Impact of comorbid depression on clinical outcomes in patients with peripheral artery disease: a systematic review and meta-analysis.

BACKGROUND: Depression is a common comorbidity in cardiovascular disease; however, its prognostic impact in peripheral artery disease (PAD) remains uncertain. This study evaluated the association between depression and clinical outcomes in patients with PAD. METHODS: PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to December 2025. Observational studies comparing PAD patients with and without depression were included. Primary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), major amputation, and major adverse limb events (MALE). Random-effects meta-analyses were performed. RESULTS: Thirteen studies involving 681,959 patients were included. Compared with those without depression, PAD patients with depression were generally younger and had a higher burden of cardiovascular and metabolic comorbidities. Depression was not significantly associated with all-cause mortality in pooled analyses of either odds ratios (OR = 2.01; 95% CI: 0.77-5.27; p = 0.15) or hazard ratios (HR = 1.15; 95% CI: 0.97-1.36; p = 0.11). However, depression was significantly associated with worse limb-related outcomes, including major amputation (OR = 1.25; 95% CI: 1.15-1.37; p < 0.001, HR = 1.36; 95% CI: 1.21-1.54; p < 0.001) and MALE (OR = 1.24, 95% CI: 1.16-1.33, p < 0.001). Depression was also associated with a higher risk of MACE in both pooled OR analysis (OR = 1.82; 95% CI: 1.02-3.26; p = 0.04) and time-to-event analysis (HR = 1.24; 95% CI: 1.15-1.35; p < 0.001). CONCLUSIONS: In PAD, comorbid depression was associated with higher MALE and MACE risks, but not all-cause mortality. These findings suggest that mental health assessment may be considered as part of comprehensive PAD care.