Galectin-3 Levels Are Elevated and Predictive of Mortality in Pulmonary Hypertension

Background Galectin-3, a novel binding-lectin involved in inflammation and fibrosis, is elevated in heart failure and is independently predictive of mortality in this condition. We sought to evaluate galectin-3 levels and its prognostic value in patients with pulmonary hypertension (PH), a known inflammatory state, in the setting of pulmonary arterial hypertension (PAH) and in heart failure with preserved ejection fraction-associated PH (HFpEF-PH). Methods We measured galectin-3 levels in 76 patients with PH; 37 patients with PAH and 39 patients with HFpEF-PH. Baseline characteristics, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels were assessed. Univariate and multivariate analyses were used to assess the prognostic value of galectin-3. Results Median (IQR) galectin-3 (ng/mL) for the entire cohort was 24.65 (IQR = 10.39, 32.90); 22.33 (IQR = 18.94, 27.30) and 28.94 (IQR = 21.67, 39.85) in the PAH and HFpEF-PH, respectively (p = 0.07). After evaluation of the galectin-3 levels by tertile, mortality rates were 16% (4/25), 34.6% (9/26), and 48% (12/25) in tertiles 1-3, respectively, and Kaplan-Meier analysis revealed a significant increase in mortality across increasing galectin- 3 tertiles (log-rank p = 0.014). On Cox regression analysis, galectin-3 was a strong predictor of mortality on both univariate HR = 2.09 per tertile (95% CI = 1.21, 3.62 per tertile; p-trend = 0.008) and multivariate analysis HR = 2.19 per tertile (95% CI = 1.06, 4.54; p-trend = 0.035) after adjusting for age, sex, race, glomerular filtration rate (eGFR), NT-proBNP, medications, and aetiology of PH (PAH vs. HFpEF-PH). Conclusion Galectin-3 is a strong, independent prognostic marker in PH, regardless of aetiology. Larger studies should further evaluate the role of galectin-3 as a prognostic biomarker and possible therapeutic target in PH.