Background/Purpose:

Patients with inflammatory
arthritis, including gout, have an increased risk of cardiovascular events and
mortality. Increased platelet reactivity is a risk marker for cardiovascular
events. The glycoprotein VI (GPVI) receptor is found exclusively on platelets
and megakaryocytes and is the predominant platelet receptor for collagen. It
remains intact on platelets under resting conditions. The proteolytic cleavage
of GPVI occurs only upon specific activation of platelets and is detectable in
the plasma as soluble GPVI (sGPVI). Therefore elevated plasma sGPVI represents
a potential biomarker for platelet hyperreactivity and hence adverse
cardiovascular outcomes

Methods:

The aim of this study
was to assess platelet reactivity, as measured by plasma sGPVI levels, in acute
gout, chronic gout, and acute calcium pyrophosphate (CPP) arthritis, and to
compare these to each other and to healthy controls. Following ethics approval
and informed consent, blood samples were taken from patients with gout and CPP
arthritis. Healthy control samples were obtained from volunteers. Demographic
and clinical data were collected for all participants. Blood samples were
processed as double spun platelet poor plasma. sGPVI levels were measured using
ELISA. Mann-Whitney U test was used to compare groups. Spearman’s Rank
Correlation Coefficient was used to assess for associations between sGPVI
levels and demographic and clinical markers. GraphPad Prism Version 6.05 and
IBM SPSS Statistics Version 20 were used for data analysis.

Results:

One hundred and six
patients were included in the study, 16 with acute gout, 5 with acute CPP
arthritis, 32 with chronic gout, and 53 healthy controls. There were no
significant differences in demographic details between the groups. Median (IQR)
sGPVI levels were 7.03 ng/ml (3.80, 9.70) in acute gout, 5.42 ng/ml (3.73,
9.63) in acute CPP arthritis, 4.28 ng/ml (2.10, 6.07) in chronic gout, and 2.05
ng/ml (1.69, 3.31)  in healthy
controls. sGPVI levels in all 3 disease groups were significantly increased
compared to healthy controls 
(p<0.05 for each) (Figure 1). GPVI levels in patients with active
gout were significantly increased compared to chronic gout (p=0.02). There was
moderate correlation between sGPVI levels and CRP (r=0.42), VASPain (r=0.42),
and VASQOL (r=0.51), and a weak correlation with ESR (r=0.35).

Conclusion:

Patients with crystal-induced
arthropathies exhibit platelet hyperactivity as demonstrated by elevated plasma
sGPVI levels.  This was particularly
evident during acute gout. Platelet hyperactivity may contribute to the
elevated cardiovascular risk in gout patients and GPVI represents an attractive
new target as an antiplatelet reagent in this patient population, for whom no
anti-thrombotic guidelines exist.

Figure 1: sGPVI levels