Laboratory assessment of HDL heterogeneity and function.

Background: Plasma concentrations of HDL cholesterol (HDL-C) and its major protein component apolipoprotein (apo) A-I are strongly inversely associated with cardiovascular risk, leading to the concept that therapy to increase HDL-C and apoA-I concentrations would be antiatherosclerotic and protective against cardiovascular events. The recent failure of the drug torcetrapib, a cholesteryl ester transfer protein inhibitor that substantially increased HDL-C concentrations, has brought focus on the issues of HDL heterogeneity and function as distinct from HDL-C concentrations.

Content: This review addresses the current state of knowledge regarding assays of HDL heterogeneity and function and their relationship to cardiovascular disease. HDL is highly heterogeneous, with subfractions that can be identified on the basis of density, size, charge, and protein composition, and the concept that certain subfractions of HDL may be better predictors of cardiovascular risk is attractive. In addition, HDL has been shown to have a variety of functions that may contribute to its cardiovascular protective effects, including promotion of macrophage cholesterol efflux and reverse cholesterol transport and antiinflammatory and nitric oxide-promoting effects.

Summary: Robust laboratory assays of HDL subfractions and functions and validation of the usefulness of these assays for predicting cardiovascular risk and assessing response to therapeutic interventions are critically important and of great interest to cardiovascular clinicians and investigators and clinical chemists.