Aims There is increasing evidence that immune mechanisms are involved in the pathogenesis of
heart failure (HF). The relationship between
neopterin and the risk of HF has yet to be investigated on a large scale. We assessed the relationship between
neopterin, a novel marker of monocyte activation, and risk of hospitalization for HF. Methods and results Among the subjects of
Pravastatin or
Atorvastatin Evaluation and
Infection Therapy-Thrombolysis in
Myocardial Infarction 22 trial, 3946 had
neopterin levels measured at study entry, on average 7 days after
acute coronary syndrome (ACS). We assessed the relationship between
neopterin and hospitalization for HF, and for death or HF over 2 years mean follow-up in a post hoc analysis using Cox regression models. Unadjusted hospitalization rates for HF increased across quartiles of
neopterin, from 0.66 to 3.97 per 100 person-years. Per 1SD increment in log (
neopterin), the adjusted risk of HF increased by 34% [hazard ratio (HR) 1.34, CI 1.10-1.64; P = 0.004]. Even after excluding individuals with a prior history of HF or recurrent ischaemic events, the relationship between
neopterin and HF hospitalization remained significant. When added to a multivariable Cox model of HF-risk containing traditional risk factors,
C-reactive protein and brain natriuretic
protein (BNP), the further addition of
neopterin significantly improved the HF-risk prediction model by likelihood ratio test analysis (P = 0.005), C-statistic (increasing from 0.743 to 0.773; P = 0.027), integrated discrimination improvement (IDI) analysis (P = 0.001), but not net reclassification improvement (NRI) analysis (P = 0.406). Similar results were obtained for the endpoint of death or HF. Conclusion
Neopterin levels are an independent predictor of HF hospitalization, and improve risk prediction over and above conventional
biomarkers.