Galectin-3 in ambulatory patients with heart failure results from the HF-ACTION study

G. Michael Felker, Mona Fiuzat, Linda K. Shaw, Robert Clare, David J. Whellan, Luca Bettari, Shailesh C. Shirolkar, Mark Donahue, Dalane W. Kitzman, Faiez Zannad, Ileana L. Pina, Christopher M. O'Connor

Research output: Contribution to journalArticle

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Abstract

Background-Galectin-3 is a soluble β-galactoside- binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. We evaluated the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure patients enrolled in the HF-ACTION study. Methods and Results-HF-ACTION was a randomized, controlled trial of exercise training in patients with chronic heart failure caused by left ventricular systolic dysfunction. Galectin-3 was assessed at baseline in a cohort of 895 HF-ACTION subjects with stored plasma samples available. The association between galectin-3 and clinical outcomes was assessed using a series of Cox proportional hazards models. Higher galectin-3 levels were associated with other measures of heart failure severity, including higher New York Heart Association class, lower systolic blood pressure, higher creatinine, higher amino-terminal proB-type natriuretic peptide (NTproBNP), and lower maximal oxygen consumption. In unadjusted analysis, there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio, 1.14 per 3-ng/mL increase in galectin-3; P=0.0001). In multivariable modeling, the prognostic impact of galectin-3 was significantly attenuated by the inclusion of other known predictors, and galectin-3 was no longer a significant predictor after the inclusion of NTproBNP. Conclusions-Galectin-3 is elevated in ambulatory heart failure patients and is associated with poor functional capacity and other known measures of heart failure severity. In univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NTproBNP.

Original languageEnglish (US)
Pages (from-to)72-78
Number of pages7
JournalCirculation: Heart Failure
Volume5
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

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Galectin 3
Heart Failure
Blood Pressure
Galactosides
Natriuretic Peptides
Left Ventricular Dysfunction
Proportional Hazards Models
Lectins
Oxygen Consumption
Creatinine
Hospitalization

Keywords

  • Biomarker
  • Heart failure
  • Prognosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Felker, G. M., Fiuzat, M., Shaw, L. K., Clare, R., Whellan, D. J., Bettari, L., ... O'Connor, C. M. (2012). Galectin-3 in ambulatory patients with heart failure results from the HF-ACTION study. Circulation: Heart Failure, 5(1), 72-78. https://doi.org/10.1161/CIRCHEARTFAILURE.111.963637

Galectin-3 in ambulatory patients with heart failure results from the HF-ACTION study. / Felker, G. Michael; Fiuzat, Mona; Shaw, Linda K.; Clare, Robert; Whellan, David J.; Bettari, Luca; Shirolkar, Shailesh C.; Donahue, Mark; Kitzman, Dalane W.; Zannad, Faiez; Pina, Ileana L.; O'Connor, Christopher M.

In: Circulation: Heart Failure, Vol. 5, No. 1, 01.2012, p. 72-78.

Research output: Contribution to journalArticle

Felker, GM, Fiuzat, M, Shaw, LK, Clare, R, Whellan, DJ, Bettari, L, Shirolkar, SC, Donahue, M, Kitzman, DW, Zannad, F, Pina, IL & O'Connor, CM 2012, 'Galectin-3 in ambulatory patients with heart failure results from the HF-ACTION study', Circulation: Heart Failure, vol. 5, no. 1, pp. 72-78. https://doi.org/10.1161/CIRCHEARTFAILURE.111.963637
Felker, G. Michael ; Fiuzat, Mona ; Shaw, Linda K. ; Clare, Robert ; Whellan, David J. ; Bettari, Luca ; Shirolkar, Shailesh C. ; Donahue, Mark ; Kitzman, Dalane W. ; Zannad, Faiez ; Pina, Ileana L. ; O'Connor, Christopher M. / Galectin-3 in ambulatory patients with heart failure results from the HF-ACTION study. In: Circulation: Heart Failure. 2012 ; Vol. 5, No. 1. pp. 72-78.
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AU - Whellan, David J.

AU - Bettari, Luca

AU - Shirolkar, Shailesh C.

AU - Donahue, Mark

AU - Kitzman, Dalane W.

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N2 - Background-Galectin-3 is a soluble β-galactoside- binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. We evaluated the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure patients enrolled in the HF-ACTION study. Methods and Results-HF-ACTION was a randomized, controlled trial of exercise training in patients with chronic heart failure caused by left ventricular systolic dysfunction. Galectin-3 was assessed at baseline in a cohort of 895 HF-ACTION subjects with stored plasma samples available. The association between galectin-3 and clinical outcomes was assessed using a series of Cox proportional hazards models. Higher galectin-3 levels were associated with other measures of heart failure severity, including higher New York Heart Association class, lower systolic blood pressure, higher creatinine, higher amino-terminal proB-type natriuretic peptide (NTproBNP), and lower maximal oxygen consumption. In unadjusted analysis, there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio, 1.14 per 3-ng/mL increase in galectin-3; P=0.0001). In multivariable modeling, the prognostic impact of galectin-3 was significantly attenuated by the inclusion of other known predictors, and galectin-3 was no longer a significant predictor after the inclusion of NTproBNP. Conclusions-Galectin-3 is elevated in ambulatory heart failure patients and is associated with poor functional capacity and other known measures of heart failure severity. In univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NTproBNP.

AB - Background-Galectin-3 is a soluble β-galactoside- binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. We evaluated the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure patients enrolled in the HF-ACTION study. Methods and Results-HF-ACTION was a randomized, controlled trial of exercise training in patients with chronic heart failure caused by left ventricular systolic dysfunction. Galectin-3 was assessed at baseline in a cohort of 895 HF-ACTION subjects with stored plasma samples available. The association between galectin-3 and clinical outcomes was assessed using a series of Cox proportional hazards models. Higher galectin-3 levels were associated with other measures of heart failure severity, including higher New York Heart Association class, lower systolic blood pressure, higher creatinine, higher amino-terminal proB-type natriuretic peptide (NTproBNP), and lower maximal oxygen consumption. In unadjusted analysis, there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio, 1.14 per 3-ng/mL increase in galectin-3; P=0.0001). In multivariable modeling, the prognostic impact of galectin-3 was significantly attenuated by the inclusion of other known predictors, and galectin-3 was no longer a significant predictor after the inclusion of NTproBNP. Conclusions-Galectin-3 is elevated in ambulatory heart failure patients and is associated with poor functional capacity and other known measures of heart failure severity. In univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NTproBNP.

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