Galectin-3 in ambulatory patients with heart failure: results from the HF-ACTION study.
BACKGROUND
Galectin-3 is a soluble ß-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.


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.


BACKGROUND
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.
Duke University Medical Center, Durham, NC 27710, USA. michael.felker@duke.edu
G Michael
GM
Felker
Mona
M
Fiuzat
Linda K
LK
Shaw
Robert
R
Clare
David J
DJ
Whellan
Luca
L
Bettari
Shailesh C
SC
Shirolkar
Mark
M
Donahue
Dalane W
DW
Kitzman
Faiez
F
Zannad
Ileana L
IL
Piña
Christopher M
CM
O'Connor
D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D019317:Evidence-Based Medicine; D005081:Exercise Therapy; D005260:Female; D005500:Follow-Up Studies; D037502:Galectin 3 / Q000097:blood*; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010045:Outpatients; D010101:Oxygen Consumption / Q000502:physiology; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D012720:Severity of Illness Index
D015415:Biomarkers; D037502:Galectin 3; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D003404:Creatinine