Neopterin - Prognostic Value

Long-Term Prognostic Value of Neopterin
A Novel Marker of Monocyte Activation in Patients With Acute Coronary Syndrome

Kausik K. Ray, MRCP, MD; David A. Morrow, MD, MPH; Marc S. Sabatine, MD, MPH; Amy Shui, MA; Nader Rifai, PhD; Christopher P. Cannon, MD; Eugene Braunwald, MD

From the Department of Public Health and Primary Care (K.K.R.), University of Cambridge, Cambridge, United Kingdom; TIMI Study Group (D.A.M., M.S.S., A.S., C.P.C., E.B.), Cardiovascular Division and the Department of Medicine, Brigham and Women’s Hospital/Harvard Medical School, Boston, Mass; and Children’s Hospital (N.R.), Boston, Mass.

Background. Monocyte activation is believed to play an important role in the pathogenesis of acute coronary syndromes (ACS). Neopterin is a soluble marker of monocyte activation, and elevated levels are of prognostic value in patients with stable coronary artery disease.

Methods and Results. Neopterin levels were measured on average at 7 days (in 3946 patients) and at 4 months (in 3369 patients) after ACS in the PRavastatin Or atorVastatin Evaluation Infection Therapy–Thrombolysis In Myocardial Infarction (PROVE IT–TIMI 22) trial. We assessed the relationship between plasma neopterin levels and the risk of death and death or acute coronary events (nonfatal myocardial infarction or unstable angina) over 2 years. Seven days after an ACS event, neopterin levels 12.11 nmol/L (upper quartile, derived from a post hoc analysis) were associated with an increased risk of death and an increased risk of death or acute coronary events after adjustment for age, gender, history of diabetes mellitus, history of hypertension, history of smoking, type of ACS presentation, use of percutaneous coronary intervention for the index event, statin regimen, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (hazard ratio, 1.86 [95% CI, 1.24 to 2.77], P=0.003; and hazard ratio, 1.33 [95% CI, 1.09 to 1.63] P=0.006, respectively). Neopterin levels 12.11 nmol/L at 4 months remained a predictor of death alone and of death or acute coronary events after multivariable adjustment that included adjustment for month 4 low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and statin regimen (hazard ratio, 2.39 [95% CI, 1.43 to 3.99], P=0.001; and hazard ratio, 1.60 [95% CI, 1.21 to 2.11], P=0.001). High-dose atorvastatin significantly attenuated the risk among subjects with neopterin levels 12.11 nmol/L at baseline (interaction P for death or acute coronary event, 0.018).
Conclusions. Increased monocyte activation detected by an elevated plasma neopterin level identifies patients at long-term risk of death or recurrent acute coronary events after ACS. Intensive statin therapy significantly attenuates the risk of recurrent events among patients with an elevated neopterin level.

Circulation. 2007;115:3071-3078.
© 2007 American Heart Association, Inc.
http://circ.ahajournals.org/cgi/content/abstract/115/24/3071