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

John J Ely,M Lon Lammey,Tony Zavaskis

doi:10.1155/2013/709740

Abstract

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.

Highlights

C-reactive protein (CRP), a phylogenetically highly conserved protein, has become an important biomarker of acute inflammation and tissue damage in humans [1,2,3]
Type II censoring will not be further discussed.) We used Little’s [61] missing completely at random (MCAR) test statistic and contingency table methods [57, 58] to test for nonrandom patterns of hsCRP data missingness relative to other factors
We first tested for the presence of bias or nonrandom patterns of missing hsCRP data relative to the covariates

Summary

Introduction

C-reactive protein (CRP), a phylogenetically highly conserved protein, has become an important biomarker of acute inflammation and tissue damage in humans [1,2,3]. Cardiovascular disease (CVD) is the primary cause of morbidity and mortality in captive chimpanzees [19,20,21,22,23,24,25] This suggested the potential utility of CRP as a biomarker of CVD in aging chimpanzees, not unlike other biomarker studies [19, 20]. There was one earlier study of CRP in chimpanzees [30], but results were limited due to small sample size (N = 37) and wide age range (10 yr old); sex differences were not evaluated, and associations with CVD or hepatitis infection were not investigated [30]. It was of interest to evaluate CRP as a potential biomarker for CVD and hepatic dysfunction and to define reference intervals in a large captive population of chimpanzees

Methods

Results

Discussion