Background: Inflammation and oxidative stress are thought to play an
important role in the pathophysiology of heart failure with preserved ejection
fraction (HFpEF) through the development of endothelial dysfunction.
Myeloperoxidase (MPO) functions as a link between oxidative stress and
inflammation and is an interesting therapeutic target. The objective of this
observational cohort study was to compare MPO levels between HFpEF and old
controls, to define clinical characteristics associated with high levels of MPO
and to assess the relation between MPO levels and vascular function.
Methods: Patients with HFpEF (N = 55) and controls 60 years (N = 18)
were prospectively included. All subjects underwent complete echocardiography and
blood sampling. MPO levels were dosed by ELISA assay. Effective arterial
elastance (Ea) and peripheral arterial tonometry (EndoPAT reactive hyperemia
index RHI and augmentation index AIx) were used to assess vascular function.
Characteristics between groups defined by the median of MPO were compared using
independent samples t-test or chi square test. Results:
Patients with HFpEF (80 8.7 years, 65% female) had higher levels of MPO
compared to controls (75 5.0 years, 72% female) (34.7 ng/mL [22.7;
44.0] vs 22.6 [18.2; 32.0], p = 0.026). MPO levels were correlated with
markers of inflammation; C-reactive protein (Pearson’s R = 0.46, p =
0.001) and neutrophile to lymphocyte ratio (R = 0.36, p = 0.031) and
with signs of left ventricular (LV) remodelling and elevated filling pressures,
namely NT-proBNP levels (R = 0.32, p = 0.019), decreased LV ejection
fraction (LVEF, R = –0.36, p = 0.008) and E/e’ ratio (R = 0.35,
p = 0.011). HFpEF patients with levels of MPO above the median were more
often men (48% vs 21%, p = 0.037) and suffered more often from
diabetes (48% vs 18%, p = 0.017). Intriguingly, they had lower indices
of vascular stiffness (augmentation index 11.1 [0.1; 30.7] vs 19.9 [10.5;
33.4], p = 0.018 and arterial elastance Ea 2.06 0.676 vs 2.43
0.721, p = 0.065) and there was no difference in endothelial
function (1.82 [1.34; 2.30] vs 1.66 [1.32; 1.95], p = 0.55).
Conclusions: HFpEF patients have higher levels of MPO than
controls, reflecting leukocyte activation and oxidative stress. Among patients,
high levels of MPO are associated with male sex, diabetic status, subtle left
ventricular dysfunction and pronounced diastolic dysfunction. The association
between oxidative stress and vascular stiffness, on the other hand could not be
demonstrated. Clinical Trial Registration: Clinical trial NCT03197350.