Backgroup: Reduced physical activity (PA) is a risk factor for the development of gout and hyperuricemia and is associated with all-cause mortality in the general population. However, the relationship between PA and all-cause mortality in patients with hyperuricemia and gout remains unclear. This study aims to investigate the association between PA levels and all-cause mortality in this population, and to explore the dose-response relationship and potential mediating mechanisms.

This retrospective cohort study used data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018, including 4,307 participants aged ≥20 years with hyperuricemia or gout. PA levels were assessed via questionnaire and categorized according to WHO guidelines as inactive, insufficiently active, or active. Weighted Cox proportional hazards models were used to evaluate the association between PA and all-cause mortality. Restricted cubic spline (RCS) analysis, subgroup analysis, restricted mean survival time (RMST) analysis, and mediation analysis were also performed. Sensitivity analyses included excluding deaths within the first 12 months of follow-up and using non-imputed data.

During follow-up, higher PA levels were significantly associated with reduced all-cause mortality. Compared with the inactive group, the active group had a significantly lower risk of death (HR =0.60, 95%CI:0.45,0.78, P < 0.001), with a more pronounced protective effect in patients with gout. RCS analysis revealed a nonlinear dose-response relationship between PA time and mortality risk. RMST analysis showed longer average survival time over 120 months in the active group. Mediation analysis suggested that neutrophil percentage (NEU%) and alkaline phosphatase (ALP) partially mediated the association between PA and mortality. Sensitivity analyses confirmed the robustness of the findings, and no significant heterogeneity was observed across subgroups.

Among patients with hyperuricemia and gout, higher levels of physical activity are significantly associated with a lower risk of all-cause mortality, potentially through anti-inflammatory and metabolic pathways. Encouraging adequate physical activity may improve long-term prognosis in this population.