Association between circulating biomarkers and epicardial adipose tissue in patients with heart failure with preserved ejection fraction

Abstract Introduction Epicardial adipose tissue (EAT), located in close proximity to the myocardium, is of particular interest due to its potential to influence cardiac structure and function in patients with heart failure with preserved ejection fraction (HFpEF). However, the exact mechanisms remain uncertain and potentially involve both local and systemic factors. Investigating circulating obesity- and inflammatory biomarkers may provide insights into these mechanisms by reflecting systemic inflammation and metabolic dysregulation potentially associated with EAT. Purpose We aimed to explore the association between EAT volume, and circulating obesity- and inflammatory related biomarkers in patients with HFpEF. Methods Heart failure patients with left ventricular ejection fraction (LVEF) >40% enrolled in the prospective multicenter VIP-HF study were analyzed cross-sectionally. EAT volume was quantified on short-axis cine-stacks on cardiac MRI and adjudicated by two reviewers. Patients were categorized into two groups based on low or high EAT volume, determined by the first and last quartile. The study outcomes were circulating obesity- and inflammatory related biomarkers using the Olink Target 96 Cardiovascular II, III and immune-oncology panel. Linear regression analysis was used to assess the association between EAT volume and biomarkers. R-squares were reported per 10 ml increase in EAT volume. Results In total 94 patients were included. Mean age was 73±8 years, 42 (45%) were women, mean LVEF was 53±6%. Mean body mass index (BMI) was 29.7±5.7 and mean volume of EAT was 206±68 ml. Patient with EAT volume ≤142 ml were classified in the low EAT group (first quartile) and patients with an EAT volume >244 ml were classified in the high EAT group (last quartile). The patients in the high EAT group, were more often female (71% vs 42%, p=0.001), had a higher BMI (34.8 kg/m2 vs 26.2 kg/m2, p<0.001) and had more often diabetes (71% vs 21%, p=0.001). Leptin and FABP-4 levels were statistically significantly higher in patients with high EAT compared with patients with low EAT (7.1 vs 8.3, p<0.001 and 6.4 vs 7.2, p=0.002 respectively; Figure 1). No statistically significant differences were detected between patients with low and high EAT for the other obesity-related biomarkers. Univariable linear regression analysis showed a statistically significant association between EAT volume and levels of Leptin (R2 0.08, p=0.007) and FABP-4 (R2 0.06, p=0.019), but not with the other biomarkers (Table 1). After adjusting for BMI, no statistically significant association were detected (Table 1). Conclusion In patients with HFpEF, increased EAT was associated with elevated levels of Leptin and FABP-4. However, this association between increased EAT and increased levels of these obesity related biomarkers seemed mainly driven by overall adiposity. Further studies are needed to explore potential systemic effects of EAT.