The inflammable truth of atherosclerosis

The multi-level inflammatory response in cardiovascular disease (CVD) and the mediators of this response are the central topics of this thesis. Part I of this thesis deals with imaging of inflammation at the level of arterial wall, bone marrow and spleen, using ¹⁸F-fluordeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT), in patients at risk for or with overt CVD. We show that both arterial wall, bone marrow and spleen (hematopoietic organs) are involved in the development of cardiovascular disease. Part II of this thesis focusses on mediators of the inflammatory response. We investigate the role of remnant cholesterol and Lp(a) in the development of cardiovascular disease. We show that remnant cholesterol induces both arterial wall inflammation as well bone marrow ‘activation’, with concomitant increased activation of monocytes due to lipid accumulation. Furthermore, we show that besides a pro-inflammatory effect of Lp(a), these particles can also have a direct atherogenic effect and thereby accelerate atherosclerotic burden itself instead of only promoting plaque vulnerability. Not only lipids are mediators of atherosclerosis, also other non-lipid driven diseases are risk factors for CVD. We show that patients with chronic kidney disease, with an increased risk of cardiovascular disease, have elevated arterial wall inflammation. Lastly, we show that treatment with anti-inflammatory therapy in patients with spondylarthritis can reduce arterial wall inflammation. Taken together, not only lipid-lowering strategies, but also anti-inflammatory treatment can reduce arterial wall inflammation.