http://download.journals.elsevierhealth.com/pdfs/journals/0002-9343/PIIS0002934312004913.pdf
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080184/
Abstract
Context
Survival
estimates help individualize goals of care for geriatric patients, but
life tables fail to account for the great variability in survival.
Physical performance measures, such as gait speed, might help account
for variability, allowing clinicians to make more individualized
estimates.
Objective
To evaluate the relationship between gait speed and survival.
Design, Setting, and Participants
Pooled
analysis of 9 cohort studies (collected between 1986 and 2000), using
individual data from 34 485 community-dwelling older adults aged 65
years or older with baseline gait speed data, followed up for 6 to 21
years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6%,
women; and 79.8%, white; and had a mean (SD) gait speed of 0.92 (0.27)
m/s.
Main Outcome Measures
Survival rates and life expectancy.
Results
There
were 17 528 deaths; the overall 5-year survival rate was 84.8%
(confidence interval [CI], 79.6%–88.8%)and 10-year survival rate was
59.7% (95%CI, 46.5%–70.6%). Gait speed was associated with survival in
all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95% CI, 0.87–0.90; P<.
001). Survival increased across the full range of gait speeds, with
significant increments per 0.1 m/s. At age 75, predicted 10-year
survival across the range of gait speeds ranged from 19% to 87% in men
and from 35% to 91% in women. Predicted survival based on age, sex, and
gait speed was as accurate as predicted based on age, sex, use of
mobility aids, and self-reported function or as age, sex, chronic
conditions, smoking history, blood pressure, body mass index, and
hospitalization.
Conclusion
In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.
Remaining
years of life vary widely in older adults, and physicians should
consider life expectancy when assessing goals of care and treatment
plans.1
However, life expectancy based on age and sex alone provides limited
information because survival is also influenced by health and functional
abilities.2
There are currently no well-established approaches to predicting life
expectancy that incorporate health and function, although several models
have been developed from individual data sources.3–5 Gait speed, also often termed walking speed, has been shown to be associated with survival among older adults in individual epidemiological cohort studies 6–12 and has been shown to reflect health and functional status.13 Gait speed has been recommended as a potentially useful clinical indicator of well-being among the older adults.14
The purpose of this study is to evaluate the association of gait speed
with survival in older adults and to determine the degree to which gait
speed explains variability in survival after accounting for age and sex.
METHODS
Overview
We used individual participant data from 9 cohort studies, baseline data for which were collected between 1986 and 2000 (Table 1).8,15,16,18–23
Each study, which included more than 400 older adults with gait speed
data at baseline, monitored survival for at least 5 years. Analyses
performed herein were conducted in 2009 and 2010. All studies required
written informed consent and institutional review board approval.
Populations
All studies recruited community-dwelling older adults. Although some sought representative samples,8,15,20,23 others focused on healthier participants,16,17 single sex,19,22 or older adults from primary care practices.21
Only participants 65 years and older with baseline gait speed data were
included in this study. Individual study goals, recruitment methods,
and target populations have been published.8,15–23
Measures
Gait
speed was calculated for each participant using distance in meters and
time in seconds. All studies used instructions to walk at usual pace and
from a standing start. The walk distance varied from 8 ft to 6 m. For 8
ft, we converted to 4-m gait speed by formula.24 For 6 m, we created a conversion formula (4-m speed=−0.0341 + (6-mspeed)×0.9816 withR2=0.93, based on a cohort of 61 individuals with concurrent 4- and 6-m walks). For 15 feet (4.57 m),23 speed was simply meters divided by time. Where available, data on fast gait speed (walk as fast as comfortably able25) and the Short Physical Performance Battery were obtained.26
Survival for each individual used study monitoring methods, including
the National Death Index and individual study follow-up. Time from gait
speed baseline to death was calculated in days. Five-year survival
status was confirmed for more than 99% of participants.
Additional
variables include sex, age, race/ethnicity (white, black, Hispanic,
other, defined by participant), height(centimeters), weight(kilograms),
body mass index (BMI), calculated as weight in kilograms divided by
height in meters squared (<25 25="25" and="and">30), smoking (never,
past, current), use of mobility aids (none, cane, walker), systolic
blood pressure, self-reports of health (excellent or very good vs good,
fair, or poor), hospitalization in the past year (yes/no), and
physician-diagnosed medical conditions (cancer, arthritis, diabetes, and
heart disease, all yes/no). Measures of self-reported functional status
were not collected in all studies and varied in content and form. We
created a dichotomous variable reflecting dependence in basic activities
of daily living (ADLs) based on report of being unable or needing help
from another person to perform any basic activity, including eating,
toileting, hygiene, transfer, bathing, and dressing. For individuals
independent in ADLs, we created a dichotomous variable reflecting
difficulty in instrumental ADLs based on report of difficulty or
dependence with shopping, meal preparation, or heavy housework due to a
health or physical problem. Participants were then classified into 1 of 3
groups; dependent in ADLs, difficulty with instrumental ADLs, or
independent. Physical activity data were collected in 6 studies, but
time frames and items varied widely. Two studies used the Physical
Activity Scale for the Elderly (PASE).27 We dichotomized the PASEs core at 100.28
We created operational definitions of other covariates that were
reasonably consistent across studies. Covariates were identical for
height, weight, BMI, and systolic blood pressure. Hospitalization within
the prior year was determined largely by self-report, and chronic
conditions were by self-report of physician diagnosis, with heart
disease encompassing angina, coronary artery disease, heart attack, and
heart failure.25>
Statistical Analysis
Descriptive
statistics summarized participant characteristics, follow-up period,
and median survival from baseline. A study-wide a priori P
value of .002 provides a conservative Bonferroni correction accounting
for atleast 25 individual statistical comparisons. Kaplan-Meier
product-limit survival curves graphically summarize lifetimes for each
gait speed category.29
For graphical purposes, gait speed was categorized into 0.2-m/s
increments with lower and upper extremes being grouped as less than 0.4
m/s and higher than 1.4 m/s.
Cox proportional hazards
regression models were used to assess associations between gait speed
and survival, adjusting for age at baseline, for which hazard ratios
(HRs) correspond to a 0.1-m/s difference in gait speed. The analyses
were repeated adjusting for height, sex, race, BMI, smoking history
systolic blood pressure, diseases, prior hospitalization, and
self-reported heath. Proportionality of hazards was verified by
examining Schoenfeld residual plots.30
Appropriateness of using gait speed as a continuous predictor was
confirmed by observing linearity in Cox models with ordered 0.2-m/s gait
speed categories. To examine the influence of early deaths, we repeated
analyses excluding deaths within 1 year of gait speed measurement and
moved up the 0 time for survival assessment (results were similar;
eTable 1 available at http://www.jama.com).
Subgroup analyses were repeated in strata by age (65–74, 75–84, or ≥85
years), sex, race, self-reported health status, smoking history, BMI,
functional status, use of mobility aids, and hospitalization and by
report of cancer, arthritis, diabetes, and heart disease.29 Results were pooled across sex because no substantial sex differences existed in HRs within subgroup strata.
To
obtain simple and clinically usable estimates of survival probability
based on sex, age, and gait speed, we fit logistic regression models
separately for each sex with dichotomized 5- and 10-year survival as the
response variable and age, gait speed, and their interaction as
continuous predictors. To obtain estimates of median survival (further
life expectancy), we fit Weibull accelerated failure–time models
separately for each with time to death as the response variable, and
age, gait speed, and their interaction as continuous predictors. To
compare ability to predict survival among candidate variables and to
determine whether gait speed improves predictive accuracy beyond other
clinical measures, we fit logistic regression models with dichotomized
5-year or 10-year survival as the response variable and various
combinations of predictors as independent variables with both linear and
squared terms for BMI. The area under the receiver operating
characteristic (ROC) curve or C statistic was used as a measure
predictive of accuracy for mortality. All study-specific statistical
analyses were performed using SAS version 9.2 (SAS Institute Inc, Cary,
North Carolina).
Age-adjusted HRs were pooled from all
studies using standard meta-analytic statistical methodology.
Heterogeneity of HRs across studies was assessed using the Q and I2 statistics.31,32
We used a random-effects model to appropriately pool the HRs on the log
scale while incorporating any heterogeneity among study estimates and
then transform back to obtain an overall HR, along with a 95% confidence
interval(CI)and P value.33 Sensitivity of the results was assessed by fitting a shared frailty34
(unrelated to the geriatric syndrome frailty) model to individual
participant data with a γ-distributed frailty parameter to account for
study effect (results similar; not shown).34,35
Five-and 10-year pointwise survival rates from the Kaplan-Meier curves
for each sex, age-group, and gait speed category combination were pooled
across studies using a random-effects model on the complementary
log-log scale36
and then appropriately inverted to obtain overall estimates of
survival, as presented in the tables. We further used the standard
random effects meta-analytic model to combine sex-specific regression
coefficients for age, gait speed, and their interaction from logistic
regression models for 5- and 10-year survival and used the overall
estimates to construct clinically usable survival probability nomograms;
combine sex-specific regression coefficients for age, gait speed, and
their interaction from accelerated failure time models for time to death
and used the overall estimates to construct clinically usable
life-expectancy nomograms; and combine areas under ROC curves obtained
from 9 studies. An increase of 0.025 in overall area under ROC curve was
interpreted as clinically relevant better accuracy.37
To appropriately combine entire survival curves across the 9 studies,
we used the generalized least squares method for joint analysis of
survival curves.38
We used a random-effects model with weights obtained by inverse of the
variance of the survival function at the median life times to pool the
median survival times for each sex, age group, and gait speed category.
We used Comprehensive Meta Analysis version 2.2 (Biostat Inc, Englewood,
New Jersey) for all meta-analytic methods and Stata SE 8 (StataCorp,
College Station, Texas) for fitting shared frailty models.
RESULTS
The 9 participating studies contributed a total of 34 485 participants (Table 1). Although most studies included men and women, 2 were sex specific.19,22
Of the total, 59.6% were women. There were substantial numbers of
African American (n=3852) and Hispanic (n=2650) participants. The
studies had a wide age range, including 1765 persons older than 85
years. Similarly, there was a wide range of gait speeds, from less than
0.4 m/s (n=1247) to more than 1.4 m/s (n=1491). Study follow-up time
ranged from 6.0 to 21.0 years, with participants followed up for a mean
of 12.2 and a median of 13.8 years. There were 17 528 total deaths
across all studies, with rates varying from 18.40% to 91.87% in
individual studies. Mortality rates appear to be related to length of
follow-up (Table 1).
To
assess consistency across studies, risk of death was estimated per
0.1-m/s higher gait speed. Age-adjusted HRs by study ranged from 0.83 to
0.94 and all were significant (P<.001; Figure 1).
We also examined the survival HRs for gait speed by study in subgroups,
including age, sex, race/ethnicity, BMI, smoking history, use of
mobility aids, prior hospitalization, self-reported health, functional
status, and selected chronic diseases. There were consistent
associations across studies, although given the large sample sizes, Q statistics were often statistically significant (details available in eFigure 1A–M available at http://www.jama.com).
For the 3 levels of functional status (independent, difficulty with
instrumental ADLs, and dependent in ADLs), the pooled HR per 0.1-m/s
increase in gait speed for those who were independent was 0.92 (P= .005), for those with difficulty in instrumental activities was also 0.92 (P<.001) but was 0.94 (P=.02)
among those dependent in ADLs. Because physical activity measures were
not sufficiently consistent across studies, effects could not be pooled.
The Osteoporotic Fractures in Men (MrOS)19 and Hispanic Established Populations for Epidemiologic Studies of the Elderly (EPESE)8
used the Physical Activity Scale for the Elderly (PASE). When
dichotomized at a score of 100 into low and high activity, MrOS had
consistent and statistically significant HRs for low (HR, 0.85; 95% CI,
0.81–0.88) and high (HR, 0.87; 95% CI, 0.84–0.90) physical activity. In
the Hispanic EPESE, the HR for low physical activity was significant
(0.92; 95% CI, 0.88–0.96) but the HR for higher physical activity was
not (0.99; 95% CI, 0.95–1.04). Pooled HRs for all subgroups except
functional status were consistently in the range of 0.81 to 0.92 and all
were significant (P<.002).
The overall HR for survival per each 0.1 m/s faster gait speed was 0.88 (95% CI, 0.87–0.90; P<.001) when pooled across all studies using a random-effects meta-analytic statistical approach (Figure 1 and eFigure 1 available at http://www.jama.com).
Further adjustment for sex, BMI, smoking status, systolic blood
pressure, diseases, prior hospitalization, and self-reported health did
not change the results (overall HR, 0.90; 95% CI, 0.89–0.91; P<.001). Using data from all studies, we created for each sex, 5- and 10-year survival tables (Table 2,
data derived from pooled Kaplan-Meier estimates evaluated at 5 and 10
years, presented in 3 age groups) and graphs (eFigure 3 and eFigure 4
predicted survival based on pooled logistic regression coefficients,
data presented with age as a continuous variable). Gait speed was
associated with differences in the probability of survival at all ages
in both sexes, but was especially informative after age 75 years. In
men, the probability of 5-year survival at age 85 ranged from 0.3 to
0.88 (eFigure 3A) and the probability of 10-year survival at age 75
years ranged from 0.18 to 0.86 (eFigure 4A). In women, the probability
of 5-year survival remained greater than 0.5 until advanced age (eFigure
3B), but 10-year survival at age 75 years ranged from 0.34 to 0.92 and
at age 80 years from 0.22 to 0.86 (eFigure 4B). Stratification by
sex-specific median height failed to show systematic differences in
survival rates between short and tall participants, so results presented
are not stratified by height. Stratification by race/ethnicity
(non-Hispanic white, black, Hispanic) suggested generally similar
survival rates by gait speed among age and sex groups. Confidence
intervals were often wide. In some subsets of slow walkers of Hispanic
descent, survival rates were 10% to 20% higher than in other groups
(eTable 2).
We also used our analyses to estimate median years of remaining life based on sex, age, and gait speed. (Figure 2,
predicted survival data are based on an accelerated failure time model
with Weibull distribution, with age as a continuous variable, and eTable
3, data are derived from pooled Kaplan-Meier estimates evaluated at 5
and 10 years in 3 age groups.) In the pooled sample, median survival in
years for the age groups 65 through 74 years was 12.6 for men and 16.8
for women; for 75 through 84 years, 7.9 for men and 10.5 for women; and
for 85 years or older, 4.6 for men and 6.4 years for women (eTable 3
available at http://www.jama.com).
Predicted years of remaining life for each sex and age increased as
gait speed increased, with a gait speed of about 0.8 m/s at the median
life expectancy at most ages for both sexes (Figure 2; a PDF of enlarged graphs is available at http://www.jama.com).
Gait speeds of 1.0 m/s or higher consistently demonstrated survival
that was longer than expected by age and sex alone. In this older adult
population, the relationship of gait speed with remaining years of life
was consistent across age groups, but the absolute number of expected
remaining years of life was larger at younger ages. For 70-year-old men,
life expectancy ranged from 7 to 23 years and for women, from 10 to 30
years.
To
compare the 5-year survival predictive ability between demographics and
gait speed vs other combinations of variables, we used areas under the
ROC curve (C statistics) in logistic regression models for individual
studies and pooled across studies (Table 3). Gait speed added substantially37
to age and sex in 7 of the 9 studies and in the pooled analysis. C
statistics for age, sex, and gait speed were greater than those for age,
sex, and chronic diseases in 4 of 9 studies, approximately equivalent
in 5 studies and inferior in no studies. C statistics for age, sex, and
gait speed were approximately equivalent to those for age, sex, chronic
diseases, BMI, systolic blood pressure, and prior hospitalization in all
9 studies and in the pooled analysis. There were 4 studies that had
sufficiently consistent data on functional status to create 3
categories: dependent in ADLs, difficulty with instrumental ADLs, and
independent. For these studies, gait speed, age, and sex yielded a C
statistic (0.741) that was not significantly different (P=.78) from age, sex, mobility aids, and functional status (P=.75; Table 3).
Predictive
Accuracy for 5- and 10-Year Survival by Individual Study and Pooled
Data Presented as Area Under the Receiver Operating Characteristic
Curves
For 10-year survival, 6 studies had sufficient follow-up time to perform many of the analyses (Table 3).
Gait speed added predictive ability to age and sex in 4 of 6 studies
and in the pooled analysis. C statistics for age, sex, and gait speed
were not significantly different from C statistics with all the other
factors for any study nor for the pooled analysis. Three studies had
sufficiently consistent data on functional status at baseline to allow
pooling. Gait speed, age, and sex yielded a C statistic (0.734) that was
not significantly different from age, sex, mobility aids, and
functional status (0.732; (P=.95; Table 3).
In
addition, we used C statistics to assess the ability of usual gait
speed to predict survival compared with other physical performance
measures, such as fast gait speed and the Short Physical Performance
Battery (SPPB), a brief measure that includes walk speed, chair rise
ability, and balance. We assessed usual vs fast gait speed in the single
study with both measures (Invecciare in Chianti18
study: usual, 0.727 [95% CI, 0.678–0.776]; fast, 0.684 [95% CI,
0.630–0.739]), suggesting that fast walks did not have an advantage in
survival prediction over usual-paced walks. Gait speed was superior to
the SPPB in the Hispanic Established Populations for the Epidemiological
Study of the Elderly8
(gait speed, 0.617; 95% CI, 0.585–0.649; SPPB, 0.574; 95% CI,
0.539–0.649); was equivalent in the following 3 studies: Health, Aging,
and Body Composition (ABC) study and ABC16
(gait speed, 0.579; 95% CI, 0.548–0.610; SPPB, 0.560; 95% CI,
0.528–0.592); Invecciare in Chianti (gait speed, 0.727; 95% CI,
0.678–0.776; SPPB, 0.738; 95% CI, 0.690–0.735); Predicting Elderly
Performance study18
(gait speed, 0.667; 95% CI, 0.610–0.724; SPPB, 0.691; 95% CI,
0.637–0.744); and worse than SPPB in the Established Populations for the
Epidemiological Study of the Elderly15 (gait speed, 0.638; 95% CI, 0.610–0.777; SPPB, 0.663; 95% CI, 0.636–0.691).
COMMENT
Gait
speed, age, and sex may offer the clinician tools for assessing
expected survival to contribute to tailoring goals of care in older
adults. The accuracy of predictions based on these 3 factors appears to
be approximately similar to more complex models involving multiple other
health-related factors, or for age, sex, use of mobility aids, and
functional status. Gait speed might help refine survival estimates in
clinical practice or research because it is simple and informative.
Why
would gait speed predict survival? Walking requires energy, movement
control, and support and places demands on multiple organ systems,
including the heart, lungs, circulatory, nervous, and musculoskeletal
systems. Slowing gait may reflect both damaged systems and a high-energy
cost of walking.13,39–54
Gait speed could be considered a simple and accessible summary
indicator of vitality because it integrates known and unrecognized
disturbances in multiple organ systems, many of which affect survival.
In addition, decreasing mobility may induce a vicious cycle of reduced
physical activity and de-conditioning that has a direct effect on health
and survival.6
The association between gait speed and survival is known.6,7,9–12,55,56
Prior analyses used single cohorts and presented results as relative
rather than absolute risk, as done herein. Similarly, mortality
prediction models have been developed.3–5,57–60
Some models use self-reported information but others also include
physiological or performance data, for a total of 4 to more than 10
predictive factors. Only a few models assess overall predictive capacity
using C statistics; the reported values are in the range found in the
present study (published area under the curve range, 0.66–0.8261 vs this study, 0.717 and 0.737).
The
strengths of this study are the very large sample of individual
participant data from multiple diverse populations of community-dwelling
elders who were followed up for many years and use of consistent
measures of performance and outcome. We provide survival estimates for a
broad range of gait speeds and calculate absolute rates and median
years of survival. Compared with prior studies that were too small to
assess potential effect modification by age, sex, race/ethnicity, and
other subgroups, we were able to assess multiple subgroup effects with
substantial power. This study has the limitations of observational
research; it cannot establish causal relationships and is vulnerable to
various forms of healthy volunteer bias. The participating study
cohorts, while large and diverse, do not represent the universe of
possible data. Our survival estimates should be validated in additional
data sets. Only 1 of the 9 studies was based in clinical practice,21
and advanced dementia is rare in populations who are competent to
consent for research. However, median years of survival in this study
resemble estimates for US adults across the sex and age range assessed.62
We were unable to assess the association of physical activity with
survival in pooled analyses because measures of activity were highly
variable across studies. Also, participants in these studies had no
prior knowledge about the meaning of walking speed. In clinical use,
participants might walk differently if they are aware of the
implications of the results. Although this study provides information on
survival, further work is needed to examine associations of other
important pooled outcomes such as disability and health care use and to
examine effects in populations more completely based in clinical
practice.
Because gait speed can be assessed by nonprofessional staff using a 4-m walkway and a stopwatch,21
it is relatively simple to measure compared with many medical
assessments. Nevertheless, methodological issues such as distance and
verbal instructions remain.63,64
Self-report is an alternative to gait speed for reflecting function.
However, significant challenges remain in the use of self-report as
well, such as choice of items and reliability, some of which can be
addressed by emerging techniques such as computer adaptive testing based
on item-response theory.65
The results found herein suggest that gait speed appears to be
especially informative in older persons who report either no function
all imitations or only difficulty with instrumental ADLs and may be less
helpful for older adults who already report dependence in basic ADLs.
The research studies analyzed herein used trained staff to measure gait
speed. Staffin clinical settings would need initial training and may
produce more variable results. Long-distance walks have become accepted
in some medical fields and may contribute information beyond short
walks.66–68
However, the longer distance and time to perform the test may limit
feasibility in many clinical settings. Although the sample size of very
slow walkers was small, our data suggest that there may be a
subpopulation who walk very slowly but survive for long periods. It
would be valuable to further characterize this subgroup.
Although
the gait speed–survival relationship seems continuous across the entire
range, cut points may help interpretation. Several authors have
proposed that gait speeds faster than 1.0 m/s suggest healthier aging
while gait speeds slower than 0.6 m/s increase the likelihood of poor
health and function.7,21 Others propose one cutoff around 0.8 m/s.13
In our data, predicted life expectancy at the median for age and sex
occurs at about 0.8 m/s; faster gait speeds predict life expectancy
beyond the median. Perhaps a gait speed faster than 1.0 m/s suggests
better than average life expectancy and above 1.2 m/s suggests
exceptional life expectancy, but additional research will be necessary
to determine this relationship.
How might gait speed be
used clinically? First, gait speed might help identify older adults with
a high probability of living for 5 or 10 more years, who may be
appropriate targets for preventive interventions that require years for
benefit. Second, gait speed might be used to identify older adults with
increased risk of early mortality, perhaps those with gait speeds slower
than 0.6 m/s. In these patients, further examination is targeted at
potentially modifiable risks to health and survival. A recommended
evaluation and management of slow walking includes cardiopulmonary,
neurological and musculoskeletal systems.6,18
Third, gait speed might promote communication. Primary clinicians might
characterize an older adult as likely to be in poor health and function
because the gait speed is 0.5 m/s. In research manuscripts, baseline
gait speed might help to characterize the overall health of older
research participants. Fourth, gait speed might be monitored overtime,
with a decline indicating a new health problem that requires evaluation.
Fifth, gait speed might be used to stratify risks from surgery or
chemotherapy. Finally, medical and behavioral interventions might be
assessed for their effect on gait speed in clinical trials. Such true
experiments could then evaluate causal pathways to determine whether
interventions that improve gait speed lead to improvements in function,
health, and longevity.
The data provided herein are
intended to aid clinicians, investigators, and health system planners
who seek simple indicators of health and survival in older adults. Gait
speed has potential to be implemented in practice, using a stop watch
and a 4-m course. From a standing start, individuals are instructed to
walk at their usual pace, as if they were walking down the street, and
given no further encouragement or instructions. The data in this article
can be used to help interpret the results. Gait speed may be a simple
and accessible indicator of the health of the older person.
References at the link.
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