Abstract
ObjectivesSoluble suppression of tumorigenicity 2 (sST2) is a member of the interleukin-1 receptor family. It is raised in various cardiovascular diseases, but its value in predicting disease severity or mortality outcomes has been controversial. Therefore, we conducted a systematic review and meta-analysis to determine whether sST2 levels differed between survivors and non-survivors of patients with cardiovascular diseases, and whether elevated sST2 levels correlated with adverse outcomes.MethodsPubMed and Embase were searched until 23rd June 2021 for studies that evaluated the relationship between sST2 levels and cardiovascular disease severity or mortality.ResultsA total of 707 entries were retrieved from both databases, of which 14 studies were included in the final meta-analysis. In acute heart failure, sST2 levels did not differ between survivors and non-survivors (mean difference [MD]: 24.2 ± 13.0 ng/ml; P = 0.06; I2: 95%). Elevated sST2 levels tend to be associated with increased mortality risk (hazard ratio [HR]: 1.12, 95 %CI: 0.99–1.27, P = 0.07; I2: 88%). In chronic heart failure, sST2 levels were higher in non-survivors than in survivors (MD: 0.19 ± 0.04 ng/ml; P = 0.001; I2: 0%) and elevated levels were associated with increased mortality risk (HR: 1.64, 95% CI: 1.27–2.12, P < 0.001; I2: 82%). sST2 levels were significantly higher in severe disease compared to less severe disease (MD: 1.56 ± 0.46 ng/ml; P = 0.001; I2: 98%). Finally, in stable coronary artery disease, sST2 levels were higher in non-survivors than survivors (MD: 3.0 ± 1.1 ng/ml; P = 0.005; I2: 80%) and elevated levels were significantly associated with increased mortality risk (HR: 1.32, 95% CI: 1.04–1.68, P < 0.05; I2: 57%).ConclusionssST2 significantly predicts disease severity and mortality in cardiovascular disease and is a good predictor of mortality in patients with stable coronary artery disease and chronic heart failure.
Highlights
The interleukin (IL)-1 receptor family is a family of receptors medi ating the activities of specific members of the IL-1 family of ligands, which are important in both innate and adaptive immune response [1]
The predictive value of soluble Suppression of Tumorigenicity 2 (ST2) (sST2) was examined in the following conditions: acute heart failure (n = 5), chronic heart failure (n = 6) and stable coronary artery disease (n = 3)
Five studies compared sST2 levels between survivors and non-survivors in acute heart failure, but one study was excluded from the meta-analysis because it did not provide any measure of dispersion [15]
Summary
The interleukin (IL)-1 receptor family is a family of receptors medi ating the activities of specific members of the IL-1 family of ligands, which are important in both innate and adaptive immune response [1]. Suppression of Tumorigenicity 2 (ST2) is a member of the IL-1 receptor family and it consists of two important isoforms, namely, ST2 ligand (ST2L) and soluble ST2 (sST2) [2]. ST2L is a transmembrane receptor while sST2 is a soluble receptor that circulates in the bloodstream [2]. Like other ligands in the IL-1 family, the binding of IL-33 and ST2L on the inflammatory cell membrane activates subsequent intracellular signaling and mediates its pro-inflammatory action [4]. SST2 acts as a decoy receptor and binds to IL-33, which reduces the amount of IL-33 available for interacting with ST2L [7]. The cardioprotective action of IL-33 is reduced when circulating sST2 levels are elevated [6]
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