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Departments of
1
Pathology and
2
Biochemistry, University of Vermont, Burlington, VT 05405.
a Address for correspondence: Department of Pathology, University of Vermont, Colchester Research Facility, 55A South Park Dr., Colchester, VT 05446. Fax 802-656-8965; e-mail rtracy{at}moose.uvm.edu
We developed a reproducible ELISA for C-reactive protein (CRP),
calibrated with WHO Reference Material, for which intra- and interassay
CVs were 3.0% and 6.0%, respectively. Analytical recovery was 97.9%.
The distribution of CRP in a healthy blood donor population (n =
143) was nongaussian, 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 the method of Fraser and Harris (Crit Rev Clin Lab Sci
1989;27:40937)], 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
0.05
(i.e., the smallest percentage change unlikely to be due to analytical
variability or CVI) was calculated as 118%, and the index
of individuality, CVI/CVG, was 0.46. This
suggests that CRP, like many clinical chemistry analytes, has limited
usefulness in detecting early disease-associated changes when used in
conjunction with a healthy reference interval. From a molecular
epidemiological standpoint, the usefulness of CRP in longitudinal
studies is suggested by the small index of individuality and by
observations that (a) short-term fluctuations were
infrequent, (b) all data stayed within the reference
interval, and (c) relative rankings of the subjects over 6
months only moderately deteriorated.
Key Words: indexing terms: inflammation cardiovascular disease variation, source of index of individuality critical difference molecular epidemiology
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