In several cross-sectional analyses, circulating baseline levels of
galectin-3, a
protein involved in myocardial
fibrosis and remodeling, have been associated with increased risk for morbidity and mortality in patients with
heart failure (HF). The importance and clinical use of repeated measurements of
galectin-3 have not yet been reported.
METHODS AND RESULTS: Plasma
galectin-3 was measured at baseline and at 3 months in patients enrolled in the Controlled
Rosuvastatin Multinational Trial in
Heart Failure (CORONA) trial (n=1329), and at baseline and at 6 months in patients enrolled in the Coordinating Study Evaluating Outcomes of Advising and Counseling Failure (COACH) trial (n=324). Patient results were analyzed by categorical and percentage changes in
galectin-3 level. A threshold value of 17.8 ng/mL or 15% change from baseline was used to categorize patients. Increasing
galectin-3 levels over time, from a low to high
galectin-3 category, were associated with significantly more HF hospitalization and mortality compared with stable or decreasing
galectin-3 levels (hazard ratio in CORONA, 1.60; 95% confidence interval, 1.13-2.25; P=0.007; hazard ratio in COACH, 2.38; 95% confidence interval, 1.02-5.55; P=0.046). In addition, patients whose
galectin-3 increased by >15% between measurements had a 50% higher relative hazard of adverse event than those whose
galectin-3 stayed within ±15% of the baseline value, independent of age, sex,
diabetes mellitus, left ventricular ejection fraction, renal function, medication (β-blocker,
angiotensin converting enzyme inhibitor, and
angiotensin receptor blocker), and N-terminal probrain
natriuretic peptide (hazard ratio in CORONA, 1.50; 95% confidence interval, 1.17-1.92; P=0.001). The impact of changing
galectin-3 levels on other secondary end points was comparable.
CONCLUSIONS: In 2 large cohorts of patients with chronic and acute decompensated HF, repeated measurements of
galectin-3 level provided important and significant prognostic value in identifying patients with HF at elevated risk for subsequent HF morbidity and mortality.