Intra-individual variation in serum C-reactive protein over 4 years: An implication for epidemiologic studies

Background Data on long-term intra-individual variability in high-sensitivity C-reactive protein (hsCRP) are needed to determine whether one measurement adequately reflects usual levels in prospective studies of on the etiology of cancer and other chronic diseases; when not reflective, the ability to statistically detect modest to moderate associations is reduced. The authors estimated the size of this source of variability and consequent attenuation of the relative risk (RR). Methods High-sensitivity C-reactive protein (hsCRP) concentration was measured using a high-sensitivity immunoturbidometric assay in sera collected at years 2, 4, and 6 from 50 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). After natural logarithmtransformation of hsCRP, analysis of variance was used to estimate the within- and between-individual variances from which the intra-class correlation coefficient (ICC) was calculated. Results The observed RR due to an ICC<1 was calculated by e^{(ln true RR*ICC)} for a range of true RRs. The 4-year ICC was 0.66. Measuring hsCRP once and assuming no other error, if the true RRs were 1.50, 2.00, and 3.00 when comparing high with low concentration, then the observed RRs would be 1.31, 1.58, and 2.06, respectively. Conclusion Investigators planning to measure hsCRP only once should design adequately sized studies to preserve inferences for hypothesized modest to moderate RRs.