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Galectin-3 levels and long-term all-cause mortality and hospitalization in heart failure patients: a meta-analysis
Wenke Cheng1,2, Rosolowski Maciej3, Holger Thiele1
1Department of Internal Medicine/Cardiology, Heart Center Leipzig at University of Leipzig, Strümpellstr. 39, 04289, Leipzig, Germany.
Insights
Higher galectin-3 levels in heart failure (HF) patients are linked to increased risks of mortality and rehospitalization. This meta-analysis confirms a dose-response relationship, indicating greater risk with higher galectin-3 concentrations.
Area of Science:
- Biomarkers in Cardiovascular Disease
- Galectin-3 and Heart Failure Pathophysiology
- Prognostic Value of Circulating Proteins
Background:
- Heart failure (HF) is a complex clinical syndrome with significant morbidity and mortality.
- Identifying reliable biomarkers for risk stratification in HF patients is crucial for improving patient outcomes.
- Galectin-3, a key mediator of cardiac remodeling and fibrosis, has emerged as a potential prognostic marker in HF.
Approach:
- A systematic meta-analysis was conducted by screening PubMed and Embase for relevant cohort studies.
- Twenty-four studies were included to investigate the association between circulating galectin-3 levels and adverse outcomes in HF patients.
- Dose-response relationships were analyzed for all-cause mortality (ACM) and ACM or HF-related rehospitalization (ACM/HFR) using random-effects models.
Key Points:
- Higher circulating galectin-3 levels were significantly associated with an increased risk of long-term ACM (HR, 1.65) and ACM/HFR (HR, 1.52) in HF patients.
- A linear, positive dose-response relationship was observed: each 1 ng/mL increase in galectin-3 was associated with a 4% increase in ACM hazard and a 3% increase in ACM/HFR hazard.
- Increased galectin-3 levels also correlated with N-terminal pro-brain natriuretic peptide and inversely with estimated glomerular filtration rate (eGFR).
Conclusions:
- Elevated circulating galectin-3 levels post-hospitalization in HF patients are a significant predictor of long-term adverse outcomes.
- The findings support galectin-3 as a valuable prognostic biomarker for risk stratification and management of heart failure.
- Further research may explore therapeutic strategies targeting galectin-3 to mitigate adverse events in HF.
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; I2 = 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; I2 = 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; I2 = 42%) and a 22% increased hazard of ACM/HFR (HR 1.22; 95% CI 1.07-1.38; I2 = 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; I2 = 41%) and an 83% higher hazard of ACM/HFR in HF patients (HR 1.83; 95% CI 1.02-3.28; I2 = 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.
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