Low Serum Uric Acid Predicts Risk of a Composite Disease Endpoint

Abstract

Background and objectives: Mortality may increase in hypouricemia as well as inhyperuricemia. We assessed the predictive value of low serum uric acid (SUA) levels on the risk of overall mortality or a composite endpoint of death and nonfatal events. Materials and Methods: In 1013 community-based middle-aged adults, free of uncontrolled diabetes and coronary heart disease at baseline, the association of sex-specific SUA tertiles with defined outcomes was evaluated prospectively by logistic regression, stratified to gender and presence of type-2 diabetes, using recent criteria. Results: Totally, 43 deaths and additional incident nonfatal events in 157 cases were recorded at a median 3.4 years' follow-up. Multivariable linear regression disclosed SUA to be significantly associated among non-diabetic individuals positively with creatinine, triglycerides, and body mass index in women further with fasted glucose. In multivariable-adjusted logistic regression analysis, sex-specifically dichotomized baseline uric acid (<5.1 and <4.1 mg/dL vs. higher values) significantly predicted the non-fatal events in the whole sample (relative risk (RR) 1.51 [95% confidence interval (CI) 1.02; 2.26]), as well as in men, while composite endpoint in the whole sample tended to rise (RR 1.38). Compared with the intermediate one, the top and bottom SUA tertiles combined tended to confer mortality risk (RR 2.40 [95% CI 0.89; 6.51]). Adverse outcomes in diabetic women were predicted by tertiles 2 and 3. Conclusions: Inverse association of SUA with adverse outcomes, especially in men, is consistent with the involvement of uric acid mass in autoimmune activation. The positive association of uric acid with adverse outcomes in diabetic women is likely mediated by concomitant high-density lipoprotein dysfunction.

Keywords: coronary heart disease; diabetic status; mortality; serum uric acid; smoking status; total cholesterol.

Figure 1

Flow diagram of the study (CHD: chronic heart disease).

Figure 2

Relative risks (RRs) of serum uric acid tertiles for mortality, non-fatal events, and the composite endpoint in the non-diabetic (lower panel) and the diabetic sample (upper panel). RRs (and 95% CIs) for non-fatal events and the composite endpoint in diabetic patients are depicted separately in the sexes owing to the gender divergence displayed.It can be observed that subsequent non-fatal events and the composite endpoint are inversely related to the baseline uric acid tertiles in the total non-diabetic and the male diabetic sample. Overall mortality carries a U-shaped risk curve regarding uric acid tertiles in the whole sample. Female diabetic patients reveal divergence with respect to non-fatal events and the composite endpoint, showing an, albeit non-significant, tendency to increased risk in the upper two tertiles.