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Clin Chem. 2016 Apr;62(4):605-16. doi: 10.1373/clinchem.2015.246850. Epub 2016 Mar 2.

Interaction of Galectin-3 Concentrations with the Treatment Effects of β-Blockers and RAS Blockade in Patients with Systolic Heart Failure: A Derivation-Validation Study from TIME-CHF and GISSI-HF.

Author information

1
Maastricht University Medical Center, Maastricht, the Netherlands; sandra.van.wijk@mumc.nl.
2
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy;
3
Cardiology, University Hospital Bruderholz, Bruderholz, Switzerland;
4
ANMCO Research Center, Florence, Italy;
5
GVM Care and Research, Maria Cecilia Hospital, Cotignola, Italy;
6
Cardiology, University Hospital Basel, Basel, Switzerland;
7
Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
8
Maastricht University Medical Center, Maastricht, the Netherlands; Cardiology, University Hospital Basel, Basel, Switzerland;

Abstract

BACKGROUND:

Galectin-3 predicts prognosis in heart failure (HF) and may help to select HF patients in need of intensified therapy.

METHODS:

This retrospective post hoc analysis included 219 patients from the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure (TIME-HF) and 631 patients from Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) with HF who had reduced ejection fraction and available galectin-3 plasma concentrations. The interaction between galectin-3, β-blockers, renin-angiotensin system (RAS) blockade, and spironolactone on outcome was evaluated in TIME-CHF and validated in GISSI-HF. End points were all-cause mortality and the composite of mortality with HF hospitalization or any hospitalization.

RESULTS:

High galectin-3 concentrations were associated with adverse outcome in both cohorts and remained significantly associated with death after multivariate adjustment [hazard ratio 2.42 (95% CI 1.17-5.01), P = 0.02, in TIME-CHF; 1.47 (1.02-2.10), P = 0.04, in GISSI-HF). In TIME-CHF, patients with low galectin-3 plasma concentrations had a better prognosis when β-blockers were up-titrated, whereas patients with high galectin-3 plasma concentrations did not (interaction P < 0.05 for mortality and death with or without hospitalization). Opposite trends were seen for RAS blockade but were not statistically significant. Patients with high galectin-3 plasma concentrations had neutral prognosis when receiving spironolactone, whereas patients with low galectin-3 plasma concentrations had worse prognosis when receiving spironolactone (interaction P < 0.10 for death with or without hospitalization). In the GISSI-HF validation cohort, these interactions were confirmed for β-blockers (P < 0.05 for all end points) and consistent for RAS blockade (P < 0.10 for death with or without hospitalization), but inconsistent for spironolactone.

CONCLUSIONS:

Galectin-3 is a mediocre prognostic marker, and galectin-3 concentrations interact with the treatment effect of β-blockers and possibly RAS blockade in patients with systolic HF.

PMID:
26936932
DOI:
10.1373/clinchem.2015.246850
[Indexed for MEDLINE]
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