Published Online
on April 26, 2004

A more recent version of this article appeared on May 11, 2004

This Article Full Text (PDF) All Versions of this Article: 109/18/2186    most recent 01.CIR.0000127958.21003.5Av1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shimpo, M. Articles by Lee, R. T. Search for Related Content PubMed PubMed Citation Articles by Shimpo, M. Articles by Lee, R. T. Related Collections Genomics Acute myocardial infarction

Submitted on July 28, 2003
Revised on February 9, 2004
Accepted on February 10, 2004

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

Masahisa Shimpo MD, PhD, David A. Morrow MD, MPH, Ellen O. Weinberg PhD, Marc S. Sabatine MD, MPH, Sabina A. Murphy MPH, Elliott M. Antman MD, and Richard T. Lee MD^*

From the Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

^* To whom correspondence should be addressed. E-mail: rlee{at}rics.bwh.harvard.edu.

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.

Key words: myocardial infarction • prognosis • receptors • interleukins

This article has been cited by other articles:

				D. A. Pascual-Figal, J. Ordonez-Llanos, P. L. Tornel, R. Vazquez, T. Puig, M. Valdes, J. Cinca, A. B. de Luna, A. Bayes-Genis, and on behalf of the MUSIC Investigators Soluble ST2 for Predicting Sudden Cardiac Death in Patients With Chronic Heart Failure and Left Ventricular Systolic Dysfunction. J. Am. Coll. Cardiol., December 1, 2009; 54(23): 2174 - 2179. [Abstract] [Full Text] [PDF]

				R. Klingenberg and G. K. Hansson Treating inflammation in atherosclerotic cardiovascular disease: emerging therapies Eur. Heart J., December 1, 2009; 30(23): 2838 - 2844. [Abstract] [Full Text] [PDF]

				K. Seki, S. Sanada, A. Y. Kudinova, M. L. Steinhauser, V. Handa, J. Gannon;, and R. T. Lee Interleukin-33 Prevents Apoptosis and Improves Survival After Experimental Myocardial Infarction Through ST2 Signaling Circ Heart Fail, November 1, 2009; 2(6): 684 - 691. [Abstract] [Full Text] [PDF]

				R. V. Shah, A. A. Chen-Tournoux, M. H. Picard, R. R.J. van Kimmenade, and J. L. Januzzi Serum Levels of the Interleukin-1 Receptor Family Member ST2, Cardiac Structure and Function, and Long-Term Mortality in Patients With Acute Dyspnea Circ Heart Fail, July 1, 2009; 2(4): 311 - 319. [Abstract] [Full Text] [PDF]

				P. N. Pushparaj, H. K. Tay, S. C. H'ng, N. Pitman, D. Xu, A. McKenzie, F. Y. Liew, and A. J. Melendez The cytokine interleukin-33 mediates anaphylactic shock PNAS, June 16, 2009; 106(24): 9773 - 9778. [Abstract] [Full Text] [PDF]

				J. Bartunek, L. Delrue, F. Van Durme, O. Muller, F. Casselman, B. De Wiest, R. Croes, S. Verstreken, M. Goethals, H. de Raedt, et al. Nonmyocardial production of ST2 protein in human hypertrophy and failure is related to diastolic load. J. Am. Coll. Cardiol., December 16, 2008; 52(25): 2166 - 2174. [Abstract] [Full Text] [PDF]

				S. U. Rehman, T. Mueller, and J. L. Januzzi Jr Characteristics of the Novel Interleukin Family Biomarker ST2 in Patients With Acute Heart Failure J. Am. Coll. Cardiol., October 28, 2008; 52(18): 1458 - 1465. [Abstract] [Full Text] [PDF]

				J. Diez Serum Soluble ST2 as a Biochemical Marker of Acute Heart Failure: Future Areas of Research J. Am. Coll. Cardiol., October 28, 2008; 52(18): 1466 - 1467. [Full Text] [PDF]

				E. Braunwald Biomarkers in Heart Failure N. Engl. J. Med., May 15, 2008; 358(20): 2148 - 2159. [Full Text] [PDF]

				M. S. Sabatine, D. A. Morrow, L. J. Higgins, C. MacGillivray, W. Guo, C. Bode, N. Rifai, C. P. Cannon, R. E. Gerszten, and R. T. Lee Complementary Roles for Biomarkers of Biomechanical Strain ST2 and N-Terminal Prohormone B-Type Natriuretic Peptide in Patients With ST-Elevation Myocardial Infarction Circulation, April 15, 2008; 117(15): 1936 - 1944. [Abstract] [Full Text] [PDF]

				T. Mueller, B. Dieplinger, A. Gegenhuber, W. Poelz, R. Pacher, and M. Haltmayer Increased Plasma Concentrations of Soluble ST2 are Predictive for 1-Year Mortality in Patients with Acute Destabilized Heart Failure Clin. Chem., April 1, 2008; 54(4): 752 - 756. [Abstract] [Full Text] [PDF]

				A. M. Miller, D. Xu, D. L. Asquith, L. Denby, Y. Li, N. Sattar, A. H. Baker, I. B. McInnes, and F. Y. Liew IL-33 reduces the development of atherosclerosis J. Exp. Med., February 18, 2008; 205(2): 339 - 346. [Abstract] [Full Text] [PDF]

				A. A. Chackerian, E. R. Oldham, E. E. Murphy, J. Schmitz, S. Pflanz, and R. A. Kastelein IL-1 Receptor Accessory Protein and ST2 Comprise the IL-33 Receptor Complex J. Immunol., August 15, 2007; 179(4): 2551 - 2555. [Abstract] [Full Text] [PDF]

				J. L. Januzzi Jr, W. F. Peacock, A. S. Maisel, C. U. Chae, R. L. Jesse, A. L. Baggish, M. O'Donoghue, R. Sakhuja, A. A. Chen, R. R.J. van Kimmenade, et al. Measurement of the Interleukin Family Member ST2 in Patients With Acute Dyspnea: Results From the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) Study J. Am. Coll. Cardiol., August 14, 2007; 50(7): 607 - 613. [Abstract] [Full Text] [PDF]

				S. Blankenberg, M. J. McQueen, M. Smieja, J. Pogue, C. Balion, E. Lonn, H. J. Rupprecht, C. Bickel, L. Tiret, F. Cambien, et al. Comparative Impact of Multiple Biomarkers and N-Terminal Pro-Brain Natriuretic Peptide in the Context of Conventional Risk Factors for the Prediction of Recurrent Cardiovascular Events in the Heart Outcomes Prevention Evaluation (HOPE) Study Circulation, July 18, 2006; 114(3): 201 - 208. [Abstract] [Full Text] [PDF]