Table of Contents
Journal of Biomarkers
Volume 2013, Article ID 709740, 13 pages
Research Article

Censored Data Analysis Reveals Effects of Age and Hepatitis C Infection on C-Reactive Protein Levels in Healthy Adult Chimpanzees (Pan troglodytes)

Alamogordo Primate Facility, Building 1303, P.O. Box 956, Holloman AFB, NM 88330-0956, USA

Received 15 October 2012; Revised 18 January 2013; Accepted 21 January 2013

Academic Editor: José Luis Martín-Ventura

Copyright © 2013 John J. Ely et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


C-reactive protein, a conserved acute-phase protein synthesized in the liver and involved in inflammation, infection, and tissue damage, is an informative biomarker for human cardiovascular disease. Out of 258 captive adult common chimpanzees (Pan troglodytes) assayed for CRP, 27.9% of the data were below the quantitation limit. Data were analyzed by the Kaplan-Meier method and results compared to other methods for handling censored data (including deletion, replacement, and imputation). Kaplan-Meier results demonstrated a modest age effect and a strong effect of HCV infection in reducing CRP but did not allow inference of reference intervals. Results of other methods varied considerably. Substitution schemes differed widely in statistical significance, with estimated group means biased by the size of the substitution constant, while inference of unbiased reference intervals was impossible. Single imputation gave reasonable statistical inferences but unreliable reference intervals. Multiple imputation gave reliable results, for both statistical inference and reference intervals, and was comparable to the Kaplan-Meier standard. Other methods should be avoided. CRP did not predict cardiovascular disease, but CRP levels were reduced by 50% in animals with hepatitis C infection and showed inverse relationships with 2 liver function enzymes. Results suggested that hsCRP can be an informative biomarker of chronic hepatic dysfunction.