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8 137 | Novel protein biomarker predictors of CAD in FH these relationships. Furthermore, it is worth considering that while FH is characterised by advanced atherosclerosis and CAD, it is a genetically distinct disease. It is therefore possible that there are additional underlying factors, unique to FH and its associated mutations, which manifest differently to a patient with CAD not associated with FH. While it is too early in this investigation to conclude that a predictive relationship exists between the loss of these peptides and disease progression, the results suggest there are grounds to support such a hypothesis. Firstly, a statistical association exists between a number of related proteins and disease. Secondly, there is a clear lack of significant association between the severity of CAD and the potential biomarkers (Table 4). This supports a hypothesis of prediction of the change in state rather than progression of severity of the condition per se . Thirdly, the significant association of age and smoking also support the hypothesis that these potential markers may be able to predict the change in disease status since age is a surrogate marker of elapsed time for each patient and smoking is a well established predictor of CAD. It is clear that a prospective study of asymptomatic FH patients to investigate CAD progression is warranted. There are several limitations associated with the present study that must be acknowledged. These include; the cross-sectional study design and inclusion of a highly selected population with a relatively small sample size. Furthermore, we did not test against other biomarkers, including genetic ones. This is particularly important given the need for novel strategies to identify CAD risk in asymptomatic adults, which add to the prognostic value provided by standard risk factors. While alternate strategies that go beyond measuring traditional risk factors are needed, they must also be better than existingnon-invasive strategies (imaging for carotid intimalmedial thickness and coronary artery calcium) and have a wide variability, which does not correlate with traditional risk factors. The strengths of the present study, however, include thewell characterised treated patient groups and the extreme selection of CAD endpoints at a relatively young age. In conclusion, the present study has identified six protein biomarkers that are associated with atherosclerotic disease progression and subsequent coronary events in treated patients with FH. As these are a group of individuals already at elevated risk of developing CAD, this offers a novel tool for more accurate prediction of risk and therefore commencement of early aggressive therapy to prevent future coronary events. Although the present study is hypothesis generating due to its cross-sectional design and needs to be tested in larger populations with prospective follow-up, this may be possible through international collaborations that utilise the power of well- characterised registry data.