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Severe depression and anxiety increased mortality risk in patients with type 2 diabetes and peripheral artery disease undergoing partial foot amputation.

In a recent study published in the Journal of Psychosomatic Research, a team of investigators examined whether depression and anxiety impacted outcomes in patients with type 2 diabetes (T2D) who had peripheral artery disease (PAD) and underwent partial foot amputation.

The prevalence of depression and anxiety is 60% higher in patients with T2D who underwent partial foot amputation compared with the general population who underwent partial foot amputation, according to the study authors.

“In addition, the presence of clinically relevant depressive symptoms in patients with T2D has been previously associated with a poor prognosis, as increased mortality rates, micro- and macrovascular complications, hospitalizations, diabetes-related complications, poorly controlled hyperglycemia, health-care costs, and a decreased QOL,” wrote Evgeniya Shalaeva, MD, and coauthors.

However, anxiety’s impact on various populations remains unclear.

“Patients with non-critical PAD or minor foot amputation are not considered to be at high perioperative risk because in-hospital and early post-operative care is usually conducted in surgical departments with a focus on the wound-healing process,” Dr. Shalaeva and colleagues explained. “As a result, the prevalence and burden of depression and anxiety in patients with T2D with non-critical PAD and indication of minor limb amputations are likely underestimated, and information regarding their impact on post-operative, long-term mortality is missing.”

Partial Foot Amputation Patient Characteristics

The prospective cohort study included 785 consecutive patients (an average 60.9 ±9.1 years of age and 35.9% women). All patients had documented T2D, uncritical PAD, an ankle-brachial index between 0.63 and 0.89 for the affected limb, and unhealed diabetic foot ulcers. In addition, the patients had no history of partial or transfemoral limb amputations for both lower extremities.

The researchers gathered data on patients’ diabetes history, complications, lifestyle characteristics, nutrition, socioeconomic status, and medications. The researchers found a high prevalence of cardiovascular comorbidities in the cohort, and more than half of participants were smokers.

Researchers had patients complete the Patient Health Questionnaire-9 (PHQ-9) at baseline, with scores of 10 or more indicating depression. The investigators used the Hamilton Anxiety Rating Scale to measure anxiety severity.

“After discharge from the surgical hospital, we examined the patients once a week during the first month, and once every 1-2 months during one-year follow-up. The clinical endpoint in this study was one-year all-cause mortality and major adverse cardiovascular events,” Dr. Shalaeva and colleagues wrote.

Impact of Depression and Anxiety

Baseline results indicated that 134 patients (17.1%) had no anxiety symptoms, 429 (54.6%) had mild symptoms, 112 (14.3%) had mild to moderate symptoms, 40 (5.1%) had moderate to severe symptoms, and 70 (8.9%) had severe anxiety.

Regarding depression, 41 (5.2%) had no symptoms, 85 (10.8%) had minimal symptoms, 328 (41.8%) had mild symptoms, 180 (22.9%) had moderate symptoms, 112 (14.3%) had moderately severe symptoms, and 39 (5.0%) had severe symptoms.

Patients who scored 10 or more on the PHQ-9 had significantly higher A1C, new T2D diagnoses, and cardiovascular complications. Patients with depression also had more severe symptoms of anxiety.

All-cause mortality at 1 year was 16.9% (n=133), with most patients (68.4%) dying due to cardiovascular complications and stroke. Mortality was significantly higher in patients with PHQ-9 scores of 10 or more compared with patients whose scores were less than 10 (25.1% vs 11%; P<0.001).

“Depressive symptom dimensions (except sleep problems) were significantly higher among patients who died from all-causes. Among somatic symptoms, the item regarding fatigue had the highest score, followed by sleep and appetite problems, whereas the lowest score was found for psychomotor [impairment],” the researchers reported.

Of note, patients with mild anxiety had lower mortality rates compared with patients who had no anxiety (P=0.032), moderate to severe symptoms (P=0.001), or severe anxiety (P<0.001).

The researchers adjusted for 1-year medication adherence and lifestyle modification compliance and found that severe depression and anxiety were both associated with 1-year all-cause mortality (HR, 3.91; 95% CI, 1.48-10.29; P=0.006; and HR, 2.26; 95% CI, 1.26-4.06; P=0.006, respectively).

Depression was also associated with poorer medication adherence and lifestyle modification compliance, which carried 3.05-fold and 2.54-fold higher mortality risks (both P<0.001).

“Our data showed that questions about negative self-feeling and suicidal ideations were independently associated with increased all-cause mortality and differed between age and gender groups. This indicates not only identification of the total PHQ-9 score is important, but specific depression dimensions may enlighten the area for preventive measures and timely patient treatment,” Dr. Shalaeva and colleagues concluded. “Screening for anxiety and depression should be considered under these circumstances to identify patients at increased risk to allow appropriate intervention.”