Cardiovascular disease beyond traditional risk factors; balancing lipids and inflammation

In this thesis we aim to identify subjects at increased cardiovascular disease risk, not recognized or optimally treated by current guidelines. Part one of this thesis concerns lipids: we assess the inflammatory potential of LDL cholesterol, and the effects of available potent LDL lowering therapies hereon. The need for and timing of treatment of other hyperlipidemias remains elusive. Remnant cholesterol has been identified as an independent risk factor for cardiovascular disease. We assess its clearance by the liver and its relation with apo-CIII levels, and show that this lipid moiety influences several inflammatory pathways.
In the second part of this thesis we investigate non-lipid driven diseases that predispose to cardiovascular risk, in which guidelines are scarce and interpretation may be difficult. Using ¹⁸F-FDG PET/CT we find increased arterial inflammation in common chronic inflammatory diseases (rheumatoid arthritis and ankylosing spondylitis). We assess the influence of anti-inflammatory treatment hereon and potential treatment with statins.
We also find increased arterial inflammation in subjects suffering from Chronic Kidney Disease or diabetes, both associated with high CVD risk. The level of arterial inflammation is largely independent of traditional risk factors and driven by measures of disease regulation, highlighting the need for additional screening and treatment options.
Although lowering of the inflammation is likely to improve cardiovascular outcomes, reduced immune responses carry increased risk of infection. Future therapies may also aim at enhancing anti-inflammatory pathways. In the final chapter of this thesis, we assess the potential of enhancing anti-inflammatory B cells on the progression of atherosclerosis.