Establishing the upper reference limit of Galectin-3 in healthy blood donors

Introduction: Galectin-3 (Gal-3) is an independent predictor of poor outcomes and mortality in patients with heart failure (HF). Thus, it has been proposed as a reliable prognostic biomarker for HF. The definition of reference intervals is mandatory for interpreting the findings of experimental studies and encouraging the routine use of biomarkers in clinical practice. To date, no study assessed the reference intervals of Gal-3 and identified the biological variables that affect its concentration in a well-defined healthy population. The aim of this study was to determine the upper reference limit (URL) of Gal-3 in a highly reliable population of healthy subjects. Materials and methods: We recruited 714 blood donors. After measuring surrogate biomarkers to identify underlying diseases, 8 subjects were excluded. A final population of 706 individuals (385 men (54.5%); median age 39 (18-65) years) was included. The URL was calculated using the nonparametric percentile approach. Results: The 97.5th percentile URL of plasma Gal-3 in our study population (90% CI) was 26.1 (23.3–31.5) ng/mL. After stratifying subjects according to age, the URL of Gal-3 was found to be considerably higher in older (> 45 years) than in younger subjects (31.5 (26.2–51.4) vs 21.8 (21–26.1) ng/mL, respectively). No sex-related differences were found in Gal-3 plasma concentration. Conclusions: We established the URL of Gal-3 in a highly selected healthy population. Our findings indicate that age is an important determinant of Gal-3 plasma concentration, so that multiple diagnostic cut-offs should be preferably used according to the different age classes.