High sensitivity immunoassays for C-reactive protein: promises and pitfalls.

C-reactive protein (CRP) has historically been measured in the clinical laboratory for the detection and monitoring of occult infection and inflammation, using immunoturbidimetric or immunonephelometric techniques. The recent commercial availability of automated high-sensitivity assays has enabled investigators to measure CRP at levels previously unattainable on a routine basis and to explore its clinical utility in apparently healthy individuals. CRP concentrations increased above the individuals' baselines but still within the normal reference intervals have been observed in association with increasing age, obesity, and smoking and in individuals with chronic infections such as Chlamydia pneumoniae and Helicobacter pylori. More importantly, however, data from prospective studies have shown CRP to be a strong and independent predictor of future coronary events in subjects with and without coronary heart disease. An algorithm for risk assessment of coronary risk employing both CRP and lipid concentrations has recently been proposed. However, in order for this approach to be incorporated into clinical practice, agreement among the various CRP methods must be achieved. Of critical importance to this process is a basic understanding of issues affecting assay performance. Factors such as assay precision, sensitivity, matrix effects, calibration, and standardization need to be addressed adequately by the in vitro diagnostic industry and the clinical laboratory.