Early inflammatory markers are independent predictors of cardiac allograft vasculopathy in heart-transplant recipients.

Abstract Background: Identification of risk is essential to prevent cardiac allograftvasculopathy (CAV) and graft failure due to CAV (GFDCAV) in heart transplantpatients, which account for 30% of all deaths. Early CAV detection involvesinvasive, risky, and expensive monitoring approaches. We determined whetherprediction of CAV and GFDCAV improves by adding inflammatory markers to apreviously 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 patientsfollowed prospectively for 8.9i5.0 years. Models were estimated for 5- and 10-year risk using (1) the first post-transplant biopsy only, or (2) all biopsies obtainedwithin 3 months. Multivariate models were adjusted for other covariates and cross-validated by bootstrapping. After adding IL-6 and CRP to the AT models, weevaluated the significance of odds ratios (ORs) associated with the additionalinflammatory variables and the degree of improvement in the area under thereceiver operating characteristic curve (AUROC). When inflammatory markerswere tested alone in prediction models, CRP (not IL-6) was a significant predictor ofCAV and GFDCAV at 5 (CAV: p,0.0001; GFDCAV: p50.005) and 10 years (CAV:p,0.0001; GFDCAV: p50.003). Adding CRP (not IL-6) to the best AT modelsimproved discriminatory power to identify patients destined to develop CAV (using1