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.