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

ObjectiveSerum 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.MethodsWe 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.ResultsAmong 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.ConclusionsSUA 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.

► SUA level independently predicts mortality in postmenopausal women not taking HRT. ► Interactions between SUA level, estrogen and mortality may underlie this association. ► SUA level did not predict mortality in men. ► SUA level did not predict mortality in postmenopausal women on HRT.