Depressive Symptoms Linked to Higher Risk of Peripheral Arterial Disease

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During follow-up, rates of incident PAD were higher among patients with depressive symptoms compared with those without depression.

An elevated level of depressive symptoms were independently linked to a higher risk of incident peripheral arterial disease (PAD) and death, according to a poster presented at the National Kidney Foundation (NKF) 2024 Spring Clinical Meeting.1 This increased risk was observed even after accounting for other known PAD risk factors.

“Among [the 37 million] adults [living in the United States] with chronic kidney disease (CKD), PAD is the third leading cause of atherosclerotic morbidity,” wrote a team of investigators including Celestin Missikpode, PhD, a biostatistician associated with the University of Illinois. “Depression affects nearly 1 in 3 adults with CKD and appears to increase cardiovascular disease via biologic and behavioral pathways.”

To evaluate if elevated depressive symptoms are a risk factor for PAD, investigators used a sample of patients from a multicenter, observational study—the Chronic Renal Insufficiency Cohort (CRIC) study—that included adults with moderate CKD from 2003 to 2021 from 7 clinical centers. Depressive symptoms were defined as a Beck Depression Inventory (BDI) score of ≥ 11. According to the assessment, a score of > 10 indicates an absence of depression, a score of 10-15 indicates mild depression, 16-23 indicates moderate depression, and ≥ 24 indicates severe depression.

Self-reported demographic information and laboratory measures were collected upon enrollment. The BDI was administered at the baseline visit. The longitudinal study involved a baseline study and follow-up appointments every 6 months.

The primary outcome was incident PAD, defined as an Ankle-Brachial Index (ABI) of < .9 or a clinically confirmed PAD (amputation or angioplasty). The associations between risk factors and outcomes were determined using Cox proportional hazards and a mediation analysis assessed the causal pathway between risk factors and outcomes.

The mean follow-up of patients in the cohort was 10.1 years, 50% had diabetes mellitus, and patients were aged 21 to 74 years. Among the entire cohort ranked from persistently low to persistently severe BIDI scores, the median age ranged from 54.5 to 57.5 years.

In total, 2757 adult patients were included in the final analytic cohort, with 25% exhibiting elevated depressive symptoms. The PAD event by Beck category was 22% in the BDI 0-10 group, 31% in the BDI 11-14 group, 29% in the BDI 15-21 group, and 8% in the BDI > 21 group.

During the follow-up period, crude rates of incident PAD were higher among patients with depressive symptoms compared with those without depression (28-31% vs 22%, respectively).

Significant directional trends for various traditional and non-traditional cardiovascular risk factors were observed in adult patients with elevated depressive symptoms compared with those without those symptoms. According to multivariable analyses that adjusted for important demographic and clinical factors, elevated depressive symptoms were independently linked to a higher risk of incident PAD (hazard ratio [HR] 1.23 — 1.48, P <.05) and incident PAD or death (HR 1.10 — 1.41, P <.05).

In the mediation analysis, smoking was the most prominent behavioral risk factor (22.9%), whereas C-reactive protein (CRP) was the most prominent biologic risk factor (.2%) mediating the relationship between incident PAD and elevated depressive symptoms. Among patients in the severely depressed cohort, 20.6% of patients reported smoking compared with 9.0% of those with a persistently low BDI score.

“Depression may be a yet unrecognizable modifiable risk factor for PAD in the setting of CKD,” wrote investigators. “Further efforts to screen, diagnose, and treat depression in CKD patients is warranted.”


  1. Nizamuddin M, Missikpode C, Chen S, Lash J, et al. Depressive Symptoms and Incident Peripheral Arterial Disease among adults in the Chronic Renal Insufficiency Cohort (CRIC) Study. Poster presented at: National Kidney Foundation 2024 Spring Clinical Meeting (SCM). Long Beach, CA. May 14 – 18, 2024.