Galectin-3 and venous thromboembolism incidence: the Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Essentials Galectin-3, an inflammatory biomarker, is involved in murine thrombogenesis. Galectin-3–binding protein is up-regulated in microparticles from deep venous thrombosis patients compared to control patients. In this prospective epidemiological study, participants with plasma galectin-3 concentrations in the highest quintile had a greater risk of incident venous thromboembolism than did those in the lowest quintile. The association of galectin-3 and VTE was not replicated in a second prospective study, but the meta-analyzed hazard ratio still indicated a positive association. Galectin-3 is associated positively with risk of venous thromboembolism. Background: The inflammatory biomarker galectin-3 contributes to pathologic conditions such as heart failure and stimulates murine thrombogenesis. Its association with venous thromboembolism (VTE) has been sparsely studied. Objectives: To assess the prospective association of plasma galectin-3 and the LGALS3 rs4644 SNP with VTE incidence. Methods: We measured plasma galectin-3 in 9916 participants in the Atherosclerosis Risk in Communities (ARIC) study cohort in 1996-1998 and identified VTEs through 2013. Using Cox regression, we estimated the hazard ratio associating galectin-3 with incident VTE over a median of 13.9 years. Replication was sought in the Cardiovascular Health Study (CHS). Results: ARIC included 21.8% blacks and 56.2% females with mean baseline age of 62.7 years. The incidence rate of VTE (n=389 events) increased across quintiles of galectin-3, with hazard ratios (95% CI) of 1 (reference), 1.13 (0.80-1.61), 1.00 (0.70-1.43), 1.36 (0.96-1.91), and 1.55 (1.09-2.19) (P-trend=.005), adjusted for age, sex, race, body mass index, diabetes status, and renal function. Results did not replicate in the CHS (124 VTE), but meta-analysis of both studies yielded a pooled hazard ratio (95% CI) for 1 SD increment in log galectin-3 of 1.10 (1.00-1.22). In ARIC, the C allele of rs4644 in the LGALS3 gene was associated with higher galectin-3 level, and in whites, with an increased rate of VTE. Conclusion: Galectin-3 levels were associated positively with VTE incidence.