Galectin-3 Levels and Long-term All-cause Mortality and Hospitalization in Heart Failure Patients: a Meta-analysis

Aims: This meta-analysis investigated the dose-response relationship between circulating galectin-3 levels and adverse outcomes in patients with heart failure (HF).

Methods And Results: PubMed and Embase were screened for studies on galectin-3 and HF. The outcomes of interest were all-cause mortality (ACM), and all-cause mortality or HF-related rehospitalization (ACM/HFR), with a follow-up time of more than 6 months. For categorical variables, comparisons between groups with the highest and lowest galectin-3 levels were pooled. For continuous variables, the risks of ACM and ACM/HFR increase per 1-standard deviation (SD) and 1-unit after logarithmic transformation galectin-3 levels were pooled. A random-effects model was employed to calculate the pooled results, and all pooled results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Besides, a dose-response analysis was performed. Twenty-four cohort studies were included. In HF patients, higher circulating galectin-3 levels were significantly associated with a higher risk of long-term ACM (HR, 1.65; 95% CI 1.28-2.13; I = 66%), and 1 ng/mL increase in galectin-3 was associated with a 4% (HR, 1.04; 95% CI 1.02-1.06; P = 0.002) increase in hazard. Similarly, higher circulating galectin-3 levels were significantly associated with a higher risk of long-term ACM/HFR (HR, 1.52; 95% CI, 1.15 to 2.00; I = 76%), and 1 ng/mL increase in galectin-3 was associated with a 3% (HR, 1.03; 95% CI 1.02-1.04; P < 0.001) increase in hazard. An increase of 1-SD in galectin-3 units was associated with a 29% increased hazard of long-term ACM (HR 1.29; 95% CI 1.13-1.48; I = 42%) and a 22% increased hazard of ACM/HFR (HR 1.22; 95% CI 1.07-1.38; I = 60%). Similarly, an increase of 1-log in galectin-3 units was associated with a 98% higher hazard of long-term ACM (HR 1.98; 95% CI 1.48-2.65; I = 41%) and an 83% higher hazard of ACM/HFR in HF patients (HR 1.83; 95% CI 1.02-3.28; I = 7%). Correlation analysis showed a moderate positive correlation between baseline galectin-3 and N terminal pro brain natriuretic peptide levels (r = 0.48, P = 0.045) and a weak negative correlation with eGFR (r = -0.39, P = 0.077).

Conclusions: Higher circulating galectin-3 levels after hospitalization of HF patients are linearly and positively associated with the risk of long-term ACM and ACM/HFR.