Myeloperoxidase as therapeutic target in HFpEF

Abstract

Abstract Background Inflammation and oxidative stress are thought to play an important role in the pathophysiology of HFpEF through the development of endothelial dysfunction. Myeloperoxidase (MPO), a leukocyte-derived enzyme, functions as a link between oxidative stress and inflammation and is an interesting therapeutic target. Purpose To compare MPO levels between HFpEF and old controls and to define clinical characteristics associated with high levels of MPO. Methods Patients with HFpEF (N=55) and controls >60 years (N=18) were prospectively included. All subjects underwent complete echocardiography and standard biology. MPO levels were dosed by ELISA assay. Endothelial function was assessed by peripheral arterial tonometry through the reactive hyperemia index (RHI). Characteristics were compared using independent samples t-test or chi square test. Results Patients with HFpEF (80±8.5 years, 65% female) had higher levels of myeloperoxidase compared to controls (74±6.2 years, 72% female) (34.7 ng/mL [22.7; 43.9] versus 22.5 [18.1; 31.9], p=0.026) (Figure 1). HFpEF patients with levels of MPO above the median were more often men and diabetic and had higher levels of NTproBNP and CRP. However, MPO levels were not associated with endothelial function measured by RHI (Table 1). Conclusion(s) HFpEF patients have higher levels of myeloperoxidase than control subjects, reflecting leukocyte activation and oxidative stress. Myeloperoxidase levels are associated with inflammation and disease severity. Myeloperoxidase inhibitors could be useful for the treatment of HFpEF patients, especially in the subgroup of patients with diabetes. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Fondation Damman