Plasma endothelin-1-related peptides as the prognostic biomarkers for heart failure

Abstract

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, P < .001), 2.47 (1.93–3.17, P < .001), and 2.27 (1.57–3.29, P < .001), respectively. In the subgroup of death as primary outcome, the pooled RRs (95% CIs) were 2.13 (1.68–2.70, P < .001), 2.55 (1.82–3.57, P < .001), and 2.02 (1.39–2.92, P < .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.

Cardiovascular biomarkers predict post‐discharge re‐hospitalization risk and mortality among Swedish heart failure patients

“…A recent metaanalysis focused on ET-1, pro-endotelin-1, and CT-pro-ET-1 demonstrated that increased levels of all three isoforms of the endothelin family were associated with poor prognosis or mortality in HF populations. 35 In the light of increased ET-1 levels and their association with elevated pulmonary vascular resistance, which in turn leads to right ventricular dilatation and failure, our association between CT-pro-ET-1 levels and right ventricular diameter are sound and logical. As ET-1 is highly expressed in the lung, it can contribute to a strong vasoconstriction of the pulmonary arteries and veins and, consequently, to pulmonary hypertension.…”

Sympathetic nervous system activation and heart failure: Current state of evidence and the pathophysiology in the light of novel biomarkers

“…When 32 studies with 18497 HF patients were summarized in the meta-analysis, it was shown that plasma ET-1 and its related peptides were associated with poor prognosis and mortality in diverse spectrum of HF populations[ 272 ]. On the other hand, a meta-analysis of randomized clinical trials showed that neurohumoral antagonism of ET receptors in HF patients improved cardiac output, pulmonary and systemic hemodynamics but had a modest effect on clinical outcomes[ 273 ].…”

Differential activation of P-TEFb complexes in the development of cardiomyocyte hypertrophy following activation of distinct GPCRs

“…Therefore, more extensive characterization of signalling molecules in patients might be important predictors of drug efficacy. Importantly, we expect that Brd4 inhibition will be less effective in severe and/or late stages of heart failure as PKA activity is reduced (41) and levels of endothelin-1 or its precursors (66–68) increases. Chronic infusion of these neurohormones with mice is required to determine how the receptor-specific effects of Brd4 inhibition effects cardiac remodelling.…”