Key result
Depression in PAD linked to ~24% higher MALE and MACE risks, but not mortality.
Why the study?
Depression is common in cardiovascular disease, but its prognostic impact in peripheral artery disease remains uncertain.
Does comorbid depression increase the risk of adverse clinical outcomes in patients with peripheral artery disease?
Meta-Analysis (n=681,959)
Does comorbid depression increase the risk of adverse clinical outcomes in patients with peripheral artery disease?
Odds Ratio: 2.01 (95% CI 0.77–5.27)
Absolute Event Rate: 20.25% vs 10.12%
p-value: p=0.15
In patients with peripheral artery disease, comorbid depression is associated with significantly increased risks of major adverse limb events and major adverse cardiovascular events, highlighting the importance of mental health assessment in comprehensive PAD care.
Depression screening may flag higher-risk PAD patients; leaves open whether treatment improves limb or survival outcomes.
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.
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Chen et al. (2026) conducted a meta-analysis in Peripheral artery disease (n=681,959). Depression vs. No depression was evaluated on All-cause mortality (OR 2.01, 95% CI 0.77-5.27, p=0.15). Comorbid depression in patients with peripheral artery disease was associated with increased risks of major adverse limb events (OR 1.24) and major adverse cardiovascular events (HR 1.24), but not all-cause mortality.
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