The adipo-fibrokine activin A is associated with metabolic abnormalities and left ventricular diastolic dysfunction in obese patients

ESC Heart Fail. 2019 Apr;6(2):362-370. doi: 10.1002/ehf2.12409. Epub 2019 Feb 6.

Abstract

Aims: Left ventricular diastolic dysfunction (LVDD) is common in obese subjects, and a relationship between epicardial adipose tissue (EAT), increased adipocytokines, and cardiovascular diseases has been reported. This study sought to examine as to whether the adipo-fibrokine activin A is a link between increased EAT, the metabolic syndrome (MetS), and LVDD in severely obese subjects.

Methods and results: In 236 obese subjects (ø body mass index 39.8 ± 7.9 kg/m2 ) with a variable degree of the MetS and in 60 healthy non-obese controls (ø body mass index 24.8 ± 3.4 kg/m2 ), serum activin A levels were measured and correlated with parameters of the MetS, epicardial fat thickness (EFT), and echocardiographic parameters of LVDD. Activin A levels were higher in obese than in non-obese subjects (362 ± 124 vs. 301 ± 94 pg/mL, P = 0.0004), increased with the number of MetS components (from 285 ± 82 with no MetS component, 323 ± 94 with one or two MetS components, to 403 ± 131 pg/mL with ≥3 MetS components, P < 0.0001) and correlated with EFT (r = 0.41, P < 0.001). Furthermore, activin A levels were related to several parameters of LVDD [e.g. left atrial size (382 ± 117 vs. 352 125 pg/mL, P = 0.024), E/e' (394 ± 108 vs. 356 ± 127 pg/mL, P = 0.005)]. LVDD was highest in MetS obese subjects with high EFT (44.3%) compared with MetS obese subjects with low EFT (27.0%), non-MetS obese subjects with high EFT (24.2%), and non-MetS obese subjects with low EFT (10.6%, P < 0.0001).

Conclusions: In severe obesity, activin A was significantly related to EFT, MetS, and LVDD, implicating MetS-related alterations in the secretory profile of EAT in the pathogenesis of obesity-related heart disease.

Keywords: Activin A; Diastolic dysfunction; Epicardial fat; Metabolic syndrome; Obesity.

MeSH terms

  • Activins / metabolism*
  • Adipose Tissue / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Body Mass Index
  • Diastole
  • Echocardiography
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / physiopathology*
  • Humans
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / etiology*
  • Middle Aged
  • Obesity / blood
  • Obesity / complications*
  • Prospective Studies
  • Risk Factors
  • Ventricular Dysfunction, Left / blood*
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / physiopathology
  • Young Adult

Substances

  • Biomarkers
  • activin A
  • Activins