15289-s-bos

94 | Chapter 6 C-IMT in our study of aggressively treated FH patients seems in the range of a healthy population. This is important since in young, newly diagnosed and mostly untreated, FH patients the C-IMT values were increased [24]. At our outpatient clinic, we perform an active screening among relatives of FH patients . Early identification, a subsequent early start of aggressive statin treatment and patient education improving lifestyle may have resulted in a C-IMT within the normal range. Additionally coronary artery calcification does not associate with carotid plaques and C-IMT, even though we do see severe coronary lesions in some patients, which questions the clinical applicability of carotid sonography in statin-treated FH patients. Lp(a) levels are not influenced by statins [12]. In line, we find large variations of the Lp(a) levels. Hence, statin treatment may compensate for the atherogenic effects of Lp(a) by either unknown mechanisms influencing of Lp(a) function or fully independent of Lp(a). Although Lp(a) is not associated with subclinical atherosclerosis determined by C-IMT, Lp(a) levels might still contribute to residual CVD risk in treated FH patients. The relationship between Lp(a) and CVD risk may be effected via pathophysiological mechanisms other than atherosclerosis. Proposed mechanisms are wound healing and fibrinolysis, in which Lp(a) also plays a role [9, 22]. Limitations Our study has some limitations. First, this study is an association study and therefore, we cannot prove or dismiss that Lp(a) has a causal effect in the residual CVD risk with this data. In addition, prospective ultrasound data was not available in these patients, and we cannot exclude that changes in plaque presence of C-IMT are associated with Lp(a). Another limitation is that carotid plaques are only scored categorical (present/absent), whereas plaque volume would be a more precise measurement. However, the device we used is not able to obtain 3D ultrasound plaque volume. Therefore, we cannot exclude different results when this 3D technique would have been used. In addition, we only used carotid ultrasound and did not look at other arteries liable to atherosclerosis. Therefore we cannot exclude different results if other arterial bed were examined. Finally theLp(a)measurement used is, likemost commerciallyavailablemeasurements, not a fully KIV-2 independent measurement, which leads to an overestimation of the low Lp(a) levels and a underestimation of high Lp(a) levels. However, since our primary analyses uses a cut-off value near the median Lp(a) level, it is unlikely that our measurement method reclassified patients into the other group.