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Patients With Gout at Increased Risk for Lower Extremity Amputation

Investigators analyzed comorbidities, such as diabetes, which has been historically associated with gout, to determine what role, if any, they played in increasing the risk of lower extremity amputation.

Regardless of other comorbidities associated with lower extremity amputation (LEA), patients with gout were at a 33% increased risk of LEA and an even higher risk for amputations below-the-knee, according to upcoming ACR presentation, “Disappearing Digits: A National Retrospective Matched Cohort Study Examining the Risk of Lower Extremity Amputation in Gout.”

A variety of comorbidities, such as diabetes and hypertension, have been historically associated with gout and may increase risk of peripheral vascular disease that can ultimately lead to LEA. Investigators determined what role, if any, they played in increasing the risk of lower extremity amputation.

The Study

This retrospective, matched-cohort study was conducted using information from the national Veterans Health Administrative data collected from approximately 556,521 patients with gout (defined as having ≥2 International Classification of Diseases [ICD-9] codes) between 1999 and 2015. These patients were then matched 1:10 by sex, birth year, and calendar year and compared with 5,368,372 non-gout controls who had not received urate-lowering therapy. ICD-9 and common procedural terminology (CPT) codes defined LEA, which was then further categorized as below-the-knee, above-the-knee, toe and transmetatarsal. Comorbidities were also identified with ICD-9 codes.

After investigators identified patients, they were followed until LEA, death, or end of study.

Multivariable Cox proportional hazards regression was used to account for comorbidities, demographics, and body mass index within the 2 cohorts. A secondary analysis categorized patients into 4 groups: those with gout and diabetes, those without gout who had a diabetes diagnosis, those without gout and diabetes, and those with gout who did not have a diabetes diagnosis.

The Findings

The mean age of patients was 67 years old and 99% were male. Throughout the course of the study, 4970 LEAs (4.2 million patient-years) were seen in the gout cohort and 24, 583 LEAs (40+ million patient-years) were documented in the control group.

After accounting for covariates, gout was associated with a numerically higher risk for LEA (HR 1.33; 95% CI 1.29-1.37) and was highest for below-the-knee amputations (HR 1.66; 95% CI 1.46-1.90). Diabetes was the risk factor most associated with LEA (HR 3.23; 95% CI 3.15-3.32).

Results from the secondary analysis indicated that patients with gout who did not have diabetes still had a 1.57-fold (95% CI 1.51-1.65) increased risk of LEA, with the highest risk found in patients with a diagnosis of both gout and diabetes.

“Further research is needed to better understand the surgical indications for these procedures, whether tophi (which can mimic osteomyelitis) are associated with heightened risk, and to what degree LEA might be prevented in this patient population through enhanced diagnostics or improved gout management,” investigators concluded.