title: Direct, inflammation-mediated and blood-pressure-mediated effects of total and abdominal adiposity on diastolic function: EPIPorto study.
abstract: BACKGROUND
  Obesity has been associated with subclinical diastolic dysfunction and increased risk of heart failure. Our aims were to evaluate the age- and sex-specific role of total and abdominal adiposity on diastolic function and to assess the direct and indirect pathophysiological mechanisms involved in this association.
  
  
  RESULTS
  Within a population-based study (EPIPorto), a total of 1063 individuals aged ≥ 45 years (62% female; 62.4 ± 10.6 years) were evaluated using echocardiography, anthropometrics, electrical bioimpedance and blood tests. Diastolic function was assessed with using EAE/ASE consensus criteria. Worse diastolic function grades were associated with increased BMI, fat mass % and waist-to-height ratio (p for trend<0.001). The inverse association between adiposity and diastolic function was stronger in men and in the younger population. In multivariate analysis, waist-to-height ratio (per cm/cm) was associated with reduced E' velocity (adjusted β: -14.4; 95% CI: -21.1 to -7.6; p<0.001) and increased E/E' ratio (adjusted β: 9.7, 95% CI: 5.4-10.0; p<0.001), among men<65 years. Both direct and indirect mechanisms were involved in the E' velocity decrease by waist-to-height ratio in participants<65 years. The effect was mainly direct in men (81.3%), while it was mostly indirect in women, through systolic blood pressure (50.8%) and inflammation (15.1%).
  
  
  CONCLUSIONS
  Adiposity, especially abdominal, was associated with worse diastolic function. This association was more important in men and in the younger population. The causal mechanisms involved were sex-specific, with mostly direct effects among men and blood-pressure-mediated among women.
authors.affiliation: EPIUnit - Institute of Public Health, University of Porto (ISPUP), Porto, Portugal; Cardiology Department, Gaia Hospital Center, Gaia, Portugal; Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal. Electronic address: fontes.carvalho@gmail.com.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fontes-Carvalho
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal; Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gonçalves
authors.affiliation: EPIUnit - Institute of Public Health, University of Porto (ISPUP), Porto, Portugal; Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Milton
authors.initials: M
authors.lastname: Severo
authors.affiliation: Heart Failure Clinic, Department of Internal Medicine, Centro Hospitalar São João, Porto, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Lourenço
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Rocha Gonçalves
authors.affiliation: Heart Failure Clinic, Department of Internal Medicine, Centro Hospitalar São João, Porto, Portugal; Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Bettencourt
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal; Department of Cardiothoracic Surgery, Centro Hospitalar São João, Porto, Portugal.
authors.forename: Adelino
authors.initials: A
authors.lastname: Leite-Moreira
authors.affiliation: EPIUnit - Institute of Public Health, University of Porto (ISPUP), Porto, Portugal; Department of Clinical Epidemiology, Predictive Medicine and Public Health, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Azevedo
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000367:Age Factors; D000368:Aged; D001794:Blood Pressure / Q000502:physiology*; D015992:Body Mass Index; D003971:Diastole / Q000502:physiology; D004452:Echocardiography; D005260:Female; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D012737:Sex Factors; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D065927:Waist-Height Ratio
chemical_list: D018836:Inflammation Mediators
keywords: Diastole; Obesity; Sex; Waist circumference