Determination of high sensitivity C-reactive protein: Clinical and analytical quality

Inflammation plays a key role in the pathophysiology of atherosclerotic disease. A number of inflammatory markers that are measurable in blood have been investigated for their ability to predict the risk of future atherosclerotic events. High-sensitivity (hs) measurement of C-reactive protein (CRP) has received a great deal of attention recently for use as an atherosclerotic risk marker. For these reasons, CRP is currently the inflammatory marker of choice. The Centers for Disease Control and Prevention (CCDC) and the American Heart Association (AHA) issued guidelines for the utility of this marker in the primary prevention setting and in patients with stable coronary disease or acute coronary syndromes. The guidelines also included specific recommendations that pertain to the laboratory aspect of CRP and defined cut-points for clinical interpretation; CRP concentrations <1 mg/L are considered low, 1-3 mg/L average, and >3 mg/L high relative risk. A number of preanalytical and analytical factors including specimen type and stability, assay imprecision, commercial availability, and standardization are reviewed here. Better control of preanalytic and analytic sources of variations will undoubtedly lead to improvement in CRP measurements. Further research is required to better define the performance characteristics necessary for assays bearing the designation hsCRP. These characteristics include developing guidelines for total analytical error from a careful review of the intraindividual biological variability of the analyte under conditions that will be encountered in clinical practice, defining allowable random and systematic error limits based on this information, validating these guidelines in the clinical setting, and completing the standardization efforts.