%0 Journal Article
%T Censored Data Analysis Reveals Effects of Age and Hepatitis C Infection on C-Reactive Protein Levels in Healthy Adult Chimpanzees (Pan troglodytes)
%A John J. Ely
%A Tony Zavaskis
%A M. Lon Lammey
%J Journal of Biomarkers
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/709740
%X 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. 1. Introduction C-reactive protein (CRP), a phylogenetically highly conserved protein, has become an important biomarker of acute inflammation and tissue damage in humans [1¨C3]. CRP is an important biomarker for many aspects of health and disease, including cardiovascular disease, type 2 diabetes, and chronic renal disease and is a predictor of all-cause mortality [2, 4¨C7]. CRP is synthesized by hepatocytes when induced by cytokines including IL-6 [1, 4]. Circulating plasma levels can rise during the acute-phase response to inflammation, infection, or trauma by 10,000-fold and decrease just as rapidly [1, 2, 8]. CRP has many biological functions related to the recognition and clearance of foreign pathogens and damaged host cells, binding chromatin and small nuclear ribonucleoproteins, which suggested a role in clearance of debris due to apoptosis and necrosis [2, 4, 8]. CRP stimulates the classical complement pathway [1, 2, 4]. Its activation by the same Fc receptors used by IgG, and its earlier response to infection, suggested a role in inducing an adaptive immune response [4]. CRP is also involved in the development of
%U http://www.hindawi.com/journals/jbm/2013/709740/