HDL cholesterol, like LDL cholesterol, can be divided into several subfractions, based on density, size and protein composition. The HDL2 subfraction (HDL2a, HDL2b) consists of larger, more buoyant particles while particles in the HDL3 subfraction (HDL3a, HDL3b, HDL3c) are smaller and denser. The largest and most buoyant HDL particle is HDL2b.

One primary function of HDL particles is to promote reverse cholesterol transport, or the movement of cholesterol from the tissues to the liver for excretion. HDL is first formed in the liver as the smaller HDL3 particles. Once released, the HDL3 particles travel in the blood where they receive cholesterol by various enzymatic events, eventually resulting in the formation of HDL2b particles. Assessment of HDL2b particles may provide a more powerful measure of cardiovascular risk that other HDL2 or HDL3 subfractions, individually or combined.