CLINICAL RESEARCH: BIOMARKERS
Measurement of the Interleukin Family Member ST2 in Patients With Acute DyspneaResults From the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) Study
James L. Januzzi, Jr, MD FACC*,
W. Frank Peacock, MD ,*,
Alan S. Maisel, MD, FACC ,
Claudia U. Chae, MD, MPH, FACC*,
Robert L. Jesse, MD, FACC ,
Aaron L. Baggish, MD*,
Michelle O'Donoghue, MD*,
Rahul Sakhuja, MD*,
Annabel A. Chen, MD*,
Roland R.J. van Kimmenade, MD||,
Kent B. Lewandrowski, MD*,
Donald M. Lloyd-Jones, MD, MSc, FACC¶ and
Alan H.B. Wu, PhD#
* Department of Medicine and Laboratory Medicine, Massachusetts General Hospital, Boston, Massachusetts
Department of Emergency Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
Department of Medicine, University of California, San Diego, California
# Department of Laboratory Medicine, University of California, San Francisco, California
Department of Medicine, Virginia Commonwealth University, Richmond, Virginia
|| Department of Medicine, University Hospital Maastricht, Maastricht, the Netherlands
¶ Department of Preventive Medicine and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Drs. Januzzi, Peacock, Maisel, Jesse, and Wu have received consulting income from Critical Care Diagnostics, holder of the license for ST2 cardiac testing. Drs. Januzzi and Maisel have received grant support, consulting income, and speaking fees from Roche Diagnostics, Inc. Dr. E. Magnus Ohman served as Guest Editor for this article
Manuscript received February 12, 2007;
revised manuscript received May 8, 2007,
accepted May 9, 2007.
* Reprint requests and correspondence: Dr. James L. Januzzi, Jr., Massachusetts General Hospital, Yawkey 5984, 55 Fruit Street, Boston, Massachusetts 02114 (Email: JJanuzzi{at}Partners.org).
Objectives: The aim of this study was to examine the value of measurement of the interleukin-1 receptor family member ST2 in patients with dyspnea.
Background: Concentrations of ST2 have been reported to be elevated in patients with heart failure (HF).
Methods: Five hundred ninety-three dyspneic patients with and without acute destabilized HF presenting to an urban emergency department were evaluated with measurements of ST2 concentrations. Independent predictors of death at 1 year were identified.
Results: Concentrations of ST2 were higher among those with acute HF compared with those without (0.50 vs. 0.15 ng/ml; p < 0.001), although amino-terminal pro-brain natriuretic peptide (NT-proBNP) was superior to ST2 for diagnosis of acute HF. Median concentrations of ST2 at presentation to the emergency department were higher among decedents than survivors at 1 year (1.08 vs. 0.18 ng/ml; p < 0.001), and in multivariable analyses, an ST2 concentration 0.20 ng/ml strongly predicted death at 1 year in dyspneic patients as a whole (HR = 5.6, 95% confidence interval [CI] 2.2 to 14.2; p < 0.001) as well as those with acute HF (hazard ratio [HR] = 9.3, 95% CI 1.3 to 17.8; p = 0.03). This risk associated with an elevated ST2 in dyspneic patients with and without HF appeared early and was sustained at 1 year after presentation (log-rank p value <0.001). A multi-marker approach with both ST2 and NT-proBNP levels identified subjects with the highest risk for death.
Conclusions: Among dyspneic patients with and without acute HF, ST2 concentrations are strongly predictive of mortality at 1 year and might be useful for prognostication when used alone or together with NT-proBNP.
|
Abbreviations and Acronyms
| | AUC = area under the curve | | CI = confidence interval | | CRP = C-reactive protein | | HF = heart failure | | IQR = interquartile range | | NT-proBNP = amino-terminal pro-brain natriuretic peptide | | NYHA = New York Heart Association | | OR = odds ratio | | PPV = positive predictive value | | ROC = receiver-operating characteristic |
|
Related Article
-
Inside This Issue of JACC
J. Am. Coll. Cardiol. 2007 50: A31-A32.
[Full Text]
[PDF]
This article has been cited by other articles:

|
 |

|
 |
 
K. Broch, T. Ueland, S. H. Nymo, J. Kjekshus, J. Hulthe, P. Muntendam, J. J. McMurray, J. Wikstrand, J. G. Cleland, P. Aukrust, et al.
Soluble ST2 is associated with adverse outcome in patients with heart failure of ischaemic aetiology
Eur J Heart Fail,
February 9, 2012;
(2012)
hfs006v2.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Bayes-Genis, M. de Antonio, A. Galan, H. Sanz, A. Urrutia, R. Cabanes, L. Cano, B. Gonzalez, C. Diez, T. Pascual, et al.
Combined use of high-sensitivity ST2 and NTproBNP to improve the prediction of death in heart failure
Eur J Heart Fail,
January 1, 2012;
14(1):
32 - 38.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. R. J. van Kimmenade and J. L. Januzzi Jr.
Emerging Biomarkers in Heart Failure
Clin. Chem.,
January 1, 2012;
58(1):
127 - 138.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Kohli, M. P. Bonaca, R. Kakkar, A. Y. Kudinova, B. M. Scirica, M. S. Sabatine, S. A. Murphy, E. Braunwald, R. T. Lee, and D. A. Morrow
Role of ST2 in Non-ST-Elevation Acute Coronary Syndrome in the MERLIN-TIMI 36 Trial
Clin. Chem.,
January 1, 2012;
58(1):
257 - 266.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. A. Pascual-Figal, S. Manzano-Fernandez, M. Boronat, T. Casas, I. P. Garrido, J. C. Bonaque, F. Pastor-Perez, M. Valdes, and J. L. Januzzi
Soluble ST2, high-sensitivity troponin T- and N-terminal pro-B-type natriuretic peptide: complementary role for risk stratification in acutely decompensated heart failure
Eur J Heart Fail,
July 1, 2011;
13(7):
718 - 725.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Kakkar and R. T. Lee
Directions from Hecate: towards a multi-marker approach for heart failure assessment
Eur J Heart Fail,
July 1, 2011;
13(7):
691 - 693.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. B. Shah, W. J. Kop, R. H. Christenson, D. B. Diercks, S. Henderson, K. Hanson, S.-Y. Li, and C. R. deFilippi
Prognostic Utility of ST2 in Patients with Acute Dyspnea and Preserved Left Ventricular Ejection Fraction
Clin. Chem.,
June 1, 2011;
57(6):
874 - 882.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H.-N. Kim and J. L. Januzzi Jr
Natriuretic Peptide Testing in Heart Failure
Circulation,
May 10, 2011;
123(18):
2015 - 2019.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Ky, B. French, K. McCloskey, J. E. Rame, E. McIntosh, P. Shahi, D. L. Dries, W. H. W. Tang, A. H. B. Wu, J. C. Fang, et al.
High-Sensitivity ST2 for Prediction of Adverse Outcomes in Chronic Heart Failure
Circ Heart Fail,
March 1, 2011;
4(2):
180 - 187.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. A. McDonagh and H. J. Dargie
13 The pathophysiology of heart failure
Oxford Textbook of Heart Failure,
January 1, 2011;
1(1):
med-9780199577729-chapter - med-9780199577729-chapter.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
J. L. Januzzi Jr., S. Rehman, T. Mueller, R. R. J. van Kimmenade, and D. M. Lloyd-Jones
Importance of Biomarkers for Long-Term Mortality Prediction in Acutely Dyspneic Patients
Clin. Chem.,
December 1, 2010;
56(12):
1814 - 1821.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. S. Jaffe
Chapter 33 The use of biomarkers for acute cardiovascular disease
The ESC Textbook of Acute and Intensive Cardiac Care,
December 1, 2010;
1(1):
med-9780199584314-chapter - med-9780199584314-chapter.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Shah, P. R. Taub, and A. Maisel
Chapter 35 Biomarkers in acute heart failure
The ESC Textbook of Acute and Intensive Cardiac Care,
December 1, 2010;
1(1):
med-9780199584314-chapter - med-9780199584314-chapter.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. V. Shah, A. A. Chen-Tournoux, M. H. Picard, R. R. J. van Kimmenade, and J. L. Januzzi
Galectin-3, cardiac structure and function, and long-term mortality in patients with acutely decompensated heart failure
Eur J Heart Fail,
August 1, 2010;
12(8):
826 - 832.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W.-C. Chen, K. D. Tran, and A. S. Maisel
Biomarkers in heart failure
Heart,
February 1, 2010;
96(4):
314 - 320.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. R.J. van Kimmenade, A. A. Mohammed, S. Uthamalingam, P. van der Meer, G. M. Felker, and J. L. Januzzi Jr
Red blood cell distribution width and 1-year mortality in acute heart failure
Eur J Heart Fail,
February 1, 2010;
12(2):
129 - 136.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. A.P. Weir, A. M. Miller, G. E.J. Murphy, S. Clements, T. Steedman, J. M.C. Connell, I. B. McInnes, H. J. Dargie, and J. J.V. McMurray
Serum Soluble ST2: A Potential Novel Mediator in Left Ventricular and Infarct Remodeling After Acute Myocardial Infarction
J. Am. Coll. Cardiol.,
January 19, 2010;
55(3):
243 - 250.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. A. Moore and J. L. Januzzi Jr
Found in Translation: Soluble ST2 and Heart Disease
J. Am. Coll. Cardiol.,
January 19, 2010;
55(3):
251 - 253.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
B Dieplinger, A Gegenhuber, M Haltmayer, and T Mueller
Evaluation of novel biomarkers for the diagnosis of acute destabilised heart failure in patients with shortness of breath
Heart,
September 15, 2009;
95(18):
1508 - 1513.
[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]
|
 |
|

|
 |

|
 |
 
K. B. Shah, W. J. Kop, R. H. Christenson, D. B. Diercks, D. Kuo, S. Henderson, K. Hanson, M. R. Mehra, and C. R. deFilippi
Lack of Diagnostic and Prognostic Utility of Circulating Plasma Myeloperoxidase Concentrations in Patients Presenting with Dyspnea
Clin. Chem.,
January 1, 2009;
55(1):
59 - 67.
[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]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
W.H. W. Tang and G. S. Francis
The Year in Heart Failure
J. Am. Coll. Cardiol.,
December 11, 2007;
50(24):
2344 - 2351.
[Full Text]
[PDF]
|
 |
|
|