Uric acid variability at midlife as an independent predictor of coronary heart disease and all-cause mortality

Background Serum uric acid (SUA) has long been associated with cardiovascular disease. Variability of serum uric acid (SUA) has seldom been examined in association with long-term morbidity and mortality. Therefore, we aimed to investigate the association between SUA variability and long-term all-cause and specific-cause mortality. Methods Among 10,059 men, aged 40–65, tenured civil servants and municipal employees in Israel, 8822 participants who were examined in 1963, 1965 and 1968 had assessment of diabetic and coronary morbidity status and SUA levels. We conducted analysis examining whether the standard deviations (SD) of Z-scores of SUA across study visits predicted coronary heart disease (CHD) and mortality. Hazard ratios (HR) associated with the SD of SUA-Z were calculated for stroke, CHD mortality and all-cause mortality associated with quartiles of the above variability. Results Multivariate analysis of 18-year CHD mortality yielded a significant association with the 1963–1968 SD of SUA-Z with age adjusted HR of CHD mortality of 0.97 (95% CI, 0.8–1.19), 1.05 (95% CI, 0.87–1.28) and 1.37 (95% CI, 1.15–1.65) for quartiles 2 to 4 respectively). The results of all-cause mortality similarly and strongly indicated increasing age-adjusted mortality risk with increasing SD of SUA-Z: HR = 1.08 (95% CI, 0.97–1.21), 1.15 (1.03–1.28) and 1.37 (1.23–1.51). No association was observed between the SD of SUA-Z and stroke mortality. Conclusion In this cohort of tenured male workers, with diverse occupations, higher variability of SUA measurement taken over 5 years was clearly predictive of 18-year CHD and all-cause mortality, above and beyond the SUA levels proper.