VARIABILITY IN THE MEASUREMENT OF C-REACTIVE PROTEIN IN HEALTHY-SUBJECTS - IMPLICATIONS FOR REFERENCE INTERVALS AND EPIDEMIOLOGIC APPLICATIONS

We developed a reproducible ELISA for C-reactive protein (CRP), calibr ated with WHO Reference Material, for which intra- and interassay CVs were 3.0% and 6.0%, respectively. Analytical recovery was 97.9%. The d istribution of CRP in a healthy blood donor population (n = 143) was n ongaussian, with 2.5th, 50th, and 97.5th percentile values of 0.08, 0. 64, and 3.11 mg/L, respectively. There was no sex-related difference, and the association with age was weak. In a study of variability [by t he method of Fraser and Harris (Grit Rev Clin Lab Sci 1989;27:409-37)] , the analytical variability was 5.2%; the within-subject variability, CVI, was 42.2%; and the between-subject variability, CVG, was 92.5%. The critical difference for sequential values significant at P less th an or equal to 0;05 (i.e., the smallest percentage change unlikely to be due to analytical variability or CVI) was calculated as 118%, and t he index of individuality, CVI/CVG, was 0.46. This suggests that CRP, like many clinical chemistry analytes, has limited usefulness in detec ting early disease-associated changes when used in conjunction with a healthy reference interval. From a molecular epidemiological standpoin t, the usefulness of CRP in longitudinal studies is suggested by the s mall index of individuality and by observations that (a) short-term fl uctuations were infrequent, (b) all data stayed within the reference i nterval, and (c) relative rankings of the subjects over 6 months only moderately deteriorated.