Peripheral artery disease (PAD) is a highly prevalent, but underdiagnosed manifestation of systemic atherosclerosis [1,2]. In symptomatic patients, lower extremity revascularization (LER) is commonly performed to improve quality of life, although patients remain at increased risk of cardiovascular (CV) events [2]. Importantly, individuals with PAD are likely to have atherosclerosis in other vascular beds [3] and are at high risk for adverse clinical outcomes [4]. However, even within this high-risk population, there is substantial heterogeneity in risk. Thus, there is a significant need to accurately estimate each patient's risk to better evaluate the benefit vs risk of any intervention.

Several peri-procedural risk assessment techniques are commonly employed [5,6] and estimation of an individual's functional capacity is recognized as important in assessing risk. The Duke Activity Status Index (DASI) is a validated questionnaire-based measure of functional capacity [7]. It correlates strongly with gold-standard measures of CV fitness [8,9] and is also predictive of peri-procedural morbidity and mortality [[9], [10], [11]]. Although informal queries of a person's maximal activities can allow for estimation of whether they have poor functional capacity (e.g. achieving <4 metabolic equivalents (METS) regularly), in individuals at high risk for peri-operative outcomes, use of a formal and validated scale such as DASI, is recommended [12].

Multiple factors contribute to determining a person's functional capacity. Whereas age is inversely associated, regular physical activity is strongly associated with greater functional capacity. Conversely, physical inactivity is associated with lower functional capacity and is an independent risk factor for CV disease and events [13]. Physical activity modulates CV risk in myriad, incompletely understood ways [14]. Some of these include the maintenance of a healthy body weight and moderation of blood pressure and insulin sensitivity. Data suggest that regular physical activity suppresses systemic and vascular inflammation; however, mechanism(s) mediating these effects are not well characterized [14,15].

Platelets are critical mediators of hemostasis but also can be pathogenic, given their roles in atherothrombosis [16]. Regular exercise and physical activity have been demonstrated to reduce platelet activity in healthy individuals [17], as well as in persons with hypertension [18], obesity, and established CV disease [19]. Platelets are also increasingly recognized as immune effector cells that can mediate vascular inflammation [20]. Notably, exercise has been shown to reduce markers of platelet-mediated inflammation, specifically in individuals with PAD [15].

Given this background, we sought to investigate the association of functional capacity quantified by DASI with incident major adverse CV and limb events (MACLE) in individuals undergoing LER and its relationship with platelet activity.