Plasma endothelin-1-related peptides as the prognostic biomarkers for heart failure A PRISMA-compliant meta-analysis

Background: Most studies reported that high plasma endothelin-1 (ET-1), big ET-1, and C-terminal proET-1 (CT-proET-1) were correlated with poor prognosis of heart failure (HF). However, available evidence remains controversial. To help solve the debate, we collected all the available studies and performed a meta-analysis. Methods: We searched the databases covering Embase, PubMed, Ovid, and Web of Science on June 28, 2017. The hazard ratio (HR) or risk ratio (RR) and its 95% confidence intervals (CIs) were collected and calculated by use of a random-effect model. Heterogeneity was assessed by Cochran′s Q test, and publication bias was assessed by funnel plots with Egger′s and Begg′s linear regression test. Results: Thirty-two studies with 18,497 patients were included in the analysis. Results showed that circulating ET-1, big ET-1, and CT-proET-1 were positively correlated with high risk of adverse outcomes, with pooled RRs (95% CIs) of 2.22 (1.82-2.71, Pl.001), 2.47 (1.93-3.17, Pl.001), and 2.27 (1.57-3.29, Pl.001), respectively. In the subgroup of death as primary outcome, the pooled RRs (95% CIs) were 2.13 (1.68-2.70, Pl.001), 2.55 (1.82-3.57, Pl.001), and 2.02 (1.39-2.92, Pl.001) for ET-1, big ET-1, and CT-proET-1, respectively. No significant publication bias was observed in this study. Conclusion: Our meta-analysis provided evidence that increased plasma levels of ET-1, big ET-1, and CT-proET-1 were associated with poor prognosis or mortality for HF populations.