See article vol. 23: 692–703
There is little evidence of the association between serum uric acid and cardiovascular mortality for non-white population. A recent study form a single Japanese cohort with 3487 subjects reported that there is a significant association between high uric acid at baseline and all-cause and cardiovascular mortalities in women; however, linearity is not mentioned1). The authors of this study tried to evaluate the association between serum uric acid levels and cardiovascular mortality with a 10-year follow-up of 36,313 subjects from 13 integrated existing cohorts regarding cardiovascular mortality in Japan and suggested that there is a J- or U-shaped association between uric acid levels and cardiovascular mortality2).
Although a U-shaped association between uric acid and cardiovascular mortality was revealed, the reason for such a U-shaped association is unclear. There may be a reverse causal bias in this study. A previous study tried to examine the causal effect of uric acid levels on cardiovascular events using Mendelian randomization and revealed a linear association between uric acid and cardiovascular events among 3315 subjects3). After trying to exclude reverse causal bias in several ways including censoring deaths in the first several years, the observed association still remained. As previously reported4), pooled data of huge number of participants enabled us to analyze in detail with large number of endpoints.
In a previous report, U-shaped association of uric-acid with loss of kidney function was observed4, 5). The same pathway may be acting between cardiovascular mortality and loss of kidney function. Although hypouricemic patients may be rare, genetic polymorphism or variants are reported to cause hypouricemia6, 7). In near future, the role of genetic differences among participants for the U-shaped association may be revealed. In addition, the combination of genetic background and environmental factors may cause each linear association to appear as a U-shaped association.
There are some sex-based differences in uric acid metabolism. In addition, subtype-specific cause is also unclear. Here we can know reveal this U-shaped association and sex heterogeneity; therefore, our next step is to reveal the reason why there are U-shaped association between serum uric acid and cardiovascular mortality with fine classified endpoints and with fine classified background.
Conflicts of Interest
None.
References
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