Association of serum leptin with future left ventricular structure and function: The Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Background/Objectives Earlier studies differ on whether serum leptin is associated with adverse or beneficial cardiac structure. We determined the association between serum leptin with subsequent cardiac structure and function. Methods Multicenter longitudinal study of Black, White, Hispanic and Asian-American men and women. Cardiac MRI (CMR) was completed 6 to 8 years after leptin was measured. Left ventricular (LV) mass and volumes were indexed to body surface area. Multivariable linear regression models were constructed to assess the associations between leptin and risk factor adjusted (age, race, gender, systolic blood pressure, anti-hypertensive usage, LDL, HDL, hyperlipidemia medication usage, diabetes, diabetic medication usage, chronic kidney disease, alcohol and tobacco use, adiponectin and BMI) CMR variables. Results Relative to participants in the lowest quintile of leptin concentration, participants in the highest quintile had a lower risk factor adjusted LV mass (-14g), LV mass index (-9g/m2), LV end diastolic volume index (LVEDVi) (-7 ml/m2), LV end systolic volume index (LVESVi) (-3 ml/m2) and stroke volume (-5 ml) (all p≤ 0.05). On regression analysis, a doubling of leptin concentration was associated with lower LV mass (-2.5g±0.7g), LV mass index (-1.7±0.3 g/m2), LVEDVi (-1.5±0.4 ml/m2), LVESVi (-0.7±0.2 ml/m2) and stroke volume (-1.0±0.5ml) (all p≤ 0.05). Conclusions Higher leptin was associated with more favorable subsequent cardiac structure. Further study is needed to assess the prognostic and therapeutic implications of these observations.

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

“…Similar to our observations, several population‐based studies, including MESA (Multi‐Ethnic Study of Atherosclerosis)10 and a previous study of elderly participants in the original cohort of FHS,29 have reported an inverse association between circulating leptin concentrations and LVM but no association with measures of LV systolic function 29. In contrast, other observational studies of men with hypertension,22 of severely obese patients23 and of patients with myocardial infarction24 have reported a positive association between leptin and cardiac hypertrophy.…”

“…Accordingly, investigators have related circulating concentrations of adipokines to imaging indices of cardiac remodeling. These prior studies have typically been conducted in small samples, or samples with an overrepresentation of obese individuals or elderly people, and usually focused on a single adipokine 10, 11, 13, 21, 22, 23, 24, 25, 26…”

“…In this context, it is noteworthy that the adipose tissue is an endocrine tissue which secretes hormones (referred to as adipokines) that mediate several of the cardiometabolic consequences of obesity. Several adipokines have receptors on cardiac myocytes,7, 8, 9 exhibit prohypertrophic and antihypertrophic effects on the myocardium,10, 11, 12, 13 and have been associated with risk of overt HF 14. Prior investigations relating adipokines to cardiac structure and function have focused on single adipokines10, 11, 15, 16, 17, 18, 19, 20, 21 and related them to traditional measures of cardiac remodeling (such as LV mass [LVM]).…”

“…Several adipokines have receptors on cardiac myocytes,7, 8, 9 exhibit prohypertrophic and antihypertrophic effects on the myocardium,10, 11, 12, 13 and have been associated with risk of overt HF 14. Prior investigations relating adipokines to cardiac structure and function have focused on single adipokines10, 11, 15, 16, 17, 18, 19, 20, 21 and related them to traditional measures of cardiac remodeling (such as LV mass [LVM]). These studies often focused on obese individuals with comorbidities16, 22, 23, 24, 25, 26, 27, 28 or the elderly20, 21, 29 and were limited by modest sample sizes.…”

Unravelling the “adipokine paradox”: When the classic proatherogenic adipokine leptin is deemed the beneficial one

“…Adipokines are the bioactive products of adipose tissue [1] and are recognised as important regulators of food intake, body metabolism and insulin resistance [2]. Adipokines are also known to affect the vascular wall and the human heart in an endocrine manner through the systemic circulation or even in a paracrine manner via their release from local depots such as perivascular or epicardial adipose tissue [3,4].…”