Long-term cardiovascular mortality risk of hyperuricemia and chronic kidney disease in a general Japanese population: NIPPON DATA90.

PURPOSE: Whether hyperuricemia (HU) independently predicts cardiovascular disease (CVD) remains debated, whereas chronic kidney disease (CKD) is a well-established risk factor. This study assessed the independent and mediated association of HU in CKD on long-term CVD mortality in a 30-year nationwide Japanese cohort. METHODS: Data from NIPPON DATA90 participants aged ≥ 30 years enrolled in 1990 and followed for up to 30 years were used. HU was defined as serum uric acid ≥ 416.4 µmol/L, and CKD as an estimated glomerular filtration rate < 60 mL/min/1.73 m² or positive proteinuria. Four baseline categories were created (neither, HU-only, CKD-only, both conditions), and analyzed via Cox models to estimate hazard ratios (HR) for CVD mortality, adjusted for age, sex, hypertension, diabetes mellitus, dyslipidemia, BMI, and history of smoking/alcohol. RESULTS: Among 7,336 participants (58.5% women; mean age 52.5 years), 807 CVD deaths occurred over a mean 24.2 years. At baseline, 86.6% had neither condition, 4.9% HU-only, 7.1% CKD-only, and 1.5% both. HU-only was not significantly associated with CVD mortality (HR 1.14, 0.81–1.61), CKD-only had significant association (1.28, 1.04–1.59), and both HU/CKD conditions had the highest risk (2.18, 1.50–3.18). Further analyses showed that HU-only was significant in women (2.44, 1.13–5.28) but not men (1.04, 0.71–1.52). CONCLUSION: Overall, CKD and coexistent HU/CKD showed to be a significant CVD mortality risk, and HU’s association with CVD mortality may be partly mediated through CKD. This study observed that HU and CKD coexistence heighten the risk of CVD mortality. Integrated management of serum urate and renal health may aid long-term CVD prevention.