Abstract
Purpose
To determine the association between light intensity physical activity and the incidence of all-cause and cardiovascular mortality in patients with peripheral artery disease (PAD) limited by claudication followed for up to 18.7 years.
Methods
A total of 528 patients with PAD and claudication were screened in Baltimore between 1994 and 2002, and 386 were deemed eligible for the study. At baseline, patients were classified into three physical activity groups: 1) physically sedentary, 2) light intensity, and 3) moderate-to-vigorous intensity based on a questionnaire. All-cause and cardiovascular mortality of patients through December 2014 was determined using the National Death Index and the U.S. Department of Veterans Affairs and the U.S. Department of Defense Suicide Data Repository.
Results
Median survival time was 9.9 years (IQR 4.9–15.7 years, range 0.38–18.7 years). During follow-up, 257 patients (66.6%) died, consisting of 40/48 (83.3%) from the sedentary group, 135/210 (64.3%) from the light intensity group, and 82/128 (64.0%) from the moderate-to-vigorous intensity group. For all-cause mortality, light intensity activity status (hazard ratio [HR]=0.523, p=0.0007) and moderate-to-vigorous intensity status (HR=0.425, p<0.0001) were significant predictors. .During follow-up, 125 patients died due to cardiovascular causes (32.4%), in which light intensity activity status (HR=0.511, p=0.0113) and moderate-to-vigorous intensity activity status (HR=0.341, p=0.0003) were significant predictors.
Conclusions
Light intensity physical activity is associated with nearly 50% lower risk of all-cause and cardiovascular mortality in high-risk patients with PAD and claudication. Furthermore, moderate-to-vigorous intensity physical activity performed regularly is associated with 58% and 66% lower risk of all-cause and cardiovascular mortality, respectively. The survival benefits associated with light intensity physical activity makes it a compelling behavioral intervention that extends beyond improving ambulation.
Keywords: Ambulation, Cardiovascular Risk Factors, Exercise, Peripheral Artery Disease, Survival, Walking
INTRODUCTION
Peripheral artery disease (PAD) is highly prevalent(1, 2) and costly,(3, 4) and is associated with increased risk for mortality.(5) PAD affects 12–22% of Americans over 65 years of age(6) and the annual Medicare costs for PAD are $3.9 billion in the United States alone.(3) PAD is a strong prognostic indicator of poor long-term survival,(7) as the relative risks for all-cause and cardiovascular mortality are approximately three times higher in patients with PAD than in individuals without PAD. The prognosis worsens as the severity of the PAD increases; relative risk for all-cause and cardiovascular mortality progressively increases with a decrease in the ankle/brachial index (ABI).(8)
The primary symptom of PAD is claudication, resulting from inadequate blood flow to the exercising musculature. Claudication leads to poor health-related quality of life due to ambulatory dysfunction,(9, 10) impaired physical function,(10) and lower physical activity.(11, 12) Ambulation is necessary to perform many activities of daily living, and it is not surprising that due to pain with ambulation individuals with PAD and claudication adopt an extremely sedentary lifestyle.(13) Low physical activity contributes to higher mortality risk in patients with PAD. Patients with claudication who regularly performed moderate-to-vigorous intensity physical activities had a lower risk of all-cause mortality than less active patients followed for up to 8.5 years.(14) In PAD patients who primarily have atypical leg pain symptoms or who are asymptomatic, higher levels of self-reported and monitored physical activity were associated with lower risk of all-cause mortality and a combined measure of cardiovascular events and cardiovascular mortality.(15) Furthermore, in PAD patients defined by an ABI < 0.90, a decrease in the number of blocks walked during the preceding week at baseline was associated with higher risk of ischemic heart disease events.(16) Slow walking speed, a surrogate measure of physical activity, was also associated with greater unadjusted risk of cardiovascular mortality,(17) as well as showing a trend of association with cardiovascular mortality after adjustment for 6-minute walk distance.(17) These studies point toward a dose response between lower levels of physical activity and higher risk of mortality and cardiovascular events. However, none have addressed whether benefits are seen with lower intensity physical activity levels, and whether these benefits are evident in patients exclusively with claudication.
Updated physical activity guidelines for US adults provide compelling evidence for the overall health benefits of performing even low amounts of moderate-to-vigorous intensity physical activity.(18) Adults who engage in only minimal moderate-to-vigorous intensity physical activity have nearly a 20% reduction in risk of all-cause mortality compared to those who are completely inactive.(19) Current ACSM guidelines also recommend patients with PAD perform moderate intensity exercise 3–5 days per week.(20) However, many patients with PAD are not capable of engaging in any moderate-to-vigorous intensity physical activity because of functional limitations imposed by claudication, but nearly all patients can at least perform light intensity physical activity.(21) It is not clear whether engaging in light intensity physical activity confers survival benefits that are seen with higher intensities of physical activity in patients with claudication. The current investigation is focused to addresses this knowledge gap.
The primary aim of this study was to determine the association between light intensity physical activity and the incidence of all-cause and cardiovascular mortality in patients with PAD limited by claudication followed for up to 18.7 years. We hypothesized that light intensity physical activity would be associated with lower incidence of all-cause and cardiovascular mortality, independent of ABI and comorbid conditions, and that participating in moderate-to-vigorous intensity physical activity would be associated with even lower incidences.
METHODS
Patients
Approval and Informed Consent
The Institutional Review Board at the University of Maryland Baltimore and the Research and Development committee at the Baltimore Veterans Affairs Maryland Health Care System (VAMHCS) approved this study. Written informed consent was obtained from each patient for the baseline assessments as previously described.(22)
Recruitment
Patients who had PAD and claudication (Fontaine Stage II and Rutherford Grade I)(2) and who were not currently exercising were recruited from the Vascular Clinic at the site of the Baltimore VAMHCS and from local newspaper and radio advertisements for possible enrollment into the study.
Medical Screening through History and Physical Examination
Screening
A total of 528 patients who volunteered to participate were screened for PAD between 1994 and 2002 in the Geriatrics, Research, Education, and Clinical Center at the Baltimore VAMHCS hospital.
Inclusion and Exclusion Criteria
Eligible patients were classified as having Fontaine stage II / Rutherford Grade I PAD(2) defined by the following inclusion criteria: (a) a history of claudication, and (b) an ABI at rest < 0.90. Patients were excluded from this study for the following conditions: (a) absence of PAD, (b) inability to obtain an ABI measure due to non-compressible vessels, (c) asymptomatic PAD (Fontaine stage I / Rutherford Grade 0), (d) rest pain or tissue loss PAD (Fontaine stage III or IV / Rutherford Grade II or III), (e) exercise tolerance limited by factors other than claudication (e.g., severe coronary artery disease, dyspnea, poorly controlled blood pressure), (f) active cancer, renal disease (serum creatinine concentration greater than 1.2 mg/dl), or liver disease, (g) not living independently at home, and (h) any missing baseline data. A total of 386 patients were included in the study and analyses.
Baseline Measurements
Medical History and Physical Examination
Demographic information, cardiovascular risk factors, co-morbid conditions, claudication history, a complete metabolic panel blood draw, and a list of current medications were obtained during a medical history and physical examination. Based on this battery of baseline assessments, patients were coded on cardiovascular risk factors and co-morbid conditions according to standard definitions(23). Medication information was used to assist in defining cardiovascular risk factors, as patients who were taking medications to treat hypertension, dyslipidemia, and diabetes were defined as having those conditions. Patients were further characterized on the presence, severity, and symptoms of PAD.
ABI
After 10 minutes of supine rest, the ankle and brachial systolic blood pressures were obtained according to standard guidelines.(24) The ABI was calculated as ankle systolic pressure / brachial systolic pressure.
Anthropometry
Height was recorded from a stadiometer (SECA, Germany) and body weight was recorded from a balance beam scale (Health-O-Meter Inc., Bridgeview, IL) without shoes. From these measurements, body mass index (BMI) was calculated as weight (kg) / height (m)2.
Physical Activity Status
The Johnson Space Center (JSC) physical activity scale was used to assess the activity level of the participants over the preceding month.(12, 14, 25, 26) The JSC physical activity scale has a strong, independent relationship with maximal oxygen uptake in men and women between the ages of 20 and 79 years,(25, 26) and is associated with peak walking time,(12) ABI,(12) and all-cause mortality in patients with PAD.(14) This 8-point Likert scale consists of the following score choices:
0 = avoid physical activities whenever possible
1 = light physical activities done occasionally
2 = moderate physical activities done regularly for less than 1 hour per week
3 = moderate physical activities done regularly for more than 1 hour per week
4 = heavy physical activities done regularly for less than 30 minutes per week
5 = heavy physical activities done regularly between 30 and 60 minutes per wee
6 = heavy physical activities done regularly between 1 and 3 hours per week
7 = heavy physical activities done regularly for more than 3 hours per week
To better assist patients in their selection, examples of light, moderate, and heavy activities were provided at the bottom of this scale. Light activities were defined as regular walking, household chores, or comparable activities which may cause light sweating. Moderate activities were defined as fast walking, jogging, or comparable activities which may cause moderate sweating. Heavy activities were defined as fast jogging, running, or comparable activities which may cause heavy sweating.
The patients were asked to select the appropriate score (0 to 7) which best described their general level of physical activity for the previous month. Patients who selected a score of 0 were placed into the physically sedentary group, those who selected a score of 1 were placed into the light intensity physical activity group. Because the number deaths attributable to cardiovascular mortality was modest in patients with a physical activity score of 2 (n=11) and with scores between 3–7 (n=21), patients who selected a score of 2 or above were placed into a single moderate-to-vigorous intensity activity group.
Survival Status at Follow-Up
Vital status of study participants through December 2014 was determined using the National Death Index (NDI) and the U.S. Department of Veterans Affairs and the U.S. Department of Defense Suicide Data Repository (SDR). Relevant records in the NDI and SDR were obtained by a search based on a combination of name, social security number, and date of birth. Date and cause of death (encoded using ICD9 or ICD10 codes) were obtained from death certificate information provided by NDI and SDR. Cardiovascular mortality included ICD9 codes 390 through 459 or ICD10 I00 through I99 for the primary cause of death. Survival status information was obtained on all of the patients in the study.
Statistical Analyses
A Cox Proportional hazards analysis was used to model the relation between physical activity and two outcome measures, all-cause mortality and cardiovascular mortality. Both analyses were adjusted for age (years), sex (reference female), BMI (centered at 28.0 kg/m2), ABI, smoking (pack-years), and five dichotomous variables: hypertension, diabetes, history of a lower-extremity revascularization, history of a stroke, and dyslipidemia (reference level for all five was risk factor not present). The proportional hazard assumption was checked by examination of log-log survival curves; plots of the residuals from each model were checked. Adjusted Kaplan Meier survival curves for all-cause mortality and cardiovascular disease-free survival were created, by sex, for a 68-year old patient, having a BMI of 28.0 kg/m2, an ABI of 0.67, a 39.9 pack-year history of smoking, and who had no other major risk factor for PAD, i.e. no history of hypertension, diabetes, hyperlipidemia, stroke, or lower-extremity revascularization. The values used for age, BMI, and ABI are the mean values for the study patients. The value used for pack-years is the median value. All other risk factors were set to zero to eliminate the association of these risk factors in the displays.
RESULTS
The demographic and clinical characteristics of patients with claudication according to baseline physical activity status are shown in Table 1. At baseline, the groups were significantly different on age (p=0.01), sex (p=0.005), obesity (p=0.02), history of cerebrovascular accidents (p=0.02), and years of survival from baseline enrollment (p<0.001) (Table 1). The median survival time for the entire sample was 9.9 years (IQR 4.9 to 15.7 years, range 0.38 to 18.7 years). Compared with individuals in the sedentary group, those in the light intensity physical activity group and the moderate-to-vigorous intensity physical activity group on average lived 5 years more (mean age of death 79 versus 74 years).
Table 1.
Baseline clinical characteristics of patients with peripheral artery disease and claudication according to baseline physical activity status.
| Variables | Sedentary Group (n = 48) |
Light Intensity Activity Group (n = 210) |
Moderate/ Vigorous Intensity Activity Group (n = 128) |
P Value |
|---|---|---|---|---|
| Age (years) | 69.0 (8.8) | 68.7 (8.8) | 66.0 (8.4) | 0.01 |
| Body Mass Index (kg/m2) | 29.1 (5.6) | 27.9 (5.0) | 27.8 (4.5) | 0.23 |
| Ankle/Brachial Index | 0.69 (0.22) | 0.66 (0.23) | 0.70 (0.20) | 0.40 |
| Survival from Enrollment (years) | 5.0 (2.1–9.6) | 9.3 (4.3–15.6) | 12.7 (7.7–16.2) | <0.001 |
| Sex (% Men) | 94 | 76 | 86 | 0.005 |
| Race (% Caucasian) | 73 | 62 | 62 | 0.33 |
| Current Smoking (% yes) | 46 | 32 | 43 | 0.17 |
| Smoking Pack-years | 51 (40) | 42 (38) | 38 (28) | 0.08 |
| Hypertension (% yes) | 60 | 72 | 72 | 0.26 |
| Dyslipidemia (% yes) | 52 | 48 | 51 | 0.83 |
| Diabetes (% yes) | 40 | 32 | 32 | 0.60 |
| Obesity (% yes) | 46 | 30 | 24 | 0.02 |
| Lower Extremity Revascularization (% yes) | 19 | 13 | 11 | 0.39 |
| Myocardial Infarction (% yes) | 35 | 28 | 23 | 0.27 |
| Cerebrovascular Accident (% yes) | 27 | 16 | 10 | 0.02 |
Values are means (SD) or number and percentage of patients with characteristics present except for survival from enrollment, which is median (IQR).
A total of 257 of the 386 patients (66.6%) died during the follow-up period, consisting of 40/48 (83.3%) from the sedentary group, 135/210 (64.3%) from the light intensity physical activity group, and 82/128 (64.0%) from the moderate-to-vigorous intensity physical activity group. The adjusted fraction of men who were alive was lower than the fraction of women at each time point. In both men and women survival followed activity level (Figure 1). Survival was lowest in the sedentary group (Act 0), intermediate in the light intensity physical activity group (Act 1), and highest in the moderate-to-vigorous intensity activity group (Act 2). Significant predictors of all-cause mortality included light intensity physical activity status (p=0.001), moderate-to-vigorous intensity physical activity status (p<0.001), age at baseline (p<0.001), male sex (p<0.001), ABI (p=0.006), smoking pack-years (p=0.022), and diabetes (p=0.004) (Table 2).
Figure 1.
Adjusted survival curves, by sex, based on mortality from all-causes among patients with peripheral artery disease and claudication, grouped according to their baseline physical activity status of sedentary (Act 0), light intensity physical activity (Act 1), and moderate-to-vigorous intensity physical activity (Act 2). The figure was produced for a male (M) and female (F) 68-years old, with a BMI of 28.0 kg/m2, an ABI of 0.67, a 39.9 pack-year smoking history, without hypertension, diabetes, hyperlipidemia, stroke, or lower extremity revascularization.
Table 2.
Multivariable Cox proportional hazards model to predict all-cause mortality from baseline measures in patients with peripheral artery disease and claudication. N=386
| Predictors | Hazard Ratio | Parameter Estimate (SE) | 95% CI | P Value |
|---|---|---|---|---|
| Age | 1.039 | 0.038 (0.008) | 1.022 to 1.056 | < 0.001 |
| Sex | ||||
| Female | 1.0 | |||
| Male | 2.915 | 1.070 (0.250) | 1.786 to 4.757 | < 0.001 |
| Body Mass Index | 0.985 | −0.015 (0.014) | 0.959 to 1.012 | 0.288 |
| Physical Activity | ||||
| Moderate/Vigorous | 0.425 | −0.855 (0.205) | 0.285 to 0.635 | <0.001 |
| Light | 0.523 | −0.648 (0.191) | 0.360 to 0.760 | 0.001 |
| Sedentary | 1.0 | |||
| Ankle/Brachial Index | 0.420 | −0.867 (0.232) | 0.226 to 0.781 | 0.006 |
| Smoking pack-years | 1.004 | 0.004 (0.002) | 1.001 to 1.008 | 0.022 |
| Hypertension | 0.992 | −0.008 (0.144) | 0.748 to 1.316 | 0.956 |
| Diabetes | 1.470 | 0.386 (0.135) | 1.128 to 1.917 | 0.004 |
| Lower Extremity Revascularization | 1.101 | 0.096 (0.181) | 0.722 to 1.568 | 0.596 |
| Cerebrovascular Accident | 1.159 | 0.148 (0.176) | 0.821 to 1.638 | 0.402 |
| Dyslipidemia | 0.924 | −0.079 (0.131) | 0.715 to 1.195 | 0.548 |
Of the 257 decedents, 125 (48.6%) died due to cardiovascular causes. For cardiovascular mortality, the adjusted fraction of men and women alive was not statistically different at any time point (Figure 2 and Table 3). Survival was lowest in the sedentary group (Act 0), intermediate in the light intensity physical activity group (Act 1), and highest in the moderate-to-vigorous intensity physical activity group (Act 2). Significant predictors of cardiovascular mortality included light intensity physical activity status (p=0.011), moderate-to-vigorous intensity physical activity status (p<0.001), age at baseline (p=0.006), and ABI (p=0.001).
Figure 2.
Adjusted survival curves, by sex, based on mortality from cardiovascular causes among patients with peripheral artery disease and claudication, grouped according to their baseline physical activity status of sedentary (Act 0), light intensity physical activity (Act 1), and moderate-to-vigorous intensity physical activity (Act 2). The figure was produced for a male (M) and female (F) 68-years old, with a BMI of 28.0 kg/m2, and ABI of 0.67, a 39.9 pack-year smoking history, without hypertension, diabetes, hyperlipidemia, stroke, or lower extremity revascularization.
Table 3.
Multivariable Cox proportional hazards model to predict cardiovascular mortality from baseline measures in patients with peripheral artery disease and claudication. N=386.
| Predictors | Hazard Ratio | Parameter Estimate (SE) | 95% CI | P Value |
|---|---|---|---|---|
| Age | 1.032 | 0.032 (0.011) | 1.009 to 1.056 | 0.006 |
| Sex | ||||
| Female | 1.0 | |||
| Male | 1.146 | 0.136 (0.251) | 0.701 to 1.874 | 0.587 |
| Body Mass Index | 0.994 | −0.006 (0.019) | 0.958 to 1.031 | 0.749 |
| Physical Activity | ||||
| Moderate/Vigorous | 0.341 | −1.077 (0.296) | 0.191 to 0.609 | < 0.001 |
| Light | 0.511 | −0.671 (0.265) | 0.304 to 0.859 | 0.011 |
| Sedentary | 1.0 | |||
| Ankle/Brachial Index | 0.243 | −1.413 (0.439) | 0.103 to 0.576 | 0.001 |
| Smoking pack-years | 0.999 | −0.001 (0.003) | 0.993 to 1.004 | 0.679 |
| Hypertension | 1.197 | 0.179 (0.218) | 0.781 to 1.833 | 0.410 |
| Diabetes | 1.426 | 0.355 (0.192) | 0.980 to 2.076 | 0.064 |
| Lower Extremity Revascularization | 1.015 | 0.015 (0.272) | 0.596 to 1.729 | 0.955 |
| Cerebrovascular Accident | 1.373 | 0.317 (0.231) | 0.873 to 2.160 | 0.170 |
| Dyslipidemia | 0.827 | −0.190 (0.188) | 0.572 to 1.194 | 0.311 |
DISCUSSION
A novel aspect to this study is the relatively long follow-up period of up to 18.7 years, with a median survival time of 9.9 years. This is the first study to examine the association between light intensity physical activity performed only occasionally on the future incidence of all-cause and cardiovascular mortality in patients with PAD and claudication. Our primary finding was that self-reported occasional light intensity physical activity, which may be far below recommended guidelines, is associated with a lower risk of all-cause mortality by 48% and the risk of cardiovascular mortality by 49%, and these associations were independent of ABI, baseline clinical characteristics, and comorbid conditions. Another major finding was that moderate-to-vigorous intensity physical activity performed regularly, which may approach the recommended guidelines, is associated with a lower risk of all-cause mortality by 58% and the risk of cardiovascular mortality by 66%, and these associations were independent of ABI, baseline clinical characteristics, and comorbid conditions.
Association of Physical Activity With All-Cause and Cardiovascular Mortality in Patients with Claudication
The beneficial association between light intensity physical activity on all-cause and cardiovascular mortality needs to be appreciated within the context of physical activity recommendations for the general population. The 2018 Physical Activity Guidelines for Americans recommends that adults perform 150–300 minutes of moderate-to-vigorous intensity physical activity each week,(18) which reduces risk for all-cause mortality by more than 30%.(19) However, when it is not possible to meet the minimum of 150 minutes of physical activity each week, performing any amount of physical activity is recommended because it lowers the risk of all-cause mortality by 20% in the general population compared to being completely inactive.(19) In comparison, the PAD patients in the current study had a 48% lower risk of all-cause mortality by merely engaging in occasional light intensity activity, which may have better long-term adherence than more vigorous activity.(27) Interestingly, patients with PAD who performed moderate-to-vigorous intensity activity, but typically less than 150 minutes per week as defined by the JSC physical activity scale for scores of 2 or 3, had a further reduction of 58% in all-cause mortality. These findings suggest that patients with claudication, who are at the extreme low end of the physical activity spectrum,(13, 21) can attain approximately 2.5 fold greater relative benefits in survival than the gains observed in the general population by merely performing a small amount of light intensity activity each week. This study supports previous work showing an association between higher levels of physical activity and lower risk of mortality and cardiovascular events in PAD patients,(14–17) and it addresses a gap in the literature in PAD patients by showing that benefits are seen with physical activity levels below a moderate level of intensity. Furthermore, the impact of light intensity physical activity on all-cause and cardiovascular mortality in PAD patients in this study addresses one of the charges set forth by the committee for the 2018 Physical Activity Guidelines for Americans(18) by specifically addressing the need to examine the potential health benefits of performing light intensity physical activity.
The 2018 Physical Activity Guidelines further recommends to limit sitting throughout the day.(18) One possible explanation of our findings that light intensity physical activity done occasionally is related to decreased all-cause and cardiovascular mortality is that these activity bouts break up long periods of inactivity.(28) We have previously shown that increased sedentary behavior is associated with higher inflammation and worse glycemic control and lipid concentrations in people with symptomatic PAD,(29) and that men who have low ambulatory function are the most likely to demonstrate prolong periods of sedentary behavior.(30) These factors may partially explain why occasionally performing bouts of light intensity physical activity is beneficial to survival. These findings agree with recent research that even short bouts of light intensity physical activity, such as standing and walking, results in improved blood pressure, glycemic control, and metabolic health, all of which have the potential to contribute to improved survival.(31, 32)
Association of Physical Activity With Mortality is Independent of Comorbid Conditions and Risk Factors
In addition to physical activity status, several other key clinical variables were associated with all-cause and cardiovascular mortality in our multivariable models. Older age, male sex, lower ABI, greater smoking pack-year history, and presence of diabetes were all associated with greater risk of all-cause mortality. Our results support previous work which found age,(14, 33, 34) ABI,(8, 14, 33) pack-year history of smoking,(34) and diabetes(15) to be independently associated with all-cause mortality, whereas male sex was found to be of borderline significance(14, 33) or not significant.(15) Interestingly, in our study hypertension, dyslipidemia, higher BMI, history of lower extremity revascularization, and history of cerebrovascular accident were not independently associated with all-cause mortality. Only a few clinical variables were significantly associated with cardiovascular mortality in our multivariable analyses, as only older age, male sex, and lower ABI were associated with greater risk of cardiovascular mortality.
It is important to note that physical activity status was significantly associated with all-cause and cardiovascular mortality after adjustment for all other variables in the multivariable models. Furthermore, light intensity physical activity was more strongly associated with all-cause mortality in our patients with claudication than all of the clinical variables considered in the multivariable model except for age and sex, and moderate-to-vigorous intensity physical activity was equally as strong of a correlate as age and sex. For cardiovascular mortality, only age and ABI were stronger correlates than light intensity physical activity, whereas moderate-to-vigorous intensity physical activity was the single strongest predictor in the model.
The benefits of supervised and home-based walking programs on claudication onset time and peak walking time in those with PAD and claudication are well established and have been given class I and IIa recommendations supported by A-level evidence from multiple randomized controlled trials and meta-analyses.(35–39) This study further adds to the literature by demonstrating that engaging in any amount of physical activity is beneficial from a survival standpoint. Importantly, the survival benefits of physical activity are independent of age, sex, cardiovascular risk factors, and comorbid conditions, suggesting that all patients with claudication may improve survival by engaging in a minimum of light intensity physical activity done occasionally. The combined benefits of improved ambulation and better survival from increased activity suggest that health care professionals should routinely assess the physical activity levels of patients with PAD and claudication. While prolonged levels of moderate-to-vigorous intensity activity may seem daunting or unattainable by many with claudication pain, our results suggest that even occasional bouts of physical activity may be beneficial. Consequently, in PAD patients with claudication who have difficulty performing exercise according to recent recommendations,(40) completing light intensity physical activities may be a viable alternative for better health outcomes than compared to engaging in no physical activity.
Limitations
There are several limitations to this study. First, this study used a retrospective, natural history follow-up study design. As such, historical data such as change in physical activity status, change in medication therapy, development of co-morbid conditions, and the number and type of interventional procedures performed during the follow-up period that are typically recorded in a prospectively designed trial were not available for the current investigation. Second, the JSC physical activity scale is a self-reported value in which patients assessed their baseline activity level over the preceding month. Self-report is prone to errors, and even if accurate, the baseline activity level over the preceding month may not reflect chronic activity level prior to the study or the activity status during the follow-up period. For example, the physical activity level of patients may have changed throughout the study from performing no physical activities during the preceding month to performing light or moderate intensity physical activities, or vice versa. A more rigorous study design that periodically determined physical activity status at specified time points would have been necessary to have greater confidence in the baseline measurement of physical activity to reflect the physical activity status during the study. Third, in the moderate-to-vigorous intensity physical activity group, only three patients selected JSC scores between 4 and 7 which define heavy physical activity done at various weekly durations. Therefore, only three would be classified as performing vigorous activities, whereas the remaining patients would be classified as engaging in moderate physical activities. We recognize that our results may not extend to those who participate in vigorous physical activity, though we have little reason to think that more exercise would be harmful to those with PAD. Fourth, the JSC physical activity scale was developed on relatively healthy men and women ranging from 20 and 79 years of age to predict maximal oxygen uptake and was not specifically developed on patients with intermittent claudication. Fifth, during the search in the NDI and SDR data bases, we assumed that individuals were alive if they were not listed as deceased. Some time is required for deaths to be recorded in the NDI and SDR, and it is possible that the mortality data is a slight underestimate due to recent deaths not having been posted at the time of our search. However, it is unlikely that the potential underestimate in mortality was biased towards either the sedentary or physically active groups.
Conclusion and Clinical Significance
In conclusion, light intensity physical activity, which may be far below recommended physical activity guidelines, is associated with lower risk of all-cause and cardiovascular mortality by nearly 50% in high-risk patients with PAD and claudication. Furthermore, moderate-to-vigorous intensity physical activity performed regularly, which may approach the recommended guidelines, is associated with 58% and 66% lower risk of all-cause and cardiovascular mortality, respectively. The clinical significance is that most patients with claudication are capable of occasionally engaging in light intensity physical activity, and the survival benefits associated with light intensity physical activity makes it a compelling behavioral intervention that extends beyond improving ambulation.
Acknowledgments
Supported by grants from the National Institute on Aging (R01-AG-16685, K01-00657), a Claude D. Pepper Older Americans Independence Center grant from NIA (P60-AG-12583 and P60-AG-28747), a Veterans Affairs Career Development Award (IK2RX001788 and IK2RX000944) and by the Geriatric Research Education, and Clinical Center grant (GRECC) from the Veterans Affairs administration. The authors have no conflicts of interest. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM.
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