15289-s-bos

122 | Chapter 8 including those involved in inflammation, coagulation and lipid metabolism, 15, 16 while other studies have identified novel predictors. 15 To date, no such study has investigated the use of iTRAQ proteomics in predicting CAD risk in a FH population. Therefore, the aim of the present study was to utilise proteomics to identify candidate protein biomarkers that may differentiate genetically confirmed FH patients at high CAD risk from those with low CAD risk. Materials & Methods Study population Sixty FH patients (40-70 yrs) from the Vascular Genetics Outpatient Clinic at the Erasmus MC were recruited. All participants had a genetically confirmed mutation in the LDLR -gene. The 60 patients were selected and stratified into 3 subgroups; (i) asymptomatic FH with a low atherosclerotic burden as defined a coronary diseased segment score of 0 (FH, n=20); (ii) asymptomatic FH with a high atherosclerotic burden as defined by a coronary diseased segment score >7 (FH + Ca, n=20); and (iii) FH with previously confirmed symptomatic CAD (myocardial infarction, percutaneous coronary intervention or coronary bypass surgery) (FH + CAD, n=20). Exclusion criteria included; a secondary cause of hypercholesterolaemia, and renal, liver and thyroid disease. Within the asymptomatic groups, additional exclusion criteria included; symptoms of CAD, history of CAD, renal insufficiency (serum creatinine >120 mmol/L), known contrast allergy and atrial fibrillation. The study was conducted in line with the Declaration of Helsinki. All patients gave a written informed consent and the study protocol was approved by the Erasmus MC Ethical Review Board. Coronary CT Angiography (CCTA) CCTA scan protocols and outcomes have previously been described. 18 Briefly, all asymptomatic FH patients underwent CCTA to determine their atherosclerotic burden. Scans were performed on a dual source CT scanner (Somatom Definition, Siemens Medical Solutions) and analysed separately by two experienced readers blinded to the patient’s status. Coronary calcium was measured in Agatston units using dedicated software. 19 In addition, using amodified 17 coronary segment model 20 the percentage of maximum luminal diameter narrowing was visually estimated and graded as either; 0%, 1-20%, 21-50%, 51-70% or >70%. Based on the narrowing per segment, 3 scores were