Serum uric acid and risk of stroke and its types: the Circulatory Risk in Communities Study (CIRCS)

The role of serum uric acid as a predictor of stroke among the general Japanese population remains controversial. We conducted a prospective cohort study of 5235 men and 8185 women aged 40-79 years at baseline between 1985 and 1994 in four Japanese communities, who were initially free from stroke, coronary heart disease, and medication for hyperuricemia or gout. Cox proportional hazards models were used to estimate sex-specific hazard ratios of stroke and its types in relation to serum uric acid level. During a median follow-up of 23.1 years, we recorded 1018 (488 men and 530 women) incident strokes, including 222 (99 and 123) intraparenchymal hemorrhages, 113 (33 and 80) subarachnoid hemorrhages and 667 (347 and 320) ischemic strokes. After adjustment for age, community and known cardiovascular risk factors, the multivariable hazard ratios (95% CIs) in the highest vs. lowest quintile of serum uric acid were 1.45 (1.07-1.96) for total stroke, 1.20 (0.65-2.20) for intraparenchymal hemorrhage, 1.46 (0.69-3.09) for subarachnoid hemorrhage and 1.61 (1.07-2.41) for ischemic stroke in women. The corresponding multivariable hazard ratios (95% CIs) in men were 1.02 (0.74-1.35), 0.83 (0.40-1.72), 1.19 (0.38-3.75) and 1.00 (0.70-1.41). Furthermore, those positive associations with risks of total and ischemic strokes in women were more evident in nonusers of antihypertensive medication than the users. In conclusion, elevated serum uric acid level is an independent predictor of total stroke in women but not in men. The positive association in women was mostly attributable to ischemic stroke and was more pronounced among nonusers of antihypertensive medication.