Galectin-3 as a candidate upstream biomarker for quantifying risks of myocardial ageing

Abstract

Aims: Galectin-3 (Gal-3) is implicated in the pathogenesis of heart failure and is also influenced by ageing. This study aims to determine the extent to which Gal-3 levels estimate odds of myocardial dysfunction in ageing cohorts, ‘upstream’ prior to clinical disease. Methods and results: Four hundred seventy-five asymptomatic subjects underwent simultaneous assessments of cardiovascular structure and function, with measurements of circulating Gal-3. Myocardial dysfunction was defined as impaired myocardial relaxation (ratio of peak velocity flow in early diastole E (m/s) to peak velocity flow in late diastole by atrial contraction A (m/s) <0.84) (mean E/A ratio 0.84 in the cohort). Of 475 subjects (mean age 68 ± 12 years, 231 women), 222 (47%) had myocardial dysfunction. Subjects with myocardial dysfunction were older (mean age 73 ± 5 vs. 64 ± 14 years, P < 0.0001), and more had hypertension (59 vs. 40%, P < 0.0001), dyslipidaemia (54 vs. 39%, P = 0.001), diabetes mellitus (25 vs. 14%, P = 0.002), higher body mass index (BMI) (24 vs. 23 kg/m2, P = 0.002), and higher heart rate (76 vs. 71 b.p.m., P = 0.0001). Participants with impaired myocardial relaxation had lower peak velocity flow in early diastole E (0.6 ± 0.1 vs. 0.8 ± 0.2 m/s, P < 0.0001), higher peak velocity flow in late diastole by atrial contraction A (0.9 ± 0.1 vs. 0.7 ± 0.2 m/s, P < 0.0001), and higher mitral valve flow deceleration time (224.7 ± 43.2 vs. 204.8 ± 33.1 m/s, P < 0.0001). Participants with impaired myocardial relaxation had higher Gal-3 levels (17.2 ± 6.2 vs. 15.5 ± 4.1, P = 0.0004) but similar B-type natriuretic peptide (37 ± 4 vs. 34 ± 29, P = 0.37) and high-sensitivity troponin I (21 ± 72 vs. 11 ± 41, P = 0.061) levels and urine microalbumin-to-creatinine ratio (4.6 ± 8.1 vs. 4.2 ± 10.8, P = 0.75) compared with those without impaired myocardial relaxation. After multivariable adjustments, Gal-3 [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.00–1.10, P = 0.039], age (OR 2.60, 95% CI 1.64–4.11, P < 0.0001), BMI (OR 2.16, 95% CI 1.44–3.23, P < 0.0001), and heart rate (OR 1.04, 95% CI 1.02–1.06, P < 0.0001) were associated with impaired myocardial relaxation. Adjusted ORs (95% CI) for myocardial dysfunction were 1.0 (ref), 1.62 (0.92–2.85), 1.92 (1.08–3.41), and 2.01 (1.11–3.66) across consecutive quartiles of Gal-3 after adjustment for age, BMI, risk factors, and heart rate. Conclusions: Among asymptomatic community-dwelling elderly adults, the highest quartile of Gal-3 was associated with two-fold increased odds of myocardial dysfunction compared with the lowest quartile of Gal-3. Gal-3 may have a role as an ‘upstream’ biomarker in estimating odds of myocardial ageing prior to clinical disease.