Within-individual variation of C-reactive protein (CRP) measurements in primary care: A retrospective cohort study

1. Single C-reactive protein (CRP) measurements can be highly misleading due to large within-person variability, especially at higher values; repeat testing and cautious interpretation are essential.

Evidence Rating Level: 2 (Good)

This large retrospective cohort study examined within-individual variation in CRP levels using real-world primary care data from the UK. Because CRP guides diagnostic and therapeutic decisions in inflammatory and infectious conditions, understanding its biological and analytical variability is critical. The authors extracted CRP results and clinical covariates from the IQVIA Medical Research Database, including 472,811 patients with at least four CRP measurements. CRP values were log-transformed, and within-individual variation was quantified using a random-effects regression model to derive a coefficient of variation (CV). The overall within-individual CV was 1.60, markedly higher than values reported in prior controlled studies (median 0.41). Variation increased substantially with higher median CRP levels, particularly above 10 mg/L. Subgroup analyses showed higher CVs in women, younger and older age groups, individuals with low BMI, and those with comorbidities such as COPD, CKD, heart failure, and cancer. Sensitivity analyses confirmed consistent findings. The authors conclude that CRP demonstrates far greater real-world variability than previously recognized. This has important implications for diagnosis and monitoring: single CRP values may misclassify disease severity or treatment thresholds, particularly at higher CRP levels, and repeat testing or cautious interpretation is warranted.

Click here to read this study in PLOS One

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