Longitudinal Change in Galectin-3 and Incident Cardiovascular Outcomes

Abstract

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.

Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

“…Recently, Gal-3 has been indicated to be involved in the following broad pathological processes: Inflammation [9], fibrosis, cell-to-cell [10,11] or cell-to-matrix [12] contacts, cell proliferation [13,14], and protection from apoptosis [15,16]. Furthermore, many studies have revealed that Gal-3 expression is detected in many disease conditions, such as heart disease [17][18][19][20][21][22][23], kidney disease [24][25][26][27], diabetes mellitus [24,25,28], viral infection [29][30][31][32], autoimmune disease [33][34][35][36], neurodegenerative disorders [37][38][39][40][41][42], and tumor formation [43][44][45][46][47][48][49][50][51][52].…”

Sex‐related differences in contemporary biomarkers for heart failure: a review

“…Indeed, longitudinal changes in galectin-3 levels predicted incident HF in both the FHS (n = 2477) and PRE-VEND (n = 5958) cohorts, also after extensive adjustment for cardiovascular risk factors. 90,91 To date, no study has examined whether longitudinal changes in galectin-3 predict new-onset HF differentially in men and women.…”

Stimulation of β‐adrenoceptors up‐regulates cardiac expression of galectin‐3 and BIM through the Hippo signalling pathway

“…Galectin‐3 (Gal‐3) is a β‐galactoside‐specific lectin that binds to intracellular and extracellular glycoproteins regulating their function particularly under diseased conditions (Meijers, Lopez‐Andres, & de Boer, ; Nguyen et al, ; Takemoto et al, ). Clinically, Gal‐3 is regarded as a biomarker predicting the risk of heart failure, atrial fibrillation, or all‐cause mortality (Filipe, Meijers, Rogier van der Velde, & de Boer, ; Ghorbani et al, ). Meanwhile, Gal‐3 is implicated as a causative mediator of cardiac inflammation and fibrosis (Nguyen et al, ; Rabinovich & Toscano, ; Suthahar et al, ; Takemoto et al, ; L. Yu et al, ).…”