Association of Circulating Adipokines With Echocardiographic Measures of Cardiac Structure and Function in a Community‐Based Cohort

Abstract

BackgroundAdipokines mediate cardiometabolic risk associated with obesity but their role in the pathogenesis of obesity‐associated heart failure remains uncertain. We investigated the associations between circulating adipokine concentrations and echocardiographic measures in a community‐based sample.Methods and ResultsWe evaluated 3514 Framingham Heart Study participants (mean age 40 years, 53.8% women) who underwent routine echocardiography and had select circulating adipokines measured, ie, leptin, soluble leptin receptor, fatty acid–binding protein 4, retinol‐binding protein 4, fetuin‐A, and adiponectin. We used multivariable linear regression, adjusting for known correlates (including weight), to relate adipokine concentrations (independent variables) to the following echocardiographic measures (dependent variables): left ventricular mass index, left atrial diameter in end systole, fractional shortening, and E/e′. In multivariable‐adjusted analysis, left ventricular mass index was inversely related to circulating leptin and fatty acid–binding protein 4 concentrations but positively related to retinol‐binding protein 4 and leptin receptor levels (P≤0.002 for all). Left atrial end‐systolic dimension was inversely related to leptin but positively related to retinol‐binding protein 4 concentrations (P≤0.0001). E/e′ was inversely related to leptin receptor levels (P=0.0002). We observed effect modification by body weight for select associations (leptin receptor and fatty acid–binding protein 4 with left ventricular mass index, and leptin with left atrial diameter in end systole; P<0.05 for interactions). Fractional shortening was not associated with any of the adipokines. No echocardiographic trait was associated with fetuin‐A or adiponectin concentrations.ConclusionsIn our cross‐sectional study of a large, young to middle‐aged, relatively healthy community‐based sample, key indices of subclinical cardiac remodeling were associated with higher or lower circulating concentrations of prohypertrophic and antihypertrophic adipokines in a context‐specific manner. These observations may offer insights into the pathogenesis of the cardiomyopathy of obesity.

<p>Leptin Levels are Associated with Subclinical Cardiac Dysfunction in Obese Adolescents</p>

“…38,39 Likewise, the Framingham Heart study found no relationship between FS and leptin levels. 18 Nonetheless, our study showed a significant relationship between leptin levels and GLS in healthy obese participants. The mechanism whereby high leptin levels alter cardiac function remains unclear, but it is hypothesized that leptin may be involved in cardiac myocyte hypertrophy, sympathoactivation, increased total peripheral resistance, oxidative stress, and/or alterations in fatty acid metabolism.…”

“…Our results supported the findings of a communitybased study, which found the inverse relationship between leptin and LVMI and LA diameter as well as the MESA study. 18,33 In contrast, some evidence shows that leptin levels are positively associated with ventricular mass in hypertensive patients and in morbid obesity. 34,35 The dissimilar results in these clinical studies are probably due to the differences in comorbidity, duration of being obese, and/or serum leptin levels of the participants.…”

“…One community-based study demonstrated that leptin levels are not related to LVFS. 18 The impact of leptin levels on human cardiac functions in the obese population has not been assessed. Likewise, UA, the final product of purine metabolism, is now considered to be a marker for metabolic and hemodynamic disorders.…”

Relation between parameters of body composition and echocardiography in patients with nonvalvular atrial fibrillation

“…These last observations may be explained by the above-mentioned data concerning the effect of adiposity (FM, VAT and EAT) on heart remodelling [7,25]. The influence is related to a direct paracrine effect of EAT, the thickness of which correlates with visceral adiposity, as well as the endocrine and proinflammatory activity of VAT [10][11][12]26]. The results of this study have some limitations.…”

“…Moreover, the associations between heart dimensions and nutritional status are complicated by the distribution of adiposity, which an example is the relationship between epicardial adipose tissue (EAT) and left atrial size that was found to be positive for patients with paroxysmal AF and negative for patients with permanent AF [10]. Such effect of fat tissue on heart remodelling and risk of arrhythmia is explained by its paracrine, endocrine and proinflammatory properties [10][11][12]. These data suggest that the association between heart morphology and function and patient nutritional status may be more complicated than simply a relationship with body size or body surface area (BSA).…”