Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction

Abstract

Aims: galectin-3 is an emerging biomarker which has been studied in relatively small heart failure (HF) cohorts with predominantly systolic HF. We studied the prognostic value of base-line galectin-3 in a large HF cohort, with preserved and reduced left ventricular ejection fraction (LVEF), and compared this to other biomarkers.

Methods: we studied 592 HF patients who had been hospitalized for HF and were followed for 18 months. The primary end-point was a composite of all-cause mortality and HF hospitalization.

Results: a doubling of galectin-3 levels was associated with a hazard ratio (HR) of 1.97 (1.62-2.42) for the primary outcome (P < 0.001). After correction for age, gender, BNP, eGFR, and diabetes the HR was 1.38 (1.07-1.78; P = 0.015). Galectin-3 levels were correlated with higher IL-6 and CRP levels (P < 0.002). Changes of galectin-3 levels after 6 months did not add prognostic information to the base-line value (n = 291); however, combining plasma galectin-3 and BNP levels increased prognostic value over either biomarker alone (ROC analysis, P < 0.05). The predictive value of galectin-3 was stronger in patients with preserved LVEF (n = 114) compared to patients with reduced LVEF (P < 0.001).

Conclusions: galectin-3 is an independent marker for outcome in HF and appears to be particularly useful in HF patients with preserved LVEF.

Figure 1

Adjusted Cox regression curves for quartiles of plasma galectin-3 showing the cumulative risk for the combined end-point all-cause mortality and hospitalization for HF.

Figure 2

Graphical depiction of the risk estimates for experiencing the primary outcome in patients with HFPEF and HFREF with increasing levels of plasma galectin-3. The distribution of (log-transformed) galectin-3 is depicted in the background in brown bars. A similar increase in galectin-3 causes a much more pronounced increase in risk in patients with HFPEF compared to patients with HFREF.

Figure 3

Combined receiver-operating characteristic (ROC) curves for brain natriuretic peptide (BNP) and galectin-3 for prediction of death or HF readmission in patients with HF after 18 months of follow-up. The ROC analysis for BNP showed an area under the curve (AUC) of 0.65 (P < 0.001); for galectin-3 the AUC is 0.67 (P = 0.004). The ROC analysis for the combination of BNP and galectin-3 shows an AUC of 0.69 (P < 0.05 versus BNP or galectin-3 alone).

Figure 4

Combined receiver-operating characteristic (ROC) curves for the prediction of death or HF readmission in patients with HF after 18 months for galectin-3 levels at base-line and galectin-3 levels at 6-month follow-up. The ROC analysis for galectin-3 levels at base-line showed an area under the curve (AUC) of 0.67 (P for predicting the death or HF readmission: 0.004); the AUC for galectin-3 levels at 6 months is 0.66 (P = 0.04). The ROC analysis for a combination of galectin-3 levels at baseline and levels at 6 months follow-up showed an AUC of 0.67 (P = NS versus galectin-3 at base-line alone).