Abstract

Introduction: Galectin-3 (gal-3) is a B-galactoside-binding lectin and is associated with increased risk of heart failure and other adverse cardiovascular outcomes. Circulating gal-3 has been implicated in promoting tissue fibrosis, leading to vascular remodeling and resultant arterial stiffening. Hypothesis: Plasma gal-3 levels will be associated with central arterial stiffness in a community-based population. Methods: We conducted a cross-sectional analysis of 4,073 participants from the Atherosclerosis Risk in Communities (ARIC) Study who attended visit 5 (2011-2013), with a mean age of 75.1±5.0 years. Central arterial stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). Association between gal-3 and arterial stiffness was assessed using multivariable linear regression models with gal-3 (log transformed) and adjustment first for age, sex, race-center, heart rate, current smoking, mean arterial pressure and use of anti-hypertensive medication (model 1), then for model 1 plus body mass index (BMI), diabetes, hypertension, LDL cholesterol and estimated glomerular filtration rate (eGFR) (model 2). Results: The median gal-3 concentration was 16.5 ng/mL (p25, p75: 13.8, 19.8) and mean cfPWV was 1163 (SD, 303) cm/s. Higher gal-3 concentrations corresponded with higher mean cfPWV and central pulse pressure (p-trends <0.001). Higher gal-3 levels were also associated with higher BMI, diabetes, hypertension, LDL cholesterol, cholesterol lowering medication use, prevalent coronary artery disease, and lower eGFR. In regression analysis, gal-3 was significantly associated with cfPWV in model 1 (ß=46.0; 95% CI 15.4-76.6, per natural log higher gal-3, p=0.003). Further adjustment in model 2 strongly attenuated the association and the coefficient was no longer significant (ß=25.0; 95% CI -8.2-58.2, per natural log increase in gal-3, p=0.14). Conclusions: Higher levels of gal-3, a known promoter of tissue fibrosis, were associated with greater central arterial stiffness. In addition, circulating gal-3 levels were also associated with many traditional risk factors such as BMI, diabetes, hypertension and eGFR; adjustment for these factors attenuated the association of gal-3 with arterial stiffness measures, suggesting mediation of the gal-3 association.

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