported no leg pain at all, whereas the
remaining 55% had atypical symptoms.

Patients with PAD span the spectrum from asymptomatic to ischemic rest pain and
threatened limb loss. Pain secondary to PAD may become misconstrued as an unrelated
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condition such as arthritis or sciatica. Elderly patients may also disregard leg pain as a
normal condition that accompanies old age. Alternately, physical inactivity or comorbid
diseases limiting ambulation may prevent even patients with severe PAD from reaching an
ischemic threshold.8 It is important to better understand the pain symptomatology in PAD to
improve diagnosis and initiation of measures to mitigate symptoms, progression, and its
associated risk for ischemic events.

To evaluate exertional leg pain in patients with and without PAD, we combined data from 3
studies and used the San Diego Claudication Questionnaire (SDCQ)9 to systematically
group exertional leg pain into 5 categories (no pain, pain on exertion and rest, noncalf pain,
atypical calf pain, and classic claudication). We used the ankle brachial index (ABI) and
history of revascularization to define PAD. Finally, we assessed whether comorbidities such
as diabetes, stroke, MI, a high body mass index (BMI) and a history of smoking were
independently related to exertional leg pain in either PAD or non-PAD patients. We
hypothesized that patients with PAD would report proportionately more classic claudication
symptoms than patients without PAD.
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Methods
Study Populations
This was a cross-sectional study combining subjects from 3 prior studies. Two were clinical
cohorts enriched with vascular patients, and 1 was a free-living population. All 3 studies
were approved by their respective institutional review committees, and all subjects involved
gave informed consent.

San Diego Veterans Administration Study—Data from the San Diego Veterans
Administration (SD-VA) study were collected between 1990 and 1994 at the San Diego
Veterans Administration Medical Center and the University of California, San Diego

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Medical Center vascular laboratories. Subjects who had visited the vascular laboratories in
these 2 hospitals in the prior 10 years were invited to return for a noninvasive vascular
examination involving the lower extremities. Detailed methods have been published.10
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Chicago Study—Subjects from this study were recruited from 3 noninvasive vascular
laboratories and from a large general medicine practice in the Chicago area between 1998
and 2000. Detailed methods have been published.8

San Diego Population Study—The San Diego Population Study (SDPS) consisted of
subjects for whom data were collected between 1995 and 1999. This cohort consisted of
current, former, and retired employees of the University of California, San Diego and their
respective spouses or significant others who were randomly selected from a database by a
computer. Selection occurred within each category of age, ethnicity, and gender for the
purposes of oversampling minorities and women to increase the underrepresented
populations. Detailed methods have been published.11

Questionnaires
The SDCQ, which uniquely allows ipsilateral determination of pain symptoms, was used in
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all 3 studies to assess leg pain.9 The laterality of the pain (right, left, or both legs) and
location (calf, thigh, or buttock) were noted. Symptoms (or no ambulatory pain) were
classified separately for each leg into 5 categories: No pain, pain on exertion and rest,
noncalf pain, atypical calf pain, and classic claudication.9 The details of classification are
given in Table 1. Note that “pain on exertion and rest” is any exercise leg or buttock pain
that at least sometimes occurs at rest, as distinguished from “rest pain,” which usually refers
to severe resting ischemic pain in severe PAD.

Each of the 3 studies had questionnaires that asked about catheter-based or surgical
interventions for PAD, as well as a history of MI or stroke. Age, gender, ethnicity, diabetes,
cigarette smoking, and statin use history were determined with standard questionnaires. BMI
was calculated as weight in kilograms divided by height in meters squared.

ABI Measurement
ABI was measured with accurate, validated methods that were comparable across the 3
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studies.

SD-VA Study—Trained vascular laboratory personnel administered noninvasive vascular

examinations, which included segmental systolic blood pressure measurements at 5
segments of the lower extremities, including the ankle, with a photoplethysmographic
sensor. Bilateral brachial systolic pressures also were measured with a
photoplethysmographic sensor.

Chicago Study—Bilateral systolic blood pressure measurements at the brachial arteries,

posterior tibial (PT) arteries, and dorsalis pedis (DP) arteries with a hand-held continuous-
wave Doppler were performed twice for each artery.

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SDPS—The noninvasive vascular examinations included systolic blood pressure

measurements of the brachial arteries and PT arteries bilaterally with a hand-held
continuous-wave Doppler. If a pressure in a PT artery could not be obtained, the DP artery
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was used. Each ankle artery was assessed twice.

PAD Definition
For these analyses, the ABI for each leg was defined as the highest (or highest average if
measured twice) ankle pressure (DP or PT) of each leg divided by the highest (or highest
average if measured twice) brachial pressure. Support for averaging the DP and PT pressure
in calculating ABI has been published.12 However, DP and PT pressures were not measured
for every subject in the SD-VA and SDPS cohorts; therefore, the highest leg pressures were
used for equivalence among the 3 cohorts. Legs with ABIs ≤0.90 or with higher ABIs but
previous intervention (surgery or angioplasty) for PAD in that leg were defined as PAD.

Exclusion Criteria
Initially, a total of 3658 subjects were examined before exclusion. Because ABI
measurements were central to the purposes of this study, subjects with absent or incomplete
ABI measurements in 1 or both legs were excluded (n=29), leaving 3629 subjects for
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analysis pertaining to the whole person. Amputation in the lower extremities, inability of the
technician to obtain a reliable systolic pressure reading from the upper extremities (brachial
artery) or the lower extremities (PT or DP arteries), or patient refusal typically accounted for
the missing or incomplete ABIs.

Analysis pertaining to individual legs used slightly different exclusion criteria. Only legs
without ABI data were excluded from leg-specific analysis, regardless of whether ABI data
were available on the contralateral leg. Of a possible 7316 legs (3658×2), 37 had missing
ABIs, leaving 7279 legs available for leg-specific analyses.

Statistical Analyses
All statistical analyses were performed on Microsoft Excel 2000 and SAS version 8.1
software for the personal computer. Leg-specific, age- and sex-adjusted frequency
distributions of pain categories were initially performed for each cohort individually and
then for all subjects combined. Leg-specific logistic regression models, adjusted by the
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generalized estimating equation technique to account for the intraindividual leg correlation,
were computed to assess independent relationships of selected risk factors to the 5 pain
categories. Each of the 4 leg pain categories was separately compared with the reference
category of no pain. Potential risk factors analyzed were age, sex, ethnicity, ABI, diabetes,
smoking history, statin use, BMI, MI, stroke, and intervention for PAD (revascularization).
Age and BMI were modeled as continuous variables; all other variables were defined
categorically. ABI was defined as a 4-category variable: ≤0.70, 0.71 to 0.99, 1.00 to 1.39,
and ≥1.40, with the normal category, 1.00 to 1.39, as the reference group. Male was the
reference variable for sex, and non-Hispanic white was the reference variable for ethnicity.

Pain concordance was defined in the following manner: (1) Concordance for no pain meant
that subjects had no exercise pain in either leg, (2) pain category concordance meant that the

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same pain category was evident in both legs, (3) unilateral pain was pain in only 1 leg, and
(4) pain category discordance indicated different pain categories in the 2 legs.
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Results
Table 2 describes the demographic and clinical characteristics of the participants in the 3
cohorts. Before exclusion, the 508 subjects from the SD-VA clinical study comprised 448
men and 60 women, with a mean age of 68.6 years. The ethnic distribution was 87.2% non-
Hispanic white, 5.5% Hispanic, 4.5% black, and 2.8% other. In this study, 65.9% had PAD.
In the Chicago clinical study, there were a total of 740 subjects; 416 were male and 324
were female, with a mean age of 70.9 years. This group was 78.1% non-Hispanic white,
1.5% Hispanic, 17.2% black, and 3.1% other. In this group, 62.4% had PAD. Of the 2410
subjects in the SD population study, 9 subjects had missing ABIs in both legs and were
excluded from demographic data, leaving 2401 subjects for analysis. Of these, 824 were
male and 1577 were female, with an overall mean age of 59.3 years. This population
consisted of 59.7% non-Hispanic white, 14.7% Hispanic, 13.5% black, and 12.1% other
(primarily Asian). In this study, 3.5% had PAD.

A total of 3629 subjects remained after exclusions; 1671 (46.0%) were male, and 1958
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(54.0%) were female. Their mean age was 62.9 years, and the ethnic distribution was as
follows: 67.2% non-Hispanic white, 10.7% Hispanic, 13.0% black, and 9.0% other
(primarily Asian). Of these subjects, 24.1% had definable PAD in 1 or both legs; 18.9% of
the 7279 total legs used for leg-specific analysis had PAD. Note that in the clinical cohorts,
most subjects had PAD and, as expected, had much higher rates of cigarette smoking,
diabetes, prior MI, and prior stroke. The low rates of statin use in the SD-VA study reflect
the fact that the data were collected in 1990 to 1994, when lipid therapy was less common
than in current clinical practice.

Table 3 shows leg-specific, age- and sex-adjusted pain distributions in the SD-VA, Chicago,
and SDPS cohorts individually and combined stratified by PAD. As expected, the SD-VA
and Chicago studies had a much higher proportion of legs with pain symptoms. In subjects
with PAD, the SD-VA and Chicago studies are similar in the distribution of the 4 pain
categories, with classic claudication being the most common, followed by pain on exertion
and rest. In contrast, subjects with PAD in the SDPS were more likely to complain of pain
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on exertion and rest or atypical calf pain than classic claudication.

Compared with the pain distribution in the PAD group, the non-PAD group had a greater
proportion of no pain and a smaller proportion of pain symptoms. However, exertional leg
pain was reported in 56%, 35%, and 12% of the non-PAD legs in the SD-VA, Chicago, and
SDPS studies, respectively. Pain (also occurring) at rest was the most common pain
symptom in legs without PAD in all 3 studies. The similarity of pain distributions in the SD-
VA and Chicago studies and the lower pain rates in the free-living population are apparent.

Table 4 shows person-specific pain concordance in subjects with unilateral PAD, bilateral
PAD, and no PAD. As expected, subjects without PAD were most likely to report
concordance for no pain (79%), and subjects with bilateral PAD were most likely to report

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concordant pain (59%). However, subjects with unilateral PAD were more likely to report
bilateral (42%) than unilateral (29%) pain. In addition, in these 29% (n=80) of subjects with
unilateral PAD and unilateral pain, PAD and pain were in the same leg in 69 subjects but in
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different legs in 11 subjects. Pain category discordance was reported in only 12.5% of
subjects with either unilateral or bilateral PAD.

Figure 1 shows the leg-specific age- and sex-adjusted mean ABI for each pain category for
all legs and stratified by PAD presence. For all legs, there was a statistically significant
stepwise decrease in the mean ABI from no pain to pain on exertion and rest, noncalf pain,
atypical calf pain, and classic claudication (P=0.002) by simple linear regression models for
monotonicity. When stratified by PAD presence, the tendency to trend was weak. Simple
linear models did not support a trend for PAD legs only (P=0.09) and non-PAD legs only
(P=0.71).

Table 5 shows leg-specific pain category distribution by PAD presence and severity with 0.1
ABI increments. As the ABI increased, the proportion of legs reporting no pain increased,
from 17% for ABIs ≤0.40 to 87% for ABIs in the 1.20 to 1.29 interval. However, as the ABI
increased further above 1.30, the proportion with no pain progressively decreased to 61%
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with an ABI ≥1.50. The proportion of subjects with classic claudication followed a similar
pattern. More than 40% of subjects with ABIs <0.60 had classic claudication compared with
22% to 36% in those with an ABI between 0.60 and 0.89. The lowest rate of classic
claudication was in the 1.00 to 1.39 ABI range (1.0% to 2.7%). However, normal ABIs
(>0.90) that were either higher or lower than the 1.00 to 1.39 range showed higher levels of
classic claudication.

Figure 2 shows leg-specific pain categories in 5 ABI groups: ≤0.90, >0.90 but with prior
PAD intervention, 0.90 to 0.99, 1.00 to 1.39, and ≥1.40. More than half the group with prior
intervention and a normal ABI had exertional leg pain, and 15% had classic claudication.
The 0.90 to 0.99 and ≥1.40 ABI groups had strikingly similar pain category distributions.
Compared with subjects with ABIs of 1.00 to 1.39, these 2 “borderline” groups had fewer
subjects with no pain and higher rates in each of the 4 pain categories, the most marked
difference being in the classic claudication category.

A leg-specific logistic multivariable regression model adjusted by the generalized estimating

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equation technique for intraindividual leg correlation was constructed to assess the
independent contributions of a number of selected risk factors to the different categories of
pain. Preliminary models showed similar results in the 3 cohorts, so they were combined for
analysis. Table 6 shows odds ratios (ORs) and probability values.

Age was associated with all pain types except exercise and rest. Women were less likely to
report pain except for noncalf pain. Compared with non-Hispanic whites, other ethnic
groups reported less atypical calf pain and classic claudication.

As expected, both lower ABI categories, ≤0.7 and 0.71 to 0.99, were independently related
to all pain groups, with the strongest associations for atypical calf pain and classic
claudication. A high ABI (≥1.40) was independently related to classic claudication, with
positive nonsignificant ORs for the other pain categories, suggesting that arterial stiffness

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masked many PAD cases. Diabetes independently contributed to all pain categories except
noncalf pain, in which it was inversely associated. Current smoking was a strong correlate of
all pain groups, and ex-smoking was correlated with classic claudication. Statin use was
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inversely associated with pain on exertion and rest but positively correlated with atypical
calf pain, possibly related to myalgia. Higher BMI was independently associated with 2 of
the 4 pain groups. A history of MI was related to both exercise/rest pain and classic
claudication.

Finally, previous intervention for PAD was positively related to all pain types except
atypical calf pain. Note that this result was independent of the ABI level after intervention
and the other variables in Table 6.

Discussion
Our results indicate that leg pain is common in PAD patients and can present in atypical
ways. In addition, leg pain is not uncommon in patients without definitive PAD, particularly
in those with borderline ABI values. These data show that in patients with normal ABIs,
pain is still inversely related to the ABI level, at least to an ABI level of 1.40, where arterial
stiffness may result in a false-negative ABI.
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These data suggest that patients who complain of bilateral leg pain, whether or not it is PAD
related, have a very strong tendency to report the same type of pain in both legs.
Interestingly, in the 80 patients with unilateral PAD and unilateral pain, the pain was not in
the leg with PAD 13.8% of the time. This finding underscores the limitation of claudication
questionnaires that do not assess symptoms separately for each leg or limitations in our own
understanding of pain-processing pathways.

Taking all patients combined, there was a stepwise decrease in average ABI from no pain,
pain on exertion and rest, noncalf pain, atypical calf pain, and classic claudication (Figure
1). This corresponds with the clinical concepts that the pain on exertion and rest groups have
a significant number of cases of nonvascular pain, that the noncalf pain group has proximal
ischemia with some reconstitution distally, and that the atypical calf pain group has on
average less severe disease than the classic claudication group, because the most common
difference between the former and latter groups is walk-through pain in the former.
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In a recent study of PAD patients who had previously come to clinical attention, there was
little correlation between the ABI and leg pain category.10 Similarly, in our data for either
PAD patients or non-PAD patients separately, there was only a weak correlation between
ABI and leg pain category. However, when these 2 groups were combined, there was a
statistically significant stepwise decrease in ABI between pain groups. This finding can be
explained by the effects of range restriction, whereby a larger ABI gradient exists between
pain categories when considering all patients versus the non-PAD only or PAD only groups
that are inherently defined by ABI and restricted to ABI >0.90 and ABI ≤0.90 or history of
prior revascularization, respectively.

We found that 63.6% of all legs had ABIs in the 1.10 to 1.30 range. The average ABI in
non-PAD persons has been reported to be ≈1.15, near the middle of this range.13 The 1.10

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to 1.19 and 1.20 to 1.29 ABI categories had similar high rates of no pain (85.3% and 87.4%)
and identical low classic claudication rates (0.8%). As one moves above and below these
categories in 0.1 ABI increments, the no pain rates decrease and classic claudication rates
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increase, although the immediately adjacent categories, 1.00 to 1.09 and 1.30 to 1.39,
maintain high no pain rates (≈80%) and low classic claudication rates (≈2%).

From the 5 ABI categories created (Figure 2), it is striking that high and low ABIs outside
the 1.00 to 1.39 range show more pain and more classic claudication. Patients with PAD and
ABIs >0.90 after intervention had pain intermediate between the groups outside the 1.00 to
1.39 range and those with ABIs ≤0.90, suggesting on average benefit from intervention but
short of restoration to normal. The pain distributions in the low-normal (0.90 to 0.99) and
high-normal (≥1.40) ABI categories were strikingly similar. This finding could suggest early
or borderline ischemia in the low-normal group, with a further ABI drop perhaps inducible
with exercise, and possibly false-negative ABIs resulting from stiff or incompressible
arteries in the high-normal group. A recent article from a large population study reported
that in men, compared with an ABI group of 1.10 to 1.29, there were significantly higher
carotid intimal medial thickness and coronary calcium scores in the 0.90 to 0.99 ABI group
and significantly higher coronary calcium scores in the ≥1.30 ABI group.14 The Strong
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Heart Study by Resnick et al15 demonstrated that in a population-based setting, individuals

in the high ABI groups (ABI ≥1.40) had associated mortality rates similar to those of low
ABI groups (ABI <0.90), whereas mortality rates were uniformly low in the 1.00 to 1.39
ABI range. Our data, taken in conjunction with the Strong Heart Study data, suggest that the
definition of a normal ABI should be revised from >0.90 to the range of 1.00 to 1.39.

The relationship between low ABI and leg pain persisted in multivariable analysis for all
pain groups, and high ABI showed an independent relationship with classic claudication.
Multiple other conditions were associated with leg pain symptoms even after consideration
of the ABI. Age, gender, ethnicity, diabetes, cigarette smoking, and previous intervention
for PAD each were significantly and independently associated with at least 3 of the 4 pain
categories. Such variables should be considered when the patient presenting with leg pain is
evaluated.

Diabetics are less likely to report pain symptoms in acute MI but are more likely to report
nonpain symptoms, including dyspnea, cough, weakness, and nausea.16 Conversely, in our
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study, diabetes was associated with more leg pain for 3 of the 4 pain categories after
adjustment for ABI level, including high ABI, but diabetes showed an inverse association
with noncalf pain. This latter result was highly significant and consistent with previous
observations showing a greater degree of infrageniculate PAD in diabetes17,18 and the lack
of an independent association between diabetes and aortoiliac disease.18 The increased risk
of diabetes for the other 3 pain categories could in part reflect peripheral neuropathy.

This study has several limitations. First, we pooled data from 3 cohort studies with different
demographic profiles and from different time periods. The SD-VA study had a higher
proportion of male subjects than the Chicago study, but these 2 studies had similar
demographic profiles and drew subjects primarily from patient populations with leg pain.
SDPS involved somewhat younger and healthier subjects with a higher proportion of

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women. However, all comparisons were adjusted for the age and sex differences; all 3
cohort studies were evaluated with the same questionnaire (SDCQ); and ABI calculations
were consistent between the 3 cohorts. In addition, had exercise ABI been routinely
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performed, particularly in subjects with borderline ABIs, many persons with normal ABIs
undoubtedly would have shown an ankle pressure decrease with exercise, which would help
explain exercise leg pain in patients with normal ABIs.

In conclusion, exertional leg pain is a common finding in adult populations, and although it
is more common in PAD patients, no category of exertional leg pain is sufficiently sensitive
or specific to be reliable for PAD diagnosis. When patients report exertional leg pain
bilaterally, they nearly always report the same pain category in both legs. In the population,
there is a stepwise decrease in the ABI as one moves from reports of no pain to pain on
exertion and rest, non-calf pain, atypical calf pain, and classic claudication. The ABI
predicts the probability of pain throughout the ABI range, and age, sex, ethnicity, diabetes,
cigarette smoking, BMI, previous MI, and previous lower-extremity intervention for PAD
are all independently associated with exertional leg pain. Finally, a normal ABI is probably
best defined as between 1.00 to 1.39.
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Acknowledgments
This research was supported by National Institutes of Health grants HL-07491, HL-42973, HL-53487 and
R01HL-58099; NIH-NCRR General Clinical Research Center Program grant MOI RR-00827; and grant RR-00048
from the National Center for Research Resources, NIH. We thank Drs Anthony Gamst and Matthew Allison for
helpful suggestions on the manuscript.

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Figure 1.
Leg-specific age- and sex-adjusted mean ABI by leg pain category.
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Figure 2.
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Leg-specific age- and sex-adjusted pain distributions for 5 distinct subgroups by ABI and
intervention history.
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TABLE 1

Pain Characteristics Assessed by the SDCQ

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Pain Category Pain Characteristics

No pain No pain in either leg or buttock on walking
Pain on exertion/rest Pain in either leg or buttock on walking
Pain sometimes begins standing still or sitting
Noncalf Pain Pain in thigh or buttock region on walking
Pain does not begin standing still or sitting
Pain is not in calf region
Atypical calf pain Pain in calf region on walking
Pain does not begin standing still or sitting
Pain differs from classic claudication pain
Classic claudication Pain in calf region on walking
Pain does not begin standing still or sitting
Pain does not disappear during walk
Pain during walk causes subject to halt or slow down
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Pain is lessened or relieved within 10 min if walking is halted

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TABLE 2

Demographic and Clinical Characteristics of Study Subjects in 3 Study Populations

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SD-VA Study (n=508)* Chicago Study (n=740)† SDPS (n=2401)‡

Mean age, n (SD) 68.6 (9.1) 70.9 (8.4) 59.3 (11.4)
Mean BMI, n (SD) 27.3 (8.0) 27.1 (6.1) 27.0 (5.3)
Male, % 88.2 56.2 34.3
White, % 87.2 78.1 59.7
Hispanic, % 5.5 1.5 14.7
Black, % 4.5 17.2 13.5
Other, % 2.8 3.1 12.1
Diabetic, % 31.1 27.6 5.2
Prior stroke, % 18.3 9.5 1.1
Prior MI, % 26.9 23.1 2.1
Smoke now, % 29.9 16.2 6.0
Quit smoking, % 55.7 60.1 43.3
Never smoked, % 14.4 23.7 50.7
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Statin use, % 6.9 39.3 7.3

Subjects with PAD,§ % 65.9 62.4 3.5

Legs with PAD,§ % 55.0 47.1 2.7

*
Fifteen legs were excluded from leg-specific analysis and 15 individuals were excluded from individual-specific analysis because of absent ABI
data in 1 leg.
†
One leg was excluded from leg-specific analysis and 1 individual was excluded from individual-specific analysis because of absent ABI data in 1
leg.
‡
Thirteen total individuals were excluded from person-specific analysis in the SDPS: 9 because of absent ABI measurement data in both legs, 3
because of absent data in 1 leg, and 1 because of absent data from the SDCQ pertaining to leg pain.
§
PAD is defined as legs with ABI ≤0.90 or previous intervention; non-PAD is defined as legs with ABI >0.90 without previous intervention.
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TABLE 3

Leg-Specific Age- and Sex-Adjusted Pain Distributions Stratified by PAD

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SD-VA Study Chicago Study SDPS Combined

PAD group
Total legs, n 551 783 131 1465
No pain, % 22.3 30.4 56.0 30.1
Pain on exertion/rest, % 18.5 17.4 22.5 18.2
Noncalf pain, % 5.0 3.8 3.9 4.2
Atypical calf pain, % 16.6 16.2 12.8 16.0
Classic claudication, % 37.6 32.2 4.8 31.4
Non-PAD group
Total legs, n 450 696 4667 5813
No pain, % 44.1 65.3 88.8 81.8
Pain on exertion/rest, % 28.8 20.0 8.4 11.7
Noncalf pain, % 2.1 2.1 0.8 1.1
Atypical calf pain, % 12.9 6.0 1.6 3.2
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Classic claudication, % 12.1 6.6 0.4 2.2

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TABLE 4

Person-Specific Age- and Sex-Adjusted Pain Concordance Stratified by PAD

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SD-VA Study Chicago Study SDPS Combined

Unilateral PAD
Total subjects, n 109 140 39 288
Concordance for no pain, % 30.2 20.1 52.8 28.2
Pain category concordance, % 50.0 42.1 18.0 41.4
Unilateral pain, % 18.9 35.0 27.3 28.4
Pain category discordance, % 0.7 2.9 2.0 2.0
Bilateral PAD
Total subjects, n 216 321 46 583
Concordance for no pain, % 13.0 18.7 44.6 19.0
Pain category concordance, % 73.9 53.1 34.0 58.3
Unilateral pain, % 12.5 24.9 21.8 20.6
Pain category discordance, % 0.6 3.3 0.0 2.1
No PAD
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Total subjects 168 278 2312 2758

Concordance for no pain, % 39.0 62.5 84.6 78.9
Pain category concordance, % 49.8 23.4 6.4 11.4
Unilateral pain, % 10.0 13.3 8.6 9.2
Pain category discordance, % 1.1 0.8 0.3 0.4
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TABLE 5

Leg-Specific Age- and Sex-Adjusted Pain Distributions for Combined Studies by 0.1 ABI Increments*

ABI
Wang et al.

Pain Category ≤0.40 0.40–0.49 0.50–0.59 0.60–0.69 0.70–0.79 0.80–0.89 0.90–0.99 1.00–1.09 1.10–1.19 1.20–1.29 1.30–1.39 1.40–1.49 ≥ 1.50 Total
Legs, n 47 120 244 265 327 312 699 1762 2122 956 193 48 33 7128
No pain, % 17.2 16.7 23.7 21.8 33.4 38.7 67.0 81.6 84.4 87.1 79.7 67.8 61.2 5136
Pain on exertion/rest, % 29.6 16.7 16.4 19.8 19.8 20.9 16.1 12.4 10.7 8.7 14.1 16.1 21.5 924
Noncalf pain, % 0.0 4.7 2.2 5.0 2.7 3.2 1.6 0.9 1.1 1.2 1.0 4.1 0.0 110
Atypical pain, % 12.0 16.1 16.3 17.9 16.0 15.3 8.4 2.8 2.5 2.0 2.6 6.1 2.7 399
Classic claudication, % 41.5 45.9 41.5 35.5 28.1 21.9 7.0 2.3 1.2 1.0 2.6 5.9 14.8 559

*
Legs with intervention and an ABI >0.90 were excluded.

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TABLE 6

Leg-Specific Generalized Estimating Equation Logistic Regression Analysis Showing ORs for Independent
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Predictors of Pain Category Versus the Reference Group of No Pain

Pain on Exertion/Rest Atypical Calf Pain

Independent Variable (n=950) Noncalf Pain (n=124) (n=409) Classic Claudication (n=580)

Age (10 y)* 1.06 1.31¶ 1.16¶ 1.35**

Female† 0.77# 0.85 0.74¶ 0.56**

Hispanic‡ 1.35¶ 0.35 0.43¶ 0.31¶

Black‡ 0.89 0.72 0.64¶ 0.52#

Other‡ 1.13 0.46 0.48¶ 0.47¶

ABI ≤0.70§ 2.34** 4.95** 10.18** 9.63**

ABI 0.71–0.99§ 1.54** 2.13# 4.09** 3.79**

ABI ≥1.4§ 1.39 3.33 1.44 2.46¶

Diabetes 2.01** 0.44¶ 2.10** 1.82**

Smoke now|| 2.91** 2.92# 2.19** 6.03**

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Quit smoking|| 1.16 1.67 1.33 2.70**

Statins 0.73¶ 1.11 1.47¶ 1.28

BMI (5 units)* 1.34** 1.33# 1.08 1.11

Stroke 1.44 1.85 0.85 1.53

MI 1.61# 1.83 1.30 2.49**
Intervention 1.37¶ 2.75** 0.91 1.51¶¶

n=5180.
*
Age and BMI are continuous variables; all other variables are defined categorically.
†
Female sex variable is compared to male reference group.
‡
Ethnicity variables are compared to non-Hispanic White reference group.
§
ABI categorical variables are compared to the 1.00 –1.39 reference group.
||
Smoke Now and Quit Smoke are compared to No Smoke reference group.
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¶
P<0.05;
#
P<0.01;
**
P<0.001. Note that the generalized estimating equation logistic model shows the independent contribution of each variable to each leg pain
category simultaneously adjusted for each of the other variables.

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