Abstract 3480: Neopterin Levels Improve Risk Prediction for Heart Failure Hospitalization Over and Above C-reactive Protein and B-type Natriuretic Peptide in the PROVE IT-TIMI 22 Study
Background There is increasing evidence that immune mechanisms are involved in the pathogenesis of CHF. We assessed the relationship between neopterin, a marker of monocyte activation, and the risk of CHF hospitalization.
Methods Among subjects in the PROVE IT-TIMI 22 trial, 3,946 had neopterin levels measured at study entry. The relationship between neopterin and risk of CHF was assessed in multivariable Cox regression models, which included demographics, type of index event, treatment allocation, as well as BNP and CRP. The incremental predictive value of neopterin over and above any given model was assessed using the likelihood ratio test (LRT).
Results Unadjusted hospitalization rates for CHF increased across quartiles of neopterin (Figure 1⇓). Per 1SD increment in log (neopterin), the risk of CHF increased by 47% (HR 1.47, 95% CI 1.24 to 1.72) after multivariable adjustment. Even after excluding individuals with a prior history of CHF or recurrent ischemic events, the relationship between neopterin and CHF hospitalization remained significant. When added to a multivariable Cox model of CHF risk containing traditional risk factors and CRP and BNP, the further addition of neopterin significantly improved the risk prediction model (LRT 17.85, p<0.0001). Similar results were obtained for the secondary endpoint of death or CHF.
Conclusion A linear relationship between neopterin level and risk of hospitalization for CHF was observed in patients with acute coronary syndromes. Neopterin significantly improved risk prediction of CHF over and above conventional biomarkers. The prognostic utility of neopterin in the development of CHF merits further evaluation.