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CLINICAL RESEARCH: BIOMARKERS

Characteristics of the Novel Interleukin Family Biomarker ST2 in Patients With Acute Heart Failure

Shafiq U. Rehman, MD^_*, Thomas Mueller, MD and James L. Januzzi, Jr, MD, FACC^_*,_*

^_* Cardiology Division and Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
Department of Laboratory Medicine, Konventhospital Barmherzige Brueder, Linz, Austria

Manuscript received May 29, 2008; revised manuscript received June 26, 2008, accepted July 10, 2008.

^_* Reprint requests and correspondence: Dr. James L. Januzzi, Jr., Cardiology Division 32 Fruit Street, Yawkey 5984, Boston, Massachusetts 02114 (Email: JJanuzzi{at}partners.org).

Objectives: The purpose of this study was to examine the patient-specific characteristics of the interleukin-1 receptor family member ST2 in patients with acute heart failure (HF).

Background: ST2 signaling is involved in the process of cardiac fibrosis and hypertrophy.

Methods: In all, 346 patients with acute HF had ST2 measured. Associations between ST2 and demographics, severity/type of HF, and other biomarkers were examined. Receiver-operator characteristic curves and multivariable Cox proportional hazards analyses evaluated the prognostic ability of ST2.

Results: The ST2 values correlated with the severity of HF (p < 0.001), left ventricular ejection fraction (r = –0.134; p = 0.014), creatinine clearance (r = –0.224; p < 0.001), B-type natriuretic peptide (r = 0.293; p < 0.001), amino terminal B-type natriuretic peptide (r = 0.413; p < 0.001), and C-reactive protein (r = 0.429; p < 0.001). ST2 was not associated with age, prior HF, or body mass index. The ST2 levels at presentation were higher among patients who died by 1 year. The area under the receiver-operator characteristic for death at 1 year was 0.71 (p < 0.001). In a multivariable Cox model containing established clinical and biochemical predictors (including natriuretic peptides), ST2 remained a predictor of mortality (hazard ratio: 2.04, 95% confidence interval: 1.30 to 3.24, p = 0.003), and was equally predictive in patients with HF and preserved or impaired systolic function. When both ST2 and natriuretic peptides were elevated, the highest rates of death were observed in cumulative hazard analysis (p < 0.001). In the presence of a low ST2 level, natriuretic peptides did not predict mortality.

Conclusions: Consistent with its proposed role in a myocardial-specific response to stretch, ST2 has strong clinical and biochemical correlates in patients with acute HF. Prognostically, ST2 is powerful in acute HF and is synergistic with natriuretic peptides for this use.

Key Words: heart failure • ST2 • NT-proBNP • mortality

Abbreviations and Acronyms   AUC = area under the curve   BNP = B-type natriuretic peptide   CI = confidence interval   CRP = C-reactive protein   HF = heart failure   IL = interleukin   NT-proBNP = amino terminal B-type natriuretic peptide   NYHA = New York Heart Association   ROC = receiver-operator characteristic   ST2 = interleukin receptor family member   ST2L = transmembrane receptor form of interleukin family member ST2

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