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Early Inflammatory Markers Are Independent Predictors of Cardiac Allograft Vasculopathy in Heart-Transplant Recipients

Author

Listed:
  • Carlos A Labarrere
  • John R Woods
  • James W Hardin
  • Beate R Jaeger
  • Marian Zembala
  • Mario C Deng
  • Ghassan S Kassab

Abstract

Background: Identification of risk is essential to prevent cardiac allograft vasculopathy (CAV) and graft failure due to CAV (GFDCAV) in heart transplant patients, which account for 30% of all deaths. Early CAV detection involves invasive, risky, and expensive monitoring approaches. We determined whether prediction of CAV and GFDCAV improves by adding inflammatory markers to a previously validated atherothrombotic (AT) model. Methods and Findings: AT and inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) were measured in heart biopsies and sera of 172 patients followed prospectively for 8.9±5.0 years. Models were estimated for 5- and 10-year risk using (1) the first post-transplant biopsy only, or (2) all biopsies obtained within 3 months. Multivariate models were adjusted for other covariates and cross-validated by bootstrapping. After adding IL-6 and CRP to the AT models, we evaluated the significance of odds ratios (ORs) associated with the additional inflammatory variables and the degree of improvement in the area under the receiver operating characteristic curve (AUROC). When inflammatory markers were tested alone in prediction models, CRP (not IL-6) was a significant predictor of CAV and GFDCAV at 5 (CAV: p

Suggested Citation

  • Carlos A Labarrere & John R Woods & James W Hardin & Beate R Jaeger & Marian Zembala & Mario C Deng & Ghassan S Kassab, 2014. "Early Inflammatory Markers Are Independent Predictors of Cardiac Allograft Vasculopathy in Heart-Transplant Recipients," PLOS ONE, Public Library of Science, vol. 9(12), pages 1-18, December.
    • Handle: RePEc:plo:pone00:0113260
    DOI: 10.1371/journal.pone.0113260
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    References listed on IDEAS

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    1. Mark B. Pepys & Gideon M. Hirschfield & Glenys A. Tennent & J. Ruth Gallimore & Melvyn C. Kahan & Vittorio Bellotti & Philip N. Hawkins & Rebecca M. Myers & Martin D. Smith & Alessandra Polara & Alexa, 2006. "Targeting C-reactive protein for the treatment of cardiovascular disease," Nature, Nature, vol. 440(7088), pages 1217-1221, April.
    2. Margaret Pepe & Holly Janes & Gary Longton & Wendy Leisenring & Polly Newcomb, 2004. "Limitations of the Odds Ratio in Gauging the Performance of a Diagnostic or Prognostic Marker," UW Biostatistics Working Paper Series 1035, Berkeley Electronic Press.
    3. Carlos A Labarrere & John R Woods & James W Hardin & Gonzalo L Campana & Miguel A Ortiz & Beate R Jaeger & Lee Ann Baldridge & Douglas E Pitts & Philip C Kirlin, 2012. "Value of the First Post-Transplant Biopsy for Predicting Long-Term Cardiac Allograft Vasculopathy (CAV) and Graft Failure in Heart Transplant Patients," PLOS ONE, Public Library of Science, vol. 7(4), pages 1-10, April.
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