Serum uric acid levels and cardiovascular mortality in a general Japanese population: the Hisayama Study

Studies on the association between serum uric acid levels and the risk of cardiovascular disease have yielded inconsistent results. We investigated the association of serum uric acid levels with cardiovascular disease mortality in a Japanese community. A total of 2633 community-dwelling Japanese people aged ≥40 years without a history of cardiovascular disease were followed up for 19 years. Serum uric acid levels were categorized into quintiles (Q1, lowest; Q5, highest). The hazard ratios for mortality from cardiovascular disease, stroke, and coronary heart disease were computed using a Cox proportional hazards model. During the follow-up, 235 subjects died from cardiovascular disease (including 84 from stroke and 53 from coronary heart disease). Risks for cardiovascular disease mortality were higher in both the Q1 and Q5 groups than in the Q3 group after adjustment for confounding factors (Q1, hazard ratio 1.50 [95% confidence interval 0.94-2.39]; Q2, 1.06 [0.66-1.72]; Q3, 1.00 [reference]; Q4, 1.44 [0.93-2.23]; and Q5, 1.89 [1.23-2.91]). A similar U-shaped association was observed for stroke mortality (Q1, 3.26 [1.29-8.25]; Q2, 2.21 [0.85-5.73]; Q3, 1.00 [reference]; Q4, 2.65 [1.07-6.58]; and Q5, 3.77 [1.54-9.24]), while coronary heart disease mortality was increased only in the Q5 group (Q1, 1.27 [0.46-3.50]; Q2, 0.85 [0.29-2.48]; Q3, 1.00 [reference]; Q4, 1.57 [0.63-3.92]; and Q5, 2.53 [1.03-6.18]). Elevated serum uric acid was suggested to be a significant risk factor for stroke or coronary heart disease mortality in a Japanese community. Conversely, the excess risk of stroke mortality in individuals with lower serum uric acid levels may indicate a possible cerebroprotective role of uric acid.