The iCORONARY Caristo biomarker study

For personalized risk modification there is need for a parameter which reliably
estimates an individual's risk for cardiovascular events in the future, and
allows for monitoring of risk modification effectiveness. CaRi Heart score
measures pericoronary inflammation on routine coronary CT, shows this as
percentile for sex and age and used this and traditional risk factors to
calculate the CaRI Risk score, an individual's risk for a (fatal if left
untreated) cardiovascular event in the next 8 years. We expect that this will
allow us to more adequately tailor cardiovascular risk modification to an
individual's risk. Additionally, we expect that with adequate risk modification
the pericoronary inflammation will decrease, which means the effectiveness of
cardiovascular risk modification could be monitored and management strategy can
be adapted.

Additionally, various biomarkers have been identified that are associated with
an elevated risk of coronary artery disease. However, their precise clinical
value remains unknown, among others due to limited validation opportunities. We
want to assess whether these biomarkers can be validated using pericoronary
inflammation, and whether they have potential additional value in risk
prediction when combined with the CaRi risk score.

We aim to assess whether risk modification effectiveness is visible on
follow-up CT and in biomarker values when comparing baseline with 12 months
follow-up in patients without significant obstructive coronary artery disease
on coronary Ct. We also aim to assess whether the biomarkers correlate with
pericoronary inflammation, whether they have added value compared to CaRi score
alone and whether CaRi score and biomarker values can be used to develop a
treatment strategy for prevention tailored to the individual patient

This prospective observational study applies to the original study design of
the iCORONARY trial, a multicenter, randomized controlled trial. All study
patients involved in the registry arm of the main study and included from the
sponsor center can opt-in and opt-out to participate in this study.

Acquisition of a CCTA delivers an effective dose of approximately 5mSv of
radiation. Normal background radiation is approximately 3mSv per year. For this
study, patients receive 2 CCTAs within a 12 month period. The risk of a
negative health impact with this radiation dose is low. We will however advise
patients to not participate in other studies involving radiation simultaneously
with this study and will not include patients that have recently received or
are planned to receive other diagnostic tests involving radiation. Iodine
contrast is needed for CCTA. Contra-indications for iodine contrast are
impaired kidney function (GFR <30ml/min or GFR<45ml/min in high risk patients)
and contrast allergies. We will not include patients with contra-indications
for iodine contrast in this study. Because the experimental results from
biomarker levels and CaRi Risk assessment will not be used in clinical
management, potential false-negative or false positive results do not carry any
risk for the patient. * Patients will be informed of the possibility of chance
findings with blood test or CCTA that might be relevant to their health and
call for additional treatment or diagnostic testing. If this occurs, patients
will be referred to their cardiologist, an different medical specialist or
their general practitioner depending on the findings.