From targeting major cardiovascular players to precision medicine

Atherosclerosis is a multifactorial and complex disorder. This thesis focusses on three of the major players in the initiation and progression of atherosclerotic cardiovascular disease (CVD): inflammation, low density lipoprotein (LDL) cholesterol and lipoprotein(a) [Lp(a)]. This thesis aims to increase understanding of who is at risk, what is driving the risk and how to target the risk in order to reduce the burden of CVD.
In part I we discuss the role of LDL- cholesterol, Lp(a) and inflammation in initiation and progression of atherosclerotic cardiovascular disease (CVD) and their role in cardiovascular risk of patients. After identification of the major players in atherosclerosis in part I, part II comprises different strategies targeting these major players. Here, the effects of both anti-inflammatory drugs and cholesterol lowering drugs are evaluated on arterial wall inflammation in different patient groups (as assessed by ¹⁸FDG PET-CT). Furthermore, we target Lp(a) both in vitro and ex vivo, with effects measured on endothelial cells as well as monocytes.
An increasing number of therapeutic interventions can target the major players in order to reduce CVD. Accurate cardiovascular disease prediction is essential to balance risk and potential benefits of novel therapeutic options. Part III of this thesis works towards a patient tailored approach for cardiovascular risk. In line, we discuss novel therapeutic options in cardiovascular risk management and supply an overview of the pros and cons of these new drugs.