Effects of menopause and hormone replacement therapy on the associations of hyperuricemia with mortality.

OBJECTIVE: Serum uric acid (SUA) levels have been associated with cardiovascular and all-cause mortality. It remains unclear whether these associations differ by gender, menopausal status and hormone replacement therapy (HRT) and whether they persist after adjustment for known cardiovascular risk factors.

METHODS: We determined the associations between fasting SUA level and death certificate-based mortality among 5856 participants of the third US National Health and Nutrition Examination Survey aged ≥20 years recruited between 1988 and 1994 and followed for mortality until December 2006 (mean follow-up: 13.5 years; maximum follow-up: 18 years). Cox proportional hazards regression analysis was used to adjust for demographic characteristics, cardiovascular risk factors and other variables potentially associated with SUA levels.

RESULTS: Among women, SUA level was associated with all-cause and cardiovascular mortality (adjusted hazard ratio [AHR] 1.17, 95% CI 1.03-1.32 and AHR 1.23 (1.01-1.51) respectively per unit increase in SUA. These associations persisted among postmenopausal but not premenopausal women. Furthermore, among postmenopausal women, significant associations were identified between SUA and all-cause (AHR 1.30 [1.11-1.51]) or cardiovascular (AHR 1.61 [1.33-1.94]) mortality only among women not taking HRT, but not among women on HRT. We did not identify associations between SUA levels and all-cause or cardiovascular mortality in men, either under or over 51 years of age, in unadjusted or adjusted analyses.

CONCLUSIONS: SUA level predicts cardiovascular and all-cause mortality independently of major predictors and risk factors in postmenopausal women not taking HRT but not in premenopausal women, postmenopausal women on HRT, or men.