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1 13 | Introduction Another approach of finding novel risk factors is using proteomics techniques. Proteomics aims to find difference in quantity in proteins of different samples, and has been used to identify novel biomarkers in several disease states, including coronary artery disease (47,48). In this thesis I aimed to identify novel markers of cardiovascular disease in long-term statin treated FH patients by applying the proteomic technique to samples of different risk groups of these FH patients. Risk in these patients was identified using coronary angiography with which we investigated a low risk group, an intermediate risk group, and a group with manifested cardiovascular disease. Cardiovascular imaging and Lp(a) Lp(a) levels in the general population are associated with AoVC (49), but the relation between AoVC and Lp(a) in FH is unknown as is the relationship between Lp(a) plasma levels and cardiovascular imaging outcomes. In this thesis I investigated whether Lp(a) was associated with the cardiovascular imaging modalities, carotid calcification, coronary calcification and aortic valve calcification. General outline of the Thesis InChapter 2, I validatedour carotidultrasonography device for use in the studies of Chapter 3 and Chapter 6. In Chapter 3, I investigated whether carotid ultrasonography outcomes were different between statin-treated FH patients and healthy controls, and whether these ultrasonography outcomes correlated with coronary atherosclerosis measured by CTCA. In Chapter 4, I continued to study the CTCA data and investigated whether long-term, statin- treated FH patients had a higher prevalence and extend of AoVC than healthy controls. The associationbetweenAoVCandLp(a) inheterozygous FHpatients is shown inChapter 5.This association is known in the general population but has not been previously investigated in FH patients. Chapter 6 focusses on the association between carotid ultrasonography outcomes and Lp(a) in statin-treated FH patients to investigate whether the residual risk of high Lp(a) levels can be depicted by this non-invasive imaging technique. In Chapter 7, the possible therapeutic possibilities in lowering Lp(a) are described, including novel agents which are currently still in development. The iTRAQ proteomics approach was used in Chapter 8 to explore novel proteins associated with coronary atherosclerosis and CVD endpoint in treated heterozygous FH patients. The summary and discussion of the thesis is presented in English (Chapter 9) and Dutch (Chapter 10).