(Circulation. 2000;101:1007.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Asymptomatic Peripheral Arterial Disease Is Independently Associated With Impaired Lower Extremity Functioning
The Women’s Health and Aging Study
From Northwestern University Medical School (M.M.M.), Chicago, Ill; Johns Hopkins University Medical School (L.F., S.L.), Baltimore, Md; and the Epidemiology, Biometry, and Demography Program at the National Institute on Aging (E.S., J.M.G.), Bethesda, Md.
Correspondence to Dr McDermott, 675 N St Clair, Suite 18-200, Chicago, IL 60611. E-mail MDM608{at}nwu.edu
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Abstract |
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Background—We report the implications of asymptomatic lower extremity peripheral arterial disease (PAD) for lower extremity functioning among participants in the Women’s Health and Aging Study, an observational study of disabled women
65 years of age
living in and around Baltimore.
Methods and Results—The ankle brachial index (ABI) and measures
of upper and lower extremity functioning were measured among study
participants. Of 933 women with ABI 
1.50, 328 (35%) had an ABI
<0.90, consistent with PAD. Sixty-three percent of PAD
participants had no exertional leg pain. Among participants without
exertional leg pain, lower ABI levels were associated with slower
walking velocity, poorer standing balance score, slower time to arise 5
times consecutively from a seated position, and fewer blocks walked per
week, adjusting for age, sex, race, cigarette smoking, and
comorbidities. ABI was not associated independently with measures of
upper extremity functioning.
Conclusions—Asymptomatic PAD is common and is independently associated with impaired lower extremity functioning. In addition to preventing cardiovascular morbidity and death, further study is warranted to identify effective interventions to improve functioning among the growing number of men and women with asymptomatic PAD.
Key Words: arteries • aging • peripheral vascular disease
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Introduction |
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Lower extremity peripheral arterial disease (PAD) affects 18% of men and women
55
years of age in general medical practices.1 PAD is
associated with a 5- to 6-fold increased risk of
cardiovascular morbidity and death.2
Although intermittent claudication has been considered the most classic
manifestation of PAD, recent data show that most men and women with PAD
do not have classic intermittent claudication symptoms.3 4
It is unclear whether men and women in a community-dwelling setting
with PAD unaccompanied by intermittent claudication have any
manifestations of PAD.
We studied the prevalence of asymptomatic PAD and its
implications for lower extremity functioning among older,
community-dwelling, disabled women participating in the Women’s Health
and Aging Study (WHAS). The WHAS is an observational study including
the one-third most disabled women 65 years of age living in and
around Baltimore, Maryland. Our study aims were (1) to describe the
prevalence of asymptomatic PAD among WHAS participants; (2)
to determine whether the number of blocks walked per week influenced
the prevalence of exertional leg pain in PAD participants; and (3) to
determine whether asymptomatic PAD was associated with
poorer lower extremity functioning.
PAD is associated with an increased burden of comorbidities that might impair all aspects of functioning. To determine whether PAD has a specific predilection for impairing lower extremity functioning, we also analyzed relations between the ankle-brachial index (ABI) and measures of upper extremity functioning.
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Methods |
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The WHAS is a prospective observational study of disabled women sponsored by the Epidemiology, Demography, and Biometry Program of the National Institute on Aging and conducted by Johns Hopkins Medical Institutions. The study was approved by the Institutional Review Board. All participants gave informed consent. Complete data on study methods have been published.5 The sampling frame consisted of 32 538 women
65 years of age residing in
12 adjacent zip code regions in Baltimore City and Baltimore County. A
stratified random sample of 6521 women was selected by the use of
Medicare enrollment files. Strata were defined by age groups: 65 to 74
years, 75 to 84 years, and 85 years. Eligibility required a
Mini-Mental Status Examination score of 18 and functional difficulty
in 2 of these 4 areas: upper extremity, mobility, higher functioning,
and basic self-care. The response rate to the screening interview was
78%. Of 1409 eligible women, 71% agreed to participate.
Data Collection
Baseline data were collected between November 1992 and January
1995. Participants underwent a baseline interview, with assessment of
health habits, medications, presence and duration of chronic diseases,
and causes and extent of difficulty with daily functioning and
activities. Within 2 weeks of the baseline visit, a study nurse
performed a 3-hour examination in each participant’s home.
Participants who reported pain in either leg while walking were categorized as having exertional leg pain. The term "asymptomatic" refers to participants without exertional leg pain. Women unable to walk were excluded from analyses.
Subjective Measures of Lower Extremity Function
Participants were asked (a) "by yourself, that is, without
help from another person or special equipment, do you have any
difficulty walking up 10 steps without resting?" and (b) "by
yourself, that is, without help from another person or special
equipment, do you have difficulty walking one-quarter mile?"
Participants were asked to report the number of times they left their
home and neighborhood in the past week. They were asked to report the
number of city blocks walked and the number of stair flights climbed in
the past week. Because results for these latter data were skewed,
responses were categorized on a 0 to 3 scale. Participants who walked
<1 block per week were categorized as 0, participants who walked 1 to
6 city blocks were categorized as 1, participants who walked 7 to 12
blocks were categorized as 2, and participants who walked >12 blocks
were categorized as 3. Participants who climbed <1 flight of stairs
were categorized as 0, participants who climbed 1 to 20 were
categorized as 1, participants who walked 21 to 40 were categorized as
2, and participants who walked >40 were categorized as 3.
Subjective Measures of Upper Extremity Function
Participants were asked (a) "by yourself, that is, without
help from another person or special equipment, do you have any
difficulty using your fingers to grasp or handle?" and (b) "by
yourself, that is, without help from another person or special
equipment, do you have any difficulty raising your arms up over your
head?"
Objective Measures of Leg Functioning
4-Meter Walk
A 4-m distance was marked out in the participant’s home, and
the participant was timed performing 2 walks at her usual pace and 1
walk at her most rapid pace. Participants lined up with both feet at
the starting line. Timing began with a verbal command. Correlation
between the 2 usual paced walks was high
(r=0.96).6 The faster of the 2 usual paced
walks was used in analyses.
Chair Stands
The chair stands measure leg strength and balance. Participants
were seated in a straight-backed chair with arms folded across their
chest and asked to stand 5 times consecutively as quickly as possible.
Time in seconds to complete 5 chair stands was recorded.
Balance Tests
Static balance was assessed with 3 increasingly difficult
standing positions: (a) feet together side by side; (b) standing with
the heel of one foot adjacent to the toes of the other foot; (c) one
foot directly in front of the other. An ordinal 0 to 4 scoring system
derived from a previous study was assigned on the basis of the
participant’s ability to hold each stand for up to 10
seconds.7
Summary Performance Score
The summary performance score, measured by a 0 to 12
ordinal scale, represents the participant’s
performance for (a) usual paced walking velocity, (b) time for
5 chair rises, and (c) standing balance score.7
Participants unable to perform a task receive a zero. A 1 to 4 score is
assigned to participants who complete each measure.7 The
summary performance score represents the sum of the
three 0 to 4 scores. This combined score predicts mortality, nursing
home admission, and disability among older men and
women.7 8
Objective Measures of Upper Extremity Function
Grip strength was measured with the use of a JAMAR hand
dynamometer (model BK-7498, Fred Sammons, Inc). Three grip strengths in
each hand were recorded. The highest strength measurement in the
strongest hand was used in analyses.
Upper extremity strength was measured by having the participant raise a 10-pound jug of water from her lap to above her head. A 0 to 3 ordinal scale was used to score performance, in which 0 represented inability to lift the jug >1 inch, 1 represented the ability to raise the jug >1 inch but to less than eye level, 2 represented the ability to lift the jug to eye level but not higher, and 3 represented the ability to lift the jug over the head.
Ankle Brachial Index
An ABI <0.90 is 95% sensitive and 99% specific for
angiographically significant PAD.9 Participants with ABI
0.90 to 1.50 were classified as not having PAD.1 2 3 4 Women
with ABI >1.50 were excluded because these participants generally have
artificially elevated lower extremity arterial pressures
from calcified lower extremity arterial
vessels.3 4 The ABI was measured with the use of a
Doppler stethoscope (Parks model 841-A). Two systolic
pressures in the right brachial artery and each posterior tibial artery
were measured, respectively. The highest pressure in each artery was
used to calculate the ABI.10 The ABI was obtained by
dividing the lower of the right and left posterior tibial pressures by
the brachial artery pressure.
Comorbidity Measurements
Disease ascertainment algorithms were developed for 17
comorbidities by the Disease Ascertainment Working Group of the
WHAS.11 These algorithms combine data from the interview,
medications, physical examination, medical record review, blood
test results, and a primary care physician questionnaire.
Statistical Analyses
2 tests and t tests were
used to compare characteristics between women with ABI <0.90 and women
with ABI 0.90 and ABI 1.50, adjusting for the age-stratified
sampling described above. 2 tests for trend
and ANOVA were used to compare performance on each functional
measure between participants with ABI <0.50, participants with ABI
0.50 to <0.90, and participants with ABI 0.90 to 1.50. Multiple
logistic regression and multiple linear regression analyses
were performed to determine the independent relation between ABI and
each functional measure, controlling for age, race, current cigarette
smoking, and comorbidities.12 13 14 Comorbidities
assessed were angina, myocardial infarction, congestive heart failure,
stroke, hip osteoarthritis, knee osteoarthritis, disk disease, spinal
stenosis, rheumatoid arthritis, hip fracture, diabetes
mellitus, pulmonary disease, Parkinson’s disease, and cancer.
These comorbidities have been shown to influence lower extremity
functioning.
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Results |
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Of 1002 WHAS participants, 933 had an ABI
1.50. Of these, 35%
had an ABI <0.90, consistent with PAD. Table 1
shows characteristics of study
participants. The prevalence of exertional leg pain was comparable
between participants with and those without PAD.
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Figure 1 shows the prevalence of back
disease and lower extremity arthritis according to ABI and presence of
exertional leg pain. Many PAD participants had arthritis or back
disease, which also might cause exertional leg pain. Thus exertional
leg pain may or may not have been a consequence of PAD. However, among
participants without exertional leg pain, a large proportion of PAD and
non-PAD participants had knee arthritis and/or hip arthritis.
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Among women who walked <4 blocks per week, we did not find linear
relations between ABI and the prevalence of exertional leg pain (data
not shown). Among women who walked 4 blocks per week, those with
poorest arterial perfusion (ABI <0.50) had the highest
prevalence of exertional leg pain, whereas women with normal ABI had
the lowest prevalence of exertional leg pain (Figure 2).
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Of 933 participants with ABI 1.50, 359 (38.4%) either had exertional
leg pain or did not walk. Of 574 participants without exertional leg
pain, 198 (34.5%) had ABI <0.90 consistent with PAD and 48
(8.4%) had ABI <0.50 consistent with severe PAD.
Table 2 shows relations between ABI
category and functioning among women without exertional leg pain. Lower
ABI values were significantly associated with poorer lower extremity
functioning. The ABI was not significantly associated with upper
extremity functioning.
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Table 3 shows regression coefficients and
odds ratios relating ABI level to lower and upper extremity
functioning. Adjusting for age, race, cigarette smoking, and
comorbidities, lower ABI levels were associated significantly with
poorer performance in all objective measures of leg functioning
except usual paced walking speed. Lower ABI levels were also associated
independently with walking fewer blocks per week and difficulty walking
one-quarter mile. In contrast, we found no significant associations
between ABI level and upper extremity functioning. Congestive heart
failure was associated independently with poorer functioning on all
measures except the subjective measures of upper extremity functioning
and 2 of the subjective measures of lower extremity functioning
(difficulty walking one-quarter mile and difficulty climbing 1 flight
of stairs).
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Discussion |
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Although only 6.7% of WHAS participants had been told by a doctor that they had PAD or intermittent claudication, 35% had an ABI <0.90, consistent with significant PAD. This prevalence of PAD was higher than that previously reported among less-selected community-dwelling populations. In the Cardiovascular Health Study, 12% of participants
65 years of age had ABI 0.90,
and in the Systolic Hypertension in the Elderly Program, 25.5%
had PAD.15 16 PAD prevalence in the WHAS was less than the
88% prevalence reported in a study of 60 nursing home residents,
however.17 Together these data suggest that disabled
persons may have a higher prevalence of PAD than nondisabled
persons.
Most women with PAD did not have exertional leg pain. We observed
an inverse relation between ABI level and exertional leg pain
prevalence among participants who walked 4 blocks per week but not
among participants who walked <4 blocks. Thus exertional leg pain
correlates with lower extremity arterial perfusion among
participants who walk even short distances outside the home. In
contrast, PAD participants who walk fewer than 4 blocks per week may
include women who experience exertional leg symptoms with any walking
activity and women who have restricted their walking activity to avoid
exertional leg symptoms. This heterogeneity may account
for the lack of association between ABI level and exertional leg pain
among women who walk <4 blocks per week.
Our data showed that asymptomatic PAD is measurably and independently associated with impaired lower extremity functioning. Decreasing ABI levels were associated with progressively poorer lower extremity functioning. Our findings are consistent with previous data showing that patients with PAD have atrophic muscles, fewer muscle fibers, and demyelination of peripheral nerves compared with patients without PAD.18 19 Lower extremity arterial ischemia may directly cause muscle atrophy and muscle fiber loss in the legs because of insufficient blood flow. Alternatively, PAD-related exertional leg symptoms may lead to inactivity, resulting in lower extremity muscle atrophy. Restriction of activity in adaptation to PAD-related leg symptoms may be an important cause of functional decline and mobility loss among women with PAD.
To minimize confounding by a greater burden of cardiovascular disease and comorbidities among participants with PAD, we adjusted analyses for comorbidities. Our results showed that ABI predicts lower extremity functioning independent of comorbidities among women without exertional leg pain. Additionally, we reasoned that if PAD is associated with impaired functioning because of PAD-related comorbidities, then PAD might be associated with impairment in both lower and upper extremity functioning. Our finding that PAD was not associated with poorer upper extremity functioning suggests that PAD-associated leg functioning impairment is not due to the high burden of comorbid illness and coronary and cerebrovascular atherosclerosis commonly associated with PAD. We did not compare cardiopulmonary fitness between the lower and upper extremities. Although it would be of interest to compare, for example, the relation between ABI level and 6-minute walk versus arm ergometry, we did not have measures assessing cardiovascular fitness by exercising the upper extremities.
To our knowledge, no previous studies have assessed the relation
between PAD and functioning among individuals without exertional leg
pain. Vogt et al20 studied 1492 women in the Study of
Osteoporotic Fractures. Participants were white, with a mean age of 71
years. Eighty-two (5.5%) had ABI 0.90, consistent with PAD.
In analyses including both symptomatic and
asymptomatic study participants and adjusting for age,
comorbidities, and other predictors of functioning, PAD was associated
independently with walking difficulty, fewer blocks walked per day, a
lower likelihood that a woman left her neighborhood once or more per
week, poorer lower extremity strength, and a lower frequency of
exercise or work intense enough to work up a sweat. PAD was not
associated independently with walking velocity or balance. Our data
build on the work by Vogt et al by demonstrating a measurable relation
between ABI level and lower extremity functioning specifically among
women without exertional leg pain. The WHAS cohort is also more
racially diverse.
WHAS participants represent the one-third most disabled women in Baltimore. Further study is necessary to determine whether our findings are generalizable to nondisabled persons. However, it is conceivable that differences in functioning between individuals with versus those without PAD would be greater in a population including nondisabled participants, since the range of mobility would be greater than that reported here.
We controlled for the higher prevalence of comorbidities in PAD in 2 ways, by adjusting for comorbidities in multivariable regression analyses and by comparing both upper and lower extremity functioning between participants with and those without PAD. While both analyses supported an independent association between PAD and lower extremity functioning, it is not possible to completely overcome the potential confounding of greater comorbidity burden (both symptomatic and asymptomatic) between PAD and non-PAD participants. Importantly, congestive heart failure was associated independently with poorer performance on objective measures of both upper and lower extremity functioning. Thus heart failure appears to have a more globally deleterious effect on functioning than PAD.
Our findings show that asymptomatic PAD affects more than one third of community-dwelling disabled women. On the basis of this high prevalence of PAD, clinicians should consider ABI screening among community-dwelling, disabled older women. Clinicians should be cognizant of the independent association between PAD and cardiovascular morbidity and death.2 16 As men and women live longer with chronic diseases, clinicians will be increasingly concerned with maintenance of functioning and prevention of disease-associated disability in older persons. On the basis of our findings, in addition to preventing cardiovascular morbidity and death, future studies should focus on improving functioning and preventing disability among individuals with asymptomatic PAD.
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Acknowledgments |
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This study was supported by contract NO1-AG-1-2112 from the National Institute on Aging. Dr McDermott is supported in part by a Robert Wood Johnson Generalist Physician Faculty Scholar Award.
Received July 30, 1999; revision received September 30, 1999; accepted October 6, 1999.
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R. S. Dieter, T. Biring, J. Tomasson, T. Gudjonsson, R. L. Brown, M. Vitcenda, J. Einerson, T. E. Tanke, and P. E. McBride Classic Intermittent Claudication Is an Uncommon Manifestation of Lower Extremity Peripheral Arterial Disease in Hospitalized Patients with Coronary Artery Disease Angiology, November 1, 2004; 55(6): 625 - 628. [Abstract] [PDF]
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A. T. Hirsch, P. Gloviczki, A. Drooz, M. Lovell, M. A. Creager, and The Board of Directors of the Vascular Disease Fou Mandate for Creation of a National Peripheral Arterial Disease Public Awareness Program: An Opportunity to Improve Cardiovascular Health Angiology, May 1, 2004; 55(3): 233 - 242. [Abstract] [PDF]
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 A. T. Hirsch, P. Gloviczki, A. Drooz, M. Lovell, and M. A. Creager Mandate for Creation of a National Peripheral Arterial Disease Public Awareness Program: An Opportunity to Improve Cardiovascular Health Vascular and Endovascular Surgery, March 1, 2004; 38(2): 121 - 130. [Abstract] [PDF]
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A. T Hirsch, P. Gloviczki, A. Drooz, M. Lovell, M. A Creager, and on behalf of The Board of Directors of the Vascula The mandate for creation of a national peripheral arterial disease public awareness program: an opportunity to improve cardiovascular health Vascular Medicine, February 1, 2004; 9(1): 78 - 86. [Abstract] [PDF]
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A. T Hirsch and D. Duprez The potential role of angiotensin-converting enzyme inhibition in peripheral arterial disease Vascular Medicine, November 1, 2003; 8(4): 273 - 278. [Abstract] [PDF]
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 E. R. Mohler III Peripheral Arterial Disease: Identification and Implications Arch Intern Med, October 27, 2003; 163(19): 2306 - 2314. [Abstract] [Full Text] [PDF]
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M. M. McDermott, P. Greenland, D. Green, J. M. Guralnik, M. H. Criqui, K. Liu, C. Chan, W. H. Pearce, L. Taylor, P. M Ridker, et al. D-Dimer, Inflammatory Markers, and Lower Extremity Functioning in Patients With and Without Peripheral Arterial Disease Circulation, July 1, 2003; 107(25): 3191 - 3198. [Abstract] [Full Text] [PDF]
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M. R Nehler, M. M McDermott, D. Treat-Jacobson, I. Chetter, and J. G Regensteiner Functional outcomes and quality of life in peripheral arterial disease: current status Vascular Medicine, May 1, 2003; 8(2): 115 - 126. [Abstract] [PDF]
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J. J. F. Belch, E. J. Topol, G. Agnelli, M. Bertrand, R. M. Califf, D. L. Clement, M. A. Creager, J. D. Easton, J. R. Gavin III, P. Greenland, et al. Critical Issues in Peripheral Arterial Disease Detection and Management: A Call to Action Arch Intern Med, April 28, 2003; 163(8): 884 - 892. [Full Text] [PDF]
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M. M. McDermott, P. Greenland, K. Liu, J. M. Guralnik, L. Celic, M. H. Criqui, C. Chan, G. J. Martin, J. Schneider, W. H. Pearce, et al. The Ankle Brachial Index Is Associated with Leg Function and Physical Activity: The Walking and Leg Circulation Study Ann Intern Med, June 18, 2002; 136(12): 873 - 883. [Abstract] [Full Text] [PDF]
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 S. Volpato, C. Blaum, H. Resnick, L. Ferrucci, L. P. Fried, and J. M. Guralnik Comorbidities and Impairments Explaining the Association Between Diabetes and Lower Extremity Disability: The Women's Health and Aging Study Diabetes Care, April 1, 2002; 25(4): 678 - 683. [Abstract] [Full Text] [PDF]
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M. McGrae McDermott, P. Greenland, K. Liu, J. M. Guralnik, M. H. Criqui, N. C. Dolan, C. Chan, L. Celic, W. H. Pearce, J. R. Schneider, et al. Leg Symptoms in Peripheral Arterial Disease: Associated Clinical Characteristics and Functional Impairment JAMA, October 3, 2001; 286(13): 1599 - 1606. [Abstract] [Full Text] [PDF]
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L. I Katzel, J. D Sorkin, C. C Powell, and A. W Gardner Comorbidities and exercise capacity in older patients with intermittent claudication Vascular Medicine, August 1, 2001; 6(3): 157 - 162. [Abstract] [PDF]
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