Gout Associated With Higher Rates of Lower Extremity Amputation

Gout, affecting up to 4% of US adults, is one of the most common forms of inflammatory arthritis. It has a higher prevalence in older adults, men, and in members of minoritized racial and ethnic groups. Gout is a result of elevated levels of uric acid in the blood (hyperuricemia) and deposits of monosodium urate (MSU) in the joints. This causes the activation of host defense mechanisms in the body and triggers inflammation and immune activation. Effective urate-lowering therapies (ULTs) exist, however, many individuals with gout still fail to lower their uric acid levels below 6 mg/dl. Because of this, the frequency and severity of gout flares increases over time.

Additionally, gout has a strong association with several comorbidities, such as cardiovascular disease, hypertension, chronic kidney disease (CKD), and diabetes. According to a study published in Arthritis & Rheumatology, “Compared with the general population, patients with gout demonstrate a greater than 25% increase in the rate of acute myocardial infarction and are more likely to develop diabetes.” Many of these comorbidities carry an increased risk of undergoing lower extremity amputation (LEA).

JAMA Open Network published a matched cohort study investigating the rates of and risk factors associated with LEA in patients with gout. Utilizing national administrative data from the US Department of Veterans Affairs Health System, the authors of the study used multivariable Cox proportional hazards regression models to assess the associations of gout and LEA. Serum urate control and treatments with ULT were examined as factors associated with LEA. The primary outcome measurement was overall LEA, as well as toe, transmetatarsal, below-the-knee, and above-the-knee amputation.

The study included a total of 5,924,918 patients. Of these, 556,521 had gout. Ninety-nine percent of patients were male, 62.1% were Hispanic, 14.5% were White non-Hispanic, 4.3% were Black non-Hispanic, and the remaining patients were classified as other. After multivariate analysis, patients with gout were more likely to undergo amputation compared with patients without gout. Below-the-knee amputations were the most common type of amputation in gout patients. Patients with poor serum urate control were associated with a 25 to 30% increase in the rate of LEA, and those who were receiving ULT were not associated with LEA rates.

“We found that gout was associated with a 20% increase in the rate of LEA. This increase was independent of comorbidities, such as diabetes, CKD, peripheral vascular disease, and others that serve as established risk factors for LEA and are more common in gout,” the authors of the study said.