Discussion

Chiang et al. stated that hyperuricemia could be a sign of a metabolic disorder that is a precursor of hypertension, hypertriglyceridemia and diabetes mellitus, and high SUA levels may play a role in CVD development.15 Kang et al. emphasized that hyperuricemia can induce CRP mRNA expression in vascular endothelium and smooth muscle cells and reduce nitric oxide (NO) release.16 In another study of a murine model with metabolic syndrome, hyperuricemia was reported to cause a proinflammatory endocrine imbalance in adipose tissue.17 Although the association of atherogenic dyslipidemia (high TG and LDL and low HDL levels) and hyperuricemia was reported in many other studies, the physiopathology of this association has not been fully elucidated yet.18,19 Inconsistent with the previous studies, we have found that there was a statistically significant increase in SUA levels in the 3rd month of ISO treatment. We have also found higher SUA levels in patients with atherogenic dyslipidemia.
Various studies reported that ISO treatment could increase the inflammatory response and oxidative stress.20,21 Among the inflammation biomarkers, we have found that only MHR values significantly increased. MPV, PLR, and PCT values did not change, and NLR values decreased significantly. We have found no correlation between hyperuricemia and these inflammation biomarkers other than MHR. There are contradictory studies in the literature about the effects of ISO on CBC test parameters.10,22,23 In contrast to the study of Önder et al., we have found a significant decrease in NLR values in the 3rd month of ISO treatment, similar to the study of Duman et al.10,23 ISO was reported to have an anti-inflammatory effect on patients with acne vulgaris by suppressing the chemotaxis of WBCs.24 It was thought that the decrease in NLR values indicated the anti-inflammatory effect of ISO.
Recent clinical and epidemiological studies have shown that MHR could predict various inflammatory diseases such as metabolic syndrome, diabetes mellitus, CVD, and acne vulgaris.8,10,13,25,26 Similarly, we have found a statistically significant increase in MHR values in the 3rd month of ISO treatment. Monocytes interact with the damaged endothelium and cause gene overexpression of proinflammatory cytokines and adhesion molecules. On the other hand, HDL-cholesterol has anti-inflammatory, antioxidant, and vasorelaxant effects.27,28 The relationships between MHR and SUA with inflammatory diseases are similar.15 We have found that MHR values and SUA levels showed a weakly positive correlation both before and after ISO treatment. As far as we know, the relationship between MHR and SUA has not been reported in patients receiving ISO treatment to date. Both of these parameters are associated with atherosclerosis and metabolic syndrome. It was found that CIMT increases after 4 months in acne patients receiving ISO treatment, so it has been suggested that long-term ISO use increased atherosclerosis risk.9 In another study, it was claimed that ISO triggered the development of subclinical atherosclerosis in men.29 In the light of all these data and the findings of our study, we can explain the atherosclerosis pathway seen in Figure 1. It was thought that the ISO-induced uric acid increase might be related to dyslipidemia. ISO may initiate the atherosclerotic process in vascular endothelial and smooth muscles, with uric acid increase and HDL decrease. An increase in MHR value is also an inflammatory marker indicating this process.
The limitations of our study were that the study was retrospective, and other commonly used systemic inflammatory markers such as high sensitive C-reactive protein, erythrocyte sedimentation rate, and d-dimer were not evaluated. We could not create a ”healthy control group” because our study was retrospective and a comprehensive study reported that there was already a relationship between SUA and MHR.
In conclusion, this study contributes to the comprehension of the relationship between ISO treatment and atherosclerosis, which has been frequently reported in the literature. However, our study is insufficient to establish a cause-result link. More comprehensive studies are needed.