Increasing blood pressure predicts levels of circulating neutrophil extracellular traps in untreated hypertensive patients

Abstract

Neutrophil extracellular traps (NETs) are increasingly implicated in the pathophysiology of cardiovascular disease; however, data regarding their clinical significance in hypertension-mediated vascular damage is scarce. We recruited untreated, newly diagnosed patients with essential hypertension (UHTs) and age- and sex- matched healthy, normotensive controls (NTs). Ambulatory blood pressure (BP) monitoring was performed with the Mobil-O-Graph-NG device. NET-specific myeloperoxidase (MPO)-DNA complexes were measured in plasma with ELISA. Carotid pulse wave velocity (PWV) was calculated by using a high-definition echo-tracking system. Skin microcirculation was assessed using laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. A total of 139 participants of whom 99 UHTs (mean age 48.9 ± 8.34 years) and 40 NTs (mean age 47.4 ± 7.38 years) were included in the study. Using categorical regression with optimal scaling, various peripheral and central BP parameters were significantly associated with MPO-DNA complexes levels; 24 h peripheral systolic BP (p < 0.001) was the strongest predictor of hypertension-related NETosis, after adjusting for potential confounders. MPO-DNA complexes levels were positively associated with mean carotid PWV (p = 0.033) and baseline flux (p = 0.017) and negatively associated with baseline to peak flux (p = 0.020) and cutaneous vascular conductance increase (p = 0.034). In multivariate analysis, carotid PWV showed an independent association with MPO-DNA complexes. Circulating NETs levels are tightly associated with BP. Of note, the 24 h peripheral SBP load is the strongest predictor of NETs burden. Moreover, NETs are strongly related to surrogate measures of micro- and macrovascular damage, suggesting their potential role as a diagnostic and/or therapeutic target in hypertension. These authors contributed equally.