Association Between Physical Activity and Mortality in Patients With Claudication

Andrew W. Gardner; Odessa Addison; Leslie I. Katzel; Polly S. Montgomery; Steven J. Prior; Monica C. Serra; John D. Sorkin

Disclosures

Med Sci Sports Exerc. 2021;53(4):732-739. 

In This Article

Discussion

A novel aspect to this study is the relatively long follow-up period of up to 18.7 yr, with a median survival time of 9.9 yr. 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 min of moderate- to vigorous-intensity physical activity each week,[17] which reduces risk for all-cause mortality by more than 30%.[18] However, when it is not possible to meet the minimum of 150 min 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 with being completely inactive.[18] 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.[26] Interestingly, patients with PAD who performed moderate- to vigorous-intensity activity, but typically less than 150 min·wk−1 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,[12,20] 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,[13–16] 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 effect 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[17] 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.[17] 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.[27] 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,[28] and that men who have low ambulatory function are the most likely to demonstrate prolong periods of sedentary behaviour.[29] 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, result in improved blood pressure, glycemic control, and metabolic health, all of which have the potential to contribute to improved survival.[30,31]

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,[13,32,33] ABI,[7,13,32] pack-year history of smoking,[33] and diabetes[14] to be independently associated with all-cause mortality, whereas male sex was found to be of borderline significance[13,32] or not significant.[14] 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 class IIa recommendations supported by A-level evidence from multiple randomized controlled trials and meta-analyses.[34–38] 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. Although 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,[39] completing light-intensity physical activities may be a viable alternative for better health outcomes than compared with 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 comorbid 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 before 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, although 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 yr 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 databases, 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 are 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 toward either the sedentary or the physically active groups.

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