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Few modifiable behaviors have been identified that are associated with slower rates of functional decline in persons with lower extremity peripheral arterial disease (PAD). We determined whether higher levels of physical activity during daily life are associated with less functional decline in persons with PAD.
The study population included 203 PAD participants who underwent vertical accelerometer-measured physical activity continuously over seven days and were followed annually for up to 4 years (mean=33.6 months). Outcomes were average annual changes in 6-minute walk performance, usual-paced and fast-paced 4-meter walking velocity, and the short performance physical battery (SPPB). Analyses adjust for age, sex, race, comorbidities, body mass index, ankle brachial index, smoking, and walking exercise frequency. Higher baseline physical activity levels measured by vertical accelerometer were associated with significantly less average annual decline in six-minute walk performance (p trend =.010), fast paced four-meter walking velocity (p trend =.002), and the SPPB (p trend =.001). Compared to the lowest baseline quartile, those in the highest baseline quartile of physical activity had less annual decline in six-minute walk performance (−50.82 feet/year vs. −107.0 feet/year, p=.019), fast paced four-meter walking speed (−.0034 meters/second/year vs. −0.111 meters/second/year, p=.002), and the SPPB (−0.074 vs. −0.829, p=.005).
Higher physical activity levels during daily life are associated with less functional decline among people with PAD. These findings may be particularly important for the large number of PAD persons without access to supervised walking exercise programs.
Lower-extremity peripheral arterial disease (PAD) affects 8 million men and women in the United States.1 Compared to those without PAD, people with PAD have greater functional impairment and more rapid functional decline.2–4 PAD persons have significantly lower physical activity levels during daily life than individuals without PAD. 4–8 Supervised exercise rehabilitation improves walking performance in people with PAD;9 however, barriers such as cost, transportation, and program availability limit access to exercise rehabilitation programs for most people with PAD.10, 11
A relationship between higher levels of physical activity during daily life and lower rates of disability has been demonstrated in non-PAD populations.12–15 However, it is unknown whether, across the lower range of physical activity levels observed in people with PAD, higher physical activity levels during daily life are associated with less functional decline.16
Among persons with PAD, we determined whether higher levels of physical activity during daily life were associated with less functional decline. If higher physical activity levels are protective against functional decline in people with PAD, then interventions to increase daily physical activity in this population may be beneficial.
The institutional review boards of Northwestern University and Catholic Health Partners Hospital approved the protocol. Participants gave written informed consent.
Participants were part of the Walking and Leg Circulation Study (WALCS),3, 4 a prospective, observational study designed to identify predictors of functional decline in PAD. Participants were identified from among consecutive patients aged 55 and older in three Chicago-area non-invasive vascular laboratories. Participants had an ABI <0.90 at their baseline visit.
Exclusion criteria have been reported.4 Patients with dementia, recent major surgery, or foot or leg amputations were excluded. Nursing home residents and wheelchair-bound patients were excluded. Non-English-speaking patients were excluded because investigators were not fluent in non-English languages. Participants who underwent lower extremity revascularization after the baseline visit were excluded from analyses after their revascularization.
A handheld Doppler probe (Nicolet Vascular Pocket Dop II; Nicolet Biomedical Inc, Golden, Colo) was used to obtain systolic pressures in the right and left brachial, dorsalis pedis, and posterior tibial arteries.17, 18 Each pressure was measured twice. The ABI was calculated by dividing the mean of the dorsalis pedis and posterior tibial pressures in each leg by the mean of the 4 brachial pressures.17 Average brachial pressures in the arm with highest pressure were used when one brachial pressure was higher than the opposite brachial pressure in both measurement sets and the 2 brachial pressures differed by 10 mm Hg or more in at least 1 measurement set, because in such cases, subclavian stenosis was possible.17, 18 The lowest leg ABI was used in analyses.
Participants were categorized into the following leg symptom categories, based on previous study3, 4, 19 asymptomatic (no exertional leg symptoms); classical intermittent claudication symptoms; leg pain on exertion and rest (exertional leg pain that sometimes begins at rest); exertional leg pain/carry on (exertional leg pain that does not cause the patient to stop walking); atypical exertional leg pain (exertional leg pain that is not consistent with any of the previous
Depressive symptoms were measured annually using the Geriatric Depression Scale Short Form (GDS-S), a 15-item questionnaire assessing the number of depressive symptoms.20 The GDS-S score ranges from 0 to 15, where 0 indicates no depressive symptoms and 15 indicates that all depressive symptoms in the GDS-S are present.
Functional performance measures were administered at baseline and annually during follow-up.
Participants sit in a straight-backed chair with arms folded across their chest and stand five times consecutively as quickly as possible. Time to complete five chair rises is measured.
Participants were asked to hold three increasingly difficult standing positions for ten seconds each: standing with feet together side-by-side and parallel (side-by-side stand), standing with feet parallel with the toes of one foot adjacent to and touching the heel of the opposite foot (semi-tandem stand), and standing with one foot directly in front of the other with both feet in a straight line (tandem stand).23, 24
Walking velocity was measured with a four-meter walk performed at “usual” and “fastest” pace. For the “usual” paced walk, participants were instructed to walk at their usual pace, “as if going down the street to the store.” Each walk was performed twice. The faster walk in each pair was used in analyses.23, 24
The short physical performance battery combines data from the usual paced four-meter walking velocity, time to rise from a seated position five times, and standing balance. Individuals receive a zero score for each task they are unable to complete. One to four scores are assigned for remaining tasks, based upon quartiles of performance for over 6,000 participants in the Established Populations for the Epidemiologic Study of the Elderly.23, 24 Scores are summed to obtain the short physical performance battery score, ranging from 0 to 12.
Physical activity levels were measured objectively and continuously over seven days with a vertical accelerometer (Caltrac, Muscle Dynamics Fitness Network, Inc, Rocklin, Calif).6, 25–29 After seven days, participants reported the number of activity units displayed on the accelerometer by telephone to investigators and mailed their accelerometer back to investigators. We programmed the accelerometer identically for all participants, which allowed us to compare physical activity levels between participants, irrespective of individual variation in age, weight, height, and sex.6, 25, 27, 28 Programmed in this way, the accelerometers measured "activity units"6, 25, 27, 28. This method of measuring physical activity in people with PAD has been validated previously.6, 8, 25 Because of limited numbers of accelerometers, we distributed them to participants (49%) whenever available.
Patient reported physical activity was measured with a questionnaire derived from the Harvard Alumni Activity Survey that has been previously validated in the Cardiovascular Health Study and the Women’s Health and Aging Study.30–32 The physical activity questionnaire asked, "During the last week, how many city blocks or their equivalent did you walk? Let 12 city blocks equal 1 mile." and "In the last week, about how many flights of stairs did you climb up? A flight is 10 steps."
Height and weight were measured at baseline. Body mass index (BMI) was calculated as weight (kilograms)/height (meters)2. Education and pack-years of cigarette smoking were determined by patient report. Participants were categorized according to their exercise behavior as follows: a) no walking for exercise; b) walking for exercise once or twice per week; c) walking for exercise three or more times per week.
Participants were contacted annually for follow-up visits. Final follow-up visits were completed between November 2002 and September, 2004. Based on previous study, individuals for whom data collection forms indicated that the participant was unable to complete functional measures at follow-up due to wheelchair-confinement, exhaustion, or other significant symptom were classified as too disabled to complete functional measures.4, 16 When no information was provided for the reason a participant refused to complete functional tests, those who met at least two of the following criteria were considered too disabled to walk: a) the participant reported walking fewer than 5 blocks during the previous week; b) the score for repeated chair rises equaled zero or one; c) the score for the standing balance test equaled zero or one. The criteria were defined prior to data analyses. Individuals who refused functional testing at follow-up and met two of these criteria were assigned the minimum value for each test not completed. The minimum value for each test was equivalent to the poorest performance among those who completed testing at the corresponding visit.
Baseline physical activity levels for each physical activity measure were categorized into quartiles. The fourth quartile represented the highest activity level. Baseline characteristics between participants who wore vertical accelerometers and those who did not wear vertical accelerometers were compared with general linear models for continuous variables and 2 tests for categorical variables, with adjustment for age and sex.
In comparing change in functioning (e.g., six minute walk distance) across different patient groups, a longitudinal or repeated measures analysis of covariance (ANCOVA) was carried out using the mixed-effects linear regression analysis.33 Analyses adjusted for baseline covariates (gender, age, and race) and a time-dependent covariate representing functional performance at the immediately preceding visit were carried out on these successive differences. Similar analyses were repeated adjusting additionally for baseline comorbidities, leg symptoms, education, depressive symptoms, and time dependent covariates (BMI, ABI, and pack-years of smoking). Associations of accelerometer data with decline in functional performance were analyzed using baseline measures of physical activity. Vertical accelerometer data were not available for most participants at subsequent follow-up visits. In contrast, patient-reported physical activity (stair flights climbed during the past week and blocks walked during the past week) were obtained annually. Therefore, time-dependent analyses were used for analyses of associations of patient-reported physical activity with functional decline. T-test pair-wise comparisons were also performed for both accelerometer-measured and patient-reported data using participants in the lowest quartile of activity as the reference.
Analyses were also repeated among PAD participants who were asymptomatic, to determine whether associations were maintained in this subset of PAD participants. To determine whether associations between accelerometer-measured physical activity and functional decline were consistent across levels of functional performance, analyses were repeated after stratifying participants according to tertile for each baseline functional measure.
Associations between physical activity and changes in functional measures were evaluated using mixed-effects models, where a subject-specific random effect is used to account for the potential correlations among successive annual differences in each functional measure of the same participant. Dependent variables in each mixed-effect regression analysis were the successive annual differences in each functional measure. Under this initial mixed-effects regression analysis, statistically valid inference is guaranteed, provided missing data caused by patient dropout is unrelated to unobserved data (i.e., any missing data are missing at random [MAR]). As a safeguard against violations to this assumption that missing data are MAR, we repeated the fully adjusted comparisons using a repeated measures pattern-mixture ANCOVA model.34,35 Because data were analyzed using successive differences, there were multiple observed patterns of missing differences in our analyses. The different patterns of missing data were included as two binary indicator covariates (centered about their means). By including patterns of missing data in analyses as centered covariates and averaging over these patterns using adjusted least squares means, one can obtain an unbiased estimate of the marginal means, adjusting for covariates.35 Analyses were performed using SAS statistical software (version 9.1, SAS Institute Inc, Cary, NC).
Four hundred sixty participants with PAD completed baseline testing in the WALCS. Of these 460 participants, 26 died or were lost to follow-up before the first follow-up visit, and 17 underwent lower extremity revascularization prior to their first follow-up visit and were excluded from analyses, leaving 417 PAD participants for analyses. Of these 417, 203 had baseline vertical accelerometer data. As shown in Table 1, there were no significant differences in characteristics of participants who wore the accelerometer versus those who did not (Table 1).
Table 2 shows characteristics of the study population across quartiles of accelerometer-measured physical activity levels. Higher baseline physical activity was associated with more blocks walked during the past week, higher ABI values, lower GDS-S scores, and better performance on each measure of lower extremity functioning at baseline.
Adjusting for age, sex, race, ABI, BMI, smoking, leg symptoms, comorbidities, missing data patterns, education, and depressive symptoms we observed significant, graded associations between accelerometer-measured physical activity at baseline and average annual decline in six-minute walk performance, fast paced walking velocity, and the SPPB (Figure 1). Compared to participants in the lowest baseline quartile of physical activity, PAD participants in the third quartile of physical activity had less decline in the usual pace 4-meter walking velocity (p=.017), the fast pace 4-meter walking velocity (p=.001) and the SPPB (p<.001). Compared to participants in the lowest baseline quartile of physical activity, those in the highest (fourth) quartile had less decline in six-minute walk performance (p=.019), fast paced walking speed (p=.002), and short physical performance battery (p=.005).
Among the 39 asymptomatic PAD participants who wore vertical accelerometers at baseline, those who were more physically active had significantly less decline in six-minute walk performance, and in usual and fastest paced walking velocity (Figure 2).
We repeated analyses after stratifying participants according to tertiles of baseline functional performance (Table 3). Within these tertiles, significant associations between accelerometer-measured physical activity and average annual functional decline were observed among participants in either or both of the lowest or middle tertiles of baseline performance for all measures except usual paced 4-meter walking velocity. Thus, higher physical activity during daily life may be of greatest benefit to PAD persons with greatest functional limitation.
Table 4 shows associations between time-dependent patient-reported physical activity and average annual functional decline. Adjusting for age, sex, race, prior year performance, ABI, BMI, smoking, leg symptoms, comorbidities, missing data patterns, education, and depressive symptoms, more blocks walked during the previous week were associated with less average annual decline in the SPPB (p trend =0.004). More stair flights climbed during the previous week were associated with less decline in the usual (p trend =0.010) and fastest pace (p trend =0.022) four-meter walking velocities.
Among people with PAD, higher levels of physical activity during daily life, measured over seven days with a vertical accelerometer, were associated with significantly less average annual decline in objectively-measured functional performance at four year follow-up compared to lower baseline levels of physical activity. Results also suggest that persons with PAD who have greatest functional impairment may benefit most from higher physical activity levels. Significant associations of higher physical activity with less functional decline were also observed within the subset of participants with asymptomatic PAD. To our knowledge, no prior studies have reported associations between physical activity during daily life and functional decline in people with PAD.
No medications are FDA approved for improving walking performance in persons with asymptomatic PAD, 36 despite the previously established finding that PAD persons who are asymptomatic are at particularly high risk of functional decline.4 While supervised treadmill exercise programs significantly improve walking performance in people with intermittent claudication9,37, barriers such as cost and transportation limit access to exercise rehabilitation programs for most people with PAD.10, 11 Thus, few PAD persons participate in supervised exercise programs.11 Identifying modifiable behaviors associated with slower rates of functional decline provides new opportunities that are non-invasive and inexpensive for preserving lower extremity performance in people with PAD.
Several mechanisms may explain the relative preservation of lower extremity functional performance in PAD persons who are more physically active during daily life. First, in persons without PAD, higher levels of physical activity may reduce systemic atherosclerosis by improving risk factors like hypertension, hyperlipidemia, and diabetes.38 If higher rates of physical activity during daily life slow the progression of lower extremity atherosclerosis, this may explain findings presented here. Second, in persons without PAD, physical activity is associated with improved peripheral arterial endothelial function and increased lower extremity blood flow.39–45 Third, physical activity may improve metabolic efficiency and improve oxygen extraction within the muscle tissue.44,45 Fourth, increased levels of physical activity could favorably alter gait, resulting in more efficient walking techniques.46,47 Finally, higher physical activity levels are inversely associated with inflammatory markers in PAD persons.48 These physiologic and metabolic changes associated with physical activity may explain the association of higher physical activity with slower functional decline among persons with PAD. However, further study is needed.
Patient-reported measures of physical activity were less strongly associated with rates of functional decline compared to associations of the vertical accelerometer measure with functional decline. Objective measures of physical activity are likely to be more accurate than patient reported physical activity levels.
This study has limitations. Only 49% of participants wore the vertical accelerometer device because of the limited availability of these monitors for study participants. However, there were no differences in baseline characteristics between participants who wore the accelerometer versus those who did not. Second, these data are observational. Associations of lower levels of physical activity with greater functional decline cannot be construed as causal. Although we adjusted for confounders including comorbidities, we cannot rule out the possibility that residual confounding, unidentified characteristics, or greater illness severity among participants with lower physical activity levels contributed to the observed differences in functional decline across physical activity groups. Third, we did not collect data on intensity of physical activity.
In conclusion, PAD persons with higher levels of physical activity during daily life have less annual decline in objectively measured functional performance measures at four-year follow-up. These findings suggest that physicians should encourage patients with PAD to increase their daily physical activity levels, because higher physical activity may protect against functional decline. Based on our findings, physicians should encourage their PAD patients to increase activity within their homes, choose stairs rather than the escalator or elevator, and walk rather than drive when traveling short distances. Future study with a clinical trial is necessary to determine whether interventions that increase physical activity levels reduce rates of functional decline in patients with PAD.
Men and women with lower extremity peripheral arterial disease (PAD) have greater functional limitation and faster rates of functional decline compared to persons without PAD. Few modifiable risk factors have been identified that are associated with slower rates of functional decline in persons with PAD. This study assessed the association of greater physical activity during daily life with the rate of decline in functional performance among patients with PAD. Two hundred and three men and women with PAD wore a vertical accelerometer for seven days at baseline for continuous objective monitoring of physical activity and were followed annually for up to 4 years. Higher baseline physical activity during daily life was associated with significantly less average annual decline in 6-minute walking distance, fast-paced four meter walking velocity, and the short performance physical battery, adjusting for confounders. In conclusion, our findings suggest that greater physical activity during daily life is associated with less decline in functional performance among persons with PAD. These findings suggest that clinicians should advise their patients with PAD to maximize physical activity during daily life. However, additional study with a randomized controlled clinical trial is warranted to determine whether interventions that increase physical activity during daily life are associated with slower rates of functional decline in persons with PAD.
Drs. McDermott, Liu, Tian, and Criqui receive grant support from the National Heart Lung and Blood Institute. Drs. Guralnik and Ferrucci are employed by the National Institutes of Health.