15289-s-bos

9 145 | Summary and Discussion Summary Since the introduction of statin therapy as cholesterol-loweringmedication in the 1990s, the life expectancy of patients with familial hypercholesterolemia (FH) has improved significantly. However, despite the wide-spread use of statins among FH patients, some still do develop CVD (1). The aim of this thesis was to develop an approach to identify the residual cardiovascular disease (CVD) risk in statin-treated FH patients. Therefore, in part 1 I investigated the value of applying imaging techniques such as carotid ultrasonography and computed tomography coronary angiography (CTCA) (chapter 2,3 and 4), and in part 2 measurement of non-traditional and traditional risk factors such as lipoprotein (a) [Lp(a)] levels in statin treated FH patients (chapter 5, 6) to distinguish who are high-risk FH patients and who not. In Chapter 7 I discussed the different treatment options of high Lp(a) levels. In Chapter 8 I concluded by using a proteomics technique to identify novel proteins that are associated with cardiovascular disease and coronary calcification in statin treated FH patients. Part 1: Cardiovascular imaging and residual cardiovascular risk in FHpatients. Subclinical atherosclerosis can be measured by carotid ultrasonography. As it is a non- invasive measurement and relatively easy to measure it is often used in clinical studies to determine cardiovascular risk. First, in chapter 2 I showed that the carotid ultrasonography technique that was used in our studies, is reliable and reproducible by performing an intra- and inter-observer validation between a traditional and semi-automatic ultrasound device. Subsequently, I studied in chapter 3whether carotid imaging results by ultrasonography, reflected by the prevalence of carotid plaques and carotid intima-media-thickness (C-IMT), are suitable for determining residual risk. Can we distinguish FH patients who use long-term statin treatment from non-FH subjects? Therefore, I compared carotid plaque prevalence and C-IMT between FH patients using long-term statin treatment and healthy non-FH controls. I showed that these outcomes were similar between the groups. In a subset of FH patients of whom a CTCA was available, I showed that carotid plaques presence was associated with coronary calcification determined by CTCA , implying that not C-IMT but carotid plaques could be of interest to determine residual risk in statin-treated FH patients.