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CLINICAL RESEARCH: BIOMARKERS

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

James L. Januzzi, Jr, MD FACC^_*,1,2,_*, W. Frank Peacock, MD^,1, Alan S. Maisel, MD, FACC^,1,2, Claudia U. Chae, MD, MPH, FACC^_*, Robert L. Jesse, MD, FACC^,1, 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^#,1

^_* 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.

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

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