Background/Purpose: Gout may increase the risk of cardiovascular events (CVEs) and bone fractures through urate deposition and chronic inflammation1,2. However, the additional effects of uncontrolled gout on these outcomes relative to controlled gout is still unclear. This study was designed to examine the risk of CVEs, fractures and mortality in people with uncontrolled versus controlled gout.

Methods: This retrospective cohort study used Optum Clinformatics DataMart® (2016-2024). Controlled gout was defined by no flares, no visible tophi during the baseline year plus normal baseline serum urate (SU) levels (i.e., pre-index SU < 6 mg/dL for three months). An uncontrolled gout group was defined using a new flare, tophi or gout-related emergency department visit or hospitalization following the use of urate-lowering therapies at baseline, along with pre-index SUs ≥6 mg/dL for three months. Outcomes included 1) a composite outcome of incident stroke/acute myocardial infarction; 2) a composite outcome of incident osteoporosis fractures identified using validated algorithms, and 3) all-cause mortality. Each outcome was analyzed in a separate analysis. We estimated inverse-probability of treatment weights (IPTW) for each comparison group using propensity scores. Poisson regressions were used to estimate incidence rates (IRs) and Cox proportional hazard models were used to generate hazard ratios (HRs). Sensitivity analysis was conducted with exact matching of all covariates.

Results: Study participants included 19,645 patients with uncontrolled (72% males; 63% aged 65+) vs. 13,126 patients with controlled (60% males; 71% aged 65+) gout for the CVE analyses, 21,237 uncontrolled vs. 13,569 controlled gout patients for the fracture analysis, and 21,292 uncontrolled vs. 13,615 controlled patients for the mortality analysis. (Table 1 shows an example of the mortality analysis). All baseline covariates were balanced after IPTW. Following IPTW, uncontrolled gout compared to controlled gout was associated with a higher rate of developing incident stroke/AMI (adjHR 2.3; 95%CI 2.2-2.5; 51 versus 23 events per 1,000 person-years), a higher rate of an incident fracture (adjHR 2.1; 95%CI 1.9-2.4; 12 versus 6 events per 1,000 person-years) and a higher mortality (adjHR 1.5; 95%CI 1.4-1.6; 60 versus 42 events per 1,000 person years, Table 2). Sensitivity analysis yielded consistent findings (Table 2).

Conclusion: Patients with uncontrolled gout experienced increased risk of CVEs, bone fractures and mortality compared to controlled gout. These findings highlight the need for clinician awareness and further research to clarify how better control of gout may improve health outcomes. References:1Clarson et al.2015. 2Tzeng et al. 2016.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-of-cardiovascular-conditions-bone-fractures-and-mortality-in-patients-with-uncontrolled-gout-in-comparison-to-those-with-controlled-gout/