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.
Highlights
IntroductionSerum uric acid (SUA) is a known endogenous antioxidant, probably functioning through the free radical scavenging capacity [1]
The baseline study sample is formed by 1013 outpatients and admitted patients, aged 40 to 79 years, who have applied between 1 January and 24 December of the year 2009 to the SiyamiErsek Center for Cardiovascular Surgery and had available values for Serum uric acid (SUA) concentrations
In non-diabetic women, the highest SUA tertile was associated with similar alterations, with elevated fasting glucose, HbA1c, and C-reactive protein, yet disclosing similar high-density lipoprotein (HDL)-cholesterol values
Summary
Serum uric acid (SUA) is a known endogenous antioxidant, probably functioning through the free radical scavenging capacity [1]. An increase in the SUA level has been considered to represent counteracted oxidative damage in subjects with atherosclerosis, based on the observation that individuals who had carotid intima-media thickness detected had higher serum total antioxidant capacity than matching controls with low thickness [2]. SUA has complex chemical and biological effects, whereby its pro-oxidant properties may explain the association of its elevated levels with hypertension, metabolic, and vascular diseases [3]. Uric acid is pro-inflammatory in rat vascular smooth muscle cells and stimulates human mononuclear cells to produce cytokines [4]. Observational studies disagree with the relationship of uric acid with mortality, and with factors modifying this relationship [5]
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