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

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/m(2), 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.