The SMART-ORACLE Study
The SMART-ORACLE Study
After having had a first cardiovascular event, there is a considerable risk of developing a
 subsequent event. Only recently, a risk prediction model was developed for this group of
 patients. Imaging techniques such as the coronary artery calcium score and contrast-enhanced
 computed tomography (CT) of the coronary and carotid arteries could be able to add improve
 this model. Imaging may further improve the prediction of future manifestations of arterial
 disease and personalize disease monitoring and treatment.
Patients with a prior cardiovascular event exhibit an elevated risk for subsequent
 cardiovascular events. The Second Manifestation of Arterial Disease Study (SMART) has
 recruited over 10,000 patients since 1996 with clinically manifest cardiovascular disease in
 a multidisciplinary single center study involving primary care physicians, cardiologists,
 neurologists, vascular surgeons, vascular medicine specialists and radiologists. Within this
 study a prediction model was developed to accurately estimate the risk for new cardiovascular
 events. It is now possible to acquire high-quality motion-free computed tomography (CT)
 images of the coronary and carotid arteries. Imaging biomarkers extracted from these images
 may further improve the prediction of future manifestations of arterial disease and
 personalize disease monitoring and medical care.

 The SMART-ORACLE study is a prospective, single center, observational cohort study aiming to
 include 1500 patients. The primary aim is to identify predictors of future cardiovascular
 events. Eligible patients will be selected via the recruitment of the original SMART study.
 Patients participating in the SMART-ORACLE study will undergo calcium scoring in multiple
 cardiovascular beds and contrast-enhanced CT-scans of the coronary and carotid arteries in
 addition to the regular SMART investigations. Patients with renal dysfunction will be either
 excluded from the study or will receive pre-hydration (depending on eGFR) to minimize the
 risk of contrast nephropathy. Follow-up with questionnaire-based assessment will take place
 every 26 weeks until death of participant or end of the SMART study, asking participants
 about possible new cardiovascular events. Endpoints will be adjudicated by a committee of
 three experts. The aim is to collect 170 future events.

 The main analysis will consist of Cox proportional hazard analysis. Imaging biomarkers will
 be added to the existing prediction model to assess their (independent) discriminatory
 capacity for future events. The c-statistic will be used to measure the discrimination of
 each model. Net reclassification improvement tables will be constructed to evaluate the added
 value of imaging markers in terms of reclassification. Based on a one-year-occurrence rate of
 subsequent cardiovascular events in the current SMART population database of 2.6%, about 6500
 person years of follow-up are needed to obtain the adequate number of endpoints.
Inclusion Criteria:

 -  History of cardiovascular event (coronary carter disease, cardiovascular disease,
 transient ischemic attack, minor stroke peripheral artery disease , abdominal aortic
 aneurysm)

 -  Diabetes Mellitus type 2

 -  Hypertension (Blood pressure>140/90 mm Hg)

 Exclusion Criteria:

 -  Known renal failure (defined as eGFR <46 ml/min/1.73 m2 estimated based on the
 modification of diet in renal disease (MDRD) formula)

 -  Previous allergic reaction to contrast, necessitating medical intervention

 -  Other contra-indication for CT-scanning (e.g. pregnancy, acute hypotension (<100 mm Hg
 systolic), clinical instability)

 -  Prior exposure to ionizing radiation for scientific purposes without advantage for the
 patient