We assessed the relationship between SUA and the cardiometabolic phenotype in the current study, and our findings show increasing mean values of metabolic syndrome factors, including LDL and cholesterol, in a dose-response manner corresponding to the SUA tertiles. These results are similar to the findings of the studies carried out previously in various countries [16–18]. According to our findings, the prevalence rates of MHO and MUHL were higher in the second and third tertiles compared to the first tertile, which had the lowest SUA. As far as we know, no studies have been published focusing on the relationship between SUA and the cardiometabolic phenotype. Therefore, we contrasted our results with previous studies that evaluated the connection between SUA and MetS. An increase in MetS due to the elevation of serum uric acid level has been reported . The results of the current study are in line with the findings of Ishizaka et al., who evaluated the relationship between SUA and MetS among participants with BMI≥25 kg/m2. They noticed that in the highest uric acid value quartile, the odds of MetS elevated by 2.27 (95% CI: 1.90–2.72) after adjusting for the confounding factors . However, in our study, after adjusting for the confounding factors, the risk of MUHO in the highest tertile was more than that of the study by Ishizaka et al. (OR 11.16 vs 2.27). This variation is potentially due to the differences in defining MetS, i.e., they considered BMI > 25 kg/m2 as a MetS marker, while we determined MetS according to ATP III, and then categorized the participants based on BMI (BMI<25 or ≥ 25 kg/m2).
Hemostasis and the relationship between SUA homeostasis and MetS are highly complex . It’s still debatable whether an elevated SUA level is a risk factor or just a biomarker in the progress and improvement of MetS . Some researchers have stated that hyperuricemia can be an exclusive component of MetS [7, 23], while other studies have proposed to consider hyperuricemia as a supplementary component of MetS [24, 25]. Elevated SUA levels will cause outcomes such as hypertension , hypertriglyceridemia, and hypercholesterolemia . The suggested procedures for the connection between SUA and MetS include the following: firstly, hyperuricemia has been proved to lead to endothelial dysfunction in human and animal bodies [28, 29]. Secondly, SUA has been shown to prevent NO production , which is a significant factor in the functioning of insulin . The defect of endothelial-formed NO is supposed to decrease blood flow to the cells, which stops the normal functioning of insulin and causes hyperinsulinemia . Therefore, hyperuricemia may play a potential role in causing and increasing insulin resistance. Similarly, insulin resistance is recognized to play an essential role in the pathogenesis of MetS . Thirdly, another role of uric acid involves inducing oxidative stress, which causes inflammation in adipocytes [33, 34] and hepatocytes . However, the complicated correlation between uric acid and oxidative stress is noteworthy because it can be paradoxical . Although uric acid is an antioxidant that disables superoxide anion, peroxynitrite, and hydroxyl radicals [37, 38], there is some evidence showing that under ischemic stress or high SUA, uric acid functions as a pro-oxidant.
Furthermore, we noticed that the prevalence of males in the third tertile (i.e., the highest SUA level) was significantly higher than the other tertiles. In line with our results, this phenomenon has been mentioned in previous studies [39, 40]. It seems that the lower tubular urate post-secretory reabsorption and the higher renal clearance of urate in women can be related to this observation.
Moreover, according to our findings, the average serum levels of liver enzymes were elevated in MHL, MHO, and MUHO individuals in a dose-response manner corresponding to SUA tertiles. Interestingly, the mean serum liver enzymes elevated with increasing SUA levels in MHL individuals. This may suggest an association between liver enzymes and SUA that is independent of BMI. At the same time, it may be an indicator that the MHL subjects in the third tertile are at risk of shifting to MUHL. Nevertheless, we did not observe the same trend in the MUHL group, which we thought might be because of the limited sample size of this group. These findings are in line with the findings of prior studies [41, 42]. For instance, Shih et al. state that individuals with hyperuricemia are more likely to have heightened liver enzymes (AST or ALT), even after adjustment . As shown in several studies, NAFLD is closely linked with obesity, dyslipidemia, diabetes mellitus, MetS, and cardiovascular disorders [43, 44]. Therefore, NAFLD is believed to be a hepatic outcome of metabolic diseases [45, 46]. It turns out that the SUA level increases in most NAFLD patients , indicating that it can be an independent predisposing factor for NAFLD [48, 49]. Additionally, hyperuricemia, even in the reference range, was a component of MetS .
The main limitation of the current study involves the fact that due to its cross-sectional design, causal inferences in the relationship between serum SUA and cardiometabolic phenotype could not be evaluated. However, the main strength of this study is that it is the first to evaluate the relationship between SUA and cardiometabolic phenotype in healthcare workers. Serum SUA is easily accessible in regular clinical practice, and it is measured using standardized techniques. It would be useful to distinguish the transition from MHO to MUHO. Therefore, it may lead to earlier and more precise identification of MHO subjects at risk of transition to MUHL, which can facilitate the administration of better preventive strategies. Another strong point of this work lies in using data from a cohort study and a large sample size.