Longitudinal Change in Galectin-3 and Incident Cardiovascular Outcomes

Background Galectin-3 (Gal-3) has been associated with heart failure (HF) and poor cardiovascular outcomes. However, the effect of longitudinal changes in Gal-3 on clinical outcomes remains unclear. Objectives We sought to study clinical determinants of change in Gal-3 among communitydwelling individuals. Further, we sought to examine the role of serial Gal-3 measurements in predicting risk of future HF, cardiovascular disease (CVD) and mortality. Methods A total of 2,477 participants of the Framingham Heart Study Offspring cohort underwent measurement of plasma Gal-3 levels at two exams (1995-1998 and 2005-2008). Linear regression was used to examine clinical correlates of change in Gal-3. Proportional hazards models were used to relate future clinical outcomes with change in Gal-3. Results The following clinical correlates were associated with greater longitudinal increases in Gal-3 levels: age, female gender, hypertension, diabetes, body-mass index, interim development of chronic kidney disease and HF (P<0.0001 for all in multivariable- model). Change in Gal-3 was associated with future HF (HR 1.39 per 1-SD increase, 95%CI 1.13-1.71), CVD (HR 1.29, 95%CI 1.11-1.51), and all-cause mortality (HR 1.30 95%CI 1.17-1.46). Change in Gal-3 was associated with both HF with preserved as well as reduced ejection fraction (P<0.05 for both). Conclusions Longitudinal changes in Gal-3 are associated with traditional cardiovascular risk factors and renal disease. In turn, change in Gal-3 predicts future HF, CVD, and mortality in the community. Future studies are needed to determine whether serial Gal-3 measures may be useful in disease prevention.