Clinical Chemistry
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Clinical Chemistry 47: 426-430, 2001;
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(Clinical Chemistry. 2001;47:426-430.)
© 2001 American Association for Clinical Chemistry, Inc.


Articles

Absence of Diurnal Variation of C-Reactive Protein Concentrations in Healthy Human Subjects

Hans K. Meier-Ewert1,a, Paul M. Ridker2,6, Nader Rifai3,6, Nick Price4, David F. Dinges4 and Janet M. Mullington5

1 Department of Cardiology, Lahey Clinic Medical Center, 41 Mall Rd., Burlington, MA 01805.

2 Center for Cardiovascular Disease Prevention, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02115.

3 Departments of Pathology and Laboratory Medicine, Harvard Medical School and Children’s Hospital, Boston, MA 02115.

4 Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104.

5 Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA 02215.

6 Leducq Center for Molecular and Genetic Epidemiology of Cardiovascular Disorders, Boston, MA 02115.
a Author for correspondence. Fax 781-744-5261; e-mail hans.k.meierewert{at}lahey.org.

Background: The concentration of C-reactive protein (CRP) in otherwise healthy subjects has been shown to predict future risk of myocardial infarction and stroke. CRP is synthesized by the liver in response to interleukin-6, the serum concentration of which is subject to diurnal variation.

Methods: To examine the existence of a time-of-day effect for baseline CRP values, we determined CRP concentrations in hourly blood samples drawn from healthy subjects (10 males, 3 females; age range, 21–35 years) during a baseline day in a controlled environment (8 h of nighttime sleep).

Results: Overall CRP concentrations were low, with only three subjects having CRP concentrations >2 mg/L. Comparison of raw data showed stability of CRP concentrations throughout the 24 h studied. When compared with cutoff values of CRP quintile derived from population-based studies, misclassification of greater than one quintile did not occur as a result of diurnal variation in any of the subjects studied. Nonparametric ANOVA comparing different time points showed no significant differences for both raw and z-transformed data. Analysis for rhythmic diurnal variation using a method fitting a cosine curve to the group data was negative.

Conclusions: Our data show that baseline CRP concentrations are not subject to time-of-day variation and thus help to explain why CRP concentrations are a better predictor of vascular risk than interleukin-6. Determination of CRP for cardiovascular risk prediction may be performed without concern for diurnal variation.




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