Soluble suppression of tumorigenicity 2 (sST2) for predicting disease severity or mortality outcomes in cardiovascular diseases: A systematic review and meta-analysis

Objectives: Soluble 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. Methods: PubMed and Embase were searched until 23rd June 2021 for studies that evaluated the relationship between sST2 levels and cardiovascular disease severity or mortality. Results: A 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; I-2: 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; I-2: 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; I-2: 0%) and elevated levels were associated with increased mortality risk (HR: 1.64, 95% CI: 1.27-2.12, P < 0.001; I-2: 82%). sST2 levels were significantly higher in severe disease compared to less severe disease (MD: 1.56 +/- 0.46 ng/ml; P = 0.001; I-2: 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; I-2: 80%) and elevated levels were significantly associated with increased mortality risk (HR: 1.32, 95% CI: 1.04-1.68, P < 0.05; I-2: 57%). Conclusions: sST2 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.