Abstract 4141141: Obesity is Associated with Impaired Angiogenesis in Patients with Heart Failure with Preserved Ejection Fraction

Background: Obesity was associated with cardiac vessel remodelling, microvascular rarefaction, and poor angiogenetic response in patients with metabolic syndrome. Aim: Since myocardial microvascular damage may represent a key parameter in the pathogenesis of heart failure with preserved ejection fraction (HFpEF) we sought to investigate a potential correlation between obesity and parameters of angiogenesis in HFpEF patients. Methods: We enrolled 30 consecutive HFpEF patients with NYHA class III, left ventricular ejection fraction (LVEF) >50%, E/e' >15, and NT-proBNP >300 pg/ml. In all patients, endothelial progenitor cells (EPCs) were mobilized by granulocyte-colony stimulating factor (G-CSF; 10 mcg/kg, 5 days) and collected via apheresis. Before EPC mobilisation we performed echocardiography and measured plasma levels of biomarkers of angiogenesis. At the time of enrolment, obesity was defined as BMI >27 kg/m 2 . Results: Obesity was present in 17 patients (57%; Group A) and absent in 13 patients (43%; Group B). The groups did not differ in age (62±8 years in Group A vs. 61±7 years in Group B, P=0.65), gender (male: 76% vs. 77%, P=0.97), serum creatinine (1.06±0.24 mg/dL vs. 1.05±0.42 mg/dL, P=0.52), LVEF (58±8% vs. 59±5%, P=0.56), or E/e’ (21.4±4.0 vs. 19.5±2.1, P=0.20). In Group B we found higher levels of NT-proBNP (2105±1015 pg/mL vs. 915±320 pg/mL in Group A, P=0.04). After G-CSF stimulation, we found significantly lower numbers of EPCs in Group A (62±48 x10 6 cells/L) than in Group B (98±54 x10 6 cells/L, P=0.01). Similarly, apheresis yielded lower numbers of EPCs in Group A (82±72 x10 6 cells vs. 187±90 x10 6 cells in Group B, P=0.01). When compared to Group B, patients in Group A had lower levels of pro-angiogenic biomarkers (agiopoietin-1: 6.8±2.3 ng/mL vs. 12.1±4.9 ng/mL, P=0.01; vascular endothelial growth factor: 22.5±18.2 pg/mL vs. 53.2±19.1 pg/mL, P=0.01), and higher levels of anti-angiogenic biomarkers (endostatin: 61.3±17.4 ng/mL vs. 31.7±12.2 ng/mL, P=0.01; thrombospondin-2: 17.1±3.9 ng/mL vs. 9.0±4.5 ng/mL, P=0.02). Conclusion: In patients with HFpEF, obesity appears to be associated with reduced mobilisation of endothelial progenitor cells and impaired angiogenesis.