Exercise effects on the link between inflammation, metabolic health and hyperuricemia: a prospective cohort study.

Background: Adiposity, insulin resistance, and lipid metabolism abnormalities are established risk factors for hyperuricemia; however, the impact of exercise on these factors remains unclear. Moreover, there is a lack of prospective data regarding the predictive value of these risk factors concerning the timing of hyperuricemia onset.

Methods: From 2017 to 2023, data were prospectively collected from annual health checkups and questionnaires. The primary outcome was the incidence of hyperuricemia, stratified into early-onset (age < 40 years) and late-onset (age > 60). Key predictive indicators included the systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (NHHR), triglyceride-glucose index (TyG), and body mass index (BMI). The effects of various exercise types on these indicators were analyzed using multivariate quantile regression models. Cox regression analyses were conducted to assess the hazard ratios (HRs) and their 95% confidence intervals (CIs) of these inflammation and metabolic indictors on hyperuricemia risk. Mediation analyses were performed to explore the roles of these indicators.

Results: Out of 23,534 participants free of hyperuricemia at baseline, 2,555 developed hyperuricemia. Regular exercise was linked to lower inflammation and metabolic indicators, particularly in their higher quantiles. SIRI, BMI, NHHR, and TyG were associated with increased hyperuricemia risk (log-rank p < 0.001), with stronger effect in the early-onset group. For early-onset hyperuricemia, HRs of the highest quantile (Q4) for NHHR, TyG, and BMI > 30 were 1.64 (95% CI, 1.27-2.12), 1.70 (1.32-2.29), and 1.84 (1.29-2.63), respectively. SIRI and SII at Q3 also indicated increased risk. NHHR mediated 5.63% of the overweight/obesity effect on overall hyperuricemia, increasing to 10.86% in early-onset cases, while TyG mediated 12.01%, which was similar to the early-onset group (11.85%).

Conclusions: Higher systemic inflammation, adiposity, and impaired lipid and glucose metabolism significantly increase hyperuricemia risk, particularly in early-onset cases. Exercise as interventions may reduce the levels of these risk factors, especially among individuals in higher quantiles.