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9 151 | Summary and Discussion between patients with CVD and healthy controls in the general population. The exact role of these novel proteins also needs to be further investigated. They might be suitable in predicting CVD risk as markers or might even be causal in CVD disease progression. Future perspectives Over a third of statin-treated FH patients still develop CVD events, it is relevant and important to identify these patients to intensify treatment, for example by initiating PCSK-9 inhibitor therapy (1). Optimal risk prediction among FH patients should be used to differentiate between those who are likely to remain asymptomatic using statin treatment and thosewhowill develop CVD events or who have experienced a CVD event and are at an increased risk of experiencing subsequent CVD events despite maximum lipid lowering therapy. It is essential to, at least to attempt, to make this differentiation because of the high costs of the PCSK-9 inhibitors. To identify these patients at risk I showed that the asymptomatic statin-treated FH patients who have carotid plaques also have more coronary atherosclerosis whereas in these patients C-IMT is unlikely to add to further risk prediction. Whether carotid ultrasonography outcomes are related to CVD events in statin-treated patients is thus far unknown and should be clarified in the future. Moreover I showed that AoVC prevalence is high in heFH patients. Since statins do not reduce AoVC once established, but are associated with a reduction in mortality in FH patients, aortic valve disease might become a growing health threat for the aging FH patients. Further research is needed to clarify whether starting statins at a young age reduces the risk of developing AoVC. It is also important to study whether the current aging heFH patient would benefit from routinely cardiac ultrasound monitoring for valve diseases as is advised by guidelines for hoFH patients. I showed that circulating Lp(a) levels in statin treated patients are associated with AoVC. Future studies will tell if specific lowering of Lp(a) levels can lower the occurrence of CVD events. Because of the association of Lp(a) levels with AoVC, it will be interesting to find out if reducing Lp(a) levels will also slow down aortic valve disease progression. Finally, I found that lower protein levels of leucine-rich alpha-2-glycoprotein (LRG1), inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3), complement C4-B (C4B), complement C1q subcomponent subunit B (C1QB), monocyte differentiation antigen (CD14) and histidine-rich glycoprotein (HRG) were associated with a higher abundance of subclinical atherosclerosis and previous CVD events in heFH patients. Whether these proteins can be used as potential biomarkers or are causally related to CVD outcome needs to be further investigated.