R3i Editorial

Low HDL cholesterol is independently predictive of cardiovascular risk and increasingly seen as a secondary prevention target to address residual cardiovascular risk even in people with low concentrations of LDL cholesterol. However, measurement of HDL cholesterol (i.e. of the cholesterol contained in HDL particles), which is part of the routine assessment of patients’ lipid profile in clinical practice, is not a good surrogate for the complex metabolism of HDL.

A large body of evidence suggests that HDL measurements that extend beyond its cholesterol content may be useful for both risk stratification and assessment of different agents, which modulate HDL particle structure, metabolism, and function, and thus reduce residual cardiovascular risk. The complexity of HDL metabolism has warranted newer methods with the dual aim of quantifying HDL quantity and further exploring HDL functionality.

Since ultracentrifugation – the earliest method for measurement of HDL subclasses as a function of size and density, different techniques, such as electrophoresis, nuclear magnetic resonance, ion mobility, apolipoprotein composition have been utilized to identify more precisely the various HDL subclasses and their concentration or quantity. Based on these techniques, different classifications of HDL particles have been proposed and their specific roles in different stages of reverse cholesterol transport, from macrophage cholesterol efflux to elimination of cholesterol through the liver have been determined or are under investigation.

In this context, there was a need for a reference center featuring the most recent advances in HDL basic science and clinical research. With the HDL Resource Center, visitors of the R3i website will have free access to slide kits of major HDL-related concepts with annotation and literature citation, overview of consensus statements from the HDL Summits I and II held in New York on February 27, 2010 and May 13-14, 2011, and interactive interviews from selected faculty who participated in HDL Summit II. The Center will be a living library related to the most important issues of HDL biology in relation with their potential clinical consequences.

One the first issues that will appear in the HDL Resource Center will be the new uniform nomenclature of HDL particles based on their size and density that I and other researchers proposed in an effort to harmonize future research in the field. The HDL Resource Center will also provide authoritative review of cellular cholesterol efflux, the major function of HDL, in order to correct long-held misconceptions regarding reverse cholesterol transport and provide a framework for evaluation of pharmaceutical agents that alter HDL concentrations and modulate HDL function.2

The 3rd HDL Summit to be held in New York in February 2012 will provide to the HDL Resource Center an opportunity to address new topics, namely: various functions of HDL and critical appraisal of the various methods that measure a particular aspect of HDL function. Future summits will address HDL subclasses and HDL functionality in diabetes patients; HDL subclasses and cardiovascular risk; and effects of HDL-directed pharmacological agents on HDL subclasses and HDL functionality.

Prospective clinical studies will be essential to establish the associations between HDL subclasses and CVD risk. As HDL-targeted therapy is potentially one the most promising approach to cardiovascular residual risk reduction, it is of paramount importance that physicians caring for high-risk CVD patients continue to receive education from lead researchers and clinicians in order to interpret the latest findings, implement best practices, and maximize patient outcomes.

It is the ambition of the HDL Resource Center to become the most effective instrument to help clinicians achieve these most desirable goals.


1. Rosenson RS, Brewer HB Jr, Chapman MJ, Fazio S, Hussain MM, Kontush A, Krauss RM, Otvos JD, Remaley AT, Schaefer EJ. HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events. Clin Chem 2011;57:392-410.
2. Rosenson RS. Cholesterol efflux and atheroprotection: Advancing the concept of reverse cholesterol transport. Circulation (in press).