Abstract
Cardiometabolic and other risk factors could render patients with gout more likely to undergo lower extremity amputation (LEA). To examine the rate of and factors associated with LEA in patients with gout. In this matched cohort study using national administrative data, multivariable Cox proportional hazards regression models were used to examine the associations of gout with LEA. In analyses limited to patients with gout, attributes of serum urate control and treatment with urate-lowering therapy were examined as factors associated with LEA. This study included patients who used US Department of Veterans Affairs services from January 1, 2000, to July 31, 2015. Patients with gout were identified using diagnostic codes and matched with up to 10 controls by age, sex, and year of benefit enrollment. Data analysis was performed from January 26, 2021, to September 3, 2021. Gout classification served as the primary independent variable of interest. In analyses limited to patients with gout, factors associated with serum urate control and urate-lowering therapy were examined. Overall LEA, as well as toe, transmetatarsal, below-the-knee, and above-the-knee amputation. This cohort study included 5 924 918 patients, 556 521 with gout (mean [SD] age, 67 [12] years; 550 963 (99.0%) male; 88 853 [16.0%] Black non-Hispanic; 16 981 [4.3%] Hispanic/Latinx; 345 818 [62.1%] White non-Hispanic; 80 929 [14.5%] with race and ethnicity data missing; and 23 940 [4.3%] classified as other) and 5 368 397 without gout (mean [SD] age, 67 [12] years; 5 314 344 [99.0%] male; 558 464 [10.4%] Black non-Hispanic; 204 291 [3.0%] Hispanic/Latinx; 3 188 504 [59.4%] White non-Hispanic; 1 257 739 [23.4%)] with race and ethnicity data missing; and 159 399 [3.0%] classified as other). Compared with patients without gout, patients with gout were more likely to undergo amputation, an increased rate that remained after adjustment (adjusted hazard ratio, 1.20; 95% CI, 1.16-1.24) and was highest for below-the-knee amputation (adjusted hazard ratio, 1.59; 95% CI, 1.39-1.81). In those with gout, poor serum urate control (mean >7 mg/dL during the preceding year) was associated with a 25% to 37% increase in the rate of amputation. In contrast, treatment with urate-lowering therapy was not associated with the LEA rate. In this matched cohort study, patients with gout were more likely to undergo LEA. This increase was independent of other comorbidities that have been associated with amputation, including diabetes and peripheral vascular disease. Serum urate control was independently associated with the LEA rate, suggesting the possibility that lower extremity amputation may be preventable in some patients.
Highlights
Gout is the most common form of inflammatory arthritis worldwide, affecting up to 4% of all adults with higher prevalence rates in older men and in members of minoritized racial and ethnic minority groups.[1]
In this matched cohort study, patients with gout were more likely to undergo lower extremity amputation (LEA). This increase was independent of other comorbidities that have been associated with amputation, including diabetes and peripheral vascular disease
From January 1, 2000, to July 31, 2015, a total of 4970 LEAs were performed during 3.4 million patient-years of follow-up in patients with gout (IR, 1.46 [95% CI, 1.42-1.50] procedures per 1000 patient-years), and 24 583 LEAs were performed during 32.1 million patient-years of follow-up in comparators (IR, 0.77 [95% CI, 0.76-0.78] procedures per 1000 patient-years) (Table 2)
Summary
Gout is the most common form of inflammatory arthritis worldwide, affecting up to 4% of all adults with higher prevalence rates in older men and in members of minoritized racial and ethnic minority groups.[1]. In the absence of effective urate-lowering therapy (ULT), flare frequency and severity increase over time, with some patients developing advanced gout characterized by tophi and chronic systemic inflammation. Gout poses a substantial and increasing burden, resulting annually in more than 200 000 emergency department visits[2,3] and total health care costs exceeding $6 billion in the US alone.[4] A significant proportion of costs are preventable, reflecting missed treatment opportunities. With an increasingly well-understood pathogenesis, gout represents a highly treatable condition with management strategies focused on anti-inflammatory agents for flares and ULT to reduce or even halt disease progression.[5,6]
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