Association of inflammation and coagulation markers with levels of C-reactive proteine in healthy volunteers

It has been demonstrated that C-reactive protein (CRP) is a strong predictive
value for cardiovascular (CV) events in asymptomatic subjects with CAD risk and
in stable angina. Moreover, CRP levels are highly predictive for intercurrent
complications or outcome in unstable angina and after acute myocardial
infarction. To date, CRP predominantly has been considered a nonspecific marker
of inflammation rather than a participant in the development and progression of
atherosclerotic lesions including plaque vulnerability.
Accumulating in vitro evidence indicates that CRP elicits direct proatherogenic
effects in endothelial cells, involving upregulation of adhesion molecules and
chemoattractant chemokines, reduction of nitric oxide (NO) synthesis, and
enhancement of plasminogen activator inhibitor (PAI)-1 expression and activity.
Likewise, CRP in monocytes stimulates the release of proinflammatory cytokines
and tissue factor (TF) through binding of the FcgRIIa receptor. The clinical
relevance of these findings has been underscored by in vivo animal studies,
showing that human CRP results in worsened outcome in experimental myocardial
infarction and increased thrombosis in response to arterial injury.
Recently, in a proof-of-principle study we evaluated the effect of human
recombinant CRP (hrCRP) infusion study on endothelial function, inflammation
and coagulation in 7 healthy volunteers using hrCRP (Biospacific). Briefly, we
measured endothelium-derived vasomotor function using venous occlusion
plethysmography at baseline, and 1h and 6h post infusion. Furthermore, blood
was drawn at baseline, and 1, 4, 8 and 24 hours after hrCRP infusion to assess
parameters of coagulation/ fibrinolysis, peripheral leukocyte phenotype,
inflammation and complement activation. The data indicate that a single bolus
of human recombinant CRP induced endothelial cell activation, a proinflammatory
response illustrated by IL-6 and IL-8 levels within 4 hours of time, and
activation of the TF-dependent coagulation pathway. Accordingly a second peak
of endogenous CRP release was noted after 24 hours. Notably, no adverse events
were recorded throughout the protocol.
Although infusion of hrCRP demonstrated an increase in inflammatory markers,
and coagulation markers, the question remains whether a difference can be found
in inflammation and coagulation parameters in healthy volunteers with elevated
CRP (2-10 mg/L) levels versus healthy volunteers with normal CRP levels (<2
mg/L).

To evaluate whether an increase in inflammatory- and coagulation parameters can
be found in healthy volunteers with elevated hsCRP levels compared to age and
BMI matched healthy volunteers with normal hsCRP levels

This study will be a single centre observational study. Volunteers will be
recruited by telephone from the database of our own Department of Vascular
Medicine, which contains volunteers who have indicated to be willing to
participate in future research. Volunteers will be asked to visit our center
for venapunction. Age and sex matched controls with normal CRP levels will be
recruited from the same database.

- Obtainment of subject informed consent
- Screening for inclusion
- Physical examination
- Venapunction for blood samples (small risk of hematoma at puncture site; some
subjects develop a vasovagal reaction)