Editorial
Frailty Progression in Chronic Limb-threatening Ischemia: A Dynamic Target for Comprehensive Care
2026 年 33 巻 3 号 p. 249-251
詳細
2026 年 33 巻 3 号 p. 249-251
See article vol. 33: 254-264
Chronic limb-threatening ischemia (CLTI) represents the terminal stage of lower extremity artery disease (LEAD) and is characterized by severe ischemia, intractable rest pain, and non-healing ulcers or gangrene. Despite advances in revascularization and wound care, the long-term prognosis remains poor, with high rates of amputation and mortality. The study published in this issue of the Journal of Atherosclerosis and Thrombosis (JAT) addresses a critical aspect of CLTI management: the progression of frailty during hospitalization and its impact on patient outcomes1).
Frailty, defined as a state of heightened vulnerability with increased dependency, is increasingly recognized as a predictor of adverse outcomes in cardiovascular diseases2, 3). A previous study has shown that frailty at admission is associated with a poor survival in CLTI patients4). The novelty of the present study lies in its emphasis on the progression of frailty. The authors reported that worsening frailty during hospitalization independently predicted a poor amputation-free survival (AFS). This finding underscores that frailty is not merely a static baseline risk factor but a dynamic process that can deteriorate under the stress of prolonged illness.
Wound healing in ischemic limbs often requires several months, and severe wounds or a poor general condition inevitably prolong hospitalization5). Prolonged bed rest accelerates sarcopenia, exacerbating frailty and promoting inflammation and nutritional deficits, thereby delaying wound healing6-8). In CLTI, this creates a vicious cycle: delayed wound healing accelerates systemic functional deterioration, which in turn impairs wound healing. Furthermore, in the present study, a poor cardiac function, anemia, and severe wounds were associated with frailty progression, suggesting a close link between frailty deterioration and adverse general conditions. These findings suggest that frailty progression in patients with CLTI is driven by not only local limb conditions but also systemic factors. Patients who receive timely and effective revascularization and wound management may experience only mild frailty progression, whereas those with prolonged healing often experience substantial deterioration. Breaking this vicious cycle is challenging; therefore, minimizing frailty progression during the healing period is a critical therapeutic target.
An important question is when interventions targeting frailty should be initiated and whether or not they can effectively suppress frailty progression. Emerging evidence has suggested that frailty is partially modifiable. Prehabilitation programs, including personalized physical, psychological, and nutritional interventions administered prior to revascularization, have been reported to reduce the incidence of postoperative delirium and shorten the hospital stay in CLTI patients9), suggesting that early intervention may be beneficial.
Another important consideration is to keep hospitalization as short as possible. Because wound healing is often protracted, a prolonged hospital stay predisposes patients to immobility and worsening frailty. If wound care could be effectively continued in outpatient clinics or community-based settings with adequate expertise, it might preserve activity levels and improve outcomes. Strengthening collaboration between hospitals and community providers is an important step in integrated CLTI management.
CLTI represents the end stage of the systemic atherosclerotic burden, at which point pharmacological therapy targeting atherosclerosis is no longer effective. Vascular lesions are often severe, revascularization may be technically challenging, and many patients already present with advanced frailty when CLTI develops. Thus, once CLTI occurs, the therapeutic focus inevitably shifts from aggressive anti-atherosclerotic interventions to comprehensive care, addressing the consequences of CLTI itself (Fig.1).
LEAD, lower-extremity artery disease; CLTI, chronic limb-threatening ischemia
This paradigm shift underscores the importance of early intervention in the natural history of LEAD. Exercise therapy and pharmacological treatment during the metabolic risk stage and intermittent claudication phase are essential to prevent or delay the progression to CLTI. Furthermore, maintaining physical activity and the functional capacity in patients with advanced atherosclerosis helps delay entry into the vicious cycle of CLTI and frailty. If mobility is preserved even after CLTI onset, there may be a greater window of opportunity before frailty progresses to an irreversible stage. Supervised exercise therapy has been shown to improve the functional capacity and delay the transition from intermittent claudication to CLTI10). Maintaining physical activity is important not only after CLTI develops but also throughout the earlier stages of disease progression.
The study in this issue of the JAT provides an important message: Frailty progression is a powerful predictor of poor outcomes in CLTI. For patients with CLTI, preventing in-hospital frailty progression through early mobilization, nutritional support, and community-based wound care may improve the survival and limb outcomes.
CLTI represents the point at which conventional vascular risk management may be exhausted and the therapeutic paradigm must shift toward comprehensive supportive care. Improving outcomes requires recognition that the treatment goals in LEAD are dynamic and evolve with disease stage: aggressive risk factor modification and exercise therapy in early disease, timely revascularization in symptomatic disease, and comprehensive care focused on preserving function in advanced CLTI. This study reminds us that, in CLTI management, the trajectory of the functional status during hospitalization is as important as the technical success of revascularization. Future research should focus on identifying high-risk patients, developing standardized protocols for frailty interventions, and evaluating community-based models of CLTI care to break the vicious cycle that threatens AFS.
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