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.
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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 |
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