The prognostic value of plasma galectin-3 in chronic heart failure patients is maintained when treated with mineralocorticoid receptor antagonists

François Koukoui, Franck Desmoulin, Michel Galinier, Manon Barutaut, Celine Caubère, Maria Francesca Evaristi, Gurbuz Murat, Rudolf De Boer, Matthieu Berry, Fatima Smih, Philippe Rouet, François Koukoui, Franck Desmoulin, Michel Galinier, Manon Barutaut, Celine Caubère, Maria Francesca Evaristi, Gurbuz Murat, Rudolf De Boer, Matthieu Berry, Fatima Smih, Philippe Rouet

Abstract

Objective: Galectin-3 (Gal-3) is considered as a myocardial fibrosis biomarker with prognostic value in heart failure (HF). Since aldosterone is a neurohormone with established fibrotic properties, we aimed to investigate if mineralocorticoid receptor antagonists (MRAs) would modulate the prognostic value of Gal-3.

Methods: The IBLOMAVED cohort comprised 427 eligible chronic HF patients (CHF) with echocardiography and heart failure biomarkers assessments (BNP). After propensity score matching CHF patients for cardiovascular risk factors, to form balanced groups, Gal-3 levels were measured at baseline in plasma from patients treated with MRAs (MRA-Plus, n=101) or not (MRA-Neg, n=101). The primary end point was all-cause mortality with a follow-up of 3 years.

Results: Gal-3 in plasma from these patients were similar with median values of 14.0 ng/mL [IQR, 9.9-19.3] and 14.4 ng/mL [IQR, 12.3-19.8] (P = 0.132) in MRA-Neg and MRA-Plus, respectively. Patients with Gal-3 ≤17.8 ng/mL had an HR of 1 (reference group) and 1.5 [0.4-5.7] in MRA-Neg and MRA-Plus, respectively (p=0.509). Patients with Gal-3 ≥ 17.8 ng/mL had an HR of 7.4 [2.2-24.6] and 9.0 [2.9-27.8] in MRA-Plus and MRA-Neg, respectively (p=0.539) and a median survival time of 2.4 years [95%CI,1.8-2.4]. Multivariate Cox proportional hazard analysis confirmed that MRA and the interaction term between MRA treatment and Gal-3 >17.8 ng/mL were not factors associated with survival.

Conclusions: MRA treatment did not impair the prognostic value of Gal-3 assessed with a 17.8 ng/mL cut off. Gal-3 levels maintained its strong prognostic value in CHF also in patients treated with MRAs. The significance of the observed lack of an interaction between Gal-3 and treatment effect of MRAs remains to be elucidated.

Trial registration: ClinicalTrials.gov NCT01024049.

Conflict of interest statement

Competing Interests: Philippe Rouet is a PLOS ONE Editorial Board member (Academic Editor) and that this does not alter the authors' adherence to PLOS ONE Editorial policies and criteria. The authors received funding from a commercial source 'BioMerieux' to perform this work and that this does not alter the authors' adherence to all PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Survival analysis of cohort by…
Fig 1. Survival analysis of cohort by the combination of MRA treatment and Gal-3 stratification.
(A) Patients were categorized in two groups according to baseline concentration of Gal >17.8 ng/mL. Hazard ratio (HR) for patients with Gal-3 > 17.8 ng/mL was 7.42 [95%CI, 5.47–27.96]; p17.8 ng/mL). P values of differences between groups are indicated. The group of patients with Gal-3 ≤ 17.8 ng/mL and without MRA treatment constitutes the reference group (HR = 1).

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