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. BackgroundThe 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.ObjectivesTo assess the prospective association of plasma galectin‐3 and the LGALS3 rs4644 SNP with VTE incidence.MethodsWe 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.ConclusionGalectin‐3 levels were associated positively with VTE incidence.

Galectin‐3 and risk of ischaemic stroke: Reasons for Geographic and Racial Differences in Stroke cohort

“…It is possible that galectin-3 has varying influences on stroke risk and outcome depending on the site of its expression and chronological context in relation to the ischaemic event. Finally, galectin-3 also relates to thrombotic potential, which might explain part of its association with stroke [26,27].…”

Inter-Relationship between Platelet-Derived Microparticles and Oxidative Stress in Patients with Venous Thromboembolism

“…The role of OxS in ischemic arterial diseases is well known, but few studies have been performed to elucidate the role of OxS in VTE [12,13] or the validity of biomarkers for the screening of individuals at risk of VTE [14,15]. It has been reported that OxS is higher in patients with VTE [16].…”

Discovery of novel plasma biomarkers for future incident venous thromboembolism by untargeted synchronous precursor selection mass spectrometry proteomics

“…Venous thromboembolism is a complex disease that occurs as a result of interactions between inherited and acquired factors [8]. Several genetic variants and the levels of numerous plasma proteins, mostly with roles in coagulation or fibrinolysis, have been shown to be associated with VTE [1,[9][10][11][12][13][14][15][16][17][18]. However, few prospective studies have successfully shown associations between protein biomarker levels at baseline and risk of future incident VTE [11,13,17,18].…”