Abstract MP17: Galectin-3 and Subsequent Risk of Lower-extremity Peripheral Artery Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Background: Galectin-3 is involved in the regulation of inflammation and the formation of fibrosis and has been liked to atherosclerosis. However, there are no studies investigating prospective associations of galectin-3 with incidence of lower-extremity peripheral artery disease (PAD). Methods: Among 9,827 ARIC participants without a history of PAD, we investigated whether galectin-3 (measured at visit 4 [1996-98]) was associated with incident clinical PAD through 2013, defined as hospitalizations with PAD diagnosis or leg revascularization. We defined PAD cases with rest pain or tissue loss as critical limb ischemia (CLI). We constructed Cox models with galectin-3 modeled categorically (quartiles) and continuously (log transformed). Results: During a median follow-up of 15.8 years, 287 participants developed PAD (105 incident CLI cases). In demographically adjusted models, galectin-3 demonstrated a dose-response association with incident PAD: hazard ratios (HRs) 2.55 (95% CI 1.80-3.61) and 1.69 (1.18-2.41) for the highest and second highest quartiles, as compared to the lowest quartile (Table; Model 1). Additional adjustment for traditional cardiovascular risk factors attenuated the associations, although the highest quartile remained borderline significant (HR 1.44 [0.99-2.07], p=0.051, Table: Model 2) and galectin-3 as a continuous variable remained significant (1.15 [1.02-1.29]). Similar results were observed for the association of galectin-3 with CLI. Conclusions: Galectin-3 was modestly associated with future risk of clinical PAD events in a community-based cohort, supporting the involvement of inflammation and fibrosis in the development of clinical PAD.