Baseline and serial measurements of galectin-3 in patients with heart failure: relationship to prognosis and effect of treatment with valsartan in the Val-HeFT

Abstract

Aims: This study was conducted to determine whether galectin-3, a β-galactoside-binding lectin, plays a role in the pathogenesis of heart failure (HF).

Methods and results: Galectin-3 was measured at baseline (n = 1650), after 4 months (n = 1346), and after 12 months (n = 1097) in the Valsartan Heart Failure Trial (Val-HeFT). Galectin-3 levels at baseline ranged from 4.8 to 53 ng/mL. Higher levels were associated with features of worse HF. In a fully adjusted Cox regression model comprising 23 other prognostic variables, baseline galectin-3 was not associated with the risks of all-cause mortality, the composite of the first morbid event, or hospitalization for HF. However, when changes in galectin-3 over time were examined, the increases in galectin-3 between baseline and 4 months were independently and significantly associated with the risks of subsequent all-cause mortality, first morbid event, and hospitalizations for HF, even after adjusting for all baseline and concurrent changes in all variables including estimated glomerular filtration rate (eGFR) and NT-proBNP. The strongest correlate of galectin-3 levels was eGFR, which accounted for 20% of the variability in galectin-3 levels at baseline. There was a significant interaction (P = 0.03) between baseline galectin-3 and the effect of valsartan on hospitalizations for HF. Valsartan caused a significant 44% reduction in hospitalizations for HF in patients with galectin-3 levels below the median level of 16.2 ng/mL, but not in patients with levels above the median.

Conclusions: Galectin-3 levels are elevated in a substantial proportion of patients with HF, particularly those with more severe HF and renal dysfunction. Galectin-3 increased over time in this cohort, and the increase was independently associated with worse outcomes. Valsartan use was associated with a reduction in hospitalizations for HF in patients with low galectin-3, but not in those with higher levels of galectin-3.