Abstract
Objective:
Among people with peripheral artery disease (PAD), perceived change in walking difficulty over time, compared with people without PAD, is unclear. Among people reporting no change in walking difficulty over time, differences in objectively measured change in walking performance between people with and without PAD are unknown.
Methods:
A total of 1289 participants were included. Eight hundred seventy-four participants with PAD (aged 71.1 ± 9.1 years) were identified from noninvasive vascular laboratories and 415 without PAD (aged 69.9 ± 7.6 years) were identified from people with normal vascular laboratory testing or general medical practices in Chicago. The Walking Impairment Questionnaire and 6-minute walk were completed at baseline and 1-year follow-up. The Walking Impairment Questionnaire assessed perceived difficulty walking due to symptoms in the calves or buttocks on a Likert scale (range, 0–4). Symptom change was determined by comparing difficulty reported at 1-year follow-up to difficulty reported at baseline.
Results:
At 1-year follow-up, 31.9% of participants with and 20.6% of participants without PAD reported walking difficulty that was improved (P < .01), whereas 41.2% vs 55%, respectively, reported walking difficulty that was unchanged (P < .01). Among all reporting no change in walking difficulty, participants with PAD declined in 6-minute walk, whereas participants without PAD improved (−10 vs +15 meters; mean difference, −25; 95% confidence interval, −38 to −13; P < .01).
Conclusions:
Most people with PAD reported improvement or no change in walking difficulty from calf or buttock symptoms at one-year follow-up. Among all participants who perceived stable walking ability, those with PAD had significant greater declines in objectively measured walking performance, compared with people without PAD.
Keywords: 6-minute walk, Mobility, Patient reported outcome measures, Peripheral artery disease
Patients with lower extremity peripheral artery disease (PAD) typically report that ischemic leg symptoms are stable or improved over time.1–3 Fewer than 5% of people with PAD develop limb threatening ischemia or require lower extremity amputation over 5-year follow-up.1–3 These findings have suggested that the natural history of lower extremity outcomes in PAD is benign.4–8
Separately, longitudinal studies have documented significantly faster annual decline in 6-minute distance in people with PAD, compared with those without PAD.9,10 To our knowledge, no prior longitudinal studies of people with PAD have simultaneously compared changes in patient-reported outcome measures focused on walking difficulty from ischemic leg symptoms with changes in objectively assessed walking performance, measured by the 6-minute walk.
Therefore, this longitudinal study compared the proportions of people with PAD and without PAD who reported improved, no change, or worse walking difficulty due to leg symptoms at 1-year follow-up. Among participants who reported walking difficulty that was unchanged, improved, or worse over 1 year, 1-year change in 6-minute walk performance was compared between people with PAD and without PAD.
METHODS
Overview.
Data were combined from three longitudinal observational studies that measured walking performance and the Walking Impairment Questionnaire (WIQ) at baseline and 1-year follow-up in people with and without PAD.11–13 Methods for these studies (Walking and Leg Circulation Study [WALCS], WALCS II, and WALCS III) were reported.9,11–13 The studies were approved by Institutional Review Boards of all participating sites. Participants provided written informed consent. Individuals who participated in more than one study were included only for the first study they participated in. No interventions were administered by investigators. Participants with lower extremity revascularization between baseline and 1-year follow-up were excluded.
Participant identification.
Participants with PAD were enrolled from noninvasive vascular laboratories and from vascular surgery, cardiology, endocrinology, geriatric, and general medical clinics at multiple Chicago-area medical centers.11–13 Participants without PAD were enrolled using lists of people with normal lower extremity vascular laboratory studies in Chicago area vascular laboratories. Participants without PAD were also enrolled from lists of consecutive people aged 55 years and older with appointments in a large general internal medicine practice at Northwestern.
Inclusion criteria.
Eligible participants with PAD had an ankle-brachial index (ABI) ≤0.90 at their baseline study visit. Eligible participants without PAD had an ABI of 0.91 to 1.40 at baseline.11–13 WALCS included participants aged 55 and older, WALCS II included participants aged 59 and older, and WALCS III had no inclusion criterion for age.11–13
Exclusion criteria.
Exclusion criteria have been described and are summarized here.11–13 Potential participants with a below- or above-knee amputation, wheelchair confinement, or foot ulcer or critical limb ischemia were excluded. Potential participants with major surgery or revascularization during the 3 months prior to enrollment or planned at the time of enrollment were excluded.
Ankle-brachial index.
The ABI was measured with a handheld Doppler probe (Nicolet Vascular Pocket Dop II) using established methods.11–15 The lowest ABI was included in analyses.
Six-minute walk test.
The 6-minute walk was measured in a 100-foot-long hallway. Participants were instructed to walk for 6 minutes, covering as much ground as possible. Whether the participant stopped to rest during the 6-minute walk test was recorded at baseline and 1-year follow-up.
Walking Impairment Questionnaire.
At baseline and 1-year follow-up, participants completed the Walking Impairment Questionnaire (WIQ), a PAD-specific questionnaire that asked participants to assess the degree of difficulty walking due to symptoms in the calves or buttocks on a Likert scale (range of 0–4, where 4 = worst).16 Participants who selected a higher (worse) score on the Likert scale at 1-year follow-up, compared with baseline, were classified as “worse” compared with baseline.17 Those who selected a lower (better) score on the Likert scale at 1-year follow-up, compared with baseline, were classified as “improved” compared with baseline. Those who selected the same score on the Likert scale at 1-year follow-up were classified as “unchanged.” Two additional WIQ questions measured difficulty walking due to thigh symptoms and difficulty walking due to hip, knee, and ankle joint symptoms, respectively, and were scored using the same methods as described for difficulty walking due to calf and buttock symptoms. The question on walking difficulty due to symptoms in the hip, knee, and ankle joints was included because patients with PAD may experience symptoms in the hip, knee, or ankle regions due to lower extremity ischemia. Results are reported using the phrase “walking difficulty” because participants were specifically asked about walking difficulty in the WIQ.
Physical activity, walking exercise, and medications.
Participants reported the number of blocks walked during the past week at baseline and 1-year follow-up. Participants were asked the number of times they had walked for exercise during the past 2 weeks and the number of minutes of exercise per session. Participants brought their medications or a list of medications to their baseline visit. The principal investigator (M.M.M.) classified each medication into one of the following groups: statin, anti-platelet drug, angiotensin-converting enzyme (ACE) inhibitor, or cilostazol.
Other measures.
Race was assessed with patient report. Body mass index (BMI) was calculated as weight (kg)/height (meters2). Comorbidities were ascertained at baseline by combining data from medical record review, medications, participant self-report, and a primary care physician questionnaire using methods from the Women’s Health and Aging Study.11–13,17
Statistical analyses.
Baseline characteristics of participants with and without PAD were compared with ꭕ2 tests for categorical variables and t-tests for continuous variables. Among people without PAD, clinical characteristics of those who reported any walking difficulty due to one or more leg symptoms were compared with those who reported no walking difficulty due to one or more leg symptoms using ꭕ2 tests for categorical variables and t-tests for continuous variables. Proportions of participants with improved, no change, or worse walking difficulty due to calf or buttock pain on the WIQ were compared between people with and without PAD using ꭕ2 tests. Similar analyses were used to compare responses to WIQ questions about difficulty walking due to thigh pain and about difficulty walking due to lower extremity joint pain between people with and without PAD. These analyses were repeated excluding participants with the best Likert scale score at baseline for analyses of improvement, excluding participants with the worst Likert scale score at baseline for analyses of decline, and excluding participants with either the highest or lowest scores for analyses of no change in walking difficulty, because of the potential for a ceiling or floor effect in participants with the highest and lowest scores, respectively. In post-hoc analyses, these analyses were repeated separately among men and women and among people who were Black and not Black, respectively. Within each category of change in walking difficulty for each questionnaire (ie, improvement, no change, worsening), mean 1-year change in ABI was compared between participants with and without PAD, adjusting for baseline ABI.
Among all participants who reported improved walking difficulty from calf or buttock pain at 1-year follow-up, mean 1-year change in 6-minute walk distance was compared between people with vs without PAD, using analyses of covariance, adjusting for baseline 6-minute walk distance, age, sex, race, BMI, smoking history, study cohort, physical activity, and comorbidities. Analyses were repeated with additional adjustment for walking exercise behavior and use of statins, cilostazol, antiplatelet drugs, and ACE inhibitors. Similar analyses were used to compare 1-year change in 6-minute walk distance between those with vs without PAD among all participants reporting no change in walking difficulty from calf or buttock pain at 1-year follow-up and among all participants reporting worse walking difficulty due to calf or buttock pain at 1-year follow-up. Analyses were repeated for questions about walking difficulty due to thigh pain and about difficulty walking due to hip, knee, and ankle symptoms. Among people who did not stop the 6-minute walk at baseline and who reported improved walking difficulty due to calf or buttock symptoms at 1-year follow-up, rates of stopping during the 6-minute walk at 1-year follow-up were compared between people with and without PAD, adjusting for age, sex, race, BMI, smoking history, study cohort, physical activity, comorbidities, medications (statins, antiplatelet, cilostazol, ACE inhibitors), and exercise behavior using logistic regression. Similar analyses were performed among people who did not stop the 6-minute walk at baseline and reported no change in walking difficulty due to calf or buttock symptoms or reported worsening of walking difficulty due to calf or buttock symptoms at 1-year follow-up, respectively. Similar analyses were performed for participants who did not stop the 6-minute walk at baseline and who reported improvement, no change, or worsening in walking difficulty due to thigh symptoms and in walking difficulty due to hip, knee, or ankle symptoms. Linear regression analyses were performed to evaluate associations of baseline ABI and 1-year change in ABI with change in 6-minute walk distance, adjusting for age, sex, race, BMI, change in BMI, smoking history, study cohort, physical activity, comorbidities, medications (statins, antiplatelet, cilostazol, ACE inhibitors), and exercise behavior. Mean change in ABI was calculated across categories of change in leg symptoms for each WIQ question, among people with and without PAD, respectively, using analyses of covariance, adjusting for baseline ABI. Statistical analyses were conducted using SAS 9.4 (SAS Institute Inc). Associations were considered statistically significant if P < .05.
RESULTS
Of 1079 participants with PAD and 486 without PAD enrolled in WALCS, WALCS II, or WALCS III; 874 of those with PAD (81%) and 415 of those without PAD (85%) completed 6-minute walk testing and one or more WIQ questions at baseline and 1-year follow-up and were included in analyses. Compared with people without PAD, participants with PAD were significantly older, included a higher proportion of men, had a significantly higher prevalence of current or former cigarette smoking, had a higher prevalence of diabetes mellitus and cardiovascular diseases, and had higher rates of using statins, anti-platelet drugs, cilostazol, and ACE inhibitors at baseline (Table I). Compared with people without PAD, participants with PAD had a lower prevalence of spinal stenosis, significantly shorter 6-minute walk distance, significantly higher (worse) scores for walking difficulty due to calf or buttock symptoms and walking difficulty due to thigh symptoms, and were less likely to engage in regular walking exercise at baseline (Table I). There were no significant differences in prevalence of knee osteoarthritis or hip osteoarthritis between participants with and without PAD (Table I).
Table I.
Baseline characteristics of participants with and without peripheral artery disease (PAD)
| PAD (n = 874) | Non-PAD (n = 415) | P value | |
|---|---|---|---|
| Age, years | 71.1 (9.1) | 69.9 (7.6) | .023 |
| Males | 527 (60.3) | 190 (45.8) | <.0001 |
| American Indian | 1 (0.1) | 0 (0.0) | .3904 |
| Asian | 4 (0.5) | 1 (0.2) | |
| Black | 199 (22.8) | 78 (18.8) | |
| White | 635 (72.7) | 312 (75.2) | |
| Other race | 29 (3.3) | 19 (4.6) | |
| Race unknown or not reported | 6 (0.7) | 5 (1.2) | |
| Current or former smoking | 729 (83.4) | 251 (60.5) | <.0001 |
| BMI, kg/m2 | 28.1 (5.7) | 28.5 (6.4) | .261 |
| ABI | 0.65 (0.15) | 1.09 (0.10) | <.0001 |
| Diabetes mellitus | 298 (34.1) | 77 (18.6) | <.0001 |
| Angina | 255 (29.2) | 84 (20.2) | .001 |
| Heart failure | 160 (18.3) | 49 (11.8) | .003 |
| Pulmonary disease | 315 (36.0) | 127 (30.6) | .055 |
| Myocardial infarction | 204 (23.3) | 58 (14.0) | <.0001 |
| Cancer | 141 (16.1) | 74 (17.8) | .445 |
| Stroke | 134 (15.3) | 21 (5.1) | <.0001 |
| Spinal stenosis | 92 (10.5) | 128 (30.8) | <.0001 |
| Hip arthritis | 31 (3.6) | 10 (2.4) | .277 |
| Knee arthritis | 90 (10.3) | 50 (12.1) | .345 |
| Statins | 477 (54.8) | 122 (29.4) | <.0001 |
| Cilostazol | 53 (6.1) | 1 (0.2) | <.0001 |
| ACE inhibitors | 286 (32.9) | 88 (21.2) | <.0001 |
| Anti-platelets medications | 565 (64.9) | 168 (40.5) | <.0001 |
| Six-minute walk, meters | 348 (117.8) | 440 (122.2) | <.0001 |
| Walking difficulty due to calf or buttock symptoms (0–4 scale, 4 = worst)a | 1.96 (1.13) | 1.06 (1.19) | <.0001 |
| Walking difficulty due to thigh symptoms (0–4 scale, 4 = worst)a | 1.17 (1.22) | 0.72 (1.05) | <.0001 |
| Walking difficulty due to pain in the hip, knee or ankle joints (0–4 scale, 4 = worst)a | 1.57 (1.21) | 1.51 (1.15) | .3884 |
| Exercised ≥3 times per week | 284 (32.5) | 163 (39.3) | .0168 |
ABI, Ankle brachial index; ACE, angiotensin-converting enzyme; BMI, body mass index.
Data are presented as mean (standard deviation) and number (percent).
Degree of difficulty scales from 0 to 4, 0 = none, 4 = very difficult.
At baseline, among participants without PAD, compared with those who reported no difficulty walking due to pain in the calves or buttocks, pain in the thighs, or pain in the lower extremity joints, those who reported difficulty walking due to one or more of these symptoms had significantly higher BMI (28.8 ± 6.7 vs 26.5 ± 4.7 kg/m2; P < .001), a higher prevalence of diabetes mellitus (22.0% vs 0%; P < .001), a higher prevalence of spinal stenosis (36.6% vs 0%), and a higher prevalence of knee osteoarthritis (14.3% vs 0%).
Compared with those without PAD, participants with PAD were more likely to report improved walking difficulty due to calf or buttock symptoms (31.9% vs 20.6%; P < .01) and improved walking difficulty due to thigh symptoms (26.5% vs 19.5%; P = .006) at 1-year follow-up (Table II). Compared with those without PAD, participants with PAD were less likely to report no change in walking difficulty due to calf or buttock symptoms(41.2% vs 55.0%; P < .01) and no change in walking difficulty due to thigh symptoms (49.9% vs 59.8%; P = .001) at 1-year follow-up (Table II). There were no significant differences in the proportions of people with vs without PAD who reported worsening of walking difficulty due to calf or buttock symptoms or worsening of walking difficulty due to thigh symptoms (Table II). There were no significant differences in the proportions of people with vs without PAD who reported improvement, no change, or worsening of walking difficulty due to lower extremity joint symptoms at 1-year follow-up (Table II). Even after excluding participants with PAD with best or worst values at baseline, 78.3% of participants with PAD reported excluding either improvement or no change in walking difficulty due to calf or buttock symptoms at 1-year follow-up (Table II). There were no meaningful differences in results when analyses were repeated separately among men and women. Among people who were Black, there were no significant differences between those with vs without PAD in the proportion of people who reported that difficulty walking due to calf or buttock symptoms or that difficulty walking due to thigh symptoms improved or did not change at 1-year follow-up (data not shown).
Table II.
One-year changes in walking difficulty in participants with and without peripheral artery disease (PAD)a
| One-year change in walking difficulty related to calf or buttock symptoms | ||||||
|---|---|---|---|---|---|---|
| Improved walking difficulty | No change in walking difficulty | Worse walking difficulty | ||||
| Rates | One-year ABI change, adjusted means (SE) | Rates | One-year ABI change, adjusted means (SE) | Rates | One-year ABI change, adjusted means (SE) | |
| PAD (n = 868) | 277 (31.9%) | 0.01 (0.01) | 358 (41.2%) | −0.01 (0.01) | 233 (26.8%) | −0.06 (0.01) |
| No PAD (n = 413) | 85 (20.6%) | 0.11 (0.03) | 227 (55.0%) | 0.03 (0.01) | 101 (24.5%) | 0.07 (0.02) |
| P value comparing PAD and non-PAD | <.001 | .004 | <.001 | .110 | .363 | <.001 |
| One year change in walking difficulty related to thigh symptoms | ||||||
| Improved walking difficulty | No change in walking difficulty | Worse walking difficulty | ||||
| Rates | One-year ABI change, adjusted means (SE) | Rates | One-year ABI change, adjusted means (SE) | Rates | One-year ABI change, adjusted means (SE) | |
| PAD (n = 867) | 230 (26.5%) | 0.00 (0.01) | 433 (49.9%) | −0.03 (0.01) | 204 (23.5%) | −0.03 (0.01) |
| No PAD (n = 410) | 80 (19.5%) | 0.06 (0.03) | 245 (59.8%) | 0.07 (0.01) | 85 (20.7%) | 0.06 (0.02) |
| P value comparing PAD and non-PAD | .006 | .109 | .001 | <.001 | .265 | .004 |
| One year change in walking difficulty related to lower extremity joint symptoms | ||||||
| Improved walking difficulty | No change in walking difficulty | Worse walking difficulty | ||||
| Rates | One-year ABI change, adjusted means (SE) | Rates | One-year ABI change, adjusted means (SE) | Rates | One-year ABI change, adjusted means (SE) | |
| PAD (n = 872) | 240 (27.5%) | −0.02 (0.01) | 395 (45.3%) | −0.01 (0.01) | 237 (27.2%) | −0.03 (0.01) |
| No PAD (n = 414) | 115 (27.8%) | 0.10 (0.02) | 185 (44.7%) | 0.05 (0.02) | 114 (27.5%) | 0.05 (0.02) |
| P value comparing PAD and non-PAD | .893 | <.001 | .837 | .004 | .924 | .006 |
| One-year changes in walking difficulty, excluding participants with poorest and best scores at baseline | ||||||
| One-year change in walking difficulty related to calf or buttock symptoms | ||||||
| Improved walking difficulty (PAD n = 746 no PAD n = 216) | No change in walking difficulty (PAD n = 682 no PAD n = 205) | Worse walking difficulty (PAD n = 804 no PAD n = 402) | ||||
| Rates | One-year ABI change, LS means (SE) | Rates | One-year ABI change, LS means (SE) | Rates | One-year ABI change, LS means (SE) | |
| PAD | 277 (37.1%) | −0.01 (0.01) | 281 (41.2%) | −0.01 (0.01) | 233 (29.0%) | −0.02 (0.01) |
| No PAD | 85 (39.4%) | 0.08 (0.02) | 77 (37.6%) | 0.08 (0.02) | 101 (25.1%) | 0.06 (0.01) |
| P value | .553 | <.001 | .351 | <.001 | .158 | <.001 |
| One-year change in walking difficulty due to thigh symptoms | ||||||
| Improved walking difficulty (PAD n = 491; no PAD n = 152) | No change in walking difficulty (PAD n = 453; no PAD n = 148) | Worse walking difficulty (PAD n = 829; no PAD n = 406) | ||||
| Rates | One-year ABI change, adjusted means (SE) | Rates | One-year ABI change, adjusted means (SE) | Rates | One-year ABI change, adjusted eans (SE) | |
| PAD | 230 (46.8%) | −0.01 (0.01) | 160 (35.3%) | −0.01 (0.01) | 204 (24.6%) | −0.02 (0.01) |
| No PAD | 80 (52.6%) | 0.07 (0.02) | 37 (25.0%) | 0.06 (0.02) | 85 (20.9%) | 0.06 (0.01) |
| P value comparing PAD & non-PAD | .212 | <.001 | .020 | .003 | .152 | <.001 |
| One-year change in walking difficulty due to lower extremity joint symptoms | ||||||
| Improved walking difficulty (PAD n = 641; no PAD n = 305) | No change in walking difficulty (PAD n = 588; no PAD n = 290) | Worse walking difficulty (PAD n = 819; no PAD n = 399) | ||||
| Rates | One-year ABI change, LS means (SE) | Rates | One-year ABI change, mean (SE) | Rates | One-year ABI change, mean (SE) | |
| PAD | 240 (37.4%) | −0.02 (0.01) | 237 (40.3%) | −0.02 (0.01) | 237 (28.9%) | −0.02 (0.01) |
| No PAD | 115 (37.7%) | 0.07 (0.01) | 114 (39.3%) | 0.06 (0.01) | 114 (28.6%) | 0.06 (0.01) |
| One-year change in walking difficulty due to lower extremity joint symptoms | ||||||
| Improved walking difficulty (PAD n = 641; no PAD n = 305) | No change in walking difficulty (PAD n = 588; no PAD n = 290) | Worse walking difficulty (PAD n = 819; no PAD n = 399) | ||||
| Rates | One-year ABI change, LS means (SE) | Rates | One-year ABI change, mean (SE) | Rates | One-year ABI change, mean (SE) | |
| P value comparing PAD & non-PAD | .938 | <.001 | .777 | <.001 | .895 | <.001 |
ABI, Ankle-brachial index; LS, least squared; SE, standard error.
One-year change in ABI data is adjusted for baseline ABI. Comparisons of ABI were made between people with and without PAD, within each leg symptom category
Participants with PAD had significantly greater declines in ABI at 1-year follow-up than those without PAD among all categories of change in walking difficulty, except for the categories of “no change in walking difficulty due to calf or buttock symptoms” and “improved walking difficulty due to thigh symptoms,” adjusting for baseline ABI (Table II). Among people with PAD, lower ABI at baseline (−7 meters/per 0.10 lower ABI) and greater 1-year decline in ABI (−6 meters/−0.10 ABI decline) were associated with greater 6-minute walk decline at 1-year follow-up, adjusting for age, sex, race, BMI, change in BMI, study cohort, physical activity, comorbidities, medications, and exercise. In these analyses, baseline weight and change in weight were not significantly associated with 6-minute walk decline.
Among participants who reported improved walking difficulty due to calf or buttock symptoms at 1-year follow-up, participants with PAD declined in 6-minute walk by 8 meters, whereas those without PAD improved 6-minute walk by 10 meters (mean difference, −18 meters, (95% CI, −0.2 to −36; P = .047), adjusting for age, sex, race, BMI, comorbidities, baseline 6-minute walk, study cohort, and physical activity (Fig). Among participants who reported no change in walking difficulty due to calf or buttock symptoms at 1-year follow-up, participants with PAD declined by 10 meters, whereas those without PAD improved by 15 meters in 6-minute walk (mean difference, −25 meters; 95% CI, −12.9 to −37.9; P < .001), adjusting for confounders (Fig). Among participants who reported worsened walking difficulty due to calf or buttock symptoms at 1-year follow-up, participants with PAD declined by 25 meters, whereas those without PAD declined by 10 meters (mean difference, −15; 95% CI, −2 to 32; P = .081), adjusting for confounders (Fig). Similar findings were observed for participants with and without PAD among participants reporting improvement, no change, and worse difficulty walking due to thigh symptoms (Fig). Among participants who reported improvement, no change, or worsening of walking difficulty due to hip, knee, or ankle symptoms, respectively, participants with PAD had significantly greater decline in 6-minute walk, compared with those without PAD (Fig). Results in the Fig were not substantially changed after additional adjustment for use of statins, cilostazol, anti-platelet drugs, or ACE inhibitors and exercise behavior.
Fig.
Adjusted change in 6-minute walk distance corresponding to change in symptoms among people with and without peripheral artery disease (PAD) (N = 1281). The figure shows change in 6-minute walk distance (y-axis) in people with and without lower extremity PAD according to change in patient reported difficulty walking due to lower extremity symptoms. A, One-year change in difficulty walking due to calf or buttock symptoms. B, One-year change in difficulty walking due to thigh symptoms. C, One-year change in difficulty walking due to pain in hips, knees, or ankle joints.
Among participants who did not stop during the 6-minute walk test at baseline and who reported improved walking difficulty due to calf or buttock symptoms at 1-year follow-up, 13.7% of people with PAD, compared with 3.9% of people without PAD became unable to complete the 6-minute walk without stopping at 1-year follow-up (P = .036) (Table III). Among participants who did not stop during the 6-minute walk test at baseline and who reported no change in walking difficulty due to calf or buttock symptoms at 1-year follow-up, 14.0% of people with PAD, compared with 2.9% of people without PAD, became unable to complete the 6-minute walk without stopping at 1-year follow-up (P ≤ .001) (Table III). Among participants who did not stop during the 6-minute walk test at baseline and reported worse walking difficulty due to calf or buttock symptoms at 1-year follow-up, 25.0% of people with PAD, compared with 10.0% of people without PAD, became unable to complete the 6-minute walk without stopping at 1-year follow-up (P < .01) (Table III). Similar differences between people with and without PAD were observed for participant reports of improvement, no change, or worsening of walking difficulty due to thigh pain and due to lower extremity joint symptoms (Table III). Among people with PAD, worsening of walking difficulty due to calf and buttock symptoms was associated with significantly greater ABI decline (P trend P = .001), and similar findings were observed among people without PAD (P trend P = .025), adjusting for baseline ABI (Table IV). There were no significant associations of change in walking difficulty due to thigh symptoms or due to lower extremity joint symptoms with change in ABI among people with or without PAD, adjusting for baseline ABI (Table IV).
Table III.
One-year change in 6-minute walk performance according to 1-year change in reported walking difficulty in participants with and without peripheral artery disease (PAD)a
| One-year change in walking difficulty related to calf or buttock symptoms | ||||||
|---|---|---|---|---|---|---|
| Improved walking difficulty (PAD n = 183; no PAD n = 77) | No change in walking difficulty (PAD n = 235; no PAD n = 207) | Worse walking difficulty (PAD n = 156; no PAD n = 90) | ||||
| Rates of becoming unable to walk for 6 minutes without stopping at 1-year follow-up | Adjusted OR for becoming unable to walk 6 minutes without stopping (95% CI) | Rates of becoming unable to walk for 6 minutes without stopping at 1-year follow-up | Adjusted OR for becoming unable to walk 6 minutes without stopping (95% CI) | Rates of becoming unable to walk for 6 minutes without stopping at 1-year follow-up | Adjusted OR for becoming unable to walk 6 minutes without stopping(95% CI) | |
| PAD | 25 (13.7%) | 2.80 (95% CI: 0.59, 13.42) | 33 (14.0%) | 3.54 (95% CI: 1.27, 9.92) | 39 (25.0%) | 4.50 (1.66–12.19) |
| No PAD | 3 (3.9%) | Reference | 6 (2.9%) | Reference | 9 (10.0%) | Reference |
| P value comparing PAD & non-PAD | .036 | .197 | <.001 | .016 | <.01 | .003 |
| One-year change in walking difficulty related to calf or buttock symptoms | ||||||
| Improved walking difficulty (PAD n = 183; no PAD n = 77) | No change in walking difficulty (PAD n = 235; no PAD n = 207) | Worse walking difficulty (PAD n = 156; no PAD n = 90) | ||||
| Rates of becoming unable to walk for 6 minutes without stopping at 1-year follow-up | Adjusted OR for becoming unable to walk 6 minutes without stopping (95% CI) | Rates of becoming unable to walk for 6 minutes without stopping at 1-year follow-up | Adjusted OR for becoming unable to walk 6 minutes without stopping (95% CI) | Rates of becoming unable to walk for 6 minutes without stopping at 1-year follow-up | Adjusted OR for becoming unable to walk 6 min. without stopping (95% CI) | |
| PAD | 23 (16.2%) | 1.83 (0.42, 7.95) | 45 (15.2%) | 5.16 (1.99, 13.34) | 30 (22.1%) | 4.40 (1.22–15.81) |
| No PAD | 5 (7.0%) | Reference | 8 (3.5%) | Reference | 6 (8.1%) | Reference |
| P value comparing PAD & non-PAD | .099 | .420 | <.001 | <.001 | .018 | .023 |
| One-year change in walking difficulty due to lower extremity joint symptoms | ||||||
| Improved walking difficulty (PAD n = 147; no PAD n = 106) | No change in walking difficulty (PAD n = 274; no PAD n = 165) | Worse walking difficulty (PAD n = 156; no PAD n = 104) | ||||
| Rates of becoming unable to walk for 6 minutes without stopping at 1-year follow-up | Adjusted OR for becoming unable to walk 6 minutes without stopping e model 2 (95% CI) | Rates of becoming unable to walk for 6 minutes without stopping at 1-year follow-up | Adjusted OR for becoming unable to walk 6 minutes without stopping e model 2 (95% CI) | Rates of becoming unable to walk for 6 minutes without stopping at 1-year follow-up | Adjusted OR for becoming unable to walk 6 minutes without stopping e model 2 (95% CI) | |
| PAD | 23 (15.6%) | 3.35 (0.92–12.14) | 38 (13.9%) | 4.79 (1.66–13.83) | 38 (24.4%) | 5.08 (1.73–14.95) |
| No PAD | 5 (4.7%) | Reference | 5 (3.0%) | Reference | 9 (8.7%) | Reference |
| P value for comparison between PAD and non-PAD | .011 | .066 | <.001 | .004 | .002 | .003 |
CI, Confidence interval; OR, odds ratio.
Analyses adjust for age, sex, race and study indicator, body mass index, smoking (current or former smoker indicator), diabetes, angina, heart failure, pulmonary disease, myocardial infarction, cancer, stroke, spinal stenosis, hip arthritis, knee arthritis, rheumatoid arthritis, change in blocks walked in the past week, statins, cilostazol, angiotensin-converting enzyme inhibitors, anti-platelets medications, exercised ≥3 times per week.
Table IV.
Change in ankle-brachial index (ABI) according to changes in walking difficulty in people with and without peripheral artery disease (PAD)a
| One-year change in walking difficulty due to calf or buttock symptoms | ||||
|---|---|---|---|---|
| Improved walking difficulty, adjusted mean (95% CI) | No change in walking difficulty, adjusted mean (95% CI) | Worse walking difficulty, adjusted mean (95% CI) | Trend P value | |
| PAD (n = 868) | 0.04 (0.02–0.06) | 0.02 (0.00–0.03) | −0.01 (−0.03 to 0.01) | .001 |
| No PAD (n = 413) | 0.00 (−0.02 to 0.02) | −0.01 (−0.03 to 0.00) | −0.03 (−0.05 to −0.01) | .025 |
| One-year change in walking difficulty due to thigh symptoms | ||||
| Improved walking difficulty, adjusted mean (95% CI) | No change in walking difficulty, adjusted mean (95% CI) | Worse walking difficulty, adjusted mean (95% CI) | Trend P value | |
| PAD (n = 867) | 0.03 (0.01–0.05) | 0.01 (0.00–0.03) | 0.01 (−0.01 to 0.03) | .324 |
| No PAD (n = 410) | −0.02 (−0.04 to 0.00) | −0.01 (−0.02 to 0.01) | −0.04 (−0.06 to −0.01) | .265 |
| One-year change in walking difficulty due to lower extremity joint symptoms | ||||
| Improved walking difficulty, adjusted mean (95% CI) | No change in walking difficulty, adjusted mean (95% CI) | Worse walking difficulty, adjusted mean (95% CI) | Trend P value | |
| PAD (n = 872) | 0.02 (0.00–0.04) | 0.02 (0.00–0.03) | 0.01 (−0.01 to 0.03) | .431 |
| No PAD (n = 414) | 0.00 (−0.02 to 0.02) | −0.02 (−0.03 to 0.00) | −0.03 (−0.05 to −0.01) | .016 |
CI, Confidence interval.
One-year change in ABI data is adjusted for baseline ABI. This general linear model compares change in the ABI within each leg symptom category among people with PAD and among people without PAD. Therefore, these adjusted values differ from values shown in Table II.
DISCUSSION
Among 874 people with PAD followed for 1 year, 75% reported either improvement or no change in walking difficulty due to calf or buttock symptoms at 1-year follow-up. Even after excluding participants with either the best or worst possible scores at baseline, to eliminate a ceiling or floor effect, more than 75% of participants with PAD reported either improvement or no change in walking difficulty at 1-year follow-up.
Even though most people with PAD reported stable or improved walking difficulty due to calf or buttock symptoms and due to thigh symptoms, mean 6-minute walk distance declined within each category of patient reported change in walking difficulty (ie, improvement, no change, worsening) among people with PAD. Among all participants who reported improvement in walking difficulty from calf or buttock symptoms at 1-year follow-up, people with PAD declined by 18 meters in 6-minute walk distance, compared with those without PAD. Among all participants reporting no change in walking difficulty from calf or buttock symptoms at 1-year follow-up, people with PAD declined by 25 meters in 6-minute walk distance, compared with those without PAD. These declines in walking performance among people with PAD were consistent with clinically meaningful changes.18,19 Participants with PAD who reported greater difficulty walking due to calf or buttock symptoms had significantly greater declines in ABI, but there were no significant associations of greater walking difficulty due to thigh symptoms with change in ABI among people with PAD.
These data suggest that many patients with PAD perceive improvement in walking difficulty over time, even though their objectively assessed walking difficulty, measured with the 6-minute walk, simultaneously declines. Therefore, patient reports may often not reflect actual changes in walking difficulty over time in people with PAD. These findings may have implications for clinicians’ ability to identify progression of walking disability in people with PAD. They also may impair clinicians’ ability to diagnose PAD. Although this study was not able to discern reasons for the discordance between participant-reported walking decline and actual walking decline, there are at least two potential explanations. First, people with PAD may reduce their physical activity to avoid ischemic leg symptoms, resulting in improved or stabilized leg symptom-related walking difficulty over time.20 However, limiting physical activity may result in further declines in actual walking ability over time. Limiting physical activity may obscure perceptions of declines in walking performance. Second, people with PAD may slow their walking speed over time to avoid ischemic leg symptoms.21 Slowing walking speed may result in a perception that walking difficulty from leg symptoms has improved but may be associated with declines in 6-minute walk performance.
These findings are relevant to clinical practice guidelines that emphasize use of patient-reported outcomes to evaluate novel treatments for patients with PAD.22 These findings support the use of 6-minute walk testing to measure actual change in walking performance. Practice guidelines should consider recommending serial 6-minute walk tests for accurate monitoring of progression of PAD-related walking disability over time. Documenting declines in 6-minute walk at follow-up visits for patients with PAD may help encourage clinicians to recommend exercise and may help convince PAD patients of the importance of exercise, even when the patient with PAD perceives stabilization or improvement in their symptoms. There is no clinical trial evidence to support using changes in the 6-minute walk test to make decisions about revascularization.
There was no significant difference between participants with and without PAD in the proportion of participants who reported that walking difficulty due to leg symptoms worsened at 1-year follow-up. There are several potential explanations for these results. First, there may be a ‘floor’ effect such that severe symptoms at baseline are not perceived as getting worse over time. However, even after excluding people with the worst leg symptoms at baseline, there were no significant differences between people with and without PAD in rates of worsening walking difficulty due to leg symptoms. Second, people with PAD may reduce their physical activity to avoid ischemic leg symptoms, resulting in perceived improvement or stabilization in leg symptom-limited walking difficulty over time.20 Third, people with PAD may slow their walking speed over time to avoid ischemic leg symptoms.21 Slowing walking speed over time may result in a perception that walking difficulty from leg symptoms has improved but may be associated with declines in 6-minute walk performance. Fourth, patient expectations regarding worsening of leg symptoms over time may be greater than the actual change in walking difficulty, resulting in a relative perception of improved walking difficulty.23
Participants without PAD were identified both from a noninvasive vascular laboratory and from general medical practices and had a 31% prevalence of spinal stenosis. It is likely that the high prevalence of spinal stenosis in those without PAD was associated with their referral to the vascular laboratory, where testing showed no evidence of PAD, and their walking difficulty was attributed to spinal stenosis. However, the high proportion of spinal stenosis in people without PAD may have minimized actual differences in change in 6-minute walk distance between people with PAD and most people without PAD, who have a lower prevalence of spinal stenosis.
This study has several limitations. First, the study duration was 1 year. Similar findings may not be observed after 1 year of follow-up. Second, prevalence of cardiovascular disease was significantly higher in people with PAD compared with those without PAD, and the prevalence of spinal stenosis was significantly higher in people without PAD compared with those with PAD. It is possible that residual or unmeasured confounding may explain some differences in findings between those with and without PAD. Third, symptoms were measured with the well-validated WIQ, but it is possible that, during an unstructured physician interview, worsening of walking difficulty due to ischemic leg symptoms would be more accurately detected. Fourth, these findings apply to people with PAD who did not undergo lower extremity revascularization between baseline and 1-year follow-up.
CONCLUSIONS
Most people with PAD reported improvement or no change in walking difficulty from calf or buttock symptoms at 1-year follow-up. People with PAD who perceived stable walking ability had significant declines in objectively measured walking performance, compared with people without PAD.
DISCLOSURES
M.M.M. reports other research support from ArtAssist, Helixmith, Mars, Chromadex, ReserveAge, and research funding from Regeneron and Helixmith.
ARTICLE HIGHLIGHTS.
Type of Research:
Longitudinal observational study of people with and without peripheral artery disease (PAD) from Chicago medical centers that excluded people with lower extremity revascularization during follow-up
Key Findings:
Of 1289 participants (874 with PAD), at 1-year follow-up, compared with non-PAD participants, participants with PAD were more likely to report improvement in walking difficulty due to calf or buttock symptoms (31.9% vs 20.6%; P < .01) but had significantly greater decline in 6-minute walk distance (mean difference, −17.9 meters [P < .001]).
Take Home Message:
Most people with PAD reported improvement or no change in walking difficulty from calf or buttock symptoms at 1-year follow-up but significantly declined in objectively measured walking performance, compared with people without PAD.
Funding
This study was supported by the National Heart Lung and Blood Institute: R01-HL58099, R01-HL71223, R01-HL083064.
Footnotes
The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest.
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