Serum Levels of the Interleukin-1 Receptor Family Member ST2 Predict Mortality and Clinical Outcome in Acute Myocardial Infarction

Background— Mechanically overloaded cardiomyocytes secrete a soluble interleukin-1 receptor family member called ST2. Serum levels of ST2 are associated with prognosis in nonischemic heart failure, but the predictive value of ST2 in patients with acute myocardial infarction is unknown. Methods and Results— ST2 levels were measured in serum from 810 patients with acute myocardial infarction in the Thrombolysis In Myocardial Infarction (TIMI) 14 (362 patients) and Enoxaparin and TNK-tPA With or Without GPIIb/IIIa Inhibitor as Reperfusion Strategy in STEMI (ENTIRE)-TIMI 23 (448 patients) clinical trials. Baseline levels of ST2 were significantly higher in those patients who died (0.379 versus 0.233 ng/mL, P =0.0001) or developed new congestive heart failure (0.287 versus 0.233 ng/mL, P =0.009) by 30 days. In an analysis of outcomes at 30 days by ST2 quartiles, both death ( P =0.001) and the combined death/heart failure end point ( P =0.001) showed a significant graded association with levels of ST2; furthermore, in-hospital death ( P =0.003) and death/heart failure ( P =0.004) were also significantly associated with higher ST2 levels. In a logistic regression analysis that controlled for important clinical factors, increasing levels of ST2 remained associated with death at 30 days ( P =0.047). ST2 levels rose during the first day after infarction and were maximal at 12 hours; ST2 levels at 12 hours were also independently associated with death at 30 days ( P <0.001). Conclusions— Serum levels of the interleukin-1 receptor family member ST2 predict mortality and heart failure in patients with acute myocardial infarction. These data suggest that ST2 may be a useful biomarker and that this novel inflammatory receptor may play a role in cardiac pathophysiology.