A Quick Measure of Functional Status in Elderly Adults

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The 6-min Walk Test*
A Quick Measure of Functional Status in Elderly
Adults
Paul L. Enright, MD; Mary Ann McBurnie, PhD; Vera Bittner, MD;
Russell P. Tracy, PhD; Robert McNamara, MD; Alice Arnold, PhD; and
Anne B. Newman, MD; for the Cardiovascular Health Study
Objectives: To determine the correlates of the total 6-min walk distance (6MWD) in a population
sample of adults > 68 years old.
Methods: The standardized 6-min walk test (6MWT) was administered to the Cardiovascular
Health Study cohort during their seventh annual examination.
Results: Of the 3,333 participants with a clinic visit, 2,281 subjects (68%) performed the 6MWT.
There were no untoward events. The mean 6MWD was 344 m (SD, 88 m). Independent general
correlates of a shorter 6MWD in linear regression models in women and men included the
following: older age, higher weight, larger waist, weaker grip strength, symptoms of depression,
and decreased mental status. Independent disease or risk factor correlates of a shorter 6MWD
included the following: a low ankle BP, use of angiotensin-converting enzyme inhibitors, and
arthritis in men and women; higher C-reactive protein, diastolic hypertension, and lower FEV1 in
women; and the use of digitalis in men. Approximately 30% of the variance in 6MWD was
explained by the linear regression models. Newly described bivariate associations of a shorter
6MWD included impaired activities of daily living; self-reported poor health; less education;
nonwhite race; a history of coronary heart disease, transient ischemic attacks, stroke, or diabetes;
and higher levels of C-reactive protein, fibrinogen, or WBC count.
Conclusions: Most community-dwelling elderly persons can quickly and safely perform this
functional status test in the outpatient clinic setting. The test may be used clinically to measure
the impact of multiple comorbidities, including cardiovascular disease, lung disease, arthritis,
diabetes, and cognitive dysfunction and depression, on exercise capacity and endurance in older
adults. Expected values should be adjusted for the patient’s age, gender, height, and weight.
(CHEST 2003; 123:387–398)
Key words: 6-min walk; elderly; exercise; functional status; heart failure
Abbreviations: 6MWD� 6-min walk distance; 6MWT� 6-min walk test; AAI� ankle-arm index;
ACE� angiotensin-converting enzyme; ADL� activities of daily living; ATS� American Thoracic Society;
AVAS� additive and variance stabilizing transformation; BMI� body mass index; CHF� congestive heart failure;
CHS � Cardiovascular Health Study; CI� confidence interval; CVD� cardiovascular disease; LVM� left ventricular
mass; MI� myocardial infarction; MMSE�Mini-Mental State Examination; TIA� transient ischemic attack
T he ability to walk for a distance is a quick andinexpensive performance-based measure, and an
important component of quality of life, since it
reflects the capacity to undertake day-to-day activi-
ties or, conversely, functional limitation.1 The 6-min
walk test (6MWT) can be performed by many el-
derly, frail, and severely limited patients who cannot
be tested using standard (and more expensive) max-
imal cycle ergometry or treadmill exercise tests.2
Walking tests are more reliable than other perfor-
For editorial comment see page 325
mance-based measures in elderly persons, such as
timed chair stands and weight lifting.3 The 6-min
walk distance (6MWD) is known to be reduced by
*From the University of Alabama at Birmingham (Dr. Bittner),
Birmingham, AL; PAD Clinical Trial Center (Dr. McBurnie),
Seattle, WA; Pediatrics (Dr. Newman), University of Pittsburgh,
Pittsburgh, PA; University of Vermont (Dr. Tracy); University of
Arizona (Dr. Enright) and private practice (Dr. McNamara),
Phoenix, AZ; University of Washington Coordinating Center (Dr.
Arnold), Seattle, WA.
This research was supported by contracts N01-HC-85079
through N01-HC-85086, N01-HC-35129, and N01-HC-15103
from the National Heart, Lung, and Blood Institute.
Manuscript received November 6, 2001; revision accepted June
6, 2002.
Correspondence to: Paul Enright, MD, 4460 East Ina Rd, Tucson,
AZ 85718; e-mail: lungguy@aol.com
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several types of diseases, including obstructive lung
disease, heart failure, arthritis, and neuromuscular
disease.4,5
Previous studies using the 6MWT were limited to
patients with a given disease, and did not include
elderly persons from several community samples.
The Cardiovascular Health Study (CHS) is a pro-
spective observational study of a general population
sample designed to study the epidemiology and risk
factors associated with cardiovascular disease (CVD)
in the elderly. The correlates of four performance-
based measures—gait speed, timed chair stands,
grip strength, and maximal inspiratory pressure—
obtained during the baseline examination of the
cohort have previously been described.6 The stan-
dardized 6MWT was included in a follow-up exam-
ination of the cohort, along with many tests of
cardiovascular and pulmonary risk factors and dis-
ease. We hypothesized that the 6MWD would be
associated with many of these factors.
Materials and Methods
Study Population
Participants in the CHS were selected using a Medicare
eligibility list provided by the US Health Care Financing Admin-
istration for the four participating communities: Forsyth County,
North Carolina; Pittsburgh, PA; Sacramento County, California;
and Washington County, Maryland. These communities are
diverse in proportion of minorities, education and income levels,
degree of urbanization, death rates, and availability of medical
care. The initial study cohort of 5,201 participants was recruited
and examined in 1989 through 1990. An additional cohort of 687
African Americans was enrolled in 1992 and 1993 in order to
enhance the representation of the study. The 6MWT was done
just once, during the seventh annual clinic examination of the
original cohort and the fourth annual examination of the added
cohort (June 1996 to May 1997).
The following were exclusion factors for study entry: institu-
tionalized, terminal illness; inability to walk, communicate, or
give informed consent; or likely to move from the area during the
next 3 years. Enrolled CHS participants were younger, more
educated, and more likely to be married and white than those
who refused or were ineligible. The CHS design and recruitment
are described in detail elsewhere.7,8 The research protocol was
reviewed and approved by the institutional review board for
human studies at the four clinical centers, and informed consent
was obtained.
Examinations
Study participants completed standardized interviews in both
the home and the field center, and extensive examinations at the
field centers at baseline and during the annual examinations. Not
all components were repeated at each annual visit. Standing
height was measured in stocking feet to the nearest centimeter
using a stadiometer, and weight was measured using a balance
beam scale, recalibrated monthly. Handgrip strength was mea-
sured using a Jamar dynamometer set at the second handle
position. The participants were seated with their wrist in a neutral
position and elbow flexed 90°. Grip strength was measured three
times for each hand, and the highest value (in kilograms) from the
participant’s dominant hand was used for our analysis. A medi-
cation inventory was obtained at each examination,9 but the
specific indication for each medication was not determined.
Participants assessed their general health by answering the
question, “Would you say, in general, your health is (excellent,
very good, good, fair, or poor)?” Limitation of instrumental
activities of daily living (ADL) was defined as trouble performing
any of the following: light or heavy housework, shopping, mealpreparation, money management, and using the telephone.
Symptoms of depression were assessed using the modified
Center for Epidemiologic Studies depression scale of 0 to 30.10
The categorical variable depression (a mood, not a diagnostic
category) was defined as a score of� 15. Good social support was
defined as a score of � 12 using a standard scale.11 Cognitive
function was assessed by trained interviewers using a modified
Mini-Mental Status Examination (MMSE),12 scored on a scale of
0 to 100 (including both serial 7s and spelling “world” back-
wards). All of the measurements described thus far were concur-
rent with the examination in which the 6MWT was done.
From 1992 through 1993, we measured each subject’s systolic
BP in both ankles (tibial arteries) and their right arm (brachial
artery) at rest in supine position, using a hand-held Doppler
transducer, and later calculated the ankle-arm index (AAI), a
sensitive subclinical measure of reduced blood flow to the legs.13
Blood was obtained while fasting, and analyzed for RBC and
WBC counts, blood chemistry, and lipoprotein levels.14 At base-
line for each cohort, blood was analyzed for C-reactive protein
levels.15 Echocardiography was performed during visits from
1995 through 1996.16
CVD Assessment
Health status was assessed at baseline through self-report of
physician diagnosis of diseases. Self-report of CVDs were vali-
dated according to standardized criteria by the medications used,
and by examination data such as BP, ECG,17 echocardiography,
and carotid ultrasound.18 Cardiovascular events occurring after
baseline and prior to the 6MWT were validated by a review of
medical records and adjudicated according to standardized cri-
teria.19
Pulmonary Assessments
Spirometry was performed according to American Thoracic
Society (ATS) criteria,20 with reference values previously ob-
tained from healthy members of our cohort.21 The smoking status
of each participant at each examination was categorized as
never-smoker, former smoker, or current smoker, using re-
sponses to the standardized ATS DLD-78 respiratory question-
naire.22
Exclusions from the 6MWT included the following: regular use
of an ambulatory aid (cane or walker); a resting oxygen saturation
� 90%; inability to walk due to musculoskeletal problems; chest
pain in the previous 4 weeks; a heart attack, angioplasty, or heart
surgery in the previous 3 months; heart rate � 50 beats/min at
rest (unless a physician or nurse determined that an AV block or
conduction problem was not the cause of the bradycardia); heart
rate � 110 beats/min at rest; acute ST-T wave changes on the
ECG; participant refusal; or judgment of the clinic staff that the
participant would probably not be able to complete the walk
safely (technician discretion). These exclusions were probably
conservative (excluding many participants who would have ea-
gerly and safely performed the test) because physicians could not
be present in the clinics during all of the examinations to assess
and treat symptomatic participants.
388 Clinical Investigations
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6MWT
The 6MWT was conducted according to a standardized proto-
col,23 using an internal hallway with the 100-foot distance marked
by colored tape on the floor. Participants were told that “the
purpose of this test is to see how far you can walk in six minutes.”
They were then instructed to “walk from end to end of the
hallway at your own pace, in order to cover as much ground as
possible.” Each minute, technicians encouraged the participants
with the standardized statements “You’re doing well” or “Keep up
the good work,” but were asked not to use other phrases.
Participants were allowed to stop and rest during the test, but
were instructed to resume walking as soon as they were able to do
so. The technician used a mechanical lap counter to count the
number of laps completed, and an electronic timer with a buzzer
that sounded 6 min after the walk started. Before the walk started
and at the end of the 6-min walk, participants were shown a
modified Borg dyspnea scale24 printed on a card and asked to
“indicate your current degree of shortness of breath” on a scale of
“0 � nothing at all” to “10 � very, very severe.” At the end of the
walk, they were asked if they had experienced any of the
following specific symptoms: dyspnea, chest pain, light-headed-
ness, or leg pain, or any other symptoms.
Statistical Methods
Preliminary descriptive analyses included frequencies, histo-
grams, and error bar plots to examine bivariate relationships with
total distance walked. For bivariate associations, Pearson �2 tests
were used to evaluate associations between categorical variables,
analysis of variance F tests for associations between continuous
and categorical variables, and t tests for partial correlations
between continuous measures.
Multiple linear regression analysis was performed to determine
relationships between total distance walked and potential predic-
tors. Variables were examined for the linearity of their relation-
ship with 6MWD using the additive and variance stabilizing
transformation (AVAS) in S-Plus (StatSci; Seattle, WA).25 AVAS
is a nonparametric regression technique that attempts to find
smooth transformations that approximate an additive model.
These transformations can be used to suggest appropriate func-
tional forms for standard linear models. Linear piecewise trans-
formations were suggested for AAI, diastolic BP (women only),
and MMSE, as was a quadratic form for weight that was centered
to reduce collinearity between the linear and quadratic terms.
Median values appeared to be reasonable cut-points for the
piecewise transformations. Analyses were stratified by gender
based on results of preliminary analyses that suggested differ-
ences in some relationships by gender, but any variable that was
entered into the model for one gender was also entered into the
model for the other gender.
A series of stepwise regressions were fit for successive blocks of
covariates. Candidate variables were stepped into the model in
the following groups: demographics (age, race, site indicators,
less than high school education); anthropometry (body mass
index [BMI], waist circumference, weight, weight squared, stand-
ing height, and arm span); clinical and subclinical disease (prev-
alence for diabetes, arthritis, angina, congestive heart failure
[CHF], claudication, myocardial infarction [MI], stroke, and
transient ischemic attack [TIA], FEV1, AAI, diastolic and brachial
and tibial systolic BP), measures of inflammation (fibrinogen,
WBC count, and C-reactive protein); smoking status (current vs
never or former); echocardiographic variables (left ventricular
mass [LVM], regional wall motion, and percentage of fractional
shortening); medications (�-blockers, diuretics, vasodilators, an-
giotensin-converting enzyme [ACE] inhibitors, calcium channel
blockers, digitalis, hypertension, insulin, lipid-lowering, and non-
steroidal anti-inflammatory drugs for both genders; and estrogen
in women); and “function” variables (grip strength, MMSE score,
and depression score). To determine entry and removal of
candidate variables from the model, p values of 0.05 and 0.06
were used, respectively. The piecewise terms were included in
the model based on partial F tests for simultaneous significance
of both coefficients. Once the stepwise selection was completed,
the final models were refit using only the selected variables in
order to minimize the amount of missing data. Appropriateness
of the functional forms was reaffirmed using AVAS.
Adjustment was not made for multiple comparisons. All p
values are presented as relative measures of the strength of the
associations and should not be strictly interpreted because of the
large number of statistical tests performed. Analyseswere carried
out using SPSS for Windows (Release 9.0; SPSS; Chicago, IL)26
and S-Plus.27
Since the 6MWD was associated with age, gender, race, height,
and weight, reference equations for the healthy subset of partici-
pants were determined using these variables as predictors of 6MWD
in a linear regression model. Participants with factors associated with
a shorter 6MWD were excluded from the healthy subset.
Results
6MWT Exclusions and Safety
Of the 3,333 participants who attended the 1996
through 1997 clinic visit, approximately one third were
excluded or chose not to try the 6MWT (Table 1).
Table 1—Participation, Exclusions, and Completion of
the 6MWT
Variables No. (%)
Refused or unable to participate 297 (6)
Interviewed outside the clinic 1,080 (23)
Year 9 clinic visit done 3,333 (71)
Total year 9 participants 4,710 (100)
Of the 3,333 patients with a year 9 clinic visit done
Excluded from 6MWT due to 766 (23)
ECG alert 31
Ambulatory aid 331
Aortic stenosis 15
Heart rate � 50 beats/min or � 110 beats/min 153
Systolic BP � 200 mm Hg or diastolic BP � 110
mm Hg
22
Recent MI, angioplasty, bypass surgery 7
New chest pain, dyspnea, or fainting 84
Resting oxygen saturation � 90% 1
Technician discretion 122
Did not participate in 6MWT (unknown reason) 158 (5)
6MWT not attempted 128 (4)
Refused at interview 34
Physically unable 2
Technician discretion 58
Other 34
6MWT partially completed 164 (5)
Refused during 6MWT description 3
Physically unable 42
6MWT stopped by the technician 88
Other reason, unknown 31
Successfully completed the 6MWT 2,117 (64)
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The 164 participants who started the walk but stopped
walking before 6 min had elapsed (partial completers)
were included in the analyses for this report. Those
who completed the walk (n� 2,117) were significantly
healthier in many respects when compared to the
partial completers, or to those who did not perform the
test (Table 2). Those with prevalent CVD (a history of
angina, MI, CHF, claudication, TIA, or stroke) were
much less likely to have tried or completed the walk.
Half of the cohort who did not attend the clinic visit
(and 37% of those who attended the clinic visit but did
not try the walk) reported that their general health was
only fair or poor, compared to only 16% of those who
completed the walk.
There were no untoward events associated with
the test (no need for emergency evaluation or ther-
apy). All participants were asked about symptoms at
the end of the walk, and approximately 75% said that
they had no symptoms (Table 3). The most common
symptoms reported by the others included leg pain,
muscle or joint pain, discomfort, or fatigue. Only 29
participants reported chest pain. Thirty-nine percent
of the 164 participants who were partial completers
reported a symptom at that point (compared to 24%
of those who walked for the entire 6 min); however,
the distribution of symptoms did not differ between
the two groups.
The mean distance walked was 362 m (1,188 feet)
for men and 332 m (1,089 feet) for women. The
6MWD distribution was skewed toward shorter dis-
tances.
Bivariate and Nonlinear Associations With 6MWD
There was a nonlinear relationship of body weight
and BMI with 6MWD (Fig 1). Patients with a low or
Table 2—Comparison of Study Participants Who Completed the 6MWT, Partial Completers, and Those Who Were
Not Tested*
Characteristics
Completed
the 6MWT
(n � 2,117)
Partial
Completers
(n � 164)
Visit Done,
No 6MWT†
(n � 1,052)
No Clinic
Visit
(n � 1,377) p Value‡
Age 77 (4) 78 (5) 79 (5) 81 (6) � 0.001
Male gender 40.3 32.9 40.3 35.2 0.005
Nonwhite race 13.9 20.7 20.8 17.4 � 0.001
Less than high school
education
22.4 22.6 27.0 35.8 � 0.001
Waist size, cm 96 (12) 99 (16) 98 (14) 98 (14) � 0.001
Weight, lb 159 (30) 162 (38) 161 (35) 151 (36) 0.33
Height, cm 164 (9) 162 (10) 163 (10) 160 (10) � 0.001
Angina 18.0 23.8 30.4 30.9 � 0.001
MI 8.5 15.9 15.3 17.4 � 0.001
CHF 5.3 6.1 15.4 18.0 � 0.001
Stroke 3.6 5.5 11.0 13.4 � 0.001
TIA 2.8 5.5 4.9 6.2 � 0.001
Claudication 2.2 5.5 4.3 5.6 � 0.001
Diabetes 13.3 14.6 16.8 8.4 � 0.001
Arthritis 28.5 36.9 42.7 37.4 � 0.001
Current smoker 6.4 11.8 8.6 9.1 0.008
Echocardiographic LVM 147 (48) 140 (39) 158 (51) 153 (53) � 0.001
Limited ADL 0.14 (0.44) 0.13 (0.39) 0.61 (1.1) 1.20 (1.8) � 0.001
Fair or poor health 15.6 27.4 37.1 50.5 � 0.001
Depression score 5.1 (4.5) 5.9 (4.6) 7.1 (5.3) 7.4 (6.2) � 0.001
Cognitive function 93 (8) 91 (10) 88 (14) 73 (25) � 0.001
*Data are presented as mean (SD) or %.
†This category includes participants who came into the clinic but refused the test, or were excluded from the test, or were unable to perform the
test because of physical, cognitive, or equipment problems.
‡p values are unadjusted, and test for a trend across the categories (four rows).
Table 3—Symptoms Reported at the End of the
6MWT*
Completers
Partial
Completers Total
Any symptoms 517/2,117 (24) 64/164 (39) 581/2,281 (25)
Chest pain 24 (4) 5 (6) 29 (4)
Lightheadedness 115 (19) 13 (17) 128 (19)
Leg pain 204 (34) 26 (33) 230 (34)
Other symptoms† 254 (43) 34 (44) 288 (43)
*Data are presented as No./total (%) or No. (%).
†The majority of these symptoms involved muscle or joint pain,
discomfort, or fatigue (n � 184). Other symptoms also included
shortness of breath, tightness or pressure in chest, wheezing
(n � 27); general weakness or fatigue (n� 26); dizziness or balance
problems (n � 14); nausea (n � 6); and miscellaneous symptoms
(n � 31). Some participants reported more than one symptom at the
end of the test.
390 Clinical Investigations
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a high weight (or BMI) did not walk as far as the
others. The upper threshold for a lower distance was
a BMI � 30 or a weight � 180 lb. We did not use
BMI in subsequent models since it forces a specific
relationship between weight and height that is less
powerful as a predictor when compared to using
both weight and weight squared in the model.
There was also a nonlinear association of ankle
BP (and AAI) with 6MWD in both men and
women (Fig 2). AVAS analysis suggested a break-
point at an AAI of 1.1 in women and 1.2 in men.
There was also a breakpoint (at 69 mm Hg) in the
relationship of diastolic (brachial) BP and 6MWD
in women (Fig 3).
For those variables that were significantly corre-
lated with 6MWD, Table 4 lists their mean values for
each quintile of 6MWD; for each categorical vari-
able, the percentages are given. Disease and risk
factors that were more likely in the lowest quintile of
distance walked included a history of any CVD,
diabetes, lower lung function, and weaker grip
strength; and higher fibrinogen, C-reactive protein,
and WBC count. Participants who reported limita-
tions in ADL, fair to poor general health, more
symptoms of depression, and those with lower cog-
nitive function (lower MMSE score) did not walk as
far. Although there was a tendency for those who did
not walk as far to have abnormal echocardiographic
findings, these trends were not significant.
Independent Predictors of 6MWD in Regression
Models
Tables 5, 6 show the independent correlates of
6MWD, using gender-specific, stepwise, linear re-
gression models. Approximately 30% of the variance
in 6MWD was explained by the final models. The
distances were approximately 7% lower at two of the
clinics (Hagerstown, MD, and Pittsburgh, PA). Age
and waist size remained strongly associated with
6MWD. The nonlinear effects of weight and AAI
also remained as strong predictors of 6MWD. Racial
differences also persisted in the final models, but
high school education became nonsignificant as dis-
ease variables entered the models.Diastolic BP, lung
function, arthritis, and C-reactive protein level re-
mained significant correlates in women.
The only echocardiographic variable that was sig-
nificant in any model was moderate-to-severe left
ventricular wall motion abnormalities in women
(p � 0.002). Since only 776 women completed this
examination, the overall strength of that model was
decreased, and so we elected not to enter echocar-
diographic variables into the final models. None of
the echocardiographic variables were significant in
any of the models for men, but the use of digitalis
and ACE inhibitors was associated with lower
6MWD, and the use of lipid-lowering medications
was associated with a higher 6MWD.
Figure 1. The association of BMI by deciles with 6MWD.
Note the shorter distance walked by obese elderly persons
(BMI � 30).
Figure 2. The relationship between the AAI of systolic BP and
6MWD. A breakpoint was found at AAI of 1.10 for women and
AAI of 1.20 for men.
Figure 3. The relationship of diastolic BP with 6MWD in
elderly women. A breakpoint was found at a diastolic BP of
69 mm Hg.
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In the final step of entering groups of variables
into the models, three functional variables were
significant: score on the MMSE, the depression
symptom score, and grip strength. When they en-
tered the models, race and education became much
less important. Participants with better cognitive
levels, fewer symptoms of depression, and a stronger
grip strength walked farther.
The following factors were not independent cor-
relates of the distance walked (p� 0.01) in the final
models: educational level, height, current smoking,
prevalent coronary heart disease (a history of MI,
angina, CHF, stroke, or claudication), or the use of
several cardiovascular medications (diuretics, antihy-
pertensives, vasodilators, �-blockers, and calcium
channel blockers), or nonsteroidal anti-inflammatory
drugs, insulin, or estrogen by women.
Reference Equations for the 6MWD
Approximately one third of the 2,115 patients who
completed the 6MWT remained in the healthy
subset (Table 7). The 437 healthy women walked a
mean of 367 m (confidence interval [CI], 249 to
479 m), and the 315 healthy men walked a mean of
400 m (CI, 280 to 532 m). The 71 healthy African-
American participants walked an average of 40 m
shorter distance than the others. The relationship of
age with 6MWD was linear. There were no signifi-
cant gender or race interaction terms with age,
Table 4—Bivariate Associations With the Distance Walked During the 6MWT*
Characteristics
Quintile of Total Distance Walked
p Value†
1
3 to 278 m
2
279 to 332 m
3
333 to 367 m
4
368 to 412 m
5
� 413 m
Age, yr 78.8 (5.0) 78.1 (4.4) 77.3 (4.2) 76.7 (4.0) 76.2 (3.3) � 0.001
Male gender 30.1 33.4 38.5 44.7 52.5 � 0.001
Nonwhite race 19.0 17.1 16.4 11.8 7.4 � 0.001
Less than high school education 29.8 28.4 23.1 18.3 12.1 � 0.001
BMI 27.5 (5.4) 27.3 (4.5) 26.8 (4.0) 26.4 (3.8) 25.8 (3.3) � 0.001
Waist size, cm 99 (15) 98 (13) 96 (12) 96 (12) 94 (11) � 0.001
Weight, lb 158 (36) 159 (31) 159 (29) 159 (28) 159 (28) 0.65
Height, cm 161 (9) 162 (9) 164 (9) 165 (9) 167 (9) � 0.001
Angina 21.1 21.2 17.3 15.4 17.3 0.020
MI 13.7 9.6 6.8 7.3 7.6 � 0.001
CHF 8.7 6.7 3.5 3.8 4.0 � 0.001
Stroke 6.7 4.9 2.6 3.0 1.3 � 0.001
TIA 6.7 4.9 2.6 3.0 1.3 0.001
Claudication 5.9 2.0 1.3 2.1 0.7 � 0.001
Diabetes 18.1 12.5 14.0 13.3 8.7 � 0.001
Arthritis 36.4 38.9 27.6 19.8 22.8 � 0.001
Systolic BP, mm Hg 138 (21) 136 (19) 135 (20) 136 (19) 134 (18) 0.003
Diastolic BP, mm Hg 69 (11) 70 (10) 69 (11) 70 (11) 71 (10) 0.065
AAI 1.07 (0.19) 1.10 (0.17) 1.14 (0.15) 1.13 (0.12) 1.16 (0.13) � 0.001
FEV1, L 1.7 (0.57) 1.8 (0.53) 1.9 (0.57) 2.1 (0.56) 2.3 (0.59) � 0.001
Grip strength, kg 24.8 (8.6) 26.0 (9.0) 27.8 (9.4) 29.7 (9.5) 32.0 (9.8) � 0.001
C-reactive protein 3.7 (7.0) 3.2 (6.0) 3.3 (6.3) 2.8 (6.0) 2.0 (3.0) � 0.001
Fibrinogen 335 (64) 325 (65) 327 (64) 314 (54) 310 (61) � 0.001
ln (WBC) 1.83 (0.28) 1.81 (0.25) 1.78 (0.28) 1.77 (0.28) 1.74 (0.25) � 0.001
Current smoker 8.9 6.6 7.3 6.6 4.5 0.019
Echocardiographic LVM‡ 147 (54) 147 (49) 144 (46) 145 (43) 148 (45) 0.97
Echocardiographic percentage
of fractional shortening‡
41.6 (9.2) 41.6 (9.0) 41.9 (8.4) 41.6 (7.8) 42.4 (8.6) 0.30
Moderate-to-severe regional
wall motion abnormality
3.4 2.7 1.9 2.1 1.9 0.15
Moderate-to-severe left
ventricular ejection fraction
decrease
2.7 3.1 1.9 2.1 1.7 0.20
Limited ADL 0.26 (0.67) 0.16 (0.44) 0.11 (0.32) 0.09 (0.31) 0.05 (0.27) � 0.001
Fair or poor health 29.8 19.2 16.0 10.8 6.0 � 0.001
Depression score 6.2 (4.8) 5.6 (4.6) 5.4 (4.6) 4.6 (4.1) 4.2 (3.9) � 0.001
Cognitive, MMSE 89.8 (11) 92.0 (7.7) 93.3 (7.4) 93.9 (6.7) 95.9 (4.8) � 0.001
*Data are presented as mean (SD) or %. ln � natural log.
†Unadjusted p values, testing for a trend across the quintiles of total distance walked.
‡Data are missing for these echocardiography variables from many subjects.
392 Clinical Investigations
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height, or weight in the model predicting 6MWD in
the healthy subset. The total amount of variance in
6MWD explained by the model (R2) was only 20%.
On average, the healthy 752 participants walked only
10.5% farther than the entire group who completed
the test.
Discussion
We found that most elderly persons can safely
perform the 6MWT to quickly measure their func-
tional status. We may be the first investigators to
describe associations of 6MWD with impaired ADL;
self-reported health; education; race; a history of
coronary heart disease, TIA, stroke, or diabetes; and
indexes of inflammation: (C-reactive protein, fibrin-
ogen, and WBC count).
The 12-min walking test was introduced in 1968 as
a guide to physical fitness,28 and later applied to
patients with COPD.29 It was then found that de-
creasing the time to 6 min did not significantly
reduce the utility of the test.23 The 6MWT has been
validated by high correlation with workloads, heart
rate, oxygen saturation, and dyspnea responses when
compared to standard bicycle ergometry and tread-
mill exercise tests in middle-aged adults30–32 and in
elderly persons.2,33
Anthropometric Correlates
Age, weight, and waist size were independently
associated with the distance walked in this analysis,
and these factors were also associated with gait speed
and timed chair stands during their baseline exami-
nation.6 The gradual reduction of skeletal muscle
Table 5—Linear Regression Models Predicting 6MWD for Women (n � 1,094), With Same Variables in Model for
Men and Women*
Blocks
Original Model Function Variables Added
Coefficient (SE) 95% CI p Value Coefficient (SE) 95% CI p Value
Demographics
Age at year 9 visit, yr � 4.4 (0.58) � 5.5 to � 3.3 � 0.001 � 3.4 (0.59) � 4.6 to � 2.3 � 0.001
Black race � 14.6 (7.1) � 28.5 to � 0.66 0.040 � 11.4 (7.2) � 25.6 to 2.8 0.115
Education less than high school � 6.2 (5.6) � 17.1 to 4.8 0.269 5.1 (5.8) � 6.3 to 16.5 0.381
Clinic � 0.001 � 0.001
Wake Forest Referent Referent
University of California, Davis 0.05 (6.6) � 12.8 to 12.9 � 6.1 (6.5) � 18.9 to 6.7
Hagerstown � 15.7 (7.1) � 29.5 to � 1.9 � 25.2 (7.1) � 39.0 to � 11.4
Pittsburgh � 35.4 (6.6) � 48.3 to � 22.5 � 41.3 (6.5) � 54.1 to � 28.5
Anthropometry
Waist circumference, cm � 1.50 (0.28) � 2.06 to � 0.95 � 0.001 � 1.23 (0.28) � 1.79 to � 0.68 � 0.001
Weight (centered), lb 0.36 (0.15) 0.07 to 0.66 0.016 0.16 (0.15) � 0.15 to 0.46 0.313
Weight squared (centered), lb � 0.006 (0.001) � 0.009 to � 0.003 � 0.001 � 0.007 (0.002) � 0.010 to � 0.003 � 0.001
Clinical
AAI 0.006 0.006
� 1.1 78.6 (25.3) 28.9 to 128.3 78.4 (24.6) 30.1 to 126.8
� 1.1 � 5.93 (30.0) � 64.8 to 52.9 0.002 � 13.3 (29.6) � 71.3to 44.8 � 0.001
Diastolic BP, mm Hg
� 69 � 0.41 to 0.91 0.23 (0.33) � 0.41 to 0.87
� 69 0.25 (0.34) � 2.2 to � 0.62 � 0.001 � 1.4 (0.39) � 2.2 to � 0.67 � 0.001
FEV1, L � 1.4 (0.40) 25.9 to 49.8 � 0.001 35.9 (6.0) 24.1 to 47.7 0.001
Arthritis 37.8 (6.1) � 31.5 to � 12.4 0.008 � 17.0 (4.9) � 26.6 to � 7.4 0.021
Stroke or TIA prevalence � 21.9 (4.9) � 46.8 to � 7.0 0.002 � 22.9 (9.9) � 42.3 to � 3.5 0.002
ln (C-reactive protein) � 26.9 (10.1) � 12.4 to � 2.8 � 7.4 (2.4) � 12.2 to � 2.6
� 7.6 (2.5)
Medications
ACE inhibitors (any reason) � 29.4 (7.1) � 43.4 to � 15.5 � 0.001 � 27.1 (6.9) � 40.7 to � 13.6 � 0.001
Digitalis � 10.0 (9.1) � 27.9 to 7.8 0.270 � 9.2 (9.0) � 26.9 to 8.4 0.305
Lipid lowering 4.5 (6.8) � 8.9 to 17.9 0.513 3.6 (6.7) � 9.4 to 16.7 0.586
Function
MMSE score � 0.001
� 95 0.89 (0.44) 0.02 to 1.76
� 95 5.6 (1.4) 2.9 to 8.4
Grip strength 1.7 (0.45) 0.78 to 2.54 � 0.001
Depression score � 1.4 (0.49) � 2.3 to � 0.41 0.005
* See Table 4 for expansion of abbreviation.
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mass and strength that generally occurs with
aging34,35 (and debilitating diseases that we did not
measure) are probably responsible for the shorter
distance walked by those � 85 years old. A taller
height is associated with a longer stride, which makes
walking more efficient, probably resulting in a longer
distance walked in the taller men and women. After
correcting for other factors, including height, elderly
men did not walk farther than elderly women (in a
model that included men and women together; data
not shown).
Obesity increases the workload for a given amount
of exercise, probably resulting in the shorter distance
walked in participants with a higher body weight or
BMI. On average, participants who were obese, as
defined by a BMI � 30, walked approximately 85%
of the distance completed by those of average body
weight. Although BMI is a clinically useful index
of obesity, exploratory analyses suggested that the
specific functional form weight/height squared
was not optimal for describing the relationship of
weight and height with 6MWD. Waist size and
body weight were more strongly associated with
6MWD than was BMI.
After correcting for age, gender, height, weight,
and other confounders, elderly African-American
women and men walked a shorter distance when
compared to white men and women in our study.
Investigators in Japan recently reported that the
mean 6MWD of healthy elderly Japanese men and
women36 was similar to that reported for whites.37,38
Cardiovascular Correlates
Participants who reported a history of any type of
CVD (a history of angina, MI, heart failure, TIA, or
stroke) did not walk as far as the others (Table 4).
This was also true in the Tucson study.37 Men
Table 6—Linear Regression Models Predicting 6MWD for Men (n � 715), With Same Variables in Model for
Men and Women*
Blocks
Original Model Function Variables Added
Coefficient (SE) 95% CI p Value Coefficient (SE) 95% CI p Value
Demographics
Age at year 9 visit, yr � 3.3 (0.70) � 4.7 to � 1.9 � 0.001 � 2.0 (0.72) � 3.4 to � 0.58 0.006
Black race � 38.8 (9.6) � 57.5 to � 20.0 � 0.001 � 25.4 (9.7) � 44.5 to � 6.3 0.009
Less than high school education � 17.2 (7.1) � 31.1 to � 3.3 0.015 � 3.3 (7.3) � 17.6 to 11.0 0.652
Clinic 0.001 0.001
Wake Forest Referent Referent
University of California, Davis 15.0 (8.5) � 1.8 to 31.7 7.6 (8.4) � 9.0 to 24.1
Hagerstown � 11.9 (9.4) � 30.2 to 6.5 � 19.8 (9.3) � 38.1 to � 1.5
Pittsburgh � 11.5 (8.6) � 28.4 to 5.4 � 17.5 (8.6) � 34.3 to � 0.6
Anthropometry
Waist circumference, cm � 2.8 (0.59) � 3.99 to � 1.69 � 0.001 � 1.97 (0.59) � 3.13 to � 0.81 0.001
Weight (centered), lb 0.73 (0.23) 0.29 to 1.18 0.001 0.36 (0.23) � 0.09 to 0.81 0.117
Weight squared (centered), lb � 0.010 (0.003) � 0.015 to � 0.004 0.001 � 0.009 (0.003) � 0.014 to � 0.003 0.002
Clinical
AAI � 0.001 � 0.001
� 1.2 119 (24) 72.7 to 165.7 106 (23) 59.7 to 151.8
� 1.2 � 36 (44) � 122.0 to 49.1 � 26 (43) � 110 to 58
Diastolic BP, mm Hg 0.27 (0.53) � 0.78 to 1.32 0.271 � 0.04 (0.52) � 1.07 to 0.99 0.237
� 71 0.64 (0.54) � 0.41 to 1.69 0.83 (0.53) � 0.21 to 1.87
� 71 8.2 (5.3) � 2.2 to 18.6 7.3 (5.2) � 2.9 to 17.6
FEV1, L � 17.8 (6.8) � 31.1 to � 4.5 0.121 � 13.6 (6.7) � 26.8 to � 0.4 0.162
Arthritis � 27.0 � 47.7 to � 6.2 0.009 � 26.1 (10.4) � 46.5 to � 5.7 0.043
Stroke or TIA prevalence 10.6 � 11.4 to 0.92 0.011 � 2.0 (3.2) � 8.2 to 4.3 0.012
ln (C-reactive protein) � 5.2 (3.1) 0.096 0.536
Medications
ACE inhibitors (any reason) � 24.5 (7.9) � 40.0 to � 9.0 0.002 � 23.5 (7.7) � 38.7 to � 8.3 0.002
Digitalis � 34.6 (9.2) � 52.7 to � 16.6 � 0.001 � 31.6 (9.0) � 49.3 to � 13.8 0.001
Lipid lowering 27.8 (9.5) 9.2 to 46.5 0.003 24.0 (9.4) 5.6 to 42.4 0.010
Function
MMSE score � 0.001
� 95 2.1 (0.51) 1.06 to 3.05
� 95 5.0 (1.9) 1.37 to 8.72
Grip strength 1.2 (0.40) 0.40 to 1.96 0.003
Depression score � 1.5 (0.72) � 2.9 to � 0.10 0.036
* See Table 4 for expansion of abbreviation.
394 Clinical Investigations
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receiving ACE inhibitors and those receiving digi-
talis walked approximately 90% as far as others. This
is probably because they were receiving these med-
ications for heart failure,39 which causes dyspnea on
exertion, limiting exercise tolerance.40 Approxi-
mately 42% of men and women who reported heart
failure were receiving an ACE inhibitor, and one half
were receiving digitalis. Use of these medications is
probably an indicator of more clinically severe CHF;
however, men receiving lipid-lowering medications
walked approximately 7% farther than other men.
Approximately 25% of men with a history of MI
and 29% of those with claudication were receiving
lipid-lowering medications. Although these medi-
cations act as markers of vascular disease, perhaps
their use improves walking distance in such pa-
tients; a future study of these medications should
investigate this possibility by including 6MWD as
an outcome measure.41
In the bivariate analyses, there were only nonsig-
nificant trends for participants with echocardio-
graphic abnormalities to walk shorter distances, and
only wall motion abnormalities in women were inde-
pendently associated with 6MWD in the models.
This lack of a relationship of echocardiographic
variables with exercise ability was previously re-
ported in patients with overt heart failure,42 perhaps
because echocardiographic measurements are done
while resting.
Both clinical and subclinical peripheral vascular dis-
ease (claudication and low AAI) were bivariately asso-
ciated with substantially shorter 6MWD (Table 4). In
the multivariate models, we used two terms for AAI
(piecewise) since we found a breakpoint in the relation-
ship between AAI and the 6MWD. The highest
6MWD was seen when the AAI was approximately 1.1
(Fig 3). 6MWD decreases as the AAI was higher or
lower than 1.1. Previous studies of AAI suggest that a
low AAI is associated with peripheral vascular disease,33
while a high AAI may be due to loss of arterial
compliance.43
Pulmonary Correlates
We found that a lower FEV1 was a strong, inde-
pendent predictor of a lower 6MWD in women. A
low FEV1 is most commonly due to obstructive lung
diseases such as COPD (due to decades of cigarette
smoking) and asthma, but is also reduced in diseases
that restrict lung volumes. Previous investigators
have used the 6MWD as a measure of the severity of
COPD and an outcome measure in COPD treat-
ment studies.23,31,44,45 We found that the FEV1 was
also associated with gait speed and grip strength in
the elderly women of this cohort.6 Current smoking
was bivariately associated with a significantly shorter
distance walked in both studies, but in the gender-
specificmodels, smoking status was replaced by
indexes of subclinical diseases that are known to be
caused by smoking.
Other Correlates
Previous studies using the 6-min walk have not
included measures of symptoms of depression, men-
tal status (MMSE), limitations of ADL, self-reported
general health, or grip strength, all of which we
found were independently associated with the
6MWD. A 1-U higher MMSE score was associated
with walking 6 m farther in women, and a similar
relationship was seen in men. The 7% lower mean
6MWD values found at two of the four clinics could
be due to technicians at those clinics less frequently
excluding frail participants, or giving less encourage-
ment to walk farther (despite the attempt to stan-
dardize the messages); or it could be due to un-
measured differences in the populations in those
communities.
Grip strength is a direct measure of skeletal
muscle strength of the hands, but it is also an index
of overall muscle strength, endurance, and dis-
ability.46 It remained a strong, independent (linear)
predictor of 6MWD in our models for both women
and men. Mean grip strength was 23 kg for women
and 40 kg for men in the 65-to 69-year age groups.
For a 10-kg increment in grip strength, men and
women walked an average of 14 m farther. A study
from Finland demonstrated that muscle strength and
Table 7—Reference Equations for the 6MWD From the
Healthy Subset of 437 Women and 315 Men
For the total distance walked in meters for women:
493 � (2.2 � height) � (0.93 � weight) � (5.3 � age), with
height in centimeters and weight in kilograms.
For men, add 17 m. Subtract 100 m for the lower limit of the
normal range.
For the total distance walked in yards for women:
539 � (6.1 � height) � (0.46 � weight) � (5.8 � age), with
height in inches and weight in pounds.
For men, add 18 yards. Subtract 109 yards for the lower limit of
the normal range.
Criteria applied sequentially to exclude participants from the
healthy subgroup:
Arthritis in hips and knees, excluded 576
FEV1 � 70% predicted, excluded 406
AAI low (� 0.90) or high (� 1.5), excluded 108
History of stroke, TIA, or claudication, excluded 84
Diabetics receiving medications, excluded 74
Weight or waist size � 95th percentile*, excluded 55
Cognitive impairment (MMSE score � 80), excluded 39
Diastolic hypertension (� 90 mm Hg), excluded 21
*Gender-specific cutpoints for obesity were � 90 kg for women
and 101 kg for men, and for high waist size 118.5 cm for women
and 116 cm for men.
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walking speed can be increased substantially by
physical exercise (either endurance or strength train-
ing) in elderly women.47
A limitation of this study is that one third of the
participants were excluded from the walk, and they
had generally poorer health than those who per-
formed the test; however, their exclusion only de-
creased the power of the analyses to detect associa-
tions with these diseases. Those entered into the
study, and those who came to the clinics for the
examination between 1996 and 1997 (the only time
the 6MWT was done) were survivors, and were
healthier than older persons in institutions or hos-
pitals.
Reference Equations for the 6MWD
The mean 6MWD in the healthy subset of partic-
ipants was 367 m (CI, 249 to 479 m) for women, and
400 m (CI, 280 to 532 m) for men. Age, gender, race,
height, and weight were all statistically significant
predictors of 6MWD in the healthy subgroup, sug-
gesting that these factors should be considered when
comparing the 6MWD of an individual patient to
healthy elderly persons; however, the reference
equations obtained from this model explained only
20% of the variation in 6MWD. The fifth percentile
of the 6MWD for the healthy participants, which
may be considered the lower limit of the normal
range, was approximately 75% of the predicted value
(mean minus lower limit of the normal range:
400 m� 100 m� 300 m for men).
Our reference equation gives predicted (mean)
6MWDs that are substantially lower than those
published by previous investigators.37,48 Our refer-
ence equations predicts distances of 430 m and
464 m for a 67-year-old white woman and man of
average height and weight, respectively, while a
study of 290 healthy adults in Tucson, AZ,37 predicts
distances of 466 m and 544 m; the study of Rikli and
Jones,48 which enrolled 7,183 older adults from 21
states, predicts distances approximately 50% greater
than ours (624 m and 689 m, respectively, for the
same woman and man).
Our choice of criteria for excluding participants
from the healthy subgroup is probably not the reason
for our lower distances, since we excluded more than
two thirds of the cohort, yet the healthy subgroup
only walked an average of 10.5% farther than the
entire cohort who completed the test. The study of
Rikli and Jones48 recruited participants using ad-
vertisements in newspapers, magazines, and jour-
nals (resulting in a recruitment bias toward highly
fit individuals), while our participants were a
community-based sample. The participants in the
study by Rikli and Jones did 8 to 10 min of warm-up
and stretching exercises before beginning the test,
walked in groups of three to six outside on a
rectangular track, and were instructed to “walk as
fast as they comfortably could, trying to cover the
maximum distance possible,” while our participants
had no warm-up, walked alone, and were instructed
to walk from end to end of the hallway at their own
pace, in order to cover as much ground as possible.
Differences in participant recruitment and test
instructions probably account for the lower distances
walked by our participants when compared to the
two other studies. The ATS has recently published
detailed guidelines for 6MWT procedures49 that
should be followed by investigators studying care-
fully selected healthy persons. This new document
states that “a practice test is not needed in most
clinical settings, but should be considered.” The
CHS 6MWT done in 1996 was performed exactly
according to the 2002 ATS guidelines, except that
the instructions given to the CHS participants were
to “walk from end to end of the hallway at your own
pace, in order to cover as much ground as possible.”
According to the new ATS guidelines, patients
should be told to “Remember that the object is to
walk as far as possible for six minutes, but don’t run
or jog.” This seemingly small difference in the
instructions may have caused the elderly CHS par-
ticipants not to walk as quickly as they would have if
the new ATS recommended instructions had been
given to them.
The 6MWT should be useful for measuring
changes in functional status (preintervention and
postintervention) in the clinical setting, but consid-
erable caution is needed when using currently avail-
able reference equations to determine if a given
patient’s 6MWD is normal or low. According to the
ATS review of previously published 6MWT studies,
the increases due to the learning effect ranged from
a mean of zero to 17%. Performance usually reaches
a plateau after two tests done within a week. The
reproducibility results from one study of 112 patients
with stable, severe COPD suggest that an improve-
ment of � 70 m in the 6MWD after an intervention
is necessary to be 95% confident that the improve-
ment was significant.50
In summary, most community-dwelling elderly
persons can perform the 6MWT. Factors associated
with a shorter distance walked are similar to those
associated with a reduced oxygen uptake at maximal
exercise reported by previous investigators. Unique
factors measured by this study included cognitive
function, symptoms of depression, limitations of
ADL, indexes of inflammation, and the use of car-
diovascular medications.
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Appendix: Participating Institutions and
Principal Investigators
Wake Forest University School of Medicine, Gregory L. Burke,
MD; ECG Reading Center, Wake Forest University, Pentti
Rautaharju, MD, PhD; University of California, Davis, John
Robbins, MD, MHS; The Johns Hopkins University, Linda P.
Fried, MD, MPH; MRI Reading Center, The Johns Hopkins
University, Nick Bryan, MD, PhD, and Norman J. Beauchamp,
MD; University of Pittsburgh, Lewis H. Kuller, MD; Echocardi-
ography Reading Center (baseline), University of California,
Irvine, Julius M. Gardin, MD; Echocardiography Reading Center
(follow-up), Georgetown Medical Center, John Gottdiener, MD;
Ultrasound Reading Center, New England Medical Center,
Boston, Daniel H. O’Leary, MD; Central Blood Analysis Labo-
ratory, University of Vermont, Russell P. Tracy, PhD; Pulmonary
Reading Center, University of Arizona, Tucson, Paul Enright,
MD; Retinal Reading Center, University of Wisconsin, Ron
Klein, MD; Coordinating Center, University of Washington,
Richard A. Kronmal, PhD; and National Heart, Lung, and Blood
Institute Project Office, Diane Bild, MD, MPH.
References
1 Guralnik J, Branch L, Cummings S, et al. Physical perfor-
mance measures in aging research. J Gerontol Med Sci 1989;
44:M141–M146
2 Peeters P, Mets T. The 6 minute walk as an appropriate
exercise test in elderly patients with chronic heart failure. J
Gerontol 1996; 51A:M147–M151
3 Jette AM, Jette DU, Ng J, et al. Are performance-based
measures sufficiently reliable for use in multicenter trials? J
Gerontol 1999; 54A:M3–M6
4 McGavin CR, Artvinli M, Naoe H, et al. Dyspnea, disability,
and distance walked: comparison of estimates of exercise
performance in respiratory disease. BMJ 1978; 2:241–243
5 Bittner V, Weiner DH, Yusuf S, et al. Prediction of mortality
and morbidity with a six minute walk test in patients with left
ventricular dysfunction. JAMA 1993; 270:1702–1707
6 Hirsch CH, Fried LP, Harris T, et al. Correlates of perfor-
mance-based measures of muscle function in the elderly: The
Cardiovascular Health Study. J Gerontol 1997; 52A:M192–
M200
7 Fried LP, Borhani NO, Enright PL, et al. The Cardiovascular
Health Study: design and rationale. Ann Epidemiol 1991;
1:263–276
8 Tell GS, Fried LP, Hermanson B, et al. Recruitment of adults
65 years and older as participants in the Cardiovascular
Health Study. Ann Epidemiol 1993; 3:358–366
9 Psaty BM, Lee M, Savage PJ, et al. Assessing the use of
medications in the elderly: methods and initial experience in
the Cardiovascular Health Study. J Clin Epidemiol 1992;
45:683–692
10 Orme J, Reis J, Herz E. Factorial and discriminate validity of
the CES-D scale. J Clin Psychol 1986; 42:28–33
11 Cohen S, Mermelstein R, Kamarck T, et al. Measuring the
functional components of social support. In: Saranson IG,
Saranson BR, eds. Social support: theory, research and
application. Dordrecht, The Netherlands: Martinus Nijhoff,
1985
12 Teng EL, Chui HC. The modified Mini-Mental State (3MS)
Examination. J Clin Psychol 1987; 48:314–318
13 Newman AB, Siscovick DS, Manolio TA, et al. Ankle-arm
index as a marker of atherosclerosis in the Cardiovascular
Health Study. Circulation 1993; 88:837–845
14 Tracy RP, Bovill EG, Fried LP, et al. The distribution of
coagulation factors VII and VIII and fibrinogen in adults over
65 years old: results for the Cardiovascular Health Study. Ann
Epidemiol 1992; 2:509–519
15 Tracy RP, Lemaitre R, Psaty BM, et al. Relationship of
C-reactive protein to risk of cardiovascular disease in the
Cardiovascular Health Study. Arterioscler Thromb Vasc Biol
1997; 17:1121–1127
16 Gardin JM, Wong ND, Bommer W, et al. Echocardiographic
design of a multicenter investigation of free-living elderly
subjects: The Cardiovascular Health Study. J Am Soc Echo-
cardiogr 1992; 5:63–72
17 Furberg CD, Manolio TA, Psaty BM, et al. Major electrocar-
diographic abnormalities in persons aged 65 years and older:
The Cardiovascular Health Study. Am J Cardiol 1992; 69:
1329–1335
18 O’Leary DH, Polak JF, Wolfson SK, et al. Use of sonography
to evaluate carotid atherosclerosis in the elderly: Cardiovas-
cular Health Study. Stroke 1991; 22:1155–1163
19 Ives DG, Fitzpatrick AL, Bild DE, et al. Surveillance and
ascertainment of cardiovascular events: The Cardiovascular
Health Study. Ann Epidemiol 1995; 5:278–285
20 American Thoracic Society. Standardization of spirometry,
1987 update. Am Rev Respir Dis 1987; 136:1285–1298
21 Enright PL, Kronmal RA, Higgins M, et al. Spirometry
reference values for women and men 65–85 years of age:
Cardiovascular Health Study. Am Rev Respir Dis 1993;
147:125–133
22 American Thoracic Society. Recommended respiratory dis-
ease questionnaires for use with adults and children in
epidemiological research. Am Rev Respir Dis 1978; 6(part
2):7–23
23 Butland RJA, Pang J, Gross ER, et al. Two, six, and 12 minute
walking tests in respiratory disease. BMJ 1982; 284:1607–1608
24 Wilson RC, Jones PW. A comparison of the visual analogue
scale and modified Borg scale for the measurement of
dyspnea during exercise. Clin Sci 1989; 76:277–282
25 Tibshirani R. Estimating transformations for regression via
additivity and variance stabilization. J Am Stat Assoc 1988;
83:394–405
26 Norusis MJ. SPSS for Windows, base system user’s guide,
release 9.0. Chicago, IL: SPSS, 1998
27 S-Plus guide to statistical and mathematical analysis, version
3.2. Seattle, WA: StatSci, 1993
28 Cooper KH. A means of assessing maximal oxygen intake.
JAMA 1968; 203:201–204
29 McGavin CR, Gupta SP, McHardy GJR. Twelve minute
walking test for assessing disability in chronic bronchitis. BMJ
1976; 1:822–823
30 Langenfeld H, Schneider B, Grimm W, et al. The six minute
walk test: an adequate exercise test for pacemaker patients?
Pacing Clin Electrophysiol 1990; 13:1761–1765
31 Spence DPS, Hay JG, Carter J, et al. Oxygen desaturation and
breathlessness during corridor walking in COPD: effect of
oxitropium bromide. Thorax 1993; 48:1145–1150
32 Bernstein ML, Despars JA, Singh NP, et al. Re-analysis of
the 12 minute walk in patients with COPD. Chest 1994;
105:163–167
33 Montgomery PS, Gardner AW. The clinical utility of a six
minute walk test in peripheral arterial occlusive disease
patients. J Am Geriatr Soc 1998; 46:706–711
34 Fleg JL, Lakatta EG. Role of muscle loss in the age-associated
reduction in Vo2max. J Appl Physiol 1988; 65:1147–1151
35 Tolep K, Kelsen SG. Effect of aging on respiratory skeletal
muscles. Clin Chest Med 1993; 3:363–378
36 Teramoto S, Ohga E, Ishii T, et al. Reference value of
six-minute walking distance in healthy middle-aged and older
subjects [letter]. Eur Respir J 2000; 15:1132–1133
www.chestjournal.org CHEST / 123 / 2 / FEBRUARY, 2003 397
Downloaded From: http://journal.publications.chestnet.org/ on 10/29/2014
37 Enright PL, Sherrill DL. Reference equations for the six
minute walk in healthy adults. Am J Respir Crit Care Med
1998; 158:1384–1387
38 Troosters T, Gosselink R, Decramer M. Six minute walking
distance in healthy elderly subjects. Eur Respir J 1999;
14:270–274
39 DeBrock V, Mets T, Romagnoli M, et al. Captopril treatment
of chronic heart failure in the very old. Gerontology 1994;
49:148–152
40 Lipkin DP, Scrivin AJ, Crake T, et al. Six minute walking test
for assessing exercise capacity in chronic heart failure. BMJ
1986; 292:653–655
41 Bittner V. Six-minute walk test in patients with cardiac
dysfunction. Cardiologia 1997; 42:897–902
42 Franciosa JA, Levine TB. Lack of correlation between exer-
cise capacity and indices of resting LV performance in heart
failure. Am J Cardiol 1981; 47:33–39
43 Montgomery PS, Gardner AW. The clinical utility of a
six-minute walk test in peripheral arterial occlusive disease
patients. J Am Geriatr Soc1998; 46:706–711
44 Mak VHF, Bugler JR, Roberts CM, et al. Effect of arterial
oxygen desaturation on six minute walk distance, perceived
effort, and perceived breathlessness in patients with airflow
limitation. Thorax 1993; 48:33–38
45 Wijkstra PJ, TenVergert EM, vanderMark ThW, et al. Rela-
tion of lung function, maximal inspiratory pressure, dyspnoea,
and quality of life with exercise capacity in patients with
COPD. Thorax 1994; 49:468–472
46 Rantanen T, Guralnik JM, Rantala RS, et al. Disability,
physical activity, and muscle strength in older women: The
Women’s Health and Aging Study. Arch Phys Med Rehab
1999; 80:130–135
47 Sipila S, Multanen J, Kallinen M, et al. Effects of strength and
endurance training on isometric muscle strength and walking
speed in elderly women. Acta Physiol Scand 1996; 156:457–464
48 Rikli RE, Jones CJ. Functional fitness normative scores for
community-residing older adults, ages 60–94. J Aging Phys
Activity 1999; 7:162–181
49 American Thoracic Society. Guidelines for the six minute
walk test. Am J Respir Crit Care Med 2002; 166:111–117
50 Redelmeier DA, Bayoumi AM, Goldstein RS, et al. Interpret-
ing small differences in functional status: the six minute walk
test in chronic lung disease patients. Am J Respir Crit Care
Med 1997; 155:1278–1282
398 Clinical Investigations
Downloaded From: http://journal.publications.chestnet.org/ on 10/29/2014