15289-s-bos

9 147 | Summary and Discussion (iTRAQ) proteomics technique in 60 specifically selected heFH patients, and discovered plasma proteins previously not related to atherosclerosis. These proteins were, as expected, part of the coagulation pathway, the inflammation pathway, and the lipid metabolism pathway. Further research is required to confirm the importance of these proteins and if they are suitable as biomarkers or even potentially targets for novel therapeutic interventions to reduce CVD risk. Discussion The introduction of statin treatment has had great impact in the survival of FH patients by increasing the life expectancy similar to that of the general population. However, some FH patients still develop CVD despite statin treatment. In this thesis I investigated the role of cardiovascular imaging and non-traditional risk factors to discriminate between FH patients who are at high risk of developing CVD despite long-term statin treatment and those with low risk of CVD. Furthermore, I investigated the prevalence of aortic valve calcifications (AoVC) in FH patients, since this is another entity of CVD which has not been studied extensively yet. Emerging lipid-lowering medication in FH patients Identifying FHpatients with high residual risk is very relevant in light of the development of novel therapeutic agents. The most promising, and recently approved therapeutic agentsareproproteinconvertasesubstillin/kexintype9(PCSK-9)inhibitors.Theproposed mechanism of the PCSK-9 protein is binding to the LDL-receptor and subsequently degradation of the LDL-receptor after internalisation in the cell. When PCSK-9 cannot bind to the LDL-receptor, the receptor will be recycled and re-emerge on the cell surface where it can bind a new LDL-cholesterol particle. PCSK-9 inhibition with monoclonal anti-bodies lowers circulating PCSK-9 and prevents LDL-receptor degradation. These monoclonal anti-bodies have been shown to greatly reduce LDL-Cholesterol levels, also in addition to maximum statin therapy, and seem to be well tolerated (3-6). The PCSK- 9 inhibitors Alirocumab and Evolocumab have been recently approved by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as an “adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heFH or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL [low-density lipoprotein]-cholesterol (7). Additionally, the first CVD outcome