Association of Depression With Inferior Amputation-Free Survival in Chronic Limb-Threatening Ischemia

Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral arterial disease) and can cause profound psychosocial distress, including depression. Depression in CLTI patients is often underdiagnosed and its impact on clinical outcomes remains unclear. This study aims to quantify the prevalence of depression in CLTI patients and quantify its impact on outcomes.

A single-center, retrospective analysis was conducted from December 2010 to January 2024. Demographics, comorbidities, ischemia metrics, limb-salvage, and survival were collected and analyzed.

Over 14 y, 801 CLTI patients (median age, 66.7; interquartile range, 59.3-74.3 y; 62.5% male) underwent 1882 revascularizations. The first episode of revascularization procedures included 697 endovascular, 241 open surgical, and 56 hybrid procedures, while 73 extremities were managed without revascularization. During the follow-up, 288 (36.0%) patients underwent minor amputations and 156 (19.5%) underwent major amputations. A total of 255 (31.8%) patients had a history of depression. Binary logistic regression modeling revealed that age (odds ratio [OR], 0.96, 95% confidence interval [CI], 0.95-0.97), female sex (OR, 2.1; 95% CI, 1.5-2.9), congestive heart failure (OR, 1.6: 95% CI, 1.2-2.2), hypothyroidism (OR, 1.6; 95% CI, 1.2-2.8), and active smoking (OR, 1.6; 95% CI, 1.2-2.2) were independently associated with depression. At a 20-mo follow-up, depressed patients had higher rates of major amputation (25.5% versus 16.7%; P = 0.003), lower Kaplan-Meier-estimated amputation-free survival (OR, 49.3; 95% CI, 42.7-55.9 mo versus 70.2, 95% CI, 64.1-76.6 mo; P < 0.001), and lower overall Kaplan-Meier-estimated survival compared to nondepressed patients (OR, 76.9; 95% CI, 65.5-88.5 versus OR, 87.9; 95% CI, 81.9-93.9 mo, P = 0.03). There were no significant differences between depressed and nondepressed patients in baseline symptoms, tissue loss, osteomyelitis, total number of procedures, reintervention rates, and bypass patency. However, depressed patients had higher percentages in Wound, Ischemia, and foot Infection (WIfI) classification ischemia grade I-0 (2.4% versus 4.9%, P < 0.05) and I-2 (11.8% versus 17.9%, P < 0.01), but a lower percentage in grade I-3 (69.7% versus 59.8%, P = 0.001). Depressed patients also had higher percentages in WIfI clinical stage 1 (5.1% versus 9.8%, P < 0.01) and lower in stage 3 (23.2% versus 16.5%, P < 0.05).

Depression is prevalent in almost one-third of CLTI patients and is associated with an increased risk of limb-loss. These findings underscore the opportunity for regimented depression screening and integrated psychosocial care in managing CLTI patients to improve outcomes, particularly for those with less ischemia at baseline, and lower WIfI risk of major amputation. Future research should explore the mechanisms linking depression to adverse outcomes and evaluate interventions to mitigate these risks.