Comparing Measures of HDL: On the Right Path with the Wrong Map

HDL cholesterol is often referred to as the “good” cholesterol. This is due to HDL involvement in transport of cholesterol from vascular plaques and peripheral tissues back to the liver during reverse cholesterol transport. Additional protective aspects attributed to HDL include antioxidant, antiinflammatory, vasodilatory, and antithrombotic activities.

This variety of HDL physiological functions is made possible by structural and compositional heterogeneity of circulating HDL particles. Direct measures of HDL activity are available but remain limited to research applications at present. Reverse cholesterol transport studies have demonstrated that the size and composition of HDL particles can influence the mechanism and capacity for cholesterol efflux and other potential protective activities (1). Thus, measurement of HDL size and composition may provide a surrogate for protective HDL activity.

In this issue of Clinical Chemistry, investigators from the Boston Heart Diagnostics group report a comparison of their HDL mapping method with 4 different clinical methods for HDL subfractionation (2). Comparing these methods is not a trivial task. The authors used a clever approach by normalizing the relative amount of large, medium, and small HDL to the total HDL reported by each method. Passing–Bablok and Bland–Altman plots for each pairing of methods were then used to compare normalized large, medium, or small HDL among 98 subjects. In this way, correlation and bias between the various methods were quantifiable.

Unfortunately, the approach of normalization cannot adequately address some confounders. First, the methods of separation are not the same. Some methods separate subfractions according to HDL size while others separate them according to HDL density. Second, …