The Presage® ST2 Assay quantitatively measures the
concentration of soluble ST2 in plasma, providing a physician with an accurate
tool to assess prognosis in patients with chronic heart failure. What follows
is a brief explanation of the science behind ST2.
ST2 (for growth STimulation expressed gene 2) is a member
of the interleukin-1 (IL1) receptor family of proteins, which play a central
role in the regulation of immune and inflammatory response. Also referred
to as cytokines, because of their cell-signaling capacity, the IL1 family was
largely studied to elucidate the link between fever and infection or
inflammation. Since initial elucidation, its diverse physiologic role now
includes the stimulation and inhibition of cells in organs including the heart.
In cardiac disease, ST2 has a biological role in the innate immunological
process and is also directly involved in a cardiac signaling pathway response
to disease or injury, which, under healthy conditions, serves to protect the
heart during pressure overload or stretch.1
Soluble ST2 has been shown to predict adverse outcomes and
death in individuals with established heart failure. Circulating ST2 is a
sensitive marker of cardiac stress or injury, as suggested by experimental
studies showing marked upregulation of ST2 gene expression in heart tissue
induced by myocardial stretch or mechanical overload.1
The two key isoforms of ST2 are ST2L (a membrane-bound
receptor) and sST2 (a soluble form found in the bloodstream). The response of
healthy cardiac tissue to injury or mechanical stress involves the production
and binding of interleukin-33 (IL-33) to ST2L, which stimulates a
cardioprotective signaling cascade that defends against fibrosis, stiffening of
the heart (cardiac remodeling), and heart failure (HF).2 Heart failure is a progressive disease which has not
cure and which requires ongoing treatment. When sST2 levels are elevated,
however, sST2 will bind to IL-33, thus reducing the beneficial effect of IL-33
through the ST2L receptor, so that cardiac fibrosis starts to develop (Fig.1).
In this way sST2 is a biomarker for worse prognosis in patients with
Fig. 1 Soluble ST2 blocks cardioprotective effect of
While all individuals have a normal level of ST2 in their
circulation, an elevated concentration of ST2 is a powerful predictor of
adverse outcomes, mortality or hospitalization, in patients with chronic heart
failure. The median normal concentration for ST2 is 18 ng/ml, while
concentrations greater than 35 ng/ml are strongly indicative of increased
ST2 concentration elevation precedes an overt change in a
patient’s symptoms, reflecting a worsening in the patient’s disease status.
Plasma ST2 thus predicts which chronic HF patients are progressing towards
worsening HF and cardiac remodeling, so that treatment can be implemented to
improve the risk profile.
ST2 provides accurate prognosis in chronic heart
The Penn Heart Failure Study (PHFS) illustrates the
significance of a high ST2 value for predicting clinically relevant outcomes,
death, heart transplant or hospitalization in patients with HF (Fig. 2).
Patients with ST2 >35 ng/ml have a 2.8x higher risk of adverse outcomes
within 30 days than patients with low ST2 concentrations. The relative risk of
adverse events in patients with ST2 > 35ng/ml persists at a level of at
least 1.8 for a follow up period of 4 years.3,4
Fig. 2 Effect of high ST2 levels on clinical outcomes in
the Penn Heart Failure Study (PHFS).