ABC | Volume 111, Nº6, December 2018

Original Article Ferreira et al Uric acid and cardiovascular risk factors Arq Bras Cardiol. 2018; 111(6):833-840 Table 4 – Comparison of participants’ laboratory variables, reactive hyperemia index and blood pressure levels according to the diagnosis of hyperuricemia Control group (n = 130) Hyperuricemia group (n = 19) p p* Metabolic Variables Glucose (mg/dL) 86.00 (79.50 – 93.00) 87.00 (81.00 – 101.00) 0.51 0.78 Insulin (µU/mL) 12.28 (8.84 – 16.95) 12.70 (9.80 – 18.96) 0.41 0.59 HOMA-IR 2.61 (1.85 – 3.64) 2.68 (2.15 – 3.70) 0.41 0.39 Total cholesterol (mg/dL) 191.35 ± 40.55 194.47 ± 30.97 0.75 0.63 HDL-cholesterol (mg/dL) 52.00 (43.00 - 59.00) 43.00 (39.00 – 51.00) 0.01 0.17 LDL-cholesterol (mg/dL) 112.00 (89.00 – 140.00) 122.00 (96.00 – 145.00) 0.41 0.47 Triglycerides (mg/dL) 98.50 (68.00 – 142.00) 132.00 (108.00 – 142.00) 0.15 0.45 Inflammatory Profile Hs-CRP (mg/L) 0.37 (0.19 – 0.65) 0.45 (0.33 – 0.63) 0.24 0.70 Adiponectin (mg/mL) 5.65 (4.27 – 8.37) 4.02 (3.26 – 5.53) 0.04 0.11 Oxidative Stress Malondialdehyde (ng/mL) 3.53 (3.10 – 4.07) 4.67 (4.03 – 5.30) 0.0004 < 0.0001 Endothelial Function Reactive hyperemia index 2.05 ± 0.46 1.68 ± 0.30 0.005 0.03 Blood Pressure Systolic BP (mmHg) 119.67 (104.00 – 127.00) 121.30 (109.30 – 132.30) 0.23 0.46 Diastolic BP (mmHg) 76.76 ± 11.57 78.81 ± 8.63 0.46 0.28 Heart Rate (bpm) 74.00 (69.00 – 80.17) 69.00 (64.33 – 76.33) 0.10 0.16 Values as mean ± standard deviation for normal distribution or as median (interquartile interval) for not normal distribution. HOMA-IR, homeostasis model assessment of insulin resistance; HDL: high density lipoprotein; LDL: low density lipoprotein; Hs-CRP: high-sensitivity C-reactive protein; BP: blood pressure. p: Control group vs.Hyperuricemia group. p*: Control group vs.Hyperuricemia group, after adjustment for age, sex and body mass index A direct association between SUA and oxidative stress as reflected by serum levels of MDA was observed in the present study. This finding is in agreement with the hypothesis suggested by some authors that the relationship of SUA with vascular and metabolic derangements is, at least, partially mediated by alterations in oxidative stress. 21,24 It is worth mentioning that the association of uric acid with oxidative stress is complex and may be paradoxical. 25 Uric acid has the ability to induce intracellular and mitochondrial oxidative stress but is a major antioxidant in human plasma 25 where it can account for roughly two-thirds of its total antioxidant capacity, through chelation of metals and oxygen radical scavenging. 20 However, there is evidence that under ischemic conditions and when SUA is above normal levels it becomes a prooxidant. 24-26 Xanthine oxidase, which is one of the two xanthine-oxireductase interconvertible isoforms, uses molecular oxygen as an electron acceptor, generating superoxide anion and other reactive oxygen species as byproducts, thereby raising oxidative stress which may ultimately contribute to CVD. 24,27 Some studies, similarly to the present investigation, observed that SUA levels were related positively with TG 3,16,28 and negatively with HDL-cholesterol. 3,18,28 The mechanisms that underlie the relationship between SUA and TG are not yet known, 29 but there are some possible explanations. According to one of them, uric acid can induce lipogenesis in the liver and can block fatty acid oxidation. 30,31 Other investigators suggest that hepatic synthesis of fatty acids is associated with “de novo” synthesis of purine, with subsequent acceleration in uric acid production. 32 In the present study hyperuricemia was associated with lower levels of serum adiponectin. Among the few studies that evaluated this association, one conducted by Park et al. 33 enrolled 841 postmenopausal women aged 50 years or older and found an inverse relationship, which was not reproduced in a cross-sectional analysis of Tromsø Study. 34 Although serum levels of CRP-hs were not significantly associated with SUA, they were higher in individuals presenting hyperuricemia. A positive association between SUA and CRP was observed in some studies carried out in octagenarians, 35 in postmenopausal women, 10 in type 2 diabetics, 36 in older persons 37 and in obese prepubertal children. 38 The impaired endothelial function observed in subjects with higher SUA levels in the present study was also found in previous studies. 4-6,9,11 However, as previously mentioned, most of them enrolled older and sick individuals, in contrast to the present study, where healthy young and middle aged subjects were recruited. According to Johnson et al. 39 uric acid may be taken up by adipocytes, where it induces oxidative stress, generates inflammatory mediators and inhibits the synthesis of adiponectin. 39 The potential increase in oxidative stress induced by SUA may also favor an inflammatory response and 837