Uncontrolled serum urate is associated with lower extremity amputations independently of other cardiometabolic risk factors, a new study finds.

In a study of nearly 6 million US veterans (mean age 67; 99% male; 16% Black), 556,521 had gout. Compared with those who did not have gout, patients with gout had a significant 20% higher risk for lower extremity amputations in adjusted analyses, Ted R. Mikuls, MD, MSPH, of the University of Nebraska Medical Center in Omaha, and colleagues reported in JAMA Network Open. The risk varied by anatomic location. Specifically, patients with gout had significant 59%, 27%, 22%, and 11% increased risks for below the knee, toe, above the knee, and transmetatarsal amputations, respectively.

These increased risks were independent of other common comorbidities such as diabetes, hypertension, chronic kidney disease, and peripheral vascular disease, which also increase amputation risk. The researchers could not assess gout severity. The findings do not support tophaceous deposits as the sole explanation for excess amputations. Other research has found that amputation is associated with worse physical functioning, lower health-related quality of life, depression, and early death.

Continue Reading

Among patients with gout in the current study, poor serum urate control (defined as mean serum urate higher than 7 mg/dL) was associated with a 25% to 37% increased risk of lower extremity amputations, the investigators reported. Treatment with urate-lowering therapy did not significantly reduce amputation risk.

According to Dr Mikuls’ team, “Further investigation is needed to understand the indications for [lower extremity amputations] procedures conducted in gout in addition to identifying potential means of prevention as a way of ultimately improving long-term outcomes in this population.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Mikuls TR, Soto Q, Petro A, et al. Comparison of rates of lower extremity amputation in patients with and without gout in the US department of Veterans Affairs health system. JAMA Netw Open. Published online January 6, 2022. doi:10.1001/jamanetworkopen.2021.42347