sST2 adds to the prognostic value of Gal-3 and BNP in chronic heart failure

Abstract

Background: The soluble form of the IL-33 receptor (sST2) and Galectin-3 (Gal-3) are fibrosis biomarkers with prognostic value in heart failure (HF). We investigated the prognostic capacity of sST2 when combined with Gal-3, and determined if the prognostic utility of sST2 is affected by mineralocorticoid receptor antagonist (MRA) therapy.

Methods: sST-2 and Gal-3 were measured in 101 stable chronic HF (CHF) patients receiving MRA therapy and compared to 97 BNP and cardiovascular risk factor matched patients not treated with MRA. sST2 and Gal-3 levels were measured to determine the relationship with all-cause mortality at 6-year follow-up.

Results: ROC curve cut-off points were defined as sST2 = 36.3 ng/mL, Gal-3 = 17.8 ng/mL, and BNP = 500 pg/mL, and had 6-year mortality hazard ratios (HR) of 7.3, 6.6 and 5.4, respectively. The combination of an elevated sST2 and Gal-3 had a HR = 4.4 [95% CI 1.9–8.9]. Combining sST2 and Gal-3 to a clinical model relevant for CHF prognosis allowed a significant reclassification of 1-year adverse outcome risk, even when BNP was included. Finally, prognostic prediction by sST2 was unaffected by MRA treatment.

Conclusion: Simultaneous sST2 and Gal-3 elevation is associated with poorer prognosis compared to either alone, regardless of BNP levels, and the prognostic capacity of sST2 is independent of MRA therapy.

Keywords:

• sST2
• BNP
• Gal-3
• heart failure
• prognosis
• mineralocorticoid receptor
• antagonists
• biomarkers

Acknowledgments

We are grateful to Eurobio and bioMérieux for the support of this study, the supply of reagents for measurements and lending us a VIDAS automat for Gal-3 measurement. We thank Sandrine Mazon for excellent assistance in samples and clinical data collections.

Authors’ contributions

M.B. participated in the analysis and interpretation of the data. P.F., W.F.P., M.F.E., C.D., C.C. and F.K. participated in interpretation of the data and revised the manuscript. M.G., F.S., P.R. conceived the study, participated in the analysis and interpretation of the data, drafted and revised the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Availability of data and material

The dataset supporting the conclusions of this article are available upon request to [email protected]