McDermott MM, Liu K, Greenland P, Guralnik JM, Criqui MH, Chan C, Pearce WH, Schneider JR, Ferrucci L, Celic L, Taylor LM, Vonesh E, Martin GJ, Clark E. Functional Decline in Peripheral Arterial DiseaseAssociations With the Ankle Brachial Index and Leg Symptoms. JAMA. 2004;292(4):453-461. doi:10.1001/jama.292.4.453
Author Affiliations: Departments of Medicine (Drs McDermott, Greenland, and Martin and Ms Celic) and Preventive Medicine (Drs McDermott, Liu, Greenland, and Vonesh and Ms Chan) and Division of Vascular Surgery, Department of Surgery (Drs Pearce and Schneider), Northwestern University Feinberg School of Medicine, Chicago, Ill; Laboratory of Epidemiology, Demography, and Biometry (Dr Guralnik) and Laboratory of Clinical Epidemiology (Dr Ferrucci), National Institute on Aging, Bethesda, Md; Department of Family and Preventive Medicine, University of California at San Diego (Dr Criqui); Division of Vascular Surgery, Department of Surgery, Evanston/Northwestern Hospital, Evanston, Ill (Dr Schneider); Oregon Health and Science University, Portland (Dr Taylor); and Division of Vascular Surgery, Department of Surgery, Catholic Health Partners, Chicago, Ill (Dr Clark).
Context Among individuals with lower-extremity peripheral arterial disease (PAD),
specific leg symptoms and the ankle brachial index (ABI) are cross-sectionally
related to the degree of functional impairment. However, relations between
these clinical characteristics and objectively measured functional decline
Objective To define whether PAD, ABI, and specific leg symptoms predict functional
decline at 2-year follow-up.
Design, Setting, and Participants Prospective cohort study among 676 consecutively identified individuals
(aged ≥55 years) with and without PAD (n = 417 and n = 259, respectively),
with baseline functional assessments occurring between October 1, 1998, and
January 31, 2000, and follow-up assessments scheduled 1 and 2 years thereafter.
PAD was defined as ABI less than 0.90, and participants with PAD were categorized
at baseline into 1 of 5 mutually exclusive symptom groups.
Main Outcome Measures Mean annual changes in 6-minute walk performance and in usual-paced
and fast-paced 4-m walking velocity, adjusted for age, sex, race, prior-year
functioning, comorbid diseases, body mass index, pack-years of cigarette smoking,
and patterns of missing data.
Results Lower baseline ABI values were associated with greater mean (95% confidence
interval) annual decline in 6-minute walk performance (−73.0 [−142
to −4.2] ft for ABI <0.50 vs −58.8 [−83.5 to −34.0]
ft for ABI 0.50 to <0.90 vs −12.6 [−40.3 to 15.1] ft for ABI
0.90-1.50, P = .02). Compared with participants without
PAD, PAD participants with leg pain on exertion and rest at baseline had greater
mean annual decline in 6-minute walk performance (−111 [−173 to
−50.0] ft vs −8.67 [−36.9 to 19.5] ft, P = .004), usual-pace 4-meter walking velocity (−0.06 [−0.09
to −0.02] m/sec vs −0.01 (−0.03 to 0.003] m/sec, P = .02), and fastest-pace 4-meter walking velocity (−0.07 [−0.11
to −0.03] m/sec vs −0.02 [−0.04 to −0.006] m/sec, P = .046). Compared with participants without PAD, asymptomatic
PAD was associated with greater mean annual decline in 6-minute walk performance
(−76.8 (−135 to −18.6] ft vs −8.67 (−36.9 to
19.5] ft, P = .04) and an increased odds ratio for
becoming unable to walk for 6 minutes continuously (3.63; 95% confidence interval,
1.58-8.36; P = .002).
Conclusions Baseline ABI and the nature of leg symptoms predict the degree of functional
decline at 2-year follow-up. Previously reported lack of worsening in claudication
symptoms over time in patients with PAD may be more related to declining functional
performance to than lack of disease progression.
Cross-sectional studies demonstrate that distinct types of leg symptoms
reported by patients with peripheral arterial disease (PAD) in the lower extremities
are associated with varying degrees of functional impairment.1,2 Severity
of PAD, as measured by the ankle brachial index (ABI), is also associated
with the degree of functional impairment.2,3 However,
relationships between the ABI, leg symptoms, and functional decline are unknown.
Observational studies in the 1960s and 1970s suggested that the natural
history of lower-extremity disease in patients with PAD and intermittent claudication
was benign.4- 6 In
these series, just 15% to 30% of individuals with claudication reported symptomatic
worsening over 5- to 10-year follow-up. Currently, many medical textbooks
and review articles report that most persons with intermittent claudication
have stabilization or improvement in their symptoms over time.7- 10 However,
symptoms may not correlate with objective measures of functional decline.
It is possible that the low rate of symptomatic worsening reported in previous
research has misled clinicians about the true natural history of PAD. However,
if patients with PAD reduce their activity to keep leg symptoms in check,
patient-reported improvement or stabilization of leg symptoms may mask PAD-associated
functional decline. Therefore, in a prospective study of men and women with
and without PAD, we assessed relationships between the ABI and specific leg
symptoms and changes in lower-extremity functioning at 2-year follow-up.
The protocol was approved by the institutional review boards of Northwestern
University and Catholic Health Partners Hospital. Participants gave written
informed consent. Our original protocol specified our aim to determine the
associations between baseline ABI categories and decline in lower-extremity
functioning. Based on recent cross-sectional data showing significant associations
between specific leg symptoms and the degree of functional impairment in patients
with PAD,1 our aim to assess the association
between specific leg symptoms and decline in lower-extremity functioning was
added after funding was obtained.
Participants were aged 55 years and older. Participants with PAD were
identified consecutively from patients who tested positive for PAD in 3 Chicago-area
noninvasive vascular laboratories. Half of the non-PAD participants were identified
consecutively from patients who tested negative for PAD. Remaining non-PAD
participants were identified consecutively from patients aged 55 years and
older in a general medicine practice at Northwestern University. Baseline
visits occurred between October 1, 1998, and January 31, 2000. Follow-up visits
were scheduled 1 and 2 years after baseline.
All participants underwent ABI testing at their baseline study visit.
PAD was defined as ABI less than 0.90.11- 14
Exclusion criteria have been previously reported.1 Patients
with dementia, recent major surgery, or foot or leg amputations were excluded,
as were nursing home residents, wheelchair-bound patients, non–English-speaking
patients (because investigators were not fluent in languages other than English),
and individuals with ABIs greater than 1.50.1,11 Individuals
with PAD diagnosed in the noninvasive vascular laboratory were excluded if
their ABI at the baseline visit indicated absence of PAD. This occasionally
occurred in patients with PAD who were revascularized after vascular laboratory
testing or in individuals with ABI values of approximately 0.90, due to measurement
variation. Patients with an ABI of 0.90 or greater and with prior lower-extremity
revascularization (n = 16) were excluded since they could not clearly be classified
as with or without PAD. Participants with PAD who underwent lower-extremity
revascularization after baseline were excluded (n = 17) since revascularization
may affect the natural history of lower-extremity functioning.
Using established methods, a hand-held Doppler probe (Nicolet Vascular
Pocket Dop II; Nicolet Biomedical Inc, Golden, Colo) was used to obtain systolic
pressures in the right brachial, dorsalis pedis, and posterior tibial arteries;
left dorsalis pedis and posterior tibial arteries; and left brachial artery.15,16 Appropriately sized cuffs were used
and deflated at a rate of 2 mm Hg per second. Systolic pressures were obtained
during deflation. Each pressure was measured twice: in the order listed and
then in reverse order. The ABI was calculated in each leg by dividing the
mean of the dorsalis pedis and posterior tibial pressures in each leg by the
mean of the 4 brachial pressures.15 Average
brachial pressures in the arm with highest pressure were used when 1 brachial
pressure was higher than the opposite brachial pressure in both measurement
sets and when the 2 brachial pressures differed by 10 mm Hg or more in at
least 1 measurement set, since in such cases subclavian stenosis was possible.15,16 The lowest leg ABI was used in analyses.
For participants with PAD, leg symptoms were classified into 1 of 5
groups based on responses to the San Diego Claudication Questionnaire,1,17 which is derived from the Rose Claudication
Questionnaire.18 Four groups had exertional
leg symptoms, based on an affirmative response to the question, "Do you get
pain in either leg or buttock on walking?" These participants were further
classified as follows based on their responses to the San Diego Claudication
Questionnaire: (1) intermittent claudication (exertional calf pain that does
not begin at rest, causes the participant to stop walking, and resolves within
10 minutes of rest); (2) leg pain on exertion and rest (exertional leg pain
that sometimes begins at rest); (3) atypical exertional leg pain/carry on
(exertional leg symptoms that do not begin at rest and do not stop the individual
while walking); and (4) atypical exertional leg pain/stop (exertional leg
symptoms that do not begin at rest, stop the individual from walking, and
do not involve the calves or resolve within 10 minutes of rest). A fifth group
was defined as asymptomatic because they reported no pain in either leg or
buttock while walking.
Algorithms developed for the Women's Health and Aging Study were used
to document comorbid diseases.19 These algorithms
combine data from patient report, physical examination, medical record review,
medications, laboratory values, and a primary care physician questionnaire.
American College of Rheumatology criteria were used to diagnose osteoarthritis
of the knee or hip.20,21 Comorbid
diseases assessed were diabetes mellitus, angina, heart failure, myocardial
infarction, stroke, arthritis of the knee, arthritis of the hip, hip fracture,
spinal stenosis, disk disease, pulmonary disease, and cancer.22- 25
Functional measures were performed by a health interviewer blinded to
the patients' ABI status.
Six-Minute Walk. The 6-minute walk measures
walking endurance and correlates with physical activity levels in patients
with PAD.26 Six-minute walk performance predicts
mortality in patients with heart failure and oxygen consumption in patients
with pulmonary disease.27,28 Corridor
walking, as performed during the 6-minute walk, is more familiar and acceptable
to older patients than treadmill walking, which can be associated with balance
problems and anxiety.29- 32 Following
a standardized protocol,33,34 participants
walked up and down a 100-ft hallway for 6 minutes after instructions to cover
as much distance as possible.
Summary Performance Score. The summary performance
score is a global measure of leg functioning that predicts mobility loss,
nursing home placement, and mortality among community dwelling elderly individuals.35,36 A score (scale, 0-4) was assigned
for performance on time to rise 5 times from a seated position, standing balance,
and 4-meter walking velocity. Individuals received a score of 0 for each task
they were unable to complete. One to 4 scores for each task were assigned
based on quartiles of performance for more than 6000 participants in the Established
Populations for the Epidemiologic Study of the Elderly.35,36 Scores
were summed to obtain the summary performance score, ranging from 0 to 12.
Repeated Chair Rises. This test measures leg
strength and balance.35,36 Participants
sat in a straight-backed chair with their arms folded across their chest and
stood 5 times consecutively as quickly as possible. The time to complete 5
chair rises was measured.
Standing Balance. PAD is associated with pathology
in lower-extremity nerves37- 40 and
impaired standing balance.2 Participants were
asked to hold 3 increasingly difficult standing positions for 10 seconds each:
standing with feet together side-by-side and parallel (side-by-side stand),
standing with feet parallel with the toes of one foot adjacent to and touching
the heel of the opposite foot (semi-tandem stand), and standing with one foot
directly in front of the other (tandem stand).35,36
Four-Meter Walking Velocity. Slower walking
speed is associated with increased risks of mobility disability, loss of the
ability to perform activities of daily living, and becoming homebound.35,36,41 Walking velocity
was measured with a 4-m walk performed at "usual" and "fastest" pace. Each
walk was performed twice. The faster walk in each pair was used in analyses.35,36
Other Measures. Height and weight were measured
at each visit. Body mass index (BMI) was calculated as weight in kilograms
divided by the square of height in meters. Cigarette smoking was assessed
by patient report.
Individuals for whom data collection forms indicated that the participant
was unable to complete functional measures at follow-up due to wheelchair
confinement, exhaustion, or other significant symptom were classified as too
disabled to complete functional measures. The principal investigator (M.M.M.)
made these decisions based on the data collection forms, blinded to all other
participant characteristics. When no information was provided for the reason
a participant refused to complete functional tests, those who met at least
2 of the following criteria were considered too disabled to walk: (1) the
participant reported walking fewer than 5 blocks during the previous week;
(2) the score for repeated chair rises equaled 0 or 1; and (3) the score for
the standing balance test equaled 0 or 1. The criteria were defined prior
to data analyses. Individuals who refused functional testing at follow-up
and met 2 of these criteria were assigned the minimum value for each test
not completed. The minimum value for each test was equivalent to the poorest
performance among those who completed testing at the corresponding visit.
We also examined the sensitivity of results by considering 2 other methods
of handling missing functional assessments for participants who returned for
testing but did not perform functional measures. In one method, a score of
0 was assigned for the missing data; in the other, the fifth percentile score
among functional assessment completers was assigned. Results for all 3 methods
were similar. Results incorporating the minimum score for handling missing
functional assessments are reported herein.
Baseline characteristics between participants with and without PAD were
compared using general linear models for continuous variables and χ2 tests for categorical variables. In comparing change in functioning
(eg, 6-minute walk distance) across different patient groups, a longitudinal
or repeated-measures analysis of covariance (ANCOVA) was carried out using
generalized estimating equations.42 Dependent
variables for each analysis were the successive annual differences in each
functional measure. For example, for the 6-minute walk, the dependent variable
was defined as the successive differences in 6-minute walk distances (ie,
the difference in distance from baseline to the first follow-up visit and
the difference in distance from the first to the second annual follow-up visit).
A repeated-measures ANCOVA adjusting for baseline covariates (sex, age, and
race) and a time-dependent covariate representing functional performance at
the immediately preceding visit were carried out on these successive differences.
Analyses were repeated adjusting additionally for baseline comorbid diseases
and for time-dependent covariates (BMI and pack-years of smoking). For analyses
that excluded participants without PAD, ABI was also an independent variable.
Handling Missing Data. Under this initial generalized
estimating equations–type analysis, statistically valid inference is
guaranteed provided missing data caused by patient dropout is unrelated to
observed or unobserved data (ie, any missing data are missing completely at
random). As a safeguard against violations to this assumption that missing
data are missing completely at random, we repeated the fully adjusted comparisons
using a repeated-measures pattern-mixture ANCOVA model.43,44 In
this model, patients may be classified into possible patterns of missing data.
Because data were analyzed using successive differences, there were only 2
possible patterns of missing differences, since patients who miss the first
follow-up visit cannot be included in analyses even if they attended the second
follow-up visit. Thus, one pattern consists of all patients with data at baseline
and at both the first and the second follow-up visits. A second pattern consists
of patients who completed the baseline visit and the first follow-up visit
but missed the second follow-up visit. The different patterns of missing data
were included as binary indicator covariates (centered about their means).
By including patterns of missing data in analyses as centered covariates and
averaging over these patterns using adjusted least-squares means, one can
obtain an unbiased estimate of the marginal means, adjusting for covariates.44 To determine the validity of our findings, analyses
were repeated among all participants with baseline and year 2 data, even if
year 1 data were missing. In these additional analyses, values for missing
data from the first follow-up visit were imputed by averaging performance
on functional assessments at baseline and at the second follow-up visit.
Among participants able to walk for 6 minutes without stopping at baseline,
multiple logistic regression analyses were used to model the odds for becoming
unable to walk for 6 minutes continuously at follow-up across baseline ABI
categories (<0.50, 0.50 to <0.70, 0.70 to <0.90, and 0.90 to <1.10,
with 1.10-1.50 as the reference group), adjusting for age, sex, race, and
comorbid diseases. Because of collinearity, these analyses did not adjust
for cigarette smoking, BMI, or diabetes. Individuals who returned for follow-up
but did not attempt the 6-minute walk and met criteria defined above for "disabled"
were classified as unable to walk for 6 minutes continuously. Fit of the logistic
regression models was assessed using Hosmer and Lemeshow statistics. All models
passed the goodness-of-fit test. Analyses were repeated to assess associations
between baseline leg symptom categories and becoming unable to walk for 6
minutes continuously at follow-up, adjusting for age, sex, race, BMI, smoking,
and comorbid diseases. Analyses were performed using SAS version 8.2 (SAS
Institute Inc, Cary, NC).
Power Analyses. Based on the sample sizes of
63 for ABI less than 0.50 and 259 for ABI 0.90 to 1.50, and assuming that
the correlation between any 2 repeated measurements was 0.7, we had 80% power
to detect a minimum detectable difference in annual change for the functional
measures between these 2 ABI groups of 0.15 SDs based on a 2-tailed test at α
= .05. For comparisons between participants with ABI 0.50 to less than 0.90
and those with ABI 0.90 to 1.50, the minimum detectable difference in annual
change of the functional measures was 0.089 SDs.
Figure 1 shows reasons for
nonparticipation among patients identified for the study. Of 707 eligible
participants who completed baseline testing, 676 (96%) completed the first
follow-up visit and were included in analyses. Among the 31 participants who
did not complete the first follow-up visit, 24 died prior to returning for
the first visit. The remainder died prior to their second follow-up visit.
Compared with the 676 participants, the 31 who did not complete the first
follow-up visit had a lower mean (SD) ABI (0.69 [0.20] vs 0.82 [0.25], P = .004), a higher prevalence of diabetes (45.2% vs 24.1%, P = .03), and poorer performance on baseline functional
measures. Compared with the 623 participants who completed all 3 visits, the
53 who missed the second follow-up visit had significantly poorer performance
on baseline functional measures, were older (mean [SD] age, 72.9 [8.6] years
vs 70.8 [8.3] years), included a lower proportion of men (45.3% vs 56.3%),
and had lower baseline ABIs (0.77 [0.23] vs 0.83 [0.25]). Only the differences
in baseline functional performance were statistically significant.
Table 1 shows characteristics
of the study population. Among participants with PAD, average mean (SD) baseline
ABI values ranged from 0.62 (0.14) for those with intermittent claudication
to 0.71 (0.11) among those with exertional pain/carry-on. Values for ABI were
not significantly different across leg symptom categories. Lower ABI values
were associated with higher mortality at 2-year follow-up (11.1% for ABI <0.50,
5.9% for ABI 0.50 to <0.90, and 3.1% for ABI 0.90 to 1.50; P = .01).
Table 2 shows associations
between baseline ABI and functional decline. Adjusting for confounders including
comorbid diseases and patterns of missing data, participants with baseline
ABI less than 0.50 and those with ABI 0.50 to less than 0.90 each had significantly
greater annual decline in 6-minute walk performance compared with those with
baseline ABIs of 0.90 or greater.
Participants with PAD having leg pain on exertion and rest and those
with asymptomatic PAD each had significantly greater annual decline in 6-minute
walk performance than did participants without PAD, adjusting for patterns
of missing data and confounders including comorbid disease. Participants with
PAD having pain on exertion and rest had significantly greater declines in
usual- and fastest-pace 4-meter walking velocity than did participants without
PAD (Table 3). Results in Table 2 and Table 3 were similar when analyses were repeated and included all
participants with data from the baseline and the second follow-up visits,
even when data from the first visit were missing.
Among 80 participants with PAD having no exertional leg symptoms at
baseline, 38 (48%) remained asymptomatic at follow-up and the remainder developed
exertional leg symptoms at the first or second follow-up visit. Participants
with asymptomatic PAD who developed exertional leg symptoms had greater mean
annual functional decline than those who remained symptomatic (–136
vs –42.9 ft for the 6-minute walk, P = .12;
–0.02 vs –0.01 m/sec for usual-pace 4-meter walk, P = .78; −0.06 vs −0.04 m/sec for fastest-pace 4-meter
walk, P = .33; –0.54 vs –0.36 for the
summary performance score, P = .17).
Table 3 analyses were repeated
among participants with PAD only (data not shown). In these analyses, the
pain/carry on group served as the reference, because previous cross-sectional
study shows that these patients with PAD have better functioning than other
leg symptom groups.1 In fully adjusted analyses,
PAD participants with pain on exertion and rest had significantly greater
decline on all outcomes than did the reference group. Respective mean annual
declines were −121.0 vs −20.9 ft for the 6-minute walk (P = .03), −0.06 vs −0.02 m/sec for usual-pace
walking velocity (P = .04); −0.07 vs −0.02
m/sec for fastest-pace walking velocity (P = .049);
and −0.82 vs −0.24 for the summary performance score (P = .04).
Figure 2 shows associations
between baseline ABI levels and becoming unable to walk for 6 minutes continuously
at follow-up among the 470 participants who walked continuously for 6 minutes
at baseline. Adjusting for confounders, participants with baseline ABIs of
less than 0.50, 0.50 to less than 0.70, and 0.70 to less than 0.90 were each
significantly more likely to become unable to walk continuously for 6 minutes,
compared with participants with ABIs of 1.10 to 1.50 (Figure 2).
Among participants with PAD who walked continuously for 6 minutes at
baseline, those with pain on exertion and rest, atypical exertional leg pain/stop,
intermittent claudication, and those who were asymptomatic at baseline were
significantly more likely to become unable to walk for 6 minutes continuously
than were participants without PAD at baseline, adjusting for confounders
Among 676 men and women age 55 years and older, participants with low
ABI levels at baseline had significantly greater decline in walking endurance
at 2-year follow-up, compared with those with normal baseline ABI levels.
Participants with ABIs less than 0.50 at baseline had a nearly 13-fold increased
risk of becoming unable to walk for 6 minutes continuously 2 years later,
relative to participants with ABIs of 1.10 to 1.50. These findings were independent
of confounders, including comorbid diseases and patterns of missing data.
Baseline leg symptoms among participants with PAD also predicted rates
of functional decline. Participants with PAD having leg pain on exertion and
rest experienced greater declines in walking endurance and walking speed than
did individuals without PAD. Participants with asymptomatic PAD had significantly
greater declines in 6-minute walk performance than did participants without
PAD. Within the group with asymptomatic PAD, greater functional decline was
observed among participants who developed exertional leg symptoms at follow-up,
compared with those who remained asymptomatic. However, these differences
were not statistically significant. Further study is needed to determine mechanisms
of functional decline in patients with asymptomatic PAD.
Among participants with PAD, leg pain on exertion and rest was associated
with significantly greater decline on all functional outcomes compared with
the leg pain/carry-on group, adjusting for confounders including the ABI.
Leg pain on exertion and rest was defined as exertional leg symptoms that
sometimes begin at rest. Thus, this leg symptom group was not synonymous with
critical limb ischemia.
To our knowledge, no prior studies have prospectively assessed relationships
between the ABI, leg symptoms, and change in objectively measured functioning
in a large cohort of men and women. Findings reported herein challenge standard
thinking regarding the natural history of leg functioning in patients with
PAD.4- 6 In previous
studies, most patients with intermittent claudication reported improvement
or stabilization in leg symptoms over 5 years of follow-up, implying a benign
natural history of lower-extremity functioning in those with PAD.4- 6 However, stabilization
or improvement in claudication symptoms does not necessarily indicate stabilization
or improvement in lower-extremity performance. Claudication symptoms may lessen
because of reductions in levels of physical activity. Our data suggest that
previously described lack of worsening in claudication symptoms over time
may be more related to declining functional performance than to lack of PAD
Based on our findings, clinicians should consider patients with PAD
at increased risk of functional decline compared with those without PAD. An
ABI less than 0.50, leg pain on exertion and rest, and asymptomatic PAD are
all associated with greater functional decline. Our findings regarding PAD
and functional decline are particularly important given the high prevalence
of undiagnosed and asymptomatic PAD.45,46 Among
men and women aged 55 years and older in a general medicine practice, 34 of
239 patients screened with the ABI (14%) had previously undiagnosed PAD.46 Of those with previously undiagnosed PAD, 19 (56%)
had no exertional leg symptoms. In the PARTNERS study of 6417 men and women
in general medical practices who underwent screening with the ABI, 821 patients
(11.8%) had newly diagnosed PAD.45 Of these,
342 (41.6%) were asymptomatic. Our findings suggest that patients with asymptomatic
PAD who develop leg symptoms are particularly likely to have undergone functional
decline and that if one waits until a patient becomes symptomatic to screen
for PAD, additional functional decline—which may or may not be reversible—will
occur prior to the detection of PAD. Further study is needed to determine
whether interventions can prevent functional decline in patients with asymptomatic
PAD prior to the onset of leg symptoms. Although an ABI less than 0.90 is
highly sensitive and specific for the presence of PAD,47 the
hand-held Doppler may not precisely detect ankle systolic pressures less than
30 mm Hg. It is also important to note that approximately 5% of patients with
PAD will have an ABI greater than 0.90 due to calcification of lower-extremity
arteries, resulting in falsely elevated lower-extremity pressures.48
Our study has some weaknesses. First, specific explanations were not
available for all participants who returned for follow-up testing but did
not perform the functional measures. Our a priori classification scheme identified
individuals likely to have been too disabled to perform functional testing
at follow-up. Second, some participants did not complete all follow-up visits.
Our statistical methods adjusted for missing data, which is expected to reduce
the influence of missing data on our findings. Third, our data may not be
generalizable to individuals who declined participation. Fourth, the group
of participants with PAD having atypical exertional leg pain/carry-on was
relatively small. We lacked statistical power to demonstrate significant differences
in some outcomes between these participants with PAD vs those without PAD.
And fifth, our data do not allow us to determine the degree to which comorbid
diseases contributed to the nature of leg symptoms or degree of functional
decline in participants with PAD. However, our findings regarding baseline
ABI levels, leg symptoms, and functional decline in those with PAD were independent
of comorbid diseases.
Reasons for the significant decline in 6-minute walk performance observed
in the group with asymptomatic PAD, but not in PAD groups with intermittent
claudication or in the atypical leg pain/stop group, cannot be discerned from
data presented here. However, some patients with asymptomatic PAD may restrict
their physical activity to prevent exertional leg symptoms.1 If
patients with asymptomatic PAD restrict their activity to a greater degree
than other patients with PAD, this phenomenon may contribute to the greater
declines in 6-minute walk performance observed in the asymptomatic group compared
with other PAD symptom groups. Further study is needed.
In conclusion, the presence and severity of PAD are associated with
significant decline in walking endurance over 2-year follow-up compared with
individuals without PAD. ABI values and leg symptoms can be used to identify
patients with PAD who are at highest risk of functional decline. Our findings
underscore the importance of using the ABI to identify persons with PAD, since
PAD is frequently undiagnosed or asymptomatic. Further study is necessary
to develop treatments to prevent functional decline in patients with PAD who
do not have classic intermittent claudication.