Circulating Galectin-3 distinguishes global aortic aging among older women

Abstract Background Traditional cardiovascular risk factors may underestimate age-associated cardiovascular risk, particularly in estimating discrepant risks between sexes. As a marker of adverse cardiovascular events, aortic stiffness may improve risk assessment, but the requirement for advanced imaging equipment restrict widespread translation of this paradigm. Conversely, circulating blood biomarkers may augment mechanistic understanding and distinguish sex-based differences in aortic stiffness. Purpose Hypothesizing that Galectin-3 (Gal-3) is associated with aortic aging among older adults, we examined sex-based differences between Gal-3 and global aortic stiffness as assessed by a novel cardiac magnetic resonance (CMR)-derived measurement of aortic global longitudinal strain (AOGLS). Methods Community older adults without cardiovascular disease underwent simultaneous CMR with serum Gal-3 quantification using chemiluminescent microparticle immunoassays. Poorer AOGLS was defined as values below the 75th percentile of AOGLS measurements. Multivariable regression models were used to assess the association of Gal-3 with AOGLS. Results Of 255 participants (mean age 70.8 ±9.1 years, LVEF 66.3 ±8.3%), 44.3% were women. Poorer AOGLS was characterized by higher Gal-3 (B coefficient = -0.101, 95%CI [-0.167, -0.034], p = 0.003), mean age (B = -0.126, 95%CI [-0.154, -0.098], p <0.001), male sex (B = -0.991, 95%CI [-0.409, -1.572], p = 0.001), history of hypertension (B = -0.777, 95%CI [-1.364, -0.189], p = 0.010), diabetes mellitus (B = -0.888, 95%CI [-1.617,-0.158], p = 0.017), smoking (B = -1.346, 95%CI [-2.15, -0.542], p=0.001), pulse rate (B = -0.032, 95%CI [-0.055, -0.01], p = 0.005), systolic BP (B = -0.014, 95%CI [-0.025, -0.004], p = 0.009), and diastolic BP (B = -0.033, 95%CI [-0.06, -0.006], p = 0.018) on univariable linear regressions; no associations were observed with urine albumin-to-creatinine ratio, serum NT-ProBNP, or hs-Troponin I. After multivariable adjustments for sex, age, significant cardiovascular risk factors (hypertension, diabetes, smoking), and pulse rate, the inverse relationship between Gal-3 and AOGLS (Figure 1) persisted (B = -0.071 95%CI [-0.135, -0.008], adj. p = 0.028, R2 = 0.217). The association between Gal-3 and AOGLS was more marked among women (Figure 2), compared to men. Among women, higher Gal-3 characterized women with poorer AOGLS (17.04 ±3.73 ng/mL vs 15.48 ±3.55 ng/mL p = 0.040) (B = -0.120, OR 0.887, 95% CI [0.787, 0.999], adj. p = 0.048), independent of age. Conclusions Galectin-3 was adversely associated with novel CMR-derived AOGLS. Among these older adults with age-associated observations in AOGLS, Gal-3 highlighted sex-based differences in AOGLS and differentiated women with poorer AOGLS from women with better AOGLS. Serum Gal-3 measurements may be useful for detecting adverse patterns of aortic aging, particularly as an early approach in community older adults.