HDL Therapeutics — Time for a Curtain Call or Time to Reconceptualize?

The identification of an inverse association between high-density lipoprotein (HDL) cholesterol levels and incident cardiovascular disease events,¹ combined with research on the role of HDL in reverse cholesterol transport, led to the exploration of therapies directed toward increasing HDL cholesterol. However, although therapies such as cholesteryl-ester transfer protein inhibitors increased HDL cholesterol levels, these therapies did not reduce the incidence of cardiovascular disease events.^1,2 Consequently, the focus of HDL therapeutics shifted to attempting to improve the functionality, or quality, of HDL, and efforts to measure and enhance cholesterol efflux capacity and thereby promote reverse cholesterol transport were initiated.^1,2 Although the …