DISCUSSION
To best of our knowledge this is the first study about relationship
between FMD response (impaired endothelial response) and blood
parameters in patients with pRP. On the other hand this is the first
report about relationship between impaired endothelial response and
MCP-1 levels in pRP. Our results indicated that patients with pRP have
higher impaired endothelial to ischemia. The incremental levels of serum
WBC, MPV, MCP-1 and fibrinogen values were detected in pRP group.
Moreover, moderate direct correlation was found between abnormal FMD
response and serum MCP-1 values.
The impaired endothelial dysfunction demonstrated in both primary and
secondary RP in previous studies. Furthermore it was shown that
microvascular derangement was found as associated with endothelial
dysfunction in RP patients 11,12 . The endothelium has
an important role in the regulation of vascular response against blood
flow‐associated shear stress and ischemia-reperfusion events.
Insufficient flow-mediated vasorelaxation response is an indicator for
increased vascular disease 13 . The dilation response
of the brachial artery after a 4-5 minutes ischemic period is a reliable
non-invasive assessment method for the evaluation of endothelium
functions. The post-ischemic brachial artery dilatation with equal to or
more than 5% of normal diameter is accepted as normal endothelial
functions. Additionally, dilatation with lower than 5% of diameter is
accepted as impaired endothelial functions 9,14 . The
FMD response was studied in patients with RP. Flavahan indicated as FMD
response is normal in pRP and it was added that cold induced disruption
of arteriovenous connections in RP cases, can lead to digital artery
spasm 15 . Mavrikakis et al. studied FMD in patients
with sRP and they detected abnormal FMD response in these patients.
Additionally, they found that ascorbic acid does not reverse endothelial
vasomotor dysfunction in their study 16 . Klein-Weigel
et al. investigate the seasonal variations in patients with RP and they
did not show abnormal FMD response in pRP 17 . However
most of the previous reports were conducted with mall RP populations.
Although our results indicated that abnormal FMD response can detected 5
(17%) of 30 healthy individuals, the abnormal FMD was detected at 30
(70%) of 43 pRP patients.
The routine blood parameters were investigated for several kinds of
vascular diseases 18 . Platelet indices were
investigated in vasospastic disorders detected with cold stimulation
test by Kadan et al. 19 . They found that the
relationship between severity of disease and MPV. Shemirani et al. found
independent relationship between pRP and higher serum MPV levels20 . Another study higher MPV was suggested as
triggering factor for pRP 21 . In same study WBC
levels were found as insignificant predictor in same study. Lau et al.
was found increased white blood cell activation in patients with RP22 . Our findings supported that MPV and WBC levels in
patients with pRP. Plasma fibrinogen is another laboratory parameter
that investigated in vasospatic disorders. Splenger et al. concluded as
increased plasma fibrinogen levels in patients with RP are related with
disrupted distal microcirculation 23 . Similarly,
higher fibrinogen levels found as associated with plasma fibrin clots
displaying impaired lysability and increased endothelial damage in pRP
by Żuk et al. 24 . In our study higher fibrinogen
levels were detected in pRP patients.
MCP-1 is an important potent regulatory chemokine that is responsible
for the migration and the infiltration of monocytes. The ischemia,
oxidative stress, released cytokines, or growth factors triggers the
biological activity of MCP-1 and leads to infiltration of
monocytes/macrophages. Rajagopalan et al. investigated to MCP-1 levels
in sRP and pRP and they found that MCP-1 levels were higher in sRP when
compared with primary type. However, they did not compare the MCP-1
levels with healthy controls and did not investigate the relation with
endothelial response 25 . MCP-1 was suspected to
pathogenesis of vasospastic outcomes of diseases that presented with sRP26,27 . However, the literature includes insufficient
reports about the relationship between impaired endothelial function and
MCP-1 levels in pRP. Furthermore, another insufficiency is about the
differences between pRP and normal population in regards to MCP-1
levels. Our results indicated that MCP-1 levels are higher in patients
with pRP and these results revealed a relation between impaired
endothelial functions and serum MCP-1 levels.
In conclusion, our findings demonstrated that MPV, WBC, fibrinogen, and
MCP-1 levels were higher in pRP patients when compare with healthy
control. It seems to be that increased MCP-1 values were related to
abnormal FMD response in pRP group. These results might be helpful for
the establishment of the pathophysiology of the RP.
Limitations of Study
The main limitation of the study is concerning about small sample size.
Although previous literature has present findings with smaller patient
groups, the comprehensive cohorts are necessary for obtaining powerful
and exact results. The second limitation is concerning the determination
of endothelial response with a single method (FMD). The endothelial
response should be confirmed with other techniques to present more
clarified findings. The third limitation is related to the nature of the
disease. If any underlying disease cannot be detected responsible for RP
then it called primary RP. However, there is multifactorial etiology for
RP and it is possible to skip diagnosis.
Acknowledgement
Funding: This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Competing Interest: The authors declare no conflict of interest.