2025 年 32 巻 9 号 p. 1098-1100
See article vol. 32: 1101-1108
Peripheral artery disease (PAD) is a prevalent and progressive atherosclerotic condition characterized by impaired limb perfusion and reduced mobility1). With a globally aging population, the burden of PAD is expected to increase, highlighting the need for comprehensive management strategies1, 2). The Behavioral Intervention by Allied Health Professionals to Promote Physical Activity (BIP) trial3) was a multicenter randomized clinical study aimed at evaluating whether brief counseling by allied health professionals could significantly increase daily step counts in individuals with PAD who were able to walk (n = 200). Participants in the intervention group received two 60-minute in-person behavioral counseling sessions and two 15-minute follow-up phone calls, whereas the control group received four 15-min phone calls delivering general health education about PAD. Both groups were advised to walk at least three times per week for a minimum of 40 min per session. Although the intervention did not significantly increase daily step counts, it did improve PAD-specific quality-of-life measures3), which have been associated with a lower risk of major adverse cardiovascular events (MACE)4).
Traditional PAD management emphasizes supervised exercise therapy for non-critical limb ischemia and revascularization for critical limb ischemia. However, the role of mental health, particularly depression, has historically received less attention despite its well-established association with poor outcomes in patients with PAD5, 6). In a timely post hoc analysis of the BIP trial, Golledge et al. examined the impact of pharmacologically treated depression on long-term physical activity in patients with PAD7). Among the 200 participants, 14.5% were diagnosed with depression and were receiving antidepressant therapy at baseline. Over 24 months of follow-up, these individuals demonstrated a significantly greater decline in objectively measured daily step counts than those without depression, even after adjusting for confounders, such as sex and chronic lung disease. These findings underscore that depression, even when treated, can adversely affect habitual PA.
A notable strength of this study lies in its use of accelerometer-based step counts to objectively and longitudinally measure daily activity, thus avoiding the limitations inherent in self-reported questionnaires and better reflecting real-world behavior. Interestingly, the decline in physical activity among patients with depression was not paralleled by deterioration in six-minute walk test (6 MWT) performance, suggesting that depression may have a greater impact on unstructured voluntary activity than on structured functional capacity8, 9).
This discrepancy highlights the critical influence of motivation and volition, which are key components of mental health, on PA maintenance in PAD patients. While patients may retain their physical ability to walk, depression may reduce their willingness or perceived capability to engage in regular physical activity. Physical inactivity promotes skeletal muscle deterioration through mechanisms such as mitochondrial dysfunction10), chronic low-grade inflammation10), lipid accumulation11), and extracellular matrix remodeling12). Exercise can counteract these deleterious effects10). Therefore, a sustained decrease in daily physical activity attributable to depression may ultimately result in diminished exercise tolerance owing to muscle dysfunction. These insights strongly support the integration of behavioral and psychological strategies into PAD care.
The present study7) was associated with some limitations. Depression was defined by a clinical diagnosis and medication use without the application of standardized psychiatric tools such as the PHQ-9 or HAM-D. Additionally, the small sample size of individuals with depression (n = 29) limits the power of detailed subgroup analyses. Despite these constraints, the findings are consistent with those of prior research, reinforcing the robust association between depression and functional decline in PAD.
From a clinical standpoint, these results call for a paradigm shift: depression should be actively screened for and managed as a core component of PAD treatment. However, pharmacological therapies alone may be inadequate. Multimodal interventions, including antidepressant medication, cognitive-behavioral therapy, supervised exercise, and social support, are likely necessary to break the bidirectional link between depression and physical inactivity. Indeed, in a related post-hoc analysis of the BIP trial4), the brief counseling intervention not only enhanced physical activity but also reduced symptoms of depression and anxiety and was associated with fewer cardiovascular events.
These findings support the routine incorporation of mental health screening in vascular clinics, ideally using brief, validated tools (e.g., the PHQ-9), and the inclusion of mental health professionals in multidisciplinary PAD care teams. Moreover, the results challenge our reliance on measures such as the 6 MWT as sole functional endpoint in PAD trials. Although such assessments remain useful, they may not adequately capture daily activities. Wearable devices and continuous activity monitoring technologies offer a more granular view of functional status, and may serve as valuable tools in both clinical and research settings. Future studies should explore the efficacy of integrated behavioral, pharmacological, and rehabilitative approaches. A deeper understanding of the mechanisms by which depression contributes to physical inactivity, such as impaired self-efficacy, fatigue, or altered pain perception, is critical for designing effective personalized interventions8, 9).
In conclusion, Golledge et al. provided compelling evidence that depression, even when pharmacologically managed, remains a significant barrier to sustaining physical activity in patients with PAD. This underscores a critical gap in current care models and advocates for a holistic, patient-centered approach that addresses both the vascular and psychological aspects of the disease. As we strive to improve the outcomes and quality of life in PAD, mental health must become a central focus of our clinical strategy.
Dr. Yasu received clinical research funding from Kowa Co., Ltd., AstraZeneca K.K., and Ono Pharmaceutical Co., Ltd.
