Neopterin predicts cardiac dysfunction following cardiac surgery

OBJECTIVES: Oxidative stress following ischaemia and reperfusion, as well as inflammation, are thought to be important for the development of cardiac dysfunction after cardiac surgery. Our main objective was to investigate whether the inflammatory biomarkers C-reactive protein (CRP), lactoferrin, neopterin and the terminal complement complex (TCC) were associated with cardiac dysfunction after cardiac surgery. Another objective was to assess whether the biomarkers could improve prediction of postoperative cardiac dysfunction compared with clinical variables only. METHODS: Blood samples and clinical data from 1018 consecutive patients undergoing cardiac surgery from 1 April 2008 to 19 April 2010 at St. Olavs University Hospital, Trondheim, Norway, were collected prospectively. The end-point was postoperative cardiac dysfunction, defined as the need for more than one inotropic agent or an intra-aortic balloon pump occurring after the operation and until the patient was discharged from the department. CRP, lactoferrin, neopterin and TCC were analysed in plasma, and we used logistic regression to evaluate the association of the biomarkers with postoperative cardiac dysfunction. We adjusted for the following clinical variables previously associated with postoperative cardiac dysfunction: urgent operation, operation type, previous cardiac surgery, chronic heart failure, pulmonary hypertension, previous myocardial infarction and haemoglobin. The likelihood ratio test, the integrated discrimination improvement and receiver operating characteristic (ROC) curves were used to assess whether the biomarkers could improve prediction of postoperative cardiac dysfunction compared with clinical variables alone. RESULTS: Neopterin was the only biomarker significantly associated with postoperative cardiac dysfunction (odds ratio 2.73, 95% confidence interval 1.65-4.51) after adjustment for clinical variables. Neopterin improved risk prediction of cardiac dysfunction following heart surgery compared with clinical variables alone according to the likelihood ratio test (P < 0.0001) and the integrated discrimination improvement (P = 0.02), particularly for patients with intermediate risks. CONCLUSIONS: Neopterin was associated with cardiac dysfunction following cardiac surgery, and improved the accuracy of risk prediction of postoperative cardiac dysfunction. At present, we do not suggest that neopterin should be measured routinely before heart surgery, but our findings support the hypothesis of the role of oxidative stress and inflammation in development of cardiac dysfunction following heart surgery.