15289-s-bos

9 153 | Summary and Discussion Proposed research • The predictive value of carotid plaques and intima media thickness on CVD events in long-term statin-treated FH patients • Prevalence of clinical relevant aortic valve pathology in aging heterozygous FH patients • Cost-effectiveness of routine cardiac ultrasound in the aging heterozygous FH patient to detect aortic valve pathology • Value of specific Lp(a) lowering medication for CVD prevention and to prevent progression of aortic valve sclerosis to clinical aortic valve stenosis • Further investigation of the value of novel proteins: “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)” as suitable biomarkers or CVD risk factors in FH and non-FH patients, and to study the potential mechanisms by which these proteins contribute in atherosclerotic disease. Overall conclusion of the Thesis In conclusion I found that imaging carotid ultrasonography outcomes were similar between asymptomatic statin-treated familial hypercholesterolemia (FH) patients and healthy controls, and that carotid plaque presence was associated with coronary calcification in these FH patients. I also showed that the prevalence and extent of aortic valve calcification (AoVC) was twice as high in heterozygous FH patients compared to non-FH controls, and that this effect is strongest in those with a LDL-receptor negative mutationandhighest untreatedLDL-cholesterol levels.This suggest a causal relationship between AoVC and LDL-cholesterol. Additionally, AoVC is also independently associated with plasma Lipoprotein (a) [Lp(a)] levels, but I did not see an effect of Lp(a) on carotid ultrasonography outcomes in asymptomatic statin-treated FH patients. Finally, I found that the absence of plasma 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) proteins were associated with subclinical atherosclerosis and previous CVD events in heterozygous FH patients.