Changes in Galectin-3 Levels over Time Predict Mortality and Morbidity in Chronic HF

Abstract

Background: Elevated circulating levels of galectin-3, a protein implicated in myocardial fibrosis and remodeling, are associated with significantly increased risk of morbidity and mortality among chronic heart failure (HF) subjects. The clinical utility of serial measurements of galectin-3, however, has not been reported. Methods: Galectin-3 was measured at baseline and at 3 months in a study comprising 1,329 subjects of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA), and at baseline and 6 months in 324 subjects of the Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH). An assay recently cleared by the U.S. Food and Drug Administration was used to measure galectin-3, and the indicated threshold value of 17.8 ng/mL was adopted to categorize subjects into 4 categories: subjects whose galectin-3 values remained either below or above 17.8 ng/mL, and subjects whose galectin-3 levels either increased or decreased between baseline and the second sampling time point. Results: Categorical changes in galectin-3 were observed in 17.3% of subjects from CORONA over 3 months, and 23.5% of subjects from COACH over 6 months. For the composite endpoint of total mortality and HF hospitalization, the outcome of subjects with a low baseline galectin-3 level that increased over time was significantly worse than that of subjects that maintained a low level (Cox hazard ratio (HR) in CORONA, 1.60 (95% CI: 1.152.22), p50.005; HR in COACH, 2.46 (95% CI: 1.05-5.73, p50.037)). Similarly, subjects with a high baseline level that decreased over time exhibited significantly fewer endpoints than subjects that remained high over time (HR in CORONA, 0.68 (95% CI: 0.49-0.94), p50.020; HR in COACH, 0.48 (95% CI: 0.27-0.87), p50.015). Analyses of multiple secondary endpoints yielded comparable results. Conclusions: In two large cohorts of chronic HF subjects, serial measurements of galectin-3 concentration are shown to provide important and significant prognostic value for morbidity and mortality risk assessment. 295