Journal Article

Refinement of the Association of Serum C-reactive Protein Concentration and Coronary Heart Disease Risk by Correction for Within-Subject Variation over Time

Wolfgang Koenig, Malte Sund, Margit Fröhlich, Hannelore Löwel, Winston L. Hutchinson and Mark B. Pepys

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 158, issue 4, pages 357-364
Published in print August 2003 | ISSN: 0002-9262
Published online August 2003 | e-ISSN: 1476-6256 | DOI: http://dx.doi.org/10.1093/aje/kwg135
Refinement of the Association of Serum C-reactive Protein Concentration and Coronary Heart Disease Risk by Correction for Within-Subject Variation over Time

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The authors sought to assess the repeatability of measurements of C-reactive protein, an independent predictor of coronary heart disease, in a large cohort of apparently healthy men and to correct earlier estimates of the association of C-reactive protein and coronary heart disease for the measurement error in this protein. They measured C-reactive protein by a high-sensitivity assay in 936 men aged 45–64 years in the MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg cohort in 1984–1985 and remeasured it 3 years later. All men were subjected to an 8-year follow-up of their cardiovascular status. The analytical variation of the assay was small, with the analytical variance component at 1 percent of the within-subject variance component, a repeatability coefficient of 25 percent, and a reliability coefficient of 1.00. In contrast, the within-subject variation of C-reactive protein corresponded to a repeatability coefficient of 740 percent and a reliability coefficient of 0.54, indicating considerable within-subject variation. Based on the authors’ estimates, three serial determinations of C-reactive protein should be done to achieve a reliability of 0.75, the value they found for total cholesterol. Correcting the hazard ratios in their original analysis of the association of coronary heart disease and high-sensitivity-assay C-reactive protein for the measurement error in C-reactive protein and covariables leads to a considerably larger estimate. The results suggest that the true association between C-reactive protein and cardiovascular risk is underestimated by a single C-reactive protein determination, and that several serial C-reactive protein measurements should be taken.

Keywords: coronary disease; inflammation; predictive value of tests; proteins; Abbreviations: CI, confidence interval; MONICA, Monitoring of Trends and Determinants in Cardiovascular Disease; VCa, analytical variance component; VCb, between-subject variance component; VCw, within-subject variance component.

Journal Article.  5342 words.  Illustrated.

Subjects: Public Health and Epidemiology

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