about heart failure
Heart Failure means that your heart is not pumping blood effectively… More >>
about st2
Measuring ST2 via a simple, non-invasive blood test….More >>

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 cardiovascular disease.

Fig. 1  Soluble ST2 blocks cardioprotective effect of IL-33

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 risk.1,3

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 failure:

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).

References

  1. Kakkar R, Lee RT. The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Disc 2008;7(10):827-840.
  2. Ahmad, Fiuzat M, Felker GM, O’Connor C. Novel biomarkers in chronic heart failure. Nat Rev Cardiol 2012 Mar 27 [E-pub ahead of print].
  3. Ky B, et al. High sensitivity ST2 for Prediction of Adverse Outcomes in Chronic Heart Failure. Circ Heart Fail 2011;4(2):180-7.
  4. Felker GM, et al. Soluble ST2 in ambulatory patients with heart failure: association with functional capacity and long term outcomes. Circ Heart Fail 2013, Nov;6(6):1172-9.