Levels and Change in Galectin-3 and Association With Cardiovascular Events: The ARIC Study

Background Circulating galectin-3 levels provide prognostic information in patients with established heart failure (HF), but the associations between galectin-3 levels and other incident cardiovascular events in asymptomatic individuals at midlife and when remeasured approximate to 15 years later are largely uncharacterized. Methods and Results Using multivariable Cox proportional hazards models, we identified associations between plasma galectin-3 levels (hazard ratio [HR] per 1 SD increase in natural log galectin-3) and incident coronary heart disease, ischemic stroke, HF hospitalization, and total mortality in ARIC (Atherosclerosis Risk in Communities) participants free of cardiovascular disease at ARIC visit 4 (1996-1998; n=9247) and at ARIC visit 5 (2011-2013; n=4829). Higher galectin-3 level at visit 4 (median age 62) was independently associated with incident coronary heart disease (adjusted HR, 1.30; 95% CI, 1.06-1.60), ischemic stroke (HR, 1.42; 95% CI, 1.01-2.00), HF (HR, 1.44; 95% CI, 1.17-1.76), and mortality (HR, 1.56; 95% CI, 1.35-1.80). At visit 5 (median age, 74), higher galectin-3 level was associated with incident HF (HR, 1.93; 95% CI, 1.15-3.24) and total mortality (HR, 1.70; 95% CI, 1.15-2.52), but not coronary heart disease or stoke. Individuals with the greatest increase in galectin-3 levels from visit 4 to visit 5 were also at increased risk of incident HF and total mortality. Conclusions In a large, biracial community-based cohort, galectin-3 measured at midlife and older age was associated with increased risk of cardiovascular events. An increase in galectin-3 levels over this period was also associated with increased risk.