High-density lipoprotein: a fall from grace?

Based on a plethora of in-vitro and in-vivo research data, high-density lipoprotein cholesterol (HDL) has been regarded as universally atheroprotective. Consequently, pharmacologically mediated HDL increase has emerged as a potential means to improve prevention and treatment of patients with atherosclerotic vascular disease. In particular, inhibition of cholesteryl ester transfer protein (CETP) was considered a promising strategy. Recently, the unanticipated and disappointing results of four large clinical trials with the CETP inhibitor torcetrapib have necessitated refinement of the HDL hypothesis. In addition, the progressive insight that HDL may actually be predominantly a carrier molecule of a wide array of proteins rather than merely a cholesterol-transporter has resulted in the interest to look beyond HDL levels alone. Here we will discuss the impact of recent developments on the HDL hypothesis as well as the advent of even more recent therapeutic developments in the HDL field.