The Clinical Value of HDL Function Measurements

Low levels of plasma high-density lipoprotein (HDL) cholesterol are independently associated with an increased risk of atherosclerotic cardiovascular disease (CVD). The mechanisms by which HDL protects against CVD are complex and multifactorial. Functions of HDL that may lead to protection from atherosclerosis include (i)removal of excess cholesterol from lipid-laden macrophage cells in the artery wall is generally believed to be the primary anti-atherogenic action of HDL, (ii) anti-oxidative properties, typically characterized by the ability of HDL to inhibit the pro-atherogenic oxidative modification of LDL and (iii) anti-inflammatory properties, such as its capacity to reduce cytokine-induced expression of adhesion molecules on endothelial cells.
On the other hand, several studies have demonstrated that HDL can lose its ability to counteract the development of atherosclerosis in certain disease states and may even become pro-atherogenic. Together with the inconsistent relationship between plasma HDL cholesterol levels and CVD on the individual level as well as the disappointing results of recent clinical trials with HDL-raising agents, these data enforced the concept that the functional quality of HDL particles may be more important than absolute HDL cholesterol mass levels. However, the importance of HDL functionality for cardiovascular risk is still poorly investigated. Therefore, the aim of this thesis was to provide more insight into the importance of HDL functionality for cardiovascular risk.
Overall, important information can be derived from measures of HDL functionality over mere HDL cholesterol mass levels. However, there is still an urgent need for large prospective studies exploring whether HDL functionality can predict disease in the general population.