Title: Which inflammatory marker tests should be used in primary care? A cohort study using CPRD
Research comparing C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and plasma viscosity (PV) in primary care is lacking. Clinicians often use multiple inflammatory markers simultaneously, leading to concerns about overuse, and difficulties with interpretation of results, which may be discrepant. The aims of this study were; firstly to compare the diagnostic accuracies of CRP, ESR and PV, and secondly to evaluate whether measuring two inflammatory markers simultaneously increases diagnostic accuracy.
Prospective cohort study in UK primary care using Clinical Practice Research Datalink. Participants were 160,000 patients with inflammatory marker testing in 2014. We compared the diagnostic test performance of inflammatory markers, singly and paired, for any relevant disease (infections, autoimmune conditions and cancers).
After excluding those with pre-existing autoimmune conditions, cancers and recent infections, 136,961 participants remained; 83,761 (62.2%) had a single inflammatory marker at the index date, and 53,200 (38.8%) had multiple inflammatory markers. For any relevant disease, only small differences were seen between the three tests; areas under receiver operator curve (AUC) ranged from 0.66–0.68. CRP had the highest overall AUC, largely because of superior performance in infection (AUC CRP 0.62 versus ESR 0.59, p<0.001). Adding a second test gave marginal improvement in the AUC for relevant disease (CRP 0.68 versus CRP+ESR 0.69, p<0.001); this is of debatable clinical significance. The negative predictive value for any single inflammatory marker was 94% (95% CI 93.8–94.2), compared to 94.1% (93.9–94.4) with multiple negative tests.
Results have important clinical implications for practicing GPs. Testing multiple inflammatory markers simultaneously does not appear to increase the ability to rule out disease. We therefore suggest that this should usually be avoided. CRP has superior diagnostic accuracy for infections, and is equivalent for autoimmune conditions and cancers; we therefore suggest this should generally be the first line test. As CRP is also cheaper, we expect that implementation of these findings could generate significant cost savings for the NHS as well as reductions in GP workload.