Direct, inflammation-mediated and blood-pressure-mediated effects of total and abdominal adiposity on diastolic function: EPIPorto study.

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.

Methods And 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.