15289-s-bos

9 149 | Summary and Discussion FH patients for whom CTCA results were available. This suggests that carotid plaque presence might distinguish low residual CVD risk FH patients from those with high residual risk. In our study the prevalence of carotid plaques was 31% in asymptomatic statin-treated FH patients at the age of 46±15 years, with 95% of carotid plaques present in those of 40 years or older. In a study in asymptomatic FH patients older than 40 years it was concluded that carotid plaques, measured by ultrasonography, were not significantly associated with coronary calcifications on CTCA (17). An explanation of this lacking association was the high prevalence of carotid plaques (93%) in this study. The results presented in that study and Chapter 3 emphasize the importance of studying the correlation between ultrasonography findings and coronary calcifications in subjects younger than 40 years (17). Currently CT coronary angiography scans, are usually not performed below the age of 40 years in asymptomatic individuals due to radiation exposure and the associated elevated long-term risk of cancer. With improvement in CT scanning techniques radiation exposure will further reduced, and in the future these studies might be possible in younger individuals. These studies might lead to a screening program among FH patients below the age of 40 years to identify those FH patients with the highest residual CVD risk. Another imaging finding reported in this thesis is the presence of AoVC measured by CTCA as was used in Chapter 4 and Chapter 5. I concluded that AoVC is more prevalent and severer in statin-treated heFH than in controls, and that the severity of AoVC was associated with higher untreated LDL-C levels which is related to LDL-receptor negative mutations as compared to carriers of LDL-receptor- defective mutations. This suggests a causal role of LDL-C in the development of AoVC. However previous clinical trials such as the SALTIRE, ASTRONOMER, and SEAS showed that statins cannot delay the progression of aortic valve sclerosis towards aortic valve stenosis (18-20). An explanation might be that the initiation and progression of AoVC are two different entities with separate pathophysiological mechanisms. The initiation of AoVC seems to be effected by the classical risk factors of atherosclerosis, including as LDL-C. These risk factors might be responsible for the differentiation of interstitial aortic valve cells to an osteogenic phenotype. These osteogenic cells cause the progressing of calcification of the valve and cannot be delayed by statins. This theory emphasizes the need of early LDL-C reduction in FH patients, to prevent early differentiation towards osteogenic cells and thereby progression to AoVC. Routine screening for aortic valve pathology by cardiac ultrasound, which is currently advised by guidelines for homozygous FH patients, could be considered in patients with heterozygous FH, especially in those with an LDL-