Association Between Baseline Depressive Symptoms and Clinical Characteristics, Biomarker Profiles, and Clinical Outcomes in Patients With Peripheral Arterial Disease Undergoing Revascularization: A Prospective Cohort Study.

Background Depressive symptoms are a common comorbidity in patients with peripheral arterial disease (PAD) and have been associated with adverse cardiovascular outcomes. However, their relationship with inflammatory and neuroendocrine biomarkers and their prognostic significance following lower extremity revascularization remains incompletely defined. This study aimed to evaluate whether baseline clinically significant depressive symptoms are associated with clinical characteristics, biomarker profiles, and 24-month clinical outcomes in patients with PAD undergoing revascularization. Methods This prospective, dual-center cohort study included 150 consecutive patients with symptomatic PAD undergoing lower limb revascularization (January 2022-December 2023). Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), with a score ≥10 indicating clinically significant depressive symptoms. Baseline levels of C-reactive protein (CRP), interleukin-6 (IL-6), and cortisol were measured. The primary endpoint was major adverse limb events (MALE) at 24 months. Kaplan-Meier and Cox regression analyses were performed, with adjustment for clinically relevant covariates, including disease severity. Results Of 150 patients, 80 (53.3%) had clinically significant depressive symptoms. Smoking (65.0% vs 37.1%; p = 0.001) and prior cardiovascular events (46.3% vs 25.7%; p = 0.01) were more frequent in this group, which also had a higher prevalence of advanced PAD (Rutherford 4-6). CRP, IL-6, and cortisol levels were higher in patients with depressive symptoms (all p < 0.001). MALE occurred in 37.5% vs 11.4% (p < 0.001). Event-free survival was lower in patients with depressive symptoms (log-rank p < 0.001). In multivariable analysis, depressive symptoms remained associated with MALE (HR: 4.03, 95% CI: 1.84-8.83; p < 0.001). However, given the baseline imbalance in disease severity and the observational design, these findings should be interpreted with caution. Conclusions Clinically significant depressive symptoms are associated with a distinct clinical and biological profile and with worse clinical outcomes in patients undergoing lower extremity revascularization for PAD. These findings suggest a potential prognostic relationship; however, the observed associations may be influenced by disease severity and other confounding factors, and further studies are required to clarify underlying mechanisms and causality.