Prognostic Value of Soluble ST2 in the Valsartan Heart Failure Trial

Study Questions:

What is the relationship between soluble ST2 (sST2), a biomarker related to inflammation, and patient outcomes in patients with heart failure (HF)?


The Val-HeFT (Valsartan Heart Failure Trial) investigators measured sST2 at baseline (n = 1,650), 4 months (n = 1,345), and 12 months (n = 1,094) in the study cohort. They then compared outcomes in these HF patients with sST2 levels.


The investigators found that at baseline, sST2 levels averaged 28.7 ± 16.2 ng/ml; significantly (p < 0.001) higher in men than women, but supranormal in only 9% and 15%, respectively. They modeled the continuous relationship between sST2 and the log hazard ratio for outcomes as two linear segments, with a significant decrease in the rate of increase in hazard ratios >33.2 ng/ml. They reported that each segment of the sST2 distribution was significantly (p < 0.0001) associated with the risks of morbid event, mortality, and hospitalization for HF. However, only sST2 values <33.2 ng/ml were significantly related to the outcomes when 23 readily available clinical variables including N-terminal pro–B-type natriuretic peptide (NT-proBNP) were included in the Cox regression model. They found that sST2 did not improve discrimination of patient outcomes. When compared to placebo, valsartan significantly (p < 0.001) reduced the rate of increase in sST2. Increases in sST2 over a 12-month period, but not decreases, were significantly associated with subsequent outcomes independent of clinical variables, sST2, and valsartan treatment.


The authors concluded that baseline sST2 was nonlinearly associated with patient outcomes, and did not provide substantial prognostic information when added to a clinical prediction model that included NT-proBNP. An increase but not decrease in sST2 was independently associated with patient outcomes.


This retrospective study suggests that sST2 does not add incremental value to current prediction models that include NT-proBNP. This could be due to the variable course of inflammatory process that accompanies HF. Prospective data are required before discounting this important biomarker of inflammation. Also, prospective data are required to determine the utility of sST2 as part of a package of biomarkers, rather than as a stand-alone predictor.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Inflammation, Biological Markers, Heart Failure, Peptide Fragments, Tetrazoles, Hospitalization, Natriuretic Peptide, Brain

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