Abstract 2256: Increased Monocyte Activation Detected By Serum Neopterin and Long-Term Risk in Patients with Acute Coronary Syndromes: Analysis From PROVE IT-TIMI 22
Background: Increased monocyte activation is implicated in the pathogenesis of acute coronary syndromes (ACS). We assessed the prognostic value of neopterin (a marker of monocyte activation) in patients with ACS in the PROVE IT-TIMI 22 trial, which randomized patients to intensive vs standard statin therapy.
Methods: We measured plasma neopterin by ELISA (ALPCO, Windham, NH ) early (average 7 days, N=3946) and at 4 months (N=3369) after ACS and assessed its relationship with the risk of death or acute coronary events (non-fatal myocardial infarction or unstable angina) over 2 years.
Results: Baseline levels of neopterin ≥75th percentile (≥ 12.1 nmol/L) were associated with an increased risk of death or acute coronary events (p<0.0001) which was independent of traditional risk factors, LDL-C, CRP and statin regimen (adjusted HR 1.27, CI 1.01–1.60, p=0.02). Similarly, an elevated neopterin level at 4 months was independently associated with the risk of subsequent death or an acute coronary event (Adjusted HR 1.55, 95% CI 1.12– 2.1, p=0.006). Notably, allocation to intensive statin therapy significantly attenuated the clinical risk associated with elevated baseline neopterin (Figure⇓).
Conclusions: We provide large scale evidence that increased levels of neopterin early and late after ACS are independently associated with the long term risk of death or acute coronary events. This observation supports the important biological role of the monocyte in the pathogenesis of ACS and the potential to modify the associated risk with statin therapy.