U‐Shaped Association Between Serum Uric Acid Level and Risk of Mortality

Abstract

In this large cohort study of men and women, both low and high uric acid levels were predictive of increased mortality, supporting a U-shaped association between serum uric acid levels and adverse health outcomes.

Association between serum uric acid levels and mortality: a nationwide community-based cohort study

“…Moreover, a similar trend was observed for cardiovascular mortality in both men and women, indicating the different threshold values of uric acid levels for mortality among men and women. Some previous studies reported the sex-specific threshold values of uric acid for all-cause mortality: uric acid levels ≥8.5 mg/dL in a male population in Japan (n = 49,413) 17 and Korea (n = 207,167) 11 and ≥7.5 mg/ dL in a female population in Korea (n = 167,996) 11 . The current study revealed that the threshold values of uric acid levels for all-cause mortality (≥7.0 mg/dL in men and ≥5.0 mg/dL in women) are lower than the previously reported values 10,11,17 .…”

“…Some previous studies reported the sex-specific threshold values of uric acid for all-cause mortality: uric acid levels ≥8.5 mg/dL in a male population in Japan (n = 49,413) 17 and Korea (n = 207,167) 11 and ≥7.5 mg/ dL in a female population in Korea (n = 167,996) 11 . The current study revealed that the threshold values of uric acid levels for all-cause mortality (≥7.0 mg/dL in men and ≥5.0 mg/dL in women) are lower than the previously reported values 10,11,17 . Similarly, a significant increase in the HR for cardiovascular mortality was detected at a lower value in the current study (≥7.0 mg/dL in men and 5.0-5.9 and ≥7.0 mg/dL in women) than in the previous study (≥9.5 mg/dL in men and ≥8.5 mg/dL in women) 11 .…”

“…Second, sex differences in the distribution of serum uric acid levels exist, and this may modify the association between serum uric acid levels and mortality 10-12 . Third, some studies showed that the association between serum uric levels and mortality was not linear, but J-shaped [11][12][13] , indicating that the conventional classification of uric acid levels, such as hyperuricemia (e.g., > 7 mg/dL) or per 1 mg/dL increase, might be inappropriate to evaluate the risk of increased serum uric acid levels on mortality.…”

“…Second, sex differences in the distribution of serum uric acid levels exist, and this may modify the association between serum uric acid levels and mortality 10-12 . Third, some studies showed that the association between serum uric levels and mortality was not linear, but J-shaped [11][12][13] , indicating that the conventional classification of uric acid levels, such as hyperuricemia (e.g., > 7 mg/dL) or per 1 mg/dL increase, might be inappropriate to evaluate the risk of increased serum uric acid levels on mortality.Considering these conditions, a large-scale study with a sufficient number of events, various correction factors, and a sex-specific reference range of uric acid is necessary to address this issue. However, in most previous studies, the conventional classification or quartile/quintile subgrouping of uric acid was used, and the number of events was insufficient to perform a multivariate analysis using a fine classification of uric acid levels.…”

Genetic predisposition to hypouricemia on whole-exome sequencing analysis and its utilities in primary screening purposes

“…In this study, we comprehensively evaluated the contribution of genetic predisposition to hypouricemia with WES data and genotyping date in 81 unrelated patients. Our approach is derived from that of the previous population-based studies on the adverse health effects of hypouricemia 20,36 . Throughout our study, we were able to evaluate the genetic markers in hypouricemia which could have a potential diagnostic role for the first time.…”