This working group sought to translate the rapidly growing body of evidence for inflammation as a key process in atherosclerosis into clinical and public health practice. Basic science and epidemiological studies have developed an impressive case that atherogenesis is essentially an inflammatory response to a variety of risk factors and the consequences of this response lead to the development of acute coronary and cerebrovascular syndromes. Although several cytokines, acute-phase reactants, and cellular responses to inflammatory stimuli potentially might be predictive of clinical disease, the laboratory tests to assess inflammation are limited to those that are employable in clinical settings, have commercially available assays that can be standardized, and have adequate precision. On the basis of these considerations, it is most reasonable to limit current assays of inflammatory markers to hs-CRP, measured twice, either fasting or nonfasting, with the average expressed in mg/L, in metabolically stable patients. Relative risk categories (low, average, high) correspond to approximate tertiles of values (<1.0, 1.0 to 3.0, and >3.0 mg/L, respectively), based on an aggregation of population studies. hs-CRP has been studied in nested case-control and prospective studies, which have shown graded, dose-response relationships to clinical CVD that remain after adjustment for other risk factors, with moderately strong associations between the lower and upper tertiles (RR ≈2.0). hs-CRP seems to add predictive value above that of currently established risk factors. The evidence, however, is not entirely consistent across published studies, and in particular, additional prospective studies are needed to more precisely define risk at various strata and to assure consistency in other age, sex, and race-ethnicity groups. On the basis of the available evidence, the Writing Group recommends against screening of the entire adult population for hs-CRP as a public health measure. The Writing Group does conclude that it is reasonable to measure hs-CRP as an adjunct to the major risk factors to further assess absolute risk for coronary disease primary prevention. At the discretion of the physician, the measurement is considered optional, based on the moderate level of evidence (Evidence Level C). In this role, hs-CRP measurement appears to be best employed to detect enhanced absolute risk in persons in whom multiple risk factor scoring projects a 10-year CHD risk in the range of 10% to 20% (Evidence Level B). However, the benefits of this strategy or any treatment based on this strategy remain uncertain. The finding of a high relative risk level of hs-CRP (>3.0 mg/L) may allow for intensification of medical therapy to further reduce risk and to motivate some patients to improve their lifestyle or comply with medications prescribed to reduce their risk. Individuals at low risk (<10% per 10 years) will be unlikely to have a high risk (>20%) identified through hs-CRP testing. Individuals at high risk (>20% risk over 10 years) or with established atherosclerotic disease generally should be treated intensively regardless of their hs-CRP levels, so the utility of hs-CRP in secondary prevention appears to be more limited. In patients with stable coronary disease or acute coronary syndromes, hs-CRP measurement may be useful as an independent marker for assessing likelihood of recurrent events, including death, myocardial infarction, or restenosis after percutaneous coronary intervention. However, secondary preventive interventions with proven efficacy should not be dependent on hs-CRP levels. Further, serial testing of hs-CRP should not be used to monitor effects of treatment. These recommendations should not be interpreted to mean that the scientific evidence is fully adequate. Randomized trials in which inflammatory marker testing was the primary intervention have not been performed to provide Level A evidence, nor have cost-effectiveness analyses been completed to assess additional costs or cost savings through the use of such tests. The currently available evidence was assessed in the formulation of these recommendations. A long list of recommendations for further research reflects the need to clarify numerous issues. Nonetheless, basic and epidemiological studies suggest that this will be a fertile topic for investigations and will help define the most effective and efficient use of inflammatory markers in the prediction of CVD.
