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

Abstract

AimsGalectin-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 resultsFour 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 twofold 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.

Impact of Galectin-3 Circulating Levels on Frailty in Elderly Patients with Systolic Heart Failure

“…Therefore, we suggest that the up-regulation of Gal-3 associated with HF development might interfere with mechanisms of premature senescence, accelerated aging and frailty development. A recent study, performed in a large population of elderly subjects, revealed that Gal-3 is associated with an impaired myocardial function in physiological ageing, describing a potential role in an early (preclinical) phase of myocardial ageing [20]. The role of Gal-3 as an independent predictor of outcomes in HF has not been confirmed; however, adding Gal-3 to the well-established NT-proBNP ameliorated the prediction of adverse outcomes [53], probably because the population of patients with higher Gal-3 were also the most-frail.…”

“…Elevated Gal-3 levels are associated with negative outcomes, while the inhibition of Gal-3 has been described as improving cardiac remodeling in experimental models of systolic HF [19]. Gal-3 levels increase with age and have been associated with comorbidities [20]. Of note, the permanent replacement of functional tissue by fibrosis is a characteristic of the aging process, and furthermore it is considered, together with inflammation, one of the hallmarks of aging.…”

Role of novel biomarkers in diabetic cardiomyopathy

“…The first evidence to support these findings were provided by Sharma et al [ 144 ] in a study which demonstrated that galectin-3 was the strongest differentially regulated gene associated with HF. Subsequently, a number of authors produced abundant evidence that successfully associated galectin-3 with HF in both animal models and in human studies, leading to the Food and Drug Administration approval of galectin-3 as a novel biomarker for predicting cardiovascular adverse events in 2010[ 145 - 149 ]. It is important to note that inhibition of galectin-3 could be an important target molecule in the HF therapeutic approach, based on its potential to undermine cardiac fibrosis and mitigate poor outcomes of HF.…”

Rapid changes of miRNAs-20, -30, −410, −515, −134, and −183 and telomerase with psychological activity: A one year study on the relaxation response and epistemological considerations

“…We emphasize that, in the same blood samples used in this work, we previously assessed the malondialdehyde and galectin-3 levels as aging 58 , 59 and cellular senescence markers, 60 , 61 , 62 , 63 demonstrating a decrease in the course of RR. 64 Numerous studies in the literature and our previous studies 12 , 19 have shown that RR causes a decrease in the levels of inflammatory cytokines and stress hormones.…”