CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: laboratory tests available to assess inflammation--performance and standardization: a background paper.

Inflammation plays a key role in atherosclerosis. A number of different biomarkers of inflammation are measurable in blood. These include cytokines, chemokines, soluble adhesion molecules, and acute-phase reactants. The first 3 groups of molecules are not routinely measured in clinical laboratories. The acute-phase reactants include C-reactive protein (CRP). This analyte is stable and is readily measured by several commercial high-sensitivity (hs) assays, and numerous clinical studies have demonstrated its usefulness as an atherosclerotic risk marker. For these reasons, CRP is currently the inflammatory marker of choice. Comparison of commercial hsCRP assays has demonstrated that many are capable of imprecision of <7% at a CRP concentration of <1 mg/L. Method comparability studies have shown good agreement among some commercial hsCRP assays in terms of quartile assignments, whereas additional standardization efforts are necessary for others. The first goal of standardization is to develop a secondary reference material with a CRP of approximately 4 mg/L. This material can be used to assist diagnostic vendors in calibrator value assignment and assay harmonization. Another project is to define clearly what performance characteristics are necessary for hsCRP assays. Preliminary estimates based on the biological variability of CRP indicate that the total allowable analytical error is between 15% and 32%. The former requirement can be met with accuracy and imprecision of <5% and the latter requirement with accuracy and imprecision of <11%. If 2 hsCRP results are averaged, then the imprecision requirements are relaxed slightly. Clinical validation of these performance requirements is also required.