ABSTRACT: Background The association between elevated serum uric acid (SUA), cardiovascular disease (CVD) risk, and carotid atherosclerosis has long been explored, and contrasting results have been reported. Therefore, the role of SUA as an independent risk factor for vascular events (VEs) and carotid atherosclerosis deserves further attention. We investigated the relationship between SUA, incident VEs, carotid intima-media thickness (cIMT), and cIMT progression in subjects at moderate-to-high CVD risk. Methods and Results In the IMPROVE (IMT-Progression as Predictors of VEs) study, 3686 participants (median age 64 years; 48% men) with ≥ 3 vascular risk factors, free from VEs at baseline, were grouped according to SUA quartiles (division points: 244-284-328 µmol/L in women, 295-336-385 µmol/L in men). Carotid-IMT and its 15-month progression, along with incident VEs, were recorded. A U-shaped association between SUA and VEs was observed in men, with 2.4-fold (P = 0.004) and 2.5-fold (P = 0.002) increased CVD risk in the first and fourth SUA quartiles as compared with the second. Adjusted hazard ratios (HRs) for cerebro-VEs in men were the highest (first and fourth quartile versus second: HR, 5.3, P = 0.010 and HR, 4.4, P = 0.023, respectively). SUA level was independently associated with cIMT progression in men (β = 0.068, P = 0.014). No significant association between SUA levels, CVD end points, and cIMT progression were found in women. Conclusions Both low and high SUA levels are associated with an increased risk of VEs in men at moderate-to-high CVD risk but not in women. Only elevated SUA levels predict cIMT progression and at a lesser but not significant extent in women.
